FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Day, TF Guo, XZ Garrett-Beal, L Yang, YZ AF Day, TF Guo, XZ Garrett-Beal, L Yang, YZ TI Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis SO DEVELOPMENTAL CELL LA English DT Article ID HAIR FOLLICLE MORPHOGENESIS; RECEPTOR-RELATED PROTEIN-5; INTEGRIN-LINKED KINASE; BETA-CATENIN; CHONDROGENIC DIFFERENTIATION; CUBITUS-INTERRUPTUS; BONE-FORMATION; IN-VITRO; CELL-DIFFERENTIATION; CALVARIAL CELLS AB Chondrocytes and osteoblasts are two primary cell types in the skeletal system that are differentiated from common mesenchymal progenitors. It is believed that osteoblast differentiation is controlled by distinct mechanisms in intramembranous and endochondral ossification. We have found that ectopic canonical Wnt signaling leads to enhanced ossification and suppression of chondrocyte formation. Conversely, genetic inactivation of β-catenin, an essential component transducing the canonical Wnt signaling, causes ectopic formation of chondrocytes at the expense of osteoblast differentiation during both intramembranous and endochondral ossification. Moreover, inactivation of β-catenin in mesenchymal progenitor cells in vitro causes chondrocyte differentiation under conditions allowing only osteoblasts to form. Our results demonstrate that R-catenin is essential in determining whether mesenchymal progenitors will become osteoblasts or chondrocytes regardless of regional locations or ossification mechanisms. Controlling Wnt/β-catenin signaling is a common molecular mechanism underlying chondrocyte and osteoblast differentiation and specification of intramembranous and endochondral ossification. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM yyang@nhgri.nih.gov NR 60 TC 797 Z9 834 U1 5 U2 49 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD MAY PY 2005 VL 8 IS 5 BP 739 EP 750 DI 10.1016/j.devcel.2005.03.016 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 926DL UT WOS:000229103000013 PM 15866164 ER PT J AU Lu, SJ Borst, DE Horowits, R AF Lu, SJ Borst, DE Horowits, R TI N-RAP expression during mouse heart development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE N-RAP; heart development; myofibril; intercalated disk; N-cadherin; alpha-actinin ID MUSCLE LIM PROTEIN; CULTURED CHICK CARDIOMYOCYTES; NEBULIN-RELATED PROTEIN; DILATED CARDIOMYOPATHY; INTERCALATED DISKS; STRIATED-MUSCLE; HYPERTROPHIC CARDIOMYOPATHY; CARDIAC MYOFIBRILLOGENESIS; FUNCTIONAL-ROLE; THIN-FILAMENTS AB N-RAP gene expression and N-RAP localization were studied during mouse heart development using semiquantitative reverse transcriptase-polymerase chain reaction and immunofluorescence. N-RAP mRNA was detected at embryonic day (E) 10.5, significantly increased from E10.5 to E16.5, and remained essentially constant from E16.5 until 21 days after birth. In E9.5-10.5 heart tissue, N-RAP protein was primarily associated with developing premyofibril structures containing a-actinin, as well as with the Z-fines and M-lines of more-mature myofibrils. In contrast, N-cadherin was concentrated in patches at the periphery of the cardiomyocytes. N-RAP labeling markedly increased between E10.5 and E16.5; almost all of the up-regulated N-RAP was associated with intercalated disk structures, and the proportion of mature sarcomeres containing N-RAP decreased. In adult hearts, specific N-RAP staining was only observed at the intercalated disks and was not found in the sarcomeres. The results are consistent with N-RAP functioning as a catalytic scaffolding molecule, with low levels of the scaffold being sufficient to repetitively catalyze key steps in myofibril assembly. Published 2005 Wiley-Liss, Inc. C1 NIAMSD, Muscle Biol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1154,MSC 8024, Bethesda, MD 20892 USA. EM horowits@helix.nih.gov FU NEI NIH HHS [EY11726] NR 43 TC 16 Z9 18 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 MAY PY 2005 VL 233 IS 1 BP 201 EP 212 DI 10.1002/dvdy.20314 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 917PD UT WOS:000228473800022 PM 15765519 ER PT J AU Nelson, KB AF Nelson, KB TI Neonatal encephalopathy: etiology and outcome SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Editorial Material ID NEWBORN ENCEPHALOPATHY; RISK-FACTORS; STROKE C1 NINDS, Neuroepidemiol Branch, Bethesda, MD USA. RP Nelson, KB (reprint author), NINDS, Neuroepidemiol Branch, Bethesda, MD USA. NR 7 TC 8 Z9 9 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD MAY PY 2005 VL 47 IS 5 BP 292 EP 292 DI 10.1017/S0012162205000563 PG 1 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 921VK UT WOS:000228793300002 PM 15892369 ER PT J AU Erickson, K Gabry, KE Schulkin, J Gold, P Lindell, S Higley, JD Champoux, M Suomi, SJ AF Erickson, K Gabry, KE Schulkin, J Gold, P Lindell, S Higley, JD Champoux, M Suomi, SJ TI Social withdrawal behaviors in nonhuman primates and changes in neuroendocrine and monoamine concentrations during a separation paradigm SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE cortisol; temperament; development; anxiety; serotonin; dopamine; norepinephrine ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; RHESUS-MONKEYS; CEREBROSPINAL-FLUID; ELECTROCHEMICAL DETECTION; PLASMA-CORTISOL; YOUNG-CHILDREN; MESSENGER-RNA; CORTICOSTERONE; STRESS; INFANT AB This study investigated relationships between withdrawal behaviors in rhesus macaques and changes in monoamine metabolite and endocrine concentrations during repeated psychosocial stress. Rhesus monkeys (N=71) experienced maternal separation in which four separations took place during four consecutive weeks. Behavioral observations were made, as well as plasma concentrations of cortisol and cerebrospinal fluid concentrations of the serotonin, dopamine, and norepinephrine metabolites were obtained. Animals were assigned to high, moderate, and low withdrawal groups, defined using baseline durations of withdrawal behaviors. Highly withdrawn animals showed less reduction than nonwithdrawn animals in serotonin metabolite concentrations over repeated separations. Highly withdrawn macaques also failed to significantly reduce cortisol concentrations across separation weeks. More adaptation in central serotonin functioning and cortisol concentrations was seen in nonwithdrawn primates than in highly withdrawn primates; these findings have implications for increased risk of developing anxiety disorders in highly inhibited children. © 2005 Wiley Periodicals, Inc. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NIAAA, Sect Primate Models & Psychopathol, Poolesville, MD USA. NICHHD, Comparat Ethol Lab, Poolesville, MD USA. RP Erickson, K (reprint author), NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. EM EricksonK@mail.nih.gov; PhilipGold@mail.nih.gov; higleyd@mail.nih.gov; suomis@mail.nih.gov NR 36 TC 26 Z9 26 U1 3 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD MAY PY 2005 VL 46 IS 4 BP 331 EP 339 DI 10.1002/dev.20061 PG 9 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 926DP UT WOS:000229103400004 PM 15832320 ER PT J AU Ma, LJ Tataranni, PA Hanson, RL Infante, AM Kobes, S Bogardus, C Baier, LJ AF Ma, LJ Tataranni, PA Hanson, RL Infante, AM Kobes, S Bogardus, C Baier, LJ TI Variations in peptide YY and Y2 receptor genes are associated with severe obesity in Pima Indian men SO DIABETES LA English DT Article ID FOOD-INTAKE; MESSENGER-RNA; GUT HORMONE; EXPRESSION; PYY3-36; MOUSE; TESTOSTERONE; POLYMORPHISM; BRAIN; FOXC2 AB Peptide YY (PYY) and Y2 receptor (Y2R) may be important in the central regulation of body weight and food intake. To determine whether genetic variation in PYY and/or Y2R may contribute to morbid obesity in humans, these genes were sequenced in 83 extremely obese Pima Indians (BMI >= 50 kg/m(2)). Sequencing of PYY identified three single nucleotide polymorphsms (SNPs) in the untranslated region. Sequencing of the Y2R coding region identified one missense (Ala172Thr) substitution and two silent substitutions. Eight additional SNPs in the 5' untranslated region of Y2R were identified from public databases. These SNPs were genotyped in 489 full-heritage adult Pimas (362 severely obese and 127 nondiabetic, nonobese subjects), who are not first-degree relatives, for association analysis. The PYY variants were not associated with obesity, whereas four variants from two haplotype blocks in Y2R were marginally associated (P = 0.054-0.067) with obesity. However, if the analysis was restricted to men (n = 167, 100 obese and 67 lean), the PYY variants and two SNPs in Y2R that were in complete linkage disequilibrium were significantly associated with severe obesity (P = 0.001 and P = 0.002, respectively). Our data suggest that the PYY-Y2R pathway may influence body weight through a sex-specific mechanism, but this finding requires confirmation in other populations. C1 NIDDK, Diabet Mol Genet Sect, NIH, Dept Hlth & Human Serv, Phoenix, AZ 85016 USA. RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, NIH, Dept Hlth & Human Serv, 4212 N 16th St, Phoenix, AZ 85016 USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [Z01 DK069071-09] NR 24 TC 41 Z9 44 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAY PY 2005 VL 54 IS 5 BP 1598 EP 1602 DI 10.2337/diabetes.54.5.1598 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 920OW UT WOS:000228701000045 PM 15855352 ER PT J AU Jovanovic, L Knopp, RH Kim, H Cefalu, WT Zhu, XD Lee, YJ Simpson, JL Mills, JL AF Jovanovic, L Knopp, RH Kim, H Cefalu, WT Zhu, XD Lee, YJ Simpson, JL Mills, JL CA Diabetes Early Pregnancy Study Grp TI Elevated pregnancy losses at high and low extremes of maternal glucose in early normal and diabetic pregnancy - Evidence for a protective adaptation in diabetes SO DIABETES CARE LA English DT Article ID SPONTANEOUS-ABORTION; GLYCEMIC CONTROL; GLYCATED ALBUMIN; SERUM-PROTEIN; BLOOD-GLUCOSE; FRUCTOSAMINE; MELLITUS; HYPOGLYCEMIA; HEMOGLOBIN; INDEX AB OBJECTIVE - Early pregnancy losses increase with marked hypergalycemia in diabetic pregnancy. However, mean loss rates do not differ from those of nondiabetic pregnancy. This observation might be explained by increased fetal losses at the extremes of glycemia in diabetic 0 and nondiabetic pregnancy. To test this hypothesis, we examined relationships of proximate measures of prior glycemia, glycated protein and fructosamine, to pregnancy loss. RESEARCH DESIGN AND METHODS - A total of 389 diabetic and 429 nondiabetic pregnant subjects participated in the Diabetes In Early pregnancy Study. Glycated protein and fructosamme measurements were standardized as multiples of Control values for each center (Z score). The logarithm of odds of pregnancy loss were Plotted against 2 scores and tested by logistic models. RESULTS - Mean pregnancy loss rates were 12%. in diabetic and 13% in normal pregnancies. However, over six intervals of glycated protein in diabetic pregnancy, fetal loss rates at the upper and lower extremes (24 and 33%, respectively) were approximately threefold higher than the four intervening rates (8-14%). The odds ratio of pregnancy loss for these extreme intervals to the intervening Intervals is 3.0 (P = 0.01). Nondiabetic losses showed a similar pattern. In confirmation, logit pregnancy losses were increased in a J-shaped curve at the glycemic extremes in normal (P < 0.019) and diabetic (P < 0.015) pregnancy. The upper glycemic extreme ITT diabetic pregnancy was two- to fivefold higher than in control pregnancy. CONCLUSIONS - Pregnancy losses are increased at the extremes of glycemia in both normal and diabetic pregnancy but at higher levels in diabetic pregnancy. The data suggest defensive adaptations against hyperglycernia in diabetic pregnancy. C1 Univ Washington, Dept Med, NW Lipid Res Clin, Seattle, WA 98104 USA. Sansum Diabet Res Fdn, Santa Barbara, CA USA. Harvard Univ, Sch Med, Dana Farber Canc Res Ctr, Boston, MA USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Knopp, RH (reprint author), Univ Washington, Dept Med, NW Lipid Res Clin, 325 9th Ave,Box 359720, Seattle, WA 98104 USA. EM rhknopp@u.washington.edu NR 29 TC 44 Z9 47 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2005 VL 28 IS 5 BP 1113 EP 1117 DI 10.2337/diacare.28.5.1113 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 920OX UT WOS:000228701100020 PM 15855575 ER PT J AU Cochran, E Musso, C Gorden, P AF Cochran, E Musso, C Gorden, P TI The use of U-500 in patients with extreme insulin resistance SO DIABETES CARE LA English DT Editorial Material ID DEPENDENT DIABETES-MELLITUS; LEPTIN-REPLACEMENT THERAPY; CLINICAL-COURSE; COMPLICATIONS; LIPODYSTROPHY; PROGRESSION; MANAGEMENT; RISK C1 NIDDK, CEB, NIH, Bethesda, MD 20892 USA. RP Cochran, E (reprint author), NIDDK, CEB, NIH, 9000 Rockville Pike,Bldg 10,CRC 6-5940, Bethesda, MD 20892 USA. EM elainec@intra.niddk.nih.gov NR 27 TC 60 Z9 60 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAY PY 2005 VL 28 IS 5 BP 1240 EP 1244 DI 10.2337/diacare.28.5.1240 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 920OX UT WOS:000228701100046 PM 15855601 ER PT J AU Blaum, CS Volpato, S Cappola, AR Chaves, P Xue, QL Guralnik, JM Fried, LP AF Blaum, CS Volpato, S Cappola, AR Chaves, P Xue, QL Guralnik, JM Fried, LP TI Diabetes, hyperglycaemia and mortality in disabled older women: The Women's Health and Ageing Study I SO DIABETIC MEDICINE LA English DT Article DE diabetes; hyperglycaemia; mortality ID ALL-CAUSE MORTALITY; IMPAIRED GLUCOSE-TOLERANCE; BODY-MASS INDEX; ELDERLY-PEOPLE; FOLLOW-UP; CARDIOVASCULAR HEALTH; POPULATION; MELLITUS; COHORT; ADULTS AB Aims Diabetes is associated with increased mortality in older adults, but the specific contributions of diabetes-associated clinical conditions and of increasing hyperglycaemia to mortality risk are unknown. We evaluated whether cardiovascular disease, comorbidities, or degree of hyperglycaemia, particularly severe hyperglycaemia, affected diabetes-related mortality risk in older, disabled women. Methods Six-year mortality follow-up of a random sample of 576 disabled women (aged 65-101 years), recruited from the Medicare eligibility list in Baltimore (MD, USA). All-cause and cardiovascular mortality were evaluated by diabetes status: no diabetes; diabetes with mild, moderate, and severe hyperglycaemia [defined by tertiles of glycosylated haemoglobin (GHB) among women with diabetes]. Results Diabetes with mild, moderate, and severe hyperglycaemia was associated with an increased hazard rate (HR) for all-cause mortality, even after adjustment for demographics, risks for cardiovascular disease, cardiovascular and non-cardiovascular conditions, and other known mortality risks. A dose-response effect was suggested [mild hyperglycaemia, HR 1.81, 95% confidence interval (CI) 1.03, 3.17; moderate hyperglycaemia, HR 2.02, 95% CI 1.34, 3.57; severe hyperglycaemia, HR 2.22, 95% CI 1.17, 4.25]. Women with diabetes had a significantly increased HR for non-cardiovascular death, but not for cardiovascular death, compared with those without diabetes. Conclusions Diabetes, whether characterized by mild, moderate or severe hyperglycaemia, appears to be an independent risk factor for excess mortality in older disabled women and this risk may increase with increasing hyperglycaemia. This mortality risk is not completely explained by vascular complications, and involves non-cardiovascular deaths. Risks and benefits of diabetes management, including glycaemic control and management of vascular and other comorbidities, should be studied in older people with complications and comorbidities. C1 Univ Michigan, Med Ctr, Div Geriatr, Dept Med, Ann Arbor, MI 48109 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Ferrara, Dipartimento Med, I-44100 Ferrara, Italy. Univ Maryland, Dept Med, Baltimore, MD 21201 USA. Univ Estado Rio De Janeiro, Ctr Studies Ageing & Care Elderly UNATI, Rio De Janeiro, Brazil. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Blaum, CS (reprint author), Univ Michigan, Med Ctr, Div Geriatr, Dept Med, Room 1111-CCGCB,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM cblaum@umich.edu RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [K08 AG0074901, N01 AG12112] NR 42 TC 9 Z9 9 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD MAY PY 2005 VL 22 IS 5 BP 543 EP 550 DI 10.1111/j.1464-5491.2005.01457.x PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 916PJ UT WOS:000228397300004 PM 15842507 ER PT J AU Sims-Mourtada, JC Bruce, S McKeller, MR Rangel, R Guzman-Rojas, L Cain, K Lopez, C Zimonjic, DB Popescu, NC Gordon, J Wilkinson, MF Martinez-Valdez, H AF Sims-Mourtada, JC Bruce, S McKeller, MR Rangel, R Guzman-Rojas, L Cain, K Lopez, C Zimonjic, DB Popescu, NC Gordon, J Wilkinson, MF Martinez-Valdez, H TI The human AKNA gene expresses multiple transcripts and protein isoforms as a result of alternative promoter usage, splicing, and polyadenylation SO DNA AND CELL BIOLOGY LA English DT Article ID IMMUNE-RESPONSES; CD40 LIGAND; B-CELLS; SEQUENCES; IDENTIFICATION; ACTIVATION; GENERATION; MECHANISM; ELEMENTS; SIGNALS AB We previously showed that the human AKNA gene encodes an AT-hook transcription factor that regulates the expression of costimulatory cell surface molecules on lymphocytes. However, AKNA cDNA probes hybridize with multiple transcripts, suggesting either the existence of other homologous genes or a complex regulation operating on a single gene. Here we report evidence for the latter, as we find that AKNA is encoded by a single gene that spans a 61-kb locus of 24 exons on the fragile FRA9E region of human chromosome 9q32. This gene gives rise to at least nine distinct transcripts, most of which are expressed in a tissue-specific manner in lymphoid organs. Many of the AKNA transcripts originate from alternative splicing; others appear to derive from differential polyadenylation and promoter usage. The alternative AKNA transcripts are predicted to encode overlapping protein isoforms, some of which (p70 and p100) are readily detectable using a polyclonal anti-AKNA antisera that we generated. We also find that AKNA PEST-dependent cleavage into p50 polypeptides is targeted to mature B cells and appears to be required for CD40 upregulation. The unusual capacity of the AKNA gene to generate multiple transcripts and proteins may reflect its functional diversity, and it may also provide a fail-safe mechanism that preserves AKNA expression. C1 Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Houston, TX 77030 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Univ Birmingham, MRC, Ctr Immune Regulat, Birmingham, W Midlands, England. RP Martinez-Valdez, H (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Immunol, Box 902,1515 Holcombe Blvd, Houston, TX 77030 USA. EM hmartine@mdanderson.org NR 30 TC 8 Z9 9 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD MAY PY 2005 VL 24 IS 5 BP 325 EP 338 DI 10.1089/dna.2005.24.325 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 924PV UT WOS:000228991800007 PM 15869410 ER PT J AU Choi, EH Kim, HS Eun, BW Kim, BI Choi, JY Lee, HJ Inada, T AF Choi, EH Kim, HS Eun, BW Kim, BI Choi, JY Lee, HJ Inada, T TI Adenovirus type 7 peptide diversity during outbreak, Korea, 1995-2000 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; GENOME TYPES; MOLECULAR EPIDEMIOLOGY; HYPERVARIABLE REGIONS; E4-6/7 PROTEIN; CHILDREN; FIBER; SEQUENCE; JAPAN; GENE AB To understand the molecular basis of observed regional shifts in the genome types of adenovirus type 7 (Ad7) isolated in Korea during nationwide outbreaks from 1995 to 2000, the genetic variabilities of Ad7d and Ad7I were studied by sequence analysis of hexon, fiber, E3, and E4 open reading frame (ORF) 6/7 peptides. One amino acid change in the receptor-binding domain of fiber and 6 amino acid variations in E4 ORF 6/7 were identified between 2 genome types, while no variations were found in hexon and E3. Phylogenetic trees based on hexon, fiber, and E4 suggested that the Ad7 epidemic was probably caused by the introduction of the Japanese Ad7d strains. Our data also provide evidence that the rapid divergence of Ad7d to a novel genome type Ad7I could have been due to viral strategies involving multiple sequence changes in E4. This result suggests fiber and E4 ORF 6/7 peptides participate in the evolution of Ad7. C1 Seoul Natl Univ, Childrens Hosp, Seoul 110744, South Korea. Natl Inst Infect Dis, Tokyo, Japan. NCI, Bethesda, MD 20892 USA. Seoul Natl Univ, Bundang Hosp, Kyonggi Do, South Korea. Seoul Natl Univ, Coll Med, Seoul, South Korea. RP Lee, HJ (reprint author), Seoul Natl Univ, Childrens Hosp, 28 Yongon Dong, Seoul 110744, South Korea. EM hoanlee@snu.ac.kr RI Choi, Eun Hwa/J-5691-2012; Lee, Hoan Jong/J-5616-2012 NR 29 TC 12 Z9 17 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2005 VL 11 IS 5 BP 649 EP 654 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 920IQ UT WOS:000228683000001 PM 15890114 ER PT J AU Carreon, T Butler, MA Ruder, AM Waters, MA Davis-King, KE Calvert, GM Schulte, PA Connally, B Ward, EM Sanderson, WT Heineman, EF Mandel, JS Morton, RF Reding, DJ Rosenman, KD Talaska, G AF Carreon, T Butler, MA Ruder, AM Waters, MA Davis-King, KE Calvert, GM Schulte, PA Connally, B Ward, EM Sanderson, WT Heineman, EF Mandel, JS Morton, RF Reding, DJ Rosenman, KD Talaska, G CA Brain Canc Collaborative Study Grp TI Gliomas and farm pesticide exposure in women: The Upper Midwest Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE brain cancer; case-control; farmers; glioma; Midwest; pesticides; women ID OCCUPATIONAL RISK-FACTORS; CENTRAL-NERVOUS-SYSTEM; BRAIN CANCER; TUMORS; SHANGHAI; STATES AB An excess incidence of brain cancer in male farmers has been noted in several studies, but few studies have focused on women. The National Institute for Occupational Safety and Health Upper Midwest Health Study evaluated effects of rural exposures for 341 female glioma cases and 528 controls, all adult (18-80 years of age) nonmetropolitan residents of Iowa, Michigan, Minnesota, and Wisconsin. On average, controls lived longer on farms than did cases. After adjusting for age, age group, education, and farm residence, no association with glioma was observed for exposure to arsenicals, benzoic acids, carbamates, chloroacetanilides, dinitroanilines, inorganics, organochlorines, organophosphates, phenoxys, triazines, or urea-based or estrogenic pesticides. An increased risk of glioma was observed for carbamate herbicides but was not statistically significant (odds ratio = 3.0; 95% confidence interval, 0.9-9.5). No association was observed between glioma and exposure to 12 widely used specific pesticides, after adjustment for age, age group, education, and any other pesticide exposure. These results were not affected after exclusion of proxy respondents (43% of cases, 2% of controls). Women were less likely than men to have applied pesticides, but more likely to have laundered pesticide-contaminated clothes. Storing pesticides in the house was associated with a statistically nonsignificant increased risk. Results show that exposure to pesticides was not associated with an increased risk of intracranial gliomas in women. Other farm-related factors could be etiologic factors and will be discussed in future reports. C1 NIOSH, Div Surveillance Hazard Evaluat & Field Studi, Cincinnati, OH 45226 USA. NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Mercy Fdn, Des Moines, IA USA. Marshfield Clin Fdn Med Res & Educ, Nat Farm Med Ctr, Marshfield, WI USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. RP Carreon, T (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studi, 4676 Columbia Pkwy,Mailstop R-16, Cincinnati, OH 45226 USA. EM carreota@ucmail.uc.edu RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 NR 37 TC 19 Z9 22 U1 2 U2 5 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 MAY PY 2005 VL 113 IS 5 BP 546 EP 551 DI 10.1289/ehp.7456 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 924ET UT WOS:000228962400032 PM 15866761 ER PT J AU Salnikow, K Kasprzak, KS AF Salnikow, K Kasprzak, KS TI Ascorbate depletion: A critical step in nickel carcinogenesis? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE ascorbate; carcinogenesis; collagens; extracellular matrix; hypoxia-inclucible transcription factor; metals; nickel; protein hydroxylation ID HYPOXIA-INDUCIBLE FACTOR; ENDOTHELIAL GROWTH-FACTOR; TERMINAL HUMAN CANCER; SURFACTANT PROTEIN-A; VITAMIN-C; PROLYL 4-HYDROXYLASE; AMINO-ACIDS; TRANSCRIPTIONAL ACTIVITY; ERYTHROPOIETIN GENE; LIPID-PEROXIDATION AB Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. Here, we challenge the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals. Instead, we propose that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype. This is concordant with the major requirement for nickel carcinogenicity, which is prolonged action on the target tissue. If DNA is not the main nickel target, is there another unique molecule that can be attacked with carcinogenic consequences? Our recent observations indicate that ascorbate may be such a molecule. Nickel depletes intracellular ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by the loss of hypoxia-inducible factor (HIF)-1 alpha: and -2 alpha hydroxylation and hypoxia-like stress. Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. Thus, the depletion of ascorbate by chronic exposure to nickel could be deleterious for lung cells and may lead to lung cancer. C1 NCI, Lab Comparat Cacinogenesis, NIH, Frederick, MD 21702 USA. RP Salnikow, K (reprint author), NCI, Lab Comparat Cacinogenesis, NIH, Bldg 538,Room 205 E, Frederick, MD 21702 USA. EM salnikow@ncifcrf.gov NR 133 TC 42 Z9 46 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2005 VL 113 IS 5 BP 577 EP 584 DI 10.1289/chp.7605 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 924ET UT WOS:000228962400037 PM 15866766 ER PT J AU Chen, AM Dietrich, KN Ware, JH Radcliffe, J Rogan, WJ AF Chen, AM Dietrich, KN Ware, JH Radcliffe, J Rogan, WJ TI IQ and blood lead from 2 to 7 years of age: Are the effects in older children the residual of high blood lead concentrations in 2-year-olds? SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chelation; developmental testing; IQ; lead poisoning; longitudinal studies ID PORT PIRIE COHORT; ENVIRONMENTAL LEAD; CHELATION-THERAPY; SCHOOL ENTRY; MU-G/DL; EXPOSURE; INTELLIGENCE; LEVEL; TODDLERS; SUCCIMER AB Increases in peak blood lead concentrations, which occur at 18-30 months of age in the United States, are thought to result in lower IQ scores at 4-6 years of age, when IQ becomes stable and measurable. Data from a prospective study conducted in Boston suggested that blood lead concentrations at 2 years of age were more predictive of cognitive deficits in older children than were later blood lead concentrations or blood lead concentrations measured concurrently with IQ. Therefore, cross-sectional associations between blood lead and IQ in school-age children have been widely interpreted as the residual effects of higher blood lead concentrations at an earlier age or the tendency of less intelligent children to ingest more leaded dust or paint chips, rather than as a causal relationship in older children. Here we analyze data from a clinical trial in which children were treated for elevated blood lead concentrations (20-44 μ g/dL) at about 2 years of age and followed until 7 years of age with serial IQ tests and measurements of blood lead. We found that cross-sectional associations increased in strength as the children became older, whereas the relation between baseline blood lead and IQ attenuated. Peak blood lead level thus does not fully account for the observed association in older children between their lower blood lead concentrations and IQ. The effect of concurrent blood level on IQ may therefore be greater than Currently believed. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Childrens Hosp Philadelphia, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Chen, AM (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 28 TC 71 Z9 78 U1 1 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 MAY PY 2005 VL 113 IS 5 BP 597 EP 601 DI 10.1289/ehp.7625 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 924ET UT WOS:000228962400040 PM 15866769 ER PT J AU Fleming, LE Backer, LC Baden, DG AF Fleming, LE Backer, LC Baden, DG TI Overview of aerosolized Florida red tide toxins: Exposures and effects SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE brevetoxins; harmful algal blooms (HABs); Karenia brevis; red tides; sensitive populations ID HUMAN HEALTH; SODIUM-CHANNELS; RAT-BRAIN; SHELLFISH; BREVETOXINS; RECEPTOR; BINDING; OCEANS AB Florida red tide is caused by Karenia brevis, a dinoflagellate that periodically blooms, releasing its potent neurotoxin, brevetoxin, into the surrounding waters and air along the coast of the Gulf of Mexico. Exposure to Florida red tide toxins has been associated with adverse human health effects and massive fish and marine mammal deaths. The articles in this mini-monograph describe the ongoing interdisciplinary and interagency research program that characterizes the exposures and health effects of aerosolized Florida red tide toxins (brevetoxins). The interdisciplinary research program uses animal models and laboratory studies to develop hypotheses and apply these findings to in situ human exposures. Our ultimate goal is to develop appropriate prevention measures and medical interventions to mitigate or prevent adverse health effects from exposure to complex mixtures of aerosolized red tide toxins. C1 NIEHS, Marine & Freshwater Biomed Sci Ctr, Miami, FL USA. Natl Sci Fdn, Natl Inst Environm Hlth Sci Oceans, Miami, FL USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Human Hlth Ctr, Miami, FL USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ N Carolina, Ctr Marine Sci, Wilmington, NC 28401 USA. RP Fleming, LE (reprint author), Univ Miami, Sch Med, Dept Epidemiol & Publ Hlth, 1801 NW 9th Ave,Highland Profess Bldg,Suite 200,R, Miami, FL 33136 USA. FU NIEHS NIH HHS [P01 ES 10594, P01 ES010594, P01 ES010594-04] NR 38 TC 51 Z9 52 U1 1 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 MAY PY 2005 VL 113 IS 5 BP 618 EP 620 DI 10.1289/ehp.7501 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 924ET UT WOS:000228962400044 PM 15866773 ER PT J AU Schwartz, DA AF Schwartz, DA TI Scientific vision: Setting forth a strategy SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM schwartzd@niehs.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 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 MAY PY 2005 VL 113 IS 5 BP A292 EP A292 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 924ET UT WOS:000228962400002 PM 15866748 ER PT J AU Misra, DP Astone, N Lynch, CD AF Misra, DP Astone, N Lynch, CD TI Maternal smoking and birth weight - Interaction with parity and mother's own in utero exposure to smoking SO EPIDEMIOLOGY LA English DT Article ID INTRAUTERINE GROWTH-RETARDATION; CIGARETTE-SMOKING; FETAL GROWTH; PRETERM DELIVERY; PREGNANCY; AGE; OUTCOMES; RECALL; WOMEN; RISK AB Background: Few studies have reported interactions between maternal smoking and other maternal characteristics and exposures. We examined maternal smoking in a cohort study for which data from 3 generations were available to examine maternal characteristics and exposures from a life-course perspective. Methods: We had data from 3 generations: women enrolled in the U.S. Collaborative Perinatal Project (CPP) between 1959 and 1965 at the Baltimore site (G1); daughters (G2) of those G1 mothers who were followed to ages 27-33 years in the Pathways to Adulthood study; and children (G3) born to the G2 women who provided pregnancy and birth information during the Pathways study. These data allowed examination of exposures that occurred to the mother during her childhood and in utero. Results: We found evidence of a 3-way interaction effect on birth weight for maternal smoking in pregnancy, maternal exposure to smoking in utero (grandmaternal smoking), and maternal parity. Maternal smoking reduced birth weight in 3 of the subgroups, with the size of the effect on birth weight moderated by parity and the mother's own in utero exposure to smoking. Conclusions: A mother's prenatal exposure to smoke may affect the birth weight of her offspring. This effect would be consistent with both the accumulation-of-risk and the fetal-programming hypotheses. C1 Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Dept Populat & Family Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD USA. US Dept HHS, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NICHHD,NIH, Bethesda, MD USA. RP Misra, DP (reprint author), Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, 1420 Washington Hts,M5015, Ann Arbor, MI 48109 USA. EM dmisra@umich.edu FU NICHD NIH HHS [P30 HD 06268] NR 29 TC 32 Z9 32 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2005 VL 16 IS 3 BP 288 EP 293 DI 10.1097/01.ede.0000158198.59544.cf PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 918SR UT WOS:000228568400004 PM 15824542 ER PT J AU Strohsnitter, WC Noller, KL Titus-Ernstoff, L Troisi, R Hatch, EE Poole, C Glynn, RJ Hsieh, CC AF Strohsnitter, WC Noller, KL Titus-Ernstoff, L Troisi, R Hatch, EE Poole, C Glynn, RJ Hsieh, CC TI Breast cancer incidence in women prenatally exposed to maternal cigarette smoke SO EPIDEMIOLOGY LA English DT Article ID ALPHA-FETOPROTEIN; PREGNANCY ESTROGENS; YOUNG-WOMEN; IN-UTERO; RISK; ESTRIOL; HCG AB Background: Clinical studies show that maternal cigarette smoking reduces pregnancy estrogen levels. Women prenatally exposed to maternal cigarette smoke may, therefore, have a lower breast cancer risk because the fetal mammary gland's exposure to maternal estrogen is decreased. Associations between prenatal maternal cigarette smoke exposure and breast cancer, however, have not been observed in previous case-control studies that relied on exposure assessment after the onset of cancer. At the start of this study, cigarette smoking history was obtained directly from the mother. Methods: The National Cooperative DES Adenosis project was a follow-up study of health outcomes in women prenatally exposed diethylstilbestrol (DES). At the start of the study, women's mothers provided information about cigarette smoking habits during the time they were pregnant with the study participant. In the current study, the breast cancer rates are compared among 4031 women who were or were not prenatally exposed to maternal cigarette smoke. The resultant relative rate (RR) is adjusted for potential confounding by other breast cancer risk factors using Poisson regression modeling. Results: Fetal exposure to maternal cigarette smoke appeared to be inversely associated with breast cancer incidence (RR = 0.49; 95% confidence interval [CI] = 0.24-1.03). The inverse association was more apparent among women whose mothers smoked 15 cigarettes or fewer per day than among daughters of heavier smokers. There were, however, too few cases to precisely estimate a possible dose-response relationship. Conclusion: These results support the hypothesis that in utero exposure to maternal cigarette smoke reduces breast cancer incidence. C1 Tufts New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Ctr Canc, Worcester, MA 01605 USA. RP Strohsnitter, WC (reprint author), Tufts New England Med Ctr, Dept Obstet & Gynecol, 750 Washington St, Boston, MA 02111 USA. EM Wstrohsnitter@tufts-nemc.org OI Hatch, Elizabeth/0000-0001-7901-3928 FU NCI NIH HHS [N01 CP 01290, CA 88891, N01 CP 01012-21, N01 CP 01288, N01 CP 01289]; NIEHS NIH HHS [P30 ES 10126] NR 25 TC 9 Z9 9 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2005 VL 16 IS 3 BP 342 EP 345 DI 10.1097/01.ede.0000158741.07645.9b PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 918SR UT WOS:000228568400012 PM 15824550 ER PT J AU Tarone, RE Inskip, PD AF Tarone, RE Inskip, PD TI Mobile phone use and acoustic neuromas SO EPIDEMIOLOGY LA English DT Letter ID CELLULAR-TELEPHONE USE; RISK C1 Int Epidemiol Inst, Rockville, MD USA. NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. RP Tarone, RE (reprint author), Int Epidemiol Inst, Rockville, MD USA. EM bob@iei.ws NR 4 TC 1 Z9 2 U1 1 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 MAY PY 2005 VL 16 IS 3 BP 414 EP 414 DI 10.1097/01.ede.0000158818.96464.2f PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 918SR UT WOS:000228568400022 PM 15824562 ER PT J AU Turkel, E Vatsa, VN AF Turkel, E Vatsa, VN TI Local preconditioners for steady and unsteady flow applications SO ESAIM-MATHEMATICAL MODELLING AND NUMERICAL ANALYSIS-MODELISATION MATHEMATIQUE ET ANALYSE NUMERIQUE LA English DT Article DE Low Mach; preconditioning; Jacobi; Dual time step; compressible Navier Stokes ID NAVIER-STOKES EQUATIONS; FLUID-DYNAMICS; DIFFERENCE; SCHEMES AB Preconditioners for hyperbolic systems are numerical artifacts to accelerate the convergence to a steady state. In addition, the preconditioner should also be included in the artificial viscosity or upwinding terms to improve the accuracy of the steady state solution. For time dependent problems we use a dual time stepping approach. The preconditioner affects the convergence rate and the accuracy of the subiterations within each physical time step. We consider two types of local preconditioners: Jacobi and low speed preconditioning. We can express the algorithm in several sets of variables while using only the conservation variables for the flux terms. We compare the effect of these various variable sets on the efficiency and accuracy of the scheme. C1 Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NIA, Hampton, VA USA. NASA, Langley Res Ctr, Hampton, VA 23665 USA. RP Turkel, E (reprint author), Tel Aviv Univ, IL-69978 Tel Aviv, Israel. RI Turkel, Eli/F-6297-2011 OI Turkel, Eli/0000-0003-4273-0303 NR 32 TC 31 Z9 31 U1 0 U2 2 PU EDP SCIENCES S A PI LES ULIS CEDEX A PA 17, AVE DU HOGGAR, PA COURTABOEUF, BP 112, F-91944 LES ULIS CEDEX A, FRANCE SN 0764-583X J9 ESAIM-MATH MODEL NUM JI ESAIM-Math. Model. Numer. Anal.-Model. Math. Anal. Numer. PD MAY-JUN PY 2005 VL 39 IS 3 BP 515 EP 535 DI 10.1051/m2an:2005021 PG 21 WC Mathematics, Applied SC Mathematics GA 953LB UT WOS:000231076700006 ER PT J AU Petersson, M Friberg, P Eisenhofer, G Lambert, G Rundqvist, B AF Petersson, M Friberg, P Eisenhofer, G Lambert, G Rundqvist, B TI Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; congestive; survival analysis; sympathetic nervous system; noradrenatine; renal circulation ID ANGIOTENSIN-CONVERTING ENZYME; AFFERENT DENERVATION PREVENTS; GLOMERULAR-FILTRATION-RATE; NERVOUS ACTIVITY; NOREPINEPHRINE; PLASMA; HYPERTENSION; MORTALITY; SURVIVAL; TRIAL AB Aims Although cardiac sympathetic activation is associated with adverse outcome in patients with chronic heart failure (CHF), the influence of renal sympathetic activity on outcome is unknown. We assessed the hypothesis that renal noradrenaline (NA) spillover is a predictor of the combined endpoint of all-cause mortality and heart transplantation in CHF. Methods and results Sixty-one patients with CHF, New York Heart Association (NYHA) I-IV (66% NYHA III-IV), and left ventricular ejection fraction (LVEF) 26 &PLUSMN; 9% (mean &PLUSMN; SD) were studied with cardiac and renal catheterizations at baseline and followed for 5.5 &PLUSMN; 3.7 years (median 5.5 years, range 12 days to 11.6 years). Nineteen deaths and 13 cases of heart transplantation were registered. Only renal NA spillover above median, 1.19 (interquartile range 0.77-1.43) nmol/min, was independently associated with an increased relative risk (RR) of the combined endpoint (RR 3.1, 95% CI 1.2-7.6, P = 0.01) in a model also including total body NA spillover, LVEF, glomerular filtration rate (GFR), renal blood flow, cardiac index, aetiology, and age. Conclusion Renal noradrenergic activation has a strong negative predictive value on outcome independent of overall sympathetic activity, GFR, and WEE These findings suggest that treatment regimens that further reduce renal noradrenergic stimulation could be advantageous by improving survival in patients with CHF. C1 Sahlgrens Univ Hosp, Cardiovasc Inst, Dept Cardiol, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Cardiovasc Inst, Dept Clin Physiol, S-41345 Gothenburg, Sweden. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Baker Heart Res Inst, Melbourne, Vic, Australia. RP Petersson, M (reprint author), Sahlgrens Univ Hosp, Cardiovasc Inst, Dept Cardiol, S-41345 Gothenburg, Sweden. EM magnus.petersson@wtab.gu.se RI Lambert, Gavin/E-7384-2010 OI Lambert, Gavin/0000-0003-0315-645X NR 39 TC 77 Z9 78 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAY PY 2005 VL 26 IS 9 BP 906 EP 913 DI 10.1093/eurheartj/ehi184 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 926BC UT WOS:000229096700012 PM 15764611 ER PT J AU Lenz, P Lowy, DR Schiller, JT AF Lenz, P Lowy, DR Schiller, JT TI Papillomavirus virus-like particles induce cytokines characteristic of innate immune responses in plasmacytoid dendritic cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE dendritic cells; human; viral infections; vaccination ID INTERFERON-PRODUCING CELLS; CPG-DNA; I INTERFERON; PERIPHERAL-BLOOD; ADAPTIVE IMMUNITY; REGULATORY CELLS; CONTROLLED TRIAL; INFLUENZA-VIRUS; CD40 LIGAND; T-CELLS AB Human papillomavirus (HPV) virus-like particles (VLP) are being extensively tested as vaccines for the prevention of HPV-associated cervical cancer. Dendritic cells (DC) acquire and present antigens, initiating innate and adaptive immune responses. It has been shown previously that DC of the myeloid lineage are capable of generating adaptive immune responses to HPVVLP in vitro. However, the capacity of plasmacytoid DC (pDC) to acquire HPV VLP and the nature of the immune response generated have not been reported. In this study we found that freshly isolated as well as CpG-matured pDC bind papillomavirus VLP and that internalization occurs preferentially in the immature pDC. In contrast to myeloid DC, pDC did not undergo phenotypic maturation upon exposure to HPV16 VLP. However, HPV16 VLP induced pDC to secrete of IFN-α and IL-6, both cytokines that play a role in the generation of antibody responses, as well as TNFα and IL-8. Given that VLP do not contain viral nucleic acids, these results indicate that viral capsids alone may be capable of inducing cytokine production by pDC. Finally, CpG-activated pDC, but not pDC exposed to HPV16 VLP, activated lymphocytes to secrete IL-10 and low levels of IFN-γ. Together these findings suggest a possible immunogenic effect of pDC in the setting of VLP vaccination. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Lenz, P (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Rm 2N212, Bethesda, MD 20892 USA. EM plenz@mail.nih.gov NR 44 TC 37 Z9 37 U1 0 U2 1 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 MAY PY 2005 VL 35 IS 5 BP 1548 EP 1556 DI 10.1002/eji.200425547 PG 9 WC Immunology SC Immunology GA 926BG UT WOS:000229097100024 PM 15832296 ER PT J AU Kuprash, DV Tumanov, AV Liepinsh, DJ Koroleva, EP Drutskaya, MS Kruglov, AA Shakhov, AN Southon, E Murphy, WJ Tessarollo, L Grivennikov, SL Nedospasov, SA AF Kuprash, DV Tumanov, AV Liepinsh, DJ Koroleva, EP Drutskaya, MS Kruglov, AA Shakhov, AN Southon, E Murphy, WJ Tessarollo, L Grivennikov, SL Nedospasov, SA TI Novel tumor necrosis factor-knockout mice that lack Peyer's patches SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cytokines; lymphoid organ development; host defense ID HEMATOPOIETIC PROGENITOR CELLS; SECONDARY LYMPHOID-TISSUES; LYMPHOTOXIN BETA-RECEPTOR; ALPHA-DEFICIENT MICE; TNF-ALPHA; LISTERIA-MONOCYTOGENES; ABNORMAL-DEVELOPMENT; ENHANCER ACTIVITY; ORGAN DEVELOPMENT; GENE-EXPRESSION AB We generated a novel tumor necrosis factor (TNF) null mutation using Cre-loxP technology. Mice homozygous for this mutation differ from their "conventional" counterparts; in particular, they completely lack Peyer's patches (PP) but retain all lymph nodes. Our analysis of these novel TNF-knockout mice supports the previously disputed notion of the involvement of TNF-TNFR1 signaling in PP organogenesis. Availability of TNF-knockout strains both with and without PP enables more definitive studies concerning the roles of TNF and PP in various immune functions and disease conditions. Here, we report that systemic ablation of TNF, but not the presence of PP per se, is critical for protection against intestinal Listeria infection in mice. C1 Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, Moscow 119991, Russia. NCI, Mol Immunoregulat Lab, Frederick, MD USA. NCI, SAIC Frederick INc, Basic Res Program, Frederick, MD 21701 USA. Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. RP Kuprash, DV (reprint author), Russian Acad Sci, VA Engelhardt Mol Biol Inst, Lab Mol Immunol, 32 Vavilov St, Moscow 119991, Russia. EM kuprash@online.ru RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016; OI Kuprash, Dmitry/0000-0002-1488-4148; kruglov, andrey/0000-0002-4597-2087 FU NCI NIH HHS [N01-CO-12400] NR 51 TC 47 Z9 55 U1 0 U2 0 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 MAY PY 2005 VL 35 IS 5 BP 1592 EP 1600 DI 10.1002/eji.200526119 PG 9 WC Immunology SC Immunology GA 926BG UT WOS:000229097100029 PM 15832287 ER PT J AU Beltaifa, S Webster, MJ Ligons, DL Fatula, RJ Herman, MM Kleinman, JE Weickert, CS AF Beltaifa, S Webster, MJ Ligons, DL Fatula, RJ Herman, MM Kleinman, JE Weickert, CS TI Discordant changes in cortical TrkC mRNA and protein during the human lifespan SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE expression; full-length; neurotrophin; post mortem; receptor; truncated; tyrosine kinase ID PREFRONTAL CORTEX; NERVOUS-SYSTEM; NEUROTROPHIC FACTOR; INTRINSIC CONNECTIONS; SIGNAL-TRANSDUCTION; RECEPTOR ISOFORMS; DENDRITIC GROWTH; OPPOSING ROLES; FULL-LENGTH; RAT TRKC AB Neurotrophin-3 (NT-3) exerts its trophic effects in brain via tyrosine kinase receptor C (trkC) signaling. TrkC splice variants produce receptors with (full-length) and without (truncated) a tyrosine kinase domain. The relative abundance of trkC isoforms and the anatomical localization of trkC in the human prefrontal cortex (PFC) in relationship to development and maturation are currently unknown. We have examined the temporo-spatial expression of trkC protein and mRNA during the development of the human PFC. We have found two major isoforms, a full-length (150 kDa) and a truncated (50 kDa) form of the trkC protein in the human PFC. We report that the full-length form is expressed at low levels throughout development while the truncated form is expressed at moderate levels early in development and increases to reach mature levels by adolescence. In contrast, trkC mRNA levels are uniformly expressed throughout most of postnatal life, but decline in ageing. TrkC protein and mRNA are expressed in both pyramidal and non-pyramidal neurons; additionally, trkC protein is detected in glia and neuropil. Our results suggest that truncated trkC is prevalent in the human PFC and that neurons and glia may be responsive to NT-3 in the PFC throughout life. C1 NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. USUHS, Dept Psychiat, Stanley Lab Brain Res, Bethesda, MD 20817 USA. RP Beltaifa, S (reprint author), NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. EM beltaifs@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011 NR 66 TC 22 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAY PY 2005 VL 21 IS 9 BP 2433 EP 2444 DI 10.1111/j.1460-9568.2005.04074.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 928PN UT WOS:000229284100012 PM 15932601 ER PT J AU Shidara, M Richmond, BJ AF Shidara, M Richmond, BJ TI Effect of visual noise on pattern recognition SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE pattern recognition; visual noise; behavioral latency; rhesus monkey ID INFERIOR TEMPORAL NEURONS; CORTEX; MEMORY; DISCRIMINATION AB We recognize objects even when they are partially degraded by visual noise. Using monkeys performing a sequential delayed match-to-sample task, we studied the relation between the amount of visual noise (5, 10, 15, 20 or 25%) degrading the eight black and white stimuli used here, and the accuracy and speed with which matching stimuli were identified. The correct response rate decreased slightly as the amount of visual noise increased for both monkeys. Even at the 25% noise level, the correct response rate was more than 80%, indicating that the monkeys can recognize the pattern they are trying to match when the pattern is masked with visual noise. In contrast, the reaction time to the match stimulus increased substantially as the amount of visual noise increased. Thus, the monkeys appear to be trading time to maintain accuracy, suggesting that the monkeys are accumulating information and/or testing hypotheses about whether the test stimulus is likely to be a match for the sample being held in short-term memory. C1 Natl Inst Adv Ind Sci & Technol AIST, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. NIMH, Neurophysiol Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Shidara, M (reprint author), Natl Inst Adv Ind Sci & Technol AIST, Neurosci Res Inst, 1-1-1 Umezono, Tsukuba, Ibaraki 3058568, Japan. EM m.shidara@aist.go.jp NR 11 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2005 VL 163 IS 2 BP 239 EP 241 DI 10.1007/s00221-005-2230-0 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 931SQ UT WOS:000229506100009 PM 15912370 ER PT J AU Shidara, M Mizuhiki, T Richmond, BJ AF Shidara, M Mizuhiki, T Richmond, BJ TI Neuronal firing in anterior cingulate neurons changes modes across trials in single states of multitrial reward schedules SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE neural coding; response variability; anterior cingulate; single unit recording; rhesus monkey ID SIGNALS AB The recorded responses of single neurons often vary considerably in the numbers of spikes emitted across repeats of a single experimental condition. Because of this irregularity and for theoretical convenience the responses are often approximated using a Poisson process. However, it has been frequently pointed out that many details of the responses, including the distribution of spike counts across similar trials, are not consistent with a Poisson process, even an inhomogeneous one. Wiener and Richmond (2003, J Neurosci 23:2394-2406) showed that the spike count distributions could usually be fitted nicely by mixtures of a few (1-3) Poisson distributions, a step they regarded as a computational convenience. Now, we find that a substantial proportion (47%) of the neuronal responses from anterior cingulate cortex, which we conceptualize as part of a system related to the balance between work and reward, have responses with multimodal firing rate distributions. When these distributions are modeled as mixtures of Poisson distributions, the proportions of the different Poisson distributions are related to behavioral state, and might be related to cognitive factors. This suggests that the neurons undergo behaviorally-related mode changes. C1 Natl Inst Adv Ind Sci & Technol AIST, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. Univ Tsukuba, Grad Sch Comprehens Human Sci, Tsukuba, Ibaraki 3058575, Japan. NIMH, Neuropsychol Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Shidara, M (reprint author), Natl Inst Adv Ind Sci & Technol AIST, Neurosci Res Inst, 1-1-1 Umezono, Tsukuba, Ibaraki 3058568, Japan. EM m.shidara@aist.go.jp NR 10 TC 15 Z9 15 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD MAY PY 2005 VL 163 IS 2 BP 242 EP 245 DI 10.1007/s00221-005-2232-y PG 4 WC Neurosciences SC Neurosciences & Neurology GA 931SQ UT WOS:000229506100010 PM 15912371 ER PT J AU Wang, Y Chang, CF Chou, J Chen, HL Deng, XL Harvey, BK Cadet, JL Bickford, PC AF Wang, Y Chang, CF Chou, J Chen, HL Deng, XL Harvey, BK Cadet, JL Bickford, PC TI Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage SO EXPERIMENTAL NEUROLOGY LA English DT Article DE nutrition; diet; ischemia; neuroprotection; apoptosis; antioxidant ID WATER-SOLUBLE ANTIOXIDANT; FOCAL CEREBRAL-ISCHEMIA; OXIDATIVE STRESS; INFARCT VOLUME; VITAMIN-A; RATS; MICE; MAXIMA; STROKE; MODEL AB Free radicals are involved in neurodegenerative disorders, such as ischemia and aging. We have previously demonstrated that treatment with diets enriched with blueberry, spinach, or spirulina have been shown to reduce neurodegenerative changes in aged animals. The purpose of this study was to determine if these diets have neuroprotective effects in focal ischemic brain. Adult male Sprague-Dawley rats were fed with equal amounts of diets (blueberry, spinach, and spirulina) or with control diet. After 4 weeks of feeding, all animals were anesthetized with chloral hydrate. The right middle cerebral artery was ligated with a 10-O suture for 60 min. The ligature was later removed to allow reperfusional injury. Animals were sacrificed and brains were removed for caspase-3 enzymatic assays and triphenyltetrazolium chloride staining at 8 and 48 h after the onset of reperfusion. A subgroup of animals was used for locomotor behavior and biochemical assays. We found that animals which received blueberry, spinach, or spirulina enriched diets had a significant reduction in the volume of infarction in the cerebral cortex and an increase in post-stroke locomotor activity. There was no difference in blood biochemistry, blood CO2, and electrolyte levels among all groups, suggesting that the protection was not indirectly mediated through the changes in physiological functions. Animals treated with blueberry, spinach, or spirulina had significantly lower caspase-3 activity in the ischemic hemisphere. In conclusion, our data suggest that chronic treatment with blueberry, spinach, or spirulina reduces ischemia/reperfusion-induced apoptosis and cerebral infarction. Published by Elsevier Inc. C1 Univ S Florida, James A Haley Va Hosp, Coll Med, Dept Neurosurg, Tampa, FL 33612 USA. Ctr Excellence Aging & Brain Repair, Tampa, FL 33612 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. RP Bickford, PC (reprint author), Univ S Florida, James A Haley Va Hosp, Coll Med, Dept Neurosurg, MDC 78,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. EM pbickfor@hsc.usf.edu RI Harvey, Brandon/A-5559-2010; Bickford, Paula/J-5970-2012 OI Bickford, Paula/0000-0001-9657-7725 FU NIA NIH HHS [AG04418] NR 33 TC 99 Z9 114 U1 2 U2 14 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 MAY PY 2005 VL 193 IS 1 BP 75 EP 84 DI 10.1016/j.expneurol.2004.12.014 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 916VB UT WOS:000228413300007 PM 15817266 ER PT J AU Boger, HA Middaugh, LD Zaman, V Hoffer, BJ Granholm, ACH AF Boger, HA Middaugh, LD Zaman, V Hoffer, BJ Granholm, ACH TI Slow progressive loss of dopamine neurons in GDNF heterozygous mice: Implications for Parkinson's disease SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 12th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY APR 28-MAY 01, 2005 CL Clearwater, FL SP Amer Soc Neural Transplantat & Repair C1 Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Aging, Charleston, SC 29425 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2005 VL 193 IS 1 BP 240 EP 240 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 916VB UT WOS:000228413300033 ER PT J AU Chen, EY Kladis, T Langenbach, R Kordower, JH AF Chen, EY Kladis, T Langenbach, R Kordower, JH TI Cox-2 deficient mice are resistant to quinolinic acid-induced excitotoxic but not to 3-nitropropionic acid-induced metabolic striatal insult SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 12th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY APR 28-MAY 01, 2005 CL Clearwater, FL SP Amer Soc Neural Transplantat & Repair C1 Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Natl Inst Environm Hlth Sci, 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2005 VL 193 IS 1 BP 242 EP 242 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 916VB UT WOS:000228413300038 ER PT J AU Freed, WJ Cai, J Chen, J Luo, Y You, ZB Fotter, E Wang, Y Harvey, B Miura, T Backman, C AF Freed, WJ Cai, J Chen, J Luo, Y You, ZB Fotter, E Wang, Y Harvey, B Miura, T Backman, C TI Derivation of dopaminergic neurons from human embryonic stem cells and initial transplantation studies in rat hosts SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 12th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY APR 28-MAY 01, 2005 CL Clearwater, FL SP Amer Soc Neural Transplantat & Repair C1 NIH, Cellular Neurobiol Res Branch, Intramural Res Program, Natl Inst Drug Abuse,DHHS, Baltimore, MD USA. NIA, Neurosci Lab, DHHS, Baltimore, MD 21224 USA. NIDA, Behav Neurosci Res Branch, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Res Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RI luo, Yu (Agnes)/E-4446-2010 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2005 VL 193 IS 1 BP 245 EP 245 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 916VB UT WOS:000228413300050 ER PT J AU Sanchez, JF Schoen, CJ Dillon-Carter, O Coggiano, M Freed, WJ AF Sanchez, JF Schoen, CJ Dillon-Carter, O Coggiano, M Freed, WJ TI Mesencephalic cell line development using SV40 T antigen fragments T155c and T155g SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 12th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY APR 28-MAY 01, 2005 CL Clearwater, FL SP Amer Soc Neural Transplantat & Repair C1 Natl Inst Drug Abuse, Dev & Plastic Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2005 VL 193 IS 1 BP 258 EP 259 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 916VB UT WOS:000228413300094 ER PT J AU Yu, G Sanberg, CD Sanberg, PR Hoffer, BJ Borlongan, CV AF Yu, G Sanberg, CD Sanberg, PR Hoffer, BJ Borlongan, CV TI Modulating the blood brain barrier to enhance neuroprotection of intra-arterial HUCB administration in acute ischemic stroke SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 12th Annual Conference of the American-Society-for-Neural-Transplantation-and-Repair CY APR 28-MAY 01, 2005 CL Clearwater, FL SP Amer Soc Neural Transplantat & Repair C1 Sanercon CCEL Therapeut Inc, Tampa, FL USA. Univ S Florida, Coll Med, Ctr Excellence Aging & Brain Repair, Tampa, FL USA. NIDA, Intramural Res Program, NIH, Baltimore, MD USA. Med Coll Georgia, Inst Mol Med Genet, Augusta, GA USA. VAMC, Res & Affiliat Serv Line, Augusta, GA USA. Med Coll Georgia, Dept Neurol, Augusta, GA 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD MAY PY 2005 VL 193 IS 1 BP 265 EP 266 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 916VB UT WOS:000228413300118 ER PT J AU Jessup, JM Lively, TG Taube, SE AF Jessup, JM Lively, TG Taube, SE TI Program for the Assessment of Clinical Cancer Tests (PACCT): implementing promising assays into clinical practice SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Editorial Material ID NEGATIVE BREAST-CANCER; ERBB-2 C1 NCI, Div Canc Treatment & Diag, Canc Diag Program, Rockville, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Taube, SE (reprint author), NCI, Div Canc Treatment & Diag, Canc Diag Program, EPN 6035A,6130 Execut Blvd, Rockville, MD 20892 USA. EM jmj25@georgetown.edu; tl82s@nih.gov; st29f@nih.gov NR 3 TC 5 Z9 5 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2005 VL 5 IS 3 BP 271 EP 273 DI 10.1586/147159.5.3.271 PG 3 WC Pathology SC Pathology GA 940SJ UT WOS:000230164100001 PM 15934805 ER PT J AU Berman, JJ Bhatia, K AF Berman, JJ Bhatia, K TI Biomedical data integration: using XML to link clinical and research data sets SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE common data elements; data integration; interoperabiltiy; translational research; XML ID PATHOLOGY DATA; INFORMATICS; PHARMACOGENOMICS; BIOINFORMATICS; INSTITUTIONS; GENOMICS; LANGUAGE; SYSTEMS; CANCER AB Data integration occurs when a query proceeds through multiple data sets, thereby relating diverse data extracted from different data sources. Data integration is particularly important to biomedical researchers since data obtained from experiments on human tissue specimens have little applied value unless they can be combined with medical data (i.e., pathologic and clinical information). In the past, research data were correlated with medical data by manually retrieving, reading, assembling and abstracting patient charts, pathology reports, radiology reports and the results of special tests and procedures. Manual annotation of research data is impractical when experiments involve hundreds or thousands of tissue specimens resulting in large, complex data collections. The purpose of this paper is to review how XML (eXtensible Markup Language) provides the fundamental tools that support biomedical data integration. The article also discusses some of the most important challenges that block the widespread availability of annotated biomedical data sets. C1 NCI, Resources Dev Branch, Canc Diag Program, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Resources Dev Branch, Canc Diag Program, EPN Room 6028,6130 Execut Blvd, Bethesda, MD 20892 USA. EM bermanj@mail.nih.gov NR 45 TC 5 Z9 5 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2005 VL 5 IS 3 BP 329 EP 336 DI 10.1586/14737159.5.3.329 PG 8 WC Pathology SC Pathology GA 940SJ UT WOS:000230164100005 PM 15934811 ER PT J AU Fischer, BM Cuellar, JG Byrd, AS Rice, AB Bonner, JC Martin, LD Voynow, JA AF Fischer, BM Cuellar, JG Byrd, AS Rice, AB Bonner, JC Martin, LD Voynow, JA TI ErbB2 activity is required for airway epithelial repair following neutrophil elastase exposure SO FASEB JOURNAL LA English DT Article; Proceedings Paper CT 17th Annual North American Cystic Fibrosis Conference CY OCT 16-19, 2003 CL Anaheim, CA DE DNA synthesis; protease ID EPIDERMAL-GROWTH-FACTOR; CELLS IN-VITRO; TYROSINE KINASE; CYSTIC-FIBROSIS; FACTOR RECEPTOR; BREAST-CANCER; LEUKOCYTE ELASTASE; GENE-EXPRESSION; CARCINOMA-CELLS; MESSENGER-RNA AB In cystic fibrosis and chronic bronchitis, airways are chronically injured by exposure to neutrophil elastase ( NE). We sought to identify factors required for epithelial repair following NE exposure. Normal human bronchial epithelial cells were treated with NE ( 50 nM, 22 h) or control vehicle. Following NE treatment, we found a marked and sustained decrease in epithelial proliferation as detected by Ki67 immunostaining. H-3-thymidine incorporation was also initially depressed but increased over 72 h in NE-treated cells, which suggests that DNA synthesis constitutes an early repair process following NE exposure. We hypothesized that ErbB2 receptor tyrosine kinase, a regulator of cancer cell proliferation, was required for epithelial DNA synthesis following NE exposure. Immediately following NE treatment, by flow cytometry analysis, we found a decrease in ErbB2 surface expression. Protein levels of the full-length 185 kD ErbB2 receptor significantly decreased following NE treatment and smaller ErbB2-positive bands, ranging in size from 23 to 40 kD, appeared, which suggests that NE caused ErbB2 degradation. By real-time RT-PCR analysis, we found no change in ErbB2 mRNA expression following NE treatment, which suggests that changes in ErbB2 protein levels were regulated at the post-translational level. Following NE treatment, full-length 185 kD ErbB2 levels increased to pretreatment levels, correlating with the increase in thymidine incorporation during the same time period. Importantly, inhibition of ErbB2 activity with AG825 ( 5 mu M) or Herceptin (3.1 mu M), an ErbB2-neutralizing antibody, blocked thymidine incorporation only in NE-treated cells. These results suggest ErbB2 is a critical factor for epithelial recovery following NE exposure. C1 Duke Univ, Med Ctr, Div Pediat Pulm Med, Dept Pediat, Durham, NC 27710 USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA. RP Voynow, JA (reprint author), Duke Univ, Med Ctr, Div Pediat Pulm Med, Dept Pediat, Box 2994, Durham, NC 27710 USA. EM voyno001@mc.duke.edu FU NHLBI NIH HHS [HL66236, HL073174] NR 47 TC 11 Z9 11 U1 0 U2 0 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 MAY PY 2005 VL 19 IS 7 BP 1374 EP + DI 10.1096/fj.04-2675fje PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 933CU UT WOS:000229602600006 PM 15923396 ER PT J AU Wistow, G Wyatt, K David, L Gao, C Bateman, O Bernstein, S Tomarev, S Segovia, L Slingsby, C Vihtelic, T AF Wistow, G Wyatt, K David, L Gao, C Bateman, O Bernstein, S Tomarev, S Segovia, L Slingsby, C Vihtelic, T TI gamma N-crystallin and the evolution of the beta gamma-crystallin superfamily in vertebrates SO FEBS JOURNAL LA English DT Article DE crystallin; eye; gene structure; intron loss; lens ID SEQUENCE TAG ANALYSIS; 6000 NONREDUNDANT TRANSCRIPTS; LENS CRYSTALLINS; NEIBANK PROJECT; GENE FAMILY; EYE LENS; SPLICE VARIANTS; S-CRYSTALLIN; HUMAN RETINA; PROTEIN AB The beta and gamma crystallins are evolutionarily related families of proteins that make up a large part of the refractive structure of the vertebrate eye lens. Each family has a distinctive gene structure that reflects a history of successive gene duplications. A survey of gamma-crystallins expressed in mammal, reptile, bird and fish species (particularly in the zebrafish, Danio rerio) has led to the discovery of gamma N-crystallin, an evolutionary bridge between the beta and gamma families. In all species examined, gamma N-crystallins have a hybrid gene structure, half beta and half gamma, and thus appear to be the 'missing link' between the beta and gamma crystallin lineages. Overall, there are four major classes of gamma-crystallin: the terrestrial group (including mammalian gamma A-F); the aquatic group (the fish gamma M-crystallins); the gamma S group; and the novel gamma N group. Like the evolutionarily ancient beta-crystallins (but unlike the terrestrial gamma A-F and aquatic gamma M groups), both the gamma S and gamma N crystallins form distinct clades with members in fish, reptiles, birds and mammals. In rodents, gamma N is expressed in nuclear fibers of the lens and, perhaps hinting at an ancestral role for the gamma-crystallins, also in the retina. Although well conserved throughout vertebrate evolution, gamma N in primates has apparently undergone major changes and possible loss of functional expression. C1 NEI, Sect Mol Struct & Funct Genom, NIH, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ London Birkbeck Coll, Dept Crystallog, London, England. Univ Maryland, Sch Med, Dept Ophthalmol, Baltimore, MD 21201 USA. Univ Nacl Autonoma Mexico, IBT, Cuernavaca, Morelos, Mexico. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. RP Wistow, G (reprint author), NEI, Sect Mol Struct & Funct Genom, NIH, Bg 7,Rm 201, Bethesda, MD 20892 USA. EM graeme@helix.nih.gov RI Segovia, Lorenzo/A-5206-2008 OI Segovia, Lorenzo/0000-0002-4291-4711 FU NEI NIH HHS [EY10572] NR 64 TC 61 Z9 68 U1 0 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD MAY PY 2005 VL 272 IS 9 BP 2276 EP 2291 DI 10.1111/j.1742-4658.2005.04655.x PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919TN UT WOS:000228640600020 PM 15853812 ER PT J AU Nelson, LM Covington, SN Rebar, RW AF Nelson, LM Covington, SN Rebar, RW TI An update: spontaneous premature ovarian failure is not an early menopause SO FERTILITY AND STERILITY LA English DT Review CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med DE premature ovarian failure; premature menopause; hypergonadotropic amenorrhea; hypergonadotropic hypergonadism; ovarian insufficiency; autoimmune oophoritis; estrogen; hormone replacement; adrenal insufficiency; hypothyroidism; FMR1; fragile X syndrome ID FOLLICLE-STIMULATING-HORMONE; FRAGILE-X PREMUTATION; ADDISONS-DISEASE; YOUNG-WOMEN; REPLACEMENT THERAPY; HYPERGONADOTROPIC AMENORRHEA; POSTMENOPAUSAL WOMEN; CLINICAL-FEATURES; CONTROLLED-TRIAL; ADRENAL-CORTEX AB Objective: To update clinicians regarding the management of women with spontaneous premature ovarian failure (POF). Design: Literature review and consensus building among three clinicians with experience in caring for women with spontaneous POF. Conclusion(s): Clearly the ovarian "failure" in this disorder is not permanent in all women. Approximately 5%-10% may conceive spontaneously and unexpectedly after the diagnosis. An integrated approach to management is best. and there is a need to first address physical and mental health issues before addressing plans for family building. Women with spontaneous POF are at increased risk of adrenal insufficiency, which should be detected and managed appropriately, especially before proceeding to ovum or embryo donation procedures. Young women with POF experience pathologically low serum E-2 levels at least intermittently. Despite the absence of controlled evidence for this specific population, physiologic replacement of ovarian steroid hormones seems rational until the age of normal menopause. The disorder may be associated with other conditions that require evaluation and management, including hypothyroidism, dry eye syndrome, abnormal karyotype, or a premutation of the FMR1 gene. Finally, clinicians need to be sensitive to the emotional aspects of this disorder when delivering the diagnosis and during subsequent management. ((c) 2005 by American Society for Reproductive Medicine.) C1 NICHHD, NIH, CRC, Intramural Res Program,Sect Womens Hlth Res,Dev E, Bethesda, MD 20892 USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. Amer Soc Reprod Med, Birmingham, AL USA. RP Nelson, LM (reprint author), NICHHD, NIH, CRC, Intramural Res Program,Sect Womens Hlth Res,Dev E, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM Lawrence_Nelson@nih.gov NR 59 TC 103 Z9 110 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 EI 1556-5653 J9 FERTIL STERIL JI Fertil. Steril. PD MAY PY 2005 VL 83 IS 5 BP 1327 EP 1332 DI 10.1016/j.fertnstert.2004.11.059 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 924WC UT WOS:000229010500001 PM 15866564 ER PT J AU Fan, JS Wilson, DM AF Fan, JS Wilson, DM TI Protein-protein interactions and posttranslational modifications in mammalian base excision repair SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE protein interaction; posttranslational modification; base excision DNA repair; free radicals ID DNA-POLYMERASE-BETA; CELL NUCLEAR ANTIGEN; STRAND-BREAK REPAIR; PURIFIED HUMAN PROTEINS; HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; HUMAN AP-ENDONUCLEASE; TRANSCRIPTION-COUPLED REPAIR; HUMAN APURINIC ENDONUCLEASE; SOMATIC G-C->T-A MUTATIONS; HUMAN FLAP ENDONUCLEASE-1 AB Base excision repair (BER) averts the cytotoxic and inutagenic effects of most endogenously produced DNA damage, including lesions that arise spontaneously due to the intrinsic instability of DNA or modifications that are formed from reactions with intracellular chemicals, such as reactive oxygen species and alkylating agents. Defects in the BER process have been associated with cancer susceptibility and neurodegenerative disorders. In its most simplistic form, BER can be fully reconstituted with a minimum of four human proteins and is completed in just five sequential steps: (i) excision of an inappropriate base by a DNA glycosylase (e.g., uracil DNA glycosylase); (ii) incision of the DNA backbone immediately adjacent to the resulting a basic site by apurinic/apyrimidimic endonuclease 1; (iii) removal of the 5'-abasic terminal fragment, and (iv) repair synthesis to fill the gap by DNA polymerase and (v) ligation to seal the remaining nick by DNA ligase 1 or a complex of DNA ligase 3 and X-ray repair cross-complementing 1. However, BER can involve the participation of other proteins as well, such as alternative DNA polymerases or one of several nonessential "auxiliary" factors. In addition, BER operates most efficiently when specific protein-protein coordination occurs. Furthermore, several BER protein activities have been shown to be regulated by posttranslational modification, and some of the physical protein interactions link BER to other DNA transaction pathways. In this review, We summarize the current state of the emerging complexities of mammalian BER, focusing on the growing number of reported proteinprotein interactions and posuranslational modifications. Published by Elsevier Inc. C1 NIA, GRC, Lab Mol Gerontol, NIH,IRP, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, GRC, Lab Mol Gerontol, NIH,IRP, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov NR 176 TC 97 Z9 102 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAY 1 PY 2005 VL 38 IS 9 BP 1121 EP 1138 DI 10.1016/j.freeradbiomed.2005.01.012 PG 18 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 917AW UT WOS:000228429200001 PM 15808410 ER PT J AU Chen, L Deng, CX AF Chen, L Deng, CX TI Roles of FGF signaling in skeletal development and human genetic diseases SO FRONTIERS IN BIOSCIENCE LA English DT Review DE FGF; fibroblast growth factor; signaling; skeletal development; enetic disease; review ID FIBROBLAST-GROWTH-FACTOR; PROTEIN-KINASE-C; VERTEBRATE LIMB DEVELOPMENT; LIGAND-BINDING SPECIFICITY; SYNDROME-LIKE PHENOTYPES; OF-FUNCTION MUTATION; FACTOR RECEPTOR 3; BONE-FORMATION; THANATOPHORIC DYSPLASIA; CHONDROCYTE PROLIFERATION AB Fibroblast growth factor receptors (FGFRs) exist as a gene family of 4 membrane bound receptor tyrosine kinases (FGFR1-4) that mediate signals of at least 22 fibroblast growth factors (FGF1-22). FGFs/FGFRs play important roles in multiple biological processes, including mesoderm induction and patterning, cell growth and migration, organ formation and bone growth. Furthermore, it has been shown that missense mutations of FGFR1-3 in human result in, at least, 14 congential bone diseases that are broadly classified into two groups: chondrodysplasia syndromes and craniosynostosis syndromes. The chondrodysplasia affects primarily the skeleton formed through endochondral ossification, resulting short-limbed dwarfisms, while the craniosynostosis affects mainly bones formed through intramembraneous ossification, leading to premature fusion of the craniofacial sutures. Using gene targeting, mouse models mimicking some of these human diseases have been created. Analysis of these mutant mice revealed essential functions of FGFs/FGFRs in skeletal development and maintenance. These models may be beneficial in future studies aimed at developing novel therapeutic strategies for FGFR-related skeletal dysplasias. In this review, we discuss the results of recent studies on FGF receptors to illustrate mechanisms through which the abnormally activated FGF/FGFR signaling results in these diseases. C1 NIH, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. Third Mil Med Univ, Daping Hosp, Ctr Med Mol Genet, Ctr Trauma, Chongqing 400042, Peoples R China. RP Chen, L (reprint author), NIH, Genet Dev & Dis Branch, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM linchen70@163.com; chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 146 TC 51 Z9 54 U1 0 U2 3 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAY 1 PY 2005 VL 10 BP 1961 EP 1976 DI 10.2741/1671 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970OP UT WOS:000232319800078 PM 15769677 ER PT J AU Takami, T Terai, S Yokoyama, Y Tanimoto, H Tajima, K Uchida, K Yamasaki, T Sakaida, I Nishina, H Thorgeirsson, SS Okita, K AF Takami, T Terai, S Yokoyama, Y Tanimoto, H Tajima, K Uchida, K Yamasaki, T Sakaida, I Nishina, H Thorgeirsson, SS Okita, K TI Human homologue of maid is a useful marker protein in hepatocarcinogenesis SO GASTROENTEROLOGY LA English DT Article ID LOOP-HELIX PROTEINS; HEPATITIS-C VIRUS; ACID-DEFINED DIET; HEPATOCELLULAR-CARCINOMA; ADENOMATOUS HYPERPLASIA; INTERFERON THERAPY; INVERSE EXPRESSION; CHOLINE-DEFICIENT; ALAGILLE-SYNDROME; JAB1 EXPRESSION AB Background & Aims: Human homologue of maid (HHM) is a helix-loop-helix (HLH) transcriptional regulatory protein that is involved in the hepatic stem cell development and differentiation. We analyzed the potential involvement of HHM in hepatocarcinogenesis. Methods: We analyzed HHM expression in the choline-deficient L-amino acid defined (CDAA) diet model of rat hepatocarcinogenesis and in human adenomatous hyperplasia (AH) and hepatocellular carcinoma (HCC) biopsy samples. We assessed the effects of HHM on cell proliferation. We screened proteins that bind to HHM protein using a yeast 2-hybrid screen. Results: High HHM expression was seen in foci and HCC induced in the rat CDAA diet model. HHM protein was expressed in 23 of 32 AH samples (72%), 19 of 28 well-differentiated HCC samples (68%), and 9 of 18 poorly-moderately differentiated HCC samples (50%). Over-expressed HHM enhanced the S phase. HHM interference RNA significantly inhibited cell proliferation. A yeast 2-hybrid screen identified Jun activation domain-binding protein I (Jab1) as a binding partner for HHM. We confirmed HHM and Jab1 binding by immunoprecipitation and immunofluorescent histochemistry. The expression of Jab1 was found in human AH and HCC samples. We found an association between levels of expression of HHM and those of Jabl in AH and HCC tissues examined (P =.027 by χ(2) test). Conclusions: High-level HHM expression was found from the very early stages of hepatocarcinogenesis, suggesting that HHM may be a useful marker protein to detect. C1 Yamaguchi Univ, Sch Med, Dept Mol Sci & Appl Med Gastroenterol & Hepatol, Minami Ku, Ube, Yamaguchi 7558505, Japan. Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Tokyo, Japan. NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD USA. RP Terai, S (reprint author), Yamaguchi Univ, Sch Med, Dept Mol Sci & Appl Med Gastroenterol & Hepatol, Minami Ku, Kogushi 1-1-1, Ube, Yamaguchi 7558505, Japan. EM terais@yamaguchi-u.ac.jp NR 37 TC 18 Z9 19 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD MAY PY 2005 VL 128 IS 5 BP 1369 EP 1380 DI 10.1053/j.gastro.2005.03.014 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 926NP UT WOS:000229130200023 PM 15887118 ER PT J AU Salani, B Damonte, P Zingone, A Barbieri, O Chou, JY D'Costa, J Arya, SK Eva, A Varesio, L AF Salani, B Damonte, P Zingone, A Barbieri, O Chou, JY D'Costa, J Arya, SK Eva, A Varesio, L TI Newborn liver gene transfer by an HIV-2-based lentiviral vector SO GENE THERAPY LA English DT Article DE newborn; liver transduction; lentiviral vector ID LONG-TERM EXPRESSION; VIRUS TYPE-1 VPR; MUCOPOLYSACCHARIDOSIS-VII DOGS; HEMATOPOIETIC STEM-CELLS; IN-UTERO INJECTION; CLOTTING FACTOR-IX; NONDIVIDING CELLS; HIGHLY EFFICIENT; NUCLEAR IMPORT; CYCLE ARREST AB Newborn gene therapy, because it can prevent the damage caused by the onset of a disease, deserves specific attention. To evaluate gene transfer in tissues of newborn mice, we used a human immunodeficiency virus (HIV)-2 based lentiviral vector pseudotyped with vesicular stomatitis virus G glycoprotein expressing the green fluorescent protein reporter gene under the control of the cytomegalovirus promoter. We found that very low doses of HIV-2 could infect and be expressed in newborn mice. Under these conditions, the virus was preferentially expressed in the liver and hepatocytes were the predominant target. The treatment was not toxic, the infected liver cells proliferated and the transduced gene was stably expressed. Adult mice could be infected by HIV-2, but the vector was detected in the liver only utilizing the sensitive method of polymerase chain reaction coupled with Southern blot. Direct comparison between newborn and adult recipients demonstrated a much greater efficiency of liver transduction in the newborn mouse. These results indicate that the combination of early intervention and low multiplicity of infection may be a strategy for preferentially and efficiently targeting newborn liver for gene therapy applications. C1 G Gaslini Inst Children, Mol Biol Lab, I-16147 Genoa, Italy. Univ Genoa, IST, Dept Oncol Biol & Genet, Genoa, Italy. NIH, Sect Cellular Differentiat, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Varesio, L (reprint author), G Gaslini Inst Children, Mol Biol Lab, Largo G Gaslini 5, I-16147 Genoa, Italy. RI Barbieri, Ottavia/E-8768-2011; Eva, Alessandra/J-8268-2016; varesio, luigi/J-8261-2016 OI Eva, Alessandra/0000-0003-2949-078X; varesio, luigi/0000-0001-5659-2218 NR 68 TC 9 Z9 9 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAY PY 2005 VL 12 IS 10 BP 803 EP 814 DI 10.1038/sj.gt.3302473 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 924QY UT WOS:000228996200002 PM 15772691 ER PT J AU Pack, SD Qin, LX Pak, E Wang, Y Ault, DO Mannan, P Jaikumar, S Stratakis, CA Oldfield, EH Zhuang, ZP Weil, RJ AF Pack, SD Qin, LX Pak, E Wang, Y Ault, DO Mannan, P Jaikumar, S Stratakis, CA Oldfield, EH Zhuang, ZP Weil, RJ TI Common genetic changes in hereditary and sporadic pituitary adenomas detected by comparative genomic hybridization SO GENES CHROMOSOMES & CANCER LA English DT Article ID TUMOR-SUPPRESSOR GENE; MCCUNE-ALBRIGHT SYNDROME; IN-SITU HYBRIDIZATION; STIMULATORY G-PROTEIN; MEN1 GENE; CHROMOSOMAL IMBALANCES; CAUSES ANEUPLOIDY; ADENYLYL-CYCLASE; CARNEY COMPLEX; ALPHA-SUBUNIT AB Twenty-four pituitary adenomas, both the sporadic type (n 18) and the type arising in association with either multiple endocrine neoplasia, type I (MEN I; n = 2), or Carney complex (CNC, n = 4) were analyzed by comparative genomic hybridization. Twenty-one (88%) tumors displayed chromosomal alterations. The number of chromosomal aberrations in each tumor varied from 2 to greater than 10. Several recurrent chromosomal abnormalities were identified in this study. The most frequently detected losses of chromosomal material involved I p (14 of 24, 58%), 11 p (I I of 24, 46%), 17 (10 of 24, 42%), 16p (9 of 24, 38%), 4 (8 of 24, 33%), 10p (6 of 24, 25%), 12 (6 of 24, 25%), 20 (6 of 24, 25%), 22q (6 of 24, 25%), 13q (5 of 24, 21%), and 9p (4 of 24, 17%). Copy number increases were detected on 4q (7 of 24, 29%), 17 (8 of 24, 33%), 19 (7 of 24, 29%), 1p (6 of 24, 25%), 5 (6 of 24, 25%), 20 (6 of 24, 25%), 6q (5 of 24, 21%), 13q21-qter (5 of 24, 21%), and 16p (5 of 24, 21%). Chromosome I I loss, which involved I I p in all cases, was the most significant finding and was common to tumors arising sporadically and in association with MEN I and CNC. In addition, the majority of the tumors (18 of 24, 75% overall and 86% of all tumors with chromosomal abnormalities) showed involvement of chromosome 1. Tumors had either loss (14 of 24, 58%) or gain (6 of 24, 25%) in the 1p32-1pter region. Finally, changes on chromosome 17, either loss or gain, occurred in 71% (17) of all 24 patients. In summary, all the tumors with chromosomal rearrangements (21 of 24, 88%), whether sporadic pituitary adenomas or those associated with MENI or CNC, had alteration(s) of Ip32, 11p, or 17. (c) 2005 Wiley-Liss, Inc. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Fudan Univ, Liver Canc Inst, Shanghai 200433, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200433, Peoples R China. Georgetown Univ, Med Ctr, Rockville, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIH, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. NICHD, Sect Genet & Endocrinol, DEB, NIH, Bethesda, MD USA. Cleveland Clin Fdn, BrainTumor Inst, Cleveland, OH 44195 USA. RP Pack, SD (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD USA. EM spack@niaid.nih.gov; weilr@ccf.org RI Pack, Svetlana/C-2020-2014 NR 63 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAY PY 2005 VL 43 IS 1 BP 72 EP 82 DI 10.1002/gcc.20162 PG 11 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 913MD UT WOS:000228154900007 PM 15704128 ER PT J AU Rouzine, IM Coffin, JM AF Rouzine, IM Coffin, JM TI Evolution of human immunodeficiency virus under selection and weak recombination SO GENETICS LA English DT Article ID IN-VIVO; LINKAGE; LIMITS; CELLS; SEX AB To predict emergence of drug resistance in patients undergoing antiretroviral therapy, we study accumulation of preexisting beneficial alleles in a haploid population of N genomes. The factors included in the model are selection with the coefficient s and recombination with the small rate per genome r (r << s root k, where (k) over bar is the average number of less-fit loci per genome). Mutation events are neglected. To describe evolution at a large number of linked loci, we generalize the analytic method we developed recently for an asexual population. We show that the distribution of genomes over the deleterious allele number moves in time as a "solitary wave" that is quasi-deterministic in the middle (on the average) but has stochastic edges. We arrive at a single-locus expression for the average accumulation rate, in which the effects of linkage, recombination, and random drift are all accounted for by the effective selection coefficient s In(Nr)/In(NA/r). At large N, the effective selection coefficient approaches the single-locus value s. Below the critical size N-c similar to 1/r, a population eventually becomes a clone, recombination cannot produce new sequences, and virus evolution stops. Taking into account finite mutation rate predicts a small, finite rate of evolution at N < N-c. We verify the accuracy of the results analytically and by Monte Carlo simulation. On the basis of our findings, we predict that partial depletion of the HfV population by combined antiretroviral therapy can suppress emergence of drug resistant strains. C1 Tufts Univ, Sch Med, Boston, MA 02111 USA. NIC, Drug Resistance Program, NIH, Ft Detrick, MD 21702 USA. RP Rouzine, IM (reprint author), Tufts Univ, Sch Med, 136 Harrison Ave, Boston, MA 02111 USA. EM irouzine@tufts.edu FU NCI NIH HHS [R01 CA089441, CA89441, R35CA44385, R37 CA089441]; NIAID NIH HHS [K25 AI001811, K25AI01811] NR 16 TC 51 Z9 51 U1 0 U2 2 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD MAY PY 2005 VL 170 IS 1 BP 7 EP 18 DI 10.1534/genetics.104.029926 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 933ZY UT WOS:000229677500003 PM 15744057 ER PT J AU Hall, MA McEwen, JE Barton, JC Walker, AP Howe, EG Reiss, JA Power, TE Ellis, SD Tucker, DC Harrison, BW McLaren, GD Ruggiero, A Thomson, EJ AF Hall, MA McEwen, JE Barton, JC Walker, AP Howe, EG Reiss, JA Power, TE Ellis, SD Tucker, DC Harrison, BW McLaren, GD Ruggiero, A Thomson, EJ TI Concerns in a primary care population about genetic discrimination by insurers SO GENETICS IN MEDICINE LA English DT Article ID COLORECTAL-CANCER; PERSPECTIVES; DECISIONS; INSURANCE; AWARENESS; FEAR AB Purpose: Fear of genetic discrimination might deter participation in research or therapy. This is a major impetus for laws limiting insurers' use of genetic information, yet there is little information about the extent of this fear in the general population and how it varies by social factors. Methods: This study measures concern about insurance problems relating to genetic testing, as part of primary-care screening for hereditary hemochromatosis (iron overload). Data come from a multiethnic, primary care-based survey of 86,859 adults in five field centers in the United States (AL, CA, DC, HI, OR), and one in Canada (Ontario). Logistic regression was used to model the probability of agreeing to the question "Genetic testing is not a good idea because you might have trouble getting or keeping your insurance." Results: Overall, 40.0% of participants agreed. Adjusting for other characteristics, African Americans and Asians were much less likely (OR = 0.52 and 0.39), and Hispanics were more likely (OR = 1.124), than Caucasians to express concern about insurance discrimination. Participants under 65 years old, US residents, and those without a high school diploma were substantially more likely to be concerned (ORs ranging from 1.4-1.6), as were participants with lower mental health scores. Education showed a nonlinear relationship, with significantly higher concern among both those with less than a high school education and those with a college degree, compared to high school graduates. Conclusions: Concern about genetic discrimination varies substantially by race and other demographic factors and by nationality. One possible explanation for lower concern about Canadians and by people over 64 is that both groups are covered by social insurance for health care (Medicare). However, US residents in states with some legal protections against genetic discrimination had more, not less, concern than either Canadians or US residents in states with no legal protections. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. NHGRI, NIH, Bethesda, MD 20892 USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Calif Irvine, Irvine, CA USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Kaiser Permanente NW, Portland, OR USA. London Ontario Hlth Sci Ctr, London, ON, Canada. Univ Alabama, Birmingham, AL USA. Howard Univ, Washington, DC 20059 USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. RP Hall, MA (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, 2000 W 1st St, Winston Salem, NC 27157 USA. RI Ellis, Shellie/I-4811-2015 OI Ellis, Shellie/0000-0002-3599-0804 FU NCRR NIH HHS [M01-RR00827, M01-RR10284]; NHLBI NIH HHS [N01-HC05186, N01-HC05192, N01-HC05189, N01-HC05190, N01-HC05188, N01-HC05191, N01-HC05185] NR 24 TC 66 Z9 66 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 2005 VL 7 IS 5 BP 311 EP 316 DI 10.1097/01.GIM.0000162874.58370.C0 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 930FT UT WOS:000229401900004 PM 15915082 ER PT J AU Ogino, S Flodman, P Wilson, RB Gold, B Grody, WW AF Ogino, S Flodman, P Wilson, RB Gold, B Grody, WW TI Risk calculations for cystic fibrosis in neonatal screening by immunoreactive trypsinogen and CFTR mutation tests SO GENETICS IN MEDICINE LA English DT Article DE Bayesian; CFTR; cystic fibrosis; genetic counseling; screening ID BAYESIAN-ANALYSIS; PREVALENCE; DIAGNOSIS; BRITTANY; INFANTS; FRANCE; IMPACT AB Purpose: Although neonatal screening (or newborn screening) for cystic fibrosis (CF) is commonly practiced, systematic methods for accurate risk calculations are currently lacking. Methods and Results: We evaluated characteristics of the immunoreactive trypsinogen (IRT) test using the published data. The probability that a neonate has a positive IRT test, if the neonate is affected, a carrier, or a noncarrier, is approximate to 1, 0.041, or 0.011, respectively. We provide methods to calculate genetic risks for a variety of commonly encountered scenarios in which neonates are positive by the IRT test. Conclusion: Our Bayesian methods permit CF disease probabilities to be calculated accurately, taking into account all relevant information. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif Irvine, Dept Pediat, Irvine, CA 92717 USA. Univ Penn, Med Ctr, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21701 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Human Genet, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90024 USA. RP Ogino, S (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD MAY-JUN PY 2005 VL 7 IS 5 BP 317 EP 327 DI 10.1097/01.GIM.0000162871.68167.8A PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 930FT UT WOS:000229401900005 PM 15915083 ER PT J AU Sharov, AA Dudekula, DB Ko, MSH AF Sharov, AA Dudekula, DB Ko, MSH TI Genome-wide assembly and analysis of alternative transcripts in mouse SO GENOME RESEARCH LA English DT Article ID MAMMALIAN GENOMES; HUMAN GENES; SEQUENCES; IDENTIFICATION; ALIGNMENT; ESTS; DATABASE; SITES; MICROARRAYS; ANNOTATION AB To build a Mouse gene index with the most comprehensive coverage of alternative transcription/splicing (ATS), we developed an algorithm and a fully automated computational pipeline for transcript assembly from expressed sequences aligned to the genome. We identified 191,946 genomic loci, which included 27,497 protein-coding genes and 11,906 additional gene candidates (e.g., nonprotein-coding, but multiexon). Comparison of the resulting gene index with TIGR, UniGene, DoTS, and ESTGenes databases revealed that it had a greater number of transcripts, a greater average number of exons and introns with proper splicing sites per gene, and longer ORFs. The 27,497 protein-coding genes had 77,138 transcripts, i.e., 2.8 transcripts per gene on average. Close examination of transcripts led to a combinatorial table of 23 types of ATS units, only nine of which were previously described, i.e., 14 types of alternative splicing, seven types of alternative starts, and two types of alternative termination. The 47%, 18%, and 14% of 20,323 multiexon protein-coding genes with proper splice sites had alternative splicings, alternative starts, and alternative terminations, respectively. The gene index with the comprehensive ATS will provide a useful platform for analyzing the nature and mechanism of ATS, as well as for designing the accurate exon-based DNA microarrays. C1 NIA, Dev Genomics & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Dev Genomics & Aging Sect, Genet Lab, NIH, 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 NR 41 TC 46 Z9 48 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD MAY PY 2005 VL 15 IS 5 BP 748 EP 754 DI 10.1101/gr.3269805 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 923WX UT WOS:000228941300016 PM 15867436 ER PT J AU Johnson, KR Zheng, QY Weston, MD Ptacek, LJ Noben-Trauth, K AF Johnson, KR Zheng, QY Weston, MD Ptacek, LJ Noben-Trauth, K TI The Mass1(frings) mutation underlies early onset hearing impairment in BUB/BnJ mice, a model for the auditory pathology of Usher syndrome IIC SO GENOMICS LA English DT Article DE hearing loss; mouse inbred strain; Frings; BUB/BnJ; VLGR1; USH2C; Mass1; Cdh23 ID PROTEIN-COUPLED RECEPTOR-1; AUDIOGENIC-SEIZURES; C57BL/6J MICE; INBRED STRAINS; VLGR1; SUSCEPTIBILITY; MORPHOLOGY; DBA/2J AB The human ortholog of the gene responsible for audiogenic seizure susceptibility in Frings and BUB/BnJ mice (mouse gene symbol Mass1) recently was shown to underlie Usher syndrome type IIC (USH2C). Here we report that the Mass1(frings) mutation is responsible for the early onset hearing impairment of BUB/BnJ mice. We found highly significant linkage of Mass1 with ABR threshold variation among mice from two backcrosses involving BUB/BnJ mice with mice of strains CAST/EiJ and MOLD/RkJ. We also show an additive effect of the Cdh23 locus in modulating the progression of hearing loss in backcross mice. Together, these two loci account for more than 70% of the total ABR threshold variation among the backcross mice at all ages. The modifying effect of the strain-specific Cdh23(ahl) variant may account for the hearing and audiogenic seizure differences observed between Frings and BUB/BnJ mice, which share the Mass mutation. During postnatal cochlear development in BUB/BnJ mice, stereocilia bundles develop abnormally and remain immature and splayed into adulthood, corresponding with the early onset hearing impairment associated with Mass(1frings) Progressive base-apex hair cell degeneration occurs at older ages, corresponding with the age-related hearing loss associated with Cdh23(ahl). The molecular basis and pathophysiology of hearing loss suggest BUB/BnJ and Frings mice as models to study cellular and molecular mechanisms underlying USH2C auditory pathology. (c) 2005 Elsevier Inc. All rights reserved. C1 Jackson Lab, Bar Harbor, ME 04609 USA. Boys Town Natl Res Hosp, Dept Genet, Ctr Study & Treatment Usher Syndrome, Omaha, NE 68131 USA. Univ Calif San Francisco, Dept Neurol, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, NIH, Rockville, MD 20850 USA. RP Johnson, KR (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA. EM krj@jax.org RI Zheng, Qing/C-1731-2012 FU NCI NIH HHS [CA34196, P30 CA034196, P30 CA034196-189007]; NCRR NIH HHS [RR01183, P40 RR001183, P40 RR001183-22]; NIDCD NIH HHS [DC005827, R01 DC005827, R01 DC005827-03, R03 DC004376, R03 DC004376-03, R21 DC005846, R21 DC005846-01A1] NR 23 TC 42 Z9 42 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2005 VL 85 IS 5 BP 582 EP 590 DI 10.1016/j.ygeno.2005.02.006 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 920BJ UT WOS:000228662000007 PM 15820310 ER PT J AU Curtiss, NP Bonifas, JM Lauchle, JO Balkman, JD Kratz, CP Emerling, BM Green, ED Le Beau, MM Shannon, KM AF Curtiss, NP Bonifas, JM Lauchle, JO Balkman, JD Kratz, CP Emerling, BM Green, ED Le Beau, MM Shannon, KM TI Isolation and analysis of candidate myeloid tumor suppressor genes from a commonly deleted segment of 7q22 SO GENOMICS LA English DT Article DE chromosome 7; acute myeloid leukemia; Myelodysplastic syndrome; monosomy 7; F-box proteins ID CHROMOSOME BAND 7Q22; LONG-ARM DELETIONS; MOLECULAR CHARACTERIZATION; CHILDHOOD MONOSOMY-7; HAPLO-INSUFFICIENT; CELL-LINE; CYCLIN-E; LEUKEMIA; CANCER; DELINEATION AB Monosomy 7 and deletions of 7q are recurring leukemia-associated cytogenetic abnormalities that correlate with adverse outcomes in children and adults. We describe a 2.52-Mb genomic DNA contig that spans a commonly deleted segment of chromosome band 7q22 identified in myeloid malignancies. This interval currently includes 14 genes, 19 predicted genes, and 5 predicted pseudogenes. We have extensively characterized the FBXL13, NAPE-PLD, and SVH genes as candidate myeloid tumor suppressors. FBXL13 encodes a novel F-box protein, SVHis a member of a gene family that contains Armadillo-like repeats, and NAPE-PLD encodes a phospholipase D-type phosphodiesterase. Analysis of a panel of leukemia specimens with monosomy 7 did not reveal mutations in these or in the candidate genes LRRC17, PRO1598,and SRPK2. This fully sequenced and annotated contig provides a resource for candidate myeloid tumor suppressor gene discovery. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Chicago, Hematol Oncol Sect, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. RP Shannon, KM (reprint author), Univ Calif San Francisco, Dept Pediat, 513 Parnassus Ave,HSE 302, San Francisco, CA 94143 USA. EM kevins@itsa.ucsf.edu FU NCI NIH HHS [CA40046, CA72614]; NIEHS NIH HHS [T32ES07106] NR 36 TC 34 Z9 37 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 0888-7543 J9 GENOMICS JI Genomics PD MAY PY 2005 VL 85 IS 5 BP 600 EP 607 DI 10.1016/j.ygeno.2005.01.013 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 920BJ UT WOS:000228662000009 PM 15820312 ER PT J AU Yabe, T Sanagi, T Schwartz, JP Yamada, H AF Yabe, T Sanagi, T Schwartz, JP Yamada, H TI Pigment epithelium-derived factor induces pro-inflammatory genes in neonatal Astrocytes through activation of NF-kappa B and CREB SO GLIA LA English DT Article DE cytokines; glial cells; chemokines; inflammation ID CEREBELLAR GRANULE CELLS; NECROSIS-FACTOR-ALPHA; FACTOR PEDF; TRANSCRIPTION FACTOR; NEUROTROPHIC FACTOR; RESPONSIVE ELEMENT; INTERLEUKIN-6 GENE; NERVOUS-SYSTEM; MOTOR-NEURONS; TUMOR-GROWTH AB Pigment epithelium-derived factor (PEPDF) is a potent and broadly acting neurotrophic factor that protects neurons in various types of cultured neurons against glutamate excitotoxicity and induced-apoptosis. Some of the effects of PEDF reflect specific changes in gene expression, mediated via activation of the transcription factor NF-kappa B in neurons. To investigate whether PEDF also modulates gene expression in astrocytes, we employed the use of RT-PCR to analyze the gene expression of certain pro-inflammatory genes and found that genes such as IL-1 beta, IL-6, TNF-alpha, MIP1 alpha, and MIP3 alpha were induced in PEDF-treated cultured neonatal astrocytes, but not in adult astrocytes. Electrophoresis mobility shift assay (EMSA) revealed that a time- and dose-dependent increase of NF-kappa B- and AP-1-DNA binding activity was observed in PEDF-treated neonatal astrocytes. Furthermore, rapid phosphorylation of CREB protein had occurred in PEDF-treated neonatal astrocytes. Upregulation of pro-inflammatory and AP-1-related genes by PEDF was blocked by overexpression of dominant negative CREB or a mutated form of I kappa B alpha. These results suggest that the induction of pro-inflammatory genes is mediated via activation of NF-kappa B, AP-1, and CREB in neonatal astrocytes. Taken together, these results demonstrate that PEDF is a multipotent factor, capable of affecting not only neurons, but also neonatal astrocytes, and suggests that it may act as a neuroimmune modulator in the developmental brain. (c) 2005 Wiley-Liss, Inc. C1 Kitasato Univ, Kitasato Inst Life Sci, Minato Ku, Tokyo 1088641, Japan. Kitasato Univ, Grad Sch Infect Control Sci, Tokyo 1088641, Japan. NINDS, Neurotroph Factors Sect, NIH, Bethesda, MD 20892 USA. Kitasato Inst, Oriental Med Res Ctr, Tokyo 108, Japan. RP Yabe, T (reprint author), Kitasato Univ, Kitasato Inst Life Sci, Minato Ku, 5-9-1 Shirokane, Tokyo 1088641, Japan. EM tyabe@lisci.kitasato-u.ac.jp NR 54 TC 35 Z9 36 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD MAY PY 2005 VL 50 IS 3 BP 223 EP 234 DI 10.1002/glia.20171 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 914SO UT WOS:000228248200004 PM 15739190 ER PT J AU Dziembowska, M Tham, TN Lau, P Vitry, S Lazarini, F Dubois-Dalcq, M AF Dziembowska, M Tham, TN Lau, P Vitry, S Lazarini, F Dubois-Dalcq, M TI A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors SO GLIA LA English DT Article DE CXCL12; striatal and oligodendrocyte precursors; migration; CXCR4 knockout mice ID CENTRAL-NERVOUS-SYSTEM; CELL-DERIVED FACTOR-1; CHEMOKINE RECEPTOR CXCR4; GLIAL PROGENITOR CELLS; SPINAL-CORD; MESSENGER-RNA; EMBRYONIC EXPRESSION; CEREBRAL-CORTEX; GRANULE CELLS; GROWTH-FACTOR AB Oligodendrocyte development is controlled by a number of survival and migratory factors. The present study shows that signaling of CXCR4 receptor by the chemokine CXCL12 regulates survival and migration of neural precursors (NP) as well as oligodendrocyte progenitors (OP). CXCR4 is expressed by E14 striatal NP and OP generated by neurospheres. In CXCR4-defective mice, the number of NP in neurosphere outgrowth was twofold less than in wild-type (WT) mice; NP radial cell migration was also decreased. In contrast, the addition of CXCL12 to WT NP increased radial migration from the sphere in a dose-dependent manner with a maximal response at 200 nM. When oligodendrocytes differentiated in neurosphere outgrowth, CXCR4 was downregulated. OP isolated from newborn brain coexpressed CXCR4 with platelet-derived growth factor receptor-a (PDGFR alpha) or chondroitin sulfate proteoglycan; receptor expression also decreased during differentiation in vitro. Neonatal OP showed a peak migratory response to 20 nM of CXCL12 in chemotactic chambers, a migration inhibited by a CXCR4 antagonist and anti-CXCL12 antibody. In the embryonic spinal cord, the number of OP-expressing PDGFR(X was reduced more than twofold in CXCR4-defective mice compared with WT and the ratio of ventral to dorsal OP was significantly increased. This indicates a defect in OP survival and their dorsal migration from the ventral cord region, probably because CXCR4(-/-) OP are unable to respond to CXCL12 made by vascular endothelia and the pia mater. We propose that CXCR4 signaling regulate survival and outward chemotactic migration of OP during embryonic and postnatal CNS development. (c) 2005 Wiley-Liss,lnc. C1 Inst Pasteur, Dept Neurosci, Paris, France. RP Dubois-Dalcq, M (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,5B16,B,Ctr Dr MSC, Bethesda, MD 20892 USA. EM mdalcq@pasteur.fr NR 50 TC 132 Z9 141 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0894-1491 J9 GLIA JI Glia PD MAY PY 2005 VL 50 IS 3 BP 258 EP 269 DI 10.1002/glia.20170 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 914SO UT WOS:000228248200007 PM 15756692 ER PT J AU Wenzel, L DeAlba, I Habbal, R Kluhsman, BC Fairclough, D Krebs, LU Anton-Culver, H Berkowitz, R Aziz, N AF Wenzel, L DeAlba, I Habbal, R Kluhsman, BC Fairclough, D Krebs, LU Anton-Culver, H Berkowitz, R Aziz, N TI Quality of life in long-term cervical cancer survivors SO GYNECOLOGIC ONCOLOGY LA English DT Article DE long-term cervical cancer survivorship; quality of life; sexual dysfunction; reproductive concerns ID IMPACT; WOMEN; RADIOTHERAPY; PREVENTION; DIAGNOSIS AB Objectives. To describe the quality of life (QOL) and long-term psychosocial sequelae of women or childbearing age diagnosed with cervical cancer 5-10 years earlier. Methods. Utilizing a cross-sectional descriptive design, 51 cervical cancer survivors and 50 age-matched control,, completed a comprehensive QOL interview. Results.Participants were predominantly married, non-Hispanic White, with a mean age at diagnosis of 37 years and a mean age at interview of 45 years. This disease-free sample enjoys a good QOL, with physical. social, and emotional functioning comparable to or better than comparative norms. However, certain psychological survivorship sequelae and reproductive concerns persist, participants reporting good QOL were less likely to report ongoing coping efforts related to having had this illness and were more likely to report greater social support, greater sexual pleasure, and less cervical cancer-specific distress. In a multiple-regression model. cancer-specific distress, spiritual well-being, maladaptive coping, and reproductive concerns accounted for 72% of the variance in QOL scores. Fifty-nine percent of respondents expressed that they would likely participate in a counseling program today to discuss psychosocial issues raised by having had cervical cancer, and 69% stated that they would have attended a support group program during the initial treatment if it had been offered. Conclusions. This information provides insight into the complex survivorship relationships between QOL and sequelae of cervical cancer for women diagnosed during childbearing years. Therefore, it is important for health care professionals to recognize that aspects of cancer survivorship continue to require attention and possible follow-up care. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92697 USA. Univ Calif Irvine, Ctr Hlth Policy Res 3, Irvine, CA 92697 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. Univ Colorado, Hlth Sci Ctr, Colorado Hlth Outcomes Program, Aurora, CO 80045 USA. Univ Colorado, Sch Nursing, Denver, CO 80262 USA. Harvard Univ, Sch Med, William H Baker Professor Gynecol, Boston, MA 02115 USA. Harvard Univ,Gillette Ctr Womens Careers, Sch Med,New England Trophoblast Dis Ctr, Dana Farber Canc Inst,Donald P Goldstein MD Troph, Brigham & Womens Hosp,Div Gynecol Oncol,Dept Obst, Boston, MA 02115 USA. NCI, DHHS, Off Canc Survirorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Wenzel, L (reprint author), Univ Calif Irvine, Dept Med, Div Epidemiol, Acad Way,Suite 220, Irvine, CA 92697 USA. EM LWenzel@uci.edu FU NCI NIH HHS [P30 CA 46934-10S2] NR 30 TC 108 Z9 112 U1 2 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD MAY PY 2005 VL 97 IS 2 BP 310 EP 317 DI 10.1016/j.ygyno.2005.01.010 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 927WK UT WOS:000229231000002 PM 15863123 ER PT J AU McCluskey, MM Alexander, SB Larkin, BD Murguia, M Wakefield, S AF McCluskey, MM Alexander, SB Larkin, BD Murguia, M Wakefield, S TI An HIV vaccine: As we build it, will they come? SO HEALTH AFFAIRS LA English DT Article ID INFECTION AB Early researchers accurately predicted that AIDS would have a globally destructive impact. However, other experts erroneously believed that they would be able to develop a vaccine against the virus in a relatively short period. More than twenty years later, scientists continue to work to achieve this goal. This paper addresses the unique obstacles faced by HIV vaccine researchers. It concludes with recommendations for how policymakers and public health officials could collaborate with researchers to overcome these obstacles and contribute to the discovery of an HIV vaccine that would save millions of lives. C1 VRC, NIH, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, HIV Vaccine Trials Network, Washington, DC USA. RP McCluskey, MM (reprint author), VRC, NIH, Bethesda, MD USA. EM mmccluskey@nih.gov NR 13 TC 8 Z9 8 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2005 VL 24 IS 3 BP 643 EP 651 DI 10.1377/hlthaff.24.3.643 PG 9 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 924YK UT WOS:000229017000009 PM 15886155 ER PT J AU Landry, S Heilman, C AF Landry, S Heilman, C TI Future directions in vaccines: The payoffs of basic research SO HEALTH AFFAIRS LA English DT Article ID TOLL-LIKE RECEPTORS; GENOME SEQUENCE; PLASMODIUM-FALCIPARUM; IMMUNE-RESPONSES; VIRUS-VACCINE; DISEASE; HIV AB Vaccine development has historically relied on approaches such as live attenuated, subunit, and whole-cell vaccine designs to present antigens to the immune system. These strategies are no longer nimble enough to rapidly address public health threats, particularly emerging infectious diseases. New vaccines will require a strong scientific base partnered with the leveraging of emerging and enabling technologies so that candidate vaccines can be developed more rapidly and with the greatest chance of proving effective. This paper focuses on new strategies, technologies, and immunologic research that will provide important opportunities for the development of new and improved vaccines. C1 US Dept HHS, Natl Vaccine Program Off, Washington, DC USA. NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD USA. RP Landry, S (reprint author), US Dept HHS, Natl Vaccine Program Off, Washington, DC USA. EM cheilman@niaid.nih.gov NR 27 TC 3 Z9 3 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD MAY-JUN PY 2005 VL 24 IS 3 BP 758 EP 769 DI 10.1377/hlthaff.24.3.758 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 924YK UT WOS:000229017000025 PM 15886171 ER PT J AU Wohl, DA Kendall, MA Owens, S Holland, G Nokta, M Spector, SA Schrier, R Fiscus, S Davis, M Jacobson, MA Currier, JS Squires, K Alston-Smith, B Andersen, J Freeman, WR Higgins, M Torriani, FJ AF Wohl, DA Kendall, MA Owens, S Holland, G Nokta, M Spector, SA Schrier, R Fiscus, S Davis, M Jacobson, MA Currier, JS Squires, K Alston-Smith, B Andersen, J Freeman, WR Higgins, M Torriani, FJ CA ACTG 379 Study Team TI The safety of discontinuation of maintenance therapy for cytomegalovirus (CMV) retinitis and incidence of immune recovery uveitis following potent antiretroviral therapy SO HIV CLINICAL TRIALS LA English DT Article DE CMV; discontinuation of therapy; immune reconstitution syndromes; immune recovery uveitis ID VIRUS-INFECTED PATIENTS; ANTICYTOMEGALOVIRUS THERAPY; AIDS PATIENTS; INFLAMMATORY REACTIONS; CIDOFOVIR; VITRITIS; ERA AB Background: Reconstitution of immune function during potent antiretroviral therapy can prompt discontinuation of maintenance cytomegalovirus (CMV) therapy but has also been associated with sight-threatening inflammatory conditions including immune recovery uveitis (IRU). Method: Patients with inactive CMV retinitis and a CD4+ cell count above 100/mm(3), receiving CMV therapy and stable combination antiretroviral therapy, were assigned to one of two groups based on willingness to discontinue CMV therapy. Results: Thirty-eight participants were enrolled: 28 discontinued anti-CMV therapy (Group 1) and 10 continued CMV treatment (Group 2). Median on-study follow-up was 16 months. One Group 1 participant who experienced an increase in plasma HIV viral load and a decline in CD4+ cell count developed confirmed progression of CMV retinitis. Progression or reactivation CMV retinitis was not observed among Group 2. IRU was present at study entry in 3 participants. Six participants in Group 1 and 3 participants in Group 2 developed IRU on-study. CMV viremia was not detected in any participants, and urinary shedding of CMV was intermittent. Conclusion: Recurrence of CMV retinitis following discontinuation of anti-CMV therapy among patients with antiretroviral-induced increases in CD4+ cell count was rare. However, IRU was common in both those who maintained and discontinued anti-CMV therapy. C1 Univ N Carolina, Chapel Hill, NC 27516 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Calif Los Angeles, Los Angeles, CA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Madison, WI USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Los Angeles, CA USA. NIH, Div Aids, Bethesda, MD 20892 USA. Tech Resources Inc, Bethesda, MD USA. RP Wohl, DA (reprint author), Univ N Carolina, CB 7215,211 A W Cameron Ave, Chapel Hill, NC 27516 USA. EM wohl@med.unc.edu RI Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 FU NCRR NIH HHS [M01 RR00046-41S1, RR00046]; NEI NIH HHS [U10 EY08067]; NIAID NIH HHS [AI25868, AI-3885, AI27670, AI27673] NR 28 TC 15 Z9 19 U1 0 U2 1 PU THOMAS LAND PUBLISHERS, INC PI ST LOUIS PA 255 JEFFERSON RD, ST LOUIS, MO 63119 USA SN 1528-4336 J9 HIV CLIN TRIALS JI HIV Clin. Trials PD MAY-JUN PY 2005 VL 6 IS 3 BP 136 EP 146 DI 10.1310/4J65-4YX1-4ET6-E5KR PG 11 WC Infectious Diseases; Pharmacology & Pharmacy SC Infectious Diseases; Pharmacology & Pharmacy GA 963PE UT WOS:000231815500002 PM 16192248 ER PT J AU Buchsbaum, BR Greer, S Chang, WL Berman, KF AF Buchsbaum, BR Greer, S Chang, WL Berman, KF TI Meta-analysis of neuroimaging studies of the Wisconsin card-sorting task and component processes SO HUMAN BRAIN MAPPING LA English DT Article DE Wisconsin Card-Sorting Test; neuroiniaging; meta-analysis; response-suppression; task-switching; executive cognition ID INFERIOR PREFRONTAL CORTEX; EVENT-RELATED FMRI; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; RESPONSE-INHIBITION TASK; WORKING-MEMORY; FRONTAL-CORTEX; TRANSIENT ACTIVATION; EXECUTIVE FUNCTIONS; COGNITIVE CONTROL AB A quantitative meta-analysis using the activation likelihood estimation (ALE) method was used to investigate the brain basis of the Wisconsin Card-Sorting Task (WCST) and two hypothesized component processes, task switching and response suppression. All three meta-analyses revealed distributed frontoparietal activation patterns consistent with the status of the WCST as an attention-demanding executive task. The WCST was associated with extensive bilateral clusters of reliable cross-study activity in the lateral prefrontal cortex, anterior cingulate cortex, and inferior parietal lobule. Task switching revealed a similar, although less robust, frontoparietal pattern with additional clusters of activity in the opercular region of the ventral prefrontal cortex, bilaterally. Response-suppression tasks, represented by studies of the go/no-go paradigm, showed a large and highly right-lateralized region of activity in the right prefrontal cortex. The activation patterns are interpreted as reflecting a neural fractionation of the cognitive components that must be integrated during the performance of the WCST. (c) 2005 Wiley-Liss, Inc. C1 NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH,IRP,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Buchsbaum, BR (reprint author), NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, NIH,IRP,Dept Hlth & Human Serv, 9000 Rockville Pike,Bldg 10,Room 4C-101, Bethesda, MD 20892 USA. EM buchsbab@intra.nimh.nih.gov NR 86 TC 209 Z9 212 U1 5 U2 46 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD MAY PY 2005 VL 25 IS 1 BP 35 EP 45 DI 10.1002/hbm.20128 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 921JE UT WOS:000228759600004 PM 15846821 ER PT J AU Wang, JH Cawley, NX Voutetakis, A Rodriguez, YM Goldsmith, CM Nieman, LK Hoque, ATMS Frank, SJ Snell, CR Loh, YP Baum, BJ AF Wang, JH Cawley, NX Voutetakis, A Rodriguez, YM Goldsmith, CM Nieman, LK Hoque, ATMS Frank, SJ Snell, CR Loh, YP Baum, BJ TI Partial redirection of transgenic human growth hormone secretion from rat salivary glands SO HUMAN GENE THERAPY LA English DT Article ID PERIPHERAL MEMBRANE-PROTEIN; PATHWAY-SORTING RECEPTOR; GRANULE CONTENT PROTEINS; MEDIATED GENE-TRANSFER; CARBOXYPEPTIDASE-E; ENDOCRINE SECRETION; NEUROENDOCRINE CELLS; SUBMANDIBULAR-GLANDS; HUMAN PROINSULIN; EXOCRINE GLANDS AB Regulated secretory pathway proteins, when delivered as transgenes to salivary glands, are secreted predominantly into saliva. This is not useful for those proteins whose therapeutic function is required systemically, for example, human growth hormone (hGH). One strategy to improve the efficiency of hGH secretion into the bloodstream involves manipulation of existing sorting signals. The C terminus of hGH is highly conserved and contains a domain similar to the regulated pathway sorting domain of pro-opiomelanocortin ( POMC). We hypothesized that, similar to POMC, mutation of this domain would divert hGH secretion from the regulated to the constitutive pathway, which in salivary glands leads to the bloodstream. Several mutations were made in the C terminus of the hGH cDNA and tested in vitro. One biologically active mutant containing E174A and E186A substitutions, and with an included C-terminal extension, was studied in greater detail. Compared with wild-type hGH, we found that this mutant hGH accumulated in the Golgi/trans-Golgi network and showed increased basal secretion in AtT20 cells, a model endocrine cell line. Importantly, in vivo, the mutant hGH displayed a relative increase in the proportion of constitutive pathway secretion seen from rat salivary glands, with a significantly lower saliva-versus-serum secretion ratio (p = 0.03). Although this mutant is unlikely to be therapeutically beneficial, these results suggest that the final destination of a transgenic secretory protein may be controlled by reengineering its sorting determinants. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Dev Neurobiol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Endocrinol Diabet & Metab, Birmingham, AL 35294 USA. Medivir UK, Cambridge CB1 9PT, England. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Dept Hlth & Human Serv, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov; bbaum@dir.nidcr.nih.gov FU NIDDK NIH HHS [DK46395] NR 47 TC 17 Z9 18 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAY PY 2005 VL 16 IS 5 BP 571 EP 583 DI 10.1089/hum.2005.16.571 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 931RR UT WOS:000229503300004 PM 15916482 ER PT J AU Kernochan, LE Russo, ML Woodling, NS Huynh, TN Avila, AM Fischbeck, KH Sumner, CJ AF Kernochan, LE Russo, ML Woodling, NS Huynh, TN Avila, AM Fischbeck, KH Sumner, CJ TI The role of histone acetylation in SMN gene expression SO HUMAN MOLECULAR GENETICS LA English DT Article ID SPINAL MUSCULAR-ATROPHY; VALPROIC ACID INCREASES; MOTOR-NEURON PROTEIN; CELLULAR-DIFFERENTIATION; SINGLE NUCLEOTIDE; PROMOTER ANALYSIS; COMPLEX; CELLS; PHENYLBUTYRATE; IDENTIFICATION AB Increasing survival motor neuron 2 (SMN2) gene expression may be an effective strategy for the treatment of spinal muscular atrophy (SMA). Histone deacetylase (HDAC) inhibitors have been shown to increase SMN transcript and protein levels, but the specific role of histone acetylation in regulating SMN gene expression has not been explored. Using chromatin immunopreciptation, we investigated the levels of acetylated H3 and H4 histones and HDACs associated with different regions of the human and mouse SMN genes in both cultured cells and tissues. We show that the SMN gene has a reproducible pattern of histone acetylation that is largely conserved among different tissues and species. A limited region of the promoter surrounding the transcriptional start site has relatively high levels of histone acetylation, whereas regions further upstream or downstream have lower levels. After HDAC inhibitor treatment, acetylated histone levels increased, particularly at upstream regions, correlating with a 2-fold increase in promoter activity. During development in mouse tissues, histone acetylation levels decreased and associated HDAC2 levels increased at the region closest to the transcriptional start site, correlating with a 40-60% decrease in SMN transcript and protein levels. These data indicate that histone acetylation modulates SMN gene expression and that pharmacological manipulation of this epigenetic determinant is feasible. HDAC2, in particular, may be a future therapeutic target for SMA. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Sumner, CJ (reprint author), NINDS, Neurogenet Branch, NIH, Bldg 35,Room 2A-1010,35 Convent Dr, Bethesda, MD 20892 USA. EM sumnerc@ninds.nih.gov FU NINDS NIH HHS [K22 NS048199, K22-NS0048199-01] NR 44 TC 97 Z9 97 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAY 1 PY 2005 VL 14 IS 9 BP 1171 EP 1182 DI 10.1093/hmg/ddi130 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 922JZ UT WOS:000228835500007 PM 15772088 ER PT J AU Thompson, MA Stumph, J Henrickson, SE Rosenwald, A Wang, Q Olson, S Brandt, SJ Roberts, J Zhang, XQ Shyr, Y Kinney, MC AF Thompson, MA Stumph, J Henrickson, SE Rosenwald, A Wang, Q Olson, S Brandt, SJ Roberts, J Zhang, XQ Shyr, Y Kinney, MC TI Differential gene expression in anaptastic lymphoma kinase-positive and anaplastic lymphoma kinase-negative anaplastic large cell lymphomas SO HUMAN PATHOLOGY LA English DT Article DE ALCL; microarray analysis; ALK expression; cyclin D3 ID NON-HODGKINS-LYMPHOMA; CYCLIN D3 EXPRESSION; CHROMOSOMAL TRANSLOCATION; SCALE ANALYSIS; ALK; NUCLEOPHOSMIN; NPM; IDENTIFICATION; TRANSFORMATION; FUSION AB Anaplastic large cell lymphoma (ALCL) is an aggressive large T- or null-cell lymphoma. Most ALCLs arising in children and young adults express a constitutively active receptor tyrosine kinase, anaplastic lymphoma kinase (ALK). Anaplastic large cell lymphomas lacking ALK are clinically heterogeneous and their pathogenesis is unknown. This study is the first complementary DNA (cDNA) microarray analysis using RNA extracted from tumor tissue (7 ALK+ ALCLs and 7 ALK- ALCLs) to identify genes differentially expressed or shared between the ALK+ and ALK- tumors. Unsupervised hierarchical clustering using the top 11 most statistically significant discriminator cDNAs correctly grouped all ALK+ and ALK- tumors. Hierarchical clustering analysis using the 44 cDNAs with the greatest differential expression between ALK+ and ALK- RNAs grouped 6 of 7 ALK+ ALCLs together and I ALK+ ALCL with the ALK- group. In general, ALK+ tumors overexpress genes encoding signal transduction molecules (SYK, LYN, CDC37) and underexpress transcription factor genes (including HOXC6 and HOXA3) compared with the ALK- group. Cyclin D3 was overexpressed in the ALK+ group and the cell cycle inhibitor p19INK4D was decreased in the ALK- group, suggesting different mechanisms of promoting G(1)/S transition. Both groups had similar proliferation rates. Genes highly expressed in both ALK- and ALK+ ALCLs included kinases (LCK, protein kinase C, vav2, and NKIAMRE) and antiapoptotic molecules, suggesting possible common pathogenetic mechanisms as well. (c) 2005 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. RP Thompson, MA (reprint author), Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA. EM mary.ann.thompson@vanderbilt.edu FU NIGMS NIH HHS [T32 GM007753] NR 35 TC 60 Z9 64 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD MAY PY 2005 VL 36 IS 5 BP 494 EP 504 DI 10.1016/j.humpath.2005.03.004 PG 11 WC Pathology SC Pathology GA 937JO UT WOS:000229920600007 PM 15948116 ER PT J AU Bhagtani, R AF Bhagtani, R TI Around the world - biomedical engineering in Vietnam today SO IEEE ENGINEERING IN MEDICINE AND BIOLOGY MAGAZINE LA English DT Article C1 Tufts Univ, Medford, MA 02155 USA. Northwestern Univ, Evanston, IL 60208 USA. Natl Inst Hlth, Bethesda, MD USA. George Washington Univ, Washington, DC USA. Harvard Univ, MIT, Cambridge, MA 02138 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Bhagtani, R (reprint author), Tufts Univ, Medford, MA 02155 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0739-5175 J9 IEEE ENG MED BIOL JI IEEE Eng. Med. Biol. Mag. PD MAY-JUN PY 2005 VL 24 IS 3 BP 7 EP + PG 6 WC Engineering, Biomedical; Medical Informatics SC Engineering; Medical Informatics GA 928BS UT WOS:000229246700007 ER PT J AU Hayes, SM Li, LQ Love, PE AF Hayes, SM Li, LQ Love, PE TI TCR signal strength influences alpha beta/gamma delta lineage fate SO IMMUNITY LA English DT Article ID T-CELL-RECEPTOR; GAMMA-TRANSGENIC MICE; EPSILON-RI-GAMMA; THYMOCYTE SELECTION; ZETA-CHAIN; LYMPHOCYTE DEVELOPMENT; MURINE THYMOCYTES; BETA; PRE; GENE AB Signals transduced by T cell antigen receptors (TCRs) have been shown to be critical for alpha beta and gamma delta T cell development, but their role in lineage determination remains poorly defined. Two models have been forwarded for alpha beta/gamma delta lineage choice: the instructive model and the stochastic model. Recent data, however, are inconsistent with either model. In this study, we devised an experimental system in which lineage fate was controlled exclusively by the gamma delta TCR. We then analyzed the impact of TCR signal strength on alpha beta/gamma delta lineage development by altering the surface expression or signaling potential of the gamma delta TCR complex. We found that increasing the gamma delta TCR signal strength favored gamma delta lineage development, whereas weakening the gamma delta TCR signal favored up lineage development. These results support a model in which the strength of the TCR signal is a critical determinant in the lineage fate decision. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM lovep@mail.nih.gov NR 46 TC 145 Z9 147 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2005 VL 22 IS 5 BP 583 EP 593 DI 10.1016/j.immuni.2005.03.014 PG 11 WC Immunology SC Immunology GA 930WG UT WOS:000229447200008 PM 15894276 ER PT J AU Bennasser, Y Le, SY Benkirane, M Jeang, KT AF Bennasser, Y Le, SY Benkirane, M Jeang, KT TI Evidence that HIV-1 encodes an siRNA and a suppressor of RNA silencing SO IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SMALL INTERFERING RNA; DOUBLE-STRANDED-RNA; TRANSACTIVATOR GENE; VIRAL SUPPRESSOR; ANIMAL VIRUS; IN-VIVO; TAT; INFECTION; IMMUNITY AB In plants and invertebrate animals, RNA silencing is a form of nucleic acid-based adaptive immunity. By contrast, jawed vertebrates have evolved complex protein-based adaptive immunity. Although short interfering RNAs (siRNAs) have been used as artificial tools to silence viral infection in human cells, it remains unknown whether mammalian viruses naturally elicit such immunity in vertebral cells. Here, we report the evidence that HIV-1 encodes viral siRNA precursors in its genome and that natural HIV-1 infection provokes nucleic acid-based immunity in human cells. To combat this cellular defense, HIV-1 has evolved in its Tat protein a suppressor of RNA silencing (SRS) function. Tat abrogates the cell's RNA-silencing defense by subverting the ability of Dicer to process precursor double-stranded RNAs into siRNAs. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, Canc Res Ctr, Frederick, MD 21702 USA. CNRS, Mol Virol Lab, Inst Genet Humaine, UPR 1142, Montpellier, France. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 55 TC 305 Z9 334 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAY PY 2005 VL 22 IS 5 BP 607 EP 619 DI 10.1016/j.immune.2005.03.010 PG 13 WC Immunology SC Immunology GA 930WG UT WOS:000229447200010 PM 15894278 ER PT J AU Diaw, L Roth, M Schwinn, DA d'Alelio, ME Green, LJ Tangrea, JA AF Diaw, L Roth, M Schwinn, DA d'Alelio, ME Green, LJ Tangrea, JA TI Characteristics of a human prostate stromal cell line related to its use in a stromal-epithelial coculture model for the study of cancer chemoprevention SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE cell line; nuclear receptors; growth factors; MMP ID GROWTH-FACTOR BETA-1; VITAMIN-D-RECEPTOR; ANDROGEN RECEPTOR; MATRIX METALLOPROTEINASES; BINDING-PROTEINS; PRIMARY CULTURES; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; 1,25-DIHYDROXYVITAMIN D-3; TISSUE INHIBITOR AB An immortalized human prostate stromal cell line (PS30) was previously established using recombinant retrovirus encoding human papillornavirus 16 gene products. In this study, we further characterize this stromal cell line for its potential use in a stromal-epithelial coculture model for prostate cancer prevention. Using reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, and immunocytochemistry, we examined expression of an, prostate-specific antigen (PSA), transforming growth factor-beta (TGF-beta), drogen receptor (AR), vitamin D receptor (VDR). and insulin-like growth factors (IGF) families and their receptors, metalloprotemases (MMP) MMP-2 and MMP-9, as well Lis the cells' ability to respond to the synthetic androgen R1881. The PS30 stromal cells do not express PSA, confirming their stromal origin. They are positive for both AR messenger ribonucleic acid (mRNA) and protein, however, they do not respond to growth stimulation by the synthetic androgen R1881. The PS30 cells express mRNA for VDR, TGF-beta s, IGFs and their receptors, as well as the MMPs. Moreover, they produce significant amounts of TGF-beta 1, TGF-beta 2, IGFBP-3, and MMP-2 proteins. Our observations confirm the use of PS30 for the study of stromal-epithelial interactions in the modulation of prostate carcinogenesis. C1 NCI, SAIC Frederick Inc, Ctr Adv Technol, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, NIH, Rockville, MD USA. Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. RP Diaw, L (reprint author), NCI, SAIC Frederick Inc, Ctr Adv Technol, Bethesda, MD 20892 USA. EM diawl@mail.nih.gov FU PHS HHS [N01 C0 12400] NR 60 TC 2 Z9 2 U1 0 U2 1 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD MAY-JUN PY 2005 VL 41 IS 5-6 BP 142 EP 148 PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 964WY UT WOS:000231912900003 PM 16153146 ER PT J AU Yu, SQ Gu, XX AF Yu, SQ Gu, XX TI Synthesis and characterization of lipooligosaccharide-based conjugate vaccines for serotype B Moraxella catarrhalis SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; BRANHAMELLA-CATARRHALIS; OTITIS-MEDIA; PULMONARY CLEARANCE; DETOXIFIED LIPOOLIGOSACCHARIDE; LIPOPOLYSACCHARIDE ANTIGENS; MONOCLONAL-ANTIBODY; IMMUNE-RESPONSE; BINDING PROTEIN; ANIMAL-MODEL AB Moraxella catarrhalis is an important cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium that elicits bactericidal antibodies. Serological studies show that three major LOS types (A, B, and C) have been identified among clinical isolates. Our previous studies demonstrated that the type A LOS-based conjugates were immunogenic in animals. In this study, LOS from type B strain 26397 was detoxitied and conjugated to tetanus toxoid (TT) or a cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT and dLOS-CRM, respectively, as vaccine candidates. The molar ratios of dLOS to TT and CRM in the conjugates were 43:1 and 19:1, respectively, while both weight ratios were around 0.9. The antigenicity of the conjugates was similar to that of the LOS, as determined by enzyme-linked immunosorbent assay using a rabbit antiserum to strain 26397. Subcutaneous immunization with each conjugate elicited a 180- to 230-fold rise of serum anti-LOS immunoglobulin G in mice and > 2,000-fold rise in rabbits. In addition, both mouse and rabbit antisera showed elevated complement-mediated bactericidal activity against the homologous strain, and a representative rabbit antiserum showed bactericidal activity against nine of twelve clinical isolates studied. The bactericidal activity of the rabbit antiserum can be fully inhibited by the type B LOS but not the A or C LOS. These results indicate that the type B LOS-based conjugates can be used as vaccine components for further investigation. C1 Natl Inst Deafness & Other Commun Disorders, Vaccine Res Facil, Rockville, MD USA. RP Gu, XX (reprint author), 5 Res Court,Room 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov NR 59 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 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2005 VL 73 IS 5 BP 2790 EP 2796 DI 10.1128/IAI.73.5.2790-2796.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 919EE UT WOS:000228600300024 PM 15845482 ER PT J AU Guyard, C Chester, EM Raffel, SJ Schrumpf, ME Policastro, PF Porcella, SF Leong, JA Schwan, TG AF Guyard, C Chester, EM Raffel, SJ Schrumpf, ME Policastro, PF Porcella, SF Leong, JA Schwan, TG TI Relapsing fever spirochetes contain chromosomal genes with unique direct tandemly repeated sequences SO INFECTION AND IMMUNITY LA English DT Article ID PROTEIN SECONDARY STRUCTURE; LYME-DISEASE SPIROCHETE; BORRELIA-BURGDORFERI; UREAPLASMA-UREALYTICUM; PHENOTYPIC VARIATION; STRUCTURE PREDICTION; MULTIGENE FAMILY; IDENTIFICATION; HERMSII; ANTIGEN AB Genome sequencing of the relapsing fever spirochetes Borrelia hermsii and Borrelia turicatae identified three open reading frames (ORFs) on the chromosomes that contained internal, tandemly repeated amino acid sequences that were absent in the Lyme disease spirochete Borrelia burgdorferi. The predicted amino acid sequences of these genes (BH0209, BH0512, and BH0553) have hydrophobic N termini, indicating that these proteins may be secreted. B. hermsii transcribed the three ORFs in vitro, and the BH0512- and BH0553-encoded proteins (PBH-512 and PBH-553) were produced in vitro and in experimentally infected mice. PBH-512 and PBH-553 were on the spirochete's outer surface, and antiserum to these proteins reduced the adherence of B. hermsii to red blood cells. PCR analyses of 28 isolates of B. hermsii and 8 isolates of B. turicatae demonstrated polymorphism in each gene correlated with the number of repeats. Serum samples from relapsing fever patients reacted with recombinant PBH-512 and PBH-553, suggesting that these proteins are produced during human infection. These polymorphic proteins may be involved in the pathogenicity of these relapsing fever spirochetes and provide a mechanism for antigenic heterogeneity within their populations. C1 Univ Massachusetts, Med Ctr, Dept Mol Genet & Microbiol, Worcester, MA 01605 USA. RP Guyard, C (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM eguyard@niaid.nih.gov OI , cyril/0000-0002-2721-0097 NR 47 TC 7 Z9 7 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 MAY PY 2005 VL 73 IS 5 BP 3025 EP 3037 DI 10.1128/IAI.73.5.3025-3037.2005 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 919EE UT WOS:000228600300052 PM 15845510 ER PT J AU Li, HL Xu, L Wang, JP Wen, YM Voung, C Otto, M Gao, Q AF Li, HL Xu, L Wang, JP Wen, YM Voung, C Otto, M Gao, Q TI Conversion of Staphylococcus epidermidis strains from commensal to invasive by expression of the ica locus encoding production of biofilm exopolysaccharide SO INFECTION AND IMMUNITY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN/HEMAGGLUTININ; CATHETER-ASSOCIATED INFECTION; FOREIGN-BODY INFECTION; RAT MODEL; PATHOGENESIS; ADHESION; PHASE AB To test if biofilm formation in Staphylococcus epidermidis is dependent on the polysaccharide intercellular adhesin, whose biosynthesis is driven by the ica locus, a plasmid containing the ica locus was transferred to three ica-negative strains. Using in vitro biofilm assays and a rat central venous catheter infection model, we confirmed the importance of the ica locus for biofilm production and pathogenesis of S. epidermidis. C1 Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol, Shanghai 200032, Peoples R China. NIAID, Rocky Mt Lab, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Gao, Q (reprint author), 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China. EM qiangao@shmu.edu.cn OI Otto, Michael/0000-0002-2222-4115 NR 17 TC 55 Z9 60 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2005 VL 73 IS 5 BP 3188 EP 3191 DI 10.1128/IAI.73.5.3188-3191.2005 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 919EE UT WOS:000228600300073 PM 15845531 ER PT J AU Seo, JY Lee, JH Kim, NW Her, E Chang, SH Ko, NY Yoo, YH Kim, JW Seo, DW Han, JW Kim, YM Choi, WS AF Seo, JY Lee, JH Kim, NW Her, E Chang, SH Ko, NY Yoo, YH Kim, JW Seo, DW Han, JW Kim, YM Choi, WS TI Effect of a fennented ginseng extract, BST204, on the expression of cyclooxygenase-2 in murine macrophages SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE COX-2; PGE(2); BST204; fermented ginseng extract; p70 S6 kinase ID NITRIC-OXIDE SYNTHASE; KAPPA-B ACTIVATION; PROSTAGLANDIN SYNTHASE; MESSENGER-RNA; CANCER CELLS; SUPPRESSION; INHIBITION; COX-2; LIPOPOLYSACCHARIDE; PROLIFERATION AB This paper investigates how BST204, a fermented ginseng extract, affects the expression and mechanism of cyclooxygenase-2 (COX-2). BST204 was prepared by incubating crude ginseng extract with ginsenoside-beta-glucosidase. Unexpectedly, BST204 had no effect on the level of COX-2 protein in unstimulated RAW 264.7 cells, and it suppressed the level of COX-2 protein and PGE(2) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It did not show any suppressive effect, though, on the COX-2 mRNA level. To investigate the suppressive mechanism of COX-2 protein, the activating phosphorylation of p70 S6 kinase and 4E-BP1, which are important for translation, were measured. The phosphorylation of p70 S6 kinase, not 4E-BP1, was increased by LPS in a time-dependent manner, and was inhibited by BST204 in a dose-dependent manner. The expression of COX-2 protein, however, was partially suppressed by rapamycin, an upstream inhibitor of p70 S6 kinase. Therefore, this paper suggests that the suppression of COX-2 protein by BST204 was partially correlated with the inhibition of p70 S6 kinase activation. (c) 2005 Elsevier B.V. All rights reserved. C1 Konkuk Univ, Dept Immunol, Coll Med, Chungju 380701, South Korea. Biosapogen, Gyeonggi Do 462120, South Korea. NCI, Pathol Lab, NIH, Rockville, MD 20852 USA. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. Duksung Womens Univ, Coll Pharm, Seoul 132714, South Korea. RP Choi, WS (reprint author), Konkuk Univ, Dept Immunol, Coll Med, Chungju 380701, South Korea. EM wahnchoi@kku.ac.kr NR 31 TC 24 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD MAY PY 2005 VL 5 IS 5 BP 929 EP 936 DI 10.1016/j.intimp.2005.01.008 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 914JB UT WOS:000228222600012 PM 15778128 ER PT J AU Huleihel, M Talishanisky, M Ford, H Marquez, VE Kelley, JA Johns, DG Agbaria, R AF Huleihel, M Talishanisky, M Ford, H Marquez, VE Kelley, JA Johns, DG Agbaria, R TI Dynamics of the antiviral activity of N-methanocarbathymidine against herpes simplex virus type 1 in cell culture SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE herpes simplex virus; herpes simplex thymidine kinase; N-methanocarbathymidine; ganciclovir; antiviral activity; phosphorylation ID INDUCED DNA-POLYMERASES; THYMIDINE KINASE; 9-(1,3-DIHYDROXY-2-PROPOXYMETHYL)GUANINE; 9-(2-HYDROXYETHOXYMETHYL)GUANINE; INHIBITION; ANALOGS; PHOSPHORYLATION; TRIPHOSPHATES; ACYCLOVIR; COMPOUND AB N-Methanocarbathymidine [(N)-MCT], a thymidine analogue, exhibits potent activity in cell culture against herpes simplex virus I (HSV-1). (N)-MCT showed higher antiviral activity than ganciclovir (GCV). Continuous treatment of Vero cells with (N)-MCT immediately or 10 h post-infection (p.i.) fully prevented the development of viral infection. However, when infected cells were treated with (N)-MCT at 12 h p.i., there was only a partial inhibition (ca. 50%). Additionally, continuous treatment of infected cells with (N)-MCT for about 48 h was sufficient to achieve full prevention of viral infection without further treatment. These findings suggest the complete loss of herpes simplex thymidine kinase (HSV-tk) activity occurs after 48 h of treatment with (N)-MCT. This study helps to understand the mechanism and dynamics of antiHSV activity of (N)-MCT, which is necessary for its future development as an antiviral drug. (C) 2005 Published by Elsevier B.V. and the International Society of Chemotherapy. C1 Ben Gurion Univ Negev, Inst Appl Biosci, IL-84105 Beer Sheva, Israel. NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RP Huleihel, M (reprint author), Ben Gurion Univ Negev, Inst Appl Biosci, POB 653, IL-84105 Beer Sheva, Israel. EM mahmoudh@bgumail.bgu.ac.il RI HULEIHEL, MAHMOUD/F-1837-2012 NR 24 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD MAY PY 2005 VL 25 IS 5 BP 427 EP 432 DI 10.1016/j.ijantimicag.2005.01.013 PG 6 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 929YE UT WOS:000229381700011 PM 15848299 ER PT J AU Hatch, EE Linet, MS Zhang, JY Fine, HA Shapiro, WR Selker, RG Black, PM Inskip, PD AF Hatch, EE Linet, MS Zhang, JY Fine, HA Shapiro, WR Selker, RG Black, PM Inskip, PD TI Reproductive and hormonal factors and risk of brain tumors in adult females SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE brain tumors; reproductive factors; glioma; meningioma; parity; age at menarche; case-control study ID CENTRAL NERVOUS-SYSTEM; BREAST-CANCER RISK; POSTMENOPAUSAL WOMEN; MEDICAL CONDITIONS; BINDING GLOBULIN; URINE ESTROGENS; 1ST PREGNANCY; UNITED-STATES; SEX; AGE AB Causes of brain tumors are largely unknown, and there is an urgent need to identify possible risk factors. Several observations point to a possible role of reproductive hormones, but few epidemiologic studies have examined whether reproductive factors, such as age at menarche and parity, are associated with brain tumor risk. We conducted a multi-center case-control study of newly diagnosed glioma (n = 212) and meningioma (n = 151) and frequency-matched controls (n = 436) in women from hospitals in Phoenix, Arizona; Boston, Massachusetts; and Pittsburgh, Pennsylvania between 1994 and 1998. Research nurses interviewed patients regarding potential risk factors for brain tumors, including reproductive factors and hormone use. Unconditional logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Risk of glioma increased with older age at menarche [OR = 1.90 (95% CI = 1.09-3.32) for age at menarche greater than or equal to 14 vs. < 12 years]. Early age at first birth was associated with reduced risk of glioma [OR = 0.43 (95% CI = 0.23-0.83) for a first birth before age 20 vs. nulliparity], but there was little effect of number of births. Exogenous hormone use was also associated with a lower risk of glioma, but risks did not vary systematically according to duration of use or age at first use. Possibly owing to low statistical power, there were few noteworthy associations between meningioma and reproductive factors, other than a nonsignificant (p = 0.09) trend of increasing risk with increasing age at menopause. The findings suggest that hormonal exposures early in life may be associated with risk of glioma, but the evidence is inconsistent and does not point clearly to a specific causal or protective hypothesis. (C) 2004 Wiley-Liss, Inc. C1 Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NCI,NIH,DHHS, Rockville, MD USA. NCI, Neurooncol Branch, NIH, DHHS,, Bethesda, MD 20892 USA. St Josephs Hosp, Barrow Neurol Inst, Dept Neurol, Phoenix, AZ USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. RP Hatch, EE (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 715 Albany St, Boston, MA 02118 USA. EM eehatch@bu.edu OI Hatch, Elizabeth/0000-0001-7901-3928 NR 59 TC 61 Z9 65 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAY 1 PY 2005 VL 114 IS 5 BP 797 EP 805 DI 10.1002/ijc.20776 PG 9 WC Oncology SC Oncology GA 904YX UT WOS:000227535600014 PM 15609304 ER PT J AU Mobasheri, A Airley, R Hewitt, SM Marples, D AF Mobasheri, A Airley, R Hewitt, SM Marples, D TI Heterogeneous expression of the aquaporin 1 (AQP1) water channel in tumors of the prostate, breast, ovary, colon and lung: A study using high density multiple human tumor tissue microarrays SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE aquaporin 1; water channel; cancer; angiogenesis; vascular permeability; multiple tumor microarray; immunohistochemistry; histomorphometric analysis ID RENAL-CELL CARCINOMA; HUMAN BRAIN-TUMORS; ANGIOGENESIS; EDEMA; METABOLISM; INDUCTION; MEDICINE; FAILURE; DISEASE; TRACT AB Aquaporin 1 (AQP 1) water channels are membrane proteins that control the permeability of endothelial and epithelial barriers by facilitating water movement across cell membranes. Recent studies suggest that AQP1 may be responsible for the high vascular permeability and interstitial fluid pressure in tumors of the brain, colon, breast and pancreas. AQP1 may also play a role in tumor angiogenesis and may be involved in development of effusions or edema fluid. The aim of the present study was to use immunohistochemistry and semi-quantitative histomorphometric analysis to compare the distribution and relative abundance of AQP I on NCI TARP human multiple tumor tissue microarrays (TMAs) with normal tissues represented on the CHTN TMAs. Immunohistochemistry and semi-quantitative histomorphometric analysis were used to compare the distribution of AQP1 in tumors of the prostate, colon, lung, breast and ovary represented on TARP TMAs with their normal counterparts on CHTN TMAs. AQP1 was expressed in capillary endothelia of all normal tissues. In most tumors AQP1 was confined to endothelial barriers. AQP1 expression was marginally higher in rnicrovascular structures in prostate and ovarian tumors and was hi-her in advanced mammary and colorectal carcinomas where AQP1 immunoreactivity was also seen in some neoplastic tumor cells. In conclusion, the AQP1 water channel is an excellent rnarker of microvasculature but it is hetero-geneously expressed in different human tumors and not necessarily expressed in all neoplastic cells. Increased AQP1 expression in some human adenocarcinomas may be a consequence of angiogenesis and important for the formation or clearance of tumour or edema. C1 Univ Liverpool, Mol Pathogenesis & Connect Tissue Res Grp, Fac Vet Sci, Liverpool L69 7ZJ, Merseyside, England. Liverpool John Moores Univ, Sch Pharm & Chem, Tumor Metab & Therapeut Res Grp, Liverpool L3 3AF, Merseyside, England. NCI, Tissue Array Res Program, Pathol Lab, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. Univ Leeds, Sch Biomed Sci, Leeds LS2 9NQ, W Yorkshire, England. RP Mobasheri, A (reprint author), Univ Liverpool, Mol Pathogenesis & Connect Tissue Res Grp, Fac Vet Sci, Liverpool L69 7ZJ, Merseyside, England. EM a.mobasheri@liverpool.ac.uk OI Hewitt, Stephen/0000-0001-8283-1788 NR 44 TC 57 Z9 86 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD MAY PY 2005 VL 26 IS 5 BP 1149 EP 1158 PG 10 WC Oncology SC Oncology GA 916TX UT WOS:000228410200001 PM 15809704 ER PT J AU Okunieff, P Cornelison, T Mester, M Liu, WM Ding, I Chen, YY Zhang, H Williams, JP Finkelstein, J AF Okunieff, P Cornelison, T Mester, M Liu, WM Ding, I Chen, YY Zhang, H Williams, JP Finkelstein, J TI Mechanism and modification of gastrointestinal soft tissue response to radiation: Role of growth factors SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Symposium on Normal Tissue Biologic Response Modifiers CY JUN 27, 2003 CL Montreal, CANADA SP Radiat Therapy Oncol Grp DE radiation damage; bowel; soft tissue response; growth factors; cytokines ID NECROSIS-FACTOR-ALPHA; STEM-CELL FACTOR; FACTOR-BETA; BONE-MARROW; PULMONARY FIBROSIS; MESSENGER-RNA; IN-VIVO; MICE; IRRADIATION; EXPRESSION AB Purpose: The negative effects of radiation on the bowel critically limit the treatment doses possible for tumors in the abdomen. The purpose of the present study was to measure mRNA levels of inflammatory cytokines in abdominally irradiated mouse bowel. Methods and Materials: Eight- to 12-week-old DBA mice were irradiated to the whole bowel in single fractions of 0 (mock irradiation), 12.5, or 13.5 Gy, and sacrificed 18-25 weeks thereafter. Gross bowel reactions were scored for bowel retraction, bowel wall thickening, mesenteric telangiectasia, and petechia. Tissues were snap frozen and processed for RNase protection assay or reverse transcription polymerase chain reaction assay, or both. Transforming growth factor beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, tumor necrosis factor alpha, interleukin-6, and interferon gamma mRNA were measured. Results: Radiation at 12.5 Gy and at 13.5 Gy produced significant bowel damage. Levels of all cytokines in irradiated mice were significantly increased (p < 0.05). Conclusions: Late radiation-related bowel fibrovascular toxicity includes cytokine signal pathways that parallel those of many other normal tissues. These cytokine responses include elevations of tumor necrosis factor a, TGF beta 1, and interleukin-6. There exist approaches for lowering these cytokine levels that do not also protect tumor, and thus a therapeutic gain is expected. Opportunities to use these cytokine measurements both to predict clinical toxicity and to develop interventions are discussed. (c) 2005 Elsevier Inc. C1 Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Pediat, Rochester, NY 14642 USA. NCI, Div Canc Prevent, NIH, Rockville, MD USA. Hosp Clin Sao Paulo, Colorectal Unit, Sao Paulo, Brazil. NCI, Organ Syst Branch, NIH, Bethesda, MD USA. RP Okunieff, P (reprint author), Univ Rochester, Med Ctr, James P Wilmot Canc Ctr, Dept Radiat Oncol, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. EM Paul_Okunieff@URMC.Rochester.edu FU NCI NIH HHS [1R13CA100307-01, P01-CA11051-30] NR 51 TC 24 Z9 26 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAY 1 PY 2005 VL 62 IS 1 BP 273 EP 278 DI 10.1016/j.ijrobp.2005.01.034 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 919YD UT WOS:000228652700038 PM 15850933 ER PT J AU Ozyildirim, AM Wistow, GJ Gao, J Wang, JH Dickinson, DP Frierson, HF Laurie, GW AF Ozyildirim, AM Wistow, GJ Gao, J Wang, JH Dickinson, DP Frierson, HF Laurie, GW TI The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID GROWTH-FACTOR; MESSENGER-RNAS; BREAST-CANCER; EXPRESSION; IDENTIFICATION; SEQUENCE; GENOME; MOUSE; SECRETION; EVOLUTION AB PURPOSE. To sequence and comprehensively analyze human and mouse lacrimal gland transcriptomes as part of the NEI-Bank project. METHODS. cDNA libraries generated from normal human and mouse lacrimal glands were sequenced and analyzed by PHRED, RepeatMasker, BLAST, and GRIST. Human "lacrimal-preferred genes" and putative gene regulatory elements were respectively identified in UniGene and ConSite, and gene clustering was analyzed by chromosomal mapping. "Hypothetical proteins," identified by keyword search, were verified by genomic alignment and queried in the Conserved Domain database and GEO Profiles. RESULTS. The top six transcripts in human and mouse differed, revealing a previously unappreciated molecular divergence. The human transcriptome is enriched with transcripts from 29 lacrimal-preferred genes and a content of poorly characterized hypothetical proteins, proportionally greater than in all other tissues. Only 45% of lacrimal preferred, but 71% of hypotheticals, have mouse orthologs. Many of the latter display apparently altered cancer expression in the CGAP SAGE library collection - often in keeping with predicted WD40, protein kinase, Src homology 2 and 3, RhoGEF, and pleckstrin homology domains involved in cell signaling. At the genomic level, lacrimal-expressed genes show some evidence of clustering, particularly on human chromosomes 9 and 12. Binding sites for TFAP2A, FOXC1, and other transcription factors are predicted. CONCLUSIONS. Interspecies divergence cautions against use of mouse models of human dry eye syndromes. Lacrimal preferred and hypothetical proteins, gene clustering, and putative gene regulatory elements together provide new clues for a molecular understanding of lacrimal gland function and mechanisms of coordinated tissue-specific transcriptional regulation. C1 Univ Virginia, Dept Cell Biol, UVa Hlth Syst, Charlottesville, VA 22908 USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA. NEI, Sect Mol Struct & Funct, Bethesda, MD USA. Med Coll Georgia, Dept Oral Biol, Augusta, GA 30912 USA. RP Laurie, GW (reprint author), Univ Virginia, Dept Cell Biol, UVa Hlth Syst, POB 800732, Charlottesville, VA 22908 USA. EM gwl6s@virginia.edu RI Laurie, Gordon/A-5244-2008; Dickinson, Douglas/B-9111-2009 FU NEI NIH HHS [R01 EY013143, EY 13143, R01 EY013143-04] NR 47 TC 36 Z9 38 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2005 VL 46 IS 5 BP 1572 EP 1580 DI 10.1167/iovs.04-1380 PG 9 WC Ophthalmology SC Ophthalmology GA 920RO UT WOS:000228708000007 PM 15851553 ER PT J AU Wojciechowski, R Congdon, N Bowie, H Munoz, B Gilbert, D West, SK AF Wojciechowski, R Congdon, N Bowie, H Munoz, B Gilbert, D West, SK TI Heritability of refractive error and familial aggregation of myopia in an elderly American population SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SINGAPORE CHINESE CHILDREN; NEAR-WORK ACTIVITY; OCULAR REFRACTION; MULTIVARIATE NORMALITY; CHROMOSOME 18P; RISK-FACTORS; LOCUS; PREVALENCE; EYE; PARAMETERS AB PURPOSE. To determine the heritability of refractive error and the familial aggregation of myopia in an older population. METHODS. Seven hundred fifty-nine siblings ( mean age, 73.4 years) in 241 families were recruited from the Salisbury Eye Evaluation ( SEE) Study in eastern Maryland. Refractive error was determined by noncycloplegic subjective refraction ( if presenting distance visual acuity was <= 20/40) or lensometry ( if best corrected visual acuity was <= 20/40 with spectacles). Participants were considered plano ( refractive error of zero) if uncorrected visual acuity was > 20/40. Preoperative refraction from medical records was used for pseudophakic subjects. Heritability of refractive error was calculated with multivariate linear regression and was estimated as twice the residual between-sibling correlation after adjusting for age, gender, and race. Logistic regression models were used to estimate the odds ratio ( OR) of myopia, given a myopic sibling relative to having a nonmyopic sibling. RESULTS. The estimated heritability of refractive error was 61% (95% confidence interval [CI]: 34% - 88%) in this population. The age-, race-, and sex-adjusted ORs of myopia were 2.65 ( 95% CI: 1.67 - 4.19), 2.25 ( 95% CI: 1.31 - 3.87), 3.00 ( 95% CI: 1.56 - 5.79), and 2.98 ( 95% CI: 1.51 - 5.87) for myopia thresholds of - 0.50, - 1.00, - 1.50, and - 2.00 D, respectively. Neither race nor gender was significantly associated with an increased risk of myopia. CONCLUSIONS. Refractive error and myopia are highly heritable in this elderly population. C1 NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dana Ctr Prevent Ophthalmol, Baltimore, MD USA. RP Wojciechowski, R (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM rwojciec@jhsph.edu OI Wojciechowski, Robert/0000-0002-9593-4652 FU NEI NIH HHS [K23 EY 00388, K23 EY000388]; NIA NIH HHS [R01 AG 16294, R01 AG016294, R01 AG016294-01] NR 43 TC 36 Z9 36 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAY PY 2005 VL 46 IS 5 BP 1588 EP 1592 DI 10.1167/iovs.04-0740 PG 5 WC Ophthalmology SC Ophthalmology GA 920RO UT WOS:000228708000009 PM 15851555 ER PT J AU Hillier, SL Moench, T Shattock, R Black, R Reichelderfer, P Veronese, F AF Hillier, SL Moench, T Shattock, R Black, R Reichelderfer, P Veronese, F TI In vitro and in vivo - The story of Nonoxynol 9 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Review DE microbicide; prevention; HIV; sexually transmitted infection; Nonoxynol-9; women; transmission; acquisition ID SPERMICIDAL COMPOUND NONOXYNOL-9; IMMUNODEFICIENCY-VIRUS TYPE-1; SODIUM DODECYL-SULFATE; ANTI-HIV ACTIVITY; EPITHELIAL-CELLS; CHLAMYDIA-TRACHOMATIS; CONTRACEPTIVE CREAM; GENITAL INFECTIONS; VAGINAL EPITHELIUM; VENEREAL DISEASE AB There is an urgent need to expand the range of interventions to prevent HIV transmission and acquisition, especially those that can be controlled by women. Microbicides, defined as antimicrobial products that can be applied topically for the prevention of HIV and other sexually transmitted infections, may offer one of the most promising preventive interventions, because they could be inexpensive, readily available, and widely acceptable. The first microbial product to be clinically evaluated contained Nonoxynol-9 (nonylpenoxypolyethoxyethanol [N-9]), a nonionic surfactant, as the active agent. This article presents a review of the in vitro, ex vivo, and animal model data on the safety of N-9 and a critical analysis of their predictive power based on the results of multiple safety and efficacy trials. C1 US Dept HHS, Off Aids Res, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. ReProtect, Baltimore, MD USA. Univ London, St Georges Med Sch, Dept Infect Dis, London, England. RP Veronese, F (reprint author), US Dept HHS, Off Aids Res, Natl Inst Hlth, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM FV10X@nih.gov NR 49 TC 133 Z9 148 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 MAY 1 PY 2005 VL 39 IS 1 BP 1 EP 8 DI 10.1097/01.qai.0000159671.25950.74 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 922BX UT WOS:000228812000001 PM 15851907 ER PT J AU Gao, PS Mathias, RA Plunkett, B Togias, A Barnes, KC Beaty, TH Huang, SK AF Gao, PS Mathias, RA Plunkett, B Togias, A Barnes, KC Beaty, TH Huang, SK TI Genetic variants of the T-cell immunoglobulin mucin 1 but not the T-cell immunoglobulin mucin 3 gene are associated with asthma in an African American population SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; single nucleotide polymorphism; T-cell immnoglobulin mucin; haplotype; hepatitis A ID FAMILY; DISEASE; IDENTIFICATION; INFORMATION; IMMUNITY; REGIONS; TESTS; TIM-1; LOCI AB Background: The T-cell immunoglobulin mucin (TIM) proteins and their genetic variants have been suggested to play a role in regulating allergic diseases. Objective: Genetic association of the sequence variants for TIM-1 and TIM-3 genes with asthma in an African American population was investigated. Methods: Both case-control and family-based association analyses were performed for a total of 7 polymorphisms, including 3 single nucleotide polymorphism (SNPs) and I insertion/deletion polymorphism in the TIM-1 and 3 SNPs in the TIM-3 genes. The exposure to hepatitis A virus as judged by seropositivity was also examined. Results: In the case-control design, the frequencies of the TT genotype for SNP rs2277025 and the homozygous deletion variant (157deIMTTTVP) in the fourth exon of the TIM-1 gene were higher among patients with patients with asthma compared with the controls (odds ratio [OR], 2.779, P =.016; and OR, 3.09, P =.022, respectively). This association was substantiated by haplotype analysis of these and 2 additional SNPs (OR, 2.48; P =.004), and also by family-based tests for the allele and haplotype carrying 157deIMTTTVP (P =.009 and P =.048, respectively). Furthermore, this association seems to exist even in the hepatitis A virus-seronegative subjects in our data. None of the 3 variants in TIM-3 genes yielded significant association with either asthma or asthma-related phenotypes. Conclusion: Our findings suggest that the genetic variants of the TIM-1 but not the TIM-3 gene contribute to asthma susceptibility in this African-American population. C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. RP Gao, PS (reprint author), Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM pgao1@jhmi.edu RI Huang, Shau-Ku/F-5509-2010 FU NHLBI NIH HHS [HL-49612]; NIAID NIH HHS [AI-52468] NR 21 TC 59 Z9 67 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 MAY PY 2005 VL 115 IS 5 BP 982 EP 988 DI 10.1016/j.jaci.2005.01.035 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 925LR UT WOS:000229055100013 PM 15867855 ER PT J AU Falk, R Hacham, M Nyska, A Foley, JF Domb, AJ Polacheck, I AF Falk, R Hacham, M Nyska, A Foley, JF Domb, AJ Polacheck, I TI Induction of interleukin-1 beta, tumour necrosis factor-alpha and apoptosis in mouse organs by amphotericin B is neutralized by conjugation with arabinogalactan SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE AMB toxicity; cytokines; AMB formulations; antifungals ID HEAT-INDUCED SUPERAGGREGATION; FAS-MEDIATED APOPTOSIS; THICK ASCENDING LIMB; ACUTE-RENAL-FAILURE; TNF-ALPHA; INDUCED NEPHROTOXICITY; FUNGAL-INFECTIONS; ANTIFUNGAL AGENTS; HENLES LOOP; EXPRESSION AB Objectives: To investigate the possibilities that: (i) organ toxicity of amphotericin B-deoxycholate (AMB-DOC) is related to induction of interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and apoptosis in target organs; and (ii) the reduced toxicity resulting from the conjugation of AMB with water-soluble arabinogalactan (AMB-AG), is related to modulation of these parameters. Methods: Organ expression of IL-1β and TNF-α was evaluated by enzyme-linked immunosorbent assay (ELISA) in mouse organ biological fluids and in situ by immunohistochemistry. Tissue damage was evaluated histologically, and apoptosis was demonstrated by terminal dUTP nick end-labelling (TUNEL) staining. AMB-AG conjugate was compared with the micellar (AMB-DOC) and liposomal (AmBisome) AMB formulations. Results: Treatment with AMB-AG or AmBisome caused no observable histopathological damage in the kidneys. In contrast, treatment with AMB-DOC resulted in disruptive changes and apoptosis in renal tubular cells. These effects were found to correlate with induction of high levels of IL-1β and TNF-α in kidney lysates. Unlike AMB-AG, AMB-DOC also induced enhanced IL-1β and TNF-α expression in lysates of lungs, brain, liver and spleen. The marked elevation of these inflammation-apoptosis-promoting cytokines after treatment with AMB-DOC may mediate its systemic and local renal damage. Treatment with AMB-AG (but not AmBisome) appears to uniquely modulate the in situ expression of IL-1β and enhance secretion of TNF-α in kidneys, effects possibly involved in prevention of apoptosis. Conclusions: AMB-related toxicity is associated with induction of IL-1β, TNF-α and apoptosis in organs. These effects were not observed with AMB-AG conjugate, suggesting its potential as a safer formulation for therapy. C1 Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Clin Microbiol & Infect Dis, IL-91120 Jerusalem, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem & Nat Prod, IL-12065 Jerusalem, Israel. RP Polacheck, I (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Dept Clin Microbiol & Infect Dis, POB 12000, IL-91120 Jerusalem, Israel. EM Itzhack.Polacheck@huji.ac.il NR 57 TC 15 Z9 15 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2005 VL 55 IS 5 BP 713 EP 720 DI 10.1093/jac/dki090 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 923TA UT WOS:000228931000017 PM 15814605 ER PT J AU Adler, A Cieslewicz, G Irvin, CG AF Adler, A Cieslewicz, G Irvin, CG TI Barometric whole body plethysmography in mice - Reply SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Letter ID INDUCED AIRWAY INFLAMMATION; HYPERRESPONSIVENESS; SENSITIZATION; ALLERGEN; HYPERREACTIVITY; RESPONSIVENESS C1 Univ Ottawa, Sch Informat Technol & Engn, Ottawa, ON K1N 6N5, Canada. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Univ Vermont, Vermont Lung Ctr, Burlington, VT 05405 USA. RP Adler, A (reprint author), Univ Ottawa, Sch Informat Technol & Engn, Ottawa, ON K1N 6N5, Canada. EM aadler@uottawa.ca NR 11 TC 0 Z9 0 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD MAY PY 2005 VL 98 IS 5 BP 1956 EP 1957 PG 2 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 920EB UT WOS:000228671100051 ER PT J AU Vuong, C Kidder, JB Jacobson, ER Otto, M Proctor, RA Somerville, GA AF Vuong, C Kidder, JB Jacobson, ER Otto, M Proctor, RA Somerville, GA TI Staphylococcus epidermidis polysaccharide intercellular adhesin production significantly increases during tricarboxylic acid cycle stress SO JOURNAL OF BACTERIOLOGY LA English DT Article ID BIOFILM FORMATION; IRON LIMITATION; FACTOR SIGMA(B); AUREUS; EXPRESSION; GROWTH; ACONITASE; ICAR; IDENTIFICATION; TRANSCRIPTION AB Staphylococcal polysaccharide intercellular adhesin (PIA) is important for the development of a mature biofilm. PIA production is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same environmental conditions are known to repress tricarboxylic acid (TCA) cycle activity, leading us to hypothesize that altering TCA cycle activity would affect PIA production. Culturing Staphylococcus epidermidis with a low concentration of the TCA cycle inhibitor fluorocitrate dramatically increased PIA production without impairing glucose catabolism, the growth rate, or the growth yields. These data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, or the redox status of the cell. These changes in the metabolic status of the bacteria result in the attenuation or augmentation of PIA production. C1 Univ Nebraska, Dept Vet & Biomed Sci, Lincoln, NE 68583 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Immunol, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI 53706 USA. Univ Nebraska, Beadle Ctr, Dept Biochem, Lincoln, NE 68588 USA. RP Somerville, GA (reprint author), Univ Nebraska, Dept Vet & Biomed Sci, 202 VBS Fair St, Lincoln, NE 68583 USA. EM gsomerville3@unl.edu RI Somerville, Greg/B-1326-2013; OI Somerville, Greg/0000-0002-0991-8737; Otto, Michael/0000-0002-2222-4115 FU NCRR NIH HHS [P20 RR-17675-02, P20 RR017675]; NIAID NIH HHS [AI42072, R01 AI042072] NR 41 TC 52 Z9 58 U1 1 U2 4 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 MAY PY 2005 VL 187 IS 9 BP 2967 EP 2973 DI 10.1128/JB.187.9.2967-2973.2005 PG 7 WC Microbiology SC Microbiology GA 919QX UT WOS:000228633800005 PM 15838022 ER PT J AU Sergueev, K Dabrazhynetskaya, A Austin, S AF Sergueev, K Dabrazhynetskaya, A Austin, S TI Plasmid partition system of the P1par family from the pWR100 virulence plasmid of Shigella flexneri SO JOURNAL OF BACTERIOLOGY LA English DT Article ID P1 PLASMID; PARB PROTEIN; SITE; SPECIFICITY; BINDING; COMPLEX; SEGREGATION; DNA AB P1par family members promote the active segregation of a variety of plasmids and plasmid prophages in gram-negative bacteria. Each has genes for ParA and ParB proteins, followed by a parS partition site. The large virulence plasmid pWR100 of Shigella flexneri contains a new P1par family member: pWR100par. Although typical parA and parB genes are present, the putative pWR100parS site is atypical in sequence and organization. However, pWR100parS promoted accurate plasmid partition in Escherichia coli when the pWR100 Par proteins were supplied. Unique BoxB hexamer motifs within parS define species specificities among previously described family members. Although substantially different from P1parS from the P1 plasmid prophage of E. coli, pWR100parS has the same BoxB sequence. As predicted, the species specificity of the two types proved identical. They also shared partition-mediated incompatibility, consistent with the proposed mechanistic link between incompatibility and species specificity. Among several informative sequence differences between pWR100parS and P1parS is the presence of a 21-bp insert at the center of the pWR100parS site. Deletion of this insert left much of the parS activity intact. Tolerance of central inserts with integral numbers of helical DNA turns reflects the critical topology of these sites, which are bent by binding the host IHF protein. C1 NCI, Gene Regulat & Chromosome Biol Lab, NCI, Ft Detrick, MD 21702 USA. RP Austin, S (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, NCI, Ft Detrick, MD 21702 USA. EM austin@ncifcrf.gov NR 25 TC 13 Z9 14 U1 0 U2 0 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 MAY PY 2005 VL 187 IS 10 BP 3369 EP 3373 DI 10.1128/JB.187.10.3369-3373.2005 PG 5 WC Microbiology SC Microbiology GA 923NO UT WOS:000228916800010 PM 15866921 ER PT J AU Chaiken, J Finney, W Knudson, PE Weinstock, RS Khan, M Bussjager, RJ Hagrman, D Hagrman, P Zhao, YW Peterson, CM Peterson, K AF Chaiken, J Finney, W Knudson, PE Weinstock, RS Khan, M Bussjager, RJ Hagrman, D Hagrman, P Zhao, YW Peterson, CM Peterson, K TI Effect of hemoglobin concentration variation on the accuracy and precision of glucose analysis using tissue modulated, noninvasive, in vivo Raman spectroscopy of human blood: a small clinical study SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Raman spectroscopy; noninvasive glucose; metabolic monitoring AB Tissue modulated Raman spectroscopy was used noninvasively to measure blood glucose concentration in people with type I and type II diabetes with HemoCue fingerstick measurements being used as reference. Including all of the 49 measurements, a Clarke error grid analysis of the noninvasive measurements showed that 72% were A range, i.e., clinically accurate, 20% were B range, i.e., clinically benign, with the remaining 8% of measurements being essentially erroneous, i.e., C, D, or E range. Rejection of 11 outliers gave a correlation coefficient of 0.80, a standard deviation of 22 mg/dL with p < 0.0001 for N=38 and places all but one of the measurements in the A and B ranges. The distribution of deviations of the noninvasive glucose measurements from the fingerstick glucose measurements is consistent with the suggestion that there are at least two systematic components in addition to the random noise associated with shot noise, charge coupled device spiking, and human factors. One component is consistent with the known variation of fingerstick glucose concentration measurements from laboratory reference measurements made using plasma or whole blood. A weak but significant correlation between the deviations of noninvasive measurements from fingerstick glucose measurements and the test subject's hemoglobin concentration was also observed. (c) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Upstate Med Univ New York, Joslin Diabet Ctr, Syracuse, NY 13210 USA. LighTouch Med Inc, Syracuse, NY 13210 USA. Natl Inst Heart Lung & Blood Dis, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD 20892 USA. RP Chaiken, J (reprint author), Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. EM jchaiken@syr.edu RI Peterson, Karen/E-8084-2015 OI Peterson, Karen/0000-0001-6737-8698 NR 20 TC 30 Z9 30 U1 1 U2 21 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2005 VL 10 IS 3 AR 031111 DI 10.1117/1.1922147 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 009QN UT WOS:000235127400012 PM 16229636 ER PT J AU Kim, M Bi, XH Horton, WE Spencer, RG Camacho, NP AF Kim, M Bi, XH Horton, WE Spencer, RG Camacho, NP TI Fourier transform infrared imaging spectroscopic analysis of tissue engineered cartilage: histologic and biochemical correlations SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE Fourier transform infrared imaging spectroscopy; tissue engineering; tissue engineered cartilage; hollow fiber bioreactor; osteoarthritis ID MAGNETIC-RESONANCE MICROSCOPY; HUMAN ARTICULAR-CARTILAGE; HOLLOW-FIBER BIOREACTOR; MRI TECHNIQUES; PROTEOGLYCANS; CHONDROCYTES; COLLAGEN; MATRIX; MODEL; OSTEOARTHRITIS AB The composition of cartilage is predictive of its in vivo performance. Therefore, the ability to assess its primary macromolecular components, proteoglycan (PG) and collagen, is of great importance. In the current study, we hypothesized that PG content and distribution in tissue engineered cartilage could be determined using Fourier-transform infrared imaging spectroscopy (FT-IRIS). The cartilage was grown from chondrocytes within a hollow fiber bioreactor (HFBR) system previously used extensively to study cartilage development. FT-IRIS analysis showed a gradient of PG content, with the highest content in the center near the nutritive fibers and the lowest near the interior surface of the HFBR. Further, we found significantly greater PG content in the region near culture medium inflow (45.0%) as compared to the outflow region (24.7%) (p < 0.001). This difference paralleled the biochemically determined glycosaminoglycan difference of 42.6% versus 27.8%. In addition, FT-IRIS-determined PG content at specific positions within the tissue sections correlated with histologically determined PG content (R=50.73, p=50.007). In summary, FT-IRIS determination of PG correlates with histological determination of PG and yields quantitatively similar results to biochemical determination of glycosaminoglycan in developing cartilage. (c) 2005 Society of Photo-Optical Instrumentation Engineers. C1 Hosp Special Surg, Musculoskeletal Imaging & Spect Lab, New York, NY 10021 USA. NIA, Nucl Magnet Resonance Unit, NIH, Baltimore, MD 21224 USA. NE Ohio Univ, Coll Med, Rootstown, OH 44272 USA. RP Camacho, NP (reprint author), Hosp Special Surg, Musculoskeletal Imaging & Spect Lab, 535 E 70th St, New York, NY 10021 USA. EM camachon@hss.edu FU NIBIB NIH HHS [EB00744, R01 EB000744] NR 40 TC 37 Z9 37 U1 1 U2 10 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD MAY-JUN PY 2005 VL 10 IS 3 AR 031105 DI 10.1117/1.1922329 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 009QN UT WOS:000235127400006 PM 16229630 ER PT J AU Ishima, R Torchia, DA AF Ishima, R Torchia, DA TI Error estimation and global fitting in transverse-relaxation dispersion experiments to determine chemical-exchange parameters SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE conformational change; chemical exchange; CPMG; NMR; R2 ID OPTIMAL SAMPLING STRATEGIES; TIME-SCALE DYNAMICS; NMR-SPECTROSCOPY; CAVITY MUTANT; T4 LYSOZYME; INTERNAL DYNAMICS; HIV-1 PROTEASE; SIDE-CHAINS; PROTEINS; CONSTANT AB Off-resonance effects can introduce significant systematic errors in R-2 measurements in constant-time Carr-Purcell-Meiboom-Gill (CPMG) transverse relaxation dispersion experiments. For an off-resonance chemical shift of 500 Hz, N-15 relaxation dispersion profiles obtained from experiment and computer simulation indicated a systematic error of ca. 3%. This error is three- to five-fold larger than the random error in R-2 caused by noise. Good estimates of total R-2 uncertainty are critical in order to obtain accurate estimates in optimized chemical exchange parameters and their uncertainties derived from chi(2) minimization of a target function. Here, we present a simple empirical approach that provides a good estimate of the total error (systematic + random) in N-15 R-2 values measured for the HIV protease. The advantage of this empirical error estimate is that it is applicable even when some of the factors that contribute to the off-resonance error are not known. These errors are incorporated into a chi(2) minimization protocol, in which the Carver-Richards equation is used fit the observed R-2 dispersion profiles, that yields optimized chemical exchange parameters and their confidence limits. Optimized parameters are also derived, using the same protein sample and data-fitting protocol, from H-1 R-2 measurements in which systematic errors are negligible. Although H-1 and N-15 relaxation profiles of individual residues were well fit, the optimized exchange parameters had large uncertainties (confidence limits). In contrast, when a single pair of exchange parameters (the exchange lifetime, sex, and the fractional population, p(a)), were constrained to globally fit all R-2 profiles for residues in the dimer interface of the protein, confidence limits were less than 8% for all optimized exchange parameters. In addition, F-tests showed that quality of the fits obtained using tau(ex), p(a) as global parameters were not improved when these parameters were free to fit the R-2 profiles of individual residues. Finally, nearly the same optimized global tau(ex), p(a) values were obtained, when the H-1 and N-15 data sets for residues in the dimer interface, were fit independently; the difference in optimized global parameters, ca. 10%, was of marginal significance according to the F-test. C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Ishima, R (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, Natl Inst Hlth, Bethesda, MD 20892 USA. EM rishima@dir.nidcr.nih.gov FU Intramural NIH HHS NR 29 TC 30 Z9 30 U1 1 U2 7 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAY PY 2005 VL 32 IS 1 BP 41 EP 54 DI 10.1007/s10858-005-3593-z PG 14 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 948MN UT WOS:000230720100005 PM 16041482 ER PT J AU Bennett, AJ DePetrillo, PB AF Bennett, AJ DePetrillo, PB TI Differential effects of MK801 and lorazepam on heart rate variability in adolescent rhesus monkeys (Macoca mulatta) SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE cardiac; heart rate variability; lorazepam; MK801; monkey; NMDA ID TIME-SERIES; PARASYMPATHETIC TONE; NONHUMAN-PRIMATES; AUTONOMIC CONTROL; SPECTRAL-ANALYSIS; VAGAL MODULATION; FRACTAL ANALYSIS; KETAMINE; ARRHYTHMIAS; DYNAMICS AB Previous research shows that ketamine significantly alters cardiac signal regulation in rhesus monkeys, however relatively little is known about the mechanism for this effect. In the study reported here the relative contributions of NMDA receptor activation on cardiac signal dynamics were determined by administering a specific NMDA antagonist, MK801, to rhesus monkeys. The general effects of sedation were assessed by measuring cardiac response to lorazepam, a sedative drug without direct NMDA receptor activity. Electrocardiographic signal dynamics were examined before and after IN administration of either MK801 (0.16 mg/kg) or lorazepam (0.48 mg/kg). Inter-beat interval time series data were analyzed in the frequency domain after Fourier transform, and a nonlinear measure of autocorrelation, the Hurst exponent (H), was derived. After MK801 administration, log [HE/Total power] increased post-infusion (M = 1.11, SD = 0.45) compared with pre-infusion values [M = -0.19, SD = 0.32, F(1,4) = 19.49, P = 0.01] while H decreased, mean pre versus post 0.52+/-S.D. 0.10 versus 0.01+/- 0.05, P = 0.0002. Lorazepam administration did not significantly alter heart rate variability measures obtained in the frequency or nonlinear domains. To our knowledge, this is the first study that has defined the effects of peripherally administered MK801 on cardiovascular dynamics in primates and establishes that peripheral administration of NMDA antagonists result in large increases the high-frequency components of cardiac rhythm and increased heart rate variability compatible with MK801-associated increases in parasympathetic outflow. C1 Wake Forest Univ, Sch Med, Dept Pharmacol Physiol, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. NIAAA, Clin Studies Lab, Unit Clin & Biochem Pharmacol, Div Intramural Clin & Biochem Res, Bethesda, MD 20892 USA. RP Bennett, AJ (reprint author), Wake Forest Univ, Sch Med, Dept Pharmacol Physiol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM abennett@wfubmc.edu FU NIAAA NIH HHS [AA013995] NR 44 TC 5 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD MAY PY 2005 VL 45 IS 5 BP 383 EP 388 DI 10.1097/01.fjc.0000156820.12339.db PG 6 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 921PH UT WOS:000228776300001 PM 15821432 ER PT J AU Modarresi, R Lafond, T Roman-Blas, JA Danielson, KG Tuan, RS Seghatoleslami, MR AF Modarresi, R Lafond, T Roman-Blas, JA Danielson, KG Tuan, RS Seghatoleslami, MR TI N-cadherin mediated distribution of beta-catenin alters MAP kinase and BMP-2 signaling on chondrogenesis-related gene expression SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE N-cacherin; chondrogenesis; C3H10T1/2; micromass; MAP kinase; BMP-2; beta-catenin; aggrecan; type II collagen ID CELL-CELL-ADHESION; MULTIPOTENTIAL MESENCHYMAL CELLS; BONE MORPHOGENETIC PROTEIN-2; RHO-FAMILY GTPASES; 3-DIMENSIONAL CULTURES; EXOGENOUS EXPRESSION; CYTOPLASMIC DOMAIN; IN-VITRO; DIFFERENTIATION; ACTIN AB We have examined the effect of calcium-dependent adhesion, mediated by N-cadherin, on cell sign a I in g during chondrogenesis Of multipotential embryonic Mouse C3H10T1/2 cells. The activity of chondrogenic genes, type 11 collagen, aggrecan, and Sox9 were examined in monolayer (non-chondrogenic), and micromass (chondrogenic) cultures of parental C3H10T1/2 cells and altered C3H10T1/2 cell lines that express a dominant negative form of N-cadherin (Delta 390TI/2) or overexpress normal N-cadherin (MNCD2-T1/2). Our findings show that missexpression or inhibition of N-cacherin in C3H10T1/2 cells results in temporal and spatial changes in expression of the chondrogenic genes Sox9, aggrecan, and collagen type II. We have also analyzed activity of the serum response factor (SRF), a nuclear target of MAP kinase signaling implicated in chondrogenesis. In semi-confluent monolayer cultures 0-minimum cell-cell contact) of C3H10T1/2, MNCD2-T1/2, or Delta 390-T1/2 cells, there was no significant change in the pattern of MAP kinase or bone morphogenetic protein-2(BMP-2)regulation of SRF. However, in micromass cultures, the effect of MAP kinase and BMP-2 on SRF activity was proportional to the nuclear localization of beta-catenin, a Wnt stabilized cytoplasmic factor that can associate with lymphoid enhancer-binding factor (LEF) to serve as a transcription factor. Our findings suggest that the extent of adherens junction formation mediated by N-cacherin can modulate the potential Wnt-induced nuclear activity of beta-catenin. Published 2005 Wiley-Liss, Inc.(dagger) C1 Thomas Jefferson Univ, Dept Med, Div Rheumatol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Orthopaed Surg Res, Philadelphia, PA 19107 USA. NIAMSD, Carilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Seghatoleslami, MR (reprint author), Thomas Jefferson Univ, Dept Med, Div Rheumatol, Room 506,233 S 10th St, Philadelphia, PA 19107 USA. EM reza.seghatoleslami@jefferson.edu OI Roman-Blas, Jorge A./0000-0003-1142-1946 FU NIDCR NIH HHS [DE12864] NR 36 TC 25 Z9 26 U1 0 U2 3 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 MAY 1 PY 2005 VL 95 IS 1 BP 53 EP 63 DI 10.1002/jcb.20396 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 921DI UT WOS:000228744000006 PM 15723280 ER PT J AU Schmidt, KC Cook, MP Qin, M Kang, J Burlin, TV Smith, CB AF Schmidt, KC Cook, MP Qin, M Kang, J Burlin, TV Smith, CB TI Measurement of regional rates of cerebral protein synthesis with L-[1-C-11]leucine and PET with correction for recycling of tissue amino acids: I. Kinetic modeling approach SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain; leucine; positron emission tomography; protein synthesis ID BRAIN TISSUE; BLOOD-FLOW; INVIVO; TOMOGRAPHY; ANESTHESIA AB Measurements of regional rates of cerebral protein synthesis (rCPS) require correction for the effect of recycling of tissue amino acids back into the precursor pool for protein synthesis. The fraction of the precursor pool derived from arterial plasma,),, can be evaluated as the steady-state ratio of the specific activity of leucine in the tissue tRNA-bound fraction to that in arterial plasma. While). can be directly measured in terminal experiments in animals, an alternative method is required for use with PET. We report a method to estimate lambda based on a kinetic model of labeled and unlabeled leucine and labeled CO2 in the tissue. The kinetic model is also used to estimate the amount of labeled protein and rCPS. We measured time courses of [C-14]leucine, [C-14]protein, and (CO2)-C-14 in the blood and brain of anesthetized rats and estimated parameters of the kinetic model from these data. Simulation studies based on the kinetic parameters were then performed to examine the feasibility of this approach for use with L-[1-C-11]leucine and PET. and rCPS were estimated with low bias, which suggests that PET can be used for quantitative measurement of rCPS with L-[1-C-11]leucine and a kinetic modeling approach for correction for recycling of tissue amino acids. C1 NIMH, Unit Neuroadaptat & Prot Metab, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. RP Schmidt, KC (reprint author), NIMH, Unit Neuroadaptat & Prot Metab, Cerebral Metab Lab, NIH, Bldg 36,Rm 1A07,36 Convent Dr, Bethesda, MD 20892 USA. EM SchmidtK@intra.nimh.nih.gov NR 12 TC 13 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2005 VL 25 IS 5 BP 617 EP 628 DI 10.1038/sj.jcbfm.9600067 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 918PX UT WOS:000228561200007 PM 15703696 ER PT J AU Smith, CB Schmidt, KC Qin, M Burlin, TV Cook, MP Kang, J Saunders, RC Bacher, JD Carson, RE Channing, MA Eckelman, WC Herscovitch, P Laverman, P Vuong, BK AF Smith, CB Schmidt, KC Qin, M Burlin, TV Cook, MP Kang, J Saunders, RC Bacher, JD Carson, RE Channing, MA Eckelman, WC Herscovitch, P Laverman, P Vuong, BK TI Measurement of regional rates of cerebral protein synthesis with L-[1-C-11]leucine and PET with correction for recycling of tissue amino acids: II. Validation in rhesus monkeys SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain; leucine; positron emission tomography; protein synthesis ID POSITRON EMISSION TOMOGRAPHY; PRECURSOR POOL; BRAIN; DEGRADATION; INHIBITION; INVIVO; TRACER; MODEL AB The confounding effect of recycling of amino acids derived from tissue protein breakdown into the precursor pool for protein synthesis has been an obstacle to adapting in vivo methods for determination of regional rates of cerebral protein synthesis (rCPS) to positron emission tomography (PET). We used a kinetic modeling approach to estimate, the fraction of the precursor pool for protein synthesis derived from arterial plasma, and to measure rCPS in three anesthetized adult monkeys dynamically scanned after a bolus injection Of L-[1-C-11]leucine. In the same animals, I was directly measured in a steady-state terminal experiment, and values showed excellent agreement with those estimated in the PET studies. In three additional monkeys rCPS was determined with the quantitative autoradiographic L-[1-C-14] leucine method. In whole brain and cerebellum, rates of protein synthesis determined with the autoradiographic method were in excellent agreement with those determined with PET, and regional values were in good agreement when differences in spatial resolution of the two methods were taken into account. Low intrasubject variability was found on repeated PET studies. Our results in anesthetized monkey indicate that, by using a kinetic modeling approach to correct for recycling of tissue amino acids, quantitatively accurate and reproducible measurement of rCPS is possible with L-[1-C-11]leucine and PET. C1 NIMH, Unit Neuroadaptat & Prot Metab, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. Univ Nijmegen, Ctr Med, Dept Nucl Med, Nijmegen, Netherlands. RP Smith, CB (reprint author), NIMH, Unit Neuroadaptat & Prot Metab, Cerebral Metab Lab, Bldg 36,Rm 1A07,36 Convent Dr, Bethesda, MD 20892 USA. EM beebec@intra.nimh.nih.gov RI Carson, Richard/H-3250-2011; Laverman, P./L-4476-2015 OI Carson, Richard/0000-0002-9338-7966; NR 25 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD MAY PY 2005 VL 25 IS 5 BP 629 EP 640 DI 10.1038/sj.jcbfm.9600066 PG 12 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 918PX UT WOS:000228561200008 PM 15703697 ER PT J AU Nanda, H Sachs, JN Petrache, HI Woolf, TB AF Nanda, H Sachs, JN Petrache, HI Woolf, TB TI Environmental effects on glycophorin A folding and structure examined through molecular simulations SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION LA English DT Article ID NEUTRON-DIFFRACTION DATA; TRANSMEMBRANE ALPHA-HELICES; DYNAMICS SIMULATIONS; X-RAY; MEMBRANE-PROTEINS; JOINT REFINEMENT; LIPID-BILAYERS; GRAMICIDIN CHANNEL; GXXXG MOTIF; WATER AB The human erythrocyte sialoglycoprotein glycophorin A (GpA) has been used extensively in experiment and simulations as a model of transmembrane helix-dimer formation, emphasizing the critical role of specific residue-residue interactions between helices in dimer stability. While the tertiary dimer structure is modulated by the hydrophobic lipid bilayer environment, we show that interactions of GpA with ordered interfacial water are commensurate to intrahelical forces. The role of lipid-water interface in stabilizing transmembrane proteins is not yet understood; however, dramatic water reordering in the presence of the transmembrane domains is observed from simulations and is possibly measurable by experiment. Interfacial interactions including anisotropic interactions with the polar headgroups might favor parallel association of transmembrane helices. To quantify forces capable of disrupting the GpA dimer, we generate folding/unfolding intermediates by replacement of the lipid bilayer with water, eliminating not only the native hydrophobic environment but also the native interfacial water region. Dramatic changes in the secondary, helical structures occur, with a transition from i,i+4 a-helix to i,i+5 pi-helix and concomitant perturbation of the tertiary structure. Enforcing the native alpha-helix secondary structure by soft dihedral restraints restores the native tertiary structure, in essence substituting for the lack of the lipid-water interface. We suggest that differentiation between interactions within the lipid bilayer, including interactions with lipid headgroups and interfacial water can enrich our understanding of the thermodynamic stability of transmembrane domains. C1 Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. RP Woolf, TB (reprint author), Johns Hopkins Univ, Sch Med, Dept Physiol, 725 N Wolfe St, Baltimore, MD 21205 USA. EM woolf@groucho.med.jhmi.edu NR 77 TC 3 Z9 3 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9618 J9 J CHEM THEORY COMPUT JI J. Chem. Theory Comput. PD MAY-JUN PY 2005 VL 1 IS 3 BP 375 EP 388 DI 10.1021/ct049928y PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 961TU UT WOS:000231685500004 PM 26641504 ER PT J AU Garvey, MA Snider, LA Leitman, SF Werden, R Swedo, SE AF Garvey, MA Snider, LA Leitman, SF Werden, R Swedo, SE TI Treatment of Sydenham's chorea with intravenous immunoglobulin, plasma exchange, or prednisone SO JOURNAL OF CHILD NEUROLOGY LA English DT Article ID RHEUMATIC-FEVER; CORTICOSTEROIDS; ANTIBODIES; SYMPTOMS AB Sydenham's chorea has been established as a postinfectious autoimmune neuropsychiatric disorder. Corticosteroids have been used to treat patients with severe disease but are not always effective, and relapses are frequent after cessation. Eighteen subjects were entered into this randomized-entry controlled trial designed to determine if intravenous immunoglobulin or plasma exchange would be superior to prednisone in decreasing the severity of chorea. Mean chorea severity for the entire group was significantly lower at the 1-month follow-up evaluation (overall 48% improvement). Although the between-group differences were not statistically significant, clinical improvements appeared to be more rapid and robust in the intravenous immunoglobulin and plasma exchange groups than in the prednisone group (mean chorea severity scores decreased by 72% in the intravenous immunoglobulin group, 50% in the plasma exchange group, and 29% in the prednisone group). Larger studies are required to confirm these clinical observations and to determine if these treatments are cost-effective for this disorder. C1 NIH, Warren G Magnuson Clin Ctr, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Snider, LA (reprint author), NIH, Warren G Magnuson Clin Ctr, Pediat & Dev Neuropsychiat Branch, 10 Ctr Dr,Room 4N208,MSC 1255, Bethesda, MD 20892 USA. EM snider1@intra.nimh.nih.gov NR 35 TC 65 Z9 68 U1 0 U2 1 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0883-0738 J9 J CHILD NEUROL JI J. Child Neurol. PD MAY PY 2005 VL 20 IS 5 BP 424 EP 429 PG 6 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 932TI UT WOS:000229575900007 PM 15968928 ER PT J AU Alesci, S Martinez, PE Kelkar, S Ilias, I Ronsaville, DS Listwak, SJ Ayala, AR Licinio, J Gold, HK Kling, MA Chrousos, GP Gold, PW AF Alesci, S Martinez, PE Kelkar, S Ilias, I Ronsaville, DS Listwak, SJ Ayala, AR Licinio, J Gold, HK Kling, MA Chrousos, GP Gold, PW TI Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: Clinical implications SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PITUITARY-ADRENAL AXIS; RECOMBINANT HUMAN INTERLEUKIN-6; CORONARY-ARTERY-DISEASE; BONE-MINERAL DENSITY; VISUAL ANALOG SCALES; BIOCHEMICAL MANIFESTATIONS; HEART-DISEASE; BLOOD-LEVELS; TIME-SERIES; HEALTHY-MEN AB Background: Major depressive disorder (MDD) is associated with increased risk for premature coronary heart disease and bone loss. Single time measurements of plasma IL-6, a good predictor of future risk for both cardiovascular disease and osteoporosis, revealed significant elevations in depressed patients. The objective of this study was to rigorously compare plasma IL-6 levels, measured over 24 h, in MDD patients and healthy controls. Given the activating role of IL-6 on the hypothalamic-pituitary-adrenal (HPA) axis, and the relevance of its dysregulation in MDD, we also analyzed the relations between IL-6 and cortisol levels. Methods: We studied nine patients and nine controls, individually matched by gender, age ( +/- 5 yr), body mass index ( +/- 2 kg/m(2)), and menstrual cycle phase. Diagnosis of MDD was confirmed by structured clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Axis I diagnostic criteria. Self-reported mood ratings were assessed by multiple visual analog scales. The rhythmicity and complexity of IL-6 and cortisol secretion were tested by cosinor analyses, approximate entropy (ApEn) and cross-ApEn algorithms. Results: MDD patients had significant mean IL-6 elevations from 1000 - 1200 h and at 1500 h ( P ranging from < 0.05 to <0.01) vs. controls. In addition, in MDD, the circadian rhythm of IL-6 was shifted by 12 h, and its physiological complexity was reduced, with no difference in the cross-ApEn of IL-6 and cortisol between the two groups, and significant time-lagged correlations only in the controls. IL-6 levels correlated significantly with mood ratings. Conclusions: We report profound morning elevations of plasma IL-6 and a reversal of its circadian rhythm in MDD patients, in the absence of hypercortisolism. These findings may be relevant to the increased risk for coronary heart disease and bone loss in MDD. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Lab Pharmacogenom, Los Angeles, CA 90095 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RP Alesci, S (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2D46,MSC 1284, Bethesda, MD 20892 USA. EM alescisa@mail.nih.gov RI Kling, Mitchel/F-4152-2010; OI Kling, Mitchel/0000-0002-2232-1409; Licinio, Julio/0000-0001-6905-5884 NR 55 TC 183 Z9 187 U1 1 U2 16 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 MAY PY 2005 VL 90 IS 5 BP 2522 EP 2530 DI 10.1210/jc.2004-1667 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 923MO UT WOS:000228914200007 PM 15705924 ER PT J AU Merke, DP Giedd, JN Keil, MF Mehlinger, SL Wiggs, EA Holzer, S Rawson, E Vaituzis, AC Stratakis, CA Chrousos, GP AF Merke, DP Giedd, JN Keil, MF Mehlinger, SL Wiggs, EA Holzer, S Rawson, E Vaituzis, AC Stratakis, CA Chrousos, GP TI Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; MAJOR DEPRESSION; HIPPOCAMPAL-FORMATION; CORTISOL-LEVELS; DISEASE; ADOLESCENTS; AMYGDALA; VOLUME; STRESS; HYPERCORTISOLISM AB Adults with Cushing syndrome frequently develop brain atrophy, memory impairment, and depression, with partial to complete resolution after cure. The effect of excess glucocorticoid exposure on the brain of children has not been systematically studied. Eleven children ( six girls, five boys; ages, 8 - 16 yr) with endogenous Cushing syndrome seen at the National Institutes of Health Clinical Center from 1999 - 2000 and 10 healthy age- and sex-matched control subjects were studied. Cognitive and psychological evaluations and magnetic resonance imaging of the brain were done before and 1 yr after cure for patients with Cushing syndrome and once for controls. The estimated duration of Cushing syndrome was 4.4 +/- 1.2 yr. When compared with control subjects, children with Cushing syndrome had significantly smaller cerebral volumes ( P < 0.001), larger ventricles ( P = 0.02), and smaller amygdala P = 0.004). At baseline, there were no significant differences in IQ between the two groups, and no psychopathology was identified. Despite reversal of cerebral atrophy 1 yr after surgical cure ( total cerebral volume, 947 +/- 94 vs. 1050 +/- 74 ml, P < 0.001; ventricular volume, 21.4 +/- 12.5 vs. 14.5 +/- 11.6 ml, P < 0.001), children with Cushing syndrome experienced a significant ( P< 0.05) decline in Wechsler IQ scores ( Full Scale, 112 +/- 19 vs. 98 +/- 14) and a decline in school performance, without any associated psychopathology. The effect of glucocorticoid excess on the brain of children appears to be different from adults. Despite rapid reversibility of cerebral atrophy, children experience a significant decline in cognitive function 1 yr after correction of hypercortisolism. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Sect Endocrinol Genet, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIMH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Merke, DP (reprint author), NIH, Bldg 10,Room 13S260,10 Ctr Dr,MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov 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 NR 55 TC 53 Z9 58 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 MAY PY 2005 VL 90 IS 5 BP 2531 EP 2536 DI 10.1210/jc.2004-2488 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 923MO UT WOS:000228914200008 PM 15741254 ER PT J AU Matochik, JA London, ED Yildiz, BO Ozata, M Caglayan, S DePaoli, AM Wong, ML Licinio, J AF Matochik, JA London, ED Yildiz, BO Ozata, M Caglayan, S DePaoli, AM Wong, ML Licinio, J TI Effect of leptin replacement on brain structure in genetically leptin-deficient adults SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID VOXEL-BASED MORPHOMETRY; HYPOTHALAMIC NEURONS; OBESITY AB The hormone leptin profoundly affects body weight and metabolism. Three human adults ( two women, 35 and 40 yr old; one man, age 27) have been identified with a recessive mutation in the ob gene, which is homologous to the mutation in ob/ob mice, and produces leptin deficiency and morbid obesity. Because leptin replacement increases brain weight and changes brain protein and DNA content in ob/ob mice, we hypothesized that analogous treatment of leptin-deficient humans would alter brain tissue composition. Volumetric T1-weighted magnetic resonance images of the brain were acquired before and at 6 and 18 months after initiation of replacement therapy ( daily sc injections of recombinant methionyl human leptin), which produced dramatic loss in body weight. We used voxel-based morphometry to test for increased gray matter tissue concentration after initiation of leptin replacement and detected increases at 6 months in the anterior cingulate gyrus, the inferior parietal lobule, and the cerebellum. These increases were maintained for over 18 months, with identical stereotaxic coordinates of the maxima for the effects. Our findings suggest that leptin can have sustained effects on tissue composition in the human brain and broaden the potential spectrum of leptin's influence beyond feeding behavior and endocrine function. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA. NIDA, Neuroimaging Res Branch, US Dept HHS, NIH, Baltimore, MD 21224 USA. Univ Calif Los Angeles, David Geffen Sch Med, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Gulhane Haydarpasa Training Hosp, Dept Endocrinol & Metab, TR-34660 Istanbul, Turkey. RP London, ED (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, C8-532 NPI,760 Westwood Plaza, Los Angeles, CA 90024 USA. EM elondon@mednet.ucla.edu RI Wong, Ma-Li/D-7903-2011; OI Licinio, Julio/0000-0001-6905-5884 FU NCRR NIH HHS [RR16996, RR000865, RR017365, RR017611]; NHGRI NIH HHS [HG002500]; NHLBI NIH HHS [K30HL04526]; NIDDK NIH HHS [DK063240, DK58851]; NIGMS NIH HHS [GM61394]; NIMH NIH HHS [MH062777] NR 13 TC 96 Z9 98 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2005 VL 90 IS 5 BP 2851 EP 2854 DI 10.1210/jc.2004-1979 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 923MO UT WOS:000228914200056 PM 15713712 ER PT J AU Lindsay, JR Jonklaas, J Oldfield, EH Nieman, LK AF Lindsay, JR Jonklaas, J Oldfield, EH Nieman, LK TI Cushing's syndrome during pregnancy: Personal experience and review of the literature SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Review ID CORTICOTROPIN-RELEASING HORMONE; SYNDROME COMPLICATING PREGNANCY; DEXAMETHASONE SUPPRESSION TEST; DIFFERENTIAL-DIAGNOSIS; MULTIPLE PREGNANCIES; STIMULATION TEST; DISEASE; ADRENOCORTICOTROPIN; CORTISOL; METYRAPONE AB Cushing's syndrome ( CS) occurs rarely during pregnancy. We investigated and treated four patients with pituitary-dependent Cushing's syndrome during pregnancy over a 15-yr period at the National Institutes of Health. Except for preservation of menses before conception, our patients presented with typical clinical features, increased urinary free cortisol, and loss of diurnal variation of cortisol. The diagnosis was facilitated, without complications, by the use of CRH testing and inferior petrosal sinus sampling in three women. Transsphenoidal pituitary surgery achieved remission in three women, but there were two fetal/neonatal deaths. This experience and review of 136 previous reports suggest that: 1) urinary free cortisol in CS patients overlaps the normal pregnant range; 2) ACTH levels are not suppressed in adrenal causes of CS, which may be identified by the 8-mg dexamethasone test; 3) inferior petrosal sinus sampling and transsphenoidal pituitary surgery, the optimal diagnostic test and treatment for nonpregnant patients with pituitary-dependent Cushing's syndrome, can safely facilitate the management of pregnant patients; and 4) surgery may achieve remission during pregnancy, but the prognosis for the fetus remains guarded. It is likely that earlier recognition and treatment would improve outcome. There is a need for development of criteria for interpretation of diagnostic tests and increased consideration of CS in pregnancy. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20057 USA. RP Nieman, LK (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bldg 10,CRC,Room 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@mail.nih.gov RI Jonklaas, Jacqueline/G-2807-2010 OI Jonklaas, Jacqueline/0000-0002-2238-2666 NR 54 TC 88 Z9 94 U1 0 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2005 VL 90 IS 5 BP 3077 EP 3083 DI 10.1210/jc.2004-2361 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 923MO UT WOS:000228914200088 PM 15705919 ER PT J AU Iyengar, P Espina, V Williams, TW Lin, Y Berry, D Jelicks, LA Lee, H Temple, K Graves, R Pollard, J Chopra, N Russell, RG Sasisekharan, R Trock, BJ Lippman, M Calvert, VS Petricoin, EF Liotta, L Dadachova, E Pestell, RG Lisanti, MP Bonaldo, P Scherer, PE AF Iyengar, P Espina, V Williams, TW Lin, Y Berry, D Jelicks, LA Lee, H Temple, K Graves, R Pollard, J Chopra, N Russell, RG Sasisekharan, R Trock, BJ Lippman, M Calvert, VS Petricoin, EF Liotta, L Dadachova, E Pestell, RG Lisanti, MP Bonaldo, P Scherer, PE TI Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OLIGODENDROCYTE PRECURSOR CELLS; BETHLEM MYOPATHY; BREAST-CANCER; EXTRACELLULAR-MATRIX; BRAIN-TUMORS; AXON GROWTH; PROTEOGLYCAN; INDUCTION; MODEL; NG2 AB The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is wen established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and β-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIα 3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI. C1 Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Cell Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Med, Bronx, NY 10461 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Mol Pharmacol, New York, NY USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Physiol & Biophys, New York, NY USA. Univ Chicago, Comm Human Nutr & Nutrit Biol, Chicago, IL 60637 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Biochem & Mol Biol, Buffalo, NY 14260 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Dev & Mol Biol, New York, NY USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pathol, New York, NY USA. Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA. MIT, Ctr Biol Engn, Cambridge, MA USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. FDA, Natl Canc Inst, Clin Proteom Program, Off Cellular & Gene Therapy,Ctr Biol Evaluat & Re, Bethesda, MD USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Nucl Med, New York, NY USA. Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35100 Padua, Italy. RP Scherer, PE (reprint author), Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Cell Biol, Jack & Pearl Resnick Campus,1300 Morris Pk Ave,Ch, Bronx, NY 10461 USA. EM scherer@aecom.yu.edu RI Lisanti, Michael/C-6866-2013; Williams, Terence/I-9614-2014; OI Espina, Virginia/0000-0001-5080-5972 FU NCI NIH HHS [CA100324, CA94173, P01 CA100324, R01 CA094173]; NIGMS NIH HHS [T32 GM007288, T32 GM07288]; Telethon [1201] NR 44 TC 151 Z9 155 U1 1 U2 8 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 MAY PY 2005 VL 115 IS 5 BP 1163 EP 1176 DI 10.1172/JCI200523424 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923KH UT WOS:000228908300017 PM 15841211 ER PT J AU Melchionda, F Fry, TJ Milliron, MJ McKirdy, MA Tagaya, Y Mackall, CL AF Melchionda, F Fry, TJ Milliron, MJ McKirdy, MA Tagaya, Y Mackall, CL TI Adjuvant IL-7 or IL-15 overcomes immunodominance and improves survival of the CD8(+) memory cell pool SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RESPONSES IN-VIVO; T-CELLS; HOMEOSTATIC PROLIFERATION; MEDIATED-IMMUNITY; DENDRITIC CELLS; INTERLEUKIN-7; VACCINE; NAIVE; CANCER; DIFFERENTIATION AB Current models of T cell memory implicate a critical role for IL-7 in the effector-to-memory transition, raising the possibility that IL-7 therapy might enhance vaccine responses. IL-7 has not been studied, to our knowledge, before now for adjuvant activity. We administered recombinant human IL-7 (rhIL-7) to mice during immunization against the male antigen HY and compared these results with those obtained from mice immunized with rhIL-2 and rhIL-15. Administration of rhIL-7 or rhIL- 15, but not rhIL-2, increased effector cells directed against these dominant antigens and dramatically enhanced CD8(+) effectors to subdominant antigens. The mechanisms by which the cytokines augmented effector pool generation were multifactorial and included rhIL-7-mediated costimulation and rhIL-15-mecliated augmentation of the proliferative burst. The contraction phase of the antigen-specific response was exaggerated in cytokine-treated mice; however, CD8(+) memory pools in rhIL-7- or rhIL-15-treated groups demonstrated superior long-term survival resulting in quantitative advantages that remained long after the cytokines were discontinued, as demonstrated by improved survival after challenge with an HY-expressing tumor undertaken several weeks after cytokine cessation. These results confirm the adjuvant activity of rhIL-15 and demonstrate that rhIL-7 also serves as a potent vaccine adjuvant that broadens immunity by augmenting responses to subdominant antigens and improving the survival of the CD8(+) T cell memory pool. C1 NCI, Canc Res Ctr, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Bologna, S Orsola M Malpighi Hosp, Dept Pediat Hematol Oncol, I-40126 Bologna, Italy. Natl Canc Inst, Canc Res Ctr, Metab Branch, Bethesda, MD USA. RP Mackall, CL (reprint author), Bldg 10,Room 13N240,10 Ctr Dr,MSC 1928, Bethesda, MD 20892 USA. EM cm35c@nih.gov NR 55 TC 160 Z9 164 U1 0 U2 1 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 MAY PY 2005 VL 115 IS 5 BP 1177 EP 1187 DI 10.1172/JCI200523134 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923KH UT WOS:000228908300018 PM 15841203 ER PT J AU Duranski, MR Greer, JJM Dejam, A Jaganmohan, S Hogg, N Langston, W Patel, RP Yet, SF Wang, XD Kevil, CG Gladwin, MT Lefer, DJ AF Duranski, MR Greer, JJM Dejam, A Jaganmohan, S Hogg, N Langston, W Patel, RP Yet, SF Wang, XD Kevil, CG Gladwin, MT Lefer, DJ TI Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CYTOCHROME-C-OXIDASE; RED-BLOOD-CELLS; MYOCARDIAL-ISCHEMIA; S-NITROSOHEMOGLOBIN; GUANYLATE-CYCLASE; XANTHINE OXIDOREDUCTASE; ACTIVATED METMYOGLOBIN; LIPID-PEROXIDATION; HYPOXIC CONDITIONS; NITROGEN MONOXIDE AB Nitrite represents a circulating and tissue storage form of NO whose bioactivation is mediated by the enzymatic action of xanthine oxidoreductase, nonenzymatic disproportionation, and reduction by deoxyhemoglobin, myoglobin, and tissue heme proteins. Because the rate of NO generation from nitrite is linearly dependent on reductions in oxygen and pH levels, we hypothesized that nitrite would be reduced to NO in ischemic tissue and exert NO-dependent protective effects. Solutions of sodium nitrite were administered in the setting of hepatic and cardiac ischemia-reperfusion (I/R) injury in mice. In hepatic I/R, nitrite exerted profound dose-dependent protective effects on cellular necrosis and apoptosis, with highly significant protective effects observed at near-physiological nitrite concentrations. In myocardial I/R injury, nitrite reduced cardiac infarct size by 67%. Consistent with hypoxia-dependent nitrite bioactivation, nitrite was reduced to NO, S-nitrosothiols, N-nitrosamines, and iron-nitrosylated heme proteins within 1-30 minutes of reperfusion. Nitrite-mediated protection of both the liver and the heart was dependent on NO generation and independent of eNOS and heme oxygenase-1 enzyme activities. These results suggest that nitrite is a biological storage reserve of NO subserving a critical function in tissue protection from ischemic injury. These studies reveal an unexpected and novel therapy for diseases such as myocardial infarction, organ preservation and transplantation, and shock states. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, Shreveport, LA 71130 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Cardiol, Shreveport, LA 71130 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, Shreveport, LA 71105 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Free Rad Biol, Birmingham, AL 35294 USA. Brigham & Womens Hosp, Div Pulm & Crit Care, Boston, MA 02115 USA. NHLBI, Vasc Therapeut Sect, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Lefer, DJ (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, 1501 Kings Highway, Shreveport, LA 71130 USA. EM mgladwin@nih.gov; dlefer@lsuhsc.edu RI Yet, Shaw-Fang/B-1067-2010; Kevil, Christopher/G-9318-2011; Lefer, David/A-6372-2012; OI Yet, Shaw-Fang/0000-0001-9097-3962; Patel, Rakesh/0000-0002-1526-4303 FU NHLBI NIH HHS [2R01 HL-60849, R01 HL060849]; NIDDK NIH HHS [P01 DK043785, P01-1 DK-43785] NR 68 TC 430 Z9 447 U1 4 U2 30 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 MAY PY 2005 VL 115 IS 5 BP 1232 EP 1240 DI 10.1172/JCI200522493 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923KH UT WOS:000228908300023 PM 15841216 ER PT J AU Osei-Hyiaman, D DePetrillo, M Pacher, P Liu, J Radaeva, S Batkai, S Harvey-White, J Mackie, K Offertaler, L Wang, L Kunos, G AF Osei-Hyiaman, D DePetrillo, M Pacher, P Liu, J Radaeva, S Batkai, S Harvey-White, J Mackie, K Offertaler, L Wang, L Kunos, G TI Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ELEMENT-BINDING PROTEIN-1C; FOOD-INTAKE; GENE-EXPRESSION; ADIPOSE-TISSUE; RAT-LIVER; HORMONAL-REGULATION; BODY-WEIGHT; MICE; ANTAGONIST; ANANDAMIDE AB Endogenous cannabinoids acting at CB, receptors stimulate appetite, and CB, antagonists show promise in the treatment of obesity. CB1-/- mice are resistant to diet-induced obesity even though their caloric intake is similar to that of wild-type mice, suggesting that endocannabinoids also regulate fat metabolism. Here, we investigated the possible role of endocannabinoids in the regulation of hepatic lipogenesis. Activation of CB1 in mice increases the hepatic gene expression of the lipogenic transcription factor SR-EBP-1c and its targets acetyl-CoA carboxylase-1 and fatty acid synthase (FAS). Treatment with a CB1 agonist also increases de novo fatty acid synthesis in the liver or in isolated hepatocytes, which express CB1. High-fat diet increases hepatic levels of the endocannabinoid anandamide (arachidonoyl ethanolamide), CB1 density, and basal rates of fatty acid synthesis, and the latter is reduced by CB1 blockade. In the hypothalamus, where FAS inhibitors elicit anorexia, SREBP-1c and FAS expression are similarly affected by CB1 ligands. We conclude that anandamide acting at hepatic CBI contributes to diet-induced obesity and that the FAS pathway may be a common molecular target for central appetitive and peripheral metabolic regulation. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Physiol, Seattle, WA 98195 USA. Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. RP Kunos, G (reprint author), NIAAA, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI Mackie, Kenneth/B-7358-2011; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Mackie, Ken/E-3715-2013; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; Mackie, Ken/0000-0001-8501-6199; FU Intramural NIH HHS [Z99 AA999999] NR 52 TC 612 Z9 636 U1 3 U2 31 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 MAY PY 2005 VL 115 IS 5 BP 1298 EP 1305 DI 10.1172/JCI200523057 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923KH UT WOS:000228908300031 PM 15864349 ER PT J AU Yamano, Y Takenouchi, N Li, HC Tomaru, U Yao, K Grant, CW Maric, DA Jacobson, S AF Yamano, Y Takenouchi, N Li, HC Tomaru, U Yao, K Grant, CW Maric, DA Jacobson, S TI Virus-induced dysfunction of CD4+CD25+T cells in patients with HTLV-I-associated neuroimmunological disease SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID REGULATORY T-CELLS; IMMUNOLOGICAL SELF-TOLERANCE; TROPICAL SPASTIC PARAPARESIS; SCURFY MOUSE MUTANT; INTESTINAL INFLAMMATION; INCREASED EXPRESSION; MYELOPATHY HAM/TSP; MULTIPLE-SCLEROSIS; NEUROLOGIC DISEASE; LEISHMANIA-MAJOR AB CD4(+)CD25(+) Tregs are important in the maintenance of immunological self tolerance and in the prevention of autoimmune diseases. As the CD4(+)CD25(+) T cell population in patients with human T cell lymphotropic virus type I-associated (HTLV-I-associated) myelopathy/tropical spastic paraparesis (HAM/TSP) has been shown to be a major reservoir for this virus, it was of interest to determine whether the frequency and function of CD4(+)CD25(+) Tregs in HAM/TSP patients might be affected. in these cells, both mRNA and protein expression of the forkhead transcription factor Foxp3, a specific marker of Tregs, were lower than those in CD4(+)CD25(+) T cells from healthy individuals. The virus-encoded transactivating HTLV-1 tax gene was demonstrated to have a direct inhibitory effect on Foxp3 expression and function of CD4(+)CD25(+) T cells. This is the first report to our knowledge demonstrating the role of a specific viral gene product (HTLV-I Tax) on the expression of genes associated with Tregs (in particular, foxp3) resulting in inhibition of Treg function. These results suggest that direct human retroviral infection of CD4(+)CD25(+) T cells may be associated with the pathogenesis of HTLV-I-associated neurologic disease. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Kagoshima City Hosp, Kagoshima, Japan. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Hokkaido Univ, Grad Sch Med, Dept Pathol Pathophysiol, Sapporo, Hokkaido, Japan. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, NIB Bldg 10,Room 5B-16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 57 TC 84 Z9 88 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2005 VL 115 IS 5 BP 1361 EP 1368 DI 10.1172/JCI200523913 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923KH UT WOS:000228908300038 PM 15864353 ER PT J AU de Jong, FA Engels, FK Mathijssen, RHJ van Zuylen, L Verweij, J Peters, RPH Sparreboom, A AF de Jong, FA Engels, FK Mathijssen, RHJ van Zuylen, L Verweij, J Peters, RPH Sparreboom, A TI Medicinal cannabis in oncology practice: Still a bridge too far? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID CHEMOTHERAPY-INDUCED NAUSEA; CANCER-ASSOCIATED ANOREXIA; SQUAMOUS-CELL CARCINOMA; MARIJUANA USE; MYOCARDIAL-INFARCTION; COMBINATION THERAPY; MULTIPLE-SCLEROSIS; MEGESTROL-ACETATE; DELTA-9-TETRAHYDROCANNABINOL; DRONABINOL C1 Erasmus Univ, Med Ctr Rotterdam, Dept Med Oncol, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. VU Univ Med Ctr, Dept Internal Med, Amsterdam, Netherlands. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. RP de Jong, FA (reprint author), Erasmus Univ, Med Ctr Rotterdam, Dept Med Oncol, Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011 NR 49 TC 13 Z9 13 U1 1 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 1 PY 2005 VL 23 IS 13 BP 2886 EP 2891 DI 10.1200/JCO.2005.04.150 PG 6 WC Oncology SC Oncology GA 922EA UT WOS:000228817900004 PM 15860846 ER PT J AU Kaplan, B Martin, BM Cohen, HI Manaster, J Kassif, Y Rehany, U Livneh, A AF Kaplan, B Martin, BM Cohen, HI Manaster, J Kassif, Y Rehany, U Livneh, A TI Primary local orbital amyloidosis: biochemical identification of the immunoglobulin light chain kappa III subtype in a small formalin fixed, paraffin wax embedded tissue sample SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID MONOCLONAL ORIGIN; PROTEINS; DEPOSITS AB Background: Amyloidosis refers to a heterogeneous group of disorders associated with the deposition of chemically distinct amyloid fibril proteins. Precise determination of chemical amyloid type has diagnostic, therapeutic, and prognostic relevance. Although immunohistochemical techniques are used routinely to determine the amyloid type, the results can be negative or inconclusive, so that biochemical characterisation is often required. The development and application of new biochemical microtechniques suitable for examination of extremely small tissue samples is essential for precise identification of the deposited amyloid proteins. Aims: To investigate biochemically the amyloid proteins present in a formalin fixed paraffin wax embedded orbital tissue from a patient with localised orbital amyloidosis in whom immunohistochemistry was not helpful in the determination of amyloid type. Methods: Extraction of amyloid proteins from fixed tissue and their identification was carried out by a recently developed microtechnique. An extremely small tissue sample was dewaxed and extracted with formic acid. The extracted material was analysed using electrophoresis, western blotting, and amino acid sequencing. Results: Biochemical examination of the extracted proteins showed the presence of immunoglobulin (Ig) derived amyloid proteins, which were composed of the N-terminal fragments of the Ig light chain kappa III subtype (AL-kappa III) ( 16, 8, and 3 kDa). Conclusions: This is the first chemically proved AL case reported in association with primary localised orbital amyloidosis. The biochemical microtechnique used was useful in achieving a precise diagnosis of amyloid disease, in a case where the results of routine immunohistochemical examination of amyloid were inconclusive. C1 Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Western Galilee Hosp, Nahariya Med Ctr, Dept Pathol, IL-22100 Nahariyya, Israel. Western Galilee Hosp, Haematol Unit, IL-22100 Nahariyya, Israel. Western Galilee Hosp, Dept Ophthalmol, IL-22100 Nahariyya, Israel. RP Kaplan, B (reprint author), Chaim Sheba Med Ctr, Heller Inst Med Res, IL-52621 Tel Hashomer, Israel. EM kaplanb@sheba.health.gov.il NR 20 TC 7 Z9 7 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD MAY PY 2005 VL 58 IS 5 BP 539 EP 542 DI 10.1136/jcp.2004.022517 PG 4 WC Pathology SC Pathology GA 920TD UT WOS:000228712100016 PM 15858128 ER PT J AU Petry, NM Stinson, FS Grant, BF AF Petry, NM Stinson, FS Grant, BF TI Comorbidity of DSM-IV pathological gambling and other psychiatric disorders: Results from 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; UNITED-STATES 1988; III-R; PERSONALITY-DISORDERS; ICD-10 ALCOHOL; DRUG MODULES; NOSOLOGICAL COMPARISONS; GENDER DIFFERENCES AB Objective: To present nationally representative data on lifetime prevalence and comorbidity of pathological gambling with other psychiatric disorders and to evaluate sex differences in the strength of the comorbid associations. Method: Data were derived from a large national sample of the United States. Some 43,093 household and group quarters residents age 18 years and older participated in the 2001-2002 survey. Prevalence and associations of lifetime pathological gambling and other lifetime psychiatric disorders are presented. The diagnostic interview was the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Fifteen symptom items operationalized the 10 pathological gambling criteria. Results: The lifetime prevalence rate of pathological gambling was 0.42%. Almost three quarters (73.2%) of pathological gamblers had an alcohol use disorder, 38.1% had a drug use disorder, 60.4% had nicotine dependence, 49.6% had a mood disorder, 41.3% had an anxiety disorder, and 60.8% had a personality disorder. A large majority of the associations between pathological gambling and substance use, mood, anxiety, and personality disorders were overwhelmingly positive and significant (p < .05), even after controlling for sociodemographic and socioeconomic characteristics. Male sex, black race, divorced/separated/widowed marital status, middle age, and living in the West and Midwest were associated with increased risk for pathological gambling. Further, associations between alcohol dependence, any drug use disorder, drug abuse, nicotine dependence, major depressive episode, and generalized anxiety disorder and pathological gambling were stronger among women than men (p > .05). Conclusion: Pathological gambling is highly comorbid with substance use, mood, anxiety, and personality disorders, suggesting that treatment for one condition should involve assessment and possible concomitant treatment for comorbid conditions. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, US Dept HHS,NIH, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, US Dept HHS,NIH, Room 3007,MS 9304,5635 Fishers Ln, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU NIAAA NIH HHS [P50 AA 03510]; NIDA NIH HHS [P50 DA 09241, R01 DA 016855, R01 DA 13444, R01 DA 14618]; NIMH NIH HHS [R01 MH 60417] NR 76 TC 563 Z9 571 U1 7 U2 38 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 MAY PY 2005 VL 66 IS 5 BP 564 EP 574 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 928WR UT WOS:000229302900004 PM 15889941 ER PT J AU McElroy, SL Suppes, T Keck, PE Black, D Frye, MA Altshuler, LL Nolen, WA Kupka, RW Leverich, GS Walden, J Grunze, H Post, RM AF McElroy, SL Suppes, T Keck, PE Black, D Frye, MA Altshuler, LL Nolen, WA Kupka, RW Leverich, GS Walden, J Grunze, H Post, RM TI Open-label adjunctive zonisamide in the treatment of bipolar disorders: A prospective trial SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID LITHIUM MAINTENANCE TREATMENT; RANDOMIZED CONTROLLED-TRIAL; CONTROLLED 18-MONTH TRIAL; I DISORDER; ANTIEPILEPTIC DRUG; DOUBLE-BLIND; OBESITY; ANTICONVULSANT; LAMOTRIGINE; MANIA AB Background: The response of 62 outpatients with DSM-IV bipolar disorders to open-label adjunctive zonisamide was evaluated in a prospective 8-week acute trial, followed by a 48-week continuation trial, conducted from June 2001 through May 2002. Method: During the acute trial, response to zonisamide was assessed weekly for the first 4 weeks and every 2 weeks for the second 4 weeks with the Clinical Global Impressions scale modified for bipolar illness (CGI-BP), the Young Mania Rating Scale (YMRS), and the Inventory for Depressive Symptomatology (IDS). During the continuation trial, patients were assessed with these scales every 4 weeks. Patients' weights and side effects were also evaluated. Outcome measures were analyzed with repeated-measures analyses of variance. Results: Patients with manic symptoms at study entry (N = 34) displayed significant reductions in CGI-BP-Mania Severity and YMRS scores in the acute and continuation (N = 19) trials (p values < .0001 and < .001, respectively). Patients with depressive symptoms at study entry (N = 22) showed significant decreases in CGI-BP-Depression Severity and IDS scores in the acute trial (p values < .001 and < .05, respectively), but only 9 patients entered the continuation trial. Among these 9 patients, maintenance of antidepressant response was mostly maintained. Initially euthymic patients (N = 6) showed no change in any rating scale scores acutely, but 2 of 4 patients who entered the continuation trial developed depressive symptoms. The 62 patients as a group showed significant weight loss in both trials (p values < .001). However, 20 patients (32%) discontinued zonisamide for worsening mood symptoms. Conclusion: Adjunctive zonisamide was associated with beneficial effects on mood and body weight in some patients with bipolar disorders, but was also associated with a high discontinuation rate due to worsening mood symptoms. Double-blind, placebo-controlled studies are necessary to determine zonisamide's thymoleptic properties, if any, in bipolar disorders. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45267 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Groningen Hosp, Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Freiburg Klinikum, Zent Innovat Therapie Bipolarer Storurgen, Freiburg, Germany. Univ Munich, Psychiat Klin, Munich, Germany. RP McElroy, SL (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, POB 670559,231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM susan.mcelroy@uc.edu RI Nolen, Willem/E-9006-2014 FU NIMH NIH HHS [R01 MH079261] NR 39 TC 51 Z9 51 U1 0 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2005 VL 66 IS 5 BP 617 EP 624 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 928WR UT WOS:000229302900012 PM 15889949 ER PT J AU Huey, ED Dustin, IH Overman, GP Mirza, N Sunderland, T AF Huey, ED Dustin, IH Overman, GP Mirza, N Sunderland, T TI Development of subtle psychotic symptoms with memantine: A case report SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Letter ID ALZHEIMERS-DISEASE; NIGHTMARES C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Huey, ED (reprint author), NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NR 14 TC 16 Z9 17 U1 0 U2 0 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD MAY PY 2005 VL 66 IS 5 BP 658 EP 659 PG 2 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 928WR UT WOS:000229302900024 PM 15889961 ER PT J AU Samanic, C Hoppin, JA Lubin, JH Blair, A Alavanja, MCR AF Samanic, C Hoppin, JA Lubin, JH Blair, A Alavanja, MCR TI Factor analysis of pesticide use patterns among pesticide applicators in the Agricultural Health Study SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE pesticides; farmers; custom applicators; factor analysis; herbicides; insecticides; fungicides; fumigants; Iowa; North Carolina ID BREAST-CANCER; RISK AB Exposure to certain pesticides has been linked with both acute and chronic adverse health outcomes such as neurotoxicity and risk for certain cancers. Univariate analyses of pesticide exposures may not capture the complexity of these exposures since use of various pesticides often occurs simultaneously, and because specific uses have changed over time. Using data from the Agricultural Health Study, a cohort study of 89,658 licensed pesticide applicators and their spouses in Iowa and North Carolina, we employed factor analysis to order to characterize underlying patterns of self-reported exposures to 50 different pesticides. Factor analysis is a statistical method used to explain the relationships between several correlated variables by reducing them to a smaller number of conceptually meaningful, composite variables, known as factors. Three factors emerged for farmer applicators (N = 45,074): (1) Iowa agriculture and herbicide use, (2) North Carolina agriculture and use of insecticides, fumigants and fungicides, and (3) older age and use of chlorinated pesticides. The patterns observed for spouses of farmers (N = 17,488) were similar to those observed for the farmers themselves, whereas five factors emerged for commercial pesticide applicators (N = 4,384): (1) herbicide use, (2) older age and use of chlorinated pesticides, (3) use of fungicides and residential pest treatments, (4) use of animal insecticides, and (5) use of fumigants. Pesticide exposures did not correlate with lifestyle characteristics such as race, smoking status or education. This heterogeneity in exposure patterns may be used to guide etiologic studies of health effects of farmers and other groups exposed to pesticides. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Samanic, C (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8115, Bethesda, MD 20892 USA. EM samanicc@mail.nih.gov NR 15 TC 7 Z9 7 U1 2 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD MAY PY 2005 VL 15 IS 3 BP 225 EP 233 DI 10.1038/sj.jea.7500396 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 925HO UT WOS:000229044400004 PM 15280893 ER PT J AU Faber, M Lamirande, EW Roberts, A Rice, AB Koprowski, H Dietzschold, B Schnell, MJ AF Faber, M Lamirande, EW Roberts, A Rice, AB Koprowski, H Dietzschold, B Schnell, MJ TI A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RECOMBINANT RABIES VIRUS; TYPE-1 GAG; HIV-1; VACCINES; MICE; LIVE; GLYCOPROTEIN; REPLICATION; INFECTION AB Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans. C1 Thomas Jefferson Univ, Dept Mol Pharmacol & Biochem, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schnell, MJ (reprint author), Thomas Jefferson Univ, Dept Mol Pharmacol & Biochem, 233 S 10th St,Suite 350 BLSB, Philadelphia, PA 19107 USA. EM matthias.schnell@jefferson.edu FU NIAID NIH HHS [R21 AI062964-01] NR 31 TC 60 Z9 69 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD MAY PY 2005 VL 86 BP 1435 EP 1440 DI 10.1099/vir0.80844-0 PN 5 PG 6 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 920VC UT WOS:000228717200022 PM 15831955 ER PT J AU Or, Z Wang, J Jamison, D AF Or, Z Wang, J Jamison, D TI International differences in the impact of doctors on health: a multilevel analysis of OECD countries SO JOURNAL OF HEALTH ECONOMICS LA English DT Article DE health system efficiency; physician effect; multilevel analysis ID LEAGUE TABLES; MANAGED CARE; PERFORMANCE; MODELS AB This paper aims to measure whether there are country variations in the efficiency of the physician workforce in reducing various measures of mortality across 21 OECD countries over 3 decades. It utilises a multilevel modelling approach both to measure country variations in physician efficiency and to explore the determinants of these variations. The results suggested that physician numbers are an important determinant of mortality across OECD countries, and cross-country heterogeneity in the effect of physician availability on health is significant. We also found that availability of advanced medical technology is an important factor intervening in this relationship. (c) 2004 Elsevier B.V. All rights reserved. C1 INSERM, U537, F-94276 Le Kremlin Bicetre, France. Univ Calif Los Angeles, Los Angeles, CA USA. NIH, Washington, DC USA. RP Or, Z (reprint author), INSERM, U537, 80 Rue Gen Leclerc, F-94276 Le Kremlin Bicetre, France. EM Or@kb.inserm.fr NR 22 TC 31 Z9 32 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-6296 J9 J HEALTH ECON JI J. Health Econ. PD MAY PY 2005 VL 24 IS 3 BP 531 EP 560 DI 10.1016/j.jhealeco.2004.09.00 PG 30 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 920UG UT WOS:000228715000006 PM 15811542 ER PT J AU Real, LA Russell, C Waller, L Smith, D Childs, J AF Real, LA Russell, C Waller, L Smith, D Childs, J TI Spatial dynamics and molecular ecology of North American rabies SO JOURNAL OF HEREDITY LA English DT Article; Proceedings Paper CT International Meeting on Genomes and Evolution 2004 CY JUN 17-20, 2004 CL Penn State Univ, State Coll, PA SP Amer Genet Assoc, Int Soc Mol Biol & Evolut HO Penn State Univ ID UNITED-STATES; RACCOON RABIES; VIRUS VARIANTS; SPREAD; FOXES; EPIDEMIOLOGY; SURVEILLANCE; CANADA AB Rabies, caused by a single-stranded RNA virus, is arguably the most important viral zoonotic disease worldwide. Although endemic throughout many regions for millennia, rabies is also undergoing epidemic expansion, often quite rapid, among wildlife populations across regions of Europe and North America. A current rabies epizootic in North America is largely attributable to the accidental introduction of a particularly well-adapted virus variant into a naive raccoon population along the Virginia/West Virginia border in the mid-1970s. We have used the extant database on the spatial and temporal occurrence of rabid raccoons across the eastern United States to construct predictive models of disease spread and have tied patterns of emergence to local environmental variables, genetic heterogeneity, and host specificity. Rabies will continue to be a remarkable model system for exploring basic issues in the temporal and spatial dynamics of expanding infectious diseases and examining ties between disease population ecology and evolutionary genetics at both micro- and macro-evolutionary time scales. C1 Emory Univ, Dept Biol, Atlanta, GA 30322 USA. Emory Univ, Ctr Dis Ecol, Atlanta, GA 30322 USA. Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. Emory Univ, Dept Biostat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Real, LA (reprint author), Emory Univ, Dept Biol, 1510 Clifton Rd NE, Atlanta, GA 30322 USA. EM lreal@emory.edu RI Russell, Colin/B-2226-2008; Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU NIAID NIH HHS [R01 AI047498] NR 34 TC 21 Z9 21 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD MAY PY 2005 VL 96 IS 3 BP 253 EP 260 DI 10.1093/jhered/esi031 PG 8 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 908ER UT WOS:000227770700010 PM 15677743 ER PT J AU Saavedra, JM AF Saavedra, JM TI Studies on genes and hypertension: a daunting task SO JOURNAL OF HYPERTENSION LA English DT Editorial Material ID ALPHA-ADDUCIN GENE; BLOOD-PRESSURE VARIATION; LOW-RENIN HYPERTENSION; SALT SENSITIVITY; GLY460TRP POLYMORPHISM; MYOCARDIAL-INFARCTION; DIURETIC THERAPY; ASSOCIATION; POPULATION; EXCRETION C1 NIMH, DIRP, Sect Pharmacol, DHHS NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, DIRP, Sect Pharmacol, DHHS NIH, 10 Ctr Dr,Bldg 10,Room 2D-57, Bethesda, MD 20892 USA. EM saavedrj@mail.nih.gov NR 43 TC 19 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD MAY PY 2005 VL 23 IS 5 BP 929 EP 932 DI 10.1097/01.hjh.0000166829.02323.b2 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 923LZ UT WOS:000228912700004 PM 15834274 ER PT J AU Song, EY VanDunk, C Kuddo, T Nelson, PG AF Song, EY VanDunk, C Kuddo, T Nelson, PG TI Measurement of Vasoactive Intestinal Peptide using a Competitive Fluorescent Microsphere Immunoassay or ELISA in human blood samples SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE ELISA; fluorescent microsphere immunoassay; VIP ID NUCLEOTIDE POLYMORPHISM ANALYSIS; FLOWMETRIX(TM) SYSTEM; MULTIPLEXED ANALYSIS; HUMAN CYTOKINES; QUANTITATION; ASSAY; ANTIBODIES; SERUM; VIP AB The concentration of Vasoactive Intestinal Peptide (VIP) as measured by recycling immunoaffinity chromatography (RIC) has been reported to be elevated in the blood of patients with autism as compared with normal subjects. In this study, we have developed a "Competitive Fluorescent Microsphere Immunoassay" (cFMI) in which VIP competes with biotinylated VIP in binding to polyclonal antibodies on microspheres. The results were obtained using the Luminex too system. We measured VIP in serum, plasma, and material eluted from dried blood spots on filter paper with both the cFMI and an ELISA procedure. We found that a purification procedure was necessary for obtaining useful results from plasma and serum, however, a preincubation step was required with the blood eluates. This newly developed cFMI was more sensitive (2.5 vs. 20.0 pg/ml), and more reproducible than the ELISA. To get accurate measurements of VIP in eluted material high sensitivity is especially important. Thus, the cFMI using the Luminex system has definite advantages over a conventional ELISA including the possibility that samples can be assayed at higher dilutions. We have determined that the VIP concentrations of serum, plasma, and dried blood spot eluate specimens as measured with the cFMI assay system were similar to those measured with ELISA. Thus, the new cFMI using Luminex system may be useful for detection of VIP in human blood samples. Published by Elsevier B.V. C1 NICHHD, LDN, NIH, Bethesda, MD 20892 USA. RP Nelson, PG (reprint author), NICHHD, LDN, NIH, Bldg 31 Room 2A25, Bethesda, MD 20892 USA. EM nelsonp@mail.nih.gov NR 24 TC 7 Z9 7 U1 1 U2 6 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 MAY PY 2005 VL 300 IS 1-2 BP 63 EP 73 DI 10.1016/j.jim.2005.02.009 PG 11 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 941MM UT WOS:000230218900006 PM 15894328 ER PT J AU Li, ZQ Lim, WK Mahesh, SP Liu, BY Nussenblatt, RB AF Li, ZQ Lim, WK Mahesh, SP Liu, BY Nussenblatt, RB TI Cutting edge: In vivo blockade of human IL-2 receptor induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MULTIPLE-SCLEROSIS; EXPRESSION; DACLIZUMAB; INTERLEUKIN-2; ACTIVATION; MECHANISMS; ANTIBODIES; THERAPY; BIOLOGY AB In vivo blockade of the human IL-2R by mAb has been used for immunosuppression in transplantation, therapy for leukemia, and autoimmune diseases. In this study, we report that administration of a humanized IL-2R blocking Ab induced a 4- to 20-fold expansion of CD56(bright) regulatory NK cells in uveitis patients over time. The induced CD56(bright) regulatory NK cells from patients exhibited similar phenotype as those naturally occurring CL56(bright) cells. Patients with active uveitis had a significantly lower level of CD56(bright) NK cells compared with normal donors (p < 0.01). In addition, the induced CD56bright, cells could secrete large amounts of IL-10 whereas CD56(dim) NK cells could not, suggesting that the induction of the CD56(bright) cells may have a beneficial effect on the remission of active uveitis. Our observation may have implications to IL-2R blockade therapy and for the potential role of CD56(bright) regulatory NK cells in autoimmune diseases. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Singapore Natl Eye Ctr, Singapore, Singapore. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10S219, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov NR 30 TC 70 Z9 71 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2005 VL 174 IS 9 BP 5187 EP 5191 PG 5 WC Immunology SC Immunology GA 919PU UT WOS:000228630800004 PM 15843513 ER PT J AU Peng, Z Beaven, MA AF Peng, Z Beaven, MA TI An essential role for phospholipase D in the activation of protein kinase C and degranulation in mast cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASOPHILIC RBL-2H3 CELLS; ADP-RIBOSYLATION FACTOR; PHOSPHATIDYLCHOLINE HYDROLYSIS; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; SIMILAR MECHANISMS; CA2+ STORES; IN-VITRO; ANTIGEN; DIACYLGLYCEROL; EXOCYTOSIS AB Activation of phospholipase D (PLD) and protein kinase C (PKC) as well as calcium mobilization are essential signals for degranulation of mast cells. However, the exact role of PLD in degranulation remains undefined. In this study we have tested the hypothesis that the PLD product, phosphatidic acid, and diacylglycerides generated therefrom might promote activation of PKC. Studies were conducted in two rodent mast cell lines that were stimulated with Ag via Fc epsilon RI and a pharmacologic agent, thapsigargin. Diversion of production of phosphatidic acid to phosphatidylbutanol (the transphosphatidylation reaction) by addition of 1-butanol suppressed both the translocation of diacylglyceride-dependent isoforms of PKC to the membrane and degranulation. Tertiary-butanol, which is not a substrate for the transphosphatidylation, had a minimal effect on PKC translocation and degranulation, and I-butanol itself had no effect on PKC translocation when PKC was stimulated directly with phorbol ester, 12-O-tetradecanoylphorbol-13-acetate. Also, in cells transfected with small inhibitory RNAs directed against PLD1 and PLD2, activation of PLD, generation of diacylglycerides, translocation of PKC, and degranulation were all suppressed. Phorbol ester, which did not stimulate degranulatian by itself, restored degranulation when used in combination with thapsigargin whether PLD function was disrupted with 1-butanol or the small inhibitory RNAs. However, degranulation was not restored when cells were costimulated with Ag and phorbol ester. These results suggested that the production of phosphatidic acid by PLD facilitates activation of PKC and, in turn, degranulation, although additional PLD-dependent processes appear to be critical for Ag-mediated degranulation. C1 NHLBI, Lab Mol Immunol, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, Dept Hlth & Human Serv, NIH, Room 8N109,Bldg 10, Bethesda, MD 20892 USA. EM beavenm@nhlbi.nih.gov NR 47 TC 38 Z9 40 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 MAY 1 PY 2005 VL 174 IS 9 BP 5201 EP 5208 PG 8 WC Immunology SC Immunology GA 919PU UT WOS:000228630800006 PM 15843515 ER PT J AU Ahmadzadeh, M Rosenberg, SA AF Ahmadzadeh, M Rosenberg, SA TI TGF-beta 1 attenuates the acquisition and expression of effector function by tumor antigen-specific human memory CD8 T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TGF-BETA; TRANSCRIPTION FACTOR; METASTATIC MELANOMA; ADOPTIVE TRANSFER; FACTOR-ALPHA; LYMPHOCYTES; INHIBITION; CANCER; RECEPTOR AB TGF-beta 1 is a potent immunoregulatory cytokine. However, its impact on the generation and effector function of Ag-specific human effector memory CD8 T cells had not been evaluated. Using Ag-specific CD8 T cells derived from melanoma patients immunized with the gp100 melanoma Ag, we demonstrate that the addition of TGF-beta 1 to the initial Ag activation cultures attenuated the gain of effector function by Ag-specific memory CD8 T cells while the phenotypic changes associated with activation and differentiation into effector memory were comparable to control cultures. These activated memory CD8 T cells consistently expressed lower mRNA levels for T-bet, suggesting a mechanism for TGF-beta 1-mediated suppression of gain of effector function in memory T cells. Moreover, TGF-beta 1 induced a modest expression of CCR7 on Ag-activated memory CD8 T cells. TGF-beta 1 also suppressed cytokine secretion by Ag-specific effector memory CD8 T cells, as well as melanoma-reactive tumor-infiltrating lymphocytes and CD8 T cell clones. These results demonstrate that TGF-beta 1 suppresses not only the acquisition but also expression of effector function on human memory CD8 T cells and tumor-infiltrating lymphocytes reactive against melanoma, suggesting that TGF-beta 1-mediated suppression can hinder the therapeutic benefits of vaccination, as well as immunotherapy in cancer patients. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, Clin Res Ctr Bldg,Room 3-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov FU Intramural NIH HHS [Z01 SC003811-33] NR 44 TC 86 Z9 100 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2005 VL 174 IS 9 BP 5215 EP 5223 PG 9 WC Immunology SC Immunology GA 919PU UT WOS:000228630800008 PM 15843517 ER PT J AU Suffia, I Reckling, SK Salay, G Belkaid, Y AF Suffia, I Reckling, SK Salay, G Belkaid, Y TI A role for CD103 in the retention of CD4(+)CD25(+) T-reg and control of Leishmania major infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ALPHA(E) (CD103)-DEFICIENT MICE; CELL INTEGRIN ALPHA(M290)BETA-7; LYMPHOCYTE-ASSOCIATED ANTIGEN; MONOCLONAL-ANTIBODY HML-1; E BETA 7; DENDRITIC CELLS; E-CADHERIN; EPITHELIAL-CELLS; MEMBRANE MOLECULE; MEDIATED-IMMUNITY AB Endogenous regulatory T cells (T,,g) play a central role in the control of excessive or misdirected immune responses against self or foreign Ags. To date, virtually no data are available on the nature of the molecules and signals involved in the trafficking and retention of T-reg in tissues where regulation is required. Here, we show that expression of alpha(E)beta(7) integrin is necessary for the homing of T-reg at site of Leishmania major infection. The vast majority of T-reg present in the dermis at steady-state conditions or during L. major infection express the a. chain (CD103) of alpha(E)beta(7). Genetically susceptible BALB/c mice that lack CD103 become resistant to infection, a phenotype that is associated with a poor capacity of T-reg to be retained in the infected site. Such susceptible phenotype can be restored when T-reg from wild-type mice were transferred in CD103(-/-) mice. The central role of CD103 in Treg retention was further demonstrated by usage of blocking Abs against CD103 and the transfer of T-reg purified from CD103(-/-) mice. Our results strongly suggest that this molecule is induced and maintained on T-reg following or just prior to their arrival in tissues. Furthermore, the expression of CD103 and the subsequent retention of T-reg in tissues is highly regulated by their exposure to Leishmania Ag and the level of activation of the APCs they encounter. Thus, CD103, by controlling T-reg retention, can contribute to the outcome of chronic infection by Leishmania. C1 Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. RP Belkaid, Y (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr, Rockville, MD 20852 USA. EM ybelkaid@niaid.nih.gov FU NIAID NIH HHS [R01AI057992-01] NR 61 TC 215 Z9 220 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2005 VL 174 IS 9 BP 5444 EP 5455 PG 12 WC Immunology SC Immunology GA 919PU UT WOS:000228630800034 PM 15845457 ER PT J AU Brittingham, KC Ruthel, G Panchal, RG Fuller, CL Ribot, WJ Hoover, TA Young, HA Anderson, AO Bavari, S AF Brittingham, KC Ruthel, G Panchal, RG Fuller, CL Ribot, WJ Hoover, TA Young, HA Anderson, AO Bavari, S TI Dendritic cells endocytose Bacillus anthracis spores: Implications for anthrax pathogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; LETHAL FACTOR CLEAVES; DRAINING LYMPH-NODES; CYCLIC-AMP; INHALATIONAL ANTHRAX; COILING PHAGOCYTOSIS; FACTOR-ALPHA; TNF-ALPHA; IN-VIVO; MACROPHAGES AB Phagocytosis of inhaled Bacillus anthracis spores and subsequent trafficking to lymph nodes are decisive events in the progression of inhalational anthrax because they initiate germination and dissemination of spores. Found in high frequency throughout the respiratory track, dendritic cells (DCs) routinely take up foreign particles and migrate to lymph nodes. However, the participation of DCs in phagocytosis and dissemination of spores has not been investigated previously. We found that human DCs readily engulfed fully pathogenic Ames and attenuated B. anthracis spores predominately by coiling phagocytosis. Spores provoked a loss of tissue-retaining chemokine receptors (CCR2, CCR5) with a concurrent increase in lymph node homing receptors (CCR7, CD11c) on the membrane of DCs. After spore infection, immature DCs displayed a mature phenotype (CD83(bright), HLA-DRbright, CD80(bright), CD86(bright), CD40(bright)) and enhanced costimulatory activity. Surprisingly, spores activated the MAPK cascade (ERK, p38) within 30 min and stimulated expression of several inflammatory response genes by 2 h. MAPK signaling was extinguished by 6 h infection, and there was a dramatic reduction of secreted TNF-alpha, IL-6, and IL-8 in the absence of DC death. This corresponded temporally with enzymatic cleavage of proximal MAPK signaling proteins (MEK-1, MEK-3, and MAP kinase kinase-4) and may indicate activity of anthrax lethal toxin. Taken together, these results suggest that B. anthracis may exploit DCs to facilitate infection. C1 USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. Dev Therapeut Program, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, 1425 Porter St, Frederick, MD 21702 USA. EM bavaris@ncifcrf.gov NR 39 TC 90 Z9 94 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 MAY 1 PY 2005 VL 174 IS 9 BP 5545 EP 5552 PG 8 WC Immunology SC Immunology GA 919PU UT WOS:000228630800045 PM 15843553 ER PT J AU Pinchuk, I Starcher, BC Livingston, B Tvninnereim, A Wu, SP Appella, E Sidney, J Sette, A Wizel, B AF Pinchuk, I Starcher, BC Livingston, B Tvninnereim, A Wu, SP Appella, E Sidney, J Sette, A Wizel, B TI A CD8(+) T cell heptaepitope minigene vaccine induces protective immunity against Chlamydia pneumoniae SO JOURNAL OF IMMUNOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; PLASMID DNA; INCLUSION MEMBRANE; LYMPHOCYTE-RESPONSES; VACUOLAR PATHOGEN; GAMMA-INTERFERON; TC1 RESPONSES; IFN-GAMMA; TRACHOMATIS; INFECTION AB An intact T cell compartment and IFN-gamma signaling are required for protective immunity against Chlamydia. In the mouse model of Chlamydia pneumoniae (Cpn) infection, this immunity is critically dependent on CD8(+) T cells. Recently we reported that Cpn-infected mice generate an MRC class I-restricted CD8(+) Tc1 response against various Cpn Ags, and that CD8(+) CTL to multiple epitopes inhibit Cpn growth in vitro. Here, we engineered a DNA minigene encoding seven H-2(b)-restricted Cpn CTL epitopes, the universal pan-DR epitope Th epitope, and an endoplasmic reticulum-translocating signal sequence. Immunization of C5713L/6 mice with this construct primed IFN-gamma-producing CD8(+) CTL against all seven CTL epitopes. CD8(+) T cell lines generated to minigene-encoded CTL epitopes secreted IFN-gamma and TNF-alpha and exhibited CTL activity upon recognition of Cpn-infected macrophages. Following intranasal challenge with Cpn, a 3.6 log reduction in mean lung bacterial numbers compared with control animals was obtained. Using a 20-fold increase in the Cpn challenging dose, minigene-vaccinated mice had a 60-fold reduction in lung bacterial loads, compared with controls. Immunization and challenge studies with beta(2)-microglobulin(-/-) mice indicated that the reduction of lung Cpn burdens was mediated by the MHC class I-dependent CD8(+) T cells to minigene-included Cpn CTL epitopes, rather than by pan-DR epitope-specific CD4(+) T cells. This constitutes the first demonstration of significant protection achieved by immunization with a CD8(+) T cell epitope-based DNA construct in a bacterial system and provides the basis for the optimal design of multicomponent anti-Cpn vaccines for humans. The Journal of Immunology, 2005. C1 Univ Texas Hlth Ctr, Ctr Pulm & Infect Dis Control, Dept Microbiol & Immunol, Tyler, TX 75708 USA. Univ Texas Hlth Ctr, Dept Biochem, Tyler, TX 75708 USA. Epimmune, San Diego, CA 92121 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. NCI, Bethesda, MD 20892 USA. RP Wizel, B (reprint author), Univ Texas Hlth Ctr, Ctr Pulm & Infect Dis Control, Dept Microbiol & Immunol, 11937 US Highway 271, Tyler, TX 75708 USA. EM bwizel@uthct.edu RI Pinchuk, Irina/A-7227-2008 OI Pinchuk, Irina/0000-0003-1505-5779 FU NHLBI NIH HHS [R01 HL7064] NR 70 TC 18 Z9 20 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2005 VL 174 IS 9 BP 5729 EP 5739 PG 11 WC Immunology SC Immunology GA 919PU UT WOS:000228630800067 PM 15843575 ER PT J AU Stroncek, DF Burns, C Martin, BM Rossi, L Marincola, FM Panelli, MC AF Stroncek, DF Burns, C Martin, BM Rossi, L Marincola, FM Panelli, MC TI Advancing cancer biotherapy with proteomics SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE interleukin 2; granulocyte colony-stimulating factor; proteomics; immunotherapy; mass spectrometry; ELISA ID COLONY-STIMULATING FACTOR; PROSTATE-CANCER; OVARIAN-CANCER; EXPRESSION PATTERNS; METASTATIC MELANOMA; ADHESION MOLECULES; RENAL-CANCER; TNF-ALPHA; SERUM; RECEPTOR AB Proteomics is becoming increasingly important for cancer biotherapy. The development of high-throughput platforms now allows the analysis of multiple proteins from small quantities of material. While these techniques are being used to discover new biomarkers, they are particularly important for assessing complex biologic processes such as immunotherapy for cancer. Recent advances in this field are reviewed, as well as the use of proteomics to assess the effectiveness and toxicities of high-dose IL-2 cancer therapy. Proteomics is becoming useful in assessing cancer biotherapies and in unraveling their mechanisms of action. High-throughput proteomic technologies have now advanced to a stage where they have the potential to become effective discovery tools for biomarkers/predictors of disease, disease recurrence, and response to therapy. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Immunogenet Sect, Bethesda, MD 20892 USA. Pierce Boston Technol Ctr, Woburn, MA USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Pisa, Dept Human Morphol & Appl Biol, I-56100 Pisa, Italy. RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Immunogenet Sect, Bldg 10,Room 1C711,10 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 46 TC 13 Z9 14 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 MAY-JUN PY 2005 VL 28 IS 3 BP 183 EP 192 DI 10.1097/01.cji.0000162781.78384.95 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 921RN UT WOS:000228782500003 PM 15838374 ER PT J AU Kawakami, K Kioi, M Liu, Q Kawakami, M Puri, RK AF Kawakami, K Kioi, M Liu, Q Kawakami, M Puri, RK TI Evidence that IL-13R alpha-2 chain in human glioma cells is responsible for the antitumor activity mediated by receptor-directed cytotoxin therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE glioblastoma; interleukin-13 receptor; immunotoxin; gene therapy; antisense oligonucleotide ID INTERLEUKIN-13 RECEPTOR; IL-13 RECEPTOR; ALPHA-2 CHAIN; SIGNAL-TRANSDUCTION; PSEUDOMONAS EXOTOXIN; TARGETED CYTOTOXIN; NECK-CANCER; IN-VIVO; TUMOR IMMUNOSURVEILLANCE; PANCREATIC TUMORS AB The interleukin-13 receptor alpha 2 (IL-13R alpha 2) chain is a primary IL-13 binding and internalization component of the IL-13R system. Previous studies have shown that human brain tumors, including glioblastoma multiforme (GBM), overexpress IL-13R alpha 2 chain, while normal brain cells do not express this protein or express very low levels of it. To target IL-13R on brain tumor cells, the authors have developed an IL-13R-directed cytotoxin termed IL13-PE38QQR to induce specific cancer cell killing. To investigate the role of IL-13R alpha 2 chain in GBM, cells were treated with antisense oligonucleotide or siRNA to IL-13R alpha 2 chain, and cellular IL-13 binding and sensitivity to IL-13 cytotoxin were assessed. IL-13R alpha 2 gene interference in GBM cells showed decreased ligand binding, and consequently IL-13 cytotoxin exhibited less cytotoxicity to these cells. The authors next evaluated the antitumor activity of IL-13 cytotoxin in native IL-13R-expressing tumors and after gene transfer of IL-13R alpha 2 by injecting plasmid in U87MG tumors subcutaneously implanted in nude mice. These mice were then treated with IL-13 cytotoxin. Mean tumor size in mice receiving intraperitoneal or intratumoral IL-13 cytotoxin was significantly smaller in control tumors; however, tumor sizes were much smaller in IL-13R alpha 2-transfected tumors. Furthermore, convection-enhanced delivery of IL-13Ra2 cDNA in intracranially established U87MG glioma followed by IL-13 cytotoxin administration by the same route mediated tumor regression and prolonged survival of animals by 164% compared with control. These results indicate that IL-13R alpha 2 chain in GBM cells is essential for IL-13 cytotoxin-induced cytotoxicity and that IL-13R alpha 2 chain plays a critical biologic role in IL-13 cytotoxin-mediated therapy for GBM. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg,29B,Room 2NN10,HFM-735, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 49 TC 26 Z9 30 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 MAY-JUN PY 2005 VL 28 IS 3 BP 193 EP 202 DI 10.1097/01.cji.0000161393.04207.e1 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 921RN UT WOS:000228782500004 PM 15838375 ER PT J AU Arndt, MAE Krauss, J Vu, BK Newton, DL Rybak, SM AF Arndt, MAE Krauss, J Vu, BK Newton, DL Rybak, SM TI A dimeric angiogenin immunofusion protein mediates selective toxicity towards CD22(+) tumor cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dimeric fusion protein; CD22; human ribonuclease; single chain Fv; cytotoxicity ID SINGLE-CHAIN FV; MONOCLONAL-ANTIBODY; RIBONUCLEOLYTIC ACTIVITY; PHASE-I; ANTI-CD22 IMMUNOTOXIN; LYMPHOMA; RNASE; RECOMBINANT; THERAPEUTICS; CYTOTOXICITY AB To improve selective cytotoxicity and pharmacokinetics of an anti-CD22 antibody single chain Fv (scFv)-ribonuclease fusion protein, a dimeric derivative was generated. Human angiogenin was fused via a (G(4)S)(3) spacer peptide to the carboxy-terminal end of the stable dimeric anti-CD22 V-L-V-H zero-linker scFv MLT-7. The dimeric fusion protein and a monovalent counterpart were produced as soluble proteins in the periplasm of Escherichia coli. Comparative studies with homogenously purified fusion proteins revealed that both constructs specifically bound to the target antigen and retained ribonucleolytic activity. However, they exhibited a markedly different capability for killing CD22(+) tumor cells. The monomeric construct inhibited protein synthesis of target cells in a dose-dependent manner, but 50% inhibition (IC50) could be achieved only at the highest tested concentration (> 350 nM). In contrast, the dimeric fusion protein efficiently killed CD22(+) Raji and Daudi tumor cell lines with IC50 values of 74 nM and 118 nM, respectively. These results show that the therapeutic potential of scFv-ANG fusion proteins can be markedly enhanced by engineering dimeric derivatives. C1 Univ Essen Gesamthsch, Inst Immunol, D-45122 Essen, Germany. Univ Essen Gesamthsch, Dept Med Oncol & Canc Res, D-45122 Essen, Germany. NCI, SAIC Frederick, Frederick, MD 21701 USA. NCI, Dev Therapeut Program, Frederick, MD 21701 USA. RP Arndt, MAE (reprint author), Univ Essen Gesamthsch, Inst Immunol, D-45122 Essen, Germany. EM rybak@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 41 TC 21 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 MAY-JUN PY 2005 VL 28 IS 3 BP 245 EP 251 DI 10.1097/01.cji.0000161396.96582.10 PG 7 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 921RN UT WOS:000228782500010 PM 15838381 ER PT J AU Huang, JP Khong, HT Dudley, ME El-Gamil, M Li, YF Rosenberg, SA Robbins, PF AF Huang, JP Khong, HT Dudley, ME El-Gamil, M Li, YF Rosenberg, SA Robbins, PF TI Survival, persistence, and progressive differentiation of adoptively transferred tumor-reactive T cells associated with tumor regression SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE cell differentiation; human; T-cell receptors; T cells; tumor immunity ID REPLICATIVE SENESCENCE; TRANSFER THERAPY; CD45 ISOFORMS; MEMORY; LYMPHOCYTES; EFFECTOR; SUBSETS; EXPRESSION; CD57; VIVO AB Objective clinical responses have been observed in approximately 50% of patients who received non-myeloablative chemotherapy prior to the adoptive transfer of autologous melanoma-reactive tumor-infiltrating lymphocytes (TILs). Recent studies carried out through the use of antibodies directed against T-cell-receptor beta chain variable region (TRBV) products, as well as by direct sequencing of the expressed TRBV gene products, indicated that clinical responses in this trial were associated with the level of persistence of adoptively transferred T cells, In an attempt to further characterize T cells that persist in vivo following adoptive transfer, five dominant T-cell clonotypes were identified in TIL 2035, an adoptively transferred TIL that was associated with the complete regression of multiple metastases. The most highly persistent clonotype, which expressed the BV1 TR gene product, recognized the MAGE-6 cancer/testis antigen in the context of IILA-A23. This clonotype was detected in peripheral blood for over 16 months following adoptive transfer, expressed relatively higher levels of the co-stimulatory markers CD28 and CD27, and possessed telomeres that were long relative to other clonotypes present in TIL 2035 that showed only short-term persistence. The long-term persistent BV1 clonotype appeared to differentiate more slowly toward an end-stage effector in vivo than short-term persistent clonotypes. as manifested by the down regulation of CD28, CD27, and CD45RO and upregulation of CD57 and CD45RA expression on these T cells. These results indicated that the differentiation stage and replicative history of individual TIL clonotypes might be associated with their ability to survive and to persist in vivo, and progressive differentiation of the persistent clonotypes occurred following adoptive transfer. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Robbins, PF (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B42, Bethesda, MD 20892 USA. EM Paul_Robbins@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 32 TC 122 Z9 123 U1 1 U2 1 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 MAY-JUN PY 2005 VL 28 IS 3 BP 258 EP 267 DI 10.1097/01.cji.0000158855.92792.7a PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 921RN UT WOS:000228782500012 PM 15838383 ER PT J AU Wawer, MJ Gray, RH Sewankambo, NK Serwadda, D Li, XB Laeyendecker, O Kiwanuka, N Kigozi, G Kiddugavu, M Lutalo, T Nalugoda, F Wabwire-Mangen, F Meehan, MP Quinn, TC AF Wawer, MJ Gray, RH Sewankambo, NK Serwadda, D Li, XB Laeyendecker, O Kiwanuka, N Kigozi, G Kiddugavu, M Lutalo, T Nalugoda, F Wabwire-Mangen, F Meehan, MP Quinn, TC TI Rates of HIV-1 transmission per coital act, by stage of HIV-1 infection, in Rakai, Uganda SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 10th Conference on Retroviruses and Opportunistic Infections CY FEB 10-14, 2003 CL BOSTON, MA ID HUMAN-IMMUNODEFICIENCY-VIRUS; HETEROSEXUAL TRANSMISSION; SEXUAL TRANSMISSION; VIRAL LOAD; COMMUNITY TRIAL; AIDS-PREVENTION; COHORT; DISEASE; PLASMA; TYPE-1 AB Background. We estimated rates of human immunodeficiency virus (HIV)-1 transmission per coital act in HIV-discordant couples by stage of infection in the index partner. Methods. We retrospectively identified 235 monogamous, HIV-discordant couples in a Ugandan population-based cohort. HIV transmission within pairs was confirmed by sequence analysis. Rates of transmission per coital act were estimated by the index partner's stage of infection (recent seroconversion or prevalent or late-stage infection). The adjusted rate ratio of transmission per coital act was estimated by multivariate Poisson regression. Results. The average rate of HIV transmission was 0.0082/coital act (95% confidence interval [CI], 0.0039-0.0150) within similar to 2.5 months after seroconversion of the index partner; 0.0015/coital act within 6-15 months after seroconversion of the index partner (95% CI, 0.0002-0.0055); 0.0007/coital act (95% CI, 0.0005-0.0010) among HIV-prevalent index partners; and 0.0028/coital act (95% CI, 0.0015-0.0041) 6-25 months before the death of the index partner. In adjusted models, early- and late-stage infection, higher HIV load, genital ulcer disease, and younger age of the index partner were significantly associated with higher rates of transmission. Conclusions. The rate of HIV transmission per coital act was highest during early-stage infection. This has implications for HIV prevention and for projecting the effects of antiretroviral treatment on HIV transmission. C1 Columbia Univ, Mailman Sch Publ Hlth, Heilbrun Dept Populat & Family Hlth, New York, NY 10032 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat & Family Hlth Sci, Baltimore, MD USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Makerere Univ, Fac Med, Kampala, Uganda. Makerere Univ, Clin Epidemiol Unit, Kampala, Uganda. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Uganda Virus Res Inst, Rakai Hlth Sci Program, Entebbe, Uganda. RP Wawer, MJ (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Heilbrun Dept Populat & Family Hlth, 60 Haven Ave,Floor B-2, New York, NY 10032 USA. EM mwawer@jhsph.edu RI Laeyendecker, Oliver/B-9331-2009; Quinn, Thomas/A-2494-2010; OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760 FU NIAID NIH HHS [R01 AI34826]; NICHD NIH HHS [5P30HDS06826] NR 31 TC 774 Z9 789 U1 6 U2 34 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2005 VL 191 IS 9 BP 1403 EP 1409 DI 10.1086/429411 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 913CS UT WOS:000228128800005 PM 15809897 ER PT J AU Malaspina, A Moir, S Orsega, SM Vasquez, J Miller, NJ Donoghue, ET Kottilil, S Gezmu, M Follmann, D Vodeiko, GM Levandowski, RA Mican, JM Fauci, AS AF Malaspina, A Moir, S Orsega, SM Vasquez, J Miller, NJ Donoghue, ET Kottilil, S Gezmu, M Follmann, D Vodeiko, GM Levandowski, RA Mican, JM Fauci, AS TI Compromised B cell responses to influenza vaccination in HIV-infected individuals SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMORAL IMMUNE-RESPONSE; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; TERM ANTIBODY-PRODUCTION; ACUTE VIRAL-INFECTION; MF59-ADJUVANTED INFLUENZA; SUBUNIT VACCINE; H5N1 INFLUENZA; PLASMA VIREMIA; BONE-MARROW AB Background. Yearly influenza vaccination, although recommended for human immunodeficiency virus (HIV) infected individuals, has not received thorough evaluation in the era of antiretroviral therapy. We assessed the impact of HIV disease on B cell responses to influenza vaccination. Methods. Sixty-four HIV-infected and 17 HIV-negative individuals received the 2003-2004 trivalent inactivated influenza vaccine. Frequencies of influenza-specific antibody-secreting cells (ASCs) were measured by enzyme-linked immunospot (ELISPOT) assay, and antibody responses were measured by hemagglutination-inhibition (HI) assay. Memory responses to influenza were measured by ELISPOT assay after polyclonal activation of B cells in vitro. Results. Prevaccination HI titers were significantly higher in HIV-negative than in HIV-infected individuals. Peak HI titers and influenza-specific ASC frequencies were directly correlated with CD4(+) T cell counts in HIV-infected individuals. Influenza-specific memory B cell responses were significantly lower in HIV-infected than in HIV-negative individuals and were directly correlated with CD4(+) T cell counts. Conclusions. HIV infection is associated with a weak antibody response to influenza vaccination that is compounded by a poor memory B cell response. CD4(+) T cell count is a critical determinant of responsiveness to influenza vaccination, and the contribution of plasma HIV RNA level is suggestive and warrants further investigation. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A02,10 Ctr Dr, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov NR 44 TC 99 Z9 100 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2005 VL 191 IS 9 BP 1442 EP 1450 DI 10.1086/429298 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 913CS UT WOS:000228128800010 PM 15809902 ER PT J AU Minguillon, J Morancho, B Kim, SJ Lopez-Botet, M Aramburu, J AF Minguillon, J Morancho, B Kim, SJ Lopez-Botet, M Aramburu, J TI Concentrations of cyclosporin A and FK506 that inhibit IL-2 induction in human T cells do not affect TGF-beta 1 biosynthesis, whereas higher doses of cyclosporin A trigger apoptosis and release of preformed TGF-beta 1 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE calcineurin; lymphocytes; immunosuppressants ID GROWTH-FACTOR-BETA; TGF-BETA; IMMUNOSUPPRESSIVE AGENTS; INDUCED NEPHROTOXICITY; TRANSPLANT RECIPIENTS; IMMUNE-RESPONSES; GENE-EXPRESSION; CALCINEURIN; NFAT; TACROLIMUS AB Cyclosporin A (CsA) and FK506 suppress T cell activation by inhibiting calcineurin and the calcineurin-dependent transcription factors nuclear factor of activated T cells (NFATc), which are central regulators of T cell function. It was reported that CsA up-regulated the transcription of transforming growth factor-beta 1 (TGF-beta 1) in lymphocytes and other cells and activated its promoter in A549 lung carcinoma cells, but the mechanisms involved are poorly understood, and it is unclear whether calcineurin plays any role. We have studied the regulation of TGF-beta 1 in normal human lymphocytes and cell lines. In Jurkat T cells, the TGF-beta 1 promoter was activated by calcineurin and NFATc and inhibited by CsA and FK506. However, the promoter was insensitive to both drugs in A549 cells. In human T cells preactivated with phytohemagglutinin, biosynthesis of TGF-beta 1, induced by the T cell receptor (TCR) or the TGF-beta receptor, was not substantially affected by CsA and FK506 concentrations (<= 1 mu M) that effectively inhibited interleukin-2 production. However, pretreatment of fresh lymphocytes with CsA or FK506 during primary TCR stimulation reduced their production of TGF-beta 1 during secondary TCR activation. Finally, high concentrations of CsA (10 mu M), in the range attained in vivo in experiments in rodents, caused apoptosis in human T cells and the release of preformed, bioactive TGF-beta 1. These effects are unlikely to owe to calcineurin inhibition, as they were not observed with FK506. Our results indicate that CsA and FK506 are not general inducers of TGF-beta 1 biosynthesis but can cause different effects on TGF-beta 1 depending on the cell type and concentrations used. C1 Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain. Univ Pompeu Fabra, Dept Expt & Hlth Sci, Barcelona, Spain. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Minguillon, J (reprint author), Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Carrer Dr Aiguader 80, Barcelona, Spain. EM jaramburu@imim.es RI Aramburu, J/G-8991-2014; Lopez-Botet, Miguel/I-5434-2014 OI Aramburu, J/0000-0001-9279-9523; Lopez-Botet, Miguel/0000-0003-4882-065X NR 46 TC 21 Z9 22 U1 1 U2 3 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 MAY PY 2005 VL 77 IS 5 BP 748 EP 758 DI 10.1189/jlb.0904503 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 922YJ UT WOS:000228875500016 PM 15716327 ER PT J AU Chang, SL Tjandra, N AF Chang, SL Tjandra, N TI Temperature dependence of protein backbone motion from carbonyl C-13 and amide N-15 NMR relaxation SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE NMR relaxation; carbonyl relaxation; protein dynamics; temperature dependence; order parameters ID CHEMICAL-SHIFT ANISOTROPY; CROSS-CORRELATED RELAXATION; POLYPEPTIDE BACKBONE; ORDER PARAMETERS; MULTIPLE FIELDS; HEAT-CAPACITY; DYNAMICS; TENSORS; BOND; SPECTROSCOPY AB The NMR spin-lattice relaxation rate (R-1) and the rotating-frame spin-lattice relaxation rate (R-1p) of amide N-15 and carbonyl C-13 (C-13') of the uniformly C-13- and N-15-labeled ubiquitin were measured at different temperatures and field strengths to investigate the temperature dependence of overall rotational diffusion and local backbone motion. Correlation between the order S-NH(2), and that of the carbonyl carbon, C was investigated. The effective S-C(2), was estimated from parameter of the N-H vector, the direct fit of the experimental relaxation rates and from the slope of 2R(2) - R-1 vs. B-2 using Lipari-Szabo formalism. The average S' decreased by 5.9%, while the average S-C(2), decreased by 4.6% from 15 to 47 &DEG; C. At the extreme low and high temperatures the difference in the temperature dependence of the order parameters vanishes. At the intermediate temperatures they do not change by the same amount but they follow the same trend. On the same peptide plane along the protein sequence, S', and S-NH(2) are highly correlated. The results suggest that fast local motion experienced at the site of the N-H vector and carbonyl nucleus is more complicated than previously thought and it cannot be easily described by one single type of motion in a broad range of temperature. Published by Elsevier Inc. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50, Bethesda, MD 20892 USA. EM nico@helix.nih.gov NR 45 TC 60 Z9 60 U1 0 U2 16 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 MAY PY 2005 VL 174 IS 1 BP 43 EP 53 DI 10.1016/j.jmr.2005.01.008 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 923VY UT WOS:000228938700004 PM 15809171 ER PT J AU Walsh, JD Wang, YX AF Walsh, JD Wang, YX TI Periodicity, planarity, residual dipolar coupling, and structures SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE RDC; periodicity; planarity; secondary structure ID PROTEIN-STRUCTURE; CHEMICAL-SHIFTS; NMR MAPS; CONFORMATION; DYNAMICS; WAVES; ALPHA AB The periodic behavior of residual dipolar couplings (RDCs) arising from nucleic acid and protein secondary structures is shown to be more complex and information-rich than previously believed. We have developed a theoretical framework which allows the bond vector orientation of nucleic acids and the peptide plane orientations of protein secondary structures to be extracted from their Dipolar waves. In this article, we focus on utilizing "Dipolar waves" of peptides to extract structure information, and describe in more detail the fundamental principles of the relationship between the periodicities in structure and RDCs, the practical procedure to extract peptide plane orientation information from RDC data, and assessment of errors using Monte-Carlo simulations. We demonstrate the utility of our method for two model a-helices, one kinked and one curved, and as well as an irregular P-strand. Published by Elsevier Inc. C1 NCI, Prot Nucleic Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. RP Wang, YX (reprint author), NCI, Prot Nucleic Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. EM wangyu@ncifcrf.gov NR 16 TC 20 Z9 20 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD MAY PY 2005 VL 174 IS 1 BP 152 EP 162 DI 10.1016/j.jmr.2005.01.018 PG 11 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 923VY UT WOS:000228938700015 PM 15809182 ER PT J AU Goncalves, LF Espinoza, J Romero, R Lee, W Treadwell, MC Huang, RW Devore, G Chaiworapongsa, T Schoen, ML Beyer, B AF Goncalves, LF Espinoza, J Romero, R Lee, W Treadwell, MC Huang, RW Devore, G Chaiworapongsa, T Schoen, ML Beyer, B TI Four-dimensional fetal echocardiography with spatiotemporal image correlation (STIC): A systematic study of standard cardiac views assessed by different observers SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE three-dimensional ultrasound; four-dimensional ultrasound; STIC; outflow tracts; aorta; pulmonary artery; 3D; 4D ID CONGENITAL HEART-DISEASE; LOW-RISK PREGNANCIES; PRENATAL-DIAGNOSIS; 4-CHAMBER VIEW; 3-DIMENSIONAL ULTRASONOGRAPHY; GREAT-ARTERIES; ACCURACY; DEFECTS; POPULATION; ULTRASOUND AB Objective. To test the agreement between observers and reproducibility of a technique to display standard cardiac views of the left and right ventricular outflow tracts from four-dimensional volume datasets acquired with Spatiotemporal Image Correlation (STIC). Methods. A technique was developed to obtain dynamic multiplanar images of the left ventricular outflow tract (LVOT) and right ventricular outflow tract (RVOT) from volume datasets acquired with STIC. Volume datasets were acquired from fetuses with normal cardiac anatomy. Twenty volume datasets of satisfactory quality were pre-selected by one investigator. The data was randomly assigned for a blinded review by two independent observers with previous experience in fetal echocardiography. Only one volume dataset was used for each fetus. After a training session, the observers obtained standardized cardiac views of the LVOT and RVOT, which were scored on a scale of 1 to 5, based on diagnostic value and image quality (1 = unacceptable, 2 = marginal, 3 = acceptable, 4 = good, and 5 = excellent). Median scores and interquartile range, as well as inter- and intraobserver agreement were calculated for each view. Results. The mean menstrual age at the time of volume acquisition was 25.5 +/- 4.5 weeks. Median scores ( interquartile range) for LVOT images, obtained by the first and second observers, were 3.5 (2.25 - 5.00) and 4 (3.00 - 5.00), respectively. The median scores ( interquartile range) for RVOT images obtained by the first and second observers were 3 ( 3.00 - 5.00) and 3 (2.00 - 4.00), respectively. The interobserver intraclass correlation coefficient for the LVOT was 0.693 (95% CI 0.380 - 0.822), and 0.696 ( 95% CI 0.382 - 0.866) for the RVOT. For the intraobserver agreement analysis, observer 1 gave higher scores to the LVOT the second time the volumes were analyzed [ LVOT: 3.50 ( 2.25 - 5.00) vs. 5.00 ( 4.00 - 5.00, p = 0.008)]. Conclusion. STIC can be reproducibly used to evaluate fetal cardiac outflow tracts by independent examiners. Slightly better image quality rating scores during the intraobserver variability trial suggests the presence of a learning curve for the manipulation and analysis of volume data obtained by STIC. C1 NICHD, Perinatol Res Branch, NIH, DHHS,Autzel Womens Hosp, Detroit, MI 48201 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. Fetal Diagnost Ctr, Pasadena, CA USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS,Autzel Womens Hosp, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 69 TC 27 Z9 30 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD MAY PY 2005 VL 17 IS 5 BP 323 EP 331 DI 10.1080/14767050500127765 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 947SS UT WOS:000230667300004 PM 16147845 ER PT J AU Leppert, PC AF Leppert, PC TI Preparation for motherhood: A vital component of primary care for women SO JOURNAL OF MIDWIFERY & WOMENS HEALTH LA English DT Letter C1 NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. RP Leppert, PC (reprint author), NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1526-9523 J9 J MIDWIFERY WOM HEAL JI J. Midwifery Women Health PD MAY-JUN PY 2005 VL 50 IS 3 BP 259 EP 259 DI 10.1016/j.jmwh.2005.02.019 PG 1 WC Nursing SC Nursing GA 926FA UT WOS:000229107300024 ER PT J AU Pesse, B Levrand, S Feihl, F Waeber, B Gavillet, B Pacher, P Liaudet, L AF Pesse, B Levrand, S Feihl, F Waeber, B Gavillet, B Pacher, P Liaudet, L TI Peroxynitrite activates ERK via Raf-1 and MEK, independently from EGF receptor and p21(Ras) in H9C2 cardiomyocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE peroxynitrite; extracellular signal-regulated kinase; cardiomyocyte; cell signaling; MAP kinase; nitration; oxidation; C-jun NH2-terminal kinase (JNK); p38 MAP kinase ID AORTIC ENDOTHELIAL-CELLS; PROTEIN-KINASE-C; NITRIC-OXIDE; HEART-FAILURE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; DIFFERENTIAL ACTIVATION; REPERFUSION INJURY; CARDIAC MYOCYTES; PATHWAY AB Peroxynitrite is a potent oxidant and nitrating species proposed as a direct effector of myocardial damage in a wide range of cardiac diseases. Whether peroxynitrite also acts indirectly, by modulating cell signal transduction pathways in the myocardium, has not been investigated. Here, we examined the ability of peroxynitrite to activate extracellular signal-related kinase (ERK), a MAP kinase which has been linked with hypertrophic and anti-apoptotic responses in the heart, in cultured H9C2 cardiomyocytes. Peroxynitrite elicited a concentration- and time-dependent activation of ERK, secondary to the upstream activation of MEK 1 (ERK kinase). Activation of MEK-ERK by peroxynitrite was related to the upstream activation of Raf-1 kinase, as ERK and MEK phosphorylation were prevented by the Raf-1 inhibitor BAY43-9006. These effects of peroxynitrite, were not associated with the activation of p21(Ras), known as a common signaling target of cellular oxidative stress. In contrast to ERK activation mediated by the epidermal growth factor (EGF), ERK activation by peroxynitrite was not prevented by AG1478 (EGF receptor inhibitor). Peroxynitrite acted through oxidative, but not nitrative chemistry, as ERK remained activated while nitration was prevented by the flavanol epicatechin. In addition to ERK, peroxynitrite also potently activated two additional members of the MAP kinase family of signaling proteins, JNK and p38. Thus, peroxynitrite activates ERK in cardiomyocytes through an unusual signaling cascade involving Raf-1 and MEK 1, independently from EGFR and P21(Ras), and also acts as a potent activator of JNK and p38. These results provide the novel concept that peroxynitrite may represent a previously unrecognized signaling molecule in various cardiac pathologies. (C) 2005 Elsevier Ltd. All rights reserved. C1 Univ Lausanne Hosp, Dept Internal Med, Div Crit Care, CH-1011 Lausanne, Switzerland. Univ Lausanne Hosp, Dept Internal Med, Div Clin Pathophysiol & Med Teaching, CH-1011 Lausanne, Switzerland. Univ Lausanne Hosp, Dept Pharmacol & Toxicol, CH-1011 Lausanne, Switzerland. NIAAA, NIH, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Liaudet, L (reprint author), Univ Lausanne Hosp, Dept Internal Med, Div Crit Care, BH 10-982, CH-1011 Lausanne, Switzerland. EM Lucas.Liaudet@chuv.hospvd.ch RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 41 TC 46 Z9 52 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2005 VL 38 IS 5 BP 765 EP 775 DI 10.1016/j.yjmcc.2005.02.020 PG 11 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 925KR UT WOS:000229052500007 PM 15850570 ER PT J AU Maloyan, A Sanbe, A Osinska, H Imahashi, K Murphy, E Robbins, J AF Maloyan, A Sanbe, A Osinska, H Imahashi, K Murphy, E Robbins, J TI Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin related cardiomyopathy SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the American Section of the International-Society-of-Heart-Research CY MAY 12-15, 2005 CL New Orleans, LA SP Int Soc Heart Res, Amer Sect C1 NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2005 VL 38 IS 5 MA 3 BP 811 EP 812 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 925KR UT WOS:000229052500015 ER PT J AU Murphy, E AF Murphy, E TI Can we harness cardioprotection to improve stem cell therapy? SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the American Section of the International-Society-of-Heart-Research CY MAY 12-15, 2005 CL New Orleans, LA SP Int Soc Heart Res, Amer Sect C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2005 VL 38 IS 5 MA 38 BP 823 EP 824 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 925KR UT WOS:000229052500050 ER PT J AU Yamamura, K Steenbergen, C Murphy, E AF Yamamura, K Steenbergen, C Murphy, E TI Cardioprotection induced by pkc activation is associated with decreased sarcoplasmic reticulum calcium content SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the American Section of the International-Society-of-Heart-Research CY MAY 12-15, 2005 CL New Orleans, LA SP Int Soc Heart Res, Amer Sect C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2005 VL 38 IS 5 MA 80 BP 838 EP 838 PG 1 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 925KR UT WOS:000229052500092 ER PT J AU Rajapakse, N Steenbergen, C Murphy, E AF Rajapakse, N Steenbergen, C Murphy, E TI AKT phosphorylates VDAC and GSK-3 beta inhibition results in dephosphorylation of akt and vdac in the rat heart SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 27th Annual Meeting of the American Section of the International-Society-of-Heart-Research CY MAY 12-15, 2005 CL New Orleans, LA SP Int Soc Heart Res, Amer Sect C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD MAY PY 2005 VL 38 IS 5 MA 110 BP 848 EP 849 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 925KR UT WOS:000229052500122 ER PT J AU Jakupciak, JP Wang, W Markowitz, ME Ally, D Coble, M Srivastava, S Maitra, A Barker, PE Sidransky, D O'Connell, CD AF Jakupciak, JP Wang, W Markowitz, ME Ally, D Coble, M Srivastava, S Maitra, A Barker, PE Sidransky, D O'Connell, CD TI Mitochondrial DNA as a cancer biomarker SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID MONONUCLEOTIDE REPEAT; PROSTATE-CANCER; MTDNA MUTATIONS; PRIMARY TUMORS; BREAST-CANCER; GENOME; REARRANGEMENTS; SEQUENCE; MUSCLE; BRAIN AB As part of a national effort to identify biomarkers for the early detection of cancer, we developed a rapid and high-throughput sequencing protocol for the detection of sequence variants in mitochondrial DNA. Here, we describe the development and implementation of this protocol for clinical samples. Heteroplasmic and homoplasmic sequence variants occur in the mitochondrial genome in patient tumors. We identified these changes by sequencing mitochondrial DNA obtained from tumors and blood from the same individual. We confirmed previously identified primary lung tumor changes and extended these findings in a small patient cohort. Eight sequence variants were identified in stage I to stage IV tumor samples. Two of the sequence variants identified (22%) were found in the D-loop region, which accounts for 6.8% of the mitochondrial genome. The other sequence variants were distributed throughout the coding region. in the forensic community, the sequence variations used for identification are localized to the D-loop region because this region appears to have a higher rate of mutation. However, in lung tumors the majority of sequence variation occurred in the coding region. Hence, incomplete mitochondrial genome sequencing, designed to scan discrete portions of the genome, misses potentially important sequence variants associated with cancer or other diseases. C1 NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. NCI, Early Detect Res Network, Rockville, MD USA. Geocenters Inc, Newton, MA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Jakupciak, JP (reprint author), NIST, Div Biotechnol, 100 Bur Dr,MS 8311, Gaithersburg, MD 20899 USA. EM johnj@nist.gov RI Coble, Michael/E-7540-2010 FU NCI NIH HHS [Y1CN2020, Y1CN010309] NR 51 TC 52 Z9 59 U1 0 U2 3 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 MAY PY 2005 VL 7 IS 2 BP 258 EP 267 DI 10.1016/S1525-1578(10)60553-3 PG 10 WC Pathology SC Pathology GA 921AP UT WOS:000228736900014 PM 15858150 ER PT J AU Cachau, RE Podjarny, AD AF Cachau, RE Podjarny, AD TI High-resolution crystallography and drug design SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Review DE macromolecular crystallography; ultra-high resolution; drug design ID ULTRA-HIGH-RESOLUTION; ALDOSE REDUCTASE; PROTEIN CRYSTALLOGRAPHY; ELECTRON-DENSITY; RNA; REFINEMENT; PRESSURE; CRYSTALS; ANGSTROM; ARP/WARP AB Ultra-high-resolution X-ray crystallography of macromolecules (i.e. resolution better than 0.8 &ANGS;) is a rising field that promises to provide new insight into the structure-function relationships of biomacromolecules. The picture emerging from macromolecular structures at this resolution is far more complex than previously understood, requiring for its study improved tools for structure refinement. analysis and annotation. Some of these problems were highlighted during the recent High Resolution Drug Design Meeting (Bischenberg-Strasbourg, France, 13-16 May 2004). We will review here some or the results and discussions that took place during that meeting and elaborate on the trends and challenges ahead in this emerging new field of research. Copyright © 2005 John Wiley & Sons, Ltd. C1 IGBMC, F-67404 Illkirch Graffenstaden, France. SAIC Frederick, NCI, ABCC, Frederick, MD 21702 USA. RP Podjarny, AD (reprint author), IGBMC, 1 Rue Laurent Fries, F-67404 Illkirch Graffenstaden, France. EM podjarny@titus.u-strasbg.fr OI Podjarny, Alberto/0000-0002-7685-1077 FU NCI NIH HHS [N01-CO-12400] NR 41 TC 14 Z9 14 U1 1 U2 9 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD MAY-JUN PY 2005 VL 18 IS 3 BP 196 EP 202 DI 10.1002/jmr.738 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 925XG UT WOS:000229086200003 PM 15782396 ER PT J AU Choi, YL Kim, CJ Matsuo, T Gaetano, C Falconi, R Suh, YL Kim, SH Shin, YK Park, SH Chi, JG Thiele, CJ AF Choi, YL Kim, CJ Matsuo, T Gaetano, C Falconi, R Suh, YL Kim, SH Shin, YK Park, SH Chi, JG Thiele, CJ TI HUlip, a human homologue of unc-33-like phosphoprotein of Caenorhabditis elegans; Immunohistochemical localization in the developing human brain and patterns of expression in nervous system tumors SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE brain tumor; development; hUlip; nervous system; neuron ID PRIMITIVE NEUROECTODERMAL TUMORS; MICROTUBULE-ASSOCIATED PROTEIN-2; RETINOIC ACID; MONOCLONAL-ANTIBODIES; NEUROBLASTOMA-CELLS; AXONAL GUIDANCE; GROWTH CONE; GENE; MARKERS; OUTGROWTH AB HUlip is a human homologue of a C. elegans gene, unc-33, that is developmentally regulated during maturation of the nervous system. HUlip is highly expressed only in the fetal brain and spinal cord, and is undetected in the adult brain. The purpose of this study was to investigate the pattern of hUlip expression in the developing human brain and nervous system tumors. Ten human brains at different developmental stages and 118 cases of nervous system tumor tissues were examined by immunohistochemistry. Twelve related tumor cell lines were also analyzed by northern blotting and immunoblotting. HUlip was expressed in late fetal and early postnatal brains; strongly in the neurons of the brain stem, basal ganglia/thalamus, and dentate gyrus of the hippocampus, and relatively weakly in the cerebral and cerebellar cortex. Among tumors, hUlip expression was easily detected in tumor cells undergoing neuronal differentiation such as ganglioneuroblastomas and ganglioneuromas. Furthermore, hUlip immunoreactivity was also found in various brain tumors showing neuronal differentiation: central neurocytomas (6 of 6 cases were positive), medulloblastomas (5/11), atypical teratoid rhabdoid tumor (1/1) and gangliogliomas (4/7). Some astrocytic tumors also showed weak positivity: astrocytomas (1 of 5 cases), anaplastic astrocytomas (2/5), and glioblastomas (3/11). Subependymal giant cell astrocytomas and subependymomas, which are of controversial histogenetic origin, showed strong hUlip immunoreactivity. The results of this study indicate that the expression of hUlip protein is distinctly restricted to the late fetal and early postnatal periods of human nervous system development and to certain subsets of nervous system tumors. The exact function of hUlip needs to be further clarified; yet the results of our study strongly imply that hUlip function is important in human nervous system development and its aberrant expression in various types of nervous system tumors suggests a role of hUlip as an oncofetal neural antigen. C1 Sungkyunkwan Univ, Samsung Med Ctr, Sch Med, Dept Diagnost Pathol, Seoul, South Korea. Seoul Natl Univ, Coll Med, Dept Pathol, Seoul 151, South Korea. Seoul Natl Univ Hosp, Clin Res Inst, Pathol Lab, Seoul 110744, South Korea. NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Regina Elena Inst Canc Res, Oncol Mol Lab, I-00161 Rome, Italy. RP Kim, CJ (reprint author), Seoul Natl Univ, Coll Med, Dept Pathol, 28 Yongon Dong, Seoul 110799, South Korea. EM cjkim@snu.ac.kr RI Shin, Young Kee/C-8929-2011; Chi, Je Geun/G-4989-2011; Seoul National University, Pathology/B-6702-2012; OI Chi, Je-Geun/0000-0002-9950-2072; Gaetano, Carlo/0000-0002-5238-1832 NR 32 TC 5 Z9 5 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAY PY 2005 VL 73 IS 1 BP 19 EP 27 DI 10.1007/s11060-004-3013-3 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 932UE UT WOS:000229578200003 PM 15933812 ER PT J AU Rassoulpour, A Wu, HQ Ferre, S Schwarcz, R AF Rassoulpour, A Wu, HQ Ferre, S Schwarcz, R TI Nanomolar concentrations of kynurenic acid reduce extracellular dopamine levels in the striatum SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alpha 7 nicotinic acetylcholine receptor; basal ganglia; glia-neuron interactions; kynurenines; neurodegenerative diseases; schizophrenia ID GLUTAMATE RELEASE; RAT-BRAIN; ACETYLCHOLINE-RECEPTORS; NICOTINIC RECEPTORS; NUCLEUS-ACCUMBENS; BASAL GANGLIA; NEURONS; NMDA; IDENTIFICATION; SCHIZOPHRENIA AB Precise regulation of dopaminergic activity is of obvious importance for the physiology and pathology of basal ganglia. We report here that nanomolar concentrations of the astrocyte-derived neuroinhibitory metabolite kynurenic acid (KYNA) potently reduce the extracellular levels of striatal dopamine in unanesthetized rats in vivo. This effect, which is initiated by the KYNA-induced blockade of alpha 7 nicotinic acetylcholine receptors, highlights the functional relevance of glia-neuron interactions in the striatum and indicates that even modest increases in the brain levels of endogenous KYNA are capable of interfering with dopaminergic neurotransmission. C1 Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. NIDA, IRP, NIH, DHHS, Baltimore, MD USA. RP Schwarcz, R (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Catonsville, MD 21228 USA. EM rschwarc@mprc.umaryland.edu RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU NICHD NIH HHS [HD 16596] NR 31 TC 91 Z9 92 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2005 VL 93 IS 3 BP 762 EP 765 DI 10.1111/j.1471-4159.2005.03134.x PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 916BW UT WOS:000228361400024 PM 15836634 ER PT J AU Mehrabian, Z Liu, LI Fiskum, G Rapoport, SI Chandrasekaran, K AF Mehrabian, Z Liu, LI Fiskum, G Rapoport, SI Chandrasekaran, K TI Regulation of mitochondrial gene expression by energy demand in neural cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE mitochondrial DNA; monensin; mRNA half-life; post-transcription; RNase-L; transcription ID CYTOCHROME-OXIDASE; NEURONAL-ACTIVITY; MESSENGER-RNA; ALZHEIMER-DISEASE; MAMMALIAN-CELLS; ATP SYNTHESIS; RAT-BRAIN; HIPPOCAMPUS; METABOLISM; ISCHEMIA AB Mitochondrial DNA (mtDNA) encodes critical subunit proteins of the oxidative phosphorylation (OXPHOS) complex that generates ATP. This study tested the hypothesis that mitochondrial gene expression in neural cells is regulated by energy demand, as modified via stimulation of cellular sodium transport. Exposure of PC12S cells to the sodium ionophore monensin (250 nM) for 1-6 h caused a 13-60% decrease in cellular ATP (from 15 to 5 nmol per mg protein at 6 h). Levels of mitochondrial DNA-encoded mRNAs (mt-mRNAs) increased significantly (150%) within the first hour of exposure to monensin, and then decreased significantly (50%) at 3-4 h. Levels of mtDNA-encoded 12S rRNA and nuclear DNA-encoded OXPHOS subunit mRNAs were not significantly affected. Exposure of primary cerebellar neuronal cultures to the excitatory amino acid glutamate caused a similar rapid and significant increase followed by a significant decrease in cell mt-mRNA levels. The monensin-induced initial increase in mt-mRNA levels was abolished by pretreatment with actinomycin D or by reducing extracellular sodium ion concentration. The monensin-induced delayed reduction in mt-mRNA levels was accelerated in the presence of actinomycin D, and was accompanied by a 67% reduction in the half-life (from 3.6 to 1.2 h). Exposure of PC12S cells to 2-deoxy-D-glucose significantly decreased cellular ATP levels (from 14.2 to 7.1 nmol per mg protein at 8 h), and increased mt-mRNA levels. These results suggest a physiological transcriptional mechanism of regulation of mitochondrial gene expression by energy demand and a post-transcriptional regulation that is independent of energy status of the cell. C1 Univ Maryland, Sch Med, Dept Anesthesiol, Baltimore, MD 21201 USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Chandrasekaran, K (reprint author), Univ Maryland, Sch Med, Dept Anesthesiol, Med Sch Teaching Facil 5-34,685 W Baltimore St, Baltimore, MD 21201 USA. EM kchandra@anesthlab.umm.edu FU NINDS NIH HHS [NS045081] NR 42 TC 18 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD MAY PY 2005 VL 93 IS 4 BP 850 EP 860 DI 10.1111/j.1471-4159.2005.03066.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 920WB UT WOS:000228721200007 PM 15857388 ER PT J AU Ziv, L Levkovitz, S Toyama, R Falcon, J Gothilf, Y AF Ziv, L Levkovitz, S Toyama, R Falcon, J Gothilf, Y TI Functional development of the zebrafish pineal gland: Light-induced expression of period2 is required for onset of the circadian clock SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE arylalkylamine-N-acetyltransferase; photoreceptor; melatonin; in situ hybridization ID SEROTONIN-N-ACETYLTRANSFERASE; GENE-EXPRESSION; INDIVIDUAL FIBROBLASTS; VERTEBRATE CLOCK; DANIO-RERIO; E-BOX; RHYTHMS; CELLS; MOUSE; OSCILLATORS AB In zebrafish, the pineal gland is a photoreceptive organ that contains an intrinsic circadian oscillator and exhibits rhythmic arylalkylamine-N-acetyltransferase (zfaanat2) mRNA expression. In the present study, we investigated the role of light and of a clock gene, zperiod2 (zper2), in the development of this rhythm. Analysis of zfaanat2 mRNA expression in the pineal gland of 3-day-old zebrafish embryos after exposure to different photoperiodic regimes indicated that light is required for proper development of the circadian clock-controlled rhythmic expression of zfaanat2, and that a 1-h light pulse is sufficient to initiate this rhythm. Analysis of zper2 mRNA expression in zebrafish embryos exposed to different photoperiodic regimes indicated that zper2 expression is transiently up-regulated by light but is not regulated by the circadian oscillator. To establish the association between light-induced zper2 expression and light-induced clock-controlled zfaanat2 rhythm, zPer2 knock-down experiments were performed. The zfaanat2 mRNA rhythm, induced by a 1-h light pulse, was abolished in zPer2 knock-down embryos. These experiments indicated that light-induced zper2 expression is crucial for establishment of the clock-controlled zfaanat2 rhythm in the zebrafish pineal gland. C1 Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. CNRS, UMR 7628, Lab Arago, Banyuls sur Mer, France. Univ Paris 06, Banyuls sur Mer, France. RP Gothilf, Y (reprint author), Tel Aviv Univ, George S Wise Fac Life Sci, Dept Zool, IL-69978 Tel Aviv, Israel. EM yoavg@tauex.tau.ac.il RI FALCON, Jack/I-5302-2013 OI FALCON, Jack/0000-0002-7572-6581 NR 46 TC 74 Z9 75 U1 0 U2 5 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD MAY PY 2005 VL 17 IS 5 BP 314 EP 320 DI 10.1111/j.1365-2826.2005.01315.x PG 7 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 922VA UT WOS:000228866800008 PM 15869567 ER PT J AU Dalakas, MC AF Dalakas, MC TI The role of IVIg in the treatment of patients with stiff person syndrome and other neurological diseases associated with anti-GAD antibodies SO JOURNAL OF NEUROLOGY LA English DT Article; Proceedings Paper CT Satellite Symposium on Questions and Dilemmas Related to the Use of Intravenous immunoglobulin in Neurological Diseases held at the 14th Meeting of the European-Neurological-Society CY JUN 26-30, 2004 CL Barcelona, SPAIN SP European Neurol Soc DE GAD antibodies; stiff person syndrome; intravenous immunoglobulin; muscle stiffness ID GLUTAMIC-ACID DECARBOXYLASE; AUTOIMMUNE NEUROMUSCULAR DISEASES; INTRAVENOUS IMMUNOGLOBULIN; AUTOANTIBODIES AB Introduction High-titre anti-GAD antibodies are characteristically seen in patients with stiff person syndrome (SPS). Other CNS disorders, rarely associated with high anti-GAD antibody titres, include: a) SPS-plus, a syndrome characterised by SPS and cerebellar ataxia; b) Batten's disease; and c) rare patients with epilepsy and idiopathic cerebellar ataxia. Currently, high-titre anti-GAD antibodies serve only as markers of an autoimmune process within the CNS because their pathogenic role in the afore-mentioned disorders has not been established. In SPS, there is evidence of autoimmune pathogenesis based on: the association of the disease with other autoimmune disorders or autoantibodies; immunogenetic background; presence of oligoclonal IgG bands in the CSF with increased intrathecal anti-GAD antibody synthesis and response to immunotherapies. SPS is the only GAD-positive CNS disease where a controlled study with immunotherapy has been conducted. Methods Sixteen anti-GAD antibody-positive patients were randomised to receive IVIg or placebo for 3 months. After a washout, they crossed to the alternative therapy for another three months. Efficacy was based on the difference in scores of the distribution of stiffness index and heightened sensitivity (spasms) from baseline to the second and third month of the infusions. Direct treatment and carry-over effect were compared for both groups. Results The stiffness scores in the IVIg-randomised patients declined significantly from month 1 through 4, but rebounded when they crossed to placebo. In contrast, the scores in the placebo-randomised group remained constant from month 1-4 but dropped significantly after crossing to IVIg. Eleven patients who received IVIg became able to walk unassisted, stopped falling and assumed household or work duties. The duration of benefit varied from 6-12 weeks or up to a year. The antiGAD(65) antibody titres declined after IVIg, but not after placebo. Conclusion Based on a controlled study, IVIg is a safe and effective therapy for SPS in patients unresponsive to other agents. Whether IVIg has a role in the other GAD-positive patients with neurological disease, or in SPS patients without GAD antibodies, remains unknown. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 24 TC 31 Z9 31 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD MAY PY 2005 VL 252 SU 1 BP 19 EP 25 DI 10.1007/s00415-005-1105-4 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 936EQ UT WOS:000229838700005 ER PT J AU Beltaifa, S Law, AJ Hyde, TM McClintock, B Herman, MM Harrison, PJ Kleinman, JE Weickert, CS AF Beltaifa, S Law, AJ Hyde, TM McClintock, B Herman, MM Harrison, PJ Kleinman, JE Weickert, CS TI Expression levels and cellular localization of ErbB receptors mRNAs in the dorsolateral prefrontal cortex in schizophrenia. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Univ Oxford, Dept Psychiat, Oxford OX1 2JD, England. NIMH, CBDB, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Psychiat, Oxford OX1 2JD, England. RI Law, Amanda/G-6372-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 25 BP 437 EP 437 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800035 ER PT J AU Quezado, M Rushing, E Santi, M Wincovitch, S Garfield, S Berman, D AF Quezado, M Rushing, E Santi, M Wincovitch, S Garfield, S Berman, D TI Evaluation of nucleic acid index in brain tumors. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 NCI, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 35 BP 439 EP 439 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800044 ER PT J AU Rushing, E Quezado, M Evangelista, R Santi, M AF Rushing, E Quezado, M Evangelista, R Santi, M TI Evaluation of Rb gene and cyclin-dependent kinase inhibitors p21 and p27 in pleomorphic xanthoastrocytoma. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 AFIP, Washington, DC USA. NCI, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 34 BP 439 EP 439 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800045 ER PT J AU Takao, M Murrell, JR Yamaguchi, K Unverzagt, FW Glazier, BS Farlow, MR Grafman, J Ghetti, B AF Takao, M Murrell, JR Yamaguchi, K Unverzagt, FW Glazier, BS Farlow, MR Grafman, J Ghetti, B TI Neuropathologic heterogeneity of Pick's disease. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Dept Pathol & Lab Med,Dept Psychiat,Dept Neurol, Indianapolis, IN USA. Mihara Mem Hosp, Gunma, Japan. NINDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 75 BP 449 EP 449 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800083 ER PT J AU Rapckwicz, A Abu-Asab, M Tsokos, M Schiffman, R Quezado, M AF Rapckwicz, A Abu-Asab, M Tsokos, M Schiffman, R Quezado, M TI Neuropathologic findings in Fabry's disease patient after enzyme replacement therapy with agalsidase beta. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 NCI, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 88 BP 452 EP 452 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800097 ER PT J AU Quezado, M Tapia, ELN Rushing, E Camphausen, K Anderson, SJ AF Quezado, M Tapia, ELN Rushing, E Camphausen, K Anderson, SJ TI Cytonectin "A do not attack molecule" is overexpressed in glioblastoma multiforme. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 NCI, NIH, Bethesda, MD 20892 USA. AFIP, Washington, DC 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 112 BP 458 EP 458 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800121 ER PT J AU Lee, YS Vortmeyer, AO Zhuang, ZP AF Lee, YS Vortmeyer, AO Zhuang, ZP TI Co-expression of erythropoietin and erythropoietin receptor in Von Hippel-Lindau disease-associated tumors. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 NINDS, Bethesda, MD 20892 USA. Catholic Univ, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 120 BP 460 EP 460 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800129 ER PT J AU Pacheco-Quinto, J de Turco, ER Refolo, L Bazan, NG Howard, A Cruz-Sanchez, F Petanceska, S Pappolla, MA AF Pacheco-Quinto, J de Turco, ER Refolo, L Bazan, NG Howard, A Cruz-Sanchez, F Petanceska, S Pappolla, MA TI Hyperhomocysteinemic triple transgenic Alzheimer's mouse model shows increased brain amyloid beta peptide levels and increased beta-secretase activity. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. NINDS, Bethesda, MD 20892 USA. Univ Catalunya, Barcelona, Spain. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 149 BP 468 EP 468 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800158 ER PT J AU Rubin, JE Gerkin, RC Bi, GQ Chow, CC AF Rubin, JE Gerkin, RC Bi, GQ Chow, CC TI Calcium time course as a signal for spike-timing-dependent plasticity SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; BIDIRECTIONAL SYNAPTIC PLASTICITY; HIPPOCAMPAL PYRAMIDAL NEURONS; POSTSYNAPTIC CALCIUM; BIOPHYSICAL MODEL; DENDRITIC SPINES; RECEPTOR-CHANNEL; NMDA; CA2+; SPECIFICITY AB Calcium has been proposed as a postsynaptic signal underlying synaptic spike-timing-dependent plasticity (STDP). We examine this hypothesis with computational modeling based on experimental results from hippocampal cultures, some of which are presented here, in which pairs and triplets of pre- and postsynaptic spikes induce potentiation and depression in a temporally asymmetric way. Specifically, we present a set of model biochemical detectors, based on plausible molecular pathways, which make direct use of the time course of the calcium signal to reproduce these experimental STDP results. Our model features a modular structure, in which long-term potentiation (LTP) and depression (LTD) components compete to determine final plasticity outcomes; one aspect of this competition is a veto through which appropriate calcium time courses suppress LTD. Simulations of our model are also shown to be consistent with classical LTP and LTD induced by several presynaptic stimulation paradigms. Overall, our results provide computational evidence that, while the postsynaptic calcium time course contains sufficient information to distinguish various experimental long-term plasticity paradigms, small changes in the properties of back-propagation of action potentials or in synaptic dynamics can alter the calcium time course in ways that will significantly affect STDP induction by any detector based exclusively on postsynaptic calcium. This may account for the variability of STDP outcomes seen within hippocampal cultures, under repeated application of a single experimental protocol, as well as for that seen in multiple spike experiments across different systems. C1 Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Neurosci, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurobiol, Pittsburgh, PA USA. NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Rubin, JE (reprint author), Univ Pittsburgh, Dept Math, 301 Thackeray Hall, Pittsburgh, PA 15260 USA. EM rubin@math.pitt.edu RI Gerkin, Richard/B-7683-2008; Chow, Carson/A-7970-2009; Bi, Guoqiang/E-5075-2013; OI Bi, Guoqiang/0000-0001-8735-3818; Gerkin, Richard C/0000-0002-2940-3378 FU NIMH NIH HHS [K01-MH-01508, P50-MH-64445, R01 MH-066962] NR 70 TC 80 Z9 82 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2005 VL 93 IS 5 BP 2600 EP 2613 DI 10.1152/jn.00803.2004 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 918VH UT WOS:000228575200022 PM 15625097 ER PT J AU Hanakawa, T Parikh, S Bruno, MK Hallett, M AF Hanakawa, T Parikh, S Bruno, MK Hallett, M TI Finger and face representations in the ipsilateral precentral motor areas in humans SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID PREMOTOR CORTEX; FUNCTIONAL REORGANIZATION; CORTICAL POTENTIALS; INFERIOR AREA-6; MACAQUE MONKEY; HAND MOVEMENTS; CHRONIC STROKE; ACTIVATION; BRAIN; FMRI AB Several human neuroimaging studies have reported activity in the precentral gyrus (PcG) ipsilateral to the side of hand movements. This activity has been interpreted as the part of the primary motor cortex (M1) that controls bilateral or ipsilateral hand movements. To better understand hand ipsilateral-PcG activity, we performed a functional MRI experiment in eight healthy right-handed adults. Behavioral tasks involved hand or lower face movements on each side or motor imagery of the same movements. Consistent with the known M1 organization, the hand contralateral-PcG activity was centered at the "hand-knob" portion of the PcG; face contralateral-PcG activity was localized ventrolateral to it. Hand ipsilateral-PcG activity was identified in most subjects. However, converging results indicated that this ipsilateral PcG activity was situated in Brodmann's area 6 in both hemispheres. The hand ipsilateral-PcG zones were active not only during hand movements but also face movements. Moreover, the hand ipsilateral-PcG zones revealed substantial imagery-related activity, which also failed to differentiate the hand and face. Statistical analyses confirmed poor effector selectivity of the hand ipsilateral PcG activity during both movement and imagery tasks. From these results, we conclude that the hand ipsilateral-PcG activity in healthy adults probably corresponds to a part of the ventral premotor cortex. In contrast, available evidence suggests that M1 contributes to controlling the ipsilateral hand in children and patients after stroke recovery. It appears that within the human PcG, there are two parallel systems potentially capable of controlling ipsilateral hand movements: ventral premotor cortex and M1. These two systems may be differentially influenced by developmental or pathologic changes. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Rm 5N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 52 TC 62 Z9 64 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2005 VL 93 IS 5 BP 2950 EP 2958 DI 10.1152/jn.00784.2004 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 918VH UT WOS:000228575200054 PM 15625099 ER PT J AU Isoda, M AF Isoda, M TI Context-dependent stimulation effects on saccade initiation in the presupplementary motor area of the monkey SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID FRONTAL EYE FIELD; MEMORY-GUIDED SACCADES; NIGRA PARS RETICULATA; NEURONAL-ACTIVITY; MACAQUE MONKEY; SUPERIOR COLLICULUS; INTRACORTICAL MICROSTIMULATION; ELECTRICAL-STIMULATION; MULTIPLE SACCADES; PREMOTOR AREAS AB Although evidence suggests that the contribution of the presupplementary motor area (pre-SMA) to voluntary motor control is effector-nonselective, the question of how electrical stimulation of the pre-SMA affects eye movements remains unanswered. To address this issue, stimulus effects of the pre-SMA of monkeys on saccade initiation were investigated during performance of a visually guided saccade task with an instructed delay period. This report describes two major findings. First, when stimuli with currents of <= 80 mu A were applied before the presentation of a GO signal, the reaction time (RT) of an upcoming saccade shortened with comparable effects on ipsi- and contraversive saccades. Second, stimuli that were delivered after the GO signal lengthened the RT; this resulted in greater effects on ipsiversive saccades. In addition, the stimulation yielded a mild impairment of saccade accuracy, particularly when the stimulation was delivered after the GO signal. By themselves, however, these stimuli did not directly elicit eye movements. Therefore the stimulus effects appeared only in the context of the behavioral task and were dependent on the phase of the task. These findings provide additional support for the hypothesis that the involvement of the pre-SMA in motor control can be linked to either eye or arm motor system dependent on behavioral context. C1 Tohoku Univ, Sch Med, Dept Physiol, Sendai, Miyagi 980, Japan. Japan Sci & Technol Agcy, Core Res Evolut Sci & Technol Program, Kawaguchi, Japan. RP Isoda, M (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,room 1A50,49 Convent Dr, Bethesda, MD 20892 USA. EM isodam@nei.nih.gov NR 59 TC 16 Z9 16 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD MAY PY 2005 VL 93 IS 5 BP 3016 EP 3022 DI 10.1152/jn.01176.2004 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 918VH UT WOS:000228575200062 PM 15703225 ER PT J AU Lim, SY Doherty, JD McBride, K Miller-Ihli, NJ Carmona, GN Stark, KD Salem, N AF Lim, SY Doherty, JD McBride, K Miller-Ihli, NJ Carmona, GN Stark, KD Salem, N TI Lead exposure and (n-3) fatty acid deficiency during rat neonatal development affect subsequent spatial task performance and olfactory discrimination SO JOURNAL OF NUTRITION LA English DT Article DE (n-3) fatty acid deficiency; neonatal development; spatial learning; olfactory discriminations; lead toxicity; Pb ID LONG-TERM POTENTIATION; MORRIS WATER MAZE; GYRUS IN-VIVO; DOCOSAHEXAENOIC ACID; DENTATE GYRUS; ASSOCIATIVE ABILITY; UNITED-STATES; BREAST-MILK; ODOR MEMORY; BLOOD LEAD AB Docosahexaenoic acid [22:6(n-3), DHA] is important for optimal infant central nervous system development, and lead (Pb) exposure during development can produce neurological deficits. Long-Evans strain rats were fed either an (n-3) deficient [(n-3) Def] diet to produce brain DHA deficiency, or an adequate [(n-3) Adq] diet through 2 generations. At the birth of the 2nd generation, the dams were subdivided into 4 groups and supplied drinking water containing either 5.27 mmol/L (Pb) or sodium (Na) acetate until weaning. Rats were killed at 3 wk (weaning) and 11 wk (maturity) for brain Pb and fatty acid analysis. Spatial task and olfactory-cued behavioral assessments were initiated at 9 wk. Rats in the (n-3) Def group had a 79% lower concentration of brain DHA compared with the (n-3) Adq group with no effect of Pb exposure. At weaning, Pb concentrations were 7.17 +/- 0.47 nmol Pb/g of brain (wet weight) in the (n-3) Adq-Pb group and 6.49 +/- 0.63 nmol Pb/g of brain (wet weight) in the (n-3) Def-Pb group. At maturity, the brains contained 1.30 +/- 0.22 and 1.07 +/- 0.12 nmol Pb/g (wet weight), respectively. In behavioral testing, significant effects of both Pb and DHA deficiency were observed in the Morris water maze probe trial and in 2-odor olfactory discrimination acquisition and olfactory-based reversal learning tasks. Both lactational Pb exposure and (n-3) fatty acid deficiency led to behavioral deficits with additive effects observed only in the acquisition of 2-odor discriminations. C1 Korea Maritime Univ, Div Ocean Sci, Pusan, South Korea. US EPA, Div Hlth Effects, Off Pesticide Programs, Washington, DC 20460 USA. NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA. USDA, Beltsville Human Nutr Res Ctr, Food Composit Lab, Beltsville, MD 20705 USA. RP Korea Maritime Univ, Div Ocean Sci, Pusan, South Korea. EM nsalem@niaaa.nih.gov RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 NR 69 TC 17 Z9 18 U1 2 U2 6 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 1019 EP 1026 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600010 PM 15867275 ER PT J AU Lim, SY Doherty, JD Salem, N AF Lim, SY Doherty, JD Salem, N TI Lead exposure and (n-3) fatty acid deficiency during rat neonatal development alter liver, plasma, and brain polyunsaturated fatty acid composition SO JOURNAL OF NUTRITION LA English DT Article DE arachidonic acid; docosahexaenoic acid; fatty acid composition; lead; (n-3) fatty acid deficiency; Pb ID DOCOSAHEXAENOIC ACID; DIETARY LEAD; PEROXIDATION; MEMBRANES; CHILDREN; RODENTS; LIPIDS AB Lead (Pb) exposure has been reported to increase arachidonic (AA) and docosahexaenoic (DHA) acids. To determine whether Pb effects on fatty acid composition are influenced by dietary (n-3) fatty acid restriction, weanling female rats were fed either an (n-3)-adequate or -deficient diet to maturity and mated. At parturition, dams in each group were subdivided to receive either 0.2% Pb or Na-acetate in their drinking water during lactation only. Pups were analyzed for fatty acid content in liver, plasma, and brain at either 3 or 11 wk. The (n-3)-deficient diets markedly decreased total (n-3) fatty acids, and increased total (n-6) fatty acids including both AA and docosapentaenoic (n-6) in each compartment (P < 0.05). The main effects of Pb were in the livers of weanling rats where there was a 56% loss in total fatty acid concentration concurrent with increased relative percentages of AA and DHA. Thus, because there was a greater percentage of liver nonessential fatty acid lost relative to the essential fatty acids (EFA), there was no net change in AA concentration. There was a diet x Pb interaction for a decrease in liver DHA concentration evident only in the (n-3)-adequate group. There were also diet x Pb interactions in plasma at 11 wk and in brain at 3 wk. These data are consistent with the hypothesis of a Pb-induced increase in fatty acid catabolism, perhaps as a source of energy. C1 Korea Maritime Univ, Div Ocean Sci, Pusan, South Korea. US EPA, Off Pesticide Programs, Div Hlth Effects, Washington, DC 20460 USA. NIAAA, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res, NIH, Rockville, MD USA. RP Korea Maritime Univ, Div Ocean Sci, Pusan, South Korea. EM nsalem@niaaa.nih.gov NR 29 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 EI 1541-6100 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 1027 EP 1033 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600011 PM 15867276 ER PT J AU Underwood, BA AF Underwood, BA TI The Interdepartmental Committee on Nutrition for National Defense Surveys: Lasting impacts SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC DE nutrition surveys; ICNND; nutrition profile; food fortification; iodine AB The Interdepartmental Committee on Nutrition for National Defense (ICNND) Surveys provided previously unavailable representative information on the food and nutrition situations of military or civilian populations in 33 developing countries. Information on related social and economic conditions also were assessed. These data provided a framework for planning follow-up programs to correct problems identified and to prevent them from recurring, such as fortification of salt with iodine and sugar with vitamin A. Educational materials specific to the nutrient content of local foods, dietary patterns, and availability within countries and cultures were also developed, such as food composition tables and dietary guidelines. In-country scientists were motivated to continue nutrition research, and, in several countries, institutes and departments of nutrition evolved. Impact was documented by improved nutritional status in several countries, although success is not always attributed directly to the impetus provided through the ICNND Surveys. Furthermore, the surveys and their leaders provided inspiration and role models for aspiring young nutritionists both within their own countries and internationally. C1 NEI, WHO, NIH, Bethesda, MD USA. RP Underwood, BA (reprint author), NEI, WHO, NIH, Bethesda, MD USA. EM bunderwo@adnc.com NR 20 TC 3 Z9 3 U1 0 U2 0 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 1276 EP 1280 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600056 PM 15867321 ER PT J AU Buchanan, D AF Buchanan, D TI Letter to the editor SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Letter ID COMMUNITY INTERVENTION TRIAL; SMOKING CESSATION COMMIT C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Buchanan, D (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAY-JUN PY 2005 VL 37 IS 3 BP 114 EP 114 DI 10.1016/S1499-4046(06)60264-9 PG 1 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 934KG UT WOS:000229707100003 PM 15915566 ER PT J AU Chiang, HS Kuo, TF Tsai, CC Lin, MC She, BR Huang, YY Lee, HS Shieh, CS Chen, MH Ramshaw, JAM Werkmeister, JA Tuan, RS Jiang, CC AF Chiang, HS Kuo, TF Tsai, CC Lin, MC She, BR Huang, YY Lee, HS Shieh, CS Chen, MH Ramshaw, JAM Werkmeister, JA Tuan, RS Jiang, CC TI Repair of porcine articular cartilage defect with autologous chondrocyte transplantation SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE autologous chondrocyte transplantation; gelatin beads; cartilage repair and regeneration ID FULL-THICKNESS DEFECTS; AUTOGENOUS PERIOSTEAL GRAFTS; CONTINUOUS PASSIVE MOTION; BIPHASIC INDENTATION; JOINT SURFACES; OSTEOARTHRITIS; DURABILITY; RABBIT AB Articular cartilage is known to have poor healing capacity after injury. Autologous chondral grafting remains the mainstay to of gelatin microbeads to deliver treat well-defined, full-thickness, symptomatic cartilage defects. We demonstrated he utilization of gel autologous chondrocytes for in vivo cartilage generation. Chondrocytes were harvested from the left forelimbs of 12 Lee-Sung pigs. The cells were expanded in monolayer culture and then seeded onto gelatin microbeads or left in monolayer. Shortly before implantation, the cell-laden beads were mixed with collagen type I gel, while the cells in monolayer Culture were collected and re-suspended in culture medium. Full-thickness cartilage defects were surgically created in the weight-bearing surface of the femoral condyles of both knees, covered by periosteal patches taken from proximal tibia, and seated with a porcine fibrin glue. In total, 48 condyles were equally allotted to experimental, control, and null groups that were filled beneath the patch with chondrocyte-laden beads ill gel, chondrocytes in plain medium solution, or nothing, respectively. The repair was examined 6 months post-surgery oil the basis of macroscopic appearance, histological scores based oil the International Cartilage Repair Society Scale, and the proportion of characteristic chondrocytes. Tensile stress-relaxation behavior was determined from uniaxial indentation tests. The experimental group scored higher than the control group in the categories of matrix nature. cell distribution pattern, and absence of mineralization, with similar surface smoothness. Both the experimental and control groups were superior to the null group in the above-mentioned categories. Viable cell populations were equal in all groups, but the proportion of characteristic chondrocytes was highest in the experimental group. Matrix stiffness was ranked as null > native cartilage > control > experimental group. Transplanted autologous chondrocytes survive and could yield hyaline-like cartilage. The application of beads and gel for transplantation helped to retain the transferred cells in situ and maintain a better chondrocyte phenotype. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. C1 Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan. Natl Taiwan Univ Hosp, Taipei 10764, Taiwan. Natl Taiwan Univ, Vet Hosp, Taipei 10764, Taiwan. Ind Technol Res Inst, Hsinchu, Taiwan. Commonwealth Sci & Ind Res Org, Melbourne, Vic, Australia. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Jiang, CC (reprint author), Natl Taiwan Univ, Inst Biomed Engn, Taipei 10764, Taiwan. EM tuanr@hih.gov; ccj@ccms.ntu.edu.tw RI Ramshaw, John/A-9411-2011; OI Jiang, Ching-Chuan/0000-0001-7954-0875; CHEN, MIN-HUEY/0000-0002-4853-1906; LEE, HSUAN-SHU/0000-0002-8017-0434; Chiang, Hongsen/0000-0001-8781-5146; KUO, TZONG-FU/0000-0002-6328-8967 NR 27 TC 42 Z9 44 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD MAY PY 2005 VL 23 IS 3 BP 584 EP 593 DI 10.1016/j.orthres.2004.11.003 PG 10 WC Orthopedics SC Orthopedics GA 929VP UT WOS:000229375000012 PM 15885479 ER PT J AU Nyska, M Shabat, S Long, PH Howard, C Ezov, N Levin-Harrus, T Mittelman, M Redlich, M Yedgar, S Nyska, A AF Nyska, M Shabat, S Long, PH Howard, C Ezov, N Levin-Harrus, T Mittelman, M Redlich, M Yedgar, S Nyska, A TI Disseminated thrombosis-induced growth plate necrosis in rat - A unique model for growth plate arrest SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE physeal growth arrest; 2-butoxtethanol; thrombosis; rat model ID FEMALE F344 RATS; HYPERCOAGULABLE STATE; INHALATION EXPOSURE; THALASSEMIA MAJOR; BETA-THALASSEMIA; PHYSEAL ARREST; 2-BUTOXYETHANOL; INJURY; OSTEOGENESIS; CHILDHOOD AB Exposure of rats to 2-butoxyethanol (BE) produces early hemolytic anemia and disseminated thrombosis. This leads to infarctions in multiple organs, including bones and cartilage. BE, administered for different durations of exposure in two separate experiments, produced metaphyseal vascular thrombosis, growth plate infarction, and partial or complete physeal growth arrest. This reproducible model may serve as a useful tool in the study of some conditions that manifest growth plate damage. The suitability of this model for investigating the pathogenesis of growth plate necrosis and as a model for potential therapy for various human growth plate disorders are discussed. C1 Sapir Med Ctr, Dept Orthopaed Surg, IL-22481 Kefar Sava, Israel. Pathol Associates Inc, Div Charles River Labs, W Chester, OH USA. Hadassah Med Ctr, Dept Orthopaed Surg, Jerusalem, Israel. Harlan Biotech Israel Ltd, Rehovot, Israel. Hasharon Hosp, Rabin Med Ctr, Dept Internal Med, IL-49372 Petah Tiqwa, Israel. Hebrew Univ Jerusalem, Fac Med Dent, Hadassah Med Sch, Dept Orthodont, IL-91010 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91010 Jerusalem, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), Sapir Med Ctr, Dept Orthopaed Surg, 48 Tchernichovsky St, IL-22481 Kefar Sava, Israel. EM nyska@intemet-zahav.net NR 37 TC 4 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD MAY-JUN PY 2005 VL 25 IS 3 BP 346 EP 350 DI 10.1097/01.bpo.0000153878.28185.2a PG 5 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 921UA UT WOS:000228789400019 PM 15832152 ER PT J AU Wilfond, BS Gollust, SE AF Wilfond, BS Gollust, SE TI Policy issues for expanding newborn screening programs: The cystic fibrosis newborn screening experience in the United States SO JOURNAL OF PEDIATRICS LA English DT Article ID EARLY DIAGNOSIS; TECHNOLOGY AB Objective To describe the screening approaches and implementation strategies for cystic fibrosis newborn screening in the 12 programs that were offered in 11 states in 2002. Study design Telephone interviews conducted in the spring of 2003 with program representatives in the 11 states. Screening approaches were defined in four overlapping categories: state mandated screening, state-wide offering, hospital based screening, and screening with informed consent. Results Screening was state mandated in seven states but was routinely offered to most infants in nine states. The primary care provider or hospital determined if screening was done in three states (four programs). Informed consent was explicitly documented in two states. In five programs, immunoreactive trypsinogen exclusively was used to identify at risk infants. In seven programs, a second tier DNA test was also used, but these programs each had distinct strategies. In Only two programs where DNA testing was performed and normal sweat tests indicated carrier status, were results routinely provided to parents "in person" at a CF center. Conclusion The diversity of approaches for screening approaches and strategies has advantages for future policy decisions, provided that data about the clinical and psychosocial impact of screening from these programs are collected and disseminated. As additional states determine that the resources are available, programs can be designed with a more favorable benefit/risk balance as a result of the successes and challenges faced by other states. C1 NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD USA. RP Wilfond, BS (reprint author), Bldg 10,Room 1C118,9000 Rockville Pike,MSC 1156, Bethesda, MD 20892 USA. NR 37 TC 24 Z9 24 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAY PY 2005 VL 146 IS 5 BP 668 EP 674 DI 10.1016/j.jpeds.2004.11.029 PG 7 WC Pediatrics SC Pediatrics GA 926FQ UT WOS:000229109000018 PM 15870672 ER PT J AU Tanda, G Ebbs, A Newman, AH Katz, JL AF Tanda, G Ebbs, A Newman, AH Katz, JL TI Effects of 4 '-chloro-3 alpha-(diphenylmethoxy)-tropane on mesostriatal, mesocortical, and mesolimbic dopamine transmission: Comparison with effects of cocaine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Neuroscience CY NOV 08-12, 2003 CL NEW ORLEANS, LA SP Soc Neurosci ID DISCRIMINATIVE STIMULUS PROPERTIES; RAT NUCLEUS-ACCUMBENS; BENZTROPINE ANALOGS; UPTAKE INHIBITORS; EXTRACELLULAR DOPAMINE; TRANSPORTER AFFINITIES; PREFRONTAL CORTEX; DRUG-ADDICTION; RHESUS-MONKEYS; IN-VITRO AB Increase in dopamine (DA) neurotransmission resulting from blockade of the DA transporter (DAT) after administration of cocaine is believed to play a major role in mediating its behavioral and reinforcing effects. Since it was hypothesized that drugs that block the DAT have cocaine-like behavioral effects, it was of interest to study in the present article the stimulant effects of cocaine on locomotor activity and on pattern of activation of DA neurotransmission in different DAergic terminal areas in rats and compare these effects with those of 4'-chloro-3 alpha- ( diphenylmethoxy)-tropane (4-Cl-BZT), a benztropine analog showing higher affinity for the DAT, but reduced behavioral effects compared with cocaine. Administration of cocaine resulted in a dose-dependent stimulation of locomotor activity and DA neurotransmission in the nucleus accumbens shell and core, dorsal caudate, and in the medial prefrontal cortex (PFCX) measured by microdialysis. At comparable doses, the effects of 4-Cl-BZT on DA levels in all brain areas except the PFCX were generally reduced compared with those of cocaine, as were the effects on locomotor activity. The differences in behavioral effects corresponded generally to differences between the drugs with regard to their stimulation of extracellular DA levels, although the mechanism(s) for the differences in extracellular DA may involve effects mediated by sites other than the DAT or differences in the efficiency of the two drugs in blocking DA uptake. Nonetheless, the present results suggest that the differences in behavioral effects between cocaine and 4-Cl-BZT are related to differences in their patterns of activation of DA transmission. C1 NIDA, Intramural Res Program, Psychobiol Sect, Medicat Discovery Res Branch,NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Medicat Diacovery Branch, NIH,DHHS, Baltimore, MD 21224 USA. RP Tanda, G (reprint author), NIDA, Intramural Res Program, Psychobiol Sect, Medicat Discovery Res Branch,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gtanda@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 42 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 613 EP 620 DI 10.1124/jpet.104.080465 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900016 PM 15681658 ER PT J AU Srimaroeng, C Chatsudthipong, V Aslamkhan, AG Pritchard, JB AF Srimaroeng, C Chatsudthipong, V Aslamkhan, AG Pritchard, JB TI Transport of the natural sweetener stevioside and its aglycone steviol by human organic anion transporter (hOAT1; SLC22A6) and hOAT3 (SLC22A8) SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-for-Cell-Biology CY DEC 13-17, 2003 CL San Francisco, CA SP Amer Soc Cell Biol ID GLYCOSIDIC SWEETENERS; PROXIMAL TUBULES; REBAUDIOSIDE-A; BLOOD-PRESSURE; IN-VITRO; RATS; METABOLISM; ABSORPTION; KIDNEY; CATION AB The natural sweetening agent stevioside and its aglycone metabolite, steviol, have been shown to inhibit transepithelial transport of para-aminohippurate (PAH) in isolated rabbit renal proximal tubules by interfering with basolateral entry. The aim of the present study was to determine which of the cloned basolateral organic anion transporters were involved in the renal transport of stevioside and steviol. This question was addressed in Xenopus laevis oocytes expressing human organic anion transporter 1 (hOAT1), 3 (hOAT3), and winter flounder OAT (fOat1). The parent compound, stevioside, had no inhibitory effect on either PAH ( hOAT1) or ES ( estrone sulfate; hOAT3) uptake. In contrast, steviol showed significant, dose-dependent inhibition of PAH and ES uptake in hOAT1- or hOAT3-expressing oocytes, respectively. The IC50 of steviol for hOAT1-mediated PAH transport was 11.1 mu M compared with 62.6 mu M for hOAT3-mediated ES uptake. The Michaelis-Menten inhibition constants (K-i) for steviol transport mediated by hOAT1 and hOAT3 were 2.0 +/- 0.3 and 5.4 +/- 2.0 mu M, respectively. Trans-stimulation of PAH efflux by steviol was assessed to determine whether steviol itself was transported by hOAT1 or hOAT3. A low concentration of 1 mu M steviol increased the efflux of [H-3] PAH (trans-stimulated) via both hOAT1 and hOAT3. In addition, it was shown by electrophysiology that steviol entry induced inward current in fOat1-expressing oocytes. In conclusion, stevioside had no interaction with either hOAT1 or hOAT3, whereas hOAT1, hOAT3, and fOat1 were all shown to be capable of steviol transport and thus, can play a role in its renal transport and excretion. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Pritchard, JB (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM pritcha3@niehs.nih.gov OI Srimaroeng, Chutima/0000-0002-5537-1023 NR 40 TC 13 Z9 16 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 621 EP 628 DI 10.1124/jpet.104.080366 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900017 PM 15644426 ER PT J AU Rusyniak, DE Tandy, SL Hekmatyar, SK Mills, E Smith, DJ Bansal, N MacLellan, D Harper, ME Sprague, JE AF Rusyniak, DE Tandy, SL Hekmatyar, SK Mills, E Smith, DJ Bansal, N MacLellan, D Harper, ME Sprague, JE TI The role of mitochondrial uncoupling in 3,4-methylenedioxymethamphetamine-mediated skeletal muscle hyperthermia and rhabdomyolysis SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 17, 2004 CL Orlando, FL SP Soc Acad Emergency Med ID ENERGY-METABOLISM; THYROID-HORMONE; UP-REGULATION; L6 MYOTUBES; RAT-LIVER; BROWN FAT; IN-VIVO; ECSTASY; METHAMPHETAMINE; AMPHETAMINE AB Use of the popular club drug ecstasy (3,4-methylenedioxymethamphetamine, MDMA) can result in life-threatening hyperthermia and rhabdomyolysis. Recent studies show a link between skeletal muscle uncoupling proteins in MDMA-mediated hyperthermia. The mechanisms by which MDMA interacts with skeletal muscle mitochondria are largely unknown. The present study was designed to comprehensively evaluate the effects of MDMA on bioenergetics and toxicity of skeletal muscle. Using P-31 nuclear magnetic resonance (NMR) and serum creatine kinase levels, we demonstrate evidence for uncoupling of oxidative phosphorylation in the skeletal muscle of MDMA ( 40 mg/kg)-treated rats. In vivo, rats treated with MDMA had significantly elevated serum creatine kinase levels, a marker of rhabdomyolysis, 4 h post-MDMA treatment ( 955 +/- 132 IU/l) compared with saline-treated controls (373.2 +/- 59 IU/l). beta-ATP signal areas after MDMA treatment showed significant reductions (15%) from the baseline values with corresponding increases in inorganic phosphate (88% increases) and decreases in intracellular pH. Clark electrode experiments on isolated skeletal muscle mitochondria in vitro ( 1 - 5 mM MDMA) and ex vivo in MDMA-treated animals demonstrated no evidence of uncoupling of oxidative phosphorylation. In vitro experiments using L6 myotubules cocultured with primary hepatocytes demonstrated the presence of uncoupling protein-3 in the L6 myotubules, but no evidence of a direct effect of MDMA or its potential metabolites on cellular creatine kinase concentrations. These findings suggest that MDMA uncouples skeletal muscle mitochondria in vivo but that this uncoupling is the result of indirect mechanisms. C1 Indiana Univ, Sch Med, Dept Emergency Med, Indianapolis, IN USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Radiol, Indianapolis, IN 46202 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Ottawa, Fac Med, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada. Virginia Polytech Inst & State Univ, Virginia Coll Osteopath Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. RP Regenstrief Inst Hlth Care, Suite R2200,1050 Wishard Blvd, Indianapolis, IN 46202 USA. EM drusynia@iupui.edu OI Rusyniak, Daniel/0000-0002-6199-0840; Harper, Mary-Ellen/0000-0003-3864-5886 NR 48 TC 18 Z9 19 U1 0 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 EI 1521-0103 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 629 EP 639 DI 10.1124/jpet.104.079236 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900018 PM 15644431 ER PT J AU Chen, SR Wess, J Pan, HL AF Chen, SR Wess, J Pan, HL TI Functional activity of the M-2 and M-4 receptor subtypes in the spinal cord studied with muscarinic acetylcholine receptor knockout mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DORSAL-HORN; CHOLINESTERASE INHIBITION; CHOLINERGIC RECEPTORS; GABA(B) RECEPTORS; DIABETIC-RATS; MU-RECEPTOR; LOCALIZATION; ANALGESIA; ACETYLTRANSFERASE; ANTINOCICEPTION AB Stimulation of spinal muscarinic acetylcholine receptors (mAChRs) produces potent analgesia. Both M-2 and M-4 mAChRs are coupled to similar G proteins (G(i/o) family) and play a critical role in the analgesic action of mAChR agonists. To determine the relative contribution of M 2 and M 4 subtypes to activation of G(i/o) proteins in the spinal cord, we examined the receptor-mediated guanosine 5'-O-(3-[S-35]thio)triphosphate ([S-35]GTP gamma S) binding in M-2 and M-4 subtype knockout (KO) mice. Basal [S-35]GTP gamma S binding in the spinal cord was similar in the wild-type controls, M-2 and M-4 single-KO, and M-2/M-4 double-KO mice. The spinal [S-35]GTP gamma S binding stimulated by either muscarine or oxotremorine-M was not significantly different among three groups of wild-type mouse strains. In M 2 single-KO and M-2/M-4 double-KO mice, the agonist-stimulated [S-35]GTP gamma S binding was completely abolished in the spinal cord. Furthermore, the agonist-stimulated [S-35]GTP gamma S binding in the spinal cord of M 4 single-KO mice was significantly reduced (similar to 15%), compared with that in wild-type controls. On the other hand, the spinal [S-35]GTP gamma S binding stimulated by a mu-opioid agonist was not significantly different between wildtype and M-2 and M-4 KO mice. This study provides complementary new evidence that M-2 is the most predominant mAChR subtype coupled to the G(i/o) proteins in the spinal cord. Furthermore, these data suggest that a small but functionally significant population of M-4 receptors exists in the mouse spinal cord. The functional activity of these M-4 receptors seems to require the presence of M-2 receptors. C1 Penn State Univ, Coll Med, Dept Anesthesiol, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Dept Neural & Behav Sci, Hershey, PA 17033 USA. NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, Bethesda, MD USA. RP Pan, HL (reprint author), Penn State Univ, Coll Med, Dept Anesthesiol, H187,500 Univ Dr, Hershey, PA 17033 USA. EM hpan@psu.edu FU NIGMS NIH HHS [GM64830]; NINDS NIH HHS [NS45602] NR 31 TC 26 Z9 30 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 765 EP 770 DI 10.1124/jpet.104.082537 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900032 PM 15665136 ER PT J AU Wee, S Anderson, KG Baumann, MH Rothman, RB Blough, BE Woolverton, WL AF Wee, S Anderson, KG Baumann, MH Rothman, RB Blough, BE Woolverton, WL TI Relationship between the serotonergic activity and reinforcing effects of a series of amphetamine analogs SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article; Proceedings Paper CT 66th Annual Scientific Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14, 2004 CL San Juan, PR SP Coll Problems Drug Dependence ID RHESUS-MONKEYS; SQUIRREL-MONKEYS; DOPAMINE TRANSPORTER; ELECTRIC-SHOCK; COCAINE; FENFLURAMINE; NOREPINEPHRINE; PHENTERMINE; PRIMATES; DRUGS AB It has been reported that among drugs with mixed actions on central nervous system monoamine systems, increased serotonergic activity is associated with decreased potency as a reinforcer. The present experiment was designed to examine this relationship for amphetamine analogs that varied in serotonin releasing potency and to evaluate whether serotonergic actions can affect reinforcing efficacy. Compounds PAL 313 and 314 are para- and meta-methylamphetamine, respectively. PAL 303 and 353 are para- and meta-fluoroamphetamine, respectively. All compounds had similar potencies as in vitro releasers of dopamine (DA) and norepinephrine ( NE) but differed in potency for 5-hydroxytryptamine (serotonin) (5-HT) release [EC50 (nanomolar) PAL 313 = 53.4; PAL 314 = 218; PAL 303 = 939; PAL 353 = 1937]. When made available to rhesus monkeys (Macaca mulatta) (n = 4) for self-administration under a fixed-ratio 25 schedule, all were positive reinforcers with biphasic dose-response functions (0.003-1.0 mg/kg) and were equipotent. PAL 313 was self-administered at a lower rate than the other compounds, which were indistinguishable. Under a progressive-ratio schedule (n = 5), all drugs were positive reinforcers. Dose-response functions increased to a maximum or were biphasic (0.01-1.0 mg/kg), and drugs were equipotent. At maximum, PAL 313 maintained less responding than other PAL drugs, which maintained similar maxima. Thus, all compounds were positive reinforcers under both schedules, consistent with their potent DA actions. Responding was lower when 5-HT potency was higher and comparable with DA and NE potency. The results suggest that the mechanism for this effect involves a decrease in reinforcing potency and efficacy among monoamine releasing agents when 5-HT releasing potency is increased relative to DA. C1 Univ Mississippi, Med Ctr, Dept Psychiat & Pharmacol & Toxicol, Jackson, MS 39216 USA. W Virginia Univ, Dept Psychol, Morgantown, WV 26506 USA. NIDA, Clin Psychopharmacol Sect, Intramural Res Program, Baltimore, MD USA. RTI Int, Sci & Engn Grp, Ctr Organ & Med Chem, Res Triangle Pk, NC USA. RP Woolverton, WL (reprint author), Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Div Neurobiol & Behav Res, 2500 N State St, Jackson, MS 39216 USA. EM wwoolverton@psychiatry.umsmed.edu FU NIDA NIH HHS [DA-10352, DA-12970, K05-DA15343] NR 39 TC 91 Z9 92 U1 3 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 848 EP 854 DI 10.1124/jpet.104.080101 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900042 PM 15677348 ER PT J AU Scheidweiler, KB Cone, EJ Moolchan, ET Huestis, MA AF Scheidweiler, KB Cone, EJ Moolchan, ET Huestis, MA TI Dose-related distribution of codeine, cocaine, and metabolites into human hair following controlled oral codeine and subcutaneous cocaine administration SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; FLIGHT MASS-SPECTROMETRY; QUANTITATIVE-DETERMINATION; ALTERNATIVE MATRICES; N-ACETYLAMPHETAMINE; SEXUAL ASSAULT; MELANIN; PIGMENTATION; AMPHETAMINE; DISPOSITION AB Hair testing for the determination of drug exposure has many useful applications. Drug incorporated into hair can be found for extended periods following drug exposure. There are few controlled drug administration studies investigating drug distribution into human hair. Ten volunteers participated in a 10-week controlled cocaine and codeine administration study while residing in the secure research ward. Weekly hair samples were collected by electric razor. During the low-dose week ( week 4), volunteers received 75 mg/70 kg cocaine subcutaneously and 60 mg/70 kg codeine orally on alternating days, a total of three doses for each drug. Similarly, during week 7, volunteers received three doses 150 mg/70 kg cocaine and 120 mg/70 kg codeine. Maximum hair concentrations (C-max) were found 1 to 3 weeks after low and high doses. Dose-related C-max values of cocaine, benzoylecgonine, ecgonine methyl ester, norcocaine, cocaethylene, and codeine were found following low and high doses. Hair analysis was performed using liquid chromatography tandem mass spectrometry. A positive linear relationship was found between total melanin content of hair and C-max of codeine, cocaine, and metabolites following high dosing. This study demonstrated dose-related concentrations of cocaine and metabolites in human hair following controlled cocaine administration. These data are the first demonstrating melanin-related incorporation of cocaine and metabolites into human hair following controlled cocaine administration. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. ConeChem Res LLC, Severna Pk, MD USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov NR 39 TC 46 Z9 48 U1 0 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 909 EP 915 DI 10.1124/jpet.104.082388 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900050 PM 15743923 ER PT J AU Tekmal, RR Liu, YG Nair, HB Jones, J Perla, RP Lubahn, DB Korach, KS Kirma, N AF Tekmal, RR Liu, YG Nair, HB Jones, J Perla, RP Lubahn, DB Korach, KS Kirma, N TI Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations in the aromatase transgenic mice SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 7th International Aromatase Conference CY SEP 06-08, 2004 CL Edinburgh, SCOTLAND DE aromatase; transgenic mice; estrogen receptor; mammary carcinogenesis ID IN-VIVO MODEL; BREAST-CANCER; OVEREXPRESSION; BETA; EXPRESSION; GLANDS; GROWTH; PHENOTYPES; INHIBITORS; LETROZOLE AB Aromatase transgenic mice exhibit hyperplastic and dysplastic changes, attesting to the importance of local estrogen in breast carcinogenesis. These mice also show increased levels of the estrogen receptor alpha and beta (ER alpha, ER beta) suggesting that this receptor may play an important role in the initiation of estrogen - mediated mammary hyperplasia observed in these mice. To address the specific role of ER alpha in the mammary development and in the induction of estrogen-mediated hyperplasia in aromatase transgenic mice, we have generated MMTV-aromatase x ER alpha knockout cross (referred as aromatase/ERKO). Even though ER beta is expressed in aromatase/ERKO mice, lack of ER alpha leads to impaired mammary growth in these mice. The data suggest that ER alpha plays an important role in the mammary gland development as well as in the induction of mammary hyperplasia in aromatase transgenic mice. Lack of ER alpha expression in the aromatase/ERKO mice resulted in a decrease in the expression of Cyclin D1, PCNA and TGF beta relative to the aromatase parental strain. The studies involving aromatase/ERKO mice show that lack of ERa results in impaired mammary development even in the presence of continuous tissue estrogen, suggesting estrogen/ER alpha-mediated actions are critical for mammary development and carcinogenesis. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. Univ Missouri, Dept Biochem & Child Hlth, Columbia, MO 65211 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Tekmal, RR (reprint author), Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, MSC7836,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM tekmal@uthscsa.edu OI Bhaskaran Nair, Hareesh Babu/0000-0002-4309-9560; Korach, Kenneth/0000-0002-7765-418X FU NCI NIH HHS [CA75018] NR 20 TC 21 Z9 27 U1 1 U2 5 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 MAY PY 2005 VL 95 IS 1-5 BP 9 EP 15 DI 10.1016/j.jsbmb.2005.04.007 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 958XE UT WOS:000231480700003 PM 15955696 ER PT J AU Zhang, PJ Land, W Lee, S Juliani, J Lefman, J Smith, SR Germain, D Kessel, M Leapman, R Rouault, TA Subramaniam, S AF Zhang, PJ Land, W Lee, S Juliani, J Lefman, J Smith, SR Germain, D Kessel, M Leapman, R Rouault, TA Subramaniam, S TI Electron tomography of degenerating neurons in mice with abnormal regulation of iron metabolism SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE iron regulatory protein; neuronal degeneration; electron tomography; electron energy loss spectroscopy; ferritin; double-walled vesicle ID PARKINSONS-DISEASE; BASAL GANGLIA; FERRITIN; PROTEIN; BRAIN; NEURODEGENERATION; CYTOPLASM; LIGHT AB Previous studies have shown that IRP1(+/-) IRP2(-/-) knockout mice develop progressive neurodegenerative symptoms similar to those observed in human movement disorders such as Parkinson's disease. Histological investigations using optical microscopy show that these IRP knockout mice display accumulation of ferritin in axonal tracts in the brain, suggesting a possible role for excess ferritin in mediating axonal degeneration. Direct observation of the 3D distribution of ferritin by electron tomography indicates that ferritin amounts are increased by 3- to 4-fold in selected regions of the brain, and structural damage is observed within the axon as evidenced by the loss of the internal network of filaments, and the invaginations of neighboring oligodendrocyte membranes into the axonal medium. While optical microscopic investigations suggest that there is a large increase in ferritin in the presumptive axonal regions of the IRP knockout mice, electron tomographic studies reveal that most of the excess ferritin is localized to double-walled vesicular compartments which are present in the interior of the axon and appear to represent invaginations of the oligodendrocyte cells into the axon. The amount of ferritin observed in the axonal space of the knockout mice is at least 10-fold less than the amount of ferritin observed in wild-type mouse axons. The surprising conclusion from our analysis, therefore, is that despite the overall increase in ferritin levels in the knockout mouse brain, ferritin is absent from axons of degenerating neurons, suggesting that trafficking is compromised in early stages of this type of neuronal degeneration. Published by Elsevier Inc. C1 Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20817 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20817 USA. NIH, Biomed Engn & Instrumentat Program, Bethesda, MD 20817 USA. RP Subramaniam, S (reprint author), Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20817 USA. EM ssl@nih.gov OI Russler-Germain, David/0000-0003-1009-2247 NR 26 TC 32 Z9 34 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY PY 2005 VL 150 IS 2 BP 144 EP 153 DI 10.1016/j.jsb.2005.012.007 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 926XS UT WOS:000229157600002 PM 15866737 ER PT J AU Arie, T Fairhurst, RM Brittain, NJ Wellems, TE Dvorak, JA AF Arie, T Fairhurst, RM Brittain, NJ Wellems, TE Dvorak, JA TI Hemogloblin C modulates the surface topography of Plasmodium falciparum-infected erythrocytes SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE atomic force microscopy; malaria; Plasmodium falciparum; hemoglobin C; knob; cytoadherence ID ATOMIC-FORCE MICROSCOPY; RED-BLOOD-CELLS; HUMAN CEREBRAL MALARIA; BINDING-SITES; MEMBRANE; BAND-3; PROTEIN; ASSOCIATION; IDENTIFICATION; SEQUESTRATION AB There is a well-established clinical association between hemoglobin genotype and innate protection against Plasmodium falciparum malaria. In contrast to normal hemoglobin A, mutant hemoglobin C is associated with substantial reductions ill the risk of severe malaria in both heterozygous AC and homozygous CC individuals. Irrespective of hemoglobin genotype, parasites may induce knob-like projections on the erythrocyte surface. The knobs play a major role in the pathogenesis of severe malaria by serving as points of adherence for P. falciparum-infected erythrocytes to microvascular endothelia. To evaluate the influence of hemoglobin genotype oil knob formation, we used a combination of atomic force and light microscopy for concomitant topographic and wide-field fluorescence imaging. Parasitized AA, AC, and CC erythrocytes showed a population of knobs with a mean width of &SIM; 70 nm. Parasitized AC and CC erythrocytes showed a second population of large knobs with a mean width of &SIM; 120 nm. Furthermore, spatial knob distribution analyses demonstrated that knobs on AC and CC erythrocytes were more aggregated than oil AA erythrocytes. These data support a model in which large knobs and their aggregates are promoted by hemoglobin C, reducing the adherence of parasitized erythrocytcs in the microvasculature and ameliorating the severity of a malaria infection. Published by Elsevier Inc. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Dvorak, JA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM JDvorak@niaid.nih.gov NR 38 TC 24 Z9 24 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY PY 2005 VL 150 IS 2 BP 163 EP 169 DI 10.1016/j.jsb.2005.02.008 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 926XS UT WOS:000229157600004 PM 15866739 ER PT J AU Baxa, U Cheng, NQ Winkler, DC Chiu, TK Davies, DR Sharma, D Inouye, H Kirschner, DA Wickner, RB Steven, AC AF Baxa, U Cheng, NQ Winkler, DC Chiu, TK Davies, DR Sharma, D Inouye, H Kirschner, DA Wickner, RB Steven, AC TI Filaments of the Ure2p prion protein have a cross-beta core structure SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE electron diffraction; X-ray diffraction; yeast prion; natively unfolded protein ID X-RAY-DIFFRACTION; FORMATION IN-VITRO; SACCHAROMYCES-CEREVISIAE; ELECTRON-MICROSCOPY; AMYLOID FIBERS; DOMAINS FORM; YEAST URE2P; CONFORMATION; NITROGEN; FIBRILS AB Formation of filaments by the Ure2 protein constitutes the molecular mechanism of the [URE3] prion in yeast. According to the &DPRIME; amyloid backbone&DPRIME; model, the N-terminal asparagine-rich domains of Ure2p polymerize to form an amyloid core fibril that is surrounded by C-terminal domains in their native conformation. Protease resistance and Congo Red binding as well as β-sheet content detected by spectroscopy-all markers for amyloid-have supported this model, as has the close resemblance between 40 &ANGS; N-domain fibrils and the fibrillar core of intact Ure2p filaments visualized by cryo-electron microscopy and scanning transmission electron microscopy. Here, we present electron diffraction and X-ray diffraction data from filaments of Ure2p, of N-domains alone, of fragments thereof, and of an N-domain-containing fusion protein that demonstrate in each case the 4.7 &ANGS; reflection that is typical for cross-β structure and highly indicative of amyloid. This reflection was observed for specimens prepared by air-drying with and without sucrose embedding. To confirm that the corresponding Structure is not an artifact of air-drying, the reflection was also demonstrated for specimens preserved in vitreous ice. Local area electron diffraction and X-ray diffraction from partially aligned specimens showed that the 4.7 &ANGS; reflection is meridional and therefore the underlying structure is cross-β. Published by Elsevier Inc. C1 Natl Inst Arthritis Musculoskeletal & Skin Dis, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Arthritis Musculoskeletal & Skin Dis, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Natl Inst Arthritis Musculoskeletal & Skin Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. RP Steven, AC (reprint author), Natl Inst Arthritis Musculoskeletal & Skin Dis, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov NR 63 TC 60 Z9 61 U1 3 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD MAY PY 2005 VL 150 IS 2 BP 170 EP 179 DI 10.1016/j.jsb.2005.02.007 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 926XS UT WOS:000229157600005 PM 15866740 ER PT J AU Wear, KA Laib, A Stuber, AP Reynolds, JC AF Wear, KA Laib, A Stuber, AP Reynolds, JC TI Comparison of measurements of phase velocity in human calcaneus to Biot theory SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ULTRASONIC WAVE-PROPAGATION; BOVINE CANCELLOUS BONE; TRABECULAR BONE; ACOUSTIC PROPAGATION; STRATIFIED MODEL; FREQUENCY RANGE; ELASTIC WAVES; CORTICAL BONE; DISPERSION; DEFORMATION AB Biot's theory for elastic propagation in porous media has previously been shown to be useful for modeling the dependence of phase velocity on porosity in bovine cancellous bone in vitro. In the present study, Biot's theory is applied to measurements of porosity-dependent phase velocity in 53 human calcanea in vitro. Porosity was measured using microcomputed tomography for some samples (n = 23) and estimated based on bone mineral densitometry for the remaining samples (n = 30). The phase velocity at 500 kHz was measured in a water tank using a through-transmission technique. Biot's theory performed well for the prediction of the dependence of sound speed on porosity. The trend was quasilinear, but both the theory and experiment show similar slight curvature. The root mean square error (RMSE) of predicted versus measured sound speed was 15.8 m/s. © 2005 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. SCANCO Med AG, CH-8303 Bassersdorf, Switzerland. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-140,12720 Twinbrook Pky, Rockville, MD 20852 USA. EM Kaw@cdrh.fda.gov NR 40 TC 46 Z9 47 U1 0 U2 3 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 MAY PY 2005 VL 117 IS 5 BP 3319 EP 3324 DI 10.1121/1.1886388 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 925QV UT WOS:000229068700063 PM 15957798 ER PT J AU Abikoff, H McGough, J Vitiello, B McCracken, J Dames, M Walkup, J Riddle, M Oatis, M Greenhill, L Skrobala, A March, J Gammon, P Robinson, J Lazell, R McMahon, DJ Ritz, L AF Abikoff, H McGough, J Vitiello, B McCracken, J Dames, M Walkup, J Riddle, M Oatis, M Greenhill, L Skrobala, A March, J Gammon, P Robinson, J Lazell, R McMahon, DJ Ritz, L CA RUPP ADHD Anxiety Study Grp TI Sequential pharmacotherapy for children with comorbid attention-deficit/hyperactivity and anxiety disorders SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity; anxiety; comorbidity; combination pharmacotherapy ID DEFICIT HYPERACTIVITY DISORDER; CRITERION VALIDITY; CONTROLLED TRIAL; ADHD CHILDREN; METHYLPHENIDATE; STIMULANT; RELIABILITY; FLUOXETINE; BEHAVIOR AB Objective: Attention-deficit/hyperactivity disorder (ADHD) is often accompanied by clinically significant anxiety, but few empirical data guide treatment of children meeting full DSM-IV criteria for ADHD and anxiety disorders (ADHD/ANX). This study examined the efficacy of sequential pharmacotherapy for ADHD/ANX children. Method: Children, age 6 to 17 years, with ADHD/ANX were titrated to optimal methylphenidate dose and assessed along with children who entered the study on a previously optimized stimulant. Children with improved ADHD who remained anxious were randomly assigned to 8 weeks of double-blind stimulant + fluvoxamine (STIM/FLV) or stimulant + placebo (STIM/PL). Primary efficacy measures were the Swanson, Nolan, Atkins, and Pelham IV Parent and Teacher Rating Scale ADHD score and the Pediatric Anxiety Rating Scale total score. ADHD, ANX, and overall Clinical Global Impressions-Improvement scores were also obtained. Results: Of the 32 medication-naive children openly treated with methylphenidate, 26 (81%) improved as to ADHD. Twenty-five children entered the randomized trial. Intent-to-treat analysis indicated no differences between the STIM/FLV (n = 15) and STIM/PL groups on the Pediatric Anxiety Rating Scale or Clinical Global Impressions-Improvement-defined responder rate. Medications in both arms were well tolerated. Conclusions: Children with ADHD/ANX have a response rate to stimulants for ADHD that is comparable with that of children with general ADHD. The benefit of adding FLV to stimulants for ANX remains unproven. C1 NYU, Ctr Child Study, New York, NY 10016 USA. Columbia Univ, New York State Psychiat Inst, New York, NY 10027 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NIMH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Abikoff, H (reprint author), NYU, Ctr Child Study, 215 Lexington Ave,14th Floor, New York, NY 10016 USA. EM abikoh01@med.nyu.edu FU NIMH NIH HHS [N01MH60005, MH01805, N01MH60016, N01MH70010, K23MH01966] NR 25 TC 65 Z9 65 U1 4 U2 9 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 MAY PY 2005 VL 44 IS 5 BP 418 EP 427 DI 10.1097/01.chi.0000155320.52322.37 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 919HW UT WOS:000228610000006 PM 15843763 ER PT J AU McClure, EB Treland, JE Snow, J Dickstein, DP Towbin, KE Charney, DS Pine, DS Leibenluft, E AF McClure, EB Treland, JE Snow, J Dickstein, DP Towbin, KE Charney, DS Pine, DS Leibenluft, E TI Memory and learning in pediatric bipolar disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE memory; bipolar disorder ID CLINICALLY REFERRED SAMPLE; PREFRONTAL CORTEX; NEUROPSYCHOLOGICAL PERFORMANCE; RATING-SCALE; ADOLESCENTS; MANIA; CHILDREN; ONSET; RELIABILITY; VALIDITY AB Objective: To test the hypothesis that patients with pediatric bipolar disorder (PBPD) would demonstrate impairment relative to diagnosis-free controls of comparable age, gender, and IQ on measures of memory functioning. Method: The authors administered a battery of verbal and visuospatial memory tests to 35 outpatients with PBPD and 20 healthy controls who participated as volunteers in this study. Groups did not differ on age, gender, or IQ. Results: Consistent with findings in adults with BPD, patients with PBPD performed more poorly than controls on measures of verbal learning/memory and delayed facial recognition memory. Impaired memory was particularly evident in patients with comorbid PBPD/attention-deficit/hyperactivity disorder or acute mood symptoms. Conclusions: These findings suggest that deficits in verbal learning and memory, as well as some aspects of visuospatial memory, characterize patients with narrow phenotype PBPD. Further research is needed, however, to clarify the roles of comorbid attention-deficit/hyperactivity disorder and acute mood state in the emergence of these deficits. Given the apparent continuity in memory dysfunction between adult BPD and narrow phenotype PBPD, research aimed at elucidating underlying neural mechanisms for this set of deficits is warranted. C1 NIMH, NIH, MAP, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP McClure, EB (reprint author), NIMH, NIH, MAP, Mood & Anxiety Disorders Program, 15K N Dr,Room 204,MSC 2670, Bethesda, MD 20892 USA. EM erin.mcclure@nih.gov RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 NR 37 TC 46 Z9 50 U1 1 U2 2 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 MAY PY 2005 VL 44 IS 5 BP 461 EP 469 DI 10.1097/01.chi.0000156660.30953.91 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 919HW UT WOS:000228610000011 PM 15843768 ER PT J AU Twede, JV Turner, JT Biesecker, LG Darling, TN AF Twede, JV Turner, JT Biesecker, LG Darling, TN TI Evolution of skin lesions in Proteus syndrome SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DIAGNOSTIC-CRITERIA; MOSAICISM; ANOMALIES; TUMORS; NEVUS AB Background: Proteus syndrome is a rare overgrowth disorder that is generally progressive, but the natural history of the skin lesions is not known. Objective: Our purpose was to document the evolution of 4 common skin lesions in 16 patients with Proteus syndrome. Results: Most epidermal nevi and vascular malformations were reported to appear in the first month of life and had little tendency for expansion or development of additional lesions. Subcutaneous lipomas and cerebriform connective tissue nevi were commonly noted in the first year of life, but not in the first month. Most patients reported that Subcutaneous lipomas and cerebriform connective tissue nevi progressively increased in size, and in most patients additional lesions developed at new locations. Of the 4 types of skin lesions, plantar cerebriform connective tissue nevi were most frequently cited as a source of symptoms. Conclusion: Skin lesions of Proteus syndrome may not appear until later infancy or early childhood, making it difficult to diagnose in young children. C1 Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD USA. RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM tdarling@usuhs.mil OI Darling, Thomas/0000-0002-5161-1974 NR 13 TC 20 Z9 21 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2005 VL 52 IS 5 BP 834 EP 838 DI 10.1016/j.jaad.2004.12.047 PG 5 WC Dermatology SC Dermatology GA 926JT UT WOS:000229120200010 PM 15858474 ER PT J AU Dwyer, JT Allison, DB Coates, PM AF Dwyer, JT Allison, DB Coates, PM TI Dietary supplements in weight reduction SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID BODY-WEIGHT; CALCIUM SUPPLEMENTATION; BONE TURNOVER; OBESE ADULTS; FAT LOSS; OVERWEIGHT; WOMEN; EFFICACY; SAFETY; METAANALYSIS AB We summarize evidence on the role of dietary supplements in weight reduction, with particular attention to their safety and benefits. Dietary supplements are used for two purposes in weight reduction: (a) providing nutrients that may be inadequate in calorie-restricted diets and (b) for their potential benefits in stimulating weight loss. The goal in planning weight-reduction diets is that total intake from food and supplements should meet recommended dietary allowance/adequate intake levels without greatly exceeding them for all nutrients, except energy. If nutrient amounts from food sources in the reducing diet fall short, dietary supplements containing a single nutrient/element or a multivitamin-mineral combination may be helpful. On hypocaloric diets, the addition of dietary supplements providing nutrients at a level equal to or below recommended dietary allowance/adequate intake levels or 100% daily value, as stated in a supplement's facts box on the label, may help dieters to achieve nutrient adequacy and maintain electrolyte balance while avoiding the risk of excessive nutrient intakes. Many botanical and other types of dietary supplements are purported to be useful for stimulating or enhancing weight loss. Evidence of their efficacy in stimulating weight loss is inconclusive at present. Although there are few examples of safety concerns related to products that are legal and on the market for this purpose, there is also a paucity of evidence on safety for this intended use. Ephedra and ephedrine-containing supplements, with or without caffeine, have been singled out in recent alerts from the Food and Drug Administration because of safety concerns, and use of products containing these substances cannot be recommended. Dietitians should periodically check the Food and Drug Administration Web site (http://www.cfsan.fda.gov) for updates and warnings and alert patients/clients to safety concerns. Dietetics professionals should also consult authoritative sources for new data on efficacy as it becomes available (ods.od.nih.gov). C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Univ Alabama, Sect Stat Genet, Dept Biostat, Birmingham, AL USA. Univ Alabama, Clin Nutr Res Ctr, Dept Nutr Sci, Birmingham, AL USA. RP Dwyer, JT (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01 MSC 7517, Bethesda, MD 20892 USA. EM DwyerJ1@od.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769; Allison, David/0000-0003-3566-9399 NR 39 TC 34 Z9 36 U1 0 U2 12 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 2005 VL 105 IS 5 SU 1 BP S80 EP S86 DI 10.1016/j.jada.2005.02.028 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 927VL UT WOS:000229228500014 PM 15867902 ER PT J AU Visser, M Simonsick, EM Colbert, LH Brach, J Rubin, SM Kritchevsky, SB Newman, AB Harris, TB AF Visser, M Simonsick, EM Colbert, LH Brach, J Rubin, SM Kritchevsky, SB Newman, AB Harris, TB CA Hlth ABC Study TI Type and intensity of activity and risk of mobility limitation: The mediating role of muscle parameters SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE exercise; walking; physical function; elderly; race ID RANDOMIZED CONTROLLED TRIAL; PHYSICAL-ACTIVITY; OLDER-ADULTS; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; ELDERLY-MEN; DISABILITY; PERFORMANCE; PREDICTORS; STRENGTH AB OBJECTIVES: To investigate the association between different types of physical activity behavior and incident mobility limitation in older men and women and to examine whether muscle parameters mediate these associations. DESIGN: Cohort study with 4.5-year follow-up. SETTING: Metropolitan areas surrounding Pittsburgh, Pennsylvania, and Memphis, Tennessee. A random sample of white Medicare beneficiaries and all age-eligible blacks. PARTICIPANTS: Three thousand seventy-five black and white men and women aged 70 to 79 with no self-reported difficulty walking one-quarter of a mile or climbing 10 steps, enrolled in the Health, Aging and Body Composition (Health ABC) Study. MEASUREMENTS: Participants were classified as exercisers (reporting >= 1,000 kcal/wk of exercise activity), lifestyle active (reporting < 1,000 kcal/wk of exercise activity and >= 2,719 kcal/wk of total physical activity), or inactive (reporting < 1,000 kcal/wk of exercise activity and < 2,719 kcal/wk of total physical activity). The study outcome, incident mobility limitation, was defined as two consecutive, semiannual self-reports of any difficulty walking one quarter of a mile or climbing 10 steps. Thigh muscle area, thigh muscle attenuation (a marker of fat infiltration in muscle), appendicular lean soft tissue mass, and isokinetic knee extensor strength were examined as potential mediators. RESULTS: Over 4.5 years, 34.3% of men and 47.4% of women developed mobility limitation. Inactive persons had twice the risk of incident mobility limitation as exercisers (hazard ratio (HR)=2.08, 95% confidence interval (CI)=1.60-2.70, for men, HR=1.98, 95% CI=1.51-2.60, for women). Lifestyle-active men and women had an intermediate risk (HR=1.47 and 1.44, respectively). For the lifestyle active and inactive, absence of walking activity conferred an additional risk of mobility limitation. Muscle parameters did not mediate the relationship between physical activity and mobility limitation, except for knee extensor strength in men. CONCLUSION: Exercise and an active lifestyle that includes walking protect against mobility loss in older men and women. Activity effects on muscle parameters do not explain this association. C1 Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, NL-1081 HV Amsterdam, Netherlands. VU Univ Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. NIA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Wisconsin, Dept Kinesiol, Madison, WI USA. Univ Pittsburgh, Dept Phys Therapy, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Visser, M (reprint author), Vrije Univ Amsterdam, Fac Earth & Life Sci, Inst Hlth Sci, Boelelaan 1085, NL-1081 HV Amsterdam, Netherlands. EM marjolein.visser@falw.vu.nl RI Brach, Jennifer/A-6912-2009; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2101, N01-AG-6-2106] NR 41 TC 51 Z9 52 U1 1 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD MAY PY 2005 VL 53 IS 5 BP 762 EP 770 DI 10.1111/j.1532-5415.2005.53257.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 921GB UT WOS:000228751100003 PM 15877550 ER PT J AU Sharp, JS Tomer, KB AF Sharp, JS Tomer, KB TI Formation of [b((n-1)) + OH+H](+) ion structural analogs by solution-phase chemistry SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID COLLISION-INDUCED DISSOCIATION; MASS-SPECTROMETRY; GAS-PHASE; PROTONATED PEPTIDES; AMINO-ACID; SEQUENCE-ANALYSIS; FRAGMENTATION; SPECTRA; IONS; REARRANGEMENT AB Derivatization of a variety of peptides by a method known to enhance anhydride formation is demonstrated by mass spectrometry to yield ions that have elemental composition and fragmentation properties identical to [b((n-1)) + OH + H](+) ions formed by gas-phase rearrangement and fragmentation. The [b((n-1)) + OH + H](+) ions formed by gas-phase rearrangement and fragmentation and the solution-phase [b((n-1)) + OH + H](+) ion structural analogs formed by derivatization. chemistry show two different forms of dissociation using multiple-collision CAD in a quadrupole ion trap and unimolecular decomposition in a TOF-TOF; one group yields identical product ions as a truncated form of the peptide with a free C-terminal carboxylic acid and fragments at the same activation energy; the other group fragments differently from the truncated peptide, being more resistant to fragmentation than the truncated peptide and yielding primarily the [b((n-2)) + OH + H](+) product ion. Nonergodic electron capture dissociation MS/MS suggests that any structural differences between the specific-fragmenting [b((n-1)) + OH + H](+) ions and the truncated peptide is at the C-terminus of the peptide. The specific-fragmentation can be readily observed by MSn experiments to occur in an iterative fashion, suggesting that the C-terminal structure of the original [b((n-1)) + OH + H](+) ion is maintained after subsequent rearrangement and fragmentation events in peptides which fragment specifically. A mechanism for the formation of specific-fragmenting and nonspecific-fragmenting [b((n-1)) + OH + H](+) ions is proposed. © 2005 American Society for Mass Spectrometry. C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Sharp, JS (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233,MD F0-04, Res Triangle Pk, NC 27709 USA. EM sharp1@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 32 TC 9 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD MAY PY 2005 VL 16 IS 5 BP 607 EP 621 DI 10.1016/j.jasms.2005.01.016 PG 15 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 922YE UT WOS:000228875000001 PM 15862763 ER PT J AU Perkins, BA Nelson, RG Ostrander, BEP Blouch, KL Krolewski, AS Myers, BD Warram, JH AF Perkins, BA Nelson, RG Ostrander, BEP Blouch, KL Krolewski, AS Myers, BD Warram, JH TI Detection of renal function decline in patients with diabetes and normal or elevated GFR by serial measurements of serum cystatin C concentration: Results of a 4-year follow-up study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GLOMERULAR-FILTRATION-RATE; KIDNEY-FUNCTION; PIMA-INDIANS; CREATININE; MARKER; CLEARANCE; PERFORMANCE; PROGRESSION; MELLITUS; HUMANS AB Research on early renal function decline in diabetes is hampered by lack of simple tools for detecting trends (particularly systematic decreases) in renal function over time when GFR is normal or elevated. This study sought to assess how well serum cystatin C meets that need. Thirty participants with type 2 diabetes in the Diabetic Renal Disease Study met these three eligibility criteria: GFR > 20 ml/min per 1.73 m 2 at baseline (based on cold iothalamate clearance), 4 yr of follow-up, and yearly measurements of iothalamate clearance and serum cystatin C. With the use of linear regression, each individual's trend in renal function over time, expressed as annual percentage change in iothalamate clearance, was determined. Serum cystatin C in mg/L was transformed to its reciprocal (100/cystatin C), and linear regression was used to determine each individual's trend over time, expressed as annual percentage change. In paired comparisons of 100/cystatin C with iothalamate clearance at each examination, the two measures were numerically similar. More important, the trends in 100/cystatin C and iothalamate clearance were strongly correlated (Spearman r = 0.77). All 20 participants with negative trends in iothalamate clearance (declining renal function) also had negative trends for 100/cystatin C. Results were discordant for only three participants. In contrast, the trends for three commonly used creatinine-based estimates of GFR compared poorly with trends in iothalamate clearance (Spearman r < 0.35). Serial measures of serum cystatin C accurately detect trends in renal function in patients with normal or elevated GFR and provide means for studying early renal function decline in diabetes. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. NIDDKD, Diabet & Arthrit Epidemiol Sect, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. Stanford Univ, Sch Med, Div Nephrol, Stanford, CA USA. RP Warram, JH (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM james.warram@joslin.harvard.edu RI Nelson, Robert/B-1470-2012 FU Intramural NIH HHS [Z01 DK069063-10]; NIDDK NIH HHS [DK67638, DK41526, DK58549, R01 DK041526, R01 DK058549, R01 DK067638] NR 34 TC 224 Z9 237 U1 1 U2 12 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 MAY PY 2005 VL 16 IS 5 BP 1404 EP 1412 DI 10.1681/ASN.2004100854 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 920UN UT WOS:000228715700028 PM 15788478 ER PT J AU Friedman, MA Levin, BE AF Friedman, MA Levin, BE TI Neurobehavioral effects of harmful algal bloom (HAB) toxins: A critical review SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE marine toxins; neurotoxins; neuropsychology; Pfiesteria piscicida; Ciguatera poisoning; Aimnesic shellfish poisoning; domoic acid; "deliritum, dementia, amnestic, cognitive disorders" ID ESTUARY-ASSOCIATED SYNDROME; DOMOIC ACID; HUMAN HEALTH; NEUROLOGIC SEQUELAE; NORTH-CAROLINA; CIGUATERA; PFIESTERIA; NEUROTOXICITY; EXPOSURE; MUSSELS AB Human exposure to naturally occurring marine toxins has been associated with a range of neurobehavioral abnormalities. The toxins are produced by harmful algal blooms (HABs) and are typically contracted through seafood consumption. The primary target of many of the HAB toxins is the neurologic system, and the neurobehavioral symptoms associated with the HAB illnesses have influenced public health policy. The HAB-related illnesses most frequently linked to neuropsychological disturbance are Amnesic Shellfish Poisoning, Ciguatera Fish Poisoning, and Possible Estuarine Associated Syndrome, which is associated with exposure to the Pfiesteria piscicida organism. Although the neurophysiologic mechanisms underlying many of the HAB illnesses have been well delineated, the literature examining the neuropsychological impairments is unclear and needs to be defined. This review is intended to introduce an emerging area of study linking HAB illnesses with neuropsychological changes. C1 Univ Miami, NIEHS, Marine & Freshwater Biomed Sci Ctr, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. RP Friedman, MA (reprint author), Carlos Albizu Univ, 2173 NW 99th Ave, Miami, FL 33172 USA. EM melissafried@yahoo.com FU NIEHS NIH HHS [T32 ES337320, ES05705] NR 52 TC 15 Z9 16 U1 4 U2 15 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD MAY PY 2005 VL 11 IS 3 BP 331 EP 338 DI 10.1017/S1355617705050381 PG 8 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 924UL UT WOS:000229005900012 PM 15892909 ER PT J AU Cole, GW Alleva, AM Reddy, RM Maxhimer, JB Zuo, JT Schrump, DS Nguyen, DM AF Cole, GW Alleva, AM Reddy, RM Maxhimer, JB Zuo, JT Schrump, DS Nguyen, DM TI The selective epidermal growth factor receptor tyrosine kinase inhibitor PD153035 suppresses expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 84th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 25-MAY 28, 2004 CL Toronto, CANADA SP Amer Assoc Thorac Surg ID LUNG-CANCER CELLS; SOLID TUMORS; NUDE-MICE; GEFITINIB; MUTATIONS; EGFR; ANGIOGENESIS; GEMCITABINE; SENSITIVITY; COMBINATION AB Objective: Malignant pleural mesothelioma is notoriously refractory to aggressive multimodality therapy. Epidermal growth factor receptor expression has been observed on malignant pleural mesothelioma cells. Epidermal growth factor receptor-mediated signaling promotes tumorigenesis and metastasis of cancer cells. The purpose of this study is to evaluate the ability of the epidermal growth factor receptor tyrosine kinase inhibitor PD153035 to abrogate the expression of prometastasis phenotypes in malignant pleural mesothelioma cells in vitro. Methods: Epidermal growth factor receptor expression of malignant pleural mesothelioma cells and primary normal cells was quantitated by means of flow cytometry. PD153035-mediated growth inhibition was determined by means of 1-(4,5-Dimethylthiazol-2-yl)-3,5-diphenylformazan and clonogenic assays. Cell motility and invasion of extracellular matrix was evaluated with in vitro wound-healing and Matrigel invasion assays, respectively. Vascular epidermal growth factor levels in conditioned media were measured by using enzyme-linked immunosorbent assay. Results: Epidermal growth factor receptor expression was detected on all 6 cultured malignant pleural mesothelioma cells, with 4 of 6 having normal receptor expression and 2 of 6 overexpressing the receptor. PD153035 suppressed cell motility and cell invasion through a Matrigel membrane, regardless of the baseline epidermal growth factor receptor expression. Decreased vascular epidermal growth factor production and significant inhibition of growth only occurred in malignant pleural mesothelioma cells that overexpress epidermal growth factor receptor. Conclusions: Epidermal growth factor receptor tyrosine kinase inhibitor PD153035 significantly inhibited motility and invasion in malignant pleural mesothelioma cells in vitro, regardless of their epidermal growth factor receptor expression levels. Inhibition of epidermal growth factor receptor-dependent signaling might be a useful strategy to diminish malignant pleural mesothelioma recurrence after aggressive cytoreductive surgery. C1 NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), Room 2B07,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA. EM Dao_Nguyen@nih.gov NR 22 TC 15 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2005 VL 129 IS 5 BP 1010 EP 1017 DI 10.1016/j.jtcvs.2004.10.040 PG 8 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 923ZD UT WOS:000228947200009 PM 15867774 ER PT J AU Horvath, KA Lu, CYJ Robert, E Pierce, GF Greene, R Sosnowski, BA Doukas, J AF Horvath, KA Lu, CYJ Robert, E Pierce, GF Greene, R Sosnowski, BA Doukas, J TI Improvement of myocardial contractility in a porcine model of chronic ischemia using a combined transmyocardial revascularization and gene therapy approach SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; CORONARY-ARTERY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; LASER REVASCULARIZATION; REFRACTORY ANGINA; MEDICAL THERAPY; ANGIOGENESIS; DELIVERY; RECOVERY; FLOW AB Objectives: The purpose of this study was to investigate whether a novel fibroblast growth factor-2 gene formulation, providing a localized and sustained availability of the adenoviral vector from a collagen-based matrix, in combination with CO2 transmyocardial laser revascularization would lead to an enhanced angiogenic response and improved myocardial function. Methods: Fibroblast growth factor-2 gene was delivered by means of an adenoviral vector (adenoviral fibroblast growth factor-2) formulated in a collagen-based matrix. The ischemic areas of 33 animals were then treated. Group I was treated with CO2 transmyocardial laser revascularization; group 2 was treated with intramyocardial injections of adenoviral fibroblast growth factor-2 in a collagen-based matrix; group 3 had a combination treatment of matrix adenoviral fibroblast growth factor-2 and CO2 transmyocardial laser revascularization; and group 4 received injections with saline-formulated adenoviral fibroblast growth factor-2. Baseline left ventricular function was assessed by echocardiography and cine magnetic resonance imaging. Studies were repeated 6 weeks after treatment. Vascular development was assessed using anti-a-actin immunohistochemistry. Results: Matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas had a 105% increase in arteriolar development versus either treatment alone (P < .05) and a 390% increase compared with saline-formulated adenoviral fibroblast growth factor-2 treatment alone (P < .05). Contractility was significantly improved in matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularization-treated areas as measured by myocardial wall thickening. This functional improvement was confirmed by cine magnetic resonance imaging, in which a 90% increase in the contractility of the treated segments was demonstrated after matrix adenoviral fibroblast growth factor-2 + transmyocardial laser revascularation. The other treatments provided significantly less restoration of myocardial function. Conclusions: The increase in angiogenesis as a result of matrix adenoviral fibroblast growth factor-2 gene therapy in combination with CO2 transmyocardial laser revascularization is greater than that seen in either therapy alone. A concomitant improvement in myocardial function was seen as a result of this angiogenic response. C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Select Genet Inc, San Diego, CA USA. RP Horvath, KA (reprint author), NHLBI, Cardiothorac Surg Branch, NIH, Bldg 10,Room 8C103,10 Ctr Dr,MSC 1754, Bethesda, MD 20892 USA. EM horvathka@mail.nih.gov NR 34 TC 10 Z9 15 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD MAY PY 2005 VL 129 IS 5 BP 1071 EP 1077 DI 10.1016/j.jtcvs.2004.10.017 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 923ZD UT WOS:000228947200017 PM 15867782 ER PT J AU Mari, G AF Mari, G TI Middle cerebral artery peak systolic velocity - Is it the standard of care for the diagnosis of fetal anemia? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Review DE fetal anemia; middle cerebral artery peak systolic velocity; pulsatility index; red cell alloimmunization ID RED-CELL ALLOIMMUNIZATION; ISOIMMUNIZED PREGNANCIES; DOPPLER ULTRASONOGRAPHY; NONINVASIVE DIAGNOSIS; FLOW-VELOCITY; INTRAUTERINE TRANSFUSION; RHESUS-ISOIMMUNIZATION; RH-ALLOIMMUNIZATION; UMBILICAL VEIN; BLOOD-FLOW AB Objective. The aim of this work was to review the use of middle cerebral artery peak systolic velocity (MCA PSV) for the diagnosis of fetal anemia. Methods. With the use of a computerized database (MEDLINE), articles on the diagnosis of fetal anemia with ultrasonography were reviewed. Other pertinent references were obtained from the references cited in these articles. in addition, my own institution's clinical experience of the past 18 years was reviewed. Results. Several ultrasonographic parameters have been used to diagnose noninvasive fetal anemia. On the basis of robust data, the MCA PSV is the best ultrasonographic parameter used in the management of fetuses at risk for anemia due to different causes. It is also superior to amniocentesis for the diagnosis of fetal anemia in cases of red cell alloimmunization. Conclusions. Middle cerebral artery peak systolic velocity is effective for diagnosis of noninvasive moderate and severe fetal anemia. This parameter should not yet be considered the global standard of care for diagnosis of fetal anemia because incorrect use by an inexperienced operator may cause more harm than good; however, if there is a reasonably close medical center with sonographers or sonologists trained to assess the MCA PSV, patients at risk for fetal anemia should be referred to this center. C1 Wayne State Univ, Dept Obstet & Gynecol, Perinatol Res Branch, NICHHD,NIH,Dept Hlth & Human Serv, Detroit, MI 48201 USA. RP Mari, G (reprint author), Wayne State Univ, Dept Obstet & Gynecol, Perinatol Res Branch, NICHHD,NIH,Dept Hlth & Human Serv, 4th Floor,Rush Ctr PRB,3990 John R, Detroit, MI 48201 USA. NR 53 TC 18 Z9 22 U1 0 U2 2 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAY PY 2005 VL 24 IS 5 BP 697 EP 702 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 920TI UT WOS:000228712600015 PM 15840801 ER PT J AU Pavlovich, CP Grubb, RL Hurley, K Glenn, GM Toro, J Schmidt, LS Torres-Cabala, C Merino, MJ Zbar, B Choyke, P Walther, MM Linehan, WM AF Pavlovich, CP Grubb, RL Hurley, K Glenn, GM Toro, J Schmidt, LS Torres-Cabala, C Merino, MJ Zbar, B Choyke, P Walther, MM Linehan, WM TI Evaluation and management of renal tumors in the Birt-Hogg-Dube syndrome SO JOURNAL OF UROLOGY LA English DT Article DE kidney; kidney neoplasms; gene expression; pneumothorax ID PARENCHYMAL SPARING SURGERY; SPONTANEOUS PNEUMOTHORAX; CELL CARCINOMA; 10-YEAR EXPERIENCE; KIDNEY NEOPLASIA AB Purpose: Herein we describe the evaluation and management of renal tumors in Birt-Hogg-Dube (BHD), an autosomal dominant disorder predisposing to cutaneous fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax and renal tumors. Materials and Methods: A total of 124 affected individuals underwent comprehensive clinical evaluation, including body computerized tomography, to determine cutaneous, pulmonary and renal manifestations of BHD. Of these individuals 14 had their renal tumors managed at our institution. Results: Of the 124 BHD affected individuals 34 (27%) had renal tumors of various histologies, most commonly hybrid oncocytic tumor and chromophobe renal carcinoma. Average age at renal tumor detection was 50.4 years and multiple tumors were found in a majority of patients. Some patients with renal tumors were identified that did not have the characteristic cutaneous hallmarks of BHD. In 4 of the 14 patients treated at our institution small (less than 3 cm) renal tumors were observed, while 10 others underwent a total of 12 renal procedures, including 4 radical and 8 partial nephrectomies. At a median of 38 months of followup 5 of these 10 patients remained free of disease, 3 had small renal tumors and 2 died of metastatic renal cancer. Conclusions: Patients with BHD are at risk for multiple renal tumors that are often malignant and can metastasize. Individuals at risk or affected by BHD should be radiographically screened for renal tumors at periodic intervals and they are best treated with nephron sparing surgical approaches. Genetic testing for this syndrome is now available. C1 NCI, Ctr Canc Res, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, SAIC Frederick Inc, Frederick, MD USA. Ctr Canc Res, Mol Imaging Program, Bethesda, MD USA. RP Linehan, WM (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, Bldg 10,Room 2B47, Bethesda, MD 20892 USA. EM UOB@nih.gov FU PHS HHS [N01-C0-12400] NR 18 TC 119 Z9 120 U1 0 U2 2 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 MAY PY 2005 VL 173 IS 5 BP 1482 EP 1486 DI 10.1097/01.ju.0000154629.45832.30 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300009 PM 15821464 ER PT J AU Datta, MW Dhir, R Dobbin, K Bosland, MC Melamed, J Becich, MJ Orenstein, JM Kajdacsy-Balla, AA Patel, A Macias, V Berman, JJ AF Datta, MW Dhir, R Dobbin, K Bosland, MC Melamed, J Becich, MJ Orenstein, JM Kajdacsy-Balla, AA Patel, A Macias, V Berman, JJ TI Prostate cancer in patients with screening serum prostate specific antigen values less than 4.0 ng/dl: Results from the cooperative prostate cancer tissue resource SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; treatment outcome; age factors; African Americans ID MEN; CARCINOMA; LEVEL; PSA AB Purpose: Prostate cancer can occur in patients with low screening serum prostate specific antigen (PSA) values (less than 4.0 ng/ml). It is currently unclear whether these tumors are different from prostate cancer in patients with high PSA levels (greater than 4.0 ng/ml). Materials and Methods: From the Cooperative Prostate Cancer Tissue Resource database through March 2004, 3,416 patients with screening PSA less than 16.0 ng/ml diagnosed with prostate cancer between 1993 and 2004 were stratified in groups based on screening serum PSA. These subsets were compared for race, age at diagnosis, clinical and pathological stage, Gleason score, positive surgical margins, posttreatment recurrent disease, and vital status. Results: We identified 468 (14%) patients with screening PSA less than 4.0 ng/ml, 142 (4.2%) of whom had a PSA of less than 2.0 ng/ml. This group included 40 black and 376 white patients. Men with low screening PSA treated with radical prostatectomy had smaller cancers, lower Gleason scores, lower pathological tumor (T) stage and lower PSA recurrence rates than men with high PSA levels (4 ng/ml or greater). These differences held true for men who were younger than 62 years or were white, whereas older or black men had tumor characteristics and outcomes similar to those with higher PSA levels. Conclusions: Young (younger than 62 years) or white patients with screening serum PSA less than 4.0 ng/ml had smaller, lower grade tumors and lower recurrence rates than patients with PSA 4.0 ng/ml or greater. This was not true for those older than 62 years and for black men. C1 NYU, Sch Med, Dept Pathol, New York, NY USA. NYU, Sch Med, Dept Environm Med, New York, NY USA. NYU, Sch Med, Dept Urol, New York, NY USA. Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. George Washington Univ, Dept Pathol, Washington, DC 20052 USA. Univ Illinois, Dept Pathol, Chicago, IL USA. NCI, Canc Diagnosis Program, Bethesda, MD USA. RP Datta, MW (reprint author), Emory Univ, Sch Med, Dept Pathol, Winship Canc Inst, Atlanta, GA 30322 USA. OI Melamed, Jonathan/0000-0003-2844-7990 FU NCI NIH HHS [U01 CA86735, P30 CA13343, U01 CA86739, U01 CA86743, U01 CA86772] NR 17 TC 7 Z9 9 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 MAY PY 2005 VL 173 IS 5 BP 1546 EP 1551 DI 10.1097/01.ju.0000154778.06649.f5 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300022 PM 15821483 ER PT J AU Meng, MV Elkin, EP Latini, DM DuChane, J Carroll, PR AF Meng, MV Elkin, EP Latini, DM DuChane, J Carroll, PR TI Treatment of patients with high risk localized prostate cancer: Results from Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; risk; epidemiology ID EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; ANTIGEN RECURRENCE; THERAPY; DISEASE; EXPERIENCE; SURVIVAL AB Purpose: Pretreatment risk assessment models facilitate more appropriate selection of treatment for prostate cancer. However, men with high risk disease remain a challenge with significant potential for primary treatment failure. We characterize patterns of treatment for high risk prostate cancer in a community based cohort. Materials and Methods: In the Cancer of the Prostate Strategic Urological Research Endeavor (CaPSURE) database, a longitudinal disease registry of men with prostate cancer, we identified those with nonmetastatic, high risk disease based on T stage, tumor grade and serum prostate specific antigen (PSA). Differences in primary treatment, and the use of neoadjuvant and adjuvant therapy in patients at low, intermediate and high risk were assessed. In the high risk cohort predictors of the type of primary treatment, and the use of neoadjuvant and adjuvant androgen therapy were identified. Results: Of the cancers 34%, 40% and 26% were low, intermediate and high risk, respectively. Differences in primary treatment type among the 3 risk groups were statistically significant (p < 0.0001) with increasing external beam radiation therapy and androgen deprivation, and decreased surgery, brachytherapy and surveillance in men with high risk cancers. In this group older age, higher PSA and nonprivate insurance were associated with decreased use of radical prostatectomy. More than half of the men at high risk receiving radiation therapy also received androgen deprivation, which was significantly higher than in the low and intermediate risk groups (p < 0.0001). Factors associated with androgen deprivation in high risk disease were primary therapy, PSA, Gleason sum, T stage, body mass index, insurance status and ethnicity. PSA and Gleason sum were the primary determinants of adjuvant radiation after prostatectomy. Conclusions: Men with high risk but nonmetastatic prostate cancer are more likely to receive radiation therapy as well as androgen deprivation with the latter as primary therapy or in conjunction with local treatment. These data stress the importance of pretreatment risk stratification, education regarding appropriate combinations of local and systemic therapies, and the consideration of novel clinical trials in patients at higher risk. C1 Univ Calif San Francisco, NCI, NIH, San Francisco, CA 94115 USA. Univ Calif San Francisco, Urol Outcomes Res Grp, Program Urol Oncol, Dept Urol, San Francisco, CA 94115 USA. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. RP Meng, MV (reprint author), Univ Calif San Francisco, NCI, NIH, 1600 Divisadero St,6th Floor, San Francisco, CA 94115 USA. EM mmeng@urol.ucsf.edu OI Latini, David/0000-0002-6161-4861 NR 20 TC 81 Z9 82 U1 1 U2 4 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 MAY PY 2005 VL 173 IS 5 BP 1557 EP 1561 DI 10.1097/01.ju.0000154610.81916.81 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300024 PM 15821485 ER PT J AU Gulley, JL Figg, WD Steinberg, SM Carter, J Hussain, MH Dahut, WL AF Gulley, JL Figg, WD Steinberg, SM Carter, J Hussain, MH Dahut, WL TI A prospective analysis of the time to normalization of serum androgens following 6 months of androgen deprivation therapy in patients on a randomized phase III clinical trial using limited hormonal therapy SO JOURNAL OF UROLOGY LA English DT Article DE testosterone; gonadorelin; prostatic neoplasms; prostate-specific antigen; clinical trial ID PROSTATE-CANCER; DOSING SCHEDULE; TESTOSTERONE; AGONIST; THALIDOMIDE; SUPPRESSION; NEOADJUVANT; PLACEBO AB Purpose: Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent therapy with gonadotropin-releasing hormone agonists (GnRH-A). While these are largely successful in decreasing testosterone (T) and dihydroxytestosterone (DHT) to castrate levels, discontinuation of such therapy often results in continued suppression of androgens for variable periods of time. We present the largest published series of patients evaluating the timing of T and DHT increase after cessation of GnRH therapy. Materials and Methods: Serial T and DHT measurements were prospectively obtained every 3 months while on GnRH-A then monthly upon discontinuation of GnRH-A. Analysis of time from the second 3-month GnRH-A administration to T and DHT increase was undertaken. Results: A total of 80 evaluable patients had a median time to T 50 ng/dl or greater of 12.9 weeks and a median time to T normalization (212 ng/dl or greater) of 16.6 weeks. Low baseline T was associated with a prolonged time to T 212 ng/dl or greater (p = 0.0086) and a similar trend was seen in patients older than 66 years (p = 0.08). There were 62 evaluable patients with a median of 14.9 weeks to DHT 150 pg/ml or greater. There was no association with Gleason score at diagnosis, on study prostate specific antigen, type of prior definitive therapy, or any prior hormonal therapy and time to increase in circulating androgens. Conclusions: After 6 months of GnRH-A therapy in these patients, DHT and T levels did not return to normal for a median of 14.9 and 16.6 weeks, respectively. C1 NCI, Genitourinary Clin Res Sect, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Gulley, JL (reprint author), NCI, Genitourinary Clin Res Sect, Med Oncol Clin Res Unit, Ctr Canc Res, 10 Ctr Dr,8B07 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 16 TC 53 Z9 54 U1 2 U2 4 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 MAY PY 2005 VL 173 IS 5 BP 1567 EP 1571 DI 10.1097/01.ju.0000154780.72631.85 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300026 PM 15821487 ER PT J AU Penson, DF McLerran, D Feng, ZD Li, L Albertsen, PC Gilliland, FD Hamilton, A Hoffman, RM Stephenson, RA Potosky, AL Stanford, JL AF Penson, DF McLerran, D Feng, ZD Li, L Albertsen, PC Gilliland, FD Hamilton, A Hoffman, RM Stephenson, RA Potosky, AL Stanford, JL TI 5-year urinary and sexual outcomes after radical prostatectomy: Results from the prostate cancer outcomes study SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; prostatectomy; urinary incontinence; impotence ID QUALITY-OF-LIFE; SILDENAFIL CITRATE; CONTINENCE; IMPOTENCE; INCONTINENCE; RADIATION; SYMPTOMS; CAPSURE; POTENCY; VIAGRA AB Purpose: Prior studies of postoperative outcomes following radical prostatectomy have been limited by selection bias and short-term followup. In this study we assessed temporal changes in urinary and sexual function up to 5 years following radical prostatectomy in a population based cohort. Materials and Methods: A sample of 1,288 men with localized prostate cancer who underwent radical prostatectomy and completed a baseline survey within 6 to 12 months of diagnosis were included in the analysis. Two and 5-year functional and quality of life data were collected, as was information on the use of erectile aids. Temporal functional changes and potentially confounding or modifying factors were assessed using longitudinal regression models. Results: Of these men 14% reported frequent urinary leakage or no urinary control 60 months after diagnosis, which was slightly higher than the 10% reporting incontinence at 24 months (p = 0.007). At 60 months 28% of the men had erections firm enough for intercourse compared with 22% at 24 months (p = 0.003). Sildenafil was the most commonly used erectile aid (43% ever used) and 45% of users reported that it helped "somewhat" or "a lot." Conclusions: Urinary and sexual dysfunction were common 5 years following radical prostatectomy in this large, community based cohort of prostate cancer survivors. While a small minority of subjects experienced changes in urinary or sexual function between years 2 and 5 after prostatectomy, functional outcomes remained relatively stable in the majority of participants. C1 Univ So Calif, Keck Sch Med, Dept Urol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Univ Connecticut, Dept Urol, Farmington, CT USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. New Mexico Vet Affairs Hlth Care Syst, Dept Med, Albuquerque, NM USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Utah, Sch Med, Div Urol, Salt Lake City, UT USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Penson, DF (reprint author), Univ So Calif, Keck Sch Med, Dept Urol, 1441 Eastlake Ave,Suite 7416, Los Angeles, CA 90089 USA. EM penson@usc.edu FU NCI NIH HHS [N01-PC-67007, N01-PC-67000, N01-PC-67005, N01-PC-67006, N01-PC-67009, N01-PC-67010] NR 24 TC 226 Z9 236 U1 0 U2 7 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 MAY PY 2005 VL 173 IS 5 BP 1701 EP 1705 DI 10.1097/01.ju.0000154637.38262.3a PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 918RC UT WOS:000228564300050 PM 15821561 ER PT J AU Gower, TL Pastey, MK Peeples, ME Collins, PL McCurdy, LH Hart, TK Guth, A Johnson, TR Graham, BS AF Gower, TL Pastey, MK Peeples, ME Collins, PL McCurdy, LH Hart, TK Guth, A Johnson, TR Graham, BS TI RhoA signaling is required for respiratory syncytial virus-induced syncytium formation and filamentous virion morphology SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; ACTIN CYTOSKELETON; PARTICLE FORMATION; MEMBRANE DOMAINS; FUSION PROTEIN; CELL-SURFACE; F-PROTEIN; IN-VITRO; ENTRY; GLYCOPROTEINS AB Respiratory syncytial virus (RSV) is an important human pathogen that can cause severe and life-threatening respiratory infections in infants, the elderly, and immunocompromised adults. RSV infection of HEp-2 cells induces the activation of RhoA, a small GTPase. We therefore asked whether RhoA signaling is important for RSV replication or syncytium formation. The treatment of HEp-2 cells with Clostridium botulinum C3, an enzyme that ADP-ribosylates and specifically inactivates RhoA, inhibited RSV-induced syncytium formation and cell-to-cell fusion, although similar levels of PFU were released into the medium and viral protein expression levels were equivalent. Treatment with another inhibitor of RhoA signaling, the Rho kinase inhibitor Y-27632, yielded similar results. Scanning electron microscopy of C3-treated infected cells showed reduced numbers of single blunted filaments, in contrast to the large clumps of long filaments in untreated infected cells. These data suggest that RhoA signaling is associated with filamentous virus morphology, cell-to-cell fusion, and syncytium formation but is dispensable for the efficient infection and production of infectious virus in vitro. Next, we developed a semiquantitative method to measure spherical and filamentous virus particles by using sucrose gradient velocity sedimentation. Fluorescence and transmission electron microscopy confirmed the separation of spherical and filamentous forms of infectious virus into two identifiable peaks. The C3 treatment of RSV-infected cells resulted in a shift to relatively more spherical virions than those from untreated cells. These data suggest that viral filamentous protuberances characteristic of RSV infection are associated with RhoA signaling, are important for filamentous virion morphology, and may play a role in initiating cell-to-cell fusion. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Microbiol, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Immunol, Nashville, TN 37212 USA. Ohio State Univ, Coll Med & Publ Hlth, Dept Pediat, Columbus, OH 43210 USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 2502,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. EM bgraham@nih.gov FU NIAID NIH HHS [R01-AI-33933, R01 AI033933] NR 53 TC 55 Z9 57 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 9 BP 5326 EP 5336 DI 10.1128/JVI.79.9.5326-5336.2005 PG 11 WC Virology SC Virology GA 917CH UT WOS:000228433100010 PM 15827147 ER PT J AU Spann, KM Tran, KC Collins, PL AF Spann, KM Tran, KC Collins, PL TI Effects of nonstructural proteins NS1 and NS2 of human respiratory syncytial virus on interferon regulatory factor 3, NF-kappa B, and proinflammatory cytokines SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSCRIPTION FACTOR; ANTIVIRAL RESPONSE; EPITHELIAL-CELLS; NUCLEAR TRANSLOCATION; INTERLEUKIN-8 GENE; IN-VITRO; ACTIVATION; NS1; INDUCTION; BETA AB Human respiratory syncytial virus (HRSV) is the leading cause of serious pediatric acute respiratory tract infections, and a better understanding is needed of the host response to HRSV and its attenuated vaccine derivatives. It has been shown previously that HRSV nonstructural proteins 1 and 2 (NS1 and NS2) inhibit the induction of alpha/beta interferon (IFN-alpha/beta) in A549 cells and human macrophages. Two principal transcription factors for the early IFN-beta and -alpha 1 response are interferon regulatory factor 3 (IRF-3) and nuclear factor kappa B (NF-kappa B). At early times postinfection, wild-type HRSV and the NS1/NS2 deletion mutants were very similar in the ability to activate IRF-3. However, once NS1 and NS2 were expressed significantly, they acted cooperatively to suppress activation and nuclear translocation of IRF-3. Since these viruses differed greatly in the induction of IFN-alpha/beta, NF-kappa B activation was evaluated in Vero cells, which lack the structural genes for IFN-alpha/beta and would preclude confounding effects of IFN-alpha/beta. This showed that deletion of the NS2 gene sharply reduced the ability of HRSV to induce activation of NF-kappa B. Since recombinant HRSVs from which the NS1 or NS2 genes have been deleted are being developed as vaccine candidates, we investigated whether the changes in activation of host transcription factors and increased IFN-alpha/beta production had an effect on the epithelial production of proinflammatory factors. Viruses lacking NS1 and/or NS2 stimulated modestly lower production of RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), interleukin 8, and tumor necrosis factor alpha compared to wild-type recombinant RSV, supporting their use as attenuated vaccine candidates. C1 NIAID, Infect Dis Lab, Bethesda, MD 20892 USA. RP Collins, PL (reprint author), NIAID, Infect Dis Lab, Bldg 50,Room 6503,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM pcollins@niaid.nih.gov RI Spann, Kirsten/B-4524-2013 OI Spann, Kirsten/0000-0003-0567-8382 NR 42 TC 148 Z9 162 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 9 BP 5353 EP 5362 DI 10.1128/JVI.79.9.5353-5362.2005 PG 10 WC Virology SC Virology GA 917CH UT WOS:000228433100013 PM 15827150 ER PT J AU Blaney, JE Matro, JM Murphy, BR Whitehead, SS AF Blaney, JE Matro, JM Murphy, BR Whitehead, SS TI Recombinant, live-attenuated tetravalent dengue virus vaccine formulations induce a balanced, broad, and protective neutralizing antibody response against each of the four serotypes in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID HEMORRHAGIC-FEVER; 3'-UNTRANSLATED REGION; MOLECULAR EVOLUTION; NONHUMAN-PRIMATES; ADULT VOLUNTEERS; DISEASE SEVERITY; VERO CELLS; TYPE-4; CANDIDATE; IMMUNOGENICITY AB Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant DENI, -2, -3, and -4, each with a 30-nucleotide deletion in the 3 ' untranslated region (Delta 30). TV-2 consists of rDEN1 Delta 30, rDEN4 Delta 30, and two antigenic chimeric viruses, rDEN2/4 Delta 30 and rDEN3/4 Delta 30, both also bearing the Delta 30 mutation. TV-3 consists of rDEN1 Delta 30, rDEN2 Delta 30, rDEN4 Delta 30, and a 10-fold higher dose of rDEN3/4 Delta 30. TV-1 and TV-2 were attenuated in SCID-HuH-7 mice with minimal interference in replication among the virus components. TV-1, -2, and -3 were attenuated in rhesus monkeys as measured by duration and peak of viremia. Each monkey immunized with TV-1 and TV-3 seroconverted to the four DEN components by day 28 with neutralization titers ranging from 1:52 to 1:273 and 1:59 to 1:144 for TV-1 and TV-3, respectively. TV-2 induced low antibody titers to DEN2 and DEN3, but a booster immunization after 4 months increased the neutralizing antibody titers to greater than 1:100 against each serotype and elicited broad neutralizing activity against 19 of 20 DEN subtypes. A single dose of TV-2 induced protection against wild-type DEN1, DEN3, and DEN4 challenge, but not DEN2. However, two doses of TV-2 or TV-3 induced protection against DEN2 challenge. Two tetravalent formulations, TV-2 and TV-3, possess properties of a successful DEN vaccine and can be considered for evaluation in clinical trials. C1 NIAID, NIH, LID, Bethesda, MD 20892 USA. RP Blaney, JE (reprint author), NIAID, NIH, LID, Twinbrook 3,Room 3W-13,12735 Twinbrook Pkwy,MSC 8, Bethesda, MD 20892 USA. EM jblaney@niaid.nih.gov NR 46 TC 110 Z9 114 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 9 BP 5516 EP 5528 DI 10.1128/JVI.79.9.5516-5528.2005 PG 13 WC Virology SC Virology GA 917CH UT WOS:000228433100029 PM 15827166 ER PT J AU Roberts, A Paddock, C Vogel, L Butter, E Zaki, S Subbarao, K AF Roberts, A Paddock, C Vogel, L Butter, E Zaki, S Subbarao, K TI Aged BALB/c mice as a model for increased severity of severe acute respiratory syndrome in elderly humans SO JOURNAL OF VIROLOGY LA English DT Article ID CORONAVIRUS SPIKE PROTEIN; SARS CORONAVIRUS; HONG-KONG; PROTECTIVE IMMUNITY; LUNG PATHOLOGY; AFRICAN-GREEN; INFECTION; IMMUNOSENESCENCE; NEUTRALIZATION; REPLICATION AB Advanced age has repeatedly been identified as an independent correlate of adverse outcome and a predictor of mortality in cases of severe acute respiratory syndrome (SARS). SARS-associated mortality may exceed 50% for persons aged 60 years or older. Heightened susceptibility of the elderly to severe SARS and the ability of SARS coronavirus to replicate in mice led us to examine whether aged mice might be susceptible to disease. We report here that viral replication in aged mice was associated with clinical illness and pneumonia, demonstrating an age-related susceptibility to SARS disease in animals that parallels the human experience. C1 NIAID, LID, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Infect Dis Pathol Act, Atlanta, GA USA. RP Roberts, A (reprint author), NIAID, LID, NIH, 50 South Dr,Room 6351,MSC 8007, Bethesda, MD 20892 USA. EM ajroberts@niaid.nih.gov NR 36 TC 99 Z9 105 U1 0 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 MAY PY 2005 VL 79 IS 9 BP 5833 EP 5838 DI 10.1128/JVI.79.9.5833-5838.2005 PG 6 WC Virology SC Virology GA 917CH UT WOS:000228433100060 PM 15827197 ER PT J AU Disbrow, GL Hanover, JA Schlegel, R AF Disbrow, GL Hanover, JA Schlegel, R TI Endoplasmic reticulum-localized human papillomavirus type 16 E5 protein alters endosomal pH but not trans-golgi pH SO JOURNAL OF VIROLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; VACUOLAR H+-ATPASE; HUMAN FORESKIN KERATINOCYTES; MAP KINASE ACTIVATION; CANINE KIDNEY-CELLS; INFLUENZA M2; CELLULAR-TRANSFORMATION; SELECTIVE PERTURBATION; ENDOCYTIC TRAFFICKING; APICAL MEMBRANE AB The human papillomavirus type 16 (HPV-16) E5 protein is a small, hydrophobic polypeptide that is expressed in virus-infected keratinocytes and alters receptor signaling pathways, apoptotic responses, and endosomal pH. Despite its ability to inhibit endosomal acidification, the HPV-16 E5 protein is found predominantly in the endoplasmic reticulum (ER), suggesting that its effect may be indirect and perhaps global. To determine whether E5 alters the pHs of additional intracellular compartments, we transduced human keratinocytes with a codon-optimized E5 vector and then quantified endosomal and trans-Golgi pHs using sensitive, compartment-specific, ratiometric pHluorin constructs. E5 protein increased endosomal pH from 5.9 to 6.9 but did not affect the normal trans-Golgi pH of 6.3. Confirming the lack of alteration in trans-Golgi pH, we observed no alterations in the acidification-dependent processing of the proH3 protein. C-terminal deletions of E5, which retained normal expression and localization in the ER, were defective for endosomal alkalization. Thus, E5 does not uniformly alkalinize intracellular compartments, and its C-terminal 10 amino acids appear to mediate interactions with critical ER targets that modulate proton pump function and/or localization. C1 Georgetown Univ, Sch Med, Dept Pathol, Washington, DC 20057 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD USA. RP Schlegel, R (reprint author), Georgetown Univ, Sch Med, Dept Pathol, Room 113,3900 Reservoir Rd NW, Washington, DC 20057 USA. EM schleger@georgetown.edu FU NCI NIH HHS [R01 CA53371, R01 CA053371] NR 65 TC 42 Z9 48 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 MAY PY 2005 VL 79 IS 9 BP 5839 EP 5846 DI 10.1128/JVI.79.9.5839-5846.2005 PG 8 WC Virology SC Virology GA 917CH UT WOS:000228433100061 PM 15827198 ER PT J AU Khan, MA Kao, S Miyagi, E Takeuchi, H Goila-Gaur, R Opi, S Gipson, CL Parslow, TG Ly, H Strebel, K AF Khan, MA Kao, S Miyagi, E Takeuchi, H Goila-Gaur, R Opi, S Gipson, CL Parslow, TG Ly, H Strebel, K TI Viral RNA is required for the association of APOBEC3G with human immunodeficiency virus type 1 nucleoprotein complexes SO JOURNAL OF VIROLOGY LA English DT Article ID VIF PROTEIN; HIV-1 VIRIONS; ENZYME APOBEC3G; GAG; DNA; CELLS; HYPERMUTATION; DIMERIZATION; DEGRADATION; PROTEASOME AB APOBEC3G (APO3G) is a host cytidine deaminase that is incorporated into human immunodeficiency virus type 1 (HIV-1) particles. We report here that viral RNA promotes stable association of APO3G with HIV-1 nucleoprotein complexes (NPC). A target sequence located within the 5'-untranslated region of the HIV-1 RNA was identified to be necessary and sufficient for efficient APO3G packaging. Fine mapping revealed a sequence normally involved in viral genomic RNA dimerization and Gag binding to be important for APO3G packaging and association with viral NPC. Our data suggest that packaging of APO3G into HIV-1 NPC is enhanced by viral RNA. C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. Emory Univ, Dept Pathol & Lab Med, Div Expt Pathol, Atlanta, GA 30322 USA. RP Strebel, K (reprint author), NIAID, NIH, Mol Microbiol Lab, 4-312,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov RI Takeuchi, Hiroaki/F-9728-2012 NR 32 TC 131 Z9 132 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 MAY PY 2005 VL 79 IS 9 BP 5870 EP 5874 DI 10.1128/JVI.79.9.5870-5874.2005 PG 5 WC Virology SC Virology GA 917CH UT WOS:000228433100066 PM 15827203 ER PT J AU Sui, JH Li, WH Roberts, A Matthews, LJ Murakami, A Vogel, L Wong, SK Subbarao, K Farzan, M Marasco, WA AF Sui, JH Li, WH Roberts, A Matthews, LJ Murakami, A Vogel, L Wong, SK Subbarao, K Farzan, M Marasco, WA TI Evaluation of human monoclonal antibody 80R for immunoprophylaxis of severe acute respiratory syndrome by an animal study, epitope mapping, and analysis of spike variants SO JOURNAL OF VIROLOGY LA English DT Article ID ANGIOTENSIN-CONVERTING ENZYME-2; SARS-ASSOCIATED CORONAVIRUS; PROTEIN; MICE; INFECTION; VIRUS; CHINA; NEUTRALIZATION; TRANSMISSION; REPLICATION AB In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Microbiol & Mol Genet, Brigham & Womens Hosp,Partners AIDS Res Ctr, Boston, MA 02115 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Marasco, WA (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Dept Med, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM wayne_marasco@dfci.harvard.edu OI Li, Wenhui/0000-0003-1305-7404; SUI, JIANHUA/0000-0002-1272-9662 FU NIAID NIH HHS [AI061318, AI053822, AI28691, AI28785, AI48436, P30 AI028691, R01 AI048436, R21 AI053822, U01 AI061318] NR 35 TC 78 Z9 87 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 5900 EP 5906 DI 10.1128/JVI.79.10.5900-5906.2005 PG 7 WC Virology SC Virology GA 922CV UT WOS:000228814400002 PM 15857975 ER PT J AU Brown, BK Darden, JM Tovanabutra, S Oblander, T Frost, J Sanders-Buell, E de Souza, MS Birx, DL McCutchan, FE Polonis, VR AF Brown, BK Darden, JM Tovanabutra, S Oblander, T Frost, J Sanders-Buell, E de Souza, MS Birx, DL McCutchan, FE Polonis, VR TI Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01 _ AE, and CRF02 _ AG, for the development and assessment of candidate vaccines SO JOURNAL OF VIROLOGY LA English DT Article ID GP120 ENVELOPE GLYCOPROTEIN; ANTIBODY-MEDIATED NEUTRALIZATION; POLYMERASE-CHAIN-REACTION; HIV-1/SIV CHIMERIC VIRUS; 2ND HYPERVARIABLE REGION; HIV TYPE-1; SUBTYPE-C; CORECEPTOR USAGE; MONOCLONAL-ANTIBODIES; SERUM NEUTRALIZATION AB A critical priority for human immunodeficiency virus type 1 (HIV-1) vaccine development is standardization of reagents and assays for evaluation of immune responses elicited by candidate vaccines. To provide a panel of viral reagents from multiple vaccine trial sites, 60 international HIV-1 isolates were expanded in peripheral blood mononuclear cells and characterized both genetically and biologically. Ten isolates each from clades A, B, C, and D and 10 isolates each from CRF01 (-) AE and CRF02 (-) AG were prepared from individuals whose HIV-1 infection was evaluated by complete genome sequencing. The main criterion for selection was that the candidate isolate was pure clade or pure circulating recombinant. After expansion in culture, the complete envelope (gp160) of each isolate was verified by sequencing. The 50% tissue culture infectious dose and p24 antigen concentration for each viral stock were determined; no correlation between these two biologic parameters was found. Syncytium formation in MT-2 cells and CCR5 or CXCR4 coreceptor usage were determined for all isolates. Isolates were also screened for neutralization by soluble CD4, a cocktail of monoclonal antibodies, and a pool of HIV-1-positive patient sera. The panel consists of 49 nonsyncytium-inducing isolates that use CCR5 as a major coreceptor and 11 syncytium-inducing isolates that use only CXCR4 or both coreceptors. Neutralization profiles suggest that the panel contains both neutralization-sensitive and -resistant isolates. This collection of HIV-1 isolates represents the six major globally prevalent strains, is exceptionally large and well characterized, and provides an important resource for standardization of immunogenicity assessment in HIV-1 vaccine trials. C1 Henry M Jackson Fdn, Rockville, MD 20850 USA. Natl Inst Hlth, Div AIDS, Bethesda, MD USA. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. Walter Reed Army Inst Res, Rockville, MD USA. RP Polonis, VR (reprint author), Henry M Jackson Fdn, 13 Taft Court,Suite 200, Rockville, MD 20850 USA. EM vpolonis@hivresearch.org NR 72 TC 100 Z9 103 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 6089 EP 6101 DI 10.1128/JVI.79.10.6089-6101.2005 PG 13 WC Virology SC Virology GA 922CV UT WOS:000228814400021 PM 15857994 ER PT J AU Song, BW Gold, B O'hUigin, C Javanbakht, H Li, X Stremlau, M Winkler, C Dean, M Sodroski, J AF Song, BW Gold, B O'hUigin, C Javanbakht, H Li, X Stremlau, M Winkler, C Dean, M Sodroski, J TI The B30.2(SPRY) domain of the retroviral restriction factor TRIM5 alpha exhibits line age-specific length and sequence variation in primates SO JOURNAL OF VIROLOGY LA English DT Article ID PROMYELOCYTIC LEUKEMIA PROTEIN; IMMUNODEFICIENCY-VIRUS TYPE-1; BABOON ENDOGENOUS VIRUS; OLD-WORLD MONKEYS; CYCLOPHILIN-A; SIMIAN CELLS; POSTENTRY RESTRICTION; REVERSE TRANSCRIPTION; B30.2-LIKE DOMAIN; MOTIF PROTEIN AB Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5 alpha, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5a has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5 alpha was analyzed by amplifying, cloning, and sequencing nonhuman primate TRIM5 orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5 alpha B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5a B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5 alpha in innate immunity against retroviruses. C1 Harvard Univ, Sch Med, Div AIDS,Dept Canc Immunol & AIDS, Dept Pathol,Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Div AIDS,Dept Canc Immunol & AIDS, Dept Pathol,Dana Farber Canc Inst, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01CO12400, N01-CO-12400]; NHLBI NIH HHS [HL54785, P50 HL054785]; NIAID NIH HHS [P30 AI028691, P30 AI28691] NR 65 TC 154 Z9 172 U1 0 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 MAY PY 2005 VL 79 IS 10 BP 6111 EP 6121 DI 10.1128/JVI.79.10.6111-6121.2005 PG 11 WC Virology SC Virology GA 922CV UT WOS:000228814400023 PM 15857996 ER PT J AU Yang, QE Stephen, AG Adelsberger, JW Roberts, PE Zhu, WM Currens, MJ Feng, YX Crise, BJ Gorelick, RJ Rein, AR Fisher, RJ Shoemaker, RH Sei, S AF Yang, QE Stephen, AG Adelsberger, JW Roberts, PE Zhu, WM Currens, MJ Feng, YX Crise, BJ Gorelick, RJ Rein, AR Fisher, RJ Shoemaker, RH Sei, S TI Discovery of small-molecule human immunodeficiency virus type 1 entry inhibitors that target the gp120-binding domain of CD4 SO JOURNAL OF VIROLOGY LA English DT Article ID RECOMBINANT SOLUBLE CD4; HIV-1 NUCLEOCAPSID PROTEIN; INFECTION IN-VITRO; ENVELOPE GLYCOPROTEIN; CHEMOKINE RECEPTOR; NEUTRALIZATION SENSITIVITY; MONOCLONAL-ANTIBODIES; ANTIVIRAL ACTIVITY; POTENT INHIBITOR; HIGHLY POTENT AB The interaction between human immunodeficiency virus type 1 (HIV-1) gp120 and the CD4 receptor is highly specific and involves relatively small contact surfaces on both proteins according to crystal structure analysis. This molecularly conserved interaction presents an excellent opportunity for antiviral targeting. Here we report a group of pentavalent antimony-containing small molecule compounds, NSC 13778 (molecular weight, 319) and its analogs, which exert a potent anti-HIV activity. These compounds block the entry of X4-, R5-, and X4/R5-tropic HIV-1 strains into CD4(+) cells but show little or no activity in CD4-negative cells or against vesicular stomatitis virus-G pseudotyped virions. The compounds compete with gp120 for binding to CD4: either immobilized on a solid phase (soluble CD4) or on the T-cell surface (native CD4 receptor) as determined by a competitive gp120 capture enzyme-linked immunosorbent assay or flow cytometry. NSC 13778 binds to an N-terminal two-domain CD4 protein, D1/D2 CD4, immobilized on a surface plasmon resonance sensor chip, and dose dependently reduces the emission intensity of intrinsic tryptophan fluorescence of D1/D2 CD4, which contains two of the three tryptophan residues in the gp120-binding domain. Furthermore, T cells incubated with the compounds alone show decreased reactivity to anti-CD4 monoclonal antibodies known to recognize the gp120-binding site. In contrast to gp120-binders that inhibit gp120-CD4 interaction by binding to gp120, these compounds appear to disrupt gp120-CD4 contact by targeting the specific gp120-binding domain of CD4. NSC 13778 may represent a prototype of a new class of HIV-1 entry inhibitors that can break into the gp120-CD4 interface and mask the gp120-binding site on the CD4 molecules, effectively repelling incoming virions. C1 NCI, SAIC Frederick, Dev Therapeut Program, Screening Technol Branch,Lab Antiviral Drug Mech, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Clin Serv Program, Frederick, MD USA. NCI, Screening Technol Branch, Frederick, MD 21702 USA. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC Frederick, AIDS Vaccine Program, Frederick, MD USA. RP Sei, S (reprint author), NCI, SAIC Frederick, Dev Therapeut Program, Screening Technol Branch,Lab Antiviral Drug Mech, Bldg 439,POB B, Frederick, MD 21702 USA. EM sei@dtpax2.ncifcrf.gov RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 76 TC 28 Z9 29 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 6122 EP 6133 DI 10.1128/JVI.79.10.6122-6133.2005 PG 12 WC Virology SC Virology GA 922CV UT WOS:000228814400024 PM 15857997 ER PT J AU Aldaz-Carroll, L Whitbeck, JC de Leon, MP Lou, H Hirao, L Isaacs, SN Moss, B Eisenberg, RJ Cohen, GH AF Aldaz-Carroll, L Whitbeck, JC de Leon, MP Lou, H Hirao, L Isaacs, SN Moss, B Eisenberg, RJ Cohen, GH TI Epitope-mapping studies define two major neutralization sites on the vaccinia virus extracellular enveloped virus glycoprotein B5R SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIN TAIL FORMATION; HERPESVIRUS ENTRY MEDIATOR; CRYSTAL-STRUCTURE; ANALYTICAL ULTRACENTRIFUGATION; NEUTRON-SCATTERING; PROTEIN B5R; X-RAY; BINDING; COMPLEMENT; ANTIBODIES AB Vaccinia extracellular enveloped virus (EEV) is critical for cell-to-cell and long-range virus spread both in vitro and in vivo. The B5R gene encodes an EEV-specific type I membrane protein that is essential for efficient EEV formation. The majority of the B5R ectodomain consists of four domains with homology to short consensus repeat domains followed by a stalk. Previous studies have shown that polyclonal antibodies raised against the B5R ectodomain inhibit EEV infection. In this study, our goal was to elucidate the antigenic structure of B5R and relate this to its function. To do this, we produced multimilligram quantities of vaccinia virus B5R as a soluble protein [B5R(275t)] using a baculovirus expression system. We then selected and characterized a panel of 26 monoclonal antibodies (MAbs) that recognize B5R(275t). Five of these MAbs neutralized EEV and inhibited comet formation. Two other MAbs were able only to neutralize EEV, while five others were able only to inhibit comet formation. This suggests that the EEV neutralization and comet inhibition assays measure different viral functions and that at least two different antigenic sites on B5R are important for these activities. We further characterized the MAbs and the antigenic structure of B5R(275t) by peptide mapping and by reciprocal MAb blocking studies using biosensor analysis. The epitopes recognized by neutralizing MAbs were localized to SCR1-SCR2 and/or the stalk of B5R(275t). Furthermore, the peptide and blocking data support the concept that SCR1 and the stalk may be in juxtaposition and may be part of the same functional domain. C1 Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Aldaz-Carroll, L (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, 240 S 40th St, Philadelphia, PA 19104 USA. EM aldaz@biochem.dental.upenn.edu RI Aldaz-Carroll, Lydia/A-6180-2008 FU CCR NIH HHS [RCE-U54-AI57168]; NIAID NIH HHS [U01 AI048487, AI48487, R21-AI-53404, U54 AI057168] NR 40 TC 58 Z9 61 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 MAY PY 2005 VL 79 IS 10 BP 6260 EP 6271 DI 10.1128/JVI.79.10.6260-6271.2005 PG 12 WC Virology SC Virology GA 922CV UT WOS:000228814400037 PM 15858010 ER PT J AU Santra, S Seaman, MS Xu, L Barouch, DH Lord, CI Lifton, MA Gorgone, DA Beaudry, KR Svehla, K Welcher, B Chakrabarti, BK Huang, Y Yang, ZY Mascola, JR Nabel, GJ Letvin, NL AF Santra, S Seaman, MS Xu, L Barouch, DH Lord, CI Lifton, MA Gorgone, DA Beaudry, KR Svehla, K Welcher, B Chakrabarti, BK Huang, Y Yang, ZY Mascola, JR Nabel, GJ Letvin, NL TI Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates SO JOURNAL OF VIROLOGY LA English DT Article ID T-LYMPHOCYTE RESPONSES; RHESUS-MONKEYS; GENETIC IMMUNIZATION; VACCINE PROTECTION; VIRAL REPLICATION; VIRUS; IMMUNOGENICITY; AIDS; INFECTION; ENVELOPE AB The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection. C1 Harvard Univ, Sch Med, Dept Med,Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Letvin, NL (reprint author), Harvard Univ, Sch Med, Dept Med,Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, RE113,POB 15732, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu NR 18 TC 108 Z9 114 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 MAY PY 2005 VL 79 IS 10 BP 6516 EP 6522 DI 10.1128/JVI.79.10.6516-6522.2005 PG 7 WC Virology SC Virology GA 922CV UT WOS:000228814400062 PM 15858035 ER PT J AU Periyasamy, SM Liu, J Tanta, F Kabak, B Wakefield, B Malhotra, D Kennedy, DJ Nadoor, A Fedorova, OV Gunning, W Xie, ZJ Bagrov, AY Shapiro, JI AF Periyasamy, SM Liu, J Tanta, F Kabak, B Wakefield, B Malhotra, D Kennedy, DJ Nadoor, A Fedorova, OV Gunning, W Xie, ZJ Bagrov, AY Shapiro, JI TI Salt loading induces redistribution of the plasmalemmal Na/K-ATPase in proximal tubule cells SO KIDNEY INTERNATIONAL LA English DT Article DE sodium; potassium; Na plus /K plus -ATPase; endocytosis; hypertension ID NA+,K+-ATPASE ALPHA-SUBUNIT; SIGNAL-TRANSDUCING FUNCTION; DIGITALIS-LIKE FACTORS; NA+-K+-ATPASE; SODIUM-PUMP; ENDOGENOUS OUABAIN; CARDIAC MYOCYTES; EPITHELIAL-CELLS; ENDOCYTOSIS; MARINOBUFAGENIN AB Background. We have reported that digitalis-like substances (cardiotonic steroids), including marinobufagenin (MBG), induce endocytosis of the plasmalemmal Na/K-ATPase in LLC-PK1 cells. "The current report addresses the potential relevance of plasmalemmal Na/K-ATPase redistribution to in vivo salt handling. Methods. Male Sprague-Dawley rats were given 1 week of a high salt (4..0% NaCl) or normal salt (0.4% NaCl) diet. Urinary sodium excretion, as well as MBG excretion, was monitored, and proximal tubules were isolated using a Percoll gradient method. Tubular Rb-86 uptake, Na/K-ATPase enzymatic activity, and Na/K-ATPase alpha 1 subunit density were determined. Results. The high salt diet increased urinary sodium (17.8 +/- 1.8 vs. 2.5 +/- 0.3 mEq/day, P < 0.01) and MBG excretion (104 +/- 12 vs. 26 +/- 4 pmol/day), and decreased proximal tubular Rb-86 uptake (0.44 +/- 0.07 vs. 1.00 +/- 0.10, P < 0.01) and Na/K-ATPase enzymatic activity (5.1 +/- 1.1 vs. 9.9 +/- 1.6 mu mol/mg pr/hr, P < 0.01) relative to the normal diet. Proximal tubular Na/K-ATPase alpha 1 protein density was decreased in the plasmalemma fraction but increased in both early and late endosomes following the high salt diet. In rats fed a high salt diet, anti-MBG antibody caused a 60% reduction in urinary sodium excretion, substantial increases in proximal tubule Rb-86 uptake, and Na/K-ATPase enzymatic activity, as well as significant decreases in the early and late endosomal Na/K-ATPase alpha 1 protein content. Conclusion. These data suggest that redistribution of tire proximal tubule Na/K-ATPase in response to endogenous cardiotonic steroids plays an important role in renal adaptation to salt loading. C1 Med Coll Ohio, Dept Med, Toledo, OH 43614 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Med Coll Ohio, Dept Pharmacol, Toledo, OH 43614 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Shapiro, JI (reprint author), Med Coll Ohio, Dept Med, 3120 Glendale Ave, Toledo, OH 43614 USA. EM jshapiro@mco.edu RI Gunning, William/E-4681-2010 FU NHLBI NIH HHS [HL57144, HL67963, HL63238] NR 44 TC 43 Z9 43 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2005 VL 67 IS 5 BP 1868 EP 1877 DI 10.1111/j.1523-1755.2005.00285.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 918XM UT WOS:000228582900031 PM 15840034 ER PT J AU Vezzoli, G Soldati, L Arcidiacono, T Terranegra, A Biasion, R Russo, CR Lauretani, F Bandinelli, S Bartali, B Cherubini, A Cusi, D Ferrucci, L AF Vezzoli, G Soldati, L Arcidiacono, T Terranegra, A Biasion, R Russo, CR Lauretani, F Bandinelli, S Bartali, B Cherubini, A Cusi, D Ferrucci, L TI Urinary calcium is a determinant of bone mineral density in elderly men participating in the InCHIANTI study SO KIDNEY INTERNATIONAL LA English DT Article DE bone mineral density; urinary calcium excretion; cytokines; hypercalciuria; calcium intake ID RENAL STONE FORMERS; IDIOPATHIC HYPERCALCIURIA; WOMEN; OSTEOPOROSIS; NEPHROLITHIASIS; METABOLISM; EXCRETION; MASS; EPIDEMIOLOGY; ABSORPTION AB Background. It is generally acknowledged that calcium excretion is a determinant of bone mineral density. Since data confirming this hypothesis are not conclusive, the present study evaluates the relationship between calcium excretion and volumetric bone mineral density (vBMD) in a sample of general population mostly composed of elderly subjects. Methods. This relationship was studied in 595 subjects in good health (M/F 302/293), selected from the InCHIANTI population, an epidemiologic survey on aging in Tuscany (Italy). Of these subjects, 432 (72.6%) were 65 years old or older. Trabecular and cortical apparent vBMDs were measured by peripheral quantitative computed tomography at right tibia and standardized to age and body mass index (BMI) in each gender (z-score). Results. Men in the highest fertile of calcium excretion had significantly lower trabecular vBMD, and were more likely to have a trabecular z-score of -1 or less. These results were confirmed in men older than 64 years, but not in women and younger men. Sodium excretion and 25-hydroxycolecalciferol (25(OH)D) were greater in men and women in the highest fertile. No differences among tertiles were observed for cortical vBMD, circulating levels of interleukin-1 beta and interleukin-6, and intake of principal nutrients and calcium. The lower levels of vBMD z-score were confirmed in men in the highest fertile of calcium excretion, standardized to creatinine clearance, sodium excretion, plasma calcium, and logarithm of circulating 25(OH)D, and resulted to be associated with calcium excretion at multiple regression analysis in men. Conclusion. High calcium excretion is associated with a decreased trabecular BMD in elderly men and may predispose men to trabecular bone loss. C1 Vita Salute Univ, Postfrad Sch Nephrol, IRCCS San Raffaele Hosp, Div Nephrol Dialysis & Hypertens, I-20132 Milan, Italy. Univ Milan, Dept Biomed Sci & Technol, I-20133 Milan, Italy. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Univ Perugia, I-06100 Perugia, Italy. NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Vezzoli, G (reprint author), Vita Salute Univ, Postfrad Sch Nephrol, IRCCS San Raffaele Hosp, Div Nephrol Dialysis & Hypertens, Via Olgettina 60, I-20132 Milan, Italy. EM vezzoli.giuseppe@hsr.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897; Vezzoli, Giuseppe/0000-0003-4481-5693; Terranegra, Annalisa/0000-0001-9274-5373 NR 39 TC 23 Z9 25 U1 0 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD MAY PY 2005 VL 67 IS 5 BP 2006 EP 2014 DI 10.1111/j.1523-1755.2005.00302.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 918XM UT WOS:000228582900048 PM 15840051 ER PT J AU Schoeffner, DJ Matheny, SL Akahane, T Factor, V Berry, A Merlino, G Thorgeirsson, UP AF Schoeffner, DJ Matheny, SL Akahane, T Factor, V Berry, A Merlino, G Thorgeirsson, UP TI VEGF contributes to mammary tumor growth in transgenic mice through paracrine and autocrine mechanisms SO LABORATORY INVESTIGATION LA English DT Article DE VEGF; mammary; transgenic; middle T; growth; Flk-1 ID VASCULAR-PERMEABILITY FACTOR; RECEPTOR TYROSINE KINASE; BREAST-CARCINOMA CELLS; NITRIC-OXIDE SYNTHASE; MIDDLE T-ONCOGENE; ENDOTHELIAL-CELLS; IN-VIVO; INDUCED ANGIOGENESIS; FACTOR EXPRESSION; SURVIVAL FACTOR AB Vascular endothelial growth factor ( VEGF) has been identified as a vascular permeability factor, angiogenic cytokine, and a survival factor. To address its role in mammary carcinogenesis, we used transgenic mice with human VEGF(165) targeted to mammary epithelial cells under the control of the mouse mammary tumor virus ( MMTV) promoter. Metastatic mammary carcinomas were induced by mating the MMTV-VEGF mice with MMTV-polyoma virus middle T-antigen (MT) mice to generate VEGF/MT mice. Tumor latency was decreased in the VEGF/MT mice, which developed mammary carcinomas with increased vasodilatation at 4 weeks of age. There was increased incidence, multiplicity, and weight of the mammary tumors in 6- and 8-week-old VEGF/MT mice, compared to their MT-only littermates. Macro- and microscopic lung metastases were detected in the VEGF/MT mice but not the MT mice at 6 and 8 weeks of age. Enhanced tumor growth was attributed to increased microvascular density (MVD), as well as increased tumor cell proliferation and survival. Angiogenesis array analysis showed that 24 of 25 differentially expressed genes were upregulated in the VEGF/MT tumors. In vitro studies revealed increased proliferative activity and upregulation of Flk-1 in the VEGF/MT tumor cells, compared with the MT-only tumor cells. Moreover, there was decreased proliferative activity with down-regulation of Flk-1 in tumor cells isolated from conditional knockout (VEGF(-/-)) MT-induced mammary carcinomas. The slow growing VEGF(-/-) tumor cells were accumulated in the G(1)/G(0) phase of the cell cycle and this was associated with stimulation of p16(ink4a) and p21(WAF1). Similarly, p16(ink4a) was stimulated in VEGF(lox/lox)/MT mammary tumor cells following Adeno-cre-mediated VEGF gene inactivation. Collectively, the data from these transgenic models indicate that VEGF contributes to mammary tumor growth through increased neovascularization, as well as autocrine stimulation of growth and inhibition of apoptosis. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, UP (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bldg 37,Room 4032A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM thorgeiu@mail.nih.gov NR 72 TC 52 Z9 57 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD MAY PY 2005 VL 85 IS 5 BP 608 EP 623 DI 10.1038/labinvest.3700258 PG 16 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 919RI UT WOS:000228634900003 PM 15765121 ER PT J AU Hampton, RR Hampstead, BM Murray, EA AF Hampton, RR Hampstead, BM Murray, EA TI Rhesus monkeys (Macaca mulatta) demonstrate robust memory for what and where, but not when, in an open-field test of memory SO LEARNING AND MOTIVATION LA English DT Article DE macaque; primate; episodic memory; spatial; hippocampus; episodic-like; nonhuman; mental time travel; semantic memory ID JAYS APHELOCOMA-COERULESCENS; EPISODIC-LIKE MEMORY; MENTAL TIME-TRAVEL; SCRUB-JAYS; SPATIAL MEMORY; HIPPOCAMPUS; ANIMALS; METACOGNITION; INFORMATION; NONHUMANS AB We adapted a paradigm developed by Clayton and Dickinson (1998), who demonstrated memory for what, where, and when in scrub jays, for use with rhesus monkeys. In the study phase of each trial, monkeys found a preferred and a less-preferred food reward in a trial-unique array of three locations in a large room. After 1 h, monkeys returned to the test room, where they found foods placed as during study. Twenty-five hours after the study phase monkeys again searched the room, but now the preferred food was replaced with a distasteful food remnant, while the less-preferred food was still present. Although monkeys remembered the locations of the foods for up to 25 h, they did not learn that the preferred food was available after the short, but not after the long delay. Thus, monkeys demonstrated long-term memory for the type and location of food but failed to demonstrate sensitivity to when they acquired that knowledge. Published by Elsevier Inc. C1 Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Hampton, RR (reprint author), Emory Univ, Dept Psychol, 532 N Kilgo Circle, Atlanta, GA 30322 USA. EM hamptonr@mail.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 NR 44 TC 59 Z9 61 U1 3 U2 24 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0023-9690 J9 LEARN MOTIV JI Learn. Motiv. PD MAY PY 2005 VL 36 IS 2 BP 245 EP 259 DI 10.1016/j.lmot.2005.02.004 PG 15 WC Psychology, Biological; Psychology, Experimental SC Psychology GA 929RQ UT WOS:000229363900010 ER PT J AU Hollander, MC Patterson, AD Salvador, JM Anver, MR Hunger, SP Fornace, AJ AF Hollander, MC Patterson, AD Salvador, JM Anver, MR Hunger, SP Fornace, AJ TI Gadd45a acts as a modifier locus for lymphoblastic lymphoma SO LEUKEMIA LA English DT Article DE tumorigenesis; Gadd45a; p53; lymphoblastic lymphoma ID GENOMIC INSTABILITY; DEFICIENT MICE; P53; CANCER; TUMORS; GENE AB Gadd45a-/- and p53-/- mice and cells derived from them share similar phenotypes, most notably genomic instability. However, p53-/- mice rapidly develop a variety of neoplasms, while Gadd45a-/- mice do not. The two proteins are involved in a regulatory feedback loop, whereby each can increase the expression or activity of the other, suggesting that common phenotypes might result from similar molecular mechanisms. Mice lacking both genes were generated to address this issue. Gadd45a-/- p53-/- mice developed tumors with a latency similar to that of tumor-prone p53-/- mice. However, while p53-/- mice developed a variety of tumor types, nearly all Gadd45a-/-p53-/- mice developed lymphoblastic lymphoma (LBL), often accompanied by mediastinal masses as is common in human patients with this tumor type. Deletion of Gadd45a in leukemia/lymphoma-prone AKR mice decreased the latency for LBL. These results indicate that Gadd45a may act as modifier locus for T-cell LBL, whereby deletion of Gadd45a enhances development of this tumor type in susceptible mice. Gadd45a is localized to 1p31.1, and 1p abnormalities have been described in T-cell lymphomas. Related human tumor samples did not show Gadd45a deletion or mutation, although changes in expression could not be ruled out. C1 NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, NIH, Grad Partnerships Program Genet, Washington, DC 20052 USA. SAIC, NCI Frederick, Frederick, MD USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. RP Hollander, MC (reprint author), NCI, Gene Response Sect, NIH, Bldg 37,Room 6144, Bethesda, MD 20892 USA. EM ch96b@nih.gov RI Fornace, Albert/A-7407-2008; Patterson, Andrew/G-3852-2012 OI Fornace, Albert/0000-0001-9695-085X; Patterson, Andrew/0000-0003-2073-0070 FU NCI NIH HHS [N01-CO-12400] NR 20 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2005 VL 19 IS 5 BP 847 EP 850 DI 10.1038/sj.leu.2403711 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 920MA UT WOS:000228692500022 PM 15744335 ER PT J AU Chen, G Zeng, W Maciejewski, JP Kcyvanfar, K Billings, EM Young, NS AF Chen, G Zeng, W Maciejewski, JP Kcyvanfar, K Billings, EM Young, NS TI Differential gene expression in hematopoietic progenitors from paroxysmal nocturnal hemoglobinuria patients reveals an apoptosis/immune response in 'normal' phenotype cells SO LEUKEMIA LA English DT Article DE paroxysmal nocturnal hemoglobinuria (PNH); glycosylphosphatidylinositol-anchored protein (GPI-AP); gene expression; microarray ID MYELODYSPLASTIC SYNDROME; STEM-CELLS; GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHOR; MICROARRAY EXPERIMENTS; LINEAR AMPLIFICATION; APLASTIC-ANEMIA; MESSENGER-RNA; IN-VITRO; RECEPTOR; LIGAND AB Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired stem cell disorder characterized clinically by intravascular hemolysis, venous thrombosis, and bone marrow failure. Despite elucidation of the biochemical and molecular defects in PNH, the pathophysiology of clonal expansion of glycosyl-phosphatidylinositol-anchored protein (GPI-AP)-deficient cells remains unexplained. In pursuit of evidence of differences between GPI-AP-normal and - deficient CD34 cells, we determined gene expression profiles of isolated marrow CD34 cells of each phenotype from PNH patients and healthy donors, using DNA microarrays. Pooled and individual patient samples revealed consistent gene expression patterns relative to normal controls. GPI-AP-normal cells from PNH patients showed upregulation of genes involved in apoptosis and the immune response. Conversely, genes associated with antiapoptotic function and hematopoietic cell proliferation and differentiation were downregulated in these cells. In contrast, the PNH clone of GPI-AP-deficient cells appeared more similar to CD34 cells of healthy individuals. Gene chip data were confirmed by other methods. Similar gene expression patterns were present in PNH that was predominantly hemolytic as in PNH associated with aplastic anemia. Our results implicate an environmental influence on hematopoietic cell proliferation, in which the PNH clone evades immune attack and destruction, while normal cells suffer a stress response followed by programmed cell death. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Bioinformat Core Facil, NIH, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10,7C-103, Bethesda, MD 20892 USA. EM youngn@nhlbi.nih.gov NR 38 TC 21 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD MAY PY 2005 VL 19 IS 5 BP 862 EP 868 DI 10.1038/sj.leu.2403678 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 920MA UT WOS:000228692500025 PM 15759038 ER PT J AU Olson, DP Taylor, BJ La, M Sather, H Reaman, GH Ivy, SP AF Olson, DP Taylor, BJ La, M Sather, H Reaman, GH Ivy, SP TI The prognostic significance of P-glycoprotein, multidrug resistance-related protein 1 and lung resistance protein in pediatric acute lymphoblastic leukemia: A retrospective study of 295 newly diagnosed patients by the Children's Oncology Group SO LEUKEMIA & LYMPHOMA LA English DT Article DE flow cytometry; MDR (multidrug resistance); pediatrics; leukemia; Pgp; MRP1 ID ACUTE MYELOID-LEUKEMIA; MAJOR VAULT PROTEIN; DRUG-RESISTANCE; CONSENSUS RECOMMENDATIONS; MULTIPLE-MYELOMA; CALCEIN-AM; CELL-LINES; PHASE-I/II; MRP GENE; EXPRESSION AB Multidrug resistance (MDR) is a phenomenon by which cells become resistant to an array of structurally unrelated chemotherapeutic agents. The prognostic value that P-glycoprotein (Pgp), multidrug resistance-related protein 1 (MRP1), and lung resistance protein (LRP) have in the setting of pediatric acute lymphoblastic leukemia (ALL) is controversial. In a retrospective study, we analyzed samples obtained from 295 similarly treated pediatric ALL patients to assess whether the overexpression and/or function of these proteins at diagnosis affects outcome. Most patients (70%, 207/295) did not overexpress an MDR protein. A small number of patients expressed functional Pgp (1%, 3/295) and some overexpressed functional MRP1 (10%, 19/295), with a statistically significant number of the latter being of T-lineage as opposed to pre-B (P < 0.001). A small number of patients (2%, 6/295) also overexpressed both Pgp and MRP1. Additional patients expressed increased levels of LRP. Elevated levels of these proteins at diagnosis did not correlate with risk factors and did not predict an adverse prognosis. Life-table estimates and Kaplan-Meier plots did not show any significant differences between patients who overexpressed an MDR protein compared with those who did not, nor was any difference noted when the different MDR+ groups were compared with one another. These data strongly support the conclusion that the overexpression of these functional drug efflux pumps at diagnosis does not contribute to treatment failure in pediatric ALL. C1 George Washington Univ, Sch Med, Ctr Canc & Blood Disorders, Childrens Natl Med Ctr, Washington, DC USA. Childrens Oncol Grp, Bethesda, MD USA. RP Taylor, BJ (reprint author), NCI, NIH, Bldg 37,Room 6008,37 Convent Dr, Bethesda, MD 20892 USA. EM TaylorBa@pop.nci.nih.gov FU NCI NIH HHS [2 U10 CA 13539-31] NR 53 TC 17 Z9 22 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 MAY PY 2005 VL 46 IS 5 BP 681 EP 691 DI 10.1080/10428190500032612 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 933IE UT WOS:000229621300005 PM 16019505 ER PT J AU Zu, YL Steinberg, SM Campo, E Hans, CP Weisenburger, DD Braziel, RM Delabie, J Gascoyne, RD Muller-Hermlink, K Pittaluga, S Raffeld, M Chan, WC Jaffe, ES AF Zu, YL Steinberg, SM Campo, E Hans, CP Weisenburger, DD Braziel, RM Delabie, J Gascoyne, RD Muller-Hermlink, K Pittaluga, S Raffeld, M Chan, WC Jaffe, ES CA Pathology Panel Lymphoma Leukemia TI Validation of tissue microarray immunohistochemistry staining and interpretation in diffuse large B-cell lymphoma SO LEUKEMIA & LYMPHOMA LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 06-12, 2004 CL Vancouver, CANADA SP US & Canadian Acad Pathol DE validation; monoclonal antibodies; tissue microarray; immunohistochemistry; diffuse large B-cell lymphoma; prognostic markers ID CHRONIC LYMPHOCYTIC-LEUKEMIA; GERMINAL CENTER; ZAP-70 EXPRESSION; HODGKINS LYMPHOMA; BCL-2 EXPRESSION; P53; TECHNOLOGY; PROTEIN; AMPLIFICATION; CARCINOMA AB Tissue microarrays (TMAs) show concordance with whole tissue sections in the immunohistochemical evaluation of tumor cells. However, potential inter-institutional variability among observers and immunohistochemical staining methods has not been fully addressed. We selected 21 cases of diffuse large B-cell lymphoma (DLBCL) to process for TMAs. Immunohistochemical stains were performed in 3 laboratories, and reviewed independently by 3 hematopathologists at the 3 institutions. Stains were scored on a 4-point scale. Statistical analyses of variation in the scoring among observers and among different institutions' stains were performed. Stains for CD3, CD10, CD20, BCL-2, BCL-6, MIB-1, and FOX-P1 revealed little variation among observers, with an average 51-82% complete agreement and 82-100% agreement +/- 1 numerical score. The rate of concordance when evaluating most stains performed in different laboratories was also relatively good, with an average of 55-72% complete agreement and 70-97% agreement +/- 1 score. However, scoring of MUM-1 and p53 stains showed wider variation, with an average of only 37 and 30% complete agreement among observers, and 11 and 45% agreement when stains from different institutions were examined. Further statistical analyses were performed to compare the observers' scoring of their own institution's stains (self-review) vs. observers' scoring of other institutions' stains (non-self). The agreement rate for the p53 stain was significantly higher when based on self-review (average 58% complete agreement) compared with an agreement rate of only 10.5% when based on a review of stains performed in another laboratory, non-self review, P < 0.01. This difference in the self- vs. non-self review was not seen when data for MUM-1 were analysed. In conclusion, most phenotypic markers used in the analysis of DLBCL can be evaluated in TMAs with adequate agreement among observers and laboratories. These include CD3, CD20, CD10, BCL-2, BCL-6, MIB-1, and FOX-P1. However, some markers, such as p53 and MUM-1, are more prone to inter-institutional variation. Variations in interpretation can be partially overcome by self- adjusted/adapt tendency, as seen with p53. Especially with newly developed markers, such as MUM-1, the development of standardized techniques for staining and interpretation is critical to reduce inter-observer variability. C1 NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res, Bethesda, MD USA. Univ Barcelona, Pathol Lab, Hosp Clin, Barcelona, Spain. Univ Nebraska Med Ctr, Dept Pathol, Omaha, NE USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR USA. Norwegian Radium Hosp, Oslo, Norway. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Univ Wurzburg, Inst Pathol, D-8700 Wurzburg, Germany. RP Jaffe, ES (reprint author), NCI, Hematopathol Sect, Pathol Lab, Ctr Canc Res, Bldg 10,Room 2N202,10 Ctr Dr MSC-1500, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 NR 37 TC 43 Z9 44 U1 0 U2 1 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 MAY PY 2005 VL 46 IS 5 BP 693 EP 701 DI 10.1080/10428190500051844 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 933IE UT WOS:000229621300006 PM 16019506 ER PT J AU Chang, LC Jones, DK Pierpaoli, C AF Chang, LC Jones, DK Pierpaoli, C TI RESTORE: Robust estimation of tensors by outlier rejection SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE robust estimation; outliers; trace; anisotropy; diffusion; tensor ID DIFFUSION-TENSOR; MRI; DISTORTION; ECHO AB Signal variability in diffusion weighted imaging (DWI) is influenced by both thermal noise and spatially and temporally varying artifacts such as subject motion and cardiac pulsation. In this paper, the effects of DWI artifacts on estimated tensor values, such as trace and fractional anisotropy, are analyzed using Monte Carlo simulations. A novel approach for robust diffusion tensor estimation, called RESTORE (for robust estimation of tensors by outlier rejection), is proposed. This method uses iteratively reweighted least-squares regression to identify potential outliers and subsequently exclude them. Results from both simulated and clinical diffusion data sets indicate that the RESTORE method improves tensor estimation compared to the commonly used linear and nonlinear least-squares tensor fitting methods and a recently proposed method based on the Geman-McClure M-estimator. The RESTORE method could potentially remove the need for cardiac gating in DWI acquisitions and should be applicable to other MR imaging techniques that use univariate or multivariate regression to fit MRI data to a model. Published 2005 Wiley-Liss, Inc.(dagger) C1 NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, NIH, Bethesda, MD 20892 USA. Inst Psychiat, Ctr Neuroimaging Sci, London, England. RP Pierpaoli, C (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, NIH, Bldg 13,Room 3W16,South Dr, Bethesda, MD 20892 USA. EM cp1a@nih.gov RI Pierpaoli, Carlo/E-1672-2011; Jones, Derek/D-1460-2009; OI Jones, Derek/0000-0003-4409-8049 NR 20 TC 257 Z9 259 U1 4 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 2005 VL 53 IS 5 BP 1088 EP 1095 DI 10.1002/mrm.20426 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 921WS UT WOS:000228796900014 PM 15844157 ER PT J AU Jones, DK Pierpaoli, C AF Jones, DK Pierpaoli, C TI Confidence mapping in diffusion tensor magnetic resonance imaging tractography using a bootstrap approach SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DT-MRI; tractography; deterministic; probabilistic; bootstrap ID DT-MRI DATA; HUMAN BRAIN; TRACKING AB The bootstrap technique is an extremely powerful nonparametric statistical procedure for determining the uncertainty in a given statistic. However, its use in diffusion tensor MRI tractography remains virtually unexplored. This work shows how the bootstrap can be used to assign confidence to results obtained with deterministic tracking algorithms. By invoking the concept of a "tract-propagator," it also underlines the important effect of local fiber architecture or architectural milieu on tracking reproducibility. Finally, the practical advantages and limitations of the technique are discussed. Not only does the bootstrap allow any deterministic tractography algorithm to be used in a probabilistic fashion, but also its model-free inclusion of all sources of variability (including those that cannot be modeled) means that it provides the most realistic approach to probabilistic tractography. Magn Pleson Med 53:1143-1149, 2005. Published 2005 Wiley-Liss, Inc. C1 Inst Psychiat, Ctr Neuroimaging Sci, London SE5 8AF, England. NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, Bethesda, MD 20892 USA. RP Jones, DK (reprint author), Inst Psychiat, Ctr Neuroimaging Sci, P089,De Crespigny Pk, London SE5 8AF, England. EM d.jones@iop.kcl.ac.uk RI Pierpaoli, Carlo/E-1672-2011; Jones, Derek/D-1460-2009; OI Jones, Derek/0000-0003-4409-8049 NR 29 TC 100 Z9 101 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 2005 VL 53 IS 5 BP 1143 EP 1149 DI 10.1002/mrm.20466 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 921WS UT WOS:000228796900021 PM 15844149 ER PT J AU Yang, YH Gu, H Silbersweig, DA Stern, E AF Yang, YH Gu, H Silbersweig, DA Stern, E TI Simultaneous perfusion and blood-oxygenation-level-dependent measurements using single-shot interleaved z-shim echo-planar imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE functional MRI; cerebral blood flow; cerebral blood oxygenation; brain activation; magnetic susceptibility; z-shim ID FIELD INHOMOGENEITIES; GRADIENT-ECHO; BOLD; FMRI; FLOW; COMPENSATION; CONSUMPTION; CORTEX; STIMULATION; DYNAMICS AB Single-shot interleaved z-shim EPI (SSIZS-EPI) was extended to a simultaneous perfusion and blood-oxygenation-level-dependent (BOLD) imaging technique that reduces susceptibility-induced signal loss while preserving rapid image acquisition. Experiments on human brains showed that images acquired with this technique had improved signal-to-noise ratio in the inferior prefrontal, meso-, and lateral-temporal lobes compared with a conventional EPI. Perfusion maps obtained from the SSIZS-EPI images at resting state illustrated substantial signal recovery in these brain areas. Perfusion and BOLD images collected with a sensorimotor paradigm demonstrated the feasibility of the technique to simultaneously measure cerebral blood flow and blood oxygenation signals associated with brain activation. Functional experiments with a neuropsychiatric paradigm showed increased brain activities in the periamygdalar regions in both perfusion and BOLD maps, consistent with a previous (H2O)-O-15 PET study. The proposed technique, with its advantages of reducing susceptibility artifacts and fast scanning speed, would be useful for obtaining more reliable measurements of functional signals, particularly in the brain regions with field inhomogeneities. Magn Reson Med 53: 1207-1211, 2005. Published 2005 Wiley-Liss, Inc. C1 NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD 21042 USA. Cornell Univ, Weill Med Coll, Dept Psychiat, Funct Neuroimaging Lab, New York, NY USA. RP Yang, YH (reprint author), NIDA, Neuroimaging Res Branch, NIH, 5500 Nathan Shock Dr,Bldg C,Room 383, Baltimore, MD 21042 USA. EM yihongyang@intra.nida.nih.gov RI Stern, Emily/E-6035-2011 NR 23 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD MAY PY 2005 VL 53 IS 5 BP 1207 EP 1211 DI 10.1002/mrm.20431 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 921WS UT WOS:000228796900032 PM 15844153 ER PT J AU Gil-Lamaignere, C Winn, RM Simitsopoulou, M Maloukou, A Walsh, TJ Roilides, E AF Gil-Lamaignere, C Winn, RM Simitsopoulou, M Maloukou, A Walsh, TJ Roilides, E TI Inteferon gamma and granulocyte-macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes against Scedosporium spp.: comparison with Aspergillus spp. SO MEDICAL MYCOLOGY LA English DT Article DE Aspergillus spp.; hyphal damage; oxidative burst; polymorphonuclear leukocyte; Scedosporium spp. ID NADPH OXIDASE COMPONENTS; INTERFERON-GAMMA; HUMAN NEUTROPHILS; PARACOCCIDIOIDES-BRASILIENSIS; INVASIVE ASPERGILLOSIS; RESPIRATORY BURST; FUNGAL-INFECTIONS; GENE-EXPRESSION; YEAST-CELLS; FUMIGATUS AB While Aspergillus spp. have been the most frequent filamentous fungi causing infections in immunocompromised patients, Scedosporium spp. are emerging as life-threatening pathogens. We studied the effects of interferon gamma ( IFN-gamma) and granulocyte-macrophage colony-stimulating factor ( GM-CSF) alone or combined on the antifungal activities of human polymorphonuclear leukocytes ( PMN) against Scedosporium apiospermum and Scedosporium prolificans. We paralleled these activities to those against Aspergillus fumigatus and Aspergillus flavus. Incubation of PMN with IFN-gamma and GM-CSF for 22 h enhanced PMN-induced hyphal damage of both Aspergillus spp. and S. prolificans ( p < 0.05) but not of S. apiospermum. However, hyphae of S. apiospermum were damaged significantly more after incubation with PMN that had been treated with IFN-gamma and GM-CSF for 2 h. In addition, incubation of PMN with GM-CSF for 2 h enhanced PMN oxidative burst measured as superoxide anion ( O-2(-)) production in response to non-opsonized hyphae of A. flavus and Scedosporium spp. ( p < 0.05). In contrast, after 2 h, IFN-gamma and GM-CSF alone did not enhance PMN O-2(-) in response to opsonized hyphae of A. flavus and Scedosporium spp.; however, the combination of IFN-gamma and GM-CSF showed significant enhancement against these species. Thus, IFN-gamma and GM-CSF, particularly in combination, demonstrate a species- and time-dependent augmentation of PMN responses to Scedosporium spp. C1 Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54642 Thessaloniki, Greece. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Roilides, E (reprint author), Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, 49 Konstantinoupoleos St, GR-54642 Thessaloniki, Greece. EM roilides@med.auth.gr NR 50 TC 27 Z9 30 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 IS 3 BP 253 EP 260 DI 10.1080/13693780412331271072 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 938HT UT WOS:000229991200007 PM 16010852 ER PT J AU Almyroudis, NG Holland, SM Segal, BH AF Almyroudis, NG Holland, SM Segal, BH TI Invasive aspergillosis in primary immunodeficiencies SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT Advances Against Aspergillosis Conference CY SEP 09-11, 2004 CL San Francisco, CA DE Aspergillus; chronic granulomatous disease; Job syndrome ID CHRONIC GRANULOMATOUS-DISEASE; BONE-MARROW-TRANSPLANTATION; RECOMBINANT INTERFERON-GAMMA; MEDIATED GENE-TRANSFER; PERIPHERAL-BLOOD PROGENITORS; HYPER-IGE SYNDROME; TERM FOLLOW-UP; PULMONARY ASPERGILLOSIS; RESPIRATORY BURST; AMPHOTERICIN-B AB Primary immunodeficiencies are rare and usually first manifest during childhood. Invasive aspergillosis is the leading cause of mortality in chronic granulomatous disease (CGD), reflecting the key role of the phagocyte NADPH oxidase in host defense against opportunistic fungi. Despite interferon-gamma prophylaxis, invasive filamentous fungal infections are a persistent problem in CGD. Key principles of management of fungal infections involve early recognition and aggressive treatment and appropriate surgical debridement of localized disease. Because CGD is a disorder of phagocyte stem cells in which the gene defects are well defined, it is a model disease to evaluate immune reconstitution through stem cell transplantation and gene therapy. Patients with the hyper-IgE syndrome with recurrent infections (Job syndrome) are prone to colonization of lung cavities (pneumatoceles) by Aspergillus species leading to local invasion and rarely disseminated infection. Other primary phagocytic disorders, T-cell disorders, and mitochondrial disorders are uncommonly associated with invasive aspergillosis. Taken together, these rare primary immunodeficiencies highlight the complex coordination of both innate and acquired pathway mediating host defense against Aspergillus infection. C1 SUNY Buffalo, Roswell Pk Canc Inst, Div Infect Dis, Buffalo, NY 14263 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Segal, BH (reprint author), SUNY Buffalo, Roswell Pk Canc Inst, Div Infect Dis, Elm & Carlton St, Buffalo, NY 14263 USA. EM brahm.segal@roswellpark.org NR 108 TC 38 Z9 42 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 SU 1 BP S247 EP S259 DI 10.1080/13693780400025203 PG 13 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 950YW UT WOS:000230896300037 PM 16110817 ER PT J AU Hope, WW Walsh, TJ Denning, DW AF Hope, WW Walsh, TJ Denning, DW TI The invasive and saprophytic syndromes due to Aspergillus spp. SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT Advances Against Aspergillosis Conference CY SEP 09-11, 2004 CL San Francisco, CA DE aspergillosis; classification; diagnosis; invasive; saprophytic ID PRIMARY CUTANEOUS ASPERGILLOSIS; CHRONIC GRANULOMATOUS-DISEASE; CENTRAL-NERVOUS-SYSTEM; RENAL-TRANSPLANT RECIPIENT; NECROTIZING PULMONARY ASPERGILLOSIS; PARA-NASAL SINUSES; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; BONE-MARROW TRANSPLANT; FATAL SUBARACHNOID HEMORRHAGE; LIPOSOMAL AMPHOTERICIN-B AB Aspergillus spp. produce a wide range of invasive and sapropytic syndromes which may involve any tissue. Within a given tissue or organ the pathology and pathogenesis varies enormously, ranging from angioinvasive disease to non-invasive saprophytic disease. The individual invasive and saprophytic syndromes in which a causative role can be attributed to Aspergillus spp. are detailed specifically with reference to the underlying pathology and pathogenesis, the clinical setting and features, and the manner in which a diagnosis can be established. C1 Wythenshawe Hosp, Educ & Res Ctr, Manchester M23 9LT, Lancs, England. Univ Manchester, Manchester, Lancs, England. NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. RP Denning, DW (reprint author), Wythenshawe Hosp, Educ & Res Ctr, Southmoor Rd, Manchester M23 9LT, Lancs, England. EM ddenning@manchester.ac.uk OI Denning, David/0000-0001-5626-2251; Hope, William/0000-0001-6187-878X NR 402 TC 101 Z9 112 U1 2 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 SU 1 BP S207 EP S238 DI 10.1080/13693780400025179 PG 32 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 950YW UT WOS:000230896300034 PM 16110814 ER PT J AU Morgan, J Wannemuehler, KA Marr, KA Hadley, S Kontoyiannis, DP Walsh, TJ Fridkin, SK Pappas, PG Warnock, DW AF Morgan, J Wannemuehler, KA Marr, KA Hadley, S Kontoyiannis, DP Walsh, TJ Fridkin, SK Pappas, PG Warnock, DW TI Incidence of invasive aspergillosis following hematopoietic stem cell and solid organ transplantation: interim results of a prospective multicenter surveillance program SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT Advances Against Aspergillosis Conference CY SEP 09-11, 2004 CL San Francisco, CA DE aspergillosis; incidence; surveillance; transplantation ID FUNGAL-INFECTIONS; RISK-FACTORS; PULMONARY ASPERGILLOSIS; MOLD INFECTIONS; AMPHOTERICIN-B; RECIPIENTS; TERREUS; EPIDEMIOLOGY; COMPLICATIONS AB The incidence of invasive aspergillosis was estimated among 4621 hematopoietic stem cell transplants (HSCT) and 4110 solid organ transplants (SOT) at 19 sites dispersed throughout the United States, during a 22 month period from I March 2001 through 31 December 2002. Cases were identified using the consensus definitions for proven and probable infection developed by the Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group of the National Institute of Allergy and Infectious Diseases. The cumulative incidence (CI) of aspergillosis was calculated for the first episode of the infection that occurred within the specified time period after transplantation. To obtain an aggregate CI for each type of transplant, data from participating sites were weighted according to the proportion of transplants followed-up for specified time periods (four and 12 months for HSCT; six and 12 months for SOT). The aggregate CI of aspergillosis at 12 months was 0.5% after autologous HSCT, 2.3% after allogeneic HSCT from an HLA-matched related donor, 3.2% after transplantation from an HLA-mismatched related donor, and 3.9% after transplantation from an unrelated donor. The aggregate Cl at 12 months was similar following myeloablative or non-myeloablative conditioning before allogeneic HSCT (3.1 vs. 3.3%). After HSCT, mortality at 3 months following diagnosis of aspergillosis ranged from 53.8% of autologous transplants to 84.6% of unrelated-donor transplants. The aggregate CI of aspergillosis at 12 months was 2.4% after lung transplantation, 0.8% after heart transplantation, 0.3% after liver transplantation, and 0.1% after kidney transplantation. After SOT, mortality at three months after diagnosis of aspergillosis ranged from 20% for lung transplants to 66.7% for heart and kidney transplants. The Aspergillus spp. associated with infections after HSCT included A. fumigatus (56%), A. flavus (18.7%), A. terreus (16%), A. niger (8%), and A. versicolor (1.3%). Those associated with infections after SOT included A. fumigatus (76.4%), A. flavus (11.8%), and A. terreus (11.8%). In conclusion, we found that invasive aspergillosis is an uncommon complication of HSCT and SOT, but one that continues to be associated with poor outcomes. Our CI figures are lower compared to those of previous reports. The reasons for this are unclear, but may be related to changes in transplantation practices, diagnostic methods, and supportive care. C1 Ctr Dis Control & Prevent, Mycot Dis Branch, Atlanta, GA 30333 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Tufts New England Med Ctr, Boston, MA USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. RP Warnock, DW (reprint author), Ctr Dis Control & Prevent, Mycot Dis Branch, 1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM DWarnock@cdc.gov NR 27 TC 209 Z9 222 U1 1 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 SU 1 BP S49 EP S58 DI 10.1080/13693780400020113 PG 10 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 950YW UT WOS:000230896300010 PM 16110792 ER PT J AU Walsh, TJ Roilides, E Cortez, K Kottilil, S Bailey, J Lyman, CA AF Walsh, TJ Roilides, E Cortez, K Kottilil, S Bailey, J Lyman, CA TI Control, immunoregulation, and expression of innate pulmonary host defenses against Aspergillus fumigatus SO MEDICAL MYCOLOGY LA English DT Article; Proceedings Paper CT Advances Against Aspergillosis Conference CY SEP 09-11, 2004 CL San Francisco, CA DE Aspergillus; cytokines; chemokines; toll-like receptors; antimicrobial peptides; macrophages ID COLONY-STIMULATING FACTOR; OPPORTUNISTIC FUNGAL PATHOGENS; HUMAN MONONUCLEAR PHAGOCYTES; EPITHELIAL-CELL LINES; NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTORS; ANTIFUNGAL ACTIVITY; CANDIDA-ALBICANS; INTERFERON-GAMMA; POLYMORPHONUCLEAR LEUKOCYTES AB The innate host defense system (IHDS) against Aspergillus fumigatus includes dedicated phagocytic cells (peripheral blood monocytes, monocyte derived macrophages, pulmonary alveolar macrophages, neutrophils, myeloid dendritic cells and natural killer cells), cytokines, chemokines, toll-like receptors, and antimicrobial peptides. During the past decade, the advances in the field of the IHDS have been enormous, allowing a better understanding of the immunopharmacological control, immunoregulation, and expression of innate host defense molecules against Aspergillus fumigatus. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Hippokrat Hosp, Dept Pediat 3, GR-54642 Thessaloniki, Greece. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N-240,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 64 TC 25 Z9 29 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD MAY PY 2005 VL 43 SU 1 BP S165 EP S172 DI 10.1080/13693780500064672 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 950YW UT WOS:000230896300027 PM 16114132 ER PT J AU Sonies, BC Almajid, P Kleta, R Bernardini, I Gahl, WA AF Sonies, BC Almajid, P Kleta, R Bernardini, I Gahl, WA TI Swallowing dysfunction in 101 patients with nephropathic cystinosis - Benefit of long-term cysteamine therapy SO MEDICINE LA English DT Article ID LEUKOCYTE GRANULAR FRACTIONS; CTNS MUTATIONS; CORNEAL CRYSTALS; GENE; CHILDREN; TRANSPORT; PROTEIN; INSUFFICIENCY; LYSOSOMES; DEPLETION AB Nephropathic cystinosis is a rare, autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene that codes for a cystine transporter in the lysosomal membrane. Affected patients store 50-100 times the normal amounts of cystine in their cells, and suffer renal tubular and glomerular disease, growth retardation, photophobia, and other systemic complications, including a myopathy and swallowing dysfunction. Using video-fluoroscopy and ultrasound examinations, we assessed the swallowing function of 101 patients with nephropathic cystinosis on their most recent admission to the National Institutes of Health Clinical Center between 1987 and 2004. These patients ranged in age from 6 to 45 years; more than half had significant complaints of swallowing difficulty. On examination of barium swallow, the oral, pharyngeal, and esophageal phases of swallowing were abnormal in 24%, 51%, and 73% of patients, respectively. The frequency of dysfunction increased with age for each phase of swallowing. Both the Swallowing Severity Score (a measure of dysfunction on barium swallow) and the Oral Muscle Composite Score (a reflection of vocal strength, oral-facial movement, and tongue and lip function) increased (that is, worsened) with the number of years that a patient was not receiving treatment with cysteamine, the cystine-depleting agent of choice in cystinosis. The severity scores decreased with the number of years on cysteamine therapy. The Swallowing Severity Score varied directly with the severity of muscle disease, but was not correlated with the presence or absence of the 57-kb CTNS deletion that commonly occurs in nephropathic cystinosis patients. We conclude that swallowing dysfunction in cystinosis presents a risk of fatal aspiration, correlates with the presence of muscle atrophy, and, based on cross-sectional data, increases in frequency with age and number of years without cysteamine treatment. Cystine-depleting therapy with cysteamine should be considered the treatment of choice for both pre- and posttransplant cystinosis patients. C1 NHGRI, Med Genet Branch, NIH, Sect Human Biiochem Genet, Bethesda, MD 20892 USA. NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Oral Motor Funct Sect, Phys Disabil Branch,Rehabil Med Dept, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, Med Genet Branch, NIH, Sect Human Biiochem Genet, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 57 TC 35 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD MAY PY 2005 VL 84 IS 3 BP 137 EP 146 DI 10.1097/01.md.0000164204.00159.d4 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 926LY UT WOS:000229125900001 PM 15879904 ER PT J AU Colbert, L Mai, V Perkins, S Tooze, J Hursting, S AF Colbert, Lisa Mai, Volker Perkins, Susan Tooze, Janet Hursting, Stephen TI Voluntary Exercise Decreases Intestinal Tumor Burden In APC(Min/+) Mice SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Colbert, Lisa] Univ Wisconsin, Madison, WI USA. [Mai, Volker] Univ Maryland, Baltimore, MD 21201 USA. [Perkins, Susan; Hursting, Stephen] NCI, Bethesda, MD 20892 USA. [Tooze, Janet] Wake Forest Univ, Winston Salem, NC 27109 USA. EM lhcolbert@education.wisc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2005 VL 37 SU 5 MA 1955 BP S377 EP S377 DI 10.1097/00005768-200505001-01954 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070302371 ER PT J AU Heesch, KC Masse, LC AF Heesch, Kristiann C. Masse, Louise C. TI Using Item Response Theory To Assess The Psychometric Properties Of The Physical Activity Enjoyment Scale SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Heesch, Kristiann C.] Univ Oklahoma, Norman, OK 73019 USA. [Masse, Louise C.] NCI, Bethesda, MD 20892 USA. EM kheesch@ou.edu RI Heesch, Kristiann/J-1288-2012 OI Heesch, Kristiann/0000-0003-1931-3683 NR 0 TC 0 Z9 0 U1 1 U2 3 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 MAY PY 2005 VL 37 SU 5 MA 1300 BP S252 EP S252 DI 10.1097/00005768-200505001-01297 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070301477 ER PT J AU Hillsdon, M Brunner, EJ Guralnik, JM Marmot, MG AF Hillsdon, Melvyn Brunner, Eric J. Guralnik, Jack M. Marmot, Michael G. TI Physical Activity Maintains Physical Function In Early Old Age. The Whitehall II Cohort Study SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Hillsdon, Melvyn; Brunner, Eric J.; Marmot, Michael G.] UCL, London, England. [Guralnik, Jack M.] NIA, 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2005 VL 37 SU 5 MA 1315 BP S256 EP S256 DI 10.1097/00005768-200505001-01312 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070301492 ER PT J AU Irwin, M McTiernan, A Baumgartner, R Baumgartner, K Bernstein, L Gilliland, F Ballard-Barbash, R AF Irwin, Melinda McTiernan, Anne Baumgartner, Rick Baumgartner, Kathy Bernstein, Leslie Gilliland, Frank Ballard-Barbash, Rachel TI A Prospective Cohort Study Of Physical Activity In Relation To Disease-free Survival Of Breast Cancer In Women Diagnosed With Breast Cancer SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Irwin, Melinda] Yale Univ, New Haven, CT USA. [McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Baumgartner, Rick; Baumgartner, Kathy] Univ New Mexico, Albuquerque, NM 87131 USA. [Bernstein, Leslie; Gilliland, Frank] Univ So Calif, Los Angeles, CA USA. [Ballard-Barbash, Rachel] NCI, Bethesda, MD 20892 USA. EM melinda.irwin@yale.edu NR 0 TC 1 Z9 1 U1 0 U2 2 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 MAY PY 2005 VL 37 SU 5 MA 1879 BP S358 EP S358 DI 10.1097/00005768-200505001-01878 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070302295 ER PT J AU Sayers, SP Guralnik, JM Brach, JS Newman, AB Fielding, RA AF Sayers, Stephen P. Guralnik, Jack M. Brach, Jennifer S. Newman, Anne B. Fielding, Roger A. TI Validation Of The 400 Meter Self-paced Walk SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Sayers, Stephen P.; Fielding, Roger A.] Boston Univ, Boston, MA 02215 USA. [Guralnik, Jack M.] NIA, NIH, Bethesda, MD 20892 USA. [Brach, Jennifer S.; Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. EM sayerss@missouri.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 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 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2005 VL 37 SU 5 MA 411 BP S73 EP S73 DI 10.1097/00005768-200505001-00410 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070300274 ER PT J AU Walsh, S Metter, J Hurley, BF Ferrucci, L Roth, SM AF Walsh, Sean Metter, Jeffrey Hurley, Ben F. Ferrucci, Luigi Roth, Stephen M. TI The R577x Polymorphism In The Actn3 Gene Is Associated With Muscle Strength In Women SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Meeting Abstract C1 [Walsh, Sean; Hurley, Ben F.; Roth, Stephen M.] Univ Maryland, College Pk, MD 20742 USA. [Metter, Jeffrey; Ferrucci, Luigi] NIA, Baltimore, MD 21224 USA. EM walshs@umd.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD MAY PY 2005 VL 37 SU 5 MA 873 BP S164 EP S164 DI 10.1097/00005768-200505001-00871 PG 1 WC Sport Sciences SC Sport Sciences GA V19KC UT WOS:000208070301124 ER PT J AU Kashmiri, SVS De Pascalis, R Gonzales, NR Schlom, J AF Kashmiri, SVS De Pascalis, R Gonzales, NR Schlom, J TI SDR grafting - a new approach to antibody humanization SO METHODS LA English DT Article DE humanized antibodies; CDR grafting; SDR grafting; inununogenicity; surface plasmon resonance; sera reactivity ID COMPLEMENTARITY-DETERMINING REGIONS; SPECIFICITY-DETERMINING RESIDUES; PROTEIN DATA-BANK; SINGLE-CHAIN FV; MONOCLONAL-ANTIBODY; ANTICARCINOMA ANTIBODY; FRAMEWORK RESIDUES; MACROMOLECULAR STRUCTURES; CYNOMOLGUS MONKEYS; SEQUENCE DATABASE AB A major impediment to the clinical utility of the murine monoclonal antibodies is their potential to elicit human anti-murine antibody (HAMA) response in patients. To circumvent this problem, murine antibodies have been genetically manipulated to progressively replace their murine content with the amino acid residues present in their human counterparts. To that end, murine antibodies have been humanized by grafting their complementarity determining regions (CDRs) onto the variable light (V-L) and variable heavy (V-H) frameworks of human immunoglobulin molecules, while retaining those murine framework residues deemed essential for the integrity of the antigen-combining site. However, the xenogeneic CDRs of the humanized antibodies may evoke anti-idiotypic (anti-Id) response in patients. To minimize the anti-Id response, a procedure to humanize xenogeneic antibodies has been described that is based on grafting, onto the human frameworks, only the specificity determining residues (SDRs), the CDR residues that are most crucial in the antibody-ligand interaction. The SDRs are identified through the help of the database of the three-dimensional structures of the antigen-antibody complexes of known structures or by mutational analysis of the antibody-combining site. An alternative approach to humanization, which involves retention of more CDR residues, is based on grafting of the 'abbreviated' CDRs, the stretches of CDR residues that include all the SDRs. A procedure to assess the reactivity of the humanized antibody to sera from patients who had been administered the murine antibody has also been described. Published by Elsevier Inc. C1 NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kashmiri, SVS (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 40 TC 41 Z9 48 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2005 VL 36 IS 1 BP 25 EP 34 DI 10.1016/j.ymeth.2005.01.003 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 924GH UT WOS:000228966500004 PM 15848072 ER PT J AU Dall'Acqua, WF Damschroder, MM Zhang, JL Woods, RM Widjaja, L Yu, J Wu, H AF Dall'Acqua, WF Damschroder, MM Zhang, JL Woods, RM Widjaja, L Yu, J Wu, H TI Antibody humanization by framework shuffling SO METHODS LA English DT Article DE antibody; framework; humanization; germline; library ID IMMUNOGLOBULIN KAPPA-LOCUS; MONOCLONAL-ANTIBODY; RAPID HUMANIZATION; BINDING PROPERTIES; IMMUNOGENICITY; CONFORMATION; RESIDUES; REGION; MOUSE; FAB AB We report here the humanization of a mouse monoclonal antibody (mAb B233) using a new technique which we call framework shuffling. rnAb B233 was raised against the human receptor tyrosine kinase EphA2 which is selectively up-regulated in many cancer cell lines and as such constitutes an attractive target for cancer therapy. The six CDRs of B233 were fused in-frame to pools of corresponding individual human frameworks. These human frameworks encompassed all known heavy and light (K) chain human germline genes. The resulting Fab combinatorial libraries were then screened for binding to the antigen. A two-step selection process, in which the light and heavy chains of the parental mAb were successively humanized, resulted in the identification of several humanized variants that retained binding to EphA2. More precisely, after conversion to human IgG1, the dissociation constants of three select fully humanized variants ranged from 3 to 48 nM. This brings the best framework-shuffled, humanized binder within 5-fold of the avidity of parental mAb B233. Importantly, these humanized IgGs also possessed biochemical activities similar to those of parental mAb B233 as judged by induction of EphA2 phosphorylation. Thus, without requiring any rational design or structural information, this new humanization approach allows to rapidly identify various human framework combinations able to support the structural feature(s) of the CDRs which are essential for binding and functional activity. © 2005 Elsevier Inc. All rights reserved. C1 Medimmune Inc, Dept Antibody Discovery & Prot Engn, Gaithersburg, MD 20878 USA. NIH, Clncl Immunotherapy Sect, Bethesda, MD 20892 USA. RP Wu, H (reprint author), Medimmune Inc, Dept Antibody Discovery & Prot Engn, 1 Medimmune Way, Gaithersburg, MD 20878 USA. EM dall'acquaw@medimmune.com; wuh@medimmune.com OI Damschroder, Melissa/0000-0001-9453-6532 NR 44 TC 34 Z9 39 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 1046-2023 J9 METHODS JI Methods PD MAY PY 2005 VL 36 IS 1 BP 43 EP 60 DI 10.1016/j.ymeth.2005.01.005 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 924GH UT WOS:000228966500006 PM 15848074 ER PT J AU Shizukuda, Y Matoba, S Mian, OY Nguyen, T Hwang, PM AF Shizukuda, Y Matoba, S Mian, OY Nguyen, T Hwang, PM TI Targeted disruption of p53 attenuates doxorubicin-induced cardiac toxicity in mice SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE cardiac toxicity; doxorubicin; p53; apoptosis; transgene ID RENIN-ANGIOTENSIN SYSTEM; INDUCED HEART-FAILURE; INDUCED APOPTOSIS; MYOCYTE APOPTOSIS; REACTIVE OXYGEN; ENDOTHELIAL-CELLS; GENE-EXPRESSION; IN-VIVO; CANCER; MODULATION AB Use of the chemotherapeutic agent doxorubicin (Dox) is limited by dose-dependent cardiotoxic effects. The molecular mechanism underlying these toxicities are incompletely understood, but previous results have demonstrated that Dox induces p53 expression. Because p53 is an important regulator of the cell birth and death we hypothesized that targeted disruption of the p53 gene would attenuate Dox-induced cardiotoxicity. To test this, female 6-8 wk old C57BL wild-type (WT) or p53 knockout (p53 KO) mice were randomized to either saline or Dox 20 mg/kg via intraperitoneal injection. Animals were serially imaged with high-frequency (14 MHz) two-dimensional echocardiography. Measurements of left ventricle (LV) systolic function as assessed by fractional shortening (FS) demonstrated a decline in WT mice as early as 4 days after Dox injection and by 2 wk demonstrated a reduction of 31 +/- 16% (P < 0.05) from the baseline. In contrast, in p53 KO mice, LV FS was unchanged over the 2 wk period following Dox injection. Apoptosis of cardiac myocytes as measured by the TUNEL and ligase reactions were significantly increased at 24 h after Dox treatment in WT mice but not in p53 KO mice. After Dox injection, levels of myocardial glutathione and Cu/Zn superoxide dismutase were preserved in p53 KO mice, but not in WT animals. These observations suggest that p53 mediated signals are likely to play a significant role in Dox-induced cardiac toxicity and that they may modulate Dox-induced oxidative stress. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Shizukuda, Y (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10-CRC,Room 6-3142,10 Ctr Dr,MSC-1454, Bethesda, MD 20892 USA. EM shizukuy@nhlbi.nih.gov OI Mian, Omar/0000-0002-8133-8120 NR 43 TC 66 Z9 67 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD MAY PY 2005 VL 273 IS 1-2 BP 25 EP 32 DI 10.1007/s11010-005-5905-8 PG 8 WC Cell Biology SC Cell Biology GA 927SC UT WOS:000229219800003 PM 16013437 ER PT J AU Qiu, HF Hu, CH Zhang, F Hwang, GJ Swanson, MJ Boonchird, C Hinnebusch, AG AF Qiu, HF Hu, CH Zhang, F Hwang, GJ Swanson, MJ Boonchird, C Hinnebusch, AG TI Interdependent recruitment of SAGA and Srb mediator by transcriptional activator Gcn4p SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; TATA-BINDING PROTEIN; IN-VIVO TARGET; CHROMATIN-MODIFYING COMPLEXES; HISTONE ACETYLTRANSFERASE; SACCHAROMYCES-CEREVISIAE; GENE-EXPRESSION; COACTIVATOR COMPLEX; FUNCTIONAL-ORGANIZATION; NATIVE COMPLEXES AB Transcriptional activation by Gcn4p is enhanced by the coactivators SWI/SNF, SAGA, and Srb mediator, which stimulate recruitment of TATA binding protein (TBP) and polymerase II to target promoters. We show that wild-type recruitment of SAGA by Gcn4p is dependent on mediator but independent of SWI/SNF function at three different promoters. Recruitment of mediator is also independent of SWI/SNF but is enhanced by SAGA at a subset of Gcn4p target genes. Recruitment of all three coactivators to ARGI is independent of the TATA element and preinitiation complex formation, whereas efficient recruitment of the general transcription factors requires the TATA box. We propose an activation pathway involving interdependent recruitment of SAGA and Srb mediator to the upstream activation sequence, enabling SWI/SNF recruitment and the binding of TBP and other general factors to the promoter. We also found that high-level recruitment of Tra1p and other SAGA subunits is independent of the Ada2p/Ada3p/Gcn5p histone acetyltransferase module but requires Spt3p in addition to subunits required for SAGA integrity. Thus, while Tra1p can bind directly to Gcn4p in vitro, it requires other SAGA subunits for efficient recruitment in vivo. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A,Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 73 TC 48 Z9 48 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2005 VL 25 IS 9 BP 3461 EP 3474 DI 10.1128/MCB.25.9.3461-3474.2005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 920HF UT WOS:000228679300007 PM 15831453 ER PT J AU Feng, YQ Warin, R Li, TH Olivier, E Besse, A Lobell, A Fu, HQ Lin, CM Aladjem, MI Bouhassira, EE AF Feng, YQ Warin, R Li, TH Olivier, E Besse, A Lobell, A Fu, HQ Lin, CM Aladjem, MI Bouhassira, EE TI The human beta-globin locus control region can silence as well as activate gene expression SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN GAMMA-GLOBIN; POSITION-EFFECT VARIEGATION; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; INTERGENIC TRANSCRIPTION; CHROMOSOMAL INTEGRATION; CHROMATIN MODIFIERS; MAMMALIAN-CELLS; REPLICATION; ORIENTATION AB Using recombinase-mediated cassette exchange to test multiple transgenes at the same site of integration, we demonstrate a novel chromatin context-dependent silencer activity of the β-globin locus control region (LCR). This silencer activity requires DNase I hypersensitive sites HS2 and HS3 but not HS4. After silencing, the silenced cassettes adopt a typical closed chromatin conformation (histone H3 and H4 deacetylation, histone H3-K4 methylation, DNA methylation, and replication in late S phase). In the absence of the LCR at the same site of integration, the chromatin remains decondensed. We demonstrate that the LCR is necessary but not sufficient to trigger these chromatin changes. We also provide evidence that this novel silencing activity is caused by transcriptional interference triggered by activation of transcription in the flanking sequences by the LCR. C1 Albert Einstein Coll Med, Div Hematol, Dept Med, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. Natl Canc Inst, Mol Pharmacol Lab, Bethesda, MD USA. RP Bouhassira, EE (reprint author), Albert Einstein Coll Med, Div Hematol, Dept Med, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM bouhassi@aecom.yu.edu RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU NHLBI NIH HHS [HL55435, P01 HL055435]; NIDDK NIH HHS [DK061799, DK56845, R01 DK056845] NR 44 TC 29 Z9 30 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 MAY PY 2005 VL 25 IS 10 BP 3864 EP 3874 DI 10.1016/MCB.25.10.3864-3874.2004 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100002 PM 15870261 ER PT J AU Goparaju, SK Jolly, PS Watterson, KR Bektas, M Alvarez, S Sarkar, S Mel, L Ishii, I Chun, J Milstien, S Spiegel, S AF Goparaju, SK Jolly, PS Watterson, KR Bektas, M Alvarez, S Sarkar, S Mel, L Ishii, I Chun, J Milstien, S Spiegel, S TI The S1P(2) receptor negatively regulates platelet-derived growth factor-induced motility and proliferation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; SMOOTH-MUSCLE-CELLS; SPHINGOSINE KINASE TYPE-2; BETA-RECEPTOR; FUNCTIONAL-CHARACTERIZATION; LYSOPHOSPHATIDIC ACID; VASCULAR MATURATION; ENDOTHELIAL-CELLS; MOLECULAR-CLONING; PDGF RECEPTOR AB Sphingosine-1-phosphate (SIP), a bioactive sphingolipid metabolite, is the ligand for five specific G protein-coupled receptors, named SIP, to SIP,. In this study, we found that cross-communication between platelet-derived growth factor receptor and SIP, serves as a negative damper of PDGF functions. Deletion of the S1P(2) receptor dramatically increased migration of mouse embryonic fibroblasts toward SIP, serum, and PDGF but not fibronectin. This enhanced migration was dependent on expression of SIP, and sphingosine kinase 1 (SphK1), the enzyme that produces SIP, as revealed by downregulation of their expression with antisense RNA and small interfering RNA, respectively. Although S1P(2) deletion had no significant effect on tyrosine phosphorylation of the PDGF receptors or activation of extracellular signal-regulated kinase 1/2 or Akt induced by PDGF, it reduced sustained PDGF-dependent p38 phosphorylation and markedly enhanced Rac activation. Surprisingly, S1P(2)-null cells not only exhibited enhanced proliferation but also markedly increased SphK1 expression and activity. Conversely, reintroduction of S1P(2) reduced DNA synthesis and expression of SphK1. Thus, S1P(2) serves as a negative regulator of PDGF-induced migration and proliferation as well as SphKI expression. Our results suggest that a complex interplay between PDGFR and SIP receptors determines their functions. C1 Virginia Commonwealth Univ, Ctr Med, Dept Biochem, Richmond, VA 23298 USA. Georgetown Univ, Ctr Med, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Natl Inst Neurosci, Dept Genet, Tokyo 1878502, Japan. Scripps Res Inst, Psychiat Disorder Inst, Helen L Dorris Neurol & Psychiat Disorder Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Natl Inst Mental Hlth, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Ctr Med, Dept Biochem, 1101 E Marshall St,Room 2-011,Sanger Hall, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Goparaju, Sravan/H-3422-2011; OI Ishii, Isao/0000-0002-5367-205X FU NCI NIH HHS [R01 CA061774, CA61774]; NIMH NIH HHS [K02 MH001723, MH01723] NR 60 TC 93 Z9 96 U1 0 U2 2 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 MAY PY 2005 VL 25 IS 10 BP 4237 EP 4249 DI 10.1128/MCB.25.10.4237-4249.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100034 PM 15870293 ER PT J AU Spiridonov, NA Wong, L Zerfas, PM Starost, MF Pack, SD Paweletz, CP Johnson, GR AF Spiridonov, NA Wong, L Zerfas, PM Starost, MF Pack, SD Paweletz, CP Johnson, GR TI Identification and characterization of SSTK, a serine/threonine protein kinase essential for male fertility SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR PROTEINS; SPERMIOGENESIS; CHROMATIN; GENE; SPERMATOGENESIS; PHOSPHORYLATION; MEIOSIS; HSP70-2; MICE; CONDENSATION AB Here we describe and characterize a small serine/threonine kinase (SSTK) which consists solely of the Nand Globes of a protein kinase catalytic domain. SSTK protein is highly conserved among mammals, and no close homologues were found in the genomes of nonmammalian organisms. SSTK specifically interacts with HSP90-1β, HSC70, and HSP70 proteins, and this association appears to be required for SSTK kinase activity. The SSTK transcript was most abundant in human and mouse testes but was also detected in all human tissues tested. In the mouse testis, SSTK protein was localized to the heads of elongating spermatids. Targeted deletion of the SSTK gene in mice resulted in male sterility due to profound impairment in motility and morphology of spermatozoa. A defect in DNA condensation in SSTK null mutants occurred in elongating spermatids at a step in spermiogenesis coincident with chromatin displacement of histones by transition proteins. SSTK phosphorylated histones H1, H2A, H2AX, and H3 but not H2B or H4 or transition protein I in vitro. These results demonstrate that SSTK is required for proper postmeiotic chromatin remodeling and male fertility. Abnormal sperm chromatin condensation is common in sterile men, and our results may provide insight into the molecular mechanisms underlying certain human infertility disorders. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Lab Immunopathol, NIH, Bethesda, MD 20892 USA. Univ Hlth Sci, Uniformed Serv, Dept Anat Physiol & Genet, Inst Mol Med, Bethesda, MD 20814 USA. RP Spiridonov, NA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, HFD-122,Bldg 29A,Rm 3B-20, Bethesda, MD 20892 USA. EM spiridonov@cber.fda.gov; johnsong@cber.fda.gov RI Spiridonov, Nikolay/B-6287-2014; Pack, Svetlana/C-2020-2014 NR 35 TC 53 Z9 58 U1 2 U2 5 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 MAY PY 2005 VL 25 IS 10 BP 4250 EP 4261 DI 10.1128/MCB.25.10.4250-4261.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100035 PM 15870294 ER PT J AU Sessoms-Sikes, S Honse, Y Lovinger, DM Colbran, RJ AF Sessoms-Sikes, S Honse, Y Lovinger, DM Colbran, RJ TI CaMKII alpha enhances the desensitization of NR2B-containing NMDA receptors by an autophosphorylation-dependent mechanism SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID PROTEIN-KINASE-II; D-ASPARTATE RECEPTORS; SYNAPTIC PLASTICITY; NR2B SUBUNIT; POSTSYNAPTIC DENSITY; HIPPOCAMPAL SLICES; VISUAL-CORTEX; RAT-BRAIN; CALCIUM/CALMODULIN; CALMODULIN AB Long-term potentiation or depression of synaptic function often requires Ca2+ influx via NMDA-type glutamate receptors (NMDARs) and changes in the autophosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) at Thr(286). Autophosphorylated CaMKII binds directly to NMDAR subunits, co-localizes with NMDARs in the postsynaptic density. and phosphorylates NR2B subunits at Ser(1303). Here, we demonstrate that CaMKIIα enhances the extent and/or rate of desensitization of NMDA-induced macroscopic currents in HEK293 cells co-expressing NR2B with either the NR1(011) or NR1(101) splice variants. without significantly changing other current parameters. In contrast, the extent of desensitization of NMDARs containing NR2A in place of NR2B is significantly decreased by co-expression of CaMKIIα. Kinases harboring K42R (inactive kinase) or T286A (autophosphorylation-deficient) mutations are defective in enhancing the desensitization of NR1/NR2B channels. In addition, the CaMKII-dependent enhancement of NR1/NR2B channel desensitization is abrogated by intracellular loading with BAPTA. These data suggest a novel mechanism for Ca2+-dependent negative-feedback regulation of NR2B-containing NMDARs in a CaMKII activity- and autophosphorylation-dependent manner that may modulate NMDAR-mediated synaptic plasticity. © 2005 Elsevier Inc. All rights reserved. C1 Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Vanderbilt Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Colbran, RJ (reprint author), Vanderbilt Univ, Sch Med, Ctr Mol Neurosci, Dept Mol Physiol & Biophys, 221 Kirkland Hall, Nashville, TN 37232 USA. EM roger.colbran@vanderbilt.edu FU Intramural NIH HHS; NIMH NIH HHS [R01-MH63232] NR 51 TC 45 Z9 53 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 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD MAY PY 2005 VL 29 IS 1 BP 139 EP 147 DI 10.1016/j.mcb.2005.01.006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 925KA UT WOS:000229050800013 PM 15866054 ER PT J AU Tyska, MJ Mackey, AT Huang, JD Copeland, NG Jenkins, NA Mooseker, MS AF Tyska, MJ Mackey, AT Huang, JD Copeland, NG Jenkins, NA Mooseker, MS TI Myosin-1a is critical for normal brush border structure and composition SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; RAT SMALL-INTESTINE; MEMBRANE MICRODOMAINS; LIPID RAFTS; VI; ORGANIZATION; CYTOSKELETON; ACTIN; COMPLEX; PROTEIN AB To develop our understanding of myosin-1a function in vivo, we have created a mouse line null for the myosin-la gene. Myosin-1a knockout mice demonstrate no overt phenotypes at the whole animal level but exhibit significant perturbations and signs of stress at the cellular level. Among these are defects in microvillar membrane morphology, distinct changes in brush-border organization, loss of numerous cytoskeletal and membrane components from the brush border, and redistribution of intermediate filament proteins into the brush border. We also observed significant ectopic recruitment of another short-tailed class I motor, myosin-1c, into the brush border of knockout enterocytes. This latter finding, a clear demonstration of functional redundancy among vertebrate myosins-I, may account for the lack of a whole animal phenotype. Nevertheless, these results indicate that myosin-1a is a critical multifunctional component of the enterocyte, required for maintaining the normal composition and highly ordered structure of the brush border. C1 Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. NCI, NIH, Ft Detrick, MD 21702 USA. Yale Univ, Dept Cell Biol, New Haven, CT 06520 USA. Yale Univ, Dept Pathol, New Haven, CT 06520 USA. RP Tyska, MJ (reprint author), Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA. EM matthew.tyska@vanderbilt.edu RI Huang, Jiandong/C-4277-2009 FU NIDDK NIH HHS [DK-55389, DK-07017, DK-10113, DK-25387, F32 DK010113, P01 DK055389, R01 DK025387, R37 DK025387, R56 DK025387, T32 DK007017] NR 48 TC 89 Z9 90 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD MAY PY 2005 VL 16 IS 5 BP 2443 EP 2457 DI 10.1091/mbc.E04-12-1116 PG 15 WC Cell Biology SC Cell Biology GA 921AU UT WOS:000228737400026 PM 15758024 ER PT J AU Haleem-Smith, H Derfoul, A Okafor, C Tuli, R Olsen, D Hall, DJ Tuan, RS AF Haleem-Smith, H Derfoul, A Okafor, C Tuli, R Olsen, D Hall, DJ Tuan, RS TI Optimization of high-efficiency transfection of adult human mesenchymal stem cells in vitro SO MOLECULAR BIOTECHNOLOGY LA English DT Article DE transfection; mesenchymal stem cells; GFP reporter; chondrogenesis ID HUMAN TRABECULAR BONE; PROGENITOR CELLS; DIFFERENTIATION; MARROW; PROMOTER; CHONDROGENESIS; TISSUE AB With the advent of recent protocols to isolate multipotent human mesenchymal stem cells (MSCs), there is a need for efficient transfection methodologies for these cells. Most standard transfection methods yield poor transfection efficiencies for MSCs (< 1%). Here we have optimized a high-efficiency transfection technique for low passage MSCs derived from adult human bone marrow. This technique is an extension of electroporation, termed amaxa Nucleofection™, where plasmid DNA is transfected directly into the cell nucleus, independent of the growth state of the cell. With this technique, we demonstrate up to 90% transfection efficiency of the viable population of MSCs, using plasmid construct containing a standard cytomegalovirus (CMV) early promoter driving expression of green fluorescent protein (GFP). Although little variation in transfection efficiency was observed between patient samples, a 2-fold difference in transfection efficiency and a 10-fold difference in expression levels per cell were seen using two distinct CMV-GFP expression plasmids. By fluorescence-activated cell sorting, the GFP expressing cells were sorted and subcultured. At 2 wk posttransfection, approx 25% of the population of sorted cells were GFP positive, and by 3 wk, nearly 10% of the cells still retained GFP expression. Transfection of these cells with plasmid containing either the collagen type I (Col I a 1) promoter or the cartilage oligomeric matrix protein (COMP) promoter, each driving expression of GFP, produced a somewhat lower transfection efficiency (approx 40%), due in part to the lower activity of transcription from these promoters compared to that of CMV. Transfection with the collagen type 11 (Col2a1) promoter linked to GFP exhibited low expression, due to the fact that collagen type 11 is not expressed in these cells. Upon culturing of the Col2a1-GFP transfected cells in a transforming growth factor- β 3 -containing medium known to induce mesenchymal chondrogensis, a significant enhancement of GFP level was seen, indicating the ability of the transfected cells to differentiate into chondrocytes and express cartilage-specific genes, such as Col2a1. Taken together, these data provide evidence of the applicability of this technique for the efficient transfection of MSCs. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, 50 S Dr,Rm 1503, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU NIAMS NIH HHS [Z01 AR41131] NR 23 TC 54 Z9 67 U1 1 U2 13 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1073-6085 J9 MOL BIOTECHNOL JI Mol. Biotechnol. PD MAY PY 2005 VL 30 IS 1 BP 9 EP 19 DI 10.1385/MB:30:1:009 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 927CY UT WOS:000229171200002 PM 15805572 ER PT J AU Bottone, FG Moon, Y Kim, JS Alston-Mills, B Ishibashi, M Eling, TE AF Bottone, FG Moon, Y Kim, JS Alston-Mills, B Ishibashi, M Eling, TE TI The anti-invasive activity of cyclooxygenase inhibitors is regulated by the transcription factor ATF3 (activating transcription factor 3) SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; PREVENT COLORECTAL ADENOMAS; BETA SUPERFAMILY MEMBER; COLON-CANCER CELLS; BREAST-CANCER; MATRIX METALLOPROTEINASE-2; DIALLYL-DISULFIDE; GENE-EXPRESSION; IN-VITRO AB We previously showed that nonsteroidal anti-inflammatory drugs (NSAID) such as sulindac sulfide, which has chemopreventive activity, modulate the expression of several genes detected by microarray analysis. Activating transcription factor 3 (ATF3) was selected for further study because it is a transcription factor involved in cell proliferation, apoptosis, and invasion, and its expression is repressed in human colorectal tumors as compared with normal adjacent tissue. In this report, we show that ATF3 mRNA and protein expression are up-regulated in HCT-116 human colorectal cancer cells following treatment with NSAIDs, troglitazone, diallyl disulfide, and resveratrol. To ascertain the biological significance of ATF3, we overexpressed full-length ATF3 protein in the sense and antisense orientations. Overexpression of ATF3 in the sense orientation decreased focus formation in vitro and reduced the size of mouse tumor xenografts by 54% in vivo. Conversely, overexpression of antisense ATF3 was protumorigenic in vitro, however, not in vivo. ATF3 in the sense orientation did not modulate apoptosis, indicating another mechanism is involved. With microarray analysis, several genes relating to invasion and metastasis were identified by ATF3 overexpression and were confirmed by real-time reverse transcription-PCR, and several of these genes were modulated by sulindac sulfide, which inhibited invasion in these cells. Furthermore, overexpression of ATF3 inhibited invasion to a similar degree as sulindac sulfide treatment, whereas antisense ATF3 increased invasion. In conclusion, ATF3 represents a novel mechanism in which NSAIDs exert their anti-invasive activity, thereby linking ATF3 and its gene regulatory activity to the biological activity of these compounds. C1 Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. RP Eling, TE (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Eling@niehs.nih.gov NR 57 TC 67 Z9 70 U1 0 U2 4 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 MAY PY 2005 VL 4 IS 5 BP 693 EP 703 DI 10.1158/1535-7163.MCT-04-0337 PG 11 WC Oncology SC Oncology GA 926DE UT WOS:000229102300001 PM 15897233 ER PT J AU Uno, T Hirabayashi, K Murai, M Yano, J Ozato, K AF Uno, T Hirabayashi, K Murai, M Yano, J Ozato, K TI The role of IFN regulatory factor-3 in the cytotoxic activity of NS-9, a polyinosinic-polycytidylic acid/cationic liposome complex, against tumor cells SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID DOUBLE-STRANDED-RNA; ACTIVATED PROTEIN-KINASE; VIRUS-INDUCED APOPTOSIS; INTERFERON ACTION; RIBOSOMAL-RNA; INFECTED-CELLS; SIGNALING PATHWAY; MAMMALIAN-CELLS; DEATH; DEGRADATION AB NS-9 is a complex of polyinosinic-polycytidylic acid and a novel cationic liposome, LIC-101. The complex has strong cytotoxic activity against tumor cells derived from epithelial or fibroblastic cells. We have investigated the mechanism of the cytotoxic activity of NS-9 using knockdown cells in which the expression of proteins of interest was inhibited by RNA interference. NS-9 showed strong cytotoxic activity against knockdown cells with reduced expression of double-stranded RNA-dependent protein kinase, RNase L, or IFIN-α/β receptor, but showed no cytotoxic activity against IFN regulatory factor-3 (IRF3) knockdown cells. In IRF3-knockdown cells, NS-9 also did not induce either the DNA fragmentation or the rRNA degradation observed in negative control cells. We conclude that IRF3 plays a crucial role in the cytotoxic activity of NS-9 against tumor cells, whereas RNA-dependent protein kinase, RNase L, or type I IFNs are not important for its activity. C1 Nippon Shinyaku Co Ltd, Discovery Res Labs, Minami Ku, Kyoto 6018550, Japan. NICHHD, Lab Mol Growth & Regulat, NIH, Bethesda, MD 20892 USA. RP Uno, T (reprint author), Nippon Shinyaku Co Ltd, Discovery Res Labs, Minami Ku, 14 Nishinosho Monguchi Cho, Kyoto 6018550, Japan. EM t.uno@po.nippon-shinyaku.co.jp NR 42 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD MAY PY 2005 VL 4 IS 5 BP 799 EP 805 DI 10.1158/1535-7163.MCT-04-0317 PG 7 WC Oncology SC Oncology GA 926DE UT WOS:000229102300012 PM 15897244 ER PT J AU Weber, TJ Siegel, RW Markille, LM Chrisler, WB Lei, XYC Colburn, NH AF Weber, TJ Siegel, RW Markille, LM Chrisler, WB Lei, XYC Colburn, NH TI A paracrine signal mediates the cell transformation response to low dose gamma radiation in JB6 cells SO MOLECULAR CARCINOGENESIS LA English DT Article DE bystander; response; radiation; paracrine; transformation ID NF-KAPPA-B; ANCHORAGE-INDEPENDENT GROWTH; MOUSE EPIDERMAL-CELLS; HUMAN KERATINOCYTES; ALPHA-PARTICLES; NEOPLASTIC TRANSFORMATION; AP-1; IRRADIATION; EXPRESSION; TRANSACTIVATION AB The carcinogenic response to radiation is complex and may involve adaptive cellular responses as well as a bystander effect mediated by paracrine or intercellular signaling activities. Using a newly developed co-culture model we have examined whether low dose gamma radiation induces the transformation of JB6 mouse epidermal cells as well as nonirradiated bystander cells. Cell transformation response is defined as the acquisition of anchorage-independent growth properties and is quantified by counting colonies on soft agar. Exposure of J136 cells to low dose (2-20 cGy) gamma radiation resulted in an approximate 1.9 +/- 0.1 and 2.8 +/- 0.5-fold increase in cell transformation response when cells were seeded at 1 X 10(4) or 1 X 10(5) cells/dish, relative to respective sham exposed controls. We developed a co-culture model where sham exposed or irradiated JB6 cells were mixed with non-irradiated JB6 cells that had been stably transfected with the enhanced yellow fluorescent protein (EYFP) to enable the distinction of fluorescent bystander-specific colonies. A significant increase in the number of bystander-specific colonies was observed in co-culture with 10 cGy irradiated JB6 cells (224 +/- 9), relative to the number of bystander-specific colonies arising in coculture with sham exposed JB6 cells (55 +/- 16). Our results indicate that low dose radiation induces the transformation of JB6 cells and that a soluble paracrine factor that is secreted by irradiated cells induces the transformation of nonirradiated bystander cells. (c) 2005 Wiley-Liss, Inc. C1 Pacific NW Natl Lab, Richland, WA 99354 USA. NCI, Lab Canc Prevent, Reg Genet Serv, Frederick, MD 21701 USA. RP Weber, TJ (reprint author), Pacific NW Natl Lab, 790 6th St,P7-56, Richland, WA 99354 USA. OI Siegel, Robert/0000-0002-0833-5580 NR 32 TC 15 Z9 17 U1 0 U2 1 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 MAY PY 2005 VL 43 IS 1 BP 31 EP 37 DI 10.1002/mc.20092 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 921UB UT WOS:000228789500004 PM 15800926 ER PT J AU Tan, DY Johnson, DA Wu, W Zeng, LF Chen, YH Chen, WY Vonderhaar, BK Walker, AM AF Tan, DY Johnson, DA Wu, W Zeng, LF Chen, YH Chen, WY Vonderhaar, BK Walker, AM TI Unmodified prolactin (PRL) and S179D PRL-initiated bioluminescence resonance energy transfer between homo- and hetero-pairs of long and short human PRL receptors in living human cells SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID OVINE PLACENTAL-LACTOGEN; BREAST-CANCER CELLS; GROWTH-HORMONE; ERYTHROPOIETIN RECEPTOR; SIGNAL-TRANSDUCTION; BINDING PROTEIN; EXPRESSION; IDENTIFICATION; DOMAIN; MILK AB We have used bioluminescence resonance energy transfer (BRET) to examine the interaction between human prolactins (PRLs) and the long (LF) and two short isoforms (SF1a and SF1b) of the human PRL receptor in living cells. cDNA sequences encoding the LF, SF1a, and SF1b were subcloned into codon-humanized vectors containing cDNAs for either Renilla reniformis luciferase (Rluc) or a green fluorescent protein (GFP(2)) with a 12- or 13-amino acid linker connecting the parts of the fusion proteins. Transfection into human embryonic kidney 293 cells demonstrated maintained function of Rluc and GFP2 when linked to the receptors, and confocal microscopy demonstrated the localization of tagged receptors in the plasma membrane by 48 h after transfection. All three tagged receptors transduced a signal, with the LF and SF1a stimulating, and SF1b inhibiting, promoter activity of an approximately 2.4-kb beta-casein-luc construct. Both unmodified PRL (U-PRL) and the molecular mimic of phosphorylated PRL, S179D PRL, induced BRET with all combinations of long and short receptor isoforms except SF1a plus SF1b. No BRET was observed with the site two-inactive mutant, G129R PRL. This is the first demonstration, 1) that species homologous PRL promotes both homo- and hetero-interaction of most long and short PRLR pairs in living cells, 2) that both U-PRL and S179D PRL are active in this regard, and 3) that there is some aspect of SF1a-SF1b structure that prevents this particular hetero-receptor pairing. In addition, we conclude that preferential pairing of different receptor isoforms is not the explanation for the different signaling initiated by U-PRL and S179D PRL. C1 Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. NCI, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. Clemson Univ, Oncol Res Inst, Greenville, SC 29605 USA. RP Walker, AM (reprint author), Univ Calif Riverside, Div Biomed Sci, Riverside, CA 92521 USA. EM Ameae.Walker@ucr.edu FU NIDDK NIH HHS [DK 61005, R01 DK061005] NR 40 TC 38 Z9 40 U1 0 U2 2 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 MAY PY 2005 VL 19 IS 5 BP 1291 EP 1303 DI 10.1210/me.2004-0304 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 920BY UT WOS:000228663900016 PM 15695371 ER PT J AU Tanpaiboon, P AF Tanpaiboon, P TI IEM digest SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID METHYLMALONIC ACIDEMIA; COMPLEMENTATION GROUP; GENE; IDENTIFICATION; TRANSPLANTATION; MANAGEMENT; METABOLISM; ACIDURIA; DEFECT C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Intramural Program, Off Rare Dis, Off Director, Bethesda, MD 20892 USA. RP Tanpaiboon, P (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM ptanpaib@mail.nih.gov NR 24 TC 19 Z9 19 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD MAY PY 2005 VL 85 IS 1 BP 2 EP 6 PG 5 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 925JO UT WOS:000229049600001 PM 15959932 ER PT J AU Swartz, CD Afshari, CA Yu, L Hall, KE Dixon, D AF Swartz, CD Afshari, CA Yu, L Hall, KE Dixon, D TI Estrogen-induced changes in IGF-I, Myb family and MAP kinase pathway genes in human uterine leiomyoma and normal uterine smooth muscle cell lines SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE A-myb; IGF-1; leiomyoma; microarray; MKP-1 ID TRANSFORMING GROWTH FACTOR-BETA-3; MESSENGER-RIBONUCLEIC-ACID; A-MYB; ADJACENT MYOMETRIUM; EXPRESSION PROFILE; HORMONE AGONIST; INSULIN; FIBROIDS; PROTEIN; RECEPTOR AB Many studies have implicated numerous hormones, growth factors, cytokines and other signal transduction molecules in the pathogenesis of uterine leiomyoma. Estrogen and estrogen-related genes are thought to play a key role in the growth of uterine leiomyomas, but the molecular mechanisms are unclear. In an attempt to investigate various pathways that might be involved in estrogen-regulated uterine leiomyoma growth as well as to identify any novel effector genes, microarray studies comparing estrogen-treated uterine leiomyoma cells (UtLM) and normal myometrial cells to untreated cells were performed. Several genes were differentially expressed in estrogen treated UtLM cells, including insulin-like growth factor-I (IGF-I) and others potentially involved in the IGF-I signalling pathway, specifically genes for A-myb, a transcription factor which promotes cell cycle progression and for MKP-1, a dual specificity phosphatase that dephosphorylates mitogen-activated protein kinase. IGF-I and A-myb were up-regulated in estrogen-treated cells while MKP-1 was down-regulated. Two other cell cycle promoting genes, c-fos and myc, were also down-regulated in estrogen treated UtLM cells. These genes are typically up-regulated in response to estrogen in some cells, notably breast epithelial cells, yet consistently have lower expression levels in uterine leiomyoma tissue when compared to autologous myometrium. Our results demonstrate some novel genes that may play a role in the growth of uterine leiomyoma, strengthen the case for involvement of the IGF-I pathway in the response of UtLM to estrogen and corroborate evidence that uterine smooth muscle cells respond to estrogen with a different gene expression pattern than that seen in epithelial cells. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Dixon, D (reprint author), NIEHS, Lab Expt Pathol, POB 12233,MD C2-09, Res Triangle Pk, NC 27709 USA. EM dixon@niehs.nih.gov NR 49 TC 49 Z9 53 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD MAY-JUN PY 2005 VL 11 IS 5-6 BP 441 EP 450 DI 10.1093/molehr/gah174 PG 10 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 949KV UT WOS:000230786200018 PM 15879465 ER PT J AU McCarron, JA Marchais-Oberwinkler, S Pike, VW Tarkiainen, J Halldin, C Sovago, J Gulyas, BZ Wikstrom, HV Farde, L AF McCarron, JA Marchais-Oberwinkler, S Pike, VW Tarkiainen, J Halldin, C Sovago, J Gulyas, BZ Wikstrom, HV Farde, L TI Two C-methyl derivatives of [C-11]WAY-100635 - Effects of an amido alpha-methyl group on metabolism and brain 5-HT1A receptor radioligand behavior in monkey SO MOLECULAR IMAGING AND BIOLOGY LA English DT Article DE 5-HT1A receptors; PET; radioligand; WAY-100635; alpha-methyl; metabolism; carbon-11 ID IN-VIVO; RADIOACTIVE METABOLITES; HUMAN PLASMA; PET; WAY-100635; BINDING; C-11; ANALOGS; WAY-100635; DELINEATION AB Purpose: [carbonyl-C-11]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl)-N-pyridinyl)cyclohexanecarboxamide ([carbonyl-C-11]WAY-100635) is an effective radioligand for imaging brain 5-HT1A receptors with positron emission tomography (PET). However, this radioligand has some drawbacks for deriving relative regional receptor densities, including rapid metabolism, which acts against accurate definition of an arterial input function for compartmental modeling, and very low nonspecific binding in brain, which detracts from the accuracy of modeling by a simplified reference tissue (cerebellum) approach. Here, in a search for a radioligand that overcomes these limitations, we investigated the effects of introducing a single methyl group at either of the carbon atoms alpha to the amide bond in [C-11]WAY-100635. Procedures: Ligands with a methyl group on the alpha carbon of the cyclohexyl group (SWAY) or the alpha carbon of the C2H4 linker ((R,S)-JWAY) were synthesized and tested for binding affinity and intrinsic activity at 5-HT1A receptors. SWAY was labeled with carbon-11 (t(1/2) = 20.4 minutes; beta(+) = 99.8%) in its O-methyl group and (R,S)-JWAY in its carbonyl group. Each radioligand was evaluated by PET experiments in cynomolgus monkey. Results: SWAY and (R,S)-JWAY were found to be high-affinity antagonists at 5-HT1A receptors. After injection of [C-11]SWAY into monkey, radioactivity uptake in brain reached a maximum of 3% at 4.5 minutes and decreased to 0.7% at 72 minutes. However, over the time span of the experiment, radioactivity concentrations in 5-HT1A receptor-rich brain regions were only fractionally higher than in cerebellum. Radioactivity represented by parent radioligand in plasma was 39% at 45 minutes. After injection of [C-11](R,S)-JWAY alone, radioactivity uptake in brain reached a maximum of 4.8% at 2.5 minutes and decreased to 1.2% at 90 minutes. At this time, radioactivity concentration in 5-HT1A receptor-rich brain regions was markedly greater than in cerebellum. In another PET experiment, the monkey was predosed with WAY-100635 before [C-11](R,S)-JWAY injection. At 90 minutes after injection, the ratio of radioactivity in 5-HT1A receptor-rich regions to that in cerebellum was reduced to near unity. Radioactivity represented by parent radioligand in plasma was 12% at 45 minutes. Conclusions: [C-11](R,S)-JWAY, but not [C-11]SWAY, gives a sizeable 5-HT1A receptor-selective PET signal in monkey. The presence of a C-methyl group adjacent to the amide bond in SWAY or (R,S)-JWAY fails to counter metabolism. C1 Hammersmith Hosp, Imperial Coll Sch Med, MRC Cyclotron Unit, London W12 0NN, England. Univ Groningen, Univ Ctr Pharm, Dept Med Chem, NL-9713 AV Groningen, Netherlands. Karolinska Inst, Karolinska Hosp, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. RP McCarron, JA (reprint author), NIMH, PET Radiopharmaceut Sci Sect, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM mccarronj@intra.nimh.nih.gov RI Sovago, Judit/G-7961-2011; Gulyas, Balazs/F-9508-2015 NR 38 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD MAY-JUN PY 2005 VL 7 IS 3 BP 209 EP 219 DI 10.1007/s11307-005-4127-5 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 936FB UT WOS:000229839800004 PM 15912425 ER PT J AU Hansen, AM Qiu, Y Yeh, N Blattner, FR Durfee, T Jin, DJ AF Hansen, AM Qiu, Y Yeh, N Blattner, FR Durfee, T Jin, DJ TI SspA is required for acid resistance in stationary phase by downregulation of H-NS in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Review ID NUCLEOID-ASSOCIATED PROTEIN; DNA-BINDING PROTEIN; GLUTAMATE-DECARBOXYLASE GENES; STRINGENT STARVATION PROTEIN; SIGMA-FACTOR SIGMA(S); SMALL RNA REGULATORS; VIBRIO-CHOLERAE; CURVED DNA; SHIGELLA-FLEXNERI; RPOS TRANSLATION AB The stringent starvation protein A (SspA) is a RNA polymerase-associated protein and is required for transcriptional activation of bacteriophage P1 late promoters. However, the role of SspA in gene expression in Escherichia coli is essentially unknown. In this work, we show that SspA is essential for cell survival during acid-induced stress. Apparently, SspA inhibits stationary-phase accumulation of H-NS, a global regulator which functions mostly as a repressor, thereby derepressing multiple stress defence systems including those for acid stress and nutrient starvation. Consequently, the gene expression pattern of the H-NS regulon is altered in the sspA mutant, leading to acid-sensitive and hypermotile phenotypes. Thus, our study indicates that SspA is a global regulator, which acts upstream of H-NS, and thereby plays an important role in the stress response of E. coli during stationary phase. In addition, our results indicate that the expression of the H-NS regulon is sensitive to small changes in the cellular level of H-NS, enabling the cell to response rapidly to environment cues. As SspA and H-NS are highly conserved among Gram-negative bacteria, of which many are pathogenic, the global role of SspA in the stress response and pathogenesis is discussed. C1 NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. Univ So Denmark Odense Univ, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. RP Jin, DJ (reprint author), NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Bldg 469,POB B, Frederick, MD 21702 USA. EM djjin@helix.nih.gov FU NIGMS NIH HHS [GM35682] NR 104 TC 42 Z9 42 U1 1 U2 9 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2005 VL 56 IS 3 BP 719 EP 734 DI 10.1111/j.1365-2958.2005.04567.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 913UM UT WOS:000228179100013 PM 15819627 ER PT J AU Winther-Larsen, HC Wolfgang, M Dunham, S van Putten, JPM Dorward, D Lovold, C Aas, FE Koomey, M AF Winther-Larsen, HC Wolfgang, M Dunham, S van Putten, JPM Dorward, D Lovold, C Aas, FE Koomey, M TI A conserved set of pilin-like molecules controls type IV pilus dynamics and organelle-associated functions in Neisseria gonorrhoeae SO MOLECULAR MICROBIOLOGY LA English DT Article ID EPITHELIAL-CELL ADHERENCE; PSEUDOMONAS-AERUGINOSA; TWITCHING MOTILITY; NATURAL TRANSFORMATION; FIMBRIAL BIOGENESIS; PROTEIN-SECRETION; ESCHERICHIA-COLI; PATHOGENIC NEISSERIAE; SURFACE MOTILITY; DNA-BINDING AB Type IV pili (Tfp) play central roles in prokaryotic cell biology and disease pathogenesis. As dynamic filamentous polymers, they undergo rounds of extension and retraction modelled as pilin subunit polymerization and depolymerization events. Currently, the molecular mechanisms and components influencing Tfp dynamics remain poorly understood. Using Neisseria gonorrhoeae as a model system, we show that mutants lacking any one of a set of five proteins sharing structural similarity to the pilus subunit are dramatically reduced in Tfp expression and that these defects are suppressed in the absence of the PilT pilus retraction protein. Thus, these molecules are not canonical assembly factors but rather act as effectors of pilus homeostasis by promoting extension/polymerization events in the presence of PilT. Furthermore, localization studies support the conclusion that these molecules form a Tfp-associated complex and influence levels of PilC, the epithelial cell adhesin, in Tfp-enriched shear fractions. This is the first time that the step at which individual pilin-like proteins impact on Tfp expression has been defined. The findings have important implications for understanding Tfp dynamics and fundamental Tfp structure/function relationships. C1 Univ Oslo, Ctr Mol Biol & Neurosci, N-0316 Oslo, Norway. Univ Oslo, Dept Mol Biosci, N-0316 Oslo, Norway. Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Pfizer Global Res & Dev, Antibacteria Mol Sci, Ann Arbor, MI 48105 USA. Univ Utrecht, Dept Immunol & Infect Dis, NL-3584 CL Utrecht, Netherlands. NIAID, Microscopy Branch, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA. RP Koomey, M (reprint author), Univ Oslo, Ctr Mol Biol & Neurosci, N-0316 Oslo, Norway. EM johnk@biotek.uio.no OI van Putten, Jos/0000-0002-4126-8172 NR 56 TC 79 Z9 80 U1 0 U2 4 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2005 VL 56 IS 4 BP 903 EP 917 DI 10.1111/j.1365-2958.2005.04591.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 925RN UT WOS:000229071100005 PM 15853879 ER PT J AU Vinella, D Albrecht, C Cashel, M D'Ari, R AF Vinella, D Albrecht, C Cashel, M D'Ari, R TI Iron limitation induces SpoT-dependent accumulation of ppGpp in Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID PENICILLIN-BINDING PROTEIN-2; GROWTH-RATE CONTROL; GUANOSINE TETRAPHOSPHATE; HELICOBACTER-PYLORI; STRINGENT RESPONSE; METABOLISM; TRANSCRIPTION; EXPRESSION; STARVATION; DIVISION AB In Escherichia coli the P-lactam mecillinam specifically inhibits penicillin-binding protein 2 (PBP2), a peptidoglycan transpeptidase essential for maintaining rod shape. We have previously shown that PBP2 inactivation results in a cell division block and that an increased concentration of the nucleotide ppGpp, effector of the RelA-dependent stringent response, confers mecillinam resistance and allows cells to divide as spheres in the absence of PBP2 activity. In this study we have characterized an insertion mutation which confers mecillinam resistance in wild-type and &UDelta; relA strains but not in &UDelta; relA &UDelta; spoT strains, devoid of ppGpp. The mutant has an insertion in the fes gene, coding for enterochelin esterase. This cytoplasmic enzyme hydrolyses enterochelin-Fe3+ complexes, making the scavenged iron available to the cells. We show that inactivation of the fes gene causes iron limitation on rich medium plates and a parallel SpoT-dependent increase of the ppGpp pool, as judged by the induction of the iron-regulated fiu::lacZ fusion and the repression of the stringently controlled P1(rrnB)::lacZ fusion respectively. We further show, by direct ppGpp assays, that iron starvation in liquid medium produces a SpoT-dependent increase of the ppGpp pool, strongly suggesting a role for iron in the balance of the two activities of SpoT, synthesis and hydrolysis of (p)ppGpp. Finally, we present evidence that ppGpp exerts direct or indirect positive control on iron uptake, suggesting a simple homeostatic regulatory circuit: iron limitation leads to an increased ppGpp pool, which increases the expression of iron uptake genes, thereby alleviating the limitation. C1 Univ Paris 07, Univ Paris 06, CNRS, Inst Jacques Monod, F-75251 Paris, France. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Vinella, D (reprint author), Univ Paris 07, Univ Paris 06, CNRS, Inst Jacques Monod, 2 Pl Jussieu, F-75251 Paris, France. EM vinella@ijm.jussieu.fr RI vinella, daniel/G-5504-2012 NR 47 TC 90 Z9 92 U1 0 U2 11 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2005 VL 56 IS 4 BP 958 EP 970 DI 10.1111/j.1365-2958.2005.04601.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 925RN UT WOS:000229071100009 PM 15853883 ER PT J AU Calcagno, AM Fostel, JN Orchekowski, RP Alston, JT Mattes, WB Siahaan, TJ Ware, JA AF Calcagno, Anna Maria Fostel, Jennifer N. Orchekowski, Randal P. Alston, James T. Mattes, William B. Siahaan, Teruna J. Ware, Joseph A. TI Modulation of cell adhesion molecules in various epithelial cell lines after treatment with PP2 SO MOLECULAR PHARMACEUTICS LA English DT Article DE E-cadherin; paracellular drug delivery; adhesion molecules; epithelial cells; PP2; SRC inhibitors AB Regulation and expression of E-cadherin and other adhesion molecules were evaluated after exposure to a selective inhibitor of the Src family of tyrosine kinases and inducer of E-cadherin, PP2. E-cadherin is located within the intercellular junction, and it is involved in the management of paracellular permeability of various epithelial barriers in the body. Epithelial cell lines HCT-116, HT29, Caco-2, LS174T, and ARPE-19 were examined for morphological, functional, protein, and mRNA changes following 20 mu M PP2 treatment. PP2 treatment caused cell clustering in Caco-2, HT29, and HCT-116 cells. E-cadherin also redistributed to the points of cell contact in Caco-2 cells. These changes suggest increased E-cadherin-dependent cell adhesion. Studies evaluating transepithelial electrical resistance, an established measurement of paracellular permeability, displayed increases in resistance for the Caco-2 cells following PP2 treatment, which correlates with our microscopy data. In addition, E-cadherin protein levels increased for all cells except HCT-116. ARPE-19 cells did not express E-cadherin at the protein or m RNA level. Expression of adhesion molecules varied for the cell lines, and only Claudin 3 mRNA expression was significantly increased in the three intestinal cell lines treated with PP2. Overall, our data suggest that E-cadherin is positively regulated by inhibition of Src tyrosine kinases at the functional and protein expression levels within these epithelial cell lines. C1 [Fostel, Jennifer N.; Orchekowski, Randal P.; Alston, James T.; Mattes, William B.; Ware, Joseph A.] Pharmacia Corp, Kalamazoo, MI 49007 USA. [Calcagno, Anna Maria; Siahaan, Teruna J.] Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA. RP Calcagno, AM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2120,37 Convent Dr,MSC4256, Bethesda, MD 20892 USA. EM calcagno@mail.nih.gov RI Calcagno, Anna Maria/A-5617-2012; OI Calcagno, Anna Maria/0000-0002-0804-2753 FU NIBIB NIH HHS [EB-00226]; NIGMS NIH HHS [GM-08359] NR 42 TC 7 Z9 8 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD MAY-JUN PY 2005 VL 2 IS 3 BP 170 EP 184 DI 10.1021/mp0499003 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JC UT WOS:000203538800002 PM 15934778 ER PT J AU Daelemans, D Pannecouque, C Pavlakis, GN Tabarrini, O De Clercq, E AF Daelemans, D Pannecouque, C Pavlakis, GN Tabarrini, O De Clercq, E TI A novel and efficient approach to discriminate between pre- and post-transcription HIV inhibitors SO MOLECULAR PHARMACOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GREEN FLUORESCENT PROTEIN; VIRAL MESSENGER-RNA; SELECTIVE-INHIBITION; ANTIVIRAL COMPOUNDS; DEXTRAN SULFATE; REPLICATION; CELLS; DERIVATIVES; MECHANISM AB Established anti-human immunodeficiency virus (HIV) treatments are not always effective or well tolerated, highlighting the need for further refinement of antiviral drug design and development. Given the multitude of molecular targets with which the anti-HIV agents can interact, studies on the mechanism of action of newly discovered HIV inhibitors are quite elaborate. In this article, we describe the use of an efficient reporter system allowing rapid discrimination between a pre- or post-transcriptional mode of action of anti-HIV compounds based on infection by a replication competent HIV-1 molecular clone expressing the green fluorescent protein as part of the nef multiply spliced RNA. Using fluorescence microscopy and flow cytometry, this system enabled us to differentiate between compounds acting at a pre- or post-transciptional level of the virus life cycle. Antiviral activities were determined for four reference compounds as well as one putative novel HIV inhibitor. The results obtained were in agreement with the known characteristics of the reference compounds and revealed that the novel compound interfered with a target before or overlapping with HIV transcription. We showed that during a single replication cycle, compounds inhibiting a molecular target occurring before or coinciding with HIV transcription suppressed GFP expression, whereas compounds interfering at a later stage ( such as protease inhibitors, which act after transcription) did not inhibit GFP expression. This GFP-based reporter system is adaptable for high-throughput screening. C1 Katholieke Univ Leuven, Rega Inst Med Res, B-3000 Louvain, Belgium. NCI, Human Retrovirus Sect, Frederick, MD 21701 USA. Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06100 Perugia, Italy. RP Daelemans, D (reprint author), Katholieke Univ Leuven, Rega Inst Med Res, Minderbroedersstr 10, B-3000 Louvain, Belgium. EM dirk.daelemans@rega.kuleuven.ac.be OI Tabarrini, Oriana/0000-0003-2693-5675 NR 37 TC 16 Z9 16 U1 0 U2 1 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 MAY PY 2005 VL 67 IS 5 BP 1574 EP 1580 DI 10.1124/mol.104.010249 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916MA UT WOS:000228387900024 PM 15728798 ER PT J AU Rapoport, JL Addington, AM Frangou, S Psych, M AF Rapoport, JL Addington, AM Frangou, S Psych, M TI The neurodevelopmental model of schizophrenia: update 2005 SO MOLECULAR PSYCHIATRY LA English DT Review DE neurodevelopment; schizophrenia; brain imaging; gene expression; genetics of development; 22q11DS ID CHILDHOOD-ONSET SCHIZOPHRENIA; COMPARATIVE GENOMIC HYBRIDIZATION; GLUTAMIC-ACID DECARBOXYLASE; CARDIO-FACIAL SYNDROME; 22Q11 DELETION SYNDROME; DUTCH-HUNGER-WINTER; GRAY-MATTER VOLUME; GENE-EXPRESSION; BRAIN-DEVELOPMENT; TEMPORAL-LOBE AB Neurodevelopmental models of schizophrenia that identify longitudinal precursors of illness have been of great heuristic importance focusing most etiologic research over the past two decades. These models have varied considerably with respect to specificity and timing of hypothesized genetic and environmental 'hits', but have largely focused on insults to prenatal brain development. With heritability around 80%, nongenetic factors impairing development must also be part of the model, and any model must also account for the wide range of age of onset. In recent years, longitudinal brain imaging studies of both early and adult (to distinguish from late ie elderly) onset populations indicate that progressive brain changes are more dynamic than previously thought, with gray matter volume loss particularly striking in adolescence and appearing to be an exaggeration of the normal developmental pattern. This supports an extended time period of abnormal neurodevelopment in schizophrenia in addition to earlier 'lesions'. Many subtle cognitive, motor, and behavioral deviations are seen years before illness onset, and these are more prominent in early onset cases. Moreover, schizophrenia susceptibility genes and chromosomal abnormalities, particularly as examined for early onset populations (ie GAD1, 22q11DS), are associated with premorbid neurodevelopmental abnormalities. Several candidate genes for schizophrenia (eg dysbindin) are associated with lower cognitive abilities in both schizophrenic and other pediatric populations more generally. Postmortem human brain and developmental animal studies document multiple and diverse effects of developmental genes (including schizophrenia susceptibility genes), at sequential stages of brain development. These may underlie the broad array of premorbid cognitive and behavioral abnormalities seen in schizophrenia, and neurodevelopmental disorders more generally. Increased specificity for the most relevant environmental risk factors such as exposure to prenatal infection, and their interaction with susceptibility genes and/or action through phase-specific altered gene expression now both strengthen and modify the neurodevelopmental theory of schizophrenia. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, Sect Neurobiol Psychosis, London WC2R 2LS, England. RP Rapoport, JL (reprint author), Bldg 10,Room 3N202,10 Ctr Dr,MSC 1600, Bethesda, MD 20892 USA. EM rapoport@helix.nih.gov RI Frangou, Sophia/A-2672-2013 NR 181 TC 515 Z9 534 U1 12 U2 89 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD MAY PY 2005 VL 10 IS 5 BP 434 EP 449 DI 10.1038/sj.mp.4001642 PG 16 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 920LZ UT WOS:000228692300006 PM 15700048 ER PT J AU Butefisch, CM Boroojerdi, B Chen, R Battaglia, F Hallett, M AF Butefisch, CM Boroojerdi, B Chen, R Battaglia, F Hallett, M TI Task-dependent intracortical inhibition is impaired in focal hand dystonia SO MOVEMENT DISORDERS LA English DT Article DE dystonia; transcranial magnetic stimulation; intracortical inhibition ID TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; WRITERS CRAMP; RECIPROCAL INHIBITION; SPASMODIC TORTICOLLIS; PARKINSONS-DISEASE; EXCITABILITY; MUSCLES; BRAIN; HEMIDYSTONIA AB We tested whether task-dependent modulation of inhibition within the motor cortex is impaired in patients with dystonia. Paired-pulse transcranial magnetic stimulation (TMS) at an interstimulus interval of 2 msec was used to measure the effect of two different tasks on short ISI intracortical inhibition (SICI) in dystonic and normal subjects. In two experiments, SICI of the fourth dorsal interosseus (4DIO) and abductor pollicis brevis (APB) muscles were measured before and at the end of the training task. In the first experiment, subjects performed a nonselective task consisting of abducting the thumb, where the APB acted as agonist and the 4DIO as synergist. In the second experiment, the function of the 4DIO was changed as the subjects were asked to consciously inhibit this muscle while abducting the thumb (selective task). Therefore, while the APB was activated in both tasks, the 4DIO was activated in the nonselective task but was in the inhibitory surround in the selective task. We found that performance of the selective but not the nonselective task resulted in increased SICI in the 4DIO of normal but not in dystonic subjects. We conclude that task-dependent SICI is disturbed in patients with dystonia. © 2005 Movement Disorder Society. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Inst Univ Dusseldorf, Neurol Therapiecentrum, Dusseldorf, Germany. Univ Toronto, Univ Hlth Network, Toronto Western Hosp, Div Neurol, Toronto, ON, Canada. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 FU Intramural NIH HHS [Z99 NS999999] NR 33 TC 44 Z9 45 U1 0 U2 4 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 MAY PY 2005 VL 20 IS 5 BP 545 EP 551 DI 10.1002/mds.20367 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 926NJ UT WOS:000229129600003 PM 15641012 ER PT J AU Puccioni-Sohler, M Papais-Alvarenga, R de Souza, PM de Franca, SC Goncalves, RR Jacobson, S AF Puccioni-Sohler, M Papais-Alvarenga, R de Souza, PM de Franca, SC Goncalves, RR Jacobson, S TI Parkinsonism in the course of HTLV-I-associated myelopathy SO MOVEMENT DISORDERS LA English DT Article DE Parkinson syndrome; HAM/TSP; HTLV-I; CSF ID CENTRAL-NERVOUS-SYSTEM; ENCEPHALOPATHY; INFECTION; HAM/TSP; DISEASE AB Parkinsonian syndromes may represent a complication of viral infection. Human T cell lymphotropic virus I (HTLV-I) is a cause of a chronic myelopathy in which encephalic involvement has been also found. We report on the case of a 60-year-old man with HTLV-I-associated myelopathy, complicated with bradykinesia, resting tremor, and cogwheel rigidity. These findings suggest that parkinsonian features may represent a neurological disorder associated with HTLV-I infection. © 2005 Movement Disorder Society. C1 Univ Fed Rio de Janeiro, Neurol Serv, ESP Hosp Univ Gaffree Guinle, HUGG UniRio, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Cerebrospinal Fluid Lab, HUCFF, Rio De Janeiro, Brazil. Cerebrospinal Fluid Neurolife Lab, Rio De Janeiro, Brazil. NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Puccioni-Sohler, M (reprint author), Rua Zenove Fevereiro 185-705, BR-2280030 Rio De Janeiro, RJ, Brazil. EM mpuccioni@hucff.ufrj.br NR 16 TC 2 Z9 2 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD MAY PY 2005 VL 20 IS 5 BP 613 EP 615 DI 10.1002/mds.20402 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 926NJ UT WOS:000229129600013 PM 15726580 ER PT J AU Bischoff, JF Chaverri, P White, JF AF Bischoff, JF Chaverri, P White, JF TI Clarification of the host substrate of Ascopolyporus and description of Ascopolyporus philodendrus sp nov. SO MYCOLOGIA LA English DT Article DE Cordyceps; endophyte; entomopathogen; epibiont; Hyperdermium; Lecanicillium; scale insect; Torrubiella ID DNA; IDENTIFICATION; MODEL AB During a recent collection trip to Barro Colorado Island, Panama, two species belonging to genus Ascopolyporus (Clavicipitaceae, Hypocreales) were collected. Species of Ascopolyporus are epibionts of their bamboo (Poaceae) host and long thought to be biotrophs of their plant hosts. However, based on morphological observations and phylogenetic evidence using large subunit ribosomal DNA data, we propose that genus Ascopolyporus is likely composed of pathogens of scale insects (Coccoideae, Homoptera). Phylogenetic analyses included Ascopolyporus spp. in a clade containing only entomopathogenic clavicipitaceous species (100% posterior probability), and the scale insect pathogen Hyperdermium bertonii was found to share the most recent common ancestor with the Ascopolyporus clade (98% posterior probability). In addition remnants of the scale insect were observed to be embedded within stromata during early stages of stroma development. Ascopolyporus philodendrus sp. nov. was described and distinguished from the type species of the genus, A. polychrous, based on perithecial size, ascus size, plant host substrate and phylogenetic evidence. Furthermore subfamily Clavicipitoideae (Clavicipitaceae) was included and well supported in a single clade (100% posterior probability). C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. USDA, Systemat Bot & Mycol Lab, Beltsville, MD 20705 USA. Rutgers State Univ, Cook Coll, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. RP Bischoff, JF (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM bischoff@ncbi.nlm.nih.gov RI White, James/C-2280-2009; OI Chaverri, Priscila/0000-0002-8486-6033 NR 24 TC 8 Z9 8 U1 0 U2 2 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD MAY-JUN PY 2005 VL 97 IS 3 BP 710 EP 717 DI 10.3852/mycologia.97.3.710 PG 8 WC Mycology SC Mycology GA 969FE UT WOS:000232218200015 PM 16392258 ER PT J AU Teng, JL Rai, T Tanaka, Y Takei, Y Nakata, T Hirasawa, M Kulkarni, AB Hirokawa, N AF Teng, JL Rai, T Tanaka, Y Takei, Y Nakata, T Hirasawa, M Kulkarni, AB Hirokawa, N TI The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium SO NATURE CELL BIOLOGY LA English DT Article ID KINESIN SUPERFAMILY PROTEIN; LEFT-RIGHT ASYMMETRY; CYCLIN D1; ORGANELLE TRANSPORT; CRE RECOMBINASE; EXPRESSION; MECHANISM; COMPLEX; CANCER; BRAIN AB In the developing brain, the organization of the neuroepithelium is maintained by a critical balance between proliferation and cell - cell adhesion of neural progenitor cells. The molecular mechanisms that underlie this are still largely unknown. Here, through analysis of a conditional knockout mouse for the Kap3 gene, we show that post-Golgi transport of N-cadherin by the KIF3 molecular motor complex is crucial for maintaining this balance. N-cadherin and β-catenin associate with the KIF3 complex by co-immunoprecipitation, and colocalize with KIF3 in cells. Furthermore, in KAP3-deficient cells, the subcellular localization of N-cadherin was disrupted. Taken together, these results suggest a potential tumour-suppressing activity for this molecular motor. C1 Univ Tokyo, Grad Sch Med, Dept Cell Biol & Anat, Bunkyo Ku, Tokyo 1130033, Japan. Natl Inst Dent & Craniofacial Res, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Hirokawa, N (reprint author), Univ Tokyo, Grad Sch Med, Dept Cell Biol & Anat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan. EM hirokawa@m.u-tokyo.ac.jp RI Takei, Yosuke/I-1828-2015 OI Takei, Yosuke/0000-0002-5026-8027 NR 50 TC 94 Z9 98 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 MAY PY 2005 VL 7 IS 5 BP 474 EP U31 DI 10.1038/ncb1249 PG 11 WC Cell Biology SC Cell Biology GA 926LA UT WOS:000229123500014 PM 15834408 ER PT J AU Paik, S Kim, CY Song, YK Kim, WS AF Paik, S Kim, CY Song, YK Kim, WS TI Technology Insight: application of molecular techniques to formalin-fixed paraffin-embedded tissues from breast cancer SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Review DE real-time reverse-transcriptase polymerase chain reaction (RT-PCR); breast cancer; formalin-fixed paraffin-embedded tissue; gene-expression profiling; primers ID GENE-EXPRESSION PATTERNS; RNA; MICROARRAY; TAMOXIFEN; TUMORS; ASSAY AB Breast cancer is a heterogenous disease in terms of both clinical behavior and molecular characteristics. To develop prognostic and predictive markers for breast cancer, it would be useful to be able to analyze formalin-fixed paraffin-embedded tissue (FPET) collected and banked from completed clinical trials. RNAs extracted from FPETs are chemically modified and fragmented, and are therefore not ideal substrates for gene-expression profiling assays. However, methods are being developed to optimize the use of such RNAs for high-throughput gene expression profiling assays. For microarray analysis, existing methods may be adequate for fresh FPET, but they do not work well with older FPET. For older samples, real-time reverse transcription-polymerase chain reaction is the method of choice for gene-expression profiling. C1 Natl Surg Adjuvant Breast & Bowel Project Fdn, Div Pathol, Mol Pathol Lab, Pittsburgh, PA 15212 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. KonKuk Univ Hosp, Dept Pathol, Seoul, South Korea. RP Paik, S (reprint author), Natl Surg Adjuvant Breast & Bowel Project Fdn, Div Pathol, Mol Pathol Lab, 4 Allegheny Ctr 5th Floor,E Commons Profess Bldg, Pittsburgh, PA 15212 USA. EM soon.paik@nsabp.org OI Paik, Soonmyung/0000-0001-9688-6480 FU NCI NIH HHS [U10CA12027] NR 17 TC 61 Z9 63 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD MAY PY 2005 VL 2 IS 5 BP 246 EP 254 DI 10.1038/ncponc0171 PG 9 WC Oncology SC Oncology GA 932ZT UT WOS:000229594200010 PM 16264960 ER PT J AU Grubb, RL Choyke, PL Pinto, PA Linehan, WM Walther, MM AF Grubb, RL Choyke, PL Pinto, PA Linehan, WM Walther, MM TI Management of von Hippel-Lindau-associated kidney cancer SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Review DE kidney neoplasm; nephrectomy; radiofrequency ablation; von Hippel-Lindau (VHL); nephron-sparing surgery ID RENAL-CELL CARCINOMA; TUMOR-SUPPRESSOR GENE; PARENCHYMAL SPARING SURGERY; GUIDED RADIOFREQUENCY ABLATION; RADIO-FREQUENCY ABLATION; INTRAOPERATIVE ULTRASOUND; 10-YEAR EXPERIENCE; DISEASE; MUTATIONS; FAMILIES AB VonHippel-Lindau disease (VHL) is an autosomal-dominant inherited condition that predisposes patients to develop renal cysts and tumors, most commonly in the second to fourth decades of life. Renal cysts and tumors have historically been a major cause of disease-related morbidity and mortality, so urologists are often called on to manage patients with VHL. Knowledge of the extrarenal manifestations of VHL (hemangioblastomas of the central nervous system and retina, endolymphatic sac tumors, pancreatic cysts, epididymal and broad-ligament cysts, and pheochromocytomas) and integration of nonurologic specialties into management teams for VHL patients will help to achieve successful outcomes. Screening for renal manifestations of VHL, by regular imaging of the abdomen, begins late in the second decade of life. Because renal tumors in VHL can be multifocal and bilateral, management can be complex. Radical nephrectomy removes all tissue at risk for forming renal tumors; however, this necessitates renal replacement therapy. In an effort to control cancer effectively while preserving native renal function and minimizing intervention, some researchers have proposed an observational strategy. Patients are screened until the largest tumor reaches 3 cm in diameter, at which time operative intervention is recommended. Nephron-sparing surgery is undertaken, whenever technically feasible, with the goal of removing all tumors in that renal unit. The role of minimally invasive technologies is currently being evaluated in selected patients with VHL renal masses. Elucidation of molecular pathways associated with VHL renal tumors may facilitate development of effective medical treatments for these lesions in the future. C1 NCI, Urol Oncol Branch, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Mol Imaging Program, NIH, Bldg 10,CRC,Room 1W-5940,10 Ctr Dr,MSC 1107, Bethesda, MD 20892 USA. EM uob@mail.nih.gov NR 49 TC 23 Z9 25 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD MAY PY 2005 VL 2 IS 5 BP 248 EP 255 DI 10.1038/ncpuro0179 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 932ZB UT WOS:000229592200011 PM 16474836 ER PT J AU Adams, DJ Dermitzakis, ET Cox, T Smith, J Davies, R Banerjee, R Bonfield, J Mullikin, JC Chung, YJ Rogers, J Bradley, A AF Adams, DJ Dermitzakis, ET Cox, T Smith, J Davies, R Banerjee, R Bonfield, J Mullikin, JC Chung, YJ Rogers, J Bradley, A TI Complex haplotypes, copy number polymorphisms and coding variation in two recently divergent mouse strains SO NATURE GENETICS LA English DT Article ID INBRED STRAINS; GENOME; MICE; EVOLUTION; MUTATIONS; DISCOVERY; GENES AB Inbred mouse strains provide the foundation for mouse genetics. By selecting for phenotypic features of interest, inbreeding drives genomic evolution and eliminates individual variation, while fixing certain sets of alleles that are responsible for the trait characteristics of the strain. Mouse strains 129Sv (129S5) and C57BL/6J, two of the most widely used inbred lines, diverged from common ancestors within the last century(1-5), yet very little is known about the genomic differences between them. By comparative genomic hybridization and sequence analysis of 129S5 short insert libraries, we identified substantial structural variation, a complex fine-scale haplotype pattern with a continuous distribution of diversity blocks, and extensive nucleotide variation, including nonsynonymous coding SNPs and stop codons. Collectively, these genomic changes denote the level and direction of allele fixation that has occurred during inbreeding and provide a basis for defining what makes these mouse strains unique. C1 Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. NHGRI, Bethesda, MD 20892 USA. RP Bradley, A (reprint author), Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. EM abradley@sanger.ac.uk RI Dermitzakis, Emmanouil/B-7687-2013; OI Bonfield, James/0000-0002-6447-4112; Smith, James/0000-0002-0445-8305 NR 28 TC 50 Z9 51 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD MAY PY 2005 VL 37 IS 5 BP 532 EP 536 DI 10.1038/ng1551 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 922TU UT WOS:000228862300024 PM 15852006 ER PT J AU Safford, M Collins, S Lutz, MA Allen, A Huang, CT Kowalski, J Blackford, A Horton, MR Drake, C Schwartz, RH Powell, JD AF Safford, M Collins, S Lutz, MA Allen, A Huang, CT Kowalski, J Blackford, A Horton, MR Drake, C Schwartz, RH Powell, JD TI Egr-2 and Egr-3 are negative regulators of T cell activation SO NATURE IMMUNOLOGY LA English DT Article ID E3 UBIQUITIN LIGASE; IN-VIVO; TRANSCRIPTION FACTOR; TOLERANCE INDUCTION; ANERGY INDUCTION; CLONAL ANERGY; FAS LIGAND; EXPRESSION; GENE; CD28 AB T cell receptor engagement in the absence of proper accessory signals leads to T cell anergy. E3 ligases are involved in maintaining the anergic state. However, the specific molecules responsible for the induction of anergy have yet to be elucidated. Using microarray analysis we have identified here early growth response gene 2 (Egr- 2) and Egr- 3 as key negative regulators of T cell activation. Overexpression of Egr2 and Egr3 was associated with an increase in the E3 ubiquitin ligase Cbl-b and inhibition of T cell activation. Conversely, T cells from Egr3(-/-) mice had lower expression of Cbl-b and were resistant to in vivo peptide-induced tolerance. These data support the idea that Egr-2 and Egr-3 are involved in promoting a T cell receptor-induced negative regulatory genetic program. C1 Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Care Ctr, Baltimore, MD 21205 USA. Chang Gung Univ, Sch Med & Hosp, Taipei, Taiwan. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Powell, JD (reprint author), Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Care Ctr, Baltimore, MD 21205 USA. EM poweljo@jhmi.edu RI Chuang, shengHao/C-8217-2012 FU NCI NIH HHS [R01 CA098109-02] NR 32 TC 223 Z9 230 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD MAY PY 2005 VL 6 IS 5 BP 472 EP 480 DI 10.1038/ni1193 PG 9 WC Immunology SC Immunology GA 919RC UT WOS:000228634300019 PM 15834410 ER PT J AU Irizarry, RA Warren, D Spencer, F Kim, IF Biswal, S Frank, BC Gabrielson, E Garcia, JGN Geoghegan, J Germino, G Griffin, C Hilmer, SC Hoffman, E Jedlicka, AE Kawasaki, E Martinez-Murillo, F Morsberger, L Lee, H Petersen, D Quackenbush, J Scott, A Wilson, M Yang, YQ Ye, SQ Yu, W AF Irizarry, RA Warren, D Spencer, F Kim, IF Biswal, S Frank, BC Gabrielson, E Garcia, JGN Geoghegan, J Germino, G Griffin, C Hilmer, SC Hoffman, E Jedlicka, AE Kawasaki, E Martinez-Murillo, F Morsberger, L Lee, H Petersen, D Quackenbush, J Scott, A Wilson, M Yang, YQ Ye, SQ Yu, W TI Multiple-laboratory comparison of microarray platforms SO NATURE METHODS LA English DT Article ID OLIGONUCLEOTIDE AB Microarray technology is a powerful tool for measuring RNA expression for thousands of genes at once. Various studies have been published comparing competing platforms with mixed results: some find agreement, others do not. As the number of researchers starting to use microarrays and the number of cross-platform meta-analysis studies rapidly increases, appropriate platform assessments become more important. Here we present results from a comparison study that offers important improvements over those previously described in the literature. In particular, we noticed that none of the previously published papers consider differences between tabs. For this study, a consortium of ten laboratories from the Washington, DC-Baltimore, USA, area was formed to compare data obtained from three widely used platforms using identical RNA samples. We used appropriate statistical analysis to demonstrate that there are relatively large differences in data obtained in tabs using the same platform, but that the results from the best-performing tabs agree rather well. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Surg, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, JHU, NIDDK,Gene Profiling Ctr, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. Inst Gen Res, Gaithersburg, MD 20878 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA. NCIs Microarray Core Facil, Ctr Adv Technol, Gaithersburg, MD 20877 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. George Washington Univ, Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20052 USA. Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. NIAID, Res Technol Branch, DIR, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21231 USA. RP Irizarry, RA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. EM rafa@jhu.edu RI Garcia, Joe/E-8862-2010; OI Germino, Gregory/0000-0002-3609-5588 FU NIDDK NIH HHS [U24DK58757] NR 15 TC 558 Z9 582 U1 3 U2 25 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 MAY PY 2005 VL 2 IS 5 BP 345 EP 349 DI 10.1038/nmeth756 PG 5 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 921UH UT WOS:000228790200012 PM 15846361 ER PT J AU Spiegel, A Nabel, E Volkow, N Landis, S Li, TK AF Spiegel, A Nabel, E Volkow, N Landis, S Li, TK TI Obesity on the brain SO NATURE NEUROSCIENCE LA English DT Editorial Material C1 NIDDKD, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NIAAA, Bethesda, MD 20892 USA. RP Spiegel, A (reprint author), NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 17 Z9 19 U1 3 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2005 VL 8 IS 5 BP 552 EP 553 DI 10.1038/nn0505-552 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 923FM UT WOS:000228895100011 PM 15856061 ER PT J AU Volkow, ND Wise, RA AF Volkow, ND Wise, RA TI How can drug addiction help us understand obesity? SO NATURE NEUROSCIENCE LA English DT Editorial Material ID CORTICOTROPIN-RELEASING FACTOR; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; ORBITOFRONTAL CORTEX; ENERGY-BALANCE; BRAIN DOPAMINE; FOOD-STIMULI; COCAINE; RATS; DEPENDENCE C1 Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Volkow, ND (reprint author), Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov RI Wise, Roy/A-6465-2012 NR 60 TC 536 Z9 542 U1 9 U2 80 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2005 VL 8 IS 5 BP 555 EP 560 DI 10.1038/nn1452 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 923FM UT WOS:000228895100012 PM 15856062 ER PT J AU Meyer-Lindenberg, A Kohn, PD Kolachana, B Kippenhan, S McInerney-Leo, A Nussbaum, R Weinberger, DR Berman, KF AF Meyer-Lindenberg, A Kohn, PD Kolachana, B Kippenhan, S McInerney-Leo, A Nussbaum, R Weinberger, DR Berman, KF TI Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype SO NATURE NEUROSCIENCE LA English DT Article ID HUMAN BRAIN; MESSENGER-RNA; SCHIZOPHRENIA; EXPRESSION; SYSTEMS; CORTEX; MEMORY AB Using multimodal neuroimaging in humans, we demonstrate specific interactions between prefrontal activity and midbrain dopaminergic synthesis. A common V(108/158)M substitution in the gene for catecholamine-O-methyltransferase (COMT), an important enzyme regulating prefrontal dopamine turnover, predicted reduced dopamine synthesis in midbrain and qualitatively affected the interaction with prefrontal cortex. These data implicate a dopaminergic tuning mechanism in prefrontal cortex and suggest a systems-level mechanism for cognitive and neuropsychiatric associations with COMT. C1 NIMH, Sect Integrat Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Sect Integrat Neuroimaging, NIH, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 15 TC 277 Z9 283 U1 1 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD MAY PY 2005 VL 8 IS 5 BP 594 EP 596 DI 10.1038/nn1438 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 923FM UT WOS:000228895100019 PM 15821730 ER PT J AU Marx, SJ AF Marx, SJ TI Molecular genetics of multiple endocrine neoplasia types 1 and 2 SO NATURE REVIEWS CANCER LA English DT Review ID MEDULLARY-THYROID CARCINOMA; HISTONE METHYLTRANSFERASE COMPLEX; DEPENDENT KINASE INHIBITORS; MEN1 GENE; MOUSE MODEL; POINT MUTATION; RET MUTATION; HUMAN CANCER; FACTOR JUND; MUTANT RET AB Six multiple endocrine neoplasia ( MEN) syndromes have received a level of attention that might seem disproportionate to their low prevalence. The attention has been given because their hormonal excesses cause striking metabolic expressions and because they might clarify pathways disrupted in more common tumours. The recent discovery of the main gene in each MEN syndrome has furthered our understanding of not only hereditary but also sporadic tumours and has fostered new avenues of research. C1 NIH, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIH, Bldg 10,Room 9C-101, Bethesda, MD 20892 USA. EM StephenM@intra.niddk.nih.gov NR 83 TC 175 Z9 181 U1 1 U2 9 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 MAY PY 2005 VL 5 IS 5 BP 367 EP 375 DI 10.1038/nrc1610 PG 9 WC Oncology SC Oncology GA 922JR UT WOS:000228834100013 PM 15864278 ER PT J AU Lichten, M AF Lichten, M TI Rad50 connects by hook or by crook SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID DOUBLE-STRAND BREAK; DNA-DAMAGE; SACCHAROMYCES-CEREVISIAE; REPAIR COMPLEX; MRE11 COMPLEX; RECOMBINATION; CHECKPOINT; NUCLEASE; PATHWAYS; DYNAMICS AB The Mre11 protein complex plays important roles in maintaining genome stability. Inter-molecular bridging by the Rad50 protein has now been shown to be critical to this complex's function. C1 NCI, Biochem Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Lichten, M (reprint author), NCI, Biochem Lab, Ctr Canc Res, Bldg 37,Room 6124, Bethesda, MD 20892 USA. EM lichten@helix.nih.gov RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 22 TC 4 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2005 VL 12 IS 5 BP 392 EP 393 DI 10.1038/nsmb0505-392 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 922UA UT WOS:000228863000008 PM 15870729 ER PT J AU Petukhova, GV Pezza, RJ Vanevski, F Ploquin, M Masson, JY Camerini-Otero, RD AF Petukhova, GV Pezza, RJ Vanevski, F Ploquin, M Masson, JY Camerini-Otero, RD TI The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID DNA STRAND EXCHANGE; RECA-LIKE RECOMBINASES; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; FISSION YEAST; MEIOSIS; CHROMOSOMES; PROMOTES; COMPLEX; RESISTANCE AB During the first meiotic division, homologous chromosomes (homologs) have to separate to opposite poles of the cell to ensure the right complement in the progeny. Homologous recombination provides a mechanism for a genome-wide homology search and physical linkage among the homologs before their orderly segregation. Rad51 and Dmc1 recombinases are the major players in these processes. Disruption of meiosis-specific HOP2 or MND1 genes leads to severe defects in homologous synapsis and an early-stage recombination failure resulting in sterility. Here we show that mouse Hop2 can efficiently form D-loops, the first recombination intermediates, but this activity is abrogated upon association with Mnd1. Furthermore, the Hop2 - Mnd1 heterodimer physically interacts with Rad51 and Dmc1 recombinases and stimulates their activity up to 35-fold. Our data reveal an interplay among Hop2, Mnd1 and Rad51 and Dmc1 in the formation of the first recombination intermediates during meiosis. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Univ Laval, Canc Res Ctr, Genome Stabil Lab, Quebec City, PQ G1R 2J6, Canada. RP Camerini-Otero, RD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, 5 Mem Dr, Bethesda, MD 20892 USA. EM rdcamerini@mail.nih.gov NR 33 TC 77 Z9 84 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD MAY PY 2005 VL 12 IS 5 BP 449 EP 453 DI 10.1038/nsmb923 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 922UA UT WOS:000228863000021 PM 15834424 ER PT J AU Bazinet, RP Lee, HJ Felder, CC Porter, AC Rapoport, SI Rosenberger, TA AF Bazinet, RP Lee, HJ Felder, CC Porter, AC Rapoport, SI Rosenberger, TA TI Rapid high-energy microwave fixation is required to determine the anandamide (N-arachidonoylethanolamine) concentration of rat brain SO NEUROCHEMICAL RESEARCH LA English DT Article DE anandamide; arachidonic acid; brain; decapitation; ischemia; microwave ID ACID AMIDE HYDROLASE; CANNABINOID RECEPTOR AGONIST; FREE FATTY-ACID; CEREBRAL-ISCHEMIA; CB1 RECEPTOR; SIGNAL-TRANSDUCTION; ENZYMATIC-SYNTHESIS; PERIPHERAL-TISSUES; ENDOGENOUS LIGAND; MOUSE-BRAIN AB Anandamide (N-arachidonoylethanolamine, AEA) is the putative endogenous ligand for the CB1 receptor. Despite being regulated enzymatically, brain AEA concentrations are quite variable and have been reported to increase in response to ischemia and post-mortem delay. Because these observations are similar to the effects of decapitation on brain concentrations of unesterified arachidonic acid and several of its metabolites, we propose that brain AEA concentrations also increase with decapitation and that immediate head-focused microwave irradiation is necessary to quantify basal brain AEA levels correctly. To test this hypothesis, we measured brain AEA levels in rats that were subjected to head-focused microwave irradiation 5 min. following decapitation (5.5 kW, 3.4 s) ( ischemic) and prior to decapitation ( controls). Brain AEA concentrations were quantified by LC/MS/MS. AEA concentrations from ischemic animals (10.01 +/- 4.41 pmol/g, mean +/- SD) were significantly higher and more variable than control concentrations (2.45 +/- 0.39 pmol/g). Thus, the basal concentration of AEA in the brain is lower than previously thought and future studies attempting to quantify brain AEA should consider using head-focused microwave fixation to prevent anomalous results. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Lilly Res Labs, Div Neurosci, Indianapolis, IN 46285 USA. Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58203 USA. RP Bazinet, RP (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg S 128, Bethesda, MD 20892 USA. EM rbazinet@mail.nih.gov NR 43 TC 53 Z9 53 U1 0 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 2005 VL 30 IS 5 BP 597 EP 601 DI 10.1007/s11064-005-2746-5 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 951EH UT WOS:000230911400002 PM 16176062 ER PT J AU Lee, HJ Ghelardoni, S Chang, L Bosetti, F Rapoport, SI Bazinet, RP AF Lee, HJ Ghelardoni, S Chang, L Bosetti, F Rapoport, SI Bazinet, RP TI Topiramate does not alter the kinetics of arachidonic or docosahexaenoic acid in brain phospholipids of the unanesthetized rat SO NEUROCHEMICAL RESEARCH LA English DT Article DE arachidonic acid; brain; bipolar disorder; mood stabilizer; anti-epileptic; topiramate; lithium; mania; turnover; metabolism; kinetics ID REFRACTORY PARTIAL EPILEPSY; PLACEBO-CONTROLLED TRIAL; CENTRAL-NERVOUS-SYSTEM; DOSE-RANGING TRIAL; BIPOLAR DISORDER; CHRONIC LITHIUM; DOUBLE-BLIND; FATTY-ACID; ADJUNCTIVE TOPIRAMATE; DAILY DOSAGES AB Interest in the potential therapeutic utility of topiramate for treating bipolar disorder was stimulated by published reports of investigator-initiated open label clinical studies. Because chronic lithium, carbamazepine and valproate decrease the turnover of arachidonic acid (AA) but not docosahexaenoic acid (DHA) in brain phospholipids of the awake rat, we tested if topiramate would produce similar results. Rats received either topiramate (20 mg/kg twice per day) or vehicle for 14 days and then while unanesthetized were infused intravenously with either [1-C-14] AA or [1-C-14] DHA for 5 min while blood was collected from the femoral artery at fixed times. Topiramate did not alter the incorporation rate of AA or DHA from their respective brain acyl-CoA pool into brain phospholipids, nor the turnover of AA and DHA in brain phospholipids. The results of our study indicate that topiramate does not possess a pharmacological property that three drugs with proven efficacy in treating bipolar disorder have in common. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bazinet, RP (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg S 128, Bethesda, MD 20892 USA. EM rbazinet@mail.nih.gov NR 50 TC 31 Z9 31 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD MAY PY 2005 VL 30 IS 5 BP 677 EP 683 DI 10.1007/s11064-005-2756-3 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 951EH UT WOS:000230911400012 PM 16176072 ER PT J AU Ernst, M Nelson, EE Jazbec, S McClure, EB Monk, CS Leibenluft, E Blair, J Pine, DS AF Ernst, M Nelson, EE Jazbec, S McClure, EB Monk, CS Leibenluft, E Blair, J Pine, DS TI Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents SO NEUROIMAGE LA English DT Article DE reward; fMRI; neuroimaging; development; limbic; ventral striatum; pediatric; maturation ID ANTERIOR CINGULATE CORTEX; STRUCTURED CLINICAL INTERVIEW; DSM-III-R; DECISION-MAKING; ORBITOFRONTAL CORTEX; PREFRONTAL CORTEX; RISK-TAKING; REWARD ANTICIPATION; FACIAL EXPRESSIONS; NEURAL RESPONSES AB Adolescents' propensity for risk-taking and reward-seeking behaviors suggests a heightened sensitivity for reward, reflected by greater feedback-related activity, changes in reward circuitry (e.g., nucleus accumbens), ane/or a lower sensitivity to potential harm reflected by weaker feedback-related activity changes in avoidance circuitry (e.g., amygdala) relative to adults. Responses of nucleus accumbens and amygdala to valenced outcomes (reward receipt and reward omission) were assayed using an event-related functional magnetic resonance imaging procedure paired with a monetary reward task in 14 adults and 16 adolescents. Bilateral amygdala and nucleus accumbens showed significantly greater activation when winning than when failing to win in both groups. Group comparisons revealed stronger activation of left nucleus accumbens by adolescents, and of left amygdala by adults. When examining responses to reward receipts and to reward omissions separately. the most robust group difference was within the amygdala during reward omission. The reduction of the fMRI BOLD signal in the amygdala in response to reward omission was larger for adults than for adolescents. Correlations showed a close link between negative emotion and amygdala decreased BOLD signal in adults, anti between positive emotion and nucleus accumbens activation in adolescents. Overall, these findings support the notion that the signal differences between positive and negative outcomes involve the nucleus accumbens more in adolescents than in adults, and the amygdala more in adults than in adolescents. These developmental differences, if replicated, may have important: implications for the development of early-onset disorders of emotion and motivation. Published by Elsevier Inc. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, 15K N Dr, Bethesda, MD 20892 USA. EM ernstm@intra.nimh.nih.gov RI Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014 OI Nelson, Eric/0000-0002-3376-2453; NR 69 TC 326 Z9 335 U1 13 U2 43 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 MAY 1 PY 2005 VL 25 IS 4 BP 1279 EP 1291 DI 10.1016/j.neuroimage.2004.12.038 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 924WJ UT WOS:000229011200026 PM 15850746 ER PT J AU Dalakas, MC AF Dalakas, MC TI Autoimmune muscular pathologies SO NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Lombardia Meeting of the Italian-Neurological-Society/Italian-Society-of-Hospital-Neurosciences CY MAY 06-07, 2005 CL Monza, ITALY SP Italian Neurol soc, Italian Soc Hosp Neurosci DE inflammatory myopathies; cytotoxic T cell; complement; co-stimulatory molecules ID DERMATOMYOSITIS; POLYMYOSITIS AB The T cell-mediated mechanism responsible for Polymyositis and inclusion Body Myositis and the complement-mediated microangiopathy associated with Dermatomyositis are reviewed. The management of autoimmune myopathies with the presently available immunotherapeutic agents as well as new therapies and ongoing trials are discussed. C1 NINDS, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM datakasm@ninds.nih.gov NR 4 TC 3 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1590-1874 J9 NEUROL SCI JI Neurol. Sci. PD MAY PY 2005 VL 26 SU 1 BP S7 EP S8 DI 10.1007/s10072-005-0390-0 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 932YO UT WOS:000229590900005 PM 15883700 ER PT J AU Elvevag, B Storms, G Heit, E Goldberg, T AF Elvevag, B Storms, G Heit, E Goldberg, T TI Category content and structure in schizophrenia: An evaluation using the instantiation principle SO NEUROPSYCHOLOGY LA English DT Article DE exemplars; prototypes; categories; semantic memory; schizophrenia ID VERBAL FLUENCY; MEMORY IMPAIRMENT; THOUGHT-DISORDER; SEMANTIC MEMORY; PROTOTYPE; ACCESS AB In numerous; studies, researchers have suggested anomalies in semantics in patients with schizophrenia. In this study, the authors addressed whether one such anomaly might reflect a difference in knowledge content or in the structure or organization of this information. Using a category member production task and a typicality rating task, the authors assessed knowledge content and found that patients' and control participants' knowledge about categories of foods and animals was very similar. In terms of structure, their findings from a mathematical model of category judgment (the instantiation model; E. Heit & L. W. Barsalou, 1996) revealed a similar category structure in patients and control participants. In conclusion, the authors suggest that the content and organization of categories in patients with schizophrenia is similar to that in healthy control participants. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Louvain, Dept Psychol, Louvain, Belgium. Univ Warwick, Dept Psychol, Warwick, England. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Room 4S235,MSC 1379, Bethesda, MD 20892 USA. EM elvevaab@intra.nimh.nih.gov RI Heit, Evan/B-1551-2010 OI Heit, Evan/0000-0003-3457-1816 NR 40 TC 13 Z9 13 U1 1 U2 2 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD MAY PY 2005 VL 19 IS 3 BP 371 EP 380 DI 10.1037/0894-4105.19.3.371 PG 10 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 929FZ UT WOS:000229328800011 PM 15910123 ER PT J AU Gray, KA Day, NL Leech, S Richardson, GA AF Gray, KA Day, NL Leech, S Richardson, GA TI Prenatal marijuana exposure: Effect on child depressive symptoms at ten years of age SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Neurobehavioral-Teratology-Society/24th Annual Meeting of the Behavioral-Toxicology-Society held in Conjunction with the 45th Annual Meeting of the Teratology-Society CY JUN 25-28, 2005 CL St Pete Beach, FL SP NeurobehavTeratol Soc, Behav Toxicol Soc, Teratol Soc DE prenalal marijuana; depression; children ID FOLLOW-UP; ALCOHOL; DISORDERS; CIGARETTES; BEHAVIOR; ADOLESCENTS; INVENTORY; AROUSAL; SLEEP; RISK AB Studies of the consequences of prenatal marijuana use have reported effects predominantly on the behavioral and cognitive development of the children. Research on other aspects of child neurobehavioral development, such as psychiatric symptomatology, has been limited. This study examines the relations between prenatal marijuana exposure (PME) and child depressive symptoms at 10 years of age. Data are from the 10-year follow-up of 633 mother-child dyads who participated in the Maternal Health Practices and Child Development Project. Maternal prenatal and current substance use, measures of the home environment, demographic status, and psychosocial characteristics were ascertained at prenatal months four and seven, at delivery, and at age 10. At age 10, the children also completed the Children's Depression Inventory (CDI) [M. Kovacs. The Children's Depression Inventory, Multi-Health Systems, Inc., North Tonawanda, NY, (1992).], a self-report measure of current depressive symptoms. Multivariate regressions were used to test trimester-specific effects of marijuana and their associations with the CDI total score, while controlling for significant prenatal predictors and significant current covariates of childhood depression. PME in the first and third trimesters predicted significantly increased levels of depressive symptoms. This finding remained significant after controlling for all identified covariates from both the prenatal period and the current phase at age 10. These findings reflect an association with the level of depressive symptoms rather than a diagnosis of a major depressive disorder. Other significant correlates of depressive symptoms in the children included maternal education, maternal tobacco use (prenatal or current), and the child's composite IQ score. These findings are consistent with recent reports that identify specific areas of the brain and specific brain functions that are associated with PME. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. NIEHS, Susceptibil & Populat Hlth Branch, Res Triangle Pk, NC 27709 USA. Univ Pittsburgh, Med Ctr, Maternal Hlth Practices & Child Dev Project, Pittsburgh, PA 15213 USA. RP Richardson, GA (reprint author), Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. EM gar@pitt.edu RI Day, Nancy/H-3171-2016 FU NIAAA NIH HHS [AA06666, AA07453]; NIDA NIH HHS [DA038774] NR 50 TC 54 Z9 55 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2005 VL 27 IS 3 BP 439 EP 448 DI 10.1016/j.ntt.2005.03.010 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 942GM UT WOS:000230270900007 PM 15869861 ER PT J AU Finnema, SJ Seneca, N Farde, L Shchukin, E Sovago, J Gulyas, B Wikstrom, HV Innis, RB Neumeyer, JL Halldin, C AF Finnema, SJ Seneca, N Farde, L Shchukin, E Sovago, J Gulyas, B Wikstrom, HV Innis, RB Neumeyer, JL Halldin, C TI A preliminary PET evaluation of the new dopamine D-2 receptor agonist [C-11]MNPA in cynomolgus monkey SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE dopamine agonist; D-2 receptor; high-affinity state; PET; monkey; [C-11]MNPA ID POSITRON-EMISSION-TOMOGRAPHY; NONHUMAN-PRIMATES; ANTERIOR-PITUITARY; D2-DOPAMINE RECEPTORS; C-11 RACLOPRIDE; AFFINITY STATES; BINDING; BRAIN; RELEASE; RODENTS AB This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D-2-like receptor agonist, (R)-2(11)-CH3O-N-n-propylnorapomorphine ([C-11]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D-2 receptor (D2R). MNPA is a selective D2-like receptor agonist with a high affinity (K-i=0.17 nM). [C-11]MNPA was successfully synthesized by direct O-methylation of(R)-2-hydroxy-NPA using [C-11]methyl iodide and was evaluated in cynomolgus monkeys. This study included baseline PET experiments and a pretreatment study using unlabeled raclopride (1 mg/kg). High uptake of radioactivity was seen in regions known to contain high D2R, with a maximum striatum-to-cerebellum ratio of 2.23 +/- 0.21 at 78 min and a maximum thalamus-to-cerebellum ratio of 1.37 +/- 0.06 at 72 min. The pretreatment study demonstrated high specific binding to D2R by reducing the striatum-to-cerebellum ratio to 1.26 at 78 min. This preliminary study indicates that the dopamine agonist [C-11]MNPA has potential as an agonist radioligand for the D-2-like receptor and has potential for examination of the high-affinity state of the D2R in human subjects and patients with neuropsychiatric disorders. (c) 2005 Elsevier Inc. All rights reserved. C1 Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. Univ Groningen, Univ Ctr Pharm, Dept Med Chem, NL-9913 AV Groningen, Netherlands. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, McLean Div,Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. RP Halldin, C (reprint author), Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. EM christer.halldin@cns.ki.se RI Sovago, Judit/G-7961-2011; Gulyas, Balazs/F-9508-2015 NR 38 TC 54 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD MAY PY 2005 VL 32 IS 4 BP 353 EP 360 DI 10.1016/j.nucmedbio.2005.01.007 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 930MR UT WOS:000229420600005 PM 15878504 ER PT J AU Ulrich, CM Danis, M Koziol, D Garrett-Mayer, E Hubbard, R Grady, C AF Ulrich, CM Danis, M Koziol, D Garrett-Mayer, E Hubbard, R Grady, C TI Does it pay to pay? A randomized trial of prepaid financial incentives and lottery incentives in surveys of nonphysician healthcare professionals SO NURSING RESEARCH LA English DT Article DE nonphysician clinicians; randomized trial; response rate; survey ID FOLLOW-UP MAILINGS; RESPONSE RATES; MONETARY INCENTIVES; MAILED QUESTIONNAIRES; PHYSICIANS; 5-DOLLAR AB Background: Monetary incentives in survey research may provide important gains from a methodological perspective in the control and reduction of survey error associated with potential nonresponse of participants. However, few studies have systematically investigated the use of monetary incentives or other methods to improve the response rates in the nonphysician clinician population. Objective: To investigate differences in response rates to a mailed self-administered survey of nonphysician clinicians who were randomized to receive a prepaid monetary incentive, a postsurvey prize drawing, or no incentive. Methods: A randomized controlled trial of financial incentives was conducted from November 2002 to February 2003. Nonphysician clinicians (nurse practitioners [NPs] and physician assistants [PAs]; N = 3,900) randomly selected to participate in a national ethics-related study were assigned randomly in equal allocations (n = 1,300 [650 NPs, 650 PAs]) to three incentive groups: (a) no incentive; (b) a $5 prepaid token incentive in the initial mailing; or (c) a chance to win one of ten $100 prize drawings upon completion and return of a self-administered survey. Results: A $5 cash incentive increased survey response rates to an adjusted 64.2 %: a 19.5 percentage point increase over the lottery group (44.7 % response rate), and a 22 percentage point increase over the control group (42.2 % response rate). Discussion: A nominal cash incentive of $5 yields a significantly higher response rate from nonphysician providers than receiving either a lottery option or no incentive. C1 Univ Penn, Sch Nursing, Philadelphia, PA 19104 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Biostat & Clin Epidemiol Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Ctr, Dept Biostat & Oncol, Baltimore, MD 21218 USA. Univ Virginia, Survey Res Ctr, Charlottesville, VA USA. RP Ulrich, CM (reprint author), Univ Penn, Sch Nursing, Room 357 NEB,420 Guardian Dr, Philadelphia, PA 19104 USA. EM culrich@nursing.upenn.edu NR 20 TC 32 Z9 32 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-6562 J9 NURS RES JI Nurs. Res. PD MAY-JUN PY 2005 VL 54 IS 3 BP 178 EP 183 PG 6 WC Nursing SC Nursing GA 930NT UT WOS:000229423600005 PM 15897793 ER PT J AU Blair, A AF Blair, A TI Occupational medicine: at a turning point or an expansion SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Editorial Material C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Cause & Prevent, Bethesda, MD 20892 USA. RP Blair, A (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Cause & Prevent, Execut Plaza S,Room 8118, Bethesda, MD 20892 USA. EM blaira@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD MAY PY 2005 VL 62 IS 5 BP 285 EP 285 DI 10.1136/oem.2004.018382 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 917KV UT WOS:000228461300003 PM 15837845 ER PT J AU Krstev, S Dosemeci, M Lissowska, J Chow, WH Zatonski, W Ward, MH AF Krstev, S Dosemeci, M Lissowska, J Chow, WH Zatonski, W Ward, MH TI Occupation and risk of stomach cancer in Poland SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID GASTRIC-CANCER; DEATH CERTIFICATES; EXPOSURES; WARSAW; ESOPHAGEAL; MORTALITY; WORKERS; CARDIA; STATES; CHINA AB Background: In spite of the dramatic decline in the incidence of stomach cancer in the twentieth century, Poland has one of the highest rates in the world. Aims: To evaluate the risk of stomach cancer by grouped occupations and industries, as well as by some specific occupational exposures. Methods: Cases (n = 443) were newly diagnosed with stomach adenocarcinomas between 1994 and 1996. Controls ( n = 479) were randomly selected from the general population in Warsaw. Results: Only a few occupations and industries were associated with significantly increased risks of stomach cancer. The most suggestive finding was for work in the leather goods industry. Risk was also significantly increased among men working in fabricated metal production and among women ever employed as managers and governmental officials. Men ever employed as teaching professionals and women employed as technical and science professionals had significantly decreased risks of stomach cancer. Among men, a significant positive trend in risk with duration of employment was observed for work in the leather industry and special trade construction. No significantly increased risks were observed for specific exposures assessed by a job-exposure matrix or by self-reports. However among men there were non-significantly increased risks with 10 or more years exposure to asbestos, metal dust, and nitrosamines assessed by a job-exposure matrix. Conclusions: Employment in the leather goods industry, special trade construction, and metal fabrication was associated with an increased risk of stomach cancer among men. However, there were only weak associations with specific exposures. Occupational exposures do not contribute substantially to the high rates of stomach cancer in Poland. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD 20892 USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. Inst Oncol, Warsaw, Poland. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov OI Lissowska, Jolanta/0000-0003-2695-5799 FU NCI NIH HHS [N01-CP-05626, N02-CP-40501, N02-CP-71103] NR 27 TC 18 Z9 18 U1 1 U2 3 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 MAY PY 2005 VL 62 IS 5 BP 318 EP 324 DI 10.1136/oem.2004.015883 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 917KV UT WOS:000228461300011 PM 15837853 ER PT J AU Loomis, D Richardson, DB Elliott, L AF Loomis, D Richardson, DB Elliott, L TI Poisson regression analysis of ungrouped data SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID MAGNETIC-FIELD EXPOSURE; ELECTRIC UTILITY WORKERS; OCCUPATIONAL EPIDEMIOLOGY; MORTALITY DATA; DOSE-RESPONSE; COHORT DATA; FOLLOW-UP; MODELS; CANCER; MISCLASSIFICATION AB Background: Poisson regression is routinely used for analysis of epidemiological data from studies of large occupational cohorts. It is typically implemented as a grouped method of data analysis in which all exposure and covariate information is categorised and person-time and events are tabulated. Aims: To describe an alternative approach to Poisson regression analysis using single units of person-time without grouping. Methods: Data for simulated and empirical cohorts were analysed by Poisson regression. In analyses of simulated data, effect estimates derived via Poisson regression without grouping were compared to those obtained under proportional hazards regression. Analyses of empirical data for a cohort of 138 900 electrical workers were used to illustrate how the ungrouped approach may be applied in analyses of actual occupational cohorts. Results: Using simulated data, Poisson regression analyses of ungrouped person-time data yield results equivalent to those obtained via proportional hazards regression: the results of both methods gave unbiased estimates of the "true'' association specified for the simulation. Analyses of empirical data confirm that grouped and ungrouped analyses provide identical results when the same models are specified. However, bias may arise when exposure-response trends are estimated via Poisson regression analyses in which exposure scores, such as category means or midpoints, are assigned to grouped data. Conclusions: Poisson regression analysis of ungrouped person-time data is a useful tool that can avoid bias associated with categorising exposure data and assigning exposure scores, and facilitate direct assessment of the consequences of exposure categorisation and score assignment on regression results. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Loomis, D (reprint author), Univ N Carolina, Dept Epidemiol, CB-7435,UNC-CH, Chapel Hill, NC 27599 USA. EM Dana.Loomis@unc.edu NR 26 TC 34 Z9 34 U1 0 U2 3 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 MAY PY 2005 VL 62 IS 5 BP 325 EP 329 DI 10.1136/oem.2004.017459 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 917KV UT WOS:000228461300012 PM 15837854 ER PT J AU Nussenblatt, RB Peterson, JS Foster, CS Rao, NA See, RF Letko, E Buggage, RR AF Nussenblatt, RB Peterson, JS Foster, CS Rao, NA See, RF Letko, E Buggage, RR TI Initial evaluation of subcutaneous daclizumab treatments for noninfectious uveitis - A multicenter noncomparative interventional case series SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 107th Annual Meeting of the American-Academy-of-Ophthalmology/Annual Meeting of the ISRS CY NOV 14-18, 2003 CL ANAHEIM, CA SP Amer Acad Ophthalmol, ISRS ID OCULAR INFLAMMATORY DISORDERS; RECEPTOR MONOCLONAL-ANTIBODY; HUMANIZED ANTIBODY; ALLOGRAFT SURVIVAL; POSTERIOR UVEITIS; TAC; INTERLEUKIN-2-RECEPTOR; INTERMEDIATE AB Purpose: To assess the feasibility of a study design that may determine whether subcutaneous administration of the interleukin-2 receptor antibody daclizumab can safely reduce the dependence on standard systemic corticosteroids or other immunosuppressive regimens in patients with sight-threatening, noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Design: Prospective, multicenter, nonrandomized, noncomparative, open-label interventional trial. Participants: Fifteen patients, 5 each at 3 clinical centers, with noninfectious intermediate, posterior, or panuveitis, who require a currently stable immunosuppression regimen of systemic corticosteroids and/or other systemic treatments to control noninfectious intraocular inflammation. Methods: After enrollment and baseline ophthalmic evaluations, 2 induction treatments were given 2 weeks apart using subcutaneous (SC) daclizumab at 2 mg/kg. Subcutaneous daclizumab maintenance treatments were then continued every 2 weeks at 1 mg/kg for 6 months. The initial immunosuppression load was tapered over 8 to 12 weeks in a staggered fashion beginning with the first induction treatment. Safety evaluations were performed at each treatment visit, with a primary efficacy evaluation at 12 weeks and a repeat efficacy evaluation at 26 weeks. Main Outcome Measures: Best-corrected visual acuity (Early Treatment of Diabetic Retinopathy Study [ETDRS] method) with a concurrent taper of concomitant systemic immunosuppression medication load (tabulated by use of a weighted scoring system) was assessed; target for success was defined as a 50% or greater reduction in concomitant immunosuppression load by 12 weeks while maintaining visual acuity within 5 ETDRS letters of baseline. Ocular inflammation was assessed at each visit with standardized grading scales. Results: Ten of 15 patients (67%) receiving SC daclizumab treatments every other week successfully achieved the primary efficacy end point of reducing their concomitant immunosuppression load by at least 50% while maintaining their baseline visual acuity at 12 and 26 weeks. Subcutaneous daclizumab injections were well tolerated with no serious adverse events observed during the 6 months of treatments, although 3 patients experienced possibly related, nonserious adverse events. Conclusions: Subcutaneous daclizumab induction treatments at 2 mg/kg followed by 1 mg/kg maintenance treatments every other week seems safe and, in most cases, may reduce the concomitant immunosuppressive load required to treat noninfectious uveitis for 12 to 26 weeks. (c) 2005 by the American Academy of Ophthalmology. C1 NEI, Lab Immunol, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Univ So Calif, Doheny Eye Inst, Los Angeles, CA USA. RP Nussenblatt, RB (reprint author), NEI, Lab Immunol, Bldg 10 Room 10S219,10 Ctr Dr,MSC 1857, Bethesda, MD 20892 USA. FU NEI NIH HHS [N01-EY-1-2113] NR 19 TC 65 Z9 68 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2005 VL 112 IS 5 BP 764 EP 770 DI 10.1016/j.ophtha.2004.12.034 PG 7 WC Ophthalmology SC Ophthalmology GA 923NC UT WOS:000228915600005 PM 15878055 ER PT J AU Srivastava, SK Martin, DF Mellow, SD Parks, DJ Dastgheib, K Chan, CC AF Srivastava, SK Martin, DF Mellow, SD Parks, DJ Dastgheib, K Chan, CC TI Pathological findings in eyes with the ganciclovir implant SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 24-29, 2004 CL Ft Lauderdale, FL SP Assoc Res Vis & Ophthalmol ID CYTOMEGALOVIRUS RETINITIS; AIDS; REMOVAL; UVEITIS AB Objective: To examine the pathologic findings of eyes treated with ganciclovir implants. Design: Retrospective consecutive case series. Participants: Thirty-three eyes from 19 AIDS patients with ganciclovir implants. Methods: Pathologic specimens collected from 1993 through 1999 at the National Eye Institute were reviewed. Thirty-three eyes from 19 patients were identified with ganciclovir implants. The submitted eyes then were sectioned through the implant site and stained with hematoxylin and eosin, periodic acid-Schiff, and other special stains when needed. Medical records, including operative and postoperative notes, were reviewed carefully. Main Outcome Measure: Light microscopic findings at and around the site of implantation. Results: Scars of surgical perforation were present in all eyes. Fibrous ingrowth developed from the implant site into the vitreous in 32 of the 33 eyes. Vitreous hemorrhage was present in 18 of the 33 eyes. Poor wound apposition was found in 2 of the 33 eyes, both of which had undergone multiple procedures. Foreign body giant cell reactions were observed in most of the eyes related to suture material. Thirty-two of the 37 implant sites were located within the pars plana, whereas the other 5 were either on the border of the pars plana and pars plicata (n = 4) or within the pars plicata (n = 1). Hyalinization, atrophic changes of the ciliary body in the area of implantation, or both were observed in 18 eyes. Conclusions: The ganciclovir implant is well tolerated within the eye. Fibrous ingrowth is present in most eyes and seems to be a benign occurrence because of its limited extension. Microscopic vitreous hemorrhage is present in many eyes, especially those that underwent multiple procedures. Poor wound apposition occurred rarely and was found only in eyes that had undergone multiple procedures. © 2005 by the American Academy of Ophthalmology. C1 NEI, Lab Immunol, NIH, Bethesda, MD 20892 USA. Emory Eye Ctr, Dept Ophthalmol, Atlanta, GA USA. RP Chan, CC (reprint author), NEI, Lab Immunol, NIH, Bldg 10,Room 10N103,10 Ctr Dr, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 19 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD MAY PY 2005 VL 112 IS 5 BP 780 EP 786 DI 10.1016/j.ophtha.2004.11.042 PG 7 WC Ophthalmology SC Ophthalmology GA 923NC UT WOS:000228915600008 PM 15878057 ER PT J AU Patel, V Ramesh, A Traicoff, JL Baibakov, G Emmert-Buck, MR Gutkind, JS Knezevic, V AF Patel, V Ramesh, A Traicoff, JL Baibakov, G Emmert-Buck, MR Gutkind, JS Knezevic, V TI Profiling EGFR activity in head and neck squamous cell carcinoma by using a novel layered membrane Western blot technology SO ORAL ONCOLOGY LA English DT Article DE Western blotting; cell signaling; EGFR; protein expression; phosphorylation; drug discovery; MLWestern ID GROWTH-FACTOR RECEPTOR; EXPRESSION; VALIDATION; ACTIVATION; TARGET; CANCER; LINES AB Given the rote of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinomas (HNSCC), several rational approaches have now been utilized to abrogate tyrosine kinase activity and its disengagement from downstream signal transducers. Monitoring the activity of these molecules could potentially be useful to determine not only drug efficacy but also to identify HNSCC patients most likely to benefit from this type of therapy. In this study we have used a novel high throughput multi-layered Western blotting (MLWestern) method that allows the detection of multiple proteins from a single experiment in order to characterize key components in the EGFR signaling pathway in HNSCC cells. Total and activated forms of EGFR and the downstream effectors, Erk and At were readily detected in HNSCC cells, where in the control cells (HaCaT) these proteins could only be detected in EGF stimulated cells. Results from conventional Western blot and MLWestern were comparable. Clustering analysis of protein expression revealed similarities in cellular response between some of the cell tines indicative of similarities in their biological response. The data indicate that MLWestern can be potentially applied to identify molecular targets that could be used for rational therapeutic intervention strategies. (c) 2005 Elsevier Ltd. All rights reserved. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Gene Syst Inc, Rockville, MD 20852 USA. NCI, Pathogenet Unit, Pathol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Patel, V (reprint author), 30 Convent Dr,Bldg 30,Room 212, Bethesda, MD 20892 USA. EM vpatet@dir.nidcr.nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 22 TC 11 Z9 13 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 2005 VL 41 IS 5 BP 503 EP 508 DI 10.1016/j.oraloncology.2004.12.010 PG 6 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 931FN UT WOS:000229471300009 PM 15878755 ER PT J AU Limb, CJ Francis, HF Lustig, LR Niparko, JK Jammal, H AF Limb, CJ Francis, HF Lustig, LR Niparko, JK Jammal, H TI Benign positional vertigo after cochlear implantation SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article AB OBJECTIVE: To identify patients who underwent cochlear implantation (CI) and who subsequently developed benign positional vertigo (BPV) after the procedure and to identify any contributing factors. STUDY DESIGN AND SETTING: Academic tertiary referral center. Cochlear implant recipients' medical records were retrospectively reviewed to identify patients with both vertigo and, more specifically, BPV. Preoperative, intraoperative, and postoperative factors were studied vis-a-vis the development of BPV. RESULTS: BPV was newly diagnosed in 12 patients after Cl. The etiology of hearing loss included presbycusis (16.6%), autoimmune inner ear disease (16.6%), congenital hearing loss (41.6%), Meniere's disease (8.3%), prematurity (8.3%), and idiopathic factors (8.3%). The onset of BPV varied after the procedure (mean &PLUSMN; SD, 292 &PLUSMN; 309 days). BPV symptoms did not affect implant performance. All patients were treated for BPV by Epley's maneuver and vestibular exercises. Symptoms disappeared in 11 patients and persisted in 1. CONCLUSIONS: BPV is an uncommon development after Cl, although it occurs more frequently than in the general population. Two theories are proposed: the introduction of bone dust into the labyrinth and the dislodging of otoconia during surgery. The diagnosis, treatment, and prognosis of BPV after Cl do not differ from those for non-CI-associated BPV. SIGNIFICANCE: Dizziness after Cl usually develops as a result of vestibular hypofunction. BPV, which is a hyperfunctioning form of vestibular dysfunction, should be recognized as a possible sequelae of CI. C1 Johns Hopkins Outpatient Ctr, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. NIDCD, NIH, Bethesda, MD USA. RP Limb, CJ (reprint author), Johns Hopkins Outpatient Ctr, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21287 USA. EM climb@jhmi.edu NR 11 TC 16 Z9 19 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD MAY PY 2005 VL 132 IS 5 BP 741 EP 745 DI 10.1016/j.otohns.2005.01.004 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 925LZ UT WOS:000229055900014 PM 15886628 ER PT J AU Dina, OA Hucho, T Yeh, J Malik-Hall, M Reichling, DB Levine, JD AF Dina, OA Hucho, T Yeh, J Malik-Hall, M Reichling, DB Levine, JD TI Primary afferent second messenger cascades interact with specific integrin subunits in producing inflammatory hyperalgesia SO PAIN LA English DT Article DE inflammation; cytoskeleton; extracellular matrix; caveolae; cholesterol; sphingomyelin ID PROTEIN-KINASE-C; CELL-CYCLE PROGRESSION; HETEROTRIMERIC G-PROTEINS; SIGNAL-TRANSDUCTION; LIPID RAFTS; EXTRACELLULAR-MATRIX; ADENYLYL-CYCLASE; PERIPHERAL-NERVE; SENSORY NEURONS; PKC-EPSILON AB We recently reported that hyperalgesia induced by the inflammatory mediator prostaglandin E-2 (PGE(2)) requires intact α 1, α 3 and β 1 integrin subunit function, whereas epinephrine-induced hyperalgesia depends on α 5 and β 1. PGE(2)-induced hyperalgesia is mediated by protein kinase A (PKA), while epinephrine-induced hyperalgesia is mediated by a combination of PKA, protein kinase Cε (PKCε) and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK). We hypothesized that inflammatory inediator-induced hyperalgesia involves specific interactions between different Subsets of integrin subunits and particular second messenger species. In the present study. function-blocking anti-integrin antibodies and antisense oligodeoxynucleotides were used to elucidate these interactions in rat. Hyperalgesia produced by an activator of adenylate cyclase (forskolin) depended on α 1, α 3 and β 1 integrins. However, hyperalgesia induced by activation of the cascade at a point farther downstream (by cAMP analog or PKA catalytic subunit) was independent of any integrins tested. In contrast. hyperalgesia induced by a specific PKCε agonist depended only on α 5 and β 1 integrins. Hyperalgesia induced by agonism of MAPK/ERK depended on all four integrin subunits tested (α 1, α 3, α 5 and β 1). Finally, disruption of lipid rafts antagonized hyperalgesia induced by PGE(2) and by forskolin, but not that induced by epinephrine. Furthermore, α 1 integrin, but not α 5, was present in detergent-resistant membrane fractions (which retain lipid raft components). These observations suggest that integrins play a critical role in inflammatory pain by interacting with components of second messenger cascades that mediate inflammatory hyperalgesia, and that such interaction with the PGE(2)-activated pathway may be organized by lipid rafts. © 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Univ Calif San Francisco, Dept Med, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, NIH Pain Ctr, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, Dept Med, Div Neurosci, Campus Box 0440,Room C-555 521, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu RI Hucho, Tim/F-8973-2010 NR 87 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD MAY PY 2005 VL 115 IS 1-2 BP 191 EP 203 DI 10.1016/j.pain.2005.02.028 PG 13 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 923XE UT WOS:000228942100020 PM 15836982 ER PT J AU Leon-Sarmiento, FE Bayona-Prieto, J Gomez, J AF Leon-Sarmiento, FE Bayona-Prieto, J Gomez, J TI Neurophysiology of blepharospasm and multiple system atrophy: clues to its pathophysiology SO PARKINSONISM & RELATED DISORDERS LA English DT Letter ID BLINK REFLEX; DYSTONIA C1 UIS Santander Univ, Sch Med, Bucaramanga, Colombia. Univ Pamplona, Pamplona, Norte De Sder, Spain. Neuro Net, Inst Neurociencias Aplicadas Neurobiol Humana & N, Bogota, Colombia. Univ Puerto Rico, Dept Family Med, San Juan, PR 00936 USA. RP Leon-Sarmiento, FE (reprint author), NINDS, Med Neurol Branch, NIH, 10 Ctr Dr,Bldg 10-5N 226, Bethesda, MD 20892 USA. EM leonf@ninds.nih.gov NR 16 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2005 VL 11 IS 3 BP 199 EP 201 DI 10.1016/j.parkreldis.2004.07.011 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 921OT UT WOS:000228774800011 PM 15823487 ER PT J AU Nathan, PC Tsokos, M Long, L Bernstein, D Wexler, LH Mackall, CL Helman, LJ AF Nathan, PC Tsokos, M Long, L Bernstein, D Wexler, LH Mackall, CL Helman, LJ TI Adjuvant chemotherapy for the treatment of advanced pediatric nonrhabdomyosarcoma soft tissue sarcoma: the National Cancer Institute experience SO PEDIATRIC BLOOD & CANCER LA English DT Article DE chemotherapy; nonrhabdomyosarcoma soft tissue sarcoma; pediatric ID RESEARCH-HOSPITAL-EXPERIENCE; EWINGS-SARCOMA; ONCOLOGY-GROUP; CHILDREN; ADOLESCENTS; RHABDOMYOSARCOMA; VINCRISTINE; DOXORUBICIN; IFOSFAMIDE; CHILDHOOD AB Background The survival of children and adolescents with advanced (unresectable or metastatic) nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) is poor. In order to clarify the role of combining chemotherapy with aggressive local control using surgery and/or radiation, we reviewed our institutional experience with the treatment of advanced pediatric NRSTS. Procedure. We reviewed the charts of all patients less than 2 1 years treated for an advanced NRSTS at the National Cancer Institute (NCI) between 1983 and 2003. Tumor pathology was confirmed and demographic, disease, and treatment data were abstracted. Survival was calculated using standard methods. Results. Of the 25 patients who were treated over the study period, 15 had metastatic disease and 10 had Unresectable or incompletely resected disease at presentation. Twenty-one patients received chemotherapy consisting of the combination of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide, and the remaining 4 received regimens that included doxorubicin. Twenty patients (80%) had a complete (5/25) or partial (15/25) response after chemotherapy alone. After the combination of chemotherapy and local control, 14 patients (56%) had a complete response (CR). The estimated 5-year overall and event-free survival (EFS) for all patients was 0.50 (standard error = 0.11) and 0.34 (standard error = 0. 10), respectively. Conclusions. The combination of chemotherapy with aggressive local control in this cohort of pediatric patients with advanced NRSTS yielded results comparable to those observed in patients with advanced sarcomas that are chemotherapy responsive. Prospective randomized trials are needed to quantify the contribution of chemotherapy and to determine the ideal regimen. Published 2004 Wiley-Liss, Inc. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Helman, LJ (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Room 13N240, Bethesda, MD 20892 USA. EM helmanl@mail.nih.gov NR 19 TC 6 Z9 6 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD MAY PY 2005 VL 44 IS 5 BP 449 EP 454 DI 10.1002/pbc.20262 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 911GI UT WOS:000227990200005 PM 15547929 ER PT J AU Schuval, S Lindsey, JC Stapleton, JT Van Dyke, RB Palumbo, P Mofenson, LM Oleske, JM Cervia, J Kovacs, A Dankner, WN Smith, E Nowak, B Ciupak, G Webb, N Eagle, M Smith, D Hennessey, R Goodman-Kerkau, M Klinzman, D Hess, G Zdunek, D Levin, MJ AF Schuval, S Lindsey, JC Stapleton, JT Van Dyke, RB Palumbo, P Mofenson, LM Oleske, JM Cervia, J Kovacs, A Dankner, WN Smith, E Nowak, B Ciupak, G Webb, N Eagle, M Smith, D Hennessey, R Goodman-Kerkau, M Klinzman, D Hess, G Zdunek, D Levin, MJ CA Pediat AIDS Clin Tri Grp Proto Tea TI GB virus C infection in children with perinatal human immunodeficiency virus infection SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE GB virus C; pediatric; human immunodeficiency virus; acquired immunodeficiency syndrome ID HEPATITIS-G VIRUS; HIV-INFECTION; ANTIRETROVIRAL THERAPY; VERTICAL TRANSMISSION; COINFECTION; RNA; PROGRESSION; DISEASE; SURVIVAL; VIREMIA AB Background: GB virus C (GBV-C) infection occurs in 20-40% of human immunodeficiency virus (HIV)-infected adults, and coinfection is associated with improved HIV disease outcome. Methods: To determine the prevalence of GBV-C infection in children who were perinatally infected with HIV, we conducted a cross-sectional prevalence survey in a cohort of perinatally infected HIV-positive children selected from a large, multicenter observational protocol. A blood specimen was obtained and tested for GBV-C viremia with the use of a qualitative GBV-C RNA assay and screened for past GBV-C infection with enzyme-linked immunosorbent assay to detect antibodies to the GBV-C envelope protein E2 (E2 Ab). Results: The 354 children who participated in the substudy were relatively healthy, with a median CD4 of 784 cells/mm(3) and median HIV-1 viral load of 1055 copies/mL. The prevalence of GBV-C viremia was 20 of 353 or 5.7% (95% confidence interval, 3.58.6%), and the prevalence of E2 Ab was 12 of 354 or 3.4% (95% confidence interval, 1.8-5.8%). GBV-C viremic patients were older than patients without past GBV-C infection (median age, 12.8 years versus 10.7 years). Median CD4(+) lymphocyte counts were highest in subjects without GBV-C infection and lowest in those with E2 Ab. Conclusions: GBV-C prevalence rates are lower in children with perinatal HIV infection than those reported for HIV-infected adults. With the exception of evidence that GBV-C viremic children had lower rates of Centers for Disease Control and Prevention HIV disease category C disease before GBV-C testing, we did not find evidence of improved HIV disease outcome in coinfected patients, but the number of HIV/GBV-C-coinfected children was small. C1 Long Isl Jewish Med Ctr, Div Allergy & Immunol, Schneider Childrens Hosp, New Hyde Pk, NY 11042 USA. Univ Iowa, Iowa City, IA USA. Iowa City VA Med Ctr, Iowa City, IA USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Natl Inst Child Hlth & Human Dev, Rockville, MD USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. PARAXEL Int, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. NIAID, Bethesda, MD 20892 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. Univ Massachusetts, Mem Hlth Ctr, Worcester, MA 01605 USA. Westat Corp, Rockville, MD USA. Univ N Carolina, Retrovirol Core Lab, Chapel Hill, NC USA. Roche Diagnost, Mannheim, Germany. Roche Diagnost, Penzberg, Germany. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Schuval, S (reprint author), Long Isl Jewish Med Ctr, Div Allergy & Immunol, Schneider Childrens Hosp, Suite 108,410 Lakeville Rd, New Hyde Pk, NY 11042 USA. EM schuval@lij.edu RI Oleske, James/C-1951-2016; OI Oleske, James/0000-0003-2305-5605; Mofenson, Lynne/0000-0002-2818-9808 FU NIAID NIH HHS [AI-41110] NR 41 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 2005 VL 24 IS 5 BP 417 EP 422 DI 10.1097/01.inf.0000160943.17750.94 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 927UQ UT WOS:000229226400004 PM 15876940 ER PT J AU Claesson, BA Trollfors, B Lagergard, T Knutsson, N Schneerson, R Robbins, JB AF Claesson, BA Trollfors, B Lagergard, T Knutsson, N Schneerson, R Robbins, JB TI Antibodies against Haemophilus influenzae type b capsular polysaccharide and tetanus toxoid before and after a booster dose of the carrier protein nine years after primary vaccination with a protein conjugate vaccine SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Haemophilits influenzae; tetanus toxoid; conjugate vaccine ID SERUM ANTIBODIES; PERSISTENCE; RESPONSES; INFANCY AB IgG antibodies against Haemophilus influenzae type b (Hib) capsular polysaccharide (CPS) and tetanus toxoid (TT) were measured for 53 children, 10 years of age, before and I month after a booster dose of diphtheria-tetanus vaccine (DT). All children had been vaccinated at 3, 5 and 12 months of age with DT and a Hib-TT conjugate. Geometric mean concentrations of Hib CPS serum IgG antibody were 4.16 and 4.30 mu g/mL before and after the DT booster, respectively. The geometric mean concentration of TT IgG antibody increased from 0.09 IU/mL to 4.58 IU/mL (P < 0.001). Hib CPS IgG levels remained well above protective titers for 9 years after 3 doses of Hib-TT appropriately spaced in infancy. A booster dose of TT did not affect Hib CPS antibody concentrations but induced a pronounced IgG response against TT. C1 Sahlgrens Univ Hosp, Dept Infect Dis, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Pediat, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Med Microbiol & Immunol, S-41345 Gothenburg, Sweden. Sahlgrens Univ Hosp, Dept Primary Hlth Care, S-41345 Gothenburg, Sweden. Univ Gothenburg, Gothenburg, Sweden. NICHHD, NIH, Bethesda, MD 20892 USA. RP Claesson, BA (reprint author), Sahlgrens Univ Hosp, Dept Infect Dis, S-41345 Gothenburg, Sweden. NR 8 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 2005 VL 24 IS 5 BP 463 EP 464 DI 10.1097/01.inf.0000160955.26151.71 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 927UQ UT WOS:000229226400015 PM 15876951 ER PT J AU Higgins, RD Delivoria-Papadopoulos, M Raju, TNK AF Higgins, RD Delivoria-Papadopoulos, M Raju, TNK TI Executive summary of the Workshop on the Border of Viability SO PEDIATRICS LA English DT Editorial Material DE prematurity; fetal death; cerebral palsy; neonatal resuscitation; intensive care; ethics ID INTRAVENTRICULAR HEMORRHAGE; CONTROLLED TRIAL; INDOMETHACIN; PREVENTION AB One of the most complex areas in perinatal-neonatal medicine remains the care of the mother delivering a newborn infant at the border of viability, referred to as "periviable" gestation. To address the knowledge gaps that preclude optimal, evidence-based care in this critical field of perinatal medicine, the National Institute of Child Health and Human Development organized a workshop in March 2004. This article provides a summary of the discussions, focusing on major knowledge gaps and prioritized suggestions for studies in this area. C1 NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. Drexel Univ, Coll Med, St Christophers Hosp Children, Dept Pediat, Philadelphia, PA 19104 USA. RP Higgins, RD (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03B,MSC 7510, Bethesda, MD 20892 USA. EM higginsr@mail.nih.gov NR 7 TC 27 Z9 27 U1 0 U2 0 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 MAY PY 2005 VL 115 IS 5 BP 1392 EP 1396 DI 10.1542/peds.2004-1989 PG 5 WC Pediatrics SC Pediatrics GA 922JM UT WOS:000228833500042 PM 15867051 ER PT J AU Batton, DG Blackmon, LR Adamkin, DH Bell, EF Denson, SE Engle, WA Martin, GI Stark, AR Barrington, KJ Raju, TNK Riley, L Tomashek, KM Wallman, C Couto, J AF Batton, DG Blackmon, LR Adamkin, DH Bell, EF Denson, SE Engle, WA Martin, GI Stark, AR Barrington, KJ Raju, TNK Riley, L Tomashek, KM Wallman, C Couto, J CA Comm Fetus Newborn 2004-2005 TI Underwater births SO PEDIATRICS LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; NEAR-DROWNING EXPERIENCE; WATER BIRTH; FIRST STAGE; LABOR; IMMERSION; BABIES C1 William Beaumont Hosp, Dept Pediat, Royal Oak, MI 48073 USA. Univ Maryland, Sch Med, Dept Pediat, Div Neonatol, Baltimore, MD 21201 USA. Univ Louisville, Dept Pediat, Louisville, KY 40202 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Univ Texas, Dept Pediat Neonatol, Houston, TX 77030 USA. Indiana Univ, Med Ctr, James Whitcomb Riley Hosp Children, Dept Pediat, Indianapolis, IN 46202 USA. Citrus Valley Med Ctr, W Covina, CA 91790 USA. Baylor Coll Med, Dept Neonatol, Houston, TX 77030 USA. Royal Victoria Hosp, Dept Neonatol, Montreal, PQ H3A 1A1, Canada. NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20847 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Ctr Dis Control & Prevent, Maternal & Infant Hlth Branch, Atlanta, GA 30333 USA. Natl Assoc Neonatal Nurses, Wellington, CO 80549 USA. Amer Acad Pediat, Div Hosp & Surg Serv, Elk Grove Village, IL 60007 USA. RP Batton, DG (reprint author), William Beaumont Hosp, Dept Pediat, 3601 W 13 Mile Rd, Royal Oak, MI 48073 USA. EM dgbatton@beaumont.edu OI Barrington, Keith/0000-0001-9669-5094 NR 22 TC 6 Z9 6 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2005 VL 115 IS 5 BP 1413 EP 1414 DI 10.1542/peds.2004-1738 PG 2 WC Pediatrics SC Pediatrics GA 922JM UT WOS:000228833500045 PM 15867054 ER PT J AU Kang, DH Gridley, G Huang, WY Engel, LS Winn, DM Brown, LM Bravo-Otero, E Wu, TX Diehl, SR Hayes, RB AF Kang, DH Gridley, G Huang, WY Engel, LS Winn, DM Brown, LM Bravo-Otero, E Wu, TX Diehl, SR Hayes, RB TI Microsatellite polymorphisms in the epidermal growth factor receptor (EGFR) gene and the transforming growth factor-alpha (TGFA) gene and risk of oral cancer in Puerto Rico SO PHARMACOGENETICS AND GENOMICS LA English DT Article DE oral cancer; EGFR; TGFA; Puerto Rico ID SQUAMOUS-CELL CARCINOMA; LUNG-CANCER; BETA-CAROTENE; NECK-CANCER; VITAMIN-A; HEAD; LEUKOPLAKIA; EXPRESSION; PREVENTION; GENOTYPE AB Objectives and methods Risks of oral cancer related to a CA microsatellite repeat polymorphism in intron 1 of the epidermal growth factor receptor (EGFR) gene and a Taql polymorphism in the transforming growth factor-α (TGFA) gene were evaluated in a population- based case-control study consisting of 157 cases and 149 controls recruited in Puerto Rico. Results Carriers of !: 16 CA repeats in EGFR showed a 1.9-fold increased risk for oral cancer (OR= 1.9, 95% Cl = 1.0-3.5). Risks also tended to increase with decreasing number of alleles with &GE; 16 CA repeats (P for trend = 0.06). Our data suggested a non-significant reduction in risk for subjects heterozygous for the TGFA polymorphism (OR = 0.6, 95% Cl = 0.2-1.3). Conclusions The EGFR-associated risk appeared to be independent of tobacco and alcohol use and may be restricted primarily to subjects who consumed low amounts of fresh fruits and vegetables (OR=5.9, 95%Cl:2.3-15.2). These data implicate dietary and molecular targets for oral cancer prevention. © 2005 Lippincott Williams & Wilkins. C1 Seoul Natl Univ, Coll Med, Inst Canc Res, Dept Prevent Med, Seoul 110799, South Korea. Mem Sloan Kettering Canc Ctr, Div Canc Epidemiol & Genet, Dept Epidemiol & Biostat, New York, NY 10021 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Puerto Rico, San Juan, PR 00936 USA. NIDCR, Craniofacial Epidemiol & Genet Branch, Bethesda, MD USA. RP Kang, DH (reprint author), Seoul Natl Univ, Coll Med, Inst Canc Res, Dept Prevent Med, 28 Yongon Dong, Seoul 110799, South Korea. EM dhkang@snu.ac.kr RI Kang, Dae Hee/E-8631-2012 NR 27 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1744-6872 J9 PHARMACOGENET GENOM JI Pharmacogenet. Genomics PD MAY PY 2005 VL 15 IS 5 BP 343 EP 347 DI 10.1097/01213011-200505000-00010 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 926BY UT WOS:000229099000010 PM 15864136 ER PT J AU Eid, NC Fant, RV Moolchan, ET Pickworth, WB AF Eid, NC Fant, RV Moolchan, ET Pickworth, WB TI Placebo cigarettes in a spaced smoking paradigm SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE smoking; cigarettes; tobacco craving; withdrawal; spaced smoking; placebo cigarettes; denicotinized cigarettes ID CARBON-MONOXIDE EXPOSURE; BRAIN MONOAMINE-OXIDASE; FILTER VENT BLOCKING; NICOTINE DELIVERY; TOBACCO SMOKING; HEART-RATE; SMOKERS; DEPRIVATION; TOPOGRAPHY; WITHDRAWAL AB Existing evidence supports the notion that nicotine delivery and recentness of smoking mediate the effects of smoking, including decreases in tobacco craving. However, smoking placebo (denicotinized) cigarettes decreases tobacco craving after overnight abstinence. The present study tested whether the recentness of smoking was an important determinant in the ability of a placebo cigarette to reduce tobacco craving. Placebo (0.07 mg nicotine) and conventional (1.1 mg nicotine) cigarettes were used in a spaced smoking paradigm. In six experimental sessions lasting 240 min, subjects smoked either a placebo or conventional nicotine cigarette in intervals of either 30, 60, or 240 min. Heart rate (HR), exhaled carbon monoxide (CO) levels, and subjective (Schuh-Stitzer, QSU) measures of tobacco craving were obtained throughout the spaced smoking paradigm. HR and CO levels increased after smoking both types of cigarettes. Increasing the interval since the last cigarette significantly (p <0.001) increased the baseline values of tobacco craving. Smoking either the placebo or the conventional cigarette caused a significant (p<0.01) reduction in the craving score after smoking. However, the nicotine yield of the cigarette did not influence these patterns. It is concluded that acute tobacco cravings can be repeatedly diminished with cigarettes that do not deliver nicotine. (C) 2005 Elsevier Inc. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. RP Pickworth, WB (reprint author), CPHRE, 6115 Falls Rd,Suite 200, Baltimore, MD 21209 USA. EM pickworthw@battelle.org NR 45 TC 8 Z9 8 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2005 VL 81 IS 1 BP 158 EP 164 DI 10.1016/j.pbb.2005.03.007 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 932BU UT WOS:000229530000020 PM 15894074 ER PT J AU Thanos, PK Katana, JM Ashby, CR Michaelides, M Gardner, EL Heidbreder, CA Volkow, ND AF Thanos, PK Katana, JM Ashby, CR Michaelides, M Gardner, EL Heidbreder, CA Volkow, ND TI The selective dopamine D3 receptor antagonist SB-277011-A attenuates ethanol consumption in ethanol preferring (P) and non-preferring (NP) rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE alcoholism; addiction; dopamine; drinking ID D-3 RECEPTOR; D2 RECEPTORS; ALCOHOL-DRINKING; PLACE PREFERENCE; COCAINE-SEEKING; KNOCKOUT MICE; BEHAVIOR; BRAIN; DEPENDENCE; LIGANDS AB The mesolimbic dopamine (DA) system plays an important role in mediating addiction to alcohol and other drugs of abuse. Recent evidence points toward the role of the DA D3 receptor (D3R) in drug-induced reward, drug-taking, as well as cue-, drug-, and stress-triggered relapse to drug-seeking behavior. Accordingly, the present study examined the effects of acute selective antagonism of the D3R on ethanol consumption in alcohol Preferring (P) and Non-Preferring (NP) rats. We employed the two-bottle choice paradigm to monitor ethanol consumption in these rats before and after treatment with 3, 10, and 30 mg/kg (i.p.) of the selective D3R antagonist SB-277011-A. Results indicated a significant attenuation in ethanol preference, intake and lick responses in P rats treated with 10 and 30 mg/kg SB-277011-A. A similar, though not as robust effect was observed in ethanol consumption in the NP rats when treated with 30 mg/kg SB-277011-A. Finally, the acute administration of SB-277011-A did not produce extrapyramidal side effects, as indicated by stable lick response-volume ratios and lick response time distributions. These results further support the notion that the D3R is important in mediating the addictive properties of alcohol and suggest that selective blockade of the D3R may constitute a new and useful target for prospective pharmacotherapeutic approaches to alcoholism. (C) 2005 Elsevier Inc. All rights reserved. C1 Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol Lab, Upton, NY 11973 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. GlaxoSmithKline Pharmaceut, Psychiat Ctr Excellence Drug Discovery, I-37135 Verona, Italy. NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Dev, Bethesda, MD 20892 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Neuropharmacol Lab, Bldg 490, Upton, NY 11973 USA. EM thanos@bnl.gov RI Michaelides, Michael/K-4736-2013 OI Michaelides, Michael/0000-0003-0398-4917 FU NIAAA NIH HHS [AA 11034, AA07611, AA07574] NR 35 TC 57 Z9 58 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD MAY PY 2005 VL 81 IS 1 BP 190 EP 197 DI 10.1016/j.pbb.2005.03.013 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 932BU UT WOS:000229530000024 PM 15894078 ER PT J AU Begg, M Pacher, P Batkai, S Osei-Hyiaman, D Offertaler, L Mo, FM Liu, H Kunos, G AF Begg, M Pacher, P Batkai, S Osei-Hyiaman, D Offertaler, L Mo, FM Liu, H Kunos, G TI Evidence for novel cannabinoid receptors SO PHARMACOLOGY & THERAPEUTICS LA English DT Review DE endocannabinoids; cannabinoid receptors; endothelium; vasodilation; hippocampus ID MESENTERIC ARTERIAL BED; ANANDAMIDE-INDUCED VASORELAXATION; ACTIVATED PROTEIN-KINASES; SENSITIVE SENSORY NERVES; LONG-TERM POTENTIATION; RAT HIPPOCAMPAL SLICE; CB1 RECEPTOR; ENDOGENOUS CANNABINOIDS; VANILLOID RECEPTORS; INVERSE AGONIST AB Cannabinoids, including the bioactive constituents of the marijuana plant, their synthetic analogs, and endogenous lipids with cannabinoid-like activity, produce their biological effects by interacting with specific receptors. To date, two G protein-coupled cannabinoid receptors have been identified by molecular cloning, CB1 receptors mainly expressed in the brain and mediating most of the neurobehavioral effects of cannabinoids and CB2 receptors expressed by immune and hematopoietic tissues. Recent findings indicate that some cannabinoid effects are not mediated by either CB1 or CB2 receptors, and in some cases there is compelling evidence to implicate additional receptors in these actions. These include transient receptor potential vanilloid 1 (TRPV1) receptors and as-yet-unidentified receptors implicated in the endothelium-dependent vasodilator effect of certain cannabinoids and in the presynaptic inhibition of glutamatergic neurotransmission in the hippocampus. The case for these additional receptors is being reviewed here. (c) 2004 Elsevier Inc. All rights reserved. C1 NIAAA, NIH, Bethesda, MD USA. RP Kunos, G (reprint author), NIAAA, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD USA. EM gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; NR 125 TC 257 Z9 276 U1 1 U2 12 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 MAY PY 2005 VL 106 IS 2 BP 133 EP 145 DI 10.1016/j.pharmthera.2004.11.005 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 929LN UT WOS:000229347700001 PM 15866316 ER PT J AU Reszka, KJ Takayama, M Sik, RH Chignell, CF Saito, I AF Reszka, KJ Takayama, M Sik, RH Chignell, CF Saito, I TI Photochemistry of naphthalene diimides: EPR study of free radical formation via photoredox process SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID BIS-NAPHTHALIMIDE; ELECTRON-TRANSFER; PI-STACKS; DNA; DERIVATIVES; IMIDE; ACID; 1,8-NAPHTHALIMIDE; HYDROPEROXIDE; MECHANISMS AB Earlier studies have shown that on exposure to UVA, hydroperoxynaphthalene diimide (IA) generates hydroxyl radicals, induces DNA strand scission, and kills cells. Here we employed electron paramagnetic resonance (EPR) and spin trapping to investigate the free radical photochemistry of IA and that of related naphthalene diimides, which are devoid of the hydroperoxyl moiety (N,N'-bis[2-methyl]-1,4,5,8-naphthaldiimide [IB], N,N'-bis[2-thiomethyl-2-methoxyethyl]-1,4,5,8-naphthaldiimide [IC]) and therefore are unable to generate hydroxyl radicals. It is shown that on UV irradiation (> 300 nm) in air-free methanol or ethanol solutions all these naphthalene diimides undergo one-electron reduction to corresponding anion radicals, positively identified by EPR. With EPR and a spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO), we found that the photogeneration of the naphthalene diimide radicals is concomitant with the formation of radicals from the solvents, presumably through electron/hydrogen atom abstraction by photoactivated diimides. Irradiation of IA, IB or IC in the presence of oxygen generates superoxide, which was detected as a DMPO adduct. The high photoreactivity of IB and IC supports the notion that hydroperoxide IA can induce oxidative damage via photoprocesses that are independent of (OH)-O-center dot generation. These observations could be pertinent to the application of naphthalene diimides as selective photonucleases, PDT anticancer agents or both. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Kyoto Univ, Fac Engn, Dept Synthet Chem, Kyoto 606, Japan. RP Reszka, KJ (reprint author), Univ Cincinnati, Dept Internal Med, 231 Albert Sabin Way,ML 0557, Cincinnati, OH 45267 USA. EM reszkakj@ucmail.uc.edu NR 24 TC 7 Z9 7 U1 5 U2 26 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD MAY-JUN PY 2005 VL 81 IS 3 BP 573 EP 580 DI 10.1562/2004-11-15-RA-372.1 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 935CP UT WOS:000229757200018 PM 16032776 ER PT J AU Clay, JR AF Clay, JR TI Axonal excitability revisited SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE action potential; K+ and Na+ channels; mathematical models ID SQUID GIANT-AXON; PERSISTENT SODIUM CURRENT; CAT NEOCORTICAL NEURONS; K+ CHANNEL ACTIVATION; VOLTAGE CLAMP DATA; SINGLE-CHANNEL; GATING CURRENTS; NERVE MEMBRANE; POTASSIUM PERMEABILITY; DELAYED-RECTIFIER AB The original papers of Hodgkin and Huxley (J. Physiol. 116 (1952a) 449,. J. Physiol. 116 (1952b) 413: J. Physiol. 116 (1952c) 497, J. Physiol. 117 (1952d) 500) have provided a benchmark in our understanding of cellular excitability. Not surprisingly, their model of the membrane action potential (AP) requires revisions even for the squid giant axon, the preparation for which it was originally formulated. The mechanisms they proposed for the voltage-gated potassium and sodium ion currents, I-K, and I-Na, respectively, have been superceded by more recent formulations that more accurately describe voltage-clamp measurements of these components. Moreover, the current-voltage relation for IK has a non-linear dependence upon driving force that is well described by the Goldman-Hodgkin-Katz (GHK) relation, rather than the linear dependence on driving force found by Hodgkin and Huxley. Furthermore, accumulation of potassium ions in the extracellular space adjacent to the axolemma appears to be significant even during a single AP. This paper describes the influence of these various modifications in their model on the mathematically reconstructed AP. The GHK and K+ accumulation results alter the shape of the AP. whereas the modifications in I-K and I-Na gating have surprisingly little effect. Perhaps the most significant change in their model concerns the amplitude of I-Na, which they appear to have overestimated by a factor of two. This modification together with the GHK and the K+ accumulation results largely remove the discrepancies between membrane excitability of the squid giant axon and the Hodszkin and Huxley. (J. Physiol. 117 (1952d) 500) model previously described (Clay, J. Neurophysiol. 80 (1998) 903). Published by Elsevier Ltd. C1 NINDS, Ion Channel Biophys Grp, NIH, Bethesda, MD 20892 USA. RP Clay, JR (reprint author), NINDS, Ion Channel Biophys Grp, NIH, Bldg 36,Rm 4D21,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jrclay@ninds.nih.gov NR 108 TC 28 Z9 29 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD MAY PY 2005 VL 88 IS 1 BP 59 EP 90 DI 10.1016/j.pbiomolbio.2003.12.004 PG 32 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 890GL UT WOS:000226499600002 PM 15561301 ER PT J AU Zheng, WJ Doniach, S AF Zheng, WJ Doniach, S TI Fold recognition aided by constraints from small angle X-ray scattering data SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE fold recognition; linear regression; neural network; small angle X-ray scattering ID PROTEIN-STRUCTURE PREDICTION; STRUCTURAL GENOMICS; SEQUENCES; SEARCH AB We performed a systematic exploration of the use of structural information derived from small angle X-ray scattering (SAXS) measurements to improve fold recognition. SAXS data provide the Fourier transform of the histogram of atomic pair distances (pair distribution function) for a given protein and hence can serve as a structural constraint on methods used to determine the native conformational fold of the protein. Here we used it to construct a similarity-based fitness score with which to evaluate candidate structures generated by a threading procedure. In order to combine the SAXS scores with the standard energy scores and other 1D profile-based scores used in threading, we made use both of a linear regression method and of a neural network-based technique to obtain optimal combined fitness scores and applied them to the ranking of candidate structures. Our results show that the use of SAXS data with gapless threading significantly improves the performance of fold recognition. C1 Stanford Univ, Dept Phys, Stanford, CA 94305 USA. Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA. Stanford Univ, Adv Mat Lab, Stanford, CA 94305 USA. NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zheng, WJ (reprint author), Stanford Univ, Dept Phys, Stanford, CA 94305 USA. EM zhengwj@helix.nih.gov OI Zheng, Wenjun/0000-0002-6236-9765 NR 23 TC 18 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD MAY PY 2005 VL 18 IS 5 BP 209 EP 219 DI 10.1093/protein/gzi026 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 934HJ UT WOS:000229699600001 PM 15845555 ER PT J AU Pollard, HB Ji, XD Jozwik, C Jacobowitz, DM AF Pollard, HB Ji, XD Jozwik, C Jacobowitz, DM TI High abundance protein profiling of cystic fibrosis lung epithelial cells SO PROTEOMICS LA English DT Article DE cystic fibrosis; epithelial cells; lung; protein; two-dimensional gel electrophoresis ID HEAT-SHOCK PROTEINS; TRANSMEMBRANE CONDUCTANCE REGULATOR; IMMOBILIZED PH GRADIENTS; CASEIN KINASE-II; MOLECULAR CHARACTERIZATION; PROTEOMIC ANALYSIS; GENE-EXPRESSION; IDENTIFICATION; PHOSPHORYLATION; HSP70 AB Protein profiles of cultured cystic fibrosis (CF) lung epithelial cells were analyzed by two-dimensional gel electrophoresis and mass spectrometry (MS). The analysis gave rise to a protein map over the pI range of 4-7, and a molecular weight range of ca. 100-10 kDa. The map contains 194 identified proteins, which were detectable by silver stain. All silver stained features were identified by matrix-assisted laser desorption/ionization-time of flight MS of tryptic peptides. Some proteins were found to be represented by multiple features on the 2-D gel. Among the high abundance proteins identified were sets of proteins associated with inflammation, including the classical NFκ B, p65 (RelA) and NFκ B, p65 (RelB). We suggest that this composite atlas of the high abundance CF lung epithelial proteome will serve as a reference database for future studies of candidate CF drugs, validating different approaches to CFTR gene therapy, and analogous investigations of other types of human lung disorders. C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Sch Med, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Inst Mol Med, Sch Med, Bethesda, MD 20814 USA. NIMH, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Jacobowitz, DM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Sch Med, Bethesda, MD 20814 USA. EM dwj@helix.nih.gov FU NHLBI NIH HHS [N01-HV-28187]; NIDDK NIH HHS [R01-DK-53051] NR 53 TC 26 Z9 26 U1 0 U2 0 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 MAY PY 2005 VL 5 IS 8 BP 2210 EP 2226 DI 10.1002/pmic.200401120 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932LJ UT WOS:000229554900020 PM 15852339 ER PT J AU Le, AD Harding, S Juzytsch, W Funk, D Shaham, Y AF Le, AD Harding, S Juzytsch, W Funk, D Shaham, Y TI Role of alpha-2 adrenoceptors in stress-induced reinstatement of alcohol seeking and alcohol self-administration in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE alpha-2 adrenoceptors; alcohol self-administration; craving; noradrenaline; reinstatement; relapse; stress ID CORTICOTROPIN-RELEASING-FACTOR; POSITIVE REINFORCING PROPERTIES; DOPAMINE-BETA-HYDROXYLASE; COCAINE-SEEKING; NORADRENERGIC MECHANISMS; ETHANOL INTAKE; EXPLORATORY ACTIVITY; DRUG DISCRIMINATION; PRIMING INJECTIONS; STRIA TERMINALIS AB Rationale and objective: Alpha-2 adrenoceptors are known to be involved in stress-induced reinstatement of heroin and cocaine seeking in laboratory animals. Here, we studied the involvement of these receptors in stress-induced reinstatement of alcohol seeking by using an agonist (lofexidine) and an antagonist (yohimbine) of these receptors, which inhibit and activate, respectively, noradrenaline transmission. We also tested the effect of lofexidine and yohimbine on alcohol self-administration. Lofexidine is used clinically for treating opiate withdrawal symptoms and yohimbine induces stress-like responses in humans and non-humans. Methods: Rats were trained to self-administer alcohol (12% w/v, 1 h/day) and after extinction of the alcohol-reinforced behavior, they were tested for the effect of lofexidine (0, 0.05 and 0.1 mg/kg, IP) on reinstatement of alcohol seeking induced by intermittent footshock stress (10 min, 0.8 mA) or for the effect of yohimbine (0, 1.25 and 2.5 mg/kg, IP) on reinstatement of alcohol seeking. Other rats were trained to self-administer alcohol, and after stable responding, the effects of lofexidine and yohimbine on alcohol self-administration were determined. Results: Pretreatment with lofexidine (0.05 mg/kg and 0.1 mg/kg) attenuated stress-induced reinstatement of alcohol seeking and also decreased alcohol self-administration. In contrast, yohimbine pretreatment potently reinstated alcohol seeking after extinction and also induced a profound increase in alcohol self-administration. Conclusions: Results indicate that activation of alpha-2 adrencoceptors is involved in both stress-induced reinstatement of alcohol seeking and alcohol self-administration. To the degree that the present results are relevant to human alcoholism, alpha-2 adrencoceptor agonists should be considered in the treatment of alcohol dependence. C1 Ctr Addict & Mental Hlth, Dept Neurosci, Toronto, ON M5S 2S1, Canada. Univ Toronto, Dept Pharmacol & Psychiat, Toronto, ON, Canada. NIDA, IRP, Behav Neurosci Branch, DHHS,NIH, Baltimore, MD USA. RP Le, AD (reprint author), Ctr Addict & Mental Hlth, Dept Neurosci, 33 Russell St, Toronto, ON M5S 2S1, Canada. EM anh_le@camh.net RI shaham, yavin/G-1306-2014 NR 72 TC 163 Z9 167 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2005 VL 179 IS 2 BP 366 EP 373 DI 10.1007/s00213-004-2036-y PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915GG UT WOS:000228285500005 PM 15551068 ER PT J AU Panlilio, LV Thorndike, EB Schindler, CW AF Panlilio, LV Thorndike, EB Schindler, CW TI Lorazepam reinstates punishment-suppressed remifentanil self-administration in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE aversive conditioning; priming; conflict; punishment; relapse; benzodiazepines; remifentanil; heroin ID CONFLICT BEHAVIOR; COCAINE-SEEKING; RHESUS-MONKEY; CHLORDIAZEPOXIDE; EXTINCTION; SHOCK; TOLERANCE; ETHANOL; RELAPSE; HEROIN AB Rationale: We recently described a reinstatement procedure that models relapse to drug abuse in cases where abstinence results from aversive consequences of drug use. The potential value of this punishment-based model of relapse depends on its sensitivity to relapse-inducing events that are ineffective in the widely used extinction-based model. Objectives: It is known that certain drugs can have antipunishment effects, but these drugs have not been tested in the punishment-based reinstatement procedure. Therefore, the effects of the benzodiazepine, lorazepam, were examined using punishment-based and extinction-based reinstatement procedures. Methods: Rats self-administered the opioid, remifentanil (4 mu g/kg per infusion). Two punishment groups were trained with response-contingent footshock that suppressed baseline rates of responding to zero. In an extinction group, remifentanil delivery was discontinued, and baseline responding stabilized at a low rate (mean=0.06 responses/min). Lorazepam (0.08-10 mg/kg, IP) was given during test sessions with the shock contingency discontinued for both punishment groups. Remifentanil delivery was maintained during testing in one punishment group but not the other. Results: Lorazepam reinstated self-administration responding in both punishment groups but not in the extinction group. Priming injections of heroin reinstated responding in both the punishment and extinction groups, but combining heroin and lorazepam did not enhance reinstatement. Conclusions: This is the first demonstration that a trigger for relapse may have different effects depending on whether aversive conditioning contributed to the achievement of abstinence. It may be important to consider potential antipunishment effects of both abused drugs and therapeutic agents in the treatment of individuals with a history of drug abuse. C1 NIDA, Schindler Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NHHS,NIH, Baltimore, MD 21224 USA. RP Panlilio, LV (reprint author), NIDA, Schindler Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NHHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lpanlili@intra.nida.nih.gov NR 43 TC 24 Z9 25 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2005 VL 179 IS 2 BP 374 EP 382 DI 10.1007/s00213-004-2040-2 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915GG UT WOS:000228285500006 PM 15821953 ER PT J AU Cheskin, LJ Hess, JM Henningfield, J Gorelick, DA AF Cheskin, LJ Hess, JM Henningfield, J Gorelick, DA TI Calorie restriction increases cigarette use in adult smokers SO PSYCHOPHARMACOLOGY LA English DT Article DE cigarettes; calorie restriction; human ID CHRONIC FOOD RESTRICTION; SMOKING-CESSATION; WEIGHT-GAIN; UNITED-STATES; BODY-WEIGHT; ALCOHOL-CONSUMPTION; HARM REDUCTION; CONTROL WOMEN; DEPRIVATION; NICOTINE AB Cigarette smokers weigh less than nonsmokers, and smokers often gain weight when they quit. This is a major barrier to smoking cessation, especially among women. However, strict dieting is not recommended during smoking cessation out of concern that it might promote relapse. This concern derives, in part, from the observation that calorie restriction increases self-administration of drugs of abuse in animals. This relationship has never been experimentally demonstrated in humans. To evaluate whether calorie restriction increases cigarette smoking in humans. Seventeen (nine males, eight females) healthy, normal-weight smokers not attempting to quit were cycled in partially counterbalanced order, double-blind, through four diets-normal calorie (2,000-2,800 kcal/day), low calorie (700 kcal/day deficit), low-carbohydrate (CHO)/normal-calorie, and low-CHO/low-calorie-for 6 days per diet in an inpatient research ward. Smoking was assessed by cigarette counts, breath carbon monoxide (CO) levels, and cigarette craving. Compared with the normal-calorie diet, while on the low-calorie diet, subjects smoked 8% more cigarettes (P < 0.02) and had 11% higher breath CO levels (P < 0.01). The low-CHO/normal-calorie diet showed no significant effect on either variable, but there was a 15% increase in breath CO levels (P < 0.05) on the low-CHO/low-calorie diet. There were no changes in self-reported cigarette craving or mood. Consistent with animal studies, moderate calorie restriction was associated with a small but statistically significant increase in cigarette smoking, with no independent effect of CHO deprivation. These findings suggest that dieting may increase smoking behavior and could impede smoking-cessation attempts. C1 NIDA, Dept Hlth & Human Serv, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Pinney Associates, Bethesda, MD USA. RP Gorelick, DA (reprint author), NIDA, Dept Hlth & Human Serv, Intramural Res Program, NIH, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU NCRR NIH HHS [5M01-RR-02719] NR 49 TC 31 Z9 32 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2005 VL 179 IS 2 BP 430 EP 436 DI 10.1007/s00213-004-2037-x PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915GG UT WOS:000228285500012 PM 15565433 ER PT J AU Goldberg, SR Panlilio, LV Harvey, DM Yasar, S Heishman, SJ Henningfield, JE AF Goldberg, SR Panlilio, LV Harvey, DM Yasar, S Heishman, SJ Henningfield, JE TI Nicotine may reinforce intravenous drug-taking behavior in drug users: reply to R. Dar and H. Frenk (2005) SO PSYCHOPHARMACOLOGY LA English DT Letter ID ABUSE LIABILITY ASSESSMENT C1 NIDA, Preclin Pharmacol Sect, DHHS, NIH, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Branch, DHHS, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. NIDA, Behav Neurosci Sect, DHHS, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. Pinney Associates, Bethesda, MD 20814 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, DHHS, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2005 VL 179 IS 2 BP 518 EP 519 DI 10.1007/s00213-004-2124-z PG 2 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915GG UT WOS:000228285500023 ER PT J AU Solinas, M Ferre, S Antoniou, K Quarta, D Justinova, Z Hockemeyer, J Pappas, LA Segal, PN Wertheim, C Muller, CE Goldberg, SR AF Solinas, M Ferre, S Antoniou, K Quarta, D Justinova, Z Hockemeyer, J Pappas, LA Segal, PN Wertheim, C Muller, CE Goldberg, SR TI Involvement of adenosine A(1) receptors in the discriminative-stimulus effects of caffeine in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE caffeine; drug discrimination; adenosine receptors; dopamine; glutamate; binding ID A(2A) RECEPTORS; XANTHINE DERIVATIVES; STRIATAL MEMBRANES; NUCLEUS-ACCUMBENS; DOPAMINE; ANTAGONISTS; HUMANS; RADIOLIGAND; GLUTAMATE; PRODRUGS AB Rationale: Caffeine is a non-selective adenosine receptor antagonist in vitro, but involvement of different adenosine receptor subtypes, particularly adenosine A(1) and A(2A) receptors, in the central effects of caffeine remains a matter of debate. Objective: Investigate the role of adenosine A(1) and A(2A) receptors in the discriminative-stimulus effects of caffeine. Methods: Rats were trained to discriminate an injection of 30 mg/kg ( i.p.) caffeine from saline. The selective A(1) receptor antagonist CPT, the selective A(2A) receptor antagonist MSX-3 and the non-selective adenosine receptor antagonist DMPX were assessed for their ability to produce caffeine-like discriminative effects. The ability of CPT, MSX-3, the A(1) receptor agonist CPA and the A(2A) receptor agonist CGS21680 to reduce the discriminative effects of caffeine was also tested. Radioligand binding experiments with membrane preparations from rat striatum and transfected mammalian cell lines were performed to characterize binding affinity profiles of the different adenosine antagonists used in the present study ( caffeine, DMPX, CPT and MSX-3) in relation to all known adenosine receptors (A(1), A(2A), A(2B), A(3)). Results: DMPX and CPT, but not MSX-3, produced significant caffeine-like discriminative effects. MSX-3, but not CPT, markedly reduced the discriminative effects of caffeine and the caffeine-like discriminative effects of CPT. Furthermore, the A(1) receptor agonist CPA, but not the A(2A) agonist CGS21680, reduced caffeine's discriminative effects. Conclusions: Adenosine A(1) receptor blockade is involved in the discriminative-stimulus effects of behaviorally relevant doses of caffeine; A(2A) receptor blockade does not play a central role in caffeine's discriminative effects and counteracts the A(1) receptor-mediated discriminative-stimulus effects of caffeine. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, IRP,NIH,DHHS, Baltimore, MD 21224 USA. Univ Athens, Sch Med, Dept Pharmacol, GR-11527 Athens, Greece. Univ Bonn, Inst Pharmaceut, D-53115 Bonn, Germany. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, IRP,NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Justinova, Zuzana/A-9109-2011; Solinas, Marcello/M-3500-2016; Muller, Christa/C-7748-2014 OI Ferre, Sergi/0000-0002-1747-1779; Justinova, Zuzana/0000-0001-5793-7484; Solinas, Marcello/0000-0002-0664-5964; Muller, Christa/0000-0002-0013-6624 NR 33 TC 29 Z9 31 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD MAY PY 2005 VL 179 IS 3 BP 576 EP 586 DI 10.1007/s00213-004-2081-6 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 922PM UT WOS:000228850000008 PM 15696333 ER PT J AU Lane, RD Laukes, C Marcus, FI Chesney, MA Sechrest, L Gear, K Fort, CL Priori, SG Schwartz, PJ Steptoe, A AF Lane, RD Laukes, C Marcus, FI Chesney, MA Sechrest, L Gear, K Fort, CL Priori, SG Schwartz, PJ Steptoe, A TI Psychological stress preceding idiopathic ventricular fibrillation SO PSYCHOSOMATIC MEDICINE LA English DT Article DE idiopathic ventricular fibrillation; sudden cardiac death; psychologic stress; coronary heart disease ID SUDDEN CARDIAC DEATH; ACUTE MYOCARDIAL-INFARCTION; APPARENTLY NORMAL HEART; ISCHEMIC HEART; ARRHYTHMIAS; MORTALITY; SUBSTRATE; SYMPTOMS; PREVENTS; TRIGGERS AB Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease (CHD), but its role in patients experiencing cardiac arrest with apparently normal hearts is unknown. This study sought to determine the role of psychosocial stress as a precipitant of cardiac arrest in patients with apparently normal hearts, so-called idiopathic ventricular fibrillation (IVF). Methods: We interviewed 25 IVF survivors (12 men, 13 women) and 25 matched comparison patients regarding life events during the 6 months and 24 hours preceding the cardiac event. The comparison group consisted of patients with an acute myocardial infarction or angina pectoris requiring angioplasty but without cardiac arrest. Judges independently rated written summaries of these interviews for psychosocial stress at each time point on a three-point scale (low, moderate, severe). Results: During the 6 months before the cardiac event, 20 patients sustaining IVF had severe/moderate stress and five had low stress, whereas 10 comparison patients had severe/moderate stress and 15 had low stress (Fisher exact p = .008). During the preceding 24 hours, nine patients with IVF had severe/moderate stress and 16 had low stress, whereas two comparison patients bad severe/moderate stress and 22 had low stress (Fisher exact p = .04) (one silent myocardial infarction could not be precisely dated). Conclusion: These data suggest that psychosocial stress is playing a role in otherwise unexplained cardiac arrest. C1 Univ Arizona, Dept Psychiat, Tucson, AZ 85724 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85724 USA. Int Heart Inst Montana, Missoula, MT USA. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. Univ Arizona, Sarver Heart Ctr, Tucson, AZ 85724 USA. Univ Pavia, Dept Cardiol, I-27100 Pavia, Italy. IRCCS, Policlin San Matteo, Pavia, Italy. UCL, Dept Epidemiol & Publ Hlth, London, England. RP Lane, RD (reprint author), Univ Arizona, Dept Psychiat, 1501 N Campbell Ave, Tucson, AZ 85724 USA. EM lane@email.arizona.edu RI Schwartz, Peter/J-4267-2016; OI Schwartz, Peter/0000-0003-0367-1048; Steptoe, Andrew/0000-0001-7808-4943 NR 32 TC 26 Z9 27 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0033-3174 EI 1534-7796 J9 PSYCHOSOM MED JI Psychosom. Med. PD MAY-JUN PY 2005 VL 67 IS 3 BP 359 EP 365 DI 10.1097/01.psy.0000160476.67536.41 PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 929MI UT WOS:000229349800004 PM 15911897 ER PT J AU Parascandola, M AF Parascandola, M TI Science, industry, and tobacco harm reduction: A case study of tobacco industry scientists' involvement in the national cancer institute's smoking and health program, 1964-1980 SO PUBLIC HEALTH REPORTS LA English DT Review ID WILLIAMSON DOCUMENTS C1 NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. RP Parascandola, M (reprint author), NCI, Tobacco Control Res Branch, 6130 Executive Blvd,MSC 7337 Executive Pl N,Rm 40, Bethesda, MD 20892 USA. EM paramark@mail.nih.gov NR 139 TC 15 Z9 15 U1 1 U2 2 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 2005 VL 120 IS 3 BP 338 EP 349 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 921RA UT WOS:000228781100021 PM 16134578 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 Adjusting lung cancer risks for temporal and spatial variations in radon concentration in dwellings in Gansu Province, China SO RADIATION RESEARCH LA English DT Article ID RESIDENTIAL RADON; INDOOR RADON; EXPOSURE ASSESSMENT; MEASUREMENT ERROR; MODELS AB Our recent study in Gansu Province, China reported an increasing risk of lung cancer with increasing residential radon concentration that was consistent with previous pooled analyses and with meta-analyses of other residential studies (Wang et al., Am. J. Epidemiol. 155, 554-564, 2002). Dosimetry used current radon measurements (1-year track-etch detectors) in homes to characterize concentrations for the previous 30 years, resulting in uncertainties in exposure and possibly reduced estimates of disease risk. We conducted a 3-year sub-study in 55 houses to model the temporal and spatial variability in radon levels and to adjust estimates of radon risk. Temporal variation represented the single largest source of uncertainty, suggesting the usefulness of multi-year measurements to assess this variation; however, substantial residual variation remained unexplained. The uncertainty adjustment increased estimates of the excess odds ratio by 50-100%, suggesting that residential radon studies using similar dosimetry may also underestimate radon effects. These results have important implications for risk assessment. (c) 2005 by Radiation Research Society. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Minist Hlth, Lab Ind Hyg, Beijing, Peoples R China. Int Epidemiol Inst, Beijing, Peoples R China. Environm Protect Agcy, Beijing, Peoples R China. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8042, Bethesda, MD 20892 USA. EM lubinj@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 FU NCI NIH HHS [Y01-CP5-0260] NR 35 TC 19 Z9 20 U1 1 U2 5 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 MAY PY 2005 VL 163 IS 5 BP 571 EP 579 DI 10.1667/RR3109 PG 9 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 918TO UT WOS:000228570700012 PM 15850419 ER PT J AU Nelson, JC Kronmal, RA Carr, JJ McNitt-Gray, MF Wong, ND Loria, CM Goldin, JG Williams, OD Detrano, R AF Nelson, JC Kronmal, RA Carr, JJ McNitt-Gray, MF Wong, ND Loria, CM Goldin, JG Williams, OD Detrano, R TI Measuring coronary calcium on CT images adjusted for attenuation differences SO RADIOLOGY LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; YOUNG-ADULTS CARDIA; ARTERY CALCIUM; RISK-FACTORS; DISEASE; ATHEROSCLEROSIS; EVENTS; PREDICTION; VARIABILITY; ANGIOGRAPHY AB PURPOSE: To quantify scanner and participant variability in attenuation values for computed tomographic (CT) images assessed for coronary calcium and define a method for standardizing attenuation values and calibrating calcium measurements. MATERIALS AND METHODS: Institutional review board approval and participant informed consent were obtained at all study sites. An image attenuation adjustment method involving the use of available calibration phantom data to define standard attenuation values was developed. The method was applied to images from two population-based multicenter studies: the Coronary Artery Risk Development in Young Adults study (3041 participants) and the Multi-Ethnic Study of Atherosclerosis (6814 participants). To quantify the variability in attenuation, analysis of variance techniques were used to compare the CT numbers of standardized torso phantom regions across study sites, and multivariate linear regression models of participant-specific calibration phantom attenuation values that included participant age, race, sex, body mass index (BMI), smoking status, and site as covariates were developed. To assess the effect of the calibration method on calcium measurements, Pearson correlation coefficients between unadjusted and attenuation-adjusted calcium measurements were computed. Multivariate models were used to examine the effect of sex, race, BMI, smoking status, unadjusted score, and site on Agatston score adjustments. RESULTS: Mean attenuation values (CT numbers) of a standard calibration phantom scanned beneath participants varied significantly according to scanner and participant BMI (P < .001 for both). Values were lowest for Siemens multi-detector row CT scanners (110.0 HU), followed by GE-Imatron electron-beam (116.0 HU) and GE LightSpeed multi-detector row scanners (121.5 HU). Values were also lower for morbidly obese (BMI, >= 40.0 kg/m(2)) participants (108.9 HU), followed by obese (BMI, 30.0-39.9 kg/m(2)) (114.8 HU), overweight (BMI, 25.0-29.9 kg/m(2)) (118.5 HU), and normal-weight or underweight (BMI, <25.0 kg/m(2)) (120.1 HU) participants. Agatston score calibration adjustments ranged from -650 to 1071 (mean, -8 +/- 50 [standard deviation]) and increased with Agatston score (P < .001). The direction and magnitude of adjustment varied significantly according to scanner and BMI (P < .001 for both) and were consistent with phantom attenuation results in that calibration resulted in score decreases for images with higher phantom attenuation values. CONCLUSION: Image attenuation values vary by scanner and participant body size, producing calcium score differences that are not due to true calcium burden disparities. Use of calibration phantoms to adjust attenuation values and calibrate calcium measurements in research studies and clinical practice may improve the comparability of such measurements between persons scanned with different scanners and within persons over time. (C) RSNA, 2005. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Wake Forest Univ, Sch Med, Dept Radiol, Winston Salem, NC 27109 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Radiol, Los Angeles, CA USA. Univ Calif Irvine, Coll Med, Div Cardiol, Heart Dis Prevent Program, Irvine, CA 92717 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. Harbor UCLA Res & Educ Inst, Div Cardiol, Los Angeles, CA USA. RP Nelson, JC (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Metropolitan Pk E,Suite 1600,1730 Minor Ave, Seattle, WA 98101 USA. EM nelson.jl@ghc.org RI Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; McNItt-Gray, Michael/0000-0003-3004-4613 FU NHLBI NIH HHS [N01 HC 95169, N01 HC 05187, N01 HC 48047, N01 HC 48048, N01 HC 48049, N01 HC 48050, N01 HC 95095, N01 HC 95159, N01 HC 95160, N01 HC 95161, N01 HC 95162, N01 HC 95163, N01 HC 95164, N01 HC 95165] NR 28 TC 62 Z9 63 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 403 EP 414 DI 10.1148/radiol.2352040515 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200010 PM 15858082 ER PT J AU Dittmar, KM Xie, JW Hunter, F Trimble, C Bur, M Frenkel, V Li, KCP AF Dittmar, KM Xie, JW Hunter, F Trimble, C Bur, M Frenkel, V Li, KCP TI Pulsed high-intensity focused ultrasound enhances systemic administration of naked DNA in squamous cell carcinoma model: Initial experience SO RADIOLOGY LA English DT Article ID MEDIATED GENE-TRANSFER; SONOPORATION IN-VITRO; SKELETAL-MUSCLE; CAROTID-ARTERY; PLASMID DNA; DELIVERY; VIVO; THERAPY; PERMEABILITY; TRANSFECTION AB PURPOSE: To determine whether exposures to pulsed high-intensity focused ultrasound can enhance local delivery and expression of a reporter gene, administered with systemic injection of naked DNA, in tumors in mice. MATERIALS AND METHODS: The study was performed according to an approved animal protocol and in compliance with guidelines of the institutional-animal care and use committee. Squamous cell carcinoma (SCC7) tumors Were induced subcutaneously in both flanks of female C3H mice (n = 3) and allowed to grow to, average size of 0.4 cm(3). In each mouse, one tumor was exposed to pulsed high- intensity focused ultrasound while a second tumor served as a control. Immediately after ultrasound exposure, a solution containing a cytomegalovirus-green fluorescent protein (GFP) reporter gene construct was injected intravenously via the tail vein. The mouse was sacrificed 24 hours later. Tissue specimens were viewed with fluorescence microscopy to determine the presence of GFP expression, and Western blot analysis was performed, at which signal intensities of expressed GFP were quantitated. A paired Student t test was used to compare mean values in controls with those in treated tumors. Histologic analyses were performed with specific techniques (hematoxylin-eosin staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) to determine whether tumor cells had been damaged by ultrasound exposure. RESULTS: GFP expression was present in all sections of tumors that received ultrasound exposure but not in control tumors. Results of signal intensity measurement at Western blot analysis showed expressed GFP to be nine times greater in, ultrasound-exposed tumors (160.2 +/- 24.5 [standard deviation]) than in controls (17.4 +/- 11.8) (P =.004, paired Student t test). Comparison of histologic sections from treated tumors with those from controls revealed no destructive effects-from ultrasound exposure. CONCLUSION: Local exposure to pulsed high-intensity focused ultrasound in tumors can enhance the delivery and expression of systemically injected naked DNA. (C) RSNA, 2005. C1 NIH, Dept Radiol, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Frenkel, V (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 1C657, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov NR 45 TC 68 Z9 73 U1 1 U2 5 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 541 EP 546 DI 10.1148/radiol.2352040254 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200027 PM 15798154 ER PT J AU Yocum, GT Wilson, LB Ashari, P Jordan, EK Frank, JA Arbab, AS AF Yocum, GT Wilson, LB Ashari, P Jordan, EK Frank, JA Arbab, AS TI Effect of human stem cells labeled with ferumoxides-poly-L-lysine on hematologic and biochemical measurements in rats SO RADIOLOGY LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; IN-VIVO TRACKING; TRANSFECTION AGENTS; NANOPARTICLES; TRAFFICKING; MONOCYTES; BRAIN AB PURPOSE: To determine whether ferumoxides-poly-L-lysine (PLL) complex-labeled mesenchymal stem cells (MSCs) or ferumoxides-PLL complex alone-alters hematologic, blood chemistry, renal function, and/or liver function measurements after being intravenously infused into rats. MATERIALS AND METHODS: Twenty-five rats (group 1) received intravenous injections of labeled MSCs, and 25 additional rats (group 2) received intravenous injections of ferumoxides-PLL complex only. Complete blood counts, liver and renal function test results, and serum electrolyte and iron concentrations were measured for 42 days after the injections and compared with those measured in five control rats (group 3). To determine the duration of labeled MSCs in the circulation, venous blood was serially drawn from five additional rats (group 4) that were injected with, labeled MSCs. Analyses of variance (ANOVA) followed by Fisher protected least significant difference post hoc tests were used to statistically analyze results. P<.05 was considered to indicate significance in all analyses. RESULTS: Administration of neither'labeled MSCs nor ferumoxides-PLL complei had a significant effect on hematologic or blood chemistry indicators of organ function. Of the parameters measured, only hemoglobin concentration and mean corpuscular volume (MCV) in the rats injected with labeled MSCs, as well as MCV. and hemoglobin, alkaline phosphatase, aspartate aminotransferase, and direct bilirubin concentrations in the rats injected with ferumoxides-PLL complex, varied significantly during the 42-day postinjection period (P <.05, ANOVA). No other measurements, including serum electrolyte and iron concentrations, changed significantly during the test period (P >.05). Furthermore, injected labeled MSCs had cleared from the peripheral circulation by 15 minutes after injection. CONCLUSION: Results indicate that infusing cells that are magnetically labeled., with ferumoxides-PLL complex into rats does not alter biochemical or hematologic measures of organ function in A clinically relevant or preclusive manner. (C) RSNA, 2005. C1 NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. RP Arbab, AS (reprint author), Henry Ford Hlth Syst, 1 Ford Pl,2F,Box 82, Detroit, MI 48188 USA. EM saali@rad.hfh.edu NR 19 TC 26 Z9 35 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 547 EP 552 DI 10.1148/radiol.2352040383 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200028 PM 15858093 ER PT J AU Yoshinaga, S Mabuchi, K Sigurdson, AJ Doody, MM Ron, E AF Yoshinaga, S Mabuchi, K Sigurdson, AJ Doody, MM Ron, E TI Increased brain cancer risk in physicians with high radiation exposure - Respond SO RADIOLOGY LA English DT Letter ID RADIOLOGISTS C1 Natl Inst Radiol Sci, Res Ctr Radiat Safety, Inage Ku, Chiba 2638555, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept HHS, Bethesda, MD USA. RP Yoshinaga, S (reprint author), Natl Inst Radiol Sci, Res Ctr Radiat Safety, Inage Ku, 4-9-1 Anagawa, Chiba 2638555, Japan. EM yosinaga@nirs.go.jp NR 7 TC 0 Z9 0 U1 1 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 710 EP 711 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200052 ER PT J AU Baird, DD Newbold, R AF Baird, DD Newbold, R TI Prenatal diethylstilbestrol (DES) exposure is associated with uterine leiomyoma development SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE diethylstilbestrol; prenatal exposure; uterine leiomyoma; uterine fibroids; epidemiology; environmental estrogens; endocrine disrupters ID HYSTERECTOMY; ESTROGENS; FIBROIDS; MICE AB Early life exposure to DES causes uterine leiomyomata in laboratory animals. We examined the relationship between prenatal DES exposure and development of uterine leiomyomata in women. Among randomly selected study participants (819 black women, 504 white women), leiomyoma status was determined by ultrasound screening (70%) or surgical record review (7%). We relied on self-report of prior diagnosis in 13%. Leiomyoma status could not be ascertained for 10% and they were excluded from analyses. Prenatal DES exposure was assessed by interview. All five of the black women who reported DES exposure had leiomyomata. Among white women, 76% who reported prenatal DES exposure had leiomyomata compared with 52% of the unexposed (adjusted odds ratio for whites: 2.4; 95% confidence interval CI: 1.1-5.4). Exposed women tended to have larger tumors. Results were robust to sensitivity analyses. Findings support experimental animal data and indicate a role for prenatal estrogen exposure in the etiology of human uterine leiomyoma. (c) 2005 Elsevier Inc. All rights reserved. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM baird@niehs.nih.gov OI Baird, Donna/0000-0002-5544-2653 NR 20 TC 57 Z9 61 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 2005 VL 20 IS 1 BP 81 EP 84 DI 10.1016/j.reprotox.2005.01.002 PG 4 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 917DZ UT WOS:000228437500010 PM 15808789 ER PT J AU Pursley, RH Salem, G Pohida, TJ Devasahayam, N Subramanian, S Krishna, MC AF Pursley, RH Salem, G Pohida, TJ Devasahayam, N Subramanian, S Krishna, MC TI Direct detection and time-locked subsampling applied to pulsed electron paramagnetic resonance imaging SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID DATA-ACQUISITION SYSTEM; SPECTROSCOPY AB The application of direct time-locked subsampling (TLSS) to Fourier transform electron paramagnetic resonance (FT-EPR) spectroscopy at radio frequencies (rf) is described. With conventional FT-EPR spectroscopy, the high Larmor frequencies (L-f) often necessitate the use of intermediate frequency (IF) stages to down convert the received free induction decay (FID) signal to a frequency that can be acquired with common data acquisition technology. However, our research focuses on in vivo studies, and consequently utilizes a FT-EPR system with a L-f of 300 MHz. This relatively low frequency L-f, in conjunction with the advent of bandpass sampling analog-to-digital conversion and signal processing technologies, has enabled us to omit the IF stage in our FT-EPR system. With this in mind, TLSS techniques have been developed to directly sample the 300 MHz FID signal at a sampling rate of 80 MHz providing a signal bandwidth of 20 MHz. The required modifications to the data acquisition and processing system specific to this application are described. Custom software developed to control the EPR system setup, acquire the signals, and post process the data, is outlined. Data was acquired applying both coherent averaging and stochastic excitation sequences. The results of these experiments demonstrate digital down conversion of the 300 MHz FID signal to quadrature baseband. Direct FID TLSS eliminates many noise sources common in EPR systems employing traditional analog receiver techniques, such as the IF mixer stage in single channel systems, and the quadrature baseband mixer stage in dual channel systems. © 2005 American Institute of Physics. C1 NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NCI, Radiol Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pursley, RH (reprint author), NIH, Signal Proc & Instrumentat Sect, Div Computat Biosci, Ctr Informat Technol, 12 South Dr,Bldg 12A-2025, Bethesda, MD 20892 USA. EM pursley@helix.nih.gov NR 15 TC 5 Z9 5 U1 2 U2 3 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD MAY PY 2005 VL 76 IS 5 AR 053709 DI 10.1063/1.1903163 PG 6 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 925PF UT WOS:000229064300035 ER PT J AU Larsen, MB Stephens, RW Brunner, N Nielsen, HJ Engelholm, LH Christensen, IJ Stetler-Stevenson, WG Hoyer-Hansen, G AF Larsen, MB Stephens, RW Brunner, N Nielsen, HJ Engelholm, LH Christensen, IJ Stetler-Stevenson, WG Hoyer-Hansen, G TI Quantification of tissue inhibitor of metalloproteinases 2 in plasma from healthy donors and cancer patients SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR; EGG-YOLK ANTIBODIES; MEMBRANE-TYPE 1; MATRIX METALLOPROTEINASES; COLORECTAL-CANCER; BREAST CARCINOMAS; ENHANCED EXPRESSION; UROKINASE RECEPTOR; UROTHELIAL CANCER; BLADDER-CANCER AB Tissue inhibitor of metalloproteinases (TIMP)-2 is a highly conserved molecule, which binds both active and latent matrix metalloproteinase (MMP)-2. TIMP-2 is also involved in the activation of MMP-2 on the cell surface. A quantitative enzyme-linked immunosorbent assay (ELISA) was established and optimized for measurement of TIMP-2 in plasma. The capturing antibody in the ELISA was a monoclonal, while the detecting antibody was a chicken polyclonal antibody recognizing the native form of human TIMP-2. The levels of TIMP-2 were measured in ethylenediaminetetraacetic acid (EDTA) and citrate plasma from healthy donors. The median values were determined as 163 ng/ml (n = 186) with a range of 109-253 ng/ml for EDTA plasma and 139 ng/ml (n = 77) with a range of 95-223 ng/ml for citrate plasma. The TIMP-2 concentration in citrate plasma from 15 patients with advanced, stage IV breast cancer had a median value of 160 ng/ml, only slightly higher but statistically distinguishable from the level found in citrate plasma from the healthy donors. In addition, the TIMP-2 concentration in EDTA plasma from colorectal cancer patients revealed a significantly higher level in plasma from patients with Dukes stage A (P = 0.01) compared with patients with more advanced Dukes stages. C1 Royal Vet & Agr Univ, Inst Vet Pathobiol, Copenhagen, Denmark. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. Univ Copenhagen, Hvidovre Hosp, Dept Surg Gastroenterol, DK-2650 Hvidovre, Denmark. NIH, Pathol Lab, Bethesda, MD 20892 USA. RP Hoyer-Hansen, G (reprint author), Finsen Inst, Strandblvd 49, DK-2100 Copenhagen, Denmark. EM gunilla@finsenlab.dk RI Stephens, Ross/A-8524-2008; Stetler-Stevenson, William/H-6956-2012; OI Stephens, Ross/0000-0001-6124-0102; Stetler-Stevenson, William/0000-0002-5500-5808; Engelholm, Lars/0000-0002-6616-1232 NR 56 TC 14 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD MAY PY 2005 VL 61 IS 5 BP 449 EP 460 DI 10.1111/j.1365-3083.2005.01585.x PG 12 WC Immunology SC Immunology GA 929UW UT WOS:000229373100008 PM 15882437 ER PT J AU Lee, JS Thorgeirsson, SS AF Lee, JS Thorgeirsson, SS TI Genetic profiling of human hepatocellular carcinoma SO SEMINARS IN LIVER DISEASE LA English DT Review DE hepatocellular carcinoma (HCC); DNA microarray; gene expression profile; comparative functional genomics ID HEPATITIS-C VIRUS; ACTIVATED RECEPTOR-ALPHA; EXPRESSION PROFILES; BETA-CATENIN; PEROXISOME PROLIFERATOR; B-VIRUS; TRANSGENIC MICE; CDNA MICROARRAY; DNA MICROARRAY; BREAST-CANCER AB The underlying molecular basis for the heterogeneity in human liver cancer, hepatocellular carcinoma (HCC), is largely unknown. As with most other human cancers, the heterogeneous nature of HCC has hampered both treatment and prognostic predictions. Global gene expression profiling of human cancers is a promising new technology for refining the diagnosis and prognosis of HCC as well as for identifying potential therapeutic targets. Improved molecular characterization of HCC from gene expression profiling studies will undoubtedly improve the prediction of treatment responses, improve the selection of treatments for specific molecular subtypes of HCC, and ultimately improve the clinical outcome of HCC patients. We review the recent advances in gene expression profiling of HCC and discuss the biological and clinical insights obtained from these studies. C1 NCI, Canc Res Ctr, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Canc Res Ctr, Expt Carcinogenesis Lab, NIH, 37 Convent Dr,Bldg 37,Room 4146, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 65 TC 35 Z9 37 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0272-8087 J9 SEMIN LIVER DIS JI Semin. Liver Dis. PD MAY PY 2005 VL 25 IS 2 BP 125 EP 132 DI 10.1055/s-2005-871192 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 933FE UT WOS:000229613500002 PM 15918141 ER PT J AU Zhou, JG Cidlowski, JA AF Zhou, JG Cidlowski, JA TI The human glucocorticoid receptor: One gene, multiple proteins and diverse responses SO STEROIDS LA English DT Article; Proceedings Paper CT FASEB Summer Research Conference on Steroid Hormone Receptors CY JUL 31-AUG 05, 2004 CL Tucson, AZ SP FASEB DE steroid; human glucocorticoid receptor; isoforms; alternative RNA splicing; alternative translation initiation; post-translational modification ID GROWTH-FACTOR-BETA; HUMAN OSTEOCALCIN PROMOTER; BOVINE PROLACTIN GENE; IN-VITRO; MESSENGER-RNA; RAT-LIVER; TRANSCRIPTIONAL ACTIVATION; MICROBIAL SUPERANTIGENS; TRANSLOCATION PROMOTER; BIOCHEMICAL-PROPERTIES AB Glucocorticoids are a vital class of endogenous steroid hormones that regulate essential biological processes including growth, development, metabolism, behavior and apoptosis. Most, if not all, of these actions are thought to be mediated through the glucocorticoid receptor. The exact mechanisms of how one hormone, via one receptor, modulates such diverse biological functions are largely unknown. However, recent studies from our lab and others have suggested that a contribution for the diversity results from multiple isoforms of the glucocorticoid receptor that result from alternative RNA splicing and translation initiation of the glucocorticoid receptor mRNA. Additionally, each isoform is subject to several post-translational modifications, including phosphorylation, ubiquitination and surnoylation, which have been shown to modulate the receptor protein stability and/or function. Together these data provide potentially diverse mechanisms to establish cell type specific regulation of gene expression by a single transcription factor. Here, we summarize the recent advances and processes that generate these receptor isoforms and these post-translational modifications. We speculate that the composition and proportion of individual isoforms expressed in particular cellular contexts account for the diverse effects of glucocorticoid hormones. Published by Elsevier Inc. C1 NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,DHHS, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signal Transduct, NIH,DHHS, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov NR 113 TC 215 Z9 223 U1 1 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD MAY-JUN PY 2005 VL 70 IS 5-7 BP 407 EP 417 DI 10.1016/j.steroids.2005.02.006 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 929JQ UT WOS:000229342800010 PM 15862824 ER PT J AU Cheng, SY AF Cheng, SY TI Isoform-dependent actions of thyroid hormone nuclear receptors: Lessons from knockin mutant mice SO STEROIDS LA English DT Article; Proceedings Paper CT FASEB Summer Research Conference on Steroid Hormone Receptors CY JUL 31-AUG 05, 2004 CL Tucson, AZ SP FASEB DE mutant thyroid hormone receptor; thyroid hormone resistance; dwarfism; mutations of the thyroid hormone receptor genes; mouse models ID DOMINANT-NEGATIVE ACTIVITY; GENERALIZED RESISTANCE; BETA-RECEPTOR; TARGETED MUTATION; LIGAND-BINDING; GENE; MODULATION; ALPHA; EXPRESSION; PHENOTYPE AB Thyroid hormone nuclear receptors (TRs) mediate the biological activities of the thyroid hormone J3) in growth, development and differentiation and in the maintenance of metabolic homeostasis. They are derived from two separate genes to yield four major T3-binding isoforms: al, alpha 1, beta 2, and beta 3. To understand whether TR isoforms, mediate specific functions in vivo, PV mutation, identified from a patient with resistance to thyroid hormone (RTH), was targeted to the TR beta (TR beta PV mice) or TR alpha gene (TR alpha 1PV mice). PV has a frame-shift mutation in the last 14 carboxyl-terminal amino acids of TR beta 1 or TR alpha 1, resulting in the loss of T3-binding and transcriptional activities. TR beta PV mice faithfully reproduce human RTH with dysfunction of the pituitary-thyroid axis, impairment in weight gain and accelerated bone development, hearing defects, abnormal regulation of serum cholesterol and increased physical activity reminiscent of attention deficithyperactivity disorder. In contrast, TR alpha 1PV mice show no abnormalities in the pituitary-thyroid axis and other discernable RTH phenotypes. In addition, TR alpha 1PV mice are dwarfs with high mortality, reduced fertility and survival, reduced glucose utilization in the brain and marked delay in bone development. These results clearly show that the molecular actions of TR alpha 1PV are distinct from those of TR beta PV in vivo. Further studies indicate that these contrasting phenotypes are mediated by distinct isoform-dependent abnormal regulation of T3-target genes in tissues. Thus, these two mutant mice provide a valuable tool for further dissecting the molecular bases of isoform-dependent actions of mutant TRs in vivo and their roles in disease. Published by Elsevier Inc. C1 NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, Bldg 37,Rm 5128,37 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov NR 35 TC 39 Z9 39 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-128X J9 STEROIDS JI Steroids PD MAY-JUN PY 2005 VL 70 IS 5-7 BP 450 EP 454 DI 10.1016/j.steroids.2005.02.003 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 929JQ UT WOS:000229342800015 PM 15862829 ER PT J AU Guy, HR AF Guy, HR TI Transmembrane interactions of alpha/beta integrin signaling SO STRUCTURE LA English DT Editorial Material ID DOMAIN; TRANSDUCTION; AFFINITY; STATE AB Kay Gottschalk (2005) has developed a new model for the structure of the transmembrane helices of an alpha/beta integrin in the resting conformation and suggests how the interactions between these helices help transmit signals across the membrane. C1 NCI, Lab Expt & Compuata Biol, NIH, Bethesda, MD 20892 USA. RP Guy, HR (reprint author), NCI, Lab Expt & Compuata Biol, NIH, 12 S Dr, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2005 VL 13 IS 5 BP 683 EP 684 DI 10.1016/j.str.2005.04.004 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 929GU UT WOS:000229330900001 PM 15893656 ER PT J AU Huang, CC Stricher, F Martin, L Decker, JM Majeed, S Barthe, P Hendrickson, WA Robinson, J Roumestand, C Sodroski, J Wyatt, R Shaw, GM Vita, C Kwong, PD AF Huang, CC Stricher, F Martin, L Decker, JM Majeed, S Barthe, P Hendrickson, WA Robinson, J Roumestand, C Sodroski, J Wyatt, R Shaw, GM Vita, C Kwong, PD TI Scorpion-toxin mimics of CD4 in complex with human immunodeficiency virus gp120: Crystal structures, molecular mimicry, and neutralization breadth SO STRUCTURE LA English DT Article ID ENVELOPE GLYCOPROTEIN; HIV-1 ENVELOPE; SOLUBLE CD4; RECEPTOR-BINDING; ATOMIC-STRUCTURE; TYPE-1; ANTIBODY; DESIGN; ENTRY; SITE AB The binding surface on CD4 for the HIV-1 gp120 envelope glycoprotein has been transplanted previously onto a scorpion-toxin scaffold. Here, we use X-ray crystallography to characterize atomic-level details of gp120 with this transplant, CD4M33. Despite known envelope flexibility, the conformation of gp120 induced by CD4M33 was so similar to that induced by CD4 that localized measures were required to distinguish ligand-induced differences from lattice variation. To investigate relationships between structure, function, and mimicry, an F23 analog of CD4M33 was devised. Structural and thermodynamic analyses showed F23 to be a better molecular mimic of CD4 than CD4M33. F23 also showed increased neutralization breadth, against diverse isolates of HIV-1, HIV-2, and SIVcpz. Our results lend insight into the stability of the CD4 bound conformation of gp120, define measures that quantify molecular mimicry as a function of evolutionary distance, and suggest how such evaluations might be useful in developing mimetic antagonists with increased neutralization breadth. C1 Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. CEA Saclay, Dept Prot Engn & Res, F-91191 Gif Sur Yvette, France. Univ Alabama, Howard Hughes Med Inst, Dept Med, Dept Microbiol, Birmingham, AL 35294 USA. Fac Pharm Montpellier, Struct Biol Ctr, F-34093 Montpellier, France. Columbia Univ, Howard Hughes Med Inst, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Kwong, PD (reprint author), Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM pdkwong@nih.gov RI MARTIN, loic/E-1627-2011 OI MARTIN, loic/0000-0002-7940-2955 NR 54 TC 79 Z9 84 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD MAY PY 2005 VL 13 IS 5 BP 755 EP 768 DI 10.1016/j.str.2005.03.006 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 929GU UT WOS:000229330900011 PM 15893666 ER PT J AU Lim, WK Buggage, RR Nussenblatt, RB AF Lim, WK Buggage, RR Nussenblatt, RB TI Serpiginous choroiditis SO SURVEY OF OPHTHALMOLOGY LA English DT Review DE ampiginous choroiditis; geographic choroiditis; geographic choroidopathy; posterior uveitis; relentless placoid chorioretinitis; serpiginous choroiditis; serpiginous choroidopathy; triple therapy ID PLACOID PIGMENT EPITHELIOPATHY; GREEN ANGIOGRAPHIC FINDINGS; GEOGRAPHIC CHOROIDITIS; FOLLOW-UP; CHOROIDOPATHY; NEOVASCULARIZATION; UVEITIS; CYCLOSPORINE; DISEASE; CHORIOCAPILLARIS AB Serpiginous choroiditis is a rare, usually bilateral, chronic, progressive, recurrent inflammation of the choroid, retinal pigment epithelium, and choriocapillaris of unknown etiology. Based on clinical presentation, it can be classified into 1) peripapillary, 2) macular, and 3) ampiginous types. The clinical course, regardless of the presentation, is progressive with multiple recurrences leading to potentially significant visual loss. Visual outcome is directly related to the involvement of the para-fovea and fovea by the lesions or secondary choroidal neovascularization. The histological findings of the lesions are atrophy of the choriocapillaris, retinal pigment epithelium and photoreceptor cells, and moderate diffuse lymphocytic infiltrates throughout the choroid. Multiple etiologies including autoimmunity, infection, vasculopathy, and degeneration were proposed but none is well supported by clinical and laboratory evidence. Fluorescein and indocyanine green angiography have been useful in the assessment of the extent and the activity of lesions. Due to the insidious and progressive clinical course, an assessment of treatment outcomes needs long term follow-up. Currently, treatment with immunosuppressive and alkylating agents have shown possible efficacy in small case series. Larger clinical studies and interventional trials are required to further our understanding of the pathogenesis, etiology, and for the evaluation of treatment strategies. © 2005 Elsevier Inc. All rights reserved. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Singapore Natl Eye Ctr, Singapore, Singapore. RP Lim, WK (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10S219, Bethesda, MD 20892 USA. NR 81 TC 55 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6257 J9 SURV OPHTHALMOL JI Surv. Ophthalmol. PD MAY-JUN PY 2005 VL 50 IS 3 BP 231 EP 244 DI 10.1016/j.survophthal.2005.02.010 PG 14 WC Ophthalmology SC Ophthalmology GA 926QT UT WOS:000229138400001 PM 15850812 ER PT J AU Alexander, M Rothman, RB Baumann, MH Endres, CJ Brasic, JR Wong, DF AF Alexander, M Rothman, RB Baumann, MH Endres, CJ Brasic, JR Wong, DF TI Noradrenergic and dopaminergic effects of (+)-amphetamine-like stimulants in the baboon Papio anubis SO SYNAPSE LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-of-Nuclear-Medicine CY JUN 19-23, 2004 CL Philadelphia, PA SP Soc Nucl Med DE amphetamine; ephedrine; phentermine; dopamine; noradrenaline; [C-11]raclopride; positron emission tomography; neuroimaging; excitatory neurotransmitters ID MONOAMINE-OXIDASE; AMPHETAMINE; PHENTERMINE; FENFLURAMINE; RELEASE; PET; PSYCHOSTIMULANTS; NOREPINEPHRINE; INHIBITION; VOLUNTEERS AB (+)-Amphetamine, (+/-)-ephedrine, and phentermine are commonly used appetite suppressants that release monoamines from nerve cells by acting as substrates for biogenic amine transporters. One key difference among the three drugs is their selectivity for norepinepbrine (NE) release vs. dopamine (DA) release. The NE/DA selectivity ratios for these drugs as determined in vitro [(EC50 NE-1)/(EC50 DA(-1))] are (+/-)ephedrine (18.6) > phentermine (6.7) > (+)-amphetamine (3.6). The in vitro data suggest that when administered in vivo, these stimulants might differ in their ability to release DA from nerve terminals in the brain. To test this hypothesis, noradrenergic effects (i.e., plasma NE) and dopaminergic effects (i.e., central DA release) were assessed when each drug was administered intravenously (1.5 mg/kg) to anesthetized baboons. Central DA release was determined via positron emission tomography using the method of [C-11]raclopride displacement. In the present investigation, high doses of these stimulants increased plasma NE and DA in parallel, but only (+)-amphetamine released central DA from neurons and decreased plasma prolactin. None of the drugs altered plasma amine metabolite levels, indicating no inhibition of monoamine oxidase activity at the administered doses. Plasma drug levels measured in baboons were higher than those measured in human patients taking prescribed doses of the drugs. Viewed collectively, the present data indicate that typical clinical doses of phentermine and (+/-)-ephedrine may not release central DA in humans, a hypothesis that should ultimately be tested in controlled clinical studies. Published 2005 Wiley-Liss, Inc.(dagger). C1 Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Nucl Med, Baltimore, MD 21287 USA. Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wong, DF (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Div Nucl Med, 601 N Caroline St,JHOC Room 3245, Baltimore, MD 21287 USA. EM dfwong@jhmi.edu RI Brasic, James/B-3503-2008 OI Brasic, James/0000-0002-3948-4853 FU NIDA NIH HHS [DA 11080, DA 09482, DA 00412] NR 25 TC 30 Z9 30 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAY PY 2005 VL 56 IS 2 BP 94 EP 99 DI 10.1002/syn.20126 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 909TA UT WOS:000227882400005 PM 15729739 ER PT J AU Ghose, S Fujita, M Morrison, P Uhl, G Murphy, DL Mozley, PD Schou, M Halldin, C Innis, R AF Ghose, S Fujita, M Morrison, P Uhl, G Murphy, DL Mozley, PD Schou, M Halldin, C Innis, R TI Specific in vitro binding of (S,S)-[H-3]MeNER to norepinephrine transporters SO SYNAPSE LA English DT Article DE NET; knockout mice; autoradiography; binding assay ID DOPAMINE TRANSPORTER; RAT-BRAIN; POSTMORTEM; NISOXETINE; COCAINE; SITES AB The aim of this study was to determine the selectivity of (SS)-2-(alpha-(2-methoxyphenoxy)benzyl)morpholine (MeNER) binding to norepinephrine transporters (NET). Quantitative autoradiography studies of NET binding were performed in brains of wildtype mice and those of mutant mice lacking one or two alleles of the NET gene. [H-3]MeNER binding in the wildtype mouse brains was consistent with previously reported distributions of NET. Highest levels were found in the locus coeruleus, thalamus, hypothalamus, and bed nucleus of stria terminalis. Specific binding in these regions was similar to 50% in the heterozygous NET mice and negligible in the NET knockout mice. Binding in the wildtype mouse brains was displaced by the NET ligand, nisoxetine, but not by the serotonin or dopamine transporter blockers, citalopram or GBR 12935. [H-3]MeNER displayed much higher affinity for NET than for SERT or DAT in homogenate binding studies. Each of these features supports the binding specificity of this candidate in vivo NET ligand. (c) 2005 Wiley-Liss, Inc.(dagger). C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, ORS, Bethesda, MD 20892 USA. NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Karolinska Hosp, Karolinska Inst, Dept Clin Neurosci, Psychiat Sect, S-17176 Stockholm, Sweden. RP Ghose, S (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. EM subroto.ghose@UTSouthwestern.edu RI Ghose, Subroto/J-6732-2016 NR 18 TC 16 Z9 16 U1 0 U2 0 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 MAY PY 2005 VL 56 IS 2 BP 100 EP 104 DI 10.1002/syn.20133 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 909TA UT WOS:000227882400006 PM 15729740 ER PT J AU Wayne, JS McDowell, CL Shields, KJ Tuan, RS AF Wayne, JS McDowell, CL Shields, KJ Tuan, RS TI In vivo response of polylactic acid-alginate scaffolds and bone marrow-derived cells for cartilage tissue engineering SO TISSUE ENGINEERING LA English DT Article ID MESENCHYMAL STEM-CELLS; ARTICULAR-CARTILAGE; OSTEOCHONDRAL DEFECTS; MECHANICAL-PROPERTIES; POLYMER SCAFFOLDS; BIPHASIC INDENTATION; REGENERATION THERAPY; PRECURSOR CELLS; REPAIR; CHONDROCYTES AB Successful application of tissue- engineering techniques to damaged biological structures is determined by functional performance in vivo. This study evaluated the in vivo response of a tissue-engineered construct composed of a polylactic acid - alginate amalgam seeded with bone marrow-derived mesenchymal stem cells and stimulated in vitro with transforming growth factor beta for cartilage tissue engineering. Constructs were placed in cylindrical osteochondral defects in the canine femoral condyle and examined 6 weeks postoperatively by gross, histological, immunohistochemical, and biomechanical analyses. In the course of 6 weeks in vivo, the defects filled with a cartilaginous tissue regardless of whether cell- seeded (experimental) or cell- free (control) constructs were implanted; however, the quality of the tissue differed between the experimental and control defects. Cell-seeded experimental defects showed more cartilage- like matrix quality, cell distribution, and proteoglycan staining. Biomechanically, experimental and control specimens exhibited similar behavior; however, both tissues were still immature compared with normal cartilage. The evidence accumulated in this study showed a modest acceleration of the in vivo healing of cellseeded constructs but also demonstrated a reparative response of cell-free constructs. This finding suggests that the constructs prepared from the PLA - alginate amalgam may serve as a means for host cell attachment. C1 Virginia Commonwealth Univ, Orthopaed Res Lab, Dept Biomed Engn, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Orthopaed Res Lab, Dept Orthoped Surg, Richmond, VA 23298 USA. Vet Affairs Med Ctr, Richmond, VA USA. NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA. RP Wayne, JS (reprint author), Virginia Commonwealth Univ, Orthopaed Res Lab, Dept Biomed Engn, POB 980694, Richmond, VA 23298 USA. EM jswayne@vcu.edu FU NIAMS NIH HHS [AR48789] NR 50 TC 76 Z9 86 U1 2 U2 13 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 MAY PY 2005 VL 11 IS 5-6 BP 953 EP 963 DI 10.1089/ten.2005.11.953 PG 11 WC Cell & Tissue Engineering SC Cell Biology GA 942ZE UT WOS:000230320600028 PM 15998234 ER PT J AU Yoshizawa, K Marsh, T Foley, JF Cai, B Peddada, S Walker, NJ Nyska, A AF Yoshizawa, K Marsh, T Foley, JF Cai, B Peddada, S Walker, NJ Nyska, A TI Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley rats SO TOXICOLOGICAL SCIENCES LA English DT Review DE acinar cells; dioxin; immunohistochemistry; pancreas; rat; vacuolation ID ARYL-HYDROCARBON RECEPTOR; DIOXIN-LIKE COMPOUNDS; XENOBIOTIC-METABOLIZING ENZYMES; AH RECEPTOR; AROMATIC-HYDROCARBONS; CELL-PROLIFERATION; PEROXISOME PROLIFERATOR; SPECIES-DIFFERENCES; CHOLECYSTOKININ-A; GENE-REGULATION AB In previous 2-year studies of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) conducted by the National Toxicology Program on female Harlan Sprague-Dawley rats, acinar-cell vacuolation, atrophy, inflammation, and arteritis developed at high incidence, and a rare occurrence of pancreatic acinar-cell adenomas and carcinomas was noted. In this investigation, we sought to identify the mechanism involved in the early formative stages of acinar-cell lesions. Pancreas from animals treated for 14 and 31 weeks with 100 ng TCDD/kg body weight or corn oil vehicle was examined immunohistochemically and/or morphometrically. Acinar-cell kinetics were analyzed using staining with hematoxylin and eosin and proliferating cell nuclear antigen. Expressions of cytochrome P450 (CYP) 1A1 and aryl hydrocarbon receptor (AhR) were evaluated to assess direct effects of TCDD exposure. The cholecystokinin-A receptor (CCK-A receptor; CCKAR) and duodenal cholecystokinin 8 (CCK) revealed the associations of dioxin treatment with hormonal changes. Amylase localization showed acinar structural changes that could affect enzymatic production. Increased apoptotic activity in acinar cells occurred in 14- and 31-week-treated animals, with an increase in proliferative activity in the latter. Also in the latter, in the vacuolated acinar cells, CYP1A1 was overexpressed, and statistically significant decreases in expressions of AhR, CCKAR, and amylase occurred. The intensity of CCKAR expression increased in nonvacuolated acinar cells; a decrease in the size of CCK-positive epithelial cells occurred in duodenum. Our findings indicate that dioxin-induced acinar-cell lesions might be related to a direct effect of TCDD on the pancreas. Increase in CYP1A1 and decrease in CCKAR expressions in vacuolated acinar cells may be involved in the pathogenesis of pancreatic lesions. Changes in the expression of CYP or CCKAR may have induced the acinar-cell tumors by initiating proliferation. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, POB 12233,Mail Drop B3-06,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012; Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 99 TC 11 Z9 11 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 MAY PY 2005 VL 85 IS 1 BP 594 EP 606 DI 10.1093/toxsci/kfi121 PG 13 WC Toxicology SC Toxicology GA 916PO UT WOS:000228398000018 PM 15716480 ER PT J AU Pritchard, JB Miller, DS AF Pritchard, JB Miller, DS TI Expression systems for cloned xenobiotic transporters SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE biology; gene; substrate ID ORGANIC ANION TRANSPORTER; RESISTANCE-ASSOCIATED PROTEIN-2; XENOPUS-LAEVIS OOCYTES; MEMBRANE-PROTEINS; P-GLYCOPROTEIN; CHOROID-PLEXUS; FUNCTIONAL-CHARACTERIZATION; TRANSCELLULAR TRANSPORT; MULTIDRUG TRANSPORTER; CATION TRANSPORTER-2 AB One challenge of modern biology is to be able to match genes and their encoded proteins with events at the molecular, cellular, tissue, and organism levels, and thus, provide a multi-level understanding of gene function and dysfunction. How well this can be done for xenobiotic transporters depends on a knowledge of the genes expressed in the tissue, the cellular locations of the gene products (do they function for uptake or efflux?), and our ability to match substrates with transporters using information obtained from cloned transporters functioning in fieterologous expression systems. Clearly, making a rational choice of expression system to use for the characterization and study of cloned xenobiotic transporters is a critical part of study design. This choice requires well-defined goals, as well as an understanding of the strengths and weaknesses of candidate expression systems. Published by Elsevier Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Pritchard, JB (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, 110 Alexander Dr,MD F1-03, Res Triangle Pk, NC 27709 USA. EM pritcha3@nichs.nih.gov NR 64 TC 10 Z9 12 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY 1 PY 2005 VL 204 IS 3 BP 256 EP 262 DI 10.1016/j.taap.2004.11.018 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 921MQ UT WOS:000228769100005 PM 15845417 ER PT J AU Benson, JM Hutt, JA Rein, K Boggs, SE Barr, EB Fleming, LE AF Benson, JM Hutt, JA Rein, K Boggs, SE Barr, EB Fleming, LE TI The toxicity of microcystin LR in mice following 7 days of inhalation exposure SO TOXICON LA English DT Article DE microcystin; inhalation; nasal epithelium; protein expression in serum ID TUMOR PROMOTION; RISK-ASSESSMENT; CYANOBACTERIA; WATER; IDENTIFICATION; AERUGINOSA; PROTEINS; CYANOTOXINS; LIPOPROTEIN; TOXICOLOGY AB Microcystins, a family of cyclic heptapeptides produced by the cyanobacteria, Microcystis aeruginosa, have documented hepatotoxic and tumor promoting activities. The purpose of this study was to evaluate the toxicity of inhaled microcystin LR (microcystin). Male BALB/c mice were exposed by nose-only inhalation to 260-265 mu g microcystin/m(3) for 7 days. The low-, mid- and high-dose groups were exposed for 0.5, 1, and 2 h, respectively. Control animals were sham exposed to aerosolized vehicle. Treatment-related microscopic lesions were observed only in the nasal cavity of the mid- and high-dose groups. These lesions consisted of minimal to moderate multifocal degeneration and necrosis of the respiratory epithelium, with variable neutrophilic inflammation and minimal to marked degeneration, necrosis, and atrophy of the olfactory epithelium. The no-adverse-effect dose for the nasal lesions was approximately 3 mu g/kg body weight, or 20 ng/cm(2) of nasal epithelium. In serum, only two protein peaks, occurring at m/zs of 11,688 and 11,829 Da, exhibited decreases in intensity that were microcystin dose-dependent. While these proteins have not been positively identified, they may be useful in the future as biomarkers of microcystin exposure in humans. (c) 2005 Elsevier Ltd. All rights reserved. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. Florida Int Univ, Dept Chem & Biochem, Miami, FL 33199 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, NIEHS, Miami, FL 33149 USA. Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Freshwater Biomed Sci Ctr, Miami, FL 33149 USA. Univ Miami, Dept Epidemiol & Publ Hlth, Miami, FL 33136 USA. Univ Miami, Div Marine Biol & Fisheries, Miami, FL 33136 USA. RP Benson, JM (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM jbenson@lrri.org FU NIEHS NIH HHS [P30ES05705, P30 ES005705, S11 ES011181, S11 ES011181-04, S11 ES011181-049001, S11 ES11181] NR 42 TC 16 Z9 18 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD MAY PY 2005 VL 45 IS 6 BP 691 EP 698 DI 10.1016/j.toxicon.2005.01.004 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 920JZ UT WOS:000228686500002 PM 15804518 ER PT J AU Brocard, CB Boucher, KK Jedeszko, C Kim, PK Walton, PA AF Brocard, CB Boucher, KK Jedeszko, C Kim, PK Walton, PA TI Requirement for microtubules and dynein motors in the earliest stages of peroxisome biogenesis SO TRAFFIC LA English DT Article DE dynactin; microinjection; motor proteins; organelle; p150Glued ID YEAST HANSENULA-POLYMORPHA; ENDOPLASMIC-RETICULUM; MEMBRANE-PROTEINS; CRYSTALLINE PEROXISOMES; TARGETING SIGNAL; LIVING CELLS; RAT-LIVER; ORGANELLE; DYNACTIN; IMPORT AB Our aim was to determine the role of microtubules in the biogenesis of peroxisomes. Fusion experiments between human PEX16- and PEX1-mutant cells in the presence of nocodazol implied that microtubules were not required for import of proteins into the peroxisomal matrix after cell fusion complementation. We further studied the importance of microtubules in the early stages of peroxisome biogenesis following the microinjection complementation of PEX16-mutant cells. In the absence of nocodazol, nuclear microinjection of plasmids expressing EGFP-SKL and Pex16p in PEX16-mutant cells resulted in the accumulation of EGFP-SKL into newly formed peroxisomes. However, pretreatment of the cells with nocodazol, prior to microinjection, resulted in the inhibition of complementation of the PEX16 mutant and the cytosolic location of the EGFP-SKL. In addition, coexpression of a dominant-negative CC1 subunit of the dynein/dynactin motor complex resulted in the inability to complement PEX16-mutant cells. Both of these treatments resulted in the cytosolic localization of expressed Pex16p. Our results demonstrate that the formation of peroxisomes via the preperoxisomal compartment is dependent upon microtubules and minus-end-directed motor proteins and that the inhibition described above occurs at a step that precedes the association of Pex16p with the vesicles that would otherwise become the peroxisomes. C1 Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada. NICHHD, Unit Organelle Biol, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Walton, PA (reprint author), Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada. EM pwalton@uwo.ca NR 56 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD MAY PY 2005 VL 6 IS 5 BP 386 EP 395 DI 10.1111/j.1600-0854.2005.00283.x PG 10 WC Cell Biology SC Cell Biology GA 913EB UT WOS:000228133300004 PM 15813749 ER PT J AU Tudisco, C Jett, BW Byrne, K Oblitas, J Leitman, SF Stroncek, DF AF Tudisco, C Jett, BW Byrne, K Oblitas, J Leitman, SF Stroncek, DF TI The value of pH as a quality control indicator for apheresis platelets SO TRANSFUSION LA English DT Article ID STORAGE; MAINTENANCE; VIABILITY AB BACKGROUND: Standards and regulations require measurement of pH as an apheresis platelet (PLT) component quality monitor. The usefulness of this quality control (QC) measure was investigated. STUDY DEISGN AND METHODS: QC data were retrospectively reviewed for apheresis PLTs collected over 4.5 years. Three collection devices were used, the Amicus (Baxter), the CS-3000 Plus (Baxter), and the MCS+ LN9000 (Haemonetics). Each month, four components from each instrument were sampled. PLT counts and component volume were measured immediately after collection, and pH, after 5 days of storage. RESULTS: A total of 668 products were studied. pH decreased as PLT concentration increased (r(2) = 0.129, p < 0.001) and as component volume decreased (r(2) = 0.086, p = 0.02). PLT concentration and volume, however, were poor predictors of a low pH. Apheresis instrument type affected pH. The 216 components collected with use of the CS-3000 device had a lower pH than components from the other two instruments. Only 13 components had a pH value less than the acceptable level of 6.2, 12 of which were collected with the CS-3000. CONCLUSIONS: For newer-model blood cell separators, pH measurements do not provide information that might identify a manufacturing problem. Because factors that influence pH are controlled or monitored for each component, evaluation of pH on a sample group provides an indication of the quality of specific component only, rather than an effective monitor of the quality of the manufacturing process. C1 NIMH, Dept Transfus Med, NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Jett, BW (reprint author), NIMH, Dept Transfus Med, NIH, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711,10 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. EM BJett@cc.nih.gov NR 19 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2005 VL 45 IS 5 BP 773 EP 778 DI 10.1111/j.1537-2995.2005.04344.x PG 6 WC Hematology SC Hematology GA 916OS UT WOS:000228395600020 PM 15847668 ER PT J AU Stojilkovic, SS Zemkova, H Van Goor, F AF Stojilkovic, SS Zemkova, H Van Goor, F TI Biophysical basis of pituitary cell type-specific Ca2+ signaling-secretion coupling SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID ACTIVATED POTASSIUM CHANNELS; GATED CALCIUM INFLUX; ANTERIOR-PITUITARY; NEONATAL GONADOTROPHS; NEUROENDOCRINE CELLS; ELECTRICAL-ACTIVITY; HORMONE RECEPTORS; ACTION-POTENTIALS; RAT GONADOTROPES; BK CHANNELS AB All secretory pituitary cells exhibit spontaneous and extracellular Ca2+-dependent electrical activity. Somatotrophs and lactotrophs fire plateau-bursting action potentials, which generate Ca2+ signals of sufficient amplitude to trigger hormone release, Gonadotrophs also fire action potentials spontaneously, but as single, high-amplitude spikes with limited ability to promote Ca2+ influx and secretion. However, Ca2+ mobilization in gonadotrophs transforms single spiking into plateau-bursting-type electrical activity and triggers secretion. Patch clamp analysis revealed that somatotrophs and lactotrophs, but not gonadotrophs, express BK (big)-type Ca2+-controlled K+ channels, activation of which is closely associated with voltage-gated Ca2+ influx. Conversely, pituitary gonadotrophs express SK (small)-type Ca2+-activated K+ channels that are colocalized with intracellular Ca2+ release sites. Activation of both channels is crucial for plateau-bursting-type rhythmic electrical activity and secretion. C1 NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Physiol, Prague 14220 4, Czech Republic. Vertex Pharmaceut, San Diego, CA 92121 USA. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Zemkova, Hana/C-1844-2012 NR 50 TC 65 Z9 65 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 2005 VL 16 IS 4 BP 152 EP 159 DI 10.1016/j.tem.2005.03.003 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MZ UT WOS:000229351500004 PM 15860411 ER PT J AU Cheng, SY AF Cheng, SY TI Thyroid hormone receptor mutations and disease: beyond thyroid hormone resistance SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID SECRETING PITUITARY-TUMOR; LIGAND-BINDING DOMAIN; MOUSE MODEL; TARGETED MUTATION; BETA-RECEPTOR; GENE-EXPRESSION; MOLECULAR-BASIS; TR-BETA; MICE; CARCINOMA AB Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that mediate the biological activities of thyroid hormone (T-3). Two THR genes (A and B), located on different chromosomes, yield four T-3-binding isoforms with highly conserved sequences in the DNA- and ligand-binding domains. Mutations of THRB cause a human genetic disease, thyroid hormone resistance syndrome (RTH). Comprehensive genomic profiling unveiled the contribution of novel change-of-function mutations of TR beta to the pathogenesis of RTH. In addition, abnormalities associated with mutations of the THRA gene have been uncovered recently. The phenotypic manifestations of mutated THRB and THRA genes are distinct, indicating isoform-dependent actions of TR mutants in vivo. Therefore, mutant TRs provide a new paradigm to understand the molecular basis of receptor disease. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov NR 54 TC 56 Z9 62 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD MAY-JUN PY 2005 VL 16 IS 4 BP 176 EP 182 DI 10.1016/j.tem.2005.03.008 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MZ UT WOS:000229351500007 PM 15860414 ER PT J AU Hauben, E Roncarolo, MG Nevo, U Schwartz, M AF Hauben, E Roncarolo, MG Nevo, U Schwartz, M TI Beneficial autoimmunity in Type 1 diabetes mellitus SO TRENDS IN IMMUNOLOGY LA English DT Article ID PANCREATIC BETA-CELLS; CD4(+) T-CELLS; RECEPTOR TRANSGENIC MICE; CENTRAL-NERVOUS-SYSTEM; NOD MICE; DENDRITIC CELLS; PROTECTIVE AUTOIMMUNITY; THERAPEUTIC VACCINATION; DNA VACCINATION; IMMUNE CELLS AB The trigger that leads to the pathogenesis of type 1 diabetes is currently unknown. It is well established that the pathophysiology of the disease is biphasic. In the first stage, leukocytes infiltrate the pancreatic islets in a response that does not cause damage. In the second phase, which occurs only in diabetes-prone individuals and strains, autoreactive T cells acquire aggressive potential and destroy the majority of the pancreatic islets. Rodents and humans exhibit a physiological ripple of apoptotic beta-cell death shortly after birth, which induces an adaptive autoimmune response towards islet-antigens, both in diabetes-prone non-obese diabetic (NOD) mice and in mice that do not develop diabetes. Here, we propose that the early T cell-mediated autoimmune response towards islet-antigens is physiological, purposeful and beneficial. C1 San Raffaele Telethon Inst Gene Therapy, HSR TIGET, I-20132 Milan, Italy. NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Hauben, E (reprint author), San Raffaele Telethon Inst Gene Therapy, HSR TIGET, Via Olgettina 58, I-20132 Milan, Italy. EM hauben.ehud@hsr.it OI RONCAROLO, Maria Grazia/0000-0002-2193-9186 FU Telethon [TGM06S01, TGT03A03, TGT06S01] NR 61 TC 22 Z9 23 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD MAY PY 2005 VL 26 IS 5 BP 248 EP 253 DI 10.1016/j.it.2005.03.004 PG 6 WC Immunology SC Immunology GA 928CY UT WOS:000229249900005 PM 15866237 ER PT J AU Epsinoza, J Goncalves, LF Lee, W Mazor, M Romero, R AF Epsinoza, J Goncalves, LF Lee, W Mazor, M Romero, R TI A novel method to improve prenatal diagnosis of abnormal systemic venous connections using three- and four-dimensional ultrasonography and 'inversion mode" SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE 3D/4D ultrasound; azygos vein; hemiazygos vein; 'inversion mode'; STIC; systemic venous connections ID INFERIOR VENA-CAVA; SPATIOTEMPORAL IMAGE CORRELATION; POWER DOPPLER ULTRASONOGRAPHY; AZYGOUS CONTINUATION; ACCESSORY HEMIAZYGOS; CORONARY SINUS; FETAL HEART; INTERRUPTION; VEIN AB Objective The precise prenatal diagnosis of abnormal venous connections of the fetal heart is challenging. Anatomical accuracy may be important in determining the best route for postnatal angiograpby, as well as the prognosis and treatment. This study was designed to determine the value of 'inversion mode, a new three-and four-dimensional (4D) rendering algorithm, in the visualization of the spatial relationships of an interrupted inferior vena cava (IVC) with azygos or hemiazygos vein continuation associated with and without heterotaxic syndromes. Methods Heart volumes were acquired using 4D ultrasonography and spatiotemporal image correlation in cases of interrupted IVC with azygos/hemiazygos continuation (n = 3). Volume datasets were rendered using the 'inversion mode' algorithm and abnormal images were compared to those generated from a library of normal fetuses. Results The 'inversion mode' rendering algorithm allowed the visualization of dilated azygos or hemiazygos veins and their spatial relationships with the descending aorta, the aortic arch, the superior vena cava, and the atria in cases of interrupted I VC with and without heterotaxic syndromes. Conclusions The 'inversion mode' algorithm improves prenatal visualization of both dilated azygos and hemiazygos veins, as well as their spatial relationships with the surrounding vascular structures. This has implications for the accurate prenatal diagnosis and management of neonates with abnormal systemic venous connections. Copyright (c) 2005 ISUOG. Published by John Wiley & Sons, Ltd. C1 Wayne State Univ, Dept Obstet & Gynecol, Hutzel Hosp, Detroit, MI USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD, NIH,DHHS,Hutzel Womens Hosp, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 25 TC 0 Z9 0 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD MAY PY 2005 VL 25 IS 5 BP 428 EP 434 DI 10.1002/uog.1877 PG 7 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 927VI UT WOS:000229228200003 ER PT J AU Tani, Y Suttie, A Flake, GP Nyska, A Maronpot, RR AF Tani, Y Suttie, A Flake, GP Nyska, A Maronpot, RR TI Epithelial-stromal tumor of the seminal vesicles in the transgenic adenocarcinoma mouse prostate model SO VETERINARY PATHOLOGY LA English DT Article DE epithelial-stromal tumor; immunohistochemistry; seminal vesicles; transgenic adenocarcinoma mouse prostate (TRAMP) ID CYSTOSARCOMA-PHYLLODES; PROLIFERATIVE LESIONS; ANDROGEN REGULATION; B6C3F1 MICE; TRAMP MODEL; CANCER; CARCINOMA; PROGRESSION; GENE AB The transgenic adenocarcinoma mouse prostate (TRAMP) model, designed for researching human prostatic cancer, was genetically engineered to harbor a transgene composed of the simian virus 40 Large-T/small-t antigen promoted by the rat probasin gene. In addition to prostatic neoplasms, the TRAMP mouse develops tumors in the seminal vesicles. This study was conducted to evaluate the pathology and histogenesis of TRAMP seminal vesicle neoplasms. Tissues of accessory sex organs harvested from 72 TRAMP mice of various ages (11-40 weeks of age) were fixed in neutral buffered formalin and stained with hematoxylin and eosin, desmin, 5-bromo-2'-deoxyuridine (BrdU, treated animals only), and SV40 Large-T antigen (SV40-Tag). In the seminal vesicles, we found neoplastic stromal cells that emerged multicentrically just beneath the epithelium, densely packed between the epithelium and the smooth muscle layer. These stromal cells frequently exhibited mitotic figures and showed BrdU incorporation and SV40-Tag protein expression in the nuclei and immunopositivity for desmin. The proliferative mesenchymal cells were lined by cuboidal to columnar epithelium. Some of the larger papillary, polypoid lesions exhibited a phyllodes pattern resembling that seen in mixed epithelial-stromal tumors of the breast, prostate, and seminal vesicles of humans. Although the epithelium was negative for SV40-Tag and showed only occasional incorporation of BrdU, it clearly participated in the biphasic proliferation, forming papillary, cystic, and tubuloglandular structures. No conclusive evidence of malignancy (invasion or metastasis) was identified. Our recommended diagnosis of this lesion in the seminal vesicles is epithelial-stromal tumor. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, NIH, POB 12233,Mail Drop B3-06, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov NR 39 TC 25 Z9 25 U1 0 U2 2 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 MAY PY 2005 VL 42 IS 3 BP 306 EP 314 DI 10.1354/vp.42-3-306 PG 9 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 925WE UT WOS:000229083200007 PM 15872376 ER PT J AU Kim, Y Reinecke, S Malarkey, DE AF Kim, Y Reinecke, S Malarkey, DE TI Cutaneous angiomatosis in a young dog SO VETERINARY PATHOLOGY LA English DT Article DE angiomatosis; cavernous; cutaneous; dogs; factor-VIII-related antigen; forelimb; hemangioma; smooth muscle actin ID HEMANGIOMAS AB A I-year-old, spayed, female, mixed-breed dog had two reddish-purple cutaneous lesions, one on the right dorsal antebrachium and the other on the right shoulder. The lesions consisted of approximately 13 X 3 cm and 15 X 10 cm, irregular, patchy regions of 0.5-3.0 cm, circular, sometimes raised, reddish-purple swellings resembling ecchymoses. The lesion on the antebrachium had been noticed since the dog was adopted at 6 months of age and appeared to have increased in size over an 11-week period, at which time skin punch biopsy revealed an infiltrative pattern of well-differentiated blood vessels leading to an interpretation that the lesion was a well-differentiated hemangiosarcoma. The second lesion was revealed when the dog had its fur shaved in that area during surgical preparation to excise the antebrachial lesion. No other skin lesions were found on the dog. Microscopically, there was a widely disseminated and infiltrative-like pattern of benign-appearing small blood vessels, which were throughout the superficial and deep dermis and subcutis. Although the disseminated nature suggested malignancy, the histologic appearance of well-differentiated small blood vessels and nonprogressive clinical features indicate that the lesions were benign. The dog has been followed for 6 years and to date has no evidence of progression of the antebrachial lesion or shoulder lesion. To the authors' knowledge, this is the first report of a congenital angiomatosis-like lesion in a young dog, with extensive involvement of the forelimb. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Malarkey, DE (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM malarkey@niehs.nih.gov NR 11 TC 14 Z9 14 U1 0 U2 4 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 MAY PY 2005 VL 42 IS 3 BP 378 EP 381 DI 10.1354/vp.42-3-378 PG 4 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 925WE UT WOS:000229083200020 PM 15872389 ER PT J AU Desimone, R AF Desimone, R TI The topological approach to perceptual organization - A neural basis for global object features SO VISUAL COGNITION LA English DT Editorial Material ID POSTERIOR PARIETAL CORTEX; VISUAL-CORTEX; SUBCORTICAL CONNECTIONS; SELECTIVE ATTENTION; MACAQUE MONKEY; AREAS V1; V4; MECHANISMS; V2 C1 NIH, Bethesda, MD 20892 USA. RP Desimone, R (reprint author), NIH, Bldg 10,Room 4N222, Bethesda, MD 20892 USA. EM desimonr@intra.nimh.nih.gov NR 23 TC 0 Z9 1 U1 0 U2 0 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1350-6285 J9 VIS COGN JI Vis. Cogn. PD MAY PY 2005 VL 12 IS 4 BP 642 EP 647 PG 6 WC Psychology, Experimental SC Psychology GA 929UV UT WOS:000229373000003 ER PT J AU Lee, GD Aruna, JH Barrett, PM Lei, DL Ingram, DK Mouton, PR AF Lee, GD Aruna, JH Barrett, PM Lei, DL Ingram, DK Mouton, PR TI Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease SO BRAIN RESEARCH BULLETIN LA English DT Article DE microvasculature; capillary segments; total capillary length; corpus callosum; space balls; unbiased stereology; design-based ID AMYLOID PRECURSOR PROTEIN; NITRIC-OXIDE SYNTHASE; NADPH-DIAPHORASE; MUTANT PRESENILIN-1; ENDOTHELIAL-CELLS; BLOOD-FLOW; MICE; BRAIN; ANGIOPATHY; PATHOLOGY AB Morphological alterations in microvasculature occur as a common finding in the brains of non-demented aged persons and patients with Alzheimer's disease. Quantifying the extent of this vascular pathology, however, has been complicated by systematic error (bias) associated with the applications of assumption- and model-based morphometric techniques to human and animal tissues. The current study used novel assumption- and model-free stereological approaches to quantify capillary parameters in the corpus callosum of a double amyloid precursor protein/presenilin-1 transgenic murine model of Alzheimer's disease. The results revealed significant reductions in the total number of capillary segments in white matter of transgenic mice compared to non-transgenic littermates, with no differences in total capillary length. These findings support the view that the expression of mutant human genes for beta-amyloid peptides alters the normal architecture of cerebral capillary vessels in the white matter of mouse brain, which may model microvasculature changes reported in Alzheimer's disease. Published by Elsevier Inc. C1 NIA, Lab Expt Gerontol, Behav Neurosci Sect, NIH, Baltimore, MD 21224 USA. Stereol Resource Ctr, Chester, MD 21619 USA. Univ Penn, Dept Neurosurg, Philadelphia, PA 19104 USA. Cent S Univ, Xiangya Sch Med, Dept Anat & Neurobiol, Changsha 410078, Hunan, Peoples R China. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Behav Neurosci Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov FU NIBIB NIH HHS [R43 EB 001605-01] NR 33 TC 36 Z9 37 U1 0 U2 0 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 APR 30 PY 2005 VL 65 IS 4 BP 317 EP 322 DI 10.1016/j.brainresbull.2004.11.024 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 920GX UT WOS:000228678500006 PM 15811597 ER PT J AU Bosetti, F Bell, JM Manickam, P AF Bosetti, F Bell, JM Manickam, P TI Microarray analysis of rat brain gene expression after chronic administration of sodium valproate SO BRAIN RESEARCH BULLETIN LA English DT Article DE valproate; microarray; brain; rat; gene expression; bipolar disorder ID SIGNAL-TRANSDUCTION PATHWAYS; BIPOLAR AFFECTIVE-DISORDER; MOOD-STABILIZING AGENTS; GROWTH-HORMONE RESPONSE; THERAPEUTIC IMPLICATIONS; PSYCHIATRIC-DISORDERS; LITHIUM-CHLORIDE; ARACHIDONIC-ACID; POSTMORTEM BRAIN; STRESS-PROTEINS AB Valproic acid has been used to treat mania and bipolar disorder, but its mechanism of action is not agreed on. We used rat genome U34A Affymetrix oligonucleotide microarrays, containing 8799 known probesets, to determine the effect of 30-day daily intraperitoneal administration of valproate (200 mg/kg) on rat brain gene expression. We found 87 down-regulated genes and 34 up-regulated genes of at least a 1.4-fold change in valproate-treated compared to control rats. The experiments were done on five independent samples for each group, each in duplicate. The genes affected are known to be involved in a variety of pathways, including synaptic transmission, ion channels and transport, G-protein signaling, lipid, glucose and aminoacid metabolism, transcriptional and translational regulation, phosphoinositol cycle, protein kinases and phosphatases, and apoptosis. Our results suggest that the therapeutic effect of valproate may involve the modulation of multiple signaling pathways. (c) 2005 Elsevier Inc. All rights reserved. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Genome Path Inc, Gaithersburg, MD 20877 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. EM frances@mail.nih.gov NR 50 TC 39 Z9 44 U1 0 U2 6 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 APR 30 PY 2005 VL 65 IS 4 BP 331 EP 338 DI 10.1016/j.brainresbull.2005.01.004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 920GX UT WOS:000228678500008 PM 15811599 ER PT J AU Halim, ND Joseph, AW Lipska, BK AF Halim, ND Joseph, AW Lipska, BK TI A novel ELISA using PVDF microplates SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE PVDF ELISA; PVDF microplates; ELISA; polyvinylidine fluoride; homogenate; protein ID QUANTITATION; ANTIBODIES; PROTEINS; ASSAY AB Here we describe the development of a novel specific, rapid ELISA system, which is performed on modified microplates where polyvinylidine fluoride (PVDF) forms the base of each well. The use of microplates with PVDF membranes as the solid phase allows for a greater binding capacity of protein in comparison to the solid phases of traditional ELISAs. The increased binding capacity of the solid phase provides for the direct binding of antigens, which can subsequently be assayed using a single, specific and well-characterized antibody. This direct assay system eliminates the need for two distinct antibodies that are often necessary in conventional two site ELISA systems. The system is able to specifically detect purified proteins as well as antigens in crude preparations of tissue homogenates. The PVDF-based ELISA performs with similar sensitivity and reproducibility as conventional two site ELISAs in tissue homogenates. The intra- and inter-assay coefficients of variation for the measurement of actin in crude rat brain homogenate were 2.36 and 5.15%, respectively. Published by Elsevier B.V. C1 NIMH, Intramural Res Program, NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Lipska, BK (reprint author), NIMH, Intramural Res Program, NIH, Clin Brain Disorders Branch, 10 Ctr Dr,Bldg 10,Rm 4N306, Bethesda, MD 20892 USA. EM lipskab@intra.nimh.nih.gov NR 12 TC 5 Z9 6 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD APR 30 PY 2005 VL 143 IS 2 BP 163 EP 168 DI 10.1016/j.jneumeth.2004.09.025 PG 6 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 920RX UT WOS:000228708900009 PM 15814149 ER PT J AU Brinton, LA Lacey, JV Trimble, EL AF Brinton, LA Lacey, JV Trimble, EL TI Hormones and endometrial cancer - new data from the Million Women Study SO LANCET LA English DT Editorial Material ID RANDOMIZED CONTROLLED-TRIAL; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; SYMPTOMS C1 NCI, Bethesda, MD 20892 USA. RP Brinton, LA (reprint author), NCI, Bethesda, MD 20892 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 13 TC 6 Z9 6 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 30 PY 2005 VL 365 IS 9470 BP 1517 EP 1518 DI 10.1016/S0140-6736(05)66431-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 921HL UT WOS:000228754800004 PM 15866289 ER PT J AU Ravitsky, V Wendler, D AF Ravitsky, V Wendler, D TI Dissolving the dilemma over forced treatment SO LANCET LA English DT Editorial Material ID LIMITS C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 6 TC 1 Z9 1 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 30 PY 2005 VL 365 IS 9470 BP 1525 EP 1526 DI 10.1016/S0140-6736(05)66436-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 921HL UT WOS:000228754800009 PM 15866294 ER PT J AU Johnston, E Dupnik, KM Gonzales, MJ Winters, MA Rhee, SY Imamichi, T Shafer, RW AF Johnston, E Dupnik, KM Gonzales, MJ Winters, MA Rhee, SY Imamichi, T Shafer, RW TI Panel of prototypical infectious molecular HIV-1 clones containing multiple nucleoside reverse transcriptase inhibitor resistance mutations SO AIDS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; EXPERIENCED PATIENTS; SUSCEPTIBILITY; PROTEASE; PATTERNS AB We have created a panel of recombinant HIV-1 infectious clones containing common patterns of reverse transcriptase (RT) mutations responsible I-or resistance to each of the currently available nucleoside reverse transcriptase inhibitors (NRTI), and we have submitted the panel to the National Institutes of Health AIDS Research and Reference Reagent Programme. Testing the activity of new antiretroviral compounds against this panel of drug-resistant clones will determine their relative activity against many clinically relevant NRTI -resistant viruses. C1 Stanford Univ, Div Infect Dis, Stanford, CA 94305 USA. Int Corp Frederick Inc, Sci Applicat, Frederick, MD USA. Natl Canc Inst, Frederick, MD USA. RP Johnston, E (reprint author), Stanford Univ, Div Infect Dis, Stanford, CA 94305 USA. RI Rhee, Soo-Yon/L-4597-2013 FU FIC NIH HHS [R25 TW009337]; NIAID NIH HHS [R01 AI046148-08, AI-46148-03, R01 AI046148]; NIGMS NIH HHS [P01 GM066524, P01 GM066524-06] NR 16 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR 29 PY 2005 VL 19 IS 7 BP 731 EP 733 DI 10.1097/01.aids.0000166098.54564.0c PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 921BT UT WOS:000228739900012 PM 15821401 ER PT J AU Yao, PJ Bushlin, I Furukawa, K AF Yao, PJ Bushlin, I Furukawa, K TI Preserved synaptic vesicle recycling in hippocampal neurons in a mouse Alzheimer's disease model SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Alzheimer's disease; triple-transgenic mouse model; synapse; synaptic vesicle recycling; FM1-43 release ID TRIPLE-TRANSGENIC MODEL; EXPRESSION PROFILE; FRONTAL-CORTEX; PROTEINS; BRAIN; TRAFFICKING; BETA AB A recently described triple-transgenic mouse model (3xTg, PSl(M146V), APP(Swe), and tau(P301L)) develops a neuropathology similar to the brains of Alzheimer's disease patients including progressive deposits of plaques and tangles [Neuron 39 (2003) 409]. These mice also show age-related deficits in hippocampal synaptic plasticity that occurs before the development of plaques and tangles. Here we report unchanged synaptic vesicle recycling, as measured by FM 1-43 release, in the hippocampal neurons of the 3xTg mice. Expression levels of presynaptic protein synaptophysin and of proteins involved in synaptic vesicle recycling including AP180, dynamin I, and synaptotagmin I also remain unaffected. These data suggest that the synaptic deficits observed in the 3xTg neurons may not arise from the preserved synaptic vesicle recycling. Published by Elsevier Inc. C1 NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Yao, PJ (reprint author), NIA, Neurosci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yaopa@grc.nia.nih.gov NR 26 TC 10 Z9 11 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 29 PY 2005 VL 330 IS 1 BP 34 EP 38 DI 10.1016/j.bbrc.2005.02.121 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 914UP UT WOS:000228253700006 PM 15781228 ER PT J AU Wellner, RB Cotrim, AP Hong, S Swaim, WD Baum, BJ AF Wellner, RB Cotrim, AP Hong, S Swaim, WD Baum, BJ TI Localization of AQP5/AQP8 chimeras in MDCK-II cells: Exchange of the N- and C-termini SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE aquaporin; protein sorting; apical membrane; basolateral membrane ID AQUAPORIN WATER CHANNELS; TRAFFICKING; EXPRESSION; MEMBRANE; POLARITY; PROTEIN; DISEASE AB AQP5 and AQP8 possess targeting/retention motifs which mediate their localization to the apical and basolateral membranes, respectively, of polarized MDCK-II cells. As targeting/retention motifs have been localized to the N- or C-termini of other AQPs, we sought the location of such motifs in AQPs 5 and 8 by exchanging their corresponding N- or C-termini and examining the expression, localization, and function of the resultant chimeras. We did not detect the expression of constructs in which the C-terminus of AQP5 was replaced by the C-terminus of AQP8. Substitution of the N-terminus of AQP8 for the N-terminus of AQP5 generated a construct which was trapped intracellularly and did not significantly facilitate transepithelial fluid movement. In contrast, modifications of the N- and C-termini of AQP8 were better tolerated. Substitution of either AQP8 terminus by the corresponding AQP5 terminus generated constructs which localized to basolateral membranes and facilitated transepithelial fluid movement. Our results suggest that, unlike the other AQP targeting/retention signals reported thus far, an AQP8 basolateral targeting/retention motif might reside between the two cytosolic termini. Published by Elsevier Inc. C1 Natl Inst Dent & Cranciofacial Res, Gene Transfer Sect, Gene Therapy & Therapeut Branch, NIH,DHHS, Bethesda, MD 20892 USA. Natl Inst Dent & Cranciofacial Res, Receptors & Signal Transduct Sect, Oral Infect & Immun Banch, NIH,DHHS, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Cranciofacial Res, Gene Transfer Sect, Gene Therapy & Therapeut Branch, NIH,DHHS, Bethesda, MD 20892 USA. EM BBaum@dir.nidcr.nih.gov NR 21 TC 4 Z9 4 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 29 PY 2005 VL 330 IS 1 BP 172 EP 177 DI 10.1016/j.bbrc.2005.02.146 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 914UP UT WOS:000228253700025 PM 15781247 ER PT J AU Xiao, BL Jiang, MT Zhao, MC Yang, DM Sutherland, C Lai, FA Walsh, MP Warltier, DC Cheng, HP Chen, SRW AF Xiao, BL Jiang, MT Zhao, MC Yang, DM Sutherland, C Lai, FA Walsh, MP Warltier, DC Cheng, HP Chen, SRW TI Characterization of a novel PKA phosphorylation site, serine-2030, reveals no PKA hyperphosphorylation of the cardiac ryanodine receptor in canine heart failure SO CIRCULATION RESEARCH LA English DT Article DE heart failure; PKA phosphorylation; ryanodine receptor; FKBP12.6; phosphospecific antibody ID PROTEIN-KINASE-A; CELLULAR BASIS; PHOSPHOLAMBAN; FKBP12.6; CA2+; STIMULATION; ARRHYTHMIAS; MYOCARDIUM; RELEASE; LEVEL AB Hyperphosphorylation of the cardiac Ca2+ release channel ( ryanodine receptor, RyR2) by protein kinase A (PKA) at serine-2808 has been proposed to be a key mechanism responsible for cardiac dysfunction in heart failure (HF). However, the sites of PKA phosphorylation in RyR2 and their phosphorylation status in HF are not well defined. Here we used various approaches to investigate the phosphorylation of RyR2 by PKA. Mutating serine-2808, which was thought to be the only PKA phosphorylation site in RyR2, did not abolish the phosphorylation of RyR2 by PKA. Two-dimensional phosphopeptide mapping revealed two major PKA phosphopeptides, one of which corresponded to the known serine-2808 site. Another, novel, PKA phosphorylation site, serine 2030, was identified by Edman sequencing. Using phospho-specific antibodies, we showed that the novel serine-2030 site was phosphorylated in rat cardiac myocytes stimulated with isoproterenol, but not in unstimulated cells, whereas serine-2808 was considerably phosphorylated before and after isoproterenol treatment. We further showed that serine-2030 was stoichiometrically phosphorylated by PKA, but not by CaMKII, and that mutations of serine-2030 altered neither the FKBP12.6-RyR2 interaction nor the Ca2+ dependence of [H-3] ryanodine binding. Moreover, the levels of phosphorylation of RyR2 at serine-2030 and serine-2808 in both failing and non-failing canine hearts were similar. Together, our data indicate that serine-2030 is a major PKA phosphorylation site in RyR2 responding to acute beta-adrenergic stimulation, and that RyR2 is not hyperphosphorylated by PKA in canine HF. C1 Univ Calgary, Dept Physiol & Biophys, Smooth Muscle Res Grp, Calgary, AB T2N 4N1, Canada. Univ Calgary, Cardiovasc Res Grp, Calgary, AB T2N 4N1, Canada. Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. Med Coll Wisconsin, Dept Anesthesiol, Milwaukee, WI 53226 USA. NIH, Cardiovasc Sci Lab, Baltimore, MD USA. Univ Wales Coll Cardiff, Wales Heart Res Inst, Cardiff CF1 1XL, S Glam, Wales. RP Jiang, MT (reprint author), Univ Calgary, Dept Physiol & Biophys, Smooth Muscle Res Grp, Calgary, AB T2N 4N1, Canada. EM mtjiang@mcw.edu; swchen@ucalgary.ca RI Xiao, Bailong/B-6187-2012 NR 22 TC 116 Z9 121 U1 1 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 APR 29 PY 2005 VL 96 IS 8 BP 847 EP 855 DI 10.1161/01.RES.0000163276.26083.e8 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 920YK UT WOS:000228731200008 PM 15790957 ER PT J AU Lucas-Lopez, C Patterson, S Blum, T Straight, AF Toth, J Slawin, AMZ Mitchison, TJ Sellers, JR Westwood, NJ AF Lucas-Lopez, C Patterson, S Blum, T Straight, AF Toth, J Slawin, AMZ Mitchison, TJ Sellers, JR Westwood, NJ TI Absolute stereochemical assignment and fluorescence tuning of the small molecule tool, (-)-blebbistatin SO EUROPEAN JOURNAL OF ORGANIC CHEMISTRY LA English DT Article DE inhibitors; asymmetric synthesis; fluorescence ID MYOSIN-II INHIBITOR; BLEBBISTATIN; OXAZIRIDINES; CHEMISTRY; CELLS; LIGHT AB (-)-Blebbistatin (1), a recently discovered small molecule inhibitor of the ATPase activity of non-muscle myosin 11 has been prepared from methyl 5-methylanthranilate (6) in three steps. This flexible synthetic route has also been used to prepare a nitro group-containing analogue 12 that has modified fluorescence properties and improved stability under microscope illumination. The key step in the synthesis of 1 and its analogues was the asymmetric hydroxylation of the quinolone intermediate 3 using the Davis oxaziridine methodology. The absolute stereochemistry of (-)-blebbistatin (1) was shown to be S by X-ray crystal structure analysis of a heavy atom (bromine) containing analogue 11, which was subsequently reduced and shown to be identical to 1. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005). C1 Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland. Univ St Andrews, Ctr Biomol Sci, St Andrews KY16 9ST, Fife, Scotland. Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Westwood, NJ (reprint author), Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland. EM njw3@st-andrews.ac.uk OI Straight, Aaron/0000-0001-5885-7881; Slawin, Alexandra/0000-0002-9527-6418 NR 25 TC 17 Z9 17 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-193X J9 EUR J ORG CHEM JI Eur. J. Org. Chem. PD APR 29 PY 2005 IS 9 BP 1736 EP 1740 DI 10.1002/ejoc.200500103 PG 5 WC Chemistry, Organic SC Chemistry GA 924DR UT WOS:000228959500004 ER PT J AU Katabami, M Donninger, H Hommura, F Leaner, VD Kinoshita, I Chick, JFB Birrer, MJ AF Katabami, M Donninger, H Hommura, F Leaner, VD Kinoshita, I Chick, JFB Birrer, MJ TI Cyclin A is a c-Jun target gene and is necessary for c-Jun-induced anchorage-independent growth in RAT1a cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BREAST-CANCER CELLS; REGULATED TRANSCRIPTION; CELLULAR-TRANSFORMATION; HEMATOPOIETIC-CELLS; EMBRYO FIBROBLASTS; DEPENDENT KINASE-2; PROTEIN-KINASE; RAT-1A CELLS; S-PHASE; EXPRESSION AB Overexpression of c-Jun enables Rat1a cells to grow in an anchorage-independent manner. We used an inducible c-Jun system under the regulation of doxycycline in Rat1a cells to identify potential c-Jun target genes necessary for c-Jun-induced anchorage-independent growth. Induction of c-Jun results in sustained expression of cyclin A in the nonadherent state with only minimal expression in the absence of c-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in which c-Jun expression was induced compared with the control cells. Chromatin immunoprecipitation demonstrated that c-Jun bound directly to the cyclin A2 promoter. Mutation analysis of the cyclin A2 promoter mapped the c-Jun regulatory site to an ATF site at position - 80. c-Jun was able to bind to this site both in vitro and in vivo, and mutation of this site completely abolished promoter activity. Cyclin A1 was also elevated in c-Jun-overexpressing Rat1a cells; however, c-Jun did not regulate this gene directly, since it did not bind directly to the cyclin A1 promoter. Suppression of cyclin A expression via the introduction of a cyclin A antisense sequences significantly reduced the ability of c-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. Taken together, these results suggest that cyclin A is a target of c-Jun and is necessary but not sufficient for c-Jun-induced anchorage-independent growth. In addition, we demonstrated that the cytoplasmic oncogenes Ras and Src transcriptionally activated the cyclin A2 promoter via the ATF site at position - 80. Using a dominant negative c-Jun mutant, TAM67, we showed that this transcriptional activation of cyclin A2 requires c-Jun. Thus, our results suggest that c-Jun is a mediator of the aberrant cyclin A2 expression associated with Ras/Src-induced transformation. C1 NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20850 USA. RP Birrer, MJ (reprint author), NCI, Dept Cell & Canc Biol, NIH, 9610 Med Ctr Dr,Rm 300, Rockville, MD 20850 USA. EM birrerm@bprb.nci.nih.gov NR 72 TC 27 Z9 30 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 APR 29 PY 2005 VL 280 IS 17 BP 16728 EP 16738 DI 10.1074/jbc.M413892200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500024 PM 15737994 ER PT J AU Wang, W Jobbagy, Z Bird, TH Eiden, MV Anderson, WB AF Wang, W Jobbagy, Z Bird, TH Eiden, MV Anderson, WB TI Cell signaling through the protein kinases cAMP-dependent protein kinase, protein kinase C epsilon, and RAF-1 regulates amphotropic murine leukemia virus envelope protein-induced syncytium formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATE-UPTAKE; RETROVIRUS RECEPTOR; MEMBRANE-FUSION; UP-REGULATION; PKC-EPSILON; LIPID RAFTS; VIRAL ENTRY; HERV-W; ACTIVATION; EXPRESSION AB Amphotropic murine leukemia virus ( A-MuLV) utilizes the PiT2 sodium-dependent phosphate transporter as its cell surface receptor to infect mammalian cells. The process of A-MuLV infection requires cleavage of the R peptide from the envelope protein. This occurs within virions thereby rendering them competent to fuse with target cells. Envelope proteins lacking the inhibitory R peptide ( e. g. envelope ( R-) proteins) induce viral envelope-mediated cell-cell fusion ( syncytium). Here we have performed studies to determine if cell signaling through protein kinases is involved in the regulation of PiT2-mediated A-MuLV envelope ( R-)-induced syncytium formation. Truncated A-MuLV retroviral envelope protein lacking the inhibitory R peptide ( R-) was used to induce viral envelope-mediated cell-cell fusion. Signaling through cyclic AMP to activate PKA was found to inhibit envelope-induced cell-cell fusion, whereas treatment of cells with PKA inhibitors H89, KT5720, and PKA Cat alpha siRNA all enhanced this cell fusion process. It was noted that activation of PKC, as well as overexpression of PKC epsilon, up-regulated A-MuLV envelope protein-induced cell-cell fusion, whereas exposure to PKC inhibitors and expression of a kinase-inactive dominant-negative mutant of PKC epsilon (K437R) inhibited syncytium formation. v-ras transformed NIH3T3 cells were highly susceptible to A-MuLV envelope-induced cell-cell fusion, whereas expression of a dominant-negative mutant of Ras (N17Ras) inhibited this cell fusion process. Importantly, activation of Raf-1 protein kinase also is required for A-MuLV envelope-induced syncytium formation. Expression of constitutively active BXB Raf supported, whereas expression of a dominant-negative mutant of Raf-1 (Raf301) blocked, A-MuLV-induced cell-cell fusion. These results indicate that specific cell signaling components are involved in regulating PiT2-mediated A-MuLV-induced cell-cell fusion. Selective pharmacological modulation of these signaling components may be an effective means of altering cell susceptibility to viral-mediated cytopathic effects. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Anderson, WB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Rm 4124,37 Convent Dr, Bethesda, MD 20892 USA. EM andersow@mail.nih.gov NR 56 TC 5 Z9 5 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 APR 29 PY 2005 VL 280 IS 17 BP 16772 EP 16783 DI 10.1074/jbc.M411537200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500029 PM 15741175 ER PT J AU Gaildrat, P Moller, M Mukda, S Humphries, A Carter, DA Ganapathy, V Klein, DC AF Gaildrat, P Moller, M Mukda, S Humphries, A Carter, DA Ganapathy, V Klein, DC TI A novel pineal-specific product of the oligopeptide transporter PepT1 gene - Circadian expression mediated by cAMP activation of an intronic promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEROTONIN N-ACETYLTRANSFERASE; O-METHYLTRANSFERASE GENE; ORPHAN NUCLEAR RECEPTOR; MESSENGER-RNA; H+/PEPTIDE COTRANSPORTER; DIURNAL RHYTHM; MELATONIN SYNTHESIS; NOCTURNAL INCREASE; HOMEOBOX GENE; GLAND AB The oligopeptide transporter 1, PepT1, is a member of the Slc15 family of 12 membrane-spanning domain transporters; PepT1 has proton/peptide cotransport activity and is selectively expressed in intestinal epithelial cells, where it is responsible for the nutritional absorption of di- and tri-peptides. Here, a novel PepT1 gene product has been identified in the rat pineal gland, termed pgPepT1. It encodes a 150-amino acid protein encompassing the C-terminal 3 membrane-spanning domains of intestinal PepT1 protein, with 3 additional N-terminal residues. Expression of pgPepT1 appears to be restricted to the pineal gland and follows a marked circadian pattern with > 100-fold higher levels of mRNA occurring at night; this is accompanied by an accumulation of membrane-associated pgPepT1 protein ( similar to 16 kDa). The daily rhythm in pgPepT1 mRNA is regulated by the well described neural pathway that controls pineal melatonin production. This includes the retina, the circadian clock in the suprachiasmatic nucleus, central structures, and projections from the superior cervical ganglia; activation of this pathway results in the release of norepinephrine. Here it was found that pgPepT1 expression is mediated by a norepinephrine 3 cyclic AMP mechanism that activates an alternative promoter located in intron 20 of the gene. pgPepT1 protein was found to have transporter-modulator activity; it could contribute to circadian changes in pineal function through this mechanism. C1 NICHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Copenhagen, Panum Inst, Inst Med Anat, DK-2200 Copenhagen, Denmark. Mahidol Univ, Neurobehav Biol Ctr, Inst Sci & Technol Res & Dev, Nakhon Pathom 73170, Thailand. Univ Wales Coll Cardiff, Sch Biosci, Cardiff CF10 3US, S Glam, Wales. Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. RP Klein, DC (reprint author), NICHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bldg 49,Rm 6A-82, Bethesda, MD 20892 USA. EM klein@helix.nih.gov RI Carter, David/A-4479-2010 OI Carter, David/0000-0002-8419-3975 FU Medical Research Council [G9724886] NR 53 TC 27 Z9 28 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 APR 29 PY 2005 VL 280 IS 17 BP 16851 EP 16860 DI 10.1074/jbc.M414587200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500039 PM 15684415 ER PT J AU Desai, SA Alkhalil, A Kang, M Ashfaq, U Nguyen, ML AF Desai, SA Alkhalil, A Kang, M Ashfaq, U Nguyen, ML TI Plasmodial surface anion channel-independent phloridzin resistance in Plasmodium falciparum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MALARIA-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; PARASITE; TRANSPORT; MEMBRANE; PERMEATION; TRANSFECTION; CULTURE; GROWTH; NA+ AB The plasmodial surface anion channel (PSAC) is an unusual ion channel induced on the human red blood cell membrane after infection with the malaria parasite, Plasmodium falciparum. Because PSAC is permeant to small metabolic precursors essential for parasite growth and is present on red blood cells infected with geographically divergent parasite isolates, it may be an ideal target for future antimalarial development. Here, we used chemically induced mutagenesis and known PSAC antagonists that inhibit in vitro parasite growth to examine whether resistance mutations in PSAC can be readily induced. Stable mutants resistant to phloridzin were generated and selected within 3 weeks after treatment with 1-methyl-3-nitro-1-nitrosoguanidine. These mutants were evaluated with osmotic lysis and electrophysiological transport assays, which indicate that PSAC inhibition by phloridzin is complex with at least two different modes of inhibition. Mutants resistant to the growth inhibitory effects of phloridzin expressed PSAC activity indistinguishable from that on sensitive parasites, indicating selection of resistance via mutations in one or more other parasite targets. Failure to induce mutations in PSAC activity is consistent with a highly constrained channel protein less susceptible to resistance mutations; whether this protein is parasiteor host-encoded remains to be determined. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rm 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009 FU Intramural NIH HHS [Z01 AI000882-07] NR 37 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 APR 29 PY 2005 VL 280 IS 17 BP 16861 EP 16867 DI 10.1074/jbc.M414629200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500040 PM 15701633 ER PT J AU Lee, DW Zhao, XH Scarselletta, S Schweinsberg, PJ Eisenberg, E Grant, BD Greene, LE AF Lee, DW Zhao, XH Scarselletta, S Schweinsberg, PJ Eisenberg, E Grant, BD Greene, LE TI ATP binding regulates oligomerization and endosome association of RME-1 family proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MUSCLE MYOSIN ATPASE; PLASMA-MEMBRANE; EHD1; COMPARTMENT; MOLECULES; MECHANISM; RECEPTOR AB Members of the RME-1/mRme-1/EHD1 protein family have recently been shown to function in the recycling of membrane proteins from recycling endosomes to the plasma membrane. RME-1 family proteins are normally found in close association with recycling endosomes and the vesicles and tubules emanating from these endosomes, consistent with the proposal that these proteins directly participate in endosomal transport. RME-1 family proteins contain a C-terminal EH (eps15 homology) domain thought to be involved in linking RME-1 to other endocytic proteins, a coiled-coil domain thought to be involved in homo-oligomerization and an N-terminal P-loop domain thought to mediate nucleotide binding. In the present study, we show that both Caenorhabditis elegans and mouse RME-1 proteins bind and hydrolyze ATP. No significant GTP binding or hydrolysis was detected. Mutation or deletion of the ATP-binding P-loop prevented RME-1 oligomerization and at the same time dissociated RME-1 from endosomes. In addition, ATP depletion caused RME-1 to lose its endosome association in the cell, resulting in cytosolic localization. Taken together, these results indicate that ATP binding is required for oligomerization of mRme-1/EHD1, which in turn is required for its association with endosomes. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. RP Greene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Dr,Rm 2537,MSC 8017, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov OI Grant, Barth/0000-0002-5943-8336 FU NIGMS NIH HHS [GM67237-01, R01 GM067237, R01 GM067237-02] NR 23 TC 47 Z9 48 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 APR 29 PY 2005 VL 280 IS 17 BP 17213 EP 17220 DI 10.1074/jbc.M412751200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500083 PM 15710626 ER PT J AU Hildesheim, J Salvador, JM Hollander, MC Fornace, AJ AF Hildesheim, J Salvador, JM Hollander, MC Fornace, AJ TI Casein kinase 2-and protein kinase A-regulated adenomatous polyposis coli and beta-catenin cellular localization is dependent on p38 MAPK SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONMELANOMA SKIN-CANCER; NUCLEAR EXPORT; SUBCELLULAR-LOCALIZATION; CYCLIN D1; PHOSPHORYLATION; APC; EXPRESSION; PATHWAY; COMPLEX; TARGET AB Skin cancer is the most common form of malignancy in the world with epidemic proportions. Identifying the biochemical and molecular mechanisms underlying the events leading to tumors is paramount to designing new and effective treatments that may aid in treating and/or preventing skin cancers. Herein we identify p38 MAPK, along with its positive modulator, Gadd45a, as important regulators of nucleocytoplasmic shuttling of the adenomatous polyposis coli (APC) tumor suppressor. APC normally functions to block beta-catenin from promoting cell proliferation and migration/invasion. Keratinocytes lacking proper p38 MAPK activation, either due to lack of Gadd45a or through the use of p38 MAPK-specific inhibitors, are unable to effectively transport APC into the nucleus. We also show that p38 MAPK is able to directly associate with and modulate both casein kinase 2 (CK2) and protein kinase A (PKA), which promote and block APC nuclear import, respectively. We demonstrate that p38 MAPK is able to not only enhance CK2 kinase activity but also suppress PKA kinase activity. Moreover, lack of normal p38 MAPK activity in either Gadd45a-null keratinocytes or in p38 MAPK inhibitor treated keratinocytes leads to decreased CK2 activity and increased PKA activity. In either case, disruption of APC nuclear import results in elevated levels of free cellular, and potentially oncogenic, beta-catenin. Numerous tumors, including skin cancers, are associated with high levels of beta-catenin, and our data indicate that p38 MAPK signaling, along with Gadd45a, may provide tumor suppressor-like functions in part by promoting APC nuclear localization and effective beta-catenin regulation. C1 NCI, Gene Response Sect, CCR, NIH, Bethesda, MD 20892 USA. RP Hildesheim, J (reprint author), NCI, Gene Response Sect, CCR, NIH, Bldg 37,Rm 6144,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM jh30h@nih.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 43 TC 25 Z9 29 U1 1 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 APR 29 PY 2005 VL 280 IS 17 BP 17221 EP 17226 DI 10.1074/jbc.M410440200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500084 PM 15649893 ER PT J AU Hansen, AM Gu, YJ Li, M Andrykovitch, M Waugh, DS Jin, DJ Ji, XH AF Hansen, AM Gu, YJ Li, M Andrykovitch, M Waugh, DS Jin, DJ Ji, XH TI Structural basis for the function of stringent starvation protein A as a transcription factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTATHIONE S-TRANSFERASES; YEAST SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; RNA-POLYMERASE; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION; GENE-EXPRESSION; VIBRIO-CHOLERAE; ACID TOLERANCE AB Stringent starvation protein A ( SspA) of Escherichia coli is an RNA polymerase-associated transcriptional activator for the lytic development of phage P1 and is essential for stationary phase-induced acid tolerance of E. coli. We report the crystal structure of Yersinia pestis SspA, which is 83% identical to E. coli SspA in amino acid sequence and is functionally complementary in supporting the lytic growth of phage P1 and acid resistance of an E. coli sspA mutant. The structure reveals that SspA assumes the characteristic fold of glutathione S-transferase (GST). However, SspA lacks GST activity and does not bind glutathione. Three regions of SspA are flexible, the N and C termini and the alpha 2-helix. The structure also reveals a conserved surface-exposed pocket composed of residues from a loop between helices alpha 3 and alpha 4. The functional roles of these structural features were investigated by assessing the ability of deletion and site-directed mutants to confer acid resistance of E. coli and to activate transcription from a phage P1 late promoter, thereby supporting the lytic growth of phage P1. The results indicate that the flexible regions are not critical for SspA function, whereas the surface pocket is important for both transcriptional activation of the phage P1 late promoter and acid resistance of E. coli. The size, shape, and property of the pocket suggest that it mediates protein-protein interactions. SspA orthologs from Y. pestis, Vibrio cholerae, and Pseudomonas aeruginosa are all functional in acid resistance of E. coli, whereas only Y. pestis SspA supports phage P1 growth. C1 NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. Univ So Denmark, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. NCI, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Jin, DJ (reprint author), NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, NIH, 1050 Boyles St,Bldg 469,Rm 127, Frederick, MD 21702 USA. EM djjin@helix.nih.gov; jix@ncifcrf.gov RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [N01-CO-24000] NR 68 TC 29 Z9 30 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 APR 29 PY 2005 VL 280 IS 17 BP 17380 EP 17391 DI 10.1074/jbc.M501444200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500103 PM 15735307 ER PT J AU Moriguchi, M Hissong, BD Gadina, M Yamaoka, K Tiffany, HL Murphy, PM Candotti, F O'Shea, JJ AF Moriguchi, M Hissong, BD Gadina, M Yamaoka, K Tiffany, HL Murphy, PM Candotti, F O'Shea, JJ TI CXCL12 signaling is independent of Jak2 and Jak3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; MICE LACKING JAK3; TYROSINE PHOSPHORYLATION; LYMPHOID DEVELOPMENT; CHEMOKINE RECEPTORS; JAK/STAT PATHWAY; FERM DOMAIN; T-CELLS; ACTIVATION; DIMERIZATION AB Janus kinases (Jaks) are a small family of cytoplasmic tyrosine kinases, critical for signaling by Type I and II cytokine receptors. The importance of Jaks in signaling by these receptors has been firmly established by analysis of mutant cell lines, the generation of Jak knock-out mice, and the identification of patients with Jak3 mutations. While a number of other ligands that do not bind Type I and II cytokine receptors have also been reported to activate Jaks, the requirement for Jaks in signaling by these receptors is less clear. Chemokines for example, which bind seven transmembrane receptors, have been reported to activate Jaks, and principally through the use of pharmacological inhibitors, it has been argued that Jaks are essential for chemokine signaling. In the present study, we focused on CXCR4, which binds the chemokine CXCL12 or stromal cell-derived factor-1, a chemokine that has been reported to activate Jak2 and Jak3. We found that the lack of Jak3 had no effect on CXCL12 signaling or chemotaxis nor did overexpression of wild-type versions of the kinase. Similarly, overexpression of wild-type or catalytically inactive Jak2 or "knocking-down" Jak2 expression using siRNA also had no effect. We also found that in primary lymphocytes, CXCL12 did not induce appreciable phosphorylation of any of the Jaks compared with cytokines for which these kinases are required. Additionally, little or no Stat ( signal transducer and activator of transcription) phosphorylation was detected. Thus, we conclude that in contrast to previous reports, Jaks, especially Jak3, are unlikely to play an essential role in chemokine signaling. C1 NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP O'Shea, JJ (reprint author), NIAMS, Mol Immunol & Inflammat Branch, NIH, Bldg 10,Rm 9N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM osheajo@mail.nih.gov NR 46 TC 29 Z9 31 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 29 PY 2005 VL 280 IS 17 BP 17408 EP 17414 DI 10.1074/jbc.M414219200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500106 PM 15611059 ER PT J AU Hee Ryu, OK Choi, SJ Firatli, E Choi, SW Hart, PS Shen, RF Wang, GH Wu, WW Hart, TC AF Hee Ryu, OK Choi, SJ Firatli, E Choi, SW Hart, PS Shen, RF Wang, GH Wu, WW Hart, TC TI Proteolysis of macrophage inflammatory protein-1 alpha isoforms LD78 beta and LD78 alpha by neutrophil-derived serine proteases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; CC CHEMOKINES; MIP-1-ALPHA; MIP-1-BETA; EXPRESSION; DISEASE; ALPHA; IDENTIFICATION; INACTIVATION AB Macrophage inflammatory protein-1 alpha (MIP-1 alpha) is a chemokine that leads to leukocyte recruitment and activation at sites of infection. Controlling chemokine activity at sites of infection is important, since excess accumulation of leukocytes may contribute to localized tissue damage. Neutrophil-derived serine proteases modulate the bioactivity of chemokine and cytokine networks through proteolytic cleavage. Because MIP-1 alpha is temporally expressed with neutrophils at sites of infection, we examined proteolysis of MIP-1 alpha in vitro by the neutrophil-derived serine proteases: cathepsin G, elastase, and proteinase 3. Recombinant human MIP-1 alpha isoforms LD78 beta and LD78 alpha were expressed and purified, and the protease cleavage sites were analyzed by mass spectrometry and peptide sequencing. Chemotactic activities of parent and cleavage molecules were also compared. Both LD78 beta and LD78 alpha were cleaved by neutrophil lysates at Thr(16)- Ser(17), Phe(24)- Ile(25), Tyr(28)- Phe(29), and Thr(31)-Ser(32). This degradation was inhibited by serine protease inhibitors phenylmethylsulfonyl fluoride and 4-(2-aminoethyl)-benzenesulfonyl fluoride. Incubation of the substrates with individual proteases revealed that cathepsin G preferentially cleaved at Phe24- Ile25 and Tyr28- Phe29, whereas elastase and proteinase 3 cleaved at Thr(16)- Ser(17) and Thr(31)- Ser(32). Proteolysis of LD78 beta resulted in loss of chemotactic activity. The role of these proteases in LD78 beta and LD78 alpha degradation was confirmed by incubation with neutrophil lysates from Papillon-Lefevre syndrome patients, demonstrating that the cell lysates containing inactivated serine proteases could not degrade LD78 beta and LD78 alpha. These findings suggest that severe periodontal tissue destruction in Papillon-Lefevre syndrome may be related to excess accumulation of LD78 beta and LD78 alpha and dysregulation of the microbial-induced inflammatory response in the periodontium. C1 NIDCR, Human Craniofacial Genet Sect, NIH, Bethesda, MD 20892 USA. Istanbul Univ, Sch Dent, Dept Periodontol, TR-34390 Istanbul, Turkey. NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. RP Hart, TC (reprint author), 10 Ctr Dr,Bldg 10,Rm 5-2531, Bethesda, MD 20892 USA. EM thart@mail.nih.gov RI FIRATLI, Erhan/E-4241-2013 OI FIRATLI, Erhan/0000-0002-4154-6929 NR 37 TC 0 Z9 0 U1 1 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 APR 29 PY 2005 VL 280 IS 17 BP 17415 EP 17421 DI 10.1074/jbc.M500340200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919JY UT WOS:000228615500107 ER PT J AU Kajava, AV Aebi, U Steven, AC AF Kajava, AV Aebi, U Steven, AC TI The parallel superpleated beta-structure as a model for amyloid fibrils of human amylin SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE atomic structure; diabetes mellitus; islet amyloid; fibrils ID SOLID-STATE NMR; DIABETES-MELLITUS; IN-VITRO; CRYSTAL-STRUCTURE; HUMAN CALCITONIN; VIRULENCE FACTOR; FULL-LENGTH; POLYPEPTIDE; FIBRILLOGENESIS; IDENTIFICATION AB Human amylin is a 37 amino acid residue peptide hormone whose fibrillogenesis has been correlated with type 2 diabetes. These fibrils are rope-like bundles of several 5 nm diameter protofilaments. Here, we propose, as a model for the protofilament, a variant of the parallel superpleated beta-structure previously derived for amyloid filaments of the yeast prion Ure2p. In the amylin model, individual polypeptides from residues 9 to 37 have a planar S-shaped fold with three beta-strands. These serpentines are stacked in register, with a 0.47 nm axial rise and a small rotational twist per step, generating an array of three parallel P-sheets in cross-beta conformation. The interior, the two "bays" sandwiched between adjacent sheets, are occupied by non-polar and by polar/uncharged residues that are predicted to form H-bonded ladders, similar to those found in P-helical proteins. The N-terminal peptide containing a disulfide bond occupies an extraneous peripheral position in the protofilament. The left-handed twist of the beta-sheets is shown to underlie left-handed coiling of amylin protofilaments in fibrils. The model is consistent with current biophysical, biochemical and genetic data and, in particular, affords a plausible explanation for why rodent amylin does not form fibrils. (c) 2005 Elsevier Ltd. All rights reserved. C1 CNRS, FRE 2593, Ctr Rech Biochim Macromol, F-34293 Montpellier, France. Univ Basel, Biozentrum, ME Muller Inst Struct Biol, CH-4056 Basel, Switzerland. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kajava, AV (reprint author), CNRS, FRE 2593, Ctr Rech Biochim Macromol, 1919 Route Mende, F-34293 Montpellier, France. EM andrey.kajava@crbm.cnrs.fr RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 37 TC 117 Z9 118 U1 0 U2 7 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 APR 29 PY 2005 VL 348 IS 2 BP 247 EP 252 DI 10.1016/j.jmb.2005.02.029 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916UD UT WOS:000228410800001 PM 15811365 ER PT J AU Gustchina, A Li, M Wunschmann, S Chapman, MD Pomes, A Wlodawer, A AF Gustchina, A Li, M Wunschmann, S Chapman, MD Pomes, A Wlodawer, A TI Crystal structure of cockroach allergen Bla g 2, an unusual zinc binding aspartic protease with a novel mode of self-inhibition SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE active site; allergy; aspartic proteases; metal binding; self-inhibition ID DUST-MITE ALLERGEN; INNER-CITY CHILDREN; SACCHAROMYCES-CEREVISIAE; RECOMBINANT ALLERGENS; IGE REACTIVITY; CELL EPITOPES; RISK-FACTORS; ACTIVE-SITE; HUMAN RENIN; P-I AB The crystal structure of Bla g 2 was solved in order to investigate the structural basis for the allergenic properties of this unusual protein. This is the first structure of an aspartic protease in which conserved glycine residues, in two canonical DTG triads, are substituted by different amino acid residues. Another unprecedented feature revealed by the structure is the single phenylalanine residue insertion on the tip of the,flap, with the side-chain occupying the SI binding pocket. This and other important amino acid substitutions in the active site region of Bla g 2 modify the interactions in the vicinity of the catalytic aspartate residues, increasing the distance between them to similar to 4 A and establishing unique direct contacts between the flap and the catalytic residues. We attribute the absence of substantial catalytic activity in Bla g 2 to these unusual features of the active site. Five disulfide bridges and a Zn-binding site confer stability to the protein, which may contribute to sensitization at lower levels of exposure than other allergens. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. INDOOR Biotechnol Inc, Charlottesville, VA 22903 USA. RP Gustchina, A (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM alla@ncifcrf.gov OI Pomes, Anna/0000-0002-8729-1829 NR 58 TC 53 Z9 55 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 APR 29 PY 2005 VL 348 IS 2 BP 433 EP 444 DI 10.1016/j.jmb.2005.02.062 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916UD UT WOS:000228410800015 PM 15811379 ER PT J AU Menetret, JF Hegde, RS Heinrich, SU Chandramouli, P Ludtke, SJ Rapoport, TA Akey, CW AF Menetret, JF Hegde, RS Heinrich, SU Chandramouli, P Ludtke, SJ Rapoport, TA Akey, CW TI Architecture of the ribosome-channel complex derived from native membranes SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ribosome-channel complex; Sec61; TRAP; co-translational translocation ID ENDOPLASMIC-RETICULUM MEMBRANE; PROTEIN-CONDUCTING CHANNEL; SIGNAL RECOGNITION PARTICLE; 80 S RIBOSOME; TRANSLOCATION CHANNEL; ANGSTROM RESOLUTION; ER MEMBRANE; 3-DIMENSIONAL STRUCTURE; EXPANSION SEGMENTS; SEC61P COMPLEX AB The mammalian Sec61 complex forms a protein translocation channel whose function depends upon its interaction with the ribosome and with membrane proteins of the endoplasmic reticulum (ER). To study these interactions, we determined structures of "native" ribosome-channel complexes derived from ER membranes. We find that the ribosome is linked to the channel by seven connections, but the junction may still provide a path for domains of nascent membrane proteins to move into the cytoplasm. In addition, the native channel is significantly larger than a channel formed by the Sec61 complex, due to the presence of a second membrane protein. We identified this component as TRAP, the translocon-associated protein complex. TRAP interacts with Sec61 through its transmembrane domain and has a prominent lumenal domain. The presence of TRAP in the native channel indicates that it may play a general role in translocation. Crystal structures of two Sec61 homologues were used to model the channel. This analysis indicates that there are four Sec61 complexes and two TRAP molecules in each native channel. Thus, we suggest that a single Sec61. complex may form a conduit for translocating polypeptides, while three copies of Sec61 play a structural role or recruit accessory factors such as TRAP. (c) 2005 Elsevier Ltd. All rights reserved. C1 Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Nacl Ctr Macromol Imaging, Verna & Marrs Mclean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Harvard Univ, Howard Hughes Med Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Cell Biol, Sch Med, Boston, MA 02115 USA. RP Akey, CW (reprint author), Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. EM cakey@bu.edu OI Akey, Christopher/0000-0002-3059-3121; Hegde, Ramanujan/0000-0001-8338-852X NR 46 TC 100 Z9 104 U1 0 U2 1 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 APR 29 PY 2005 VL 348 IS 2 BP 445 EP 457 DI 10.1016/j.jmb.2005.02.053 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916UD UT WOS:000228410800016 PM 15811380 ER PT J AU Lu, NZ Cidlowski, JA AF Lu, NZ Cidlowski, JA TI Translational regulatory mechanisms generate N-terminal glucocorticoid receptor isoforms with unique transcriptional target genes SO MOLECULAR CELL LA English DT Article ID ESTROGEN-RECEPTOR; LIVING CELLS; PROTEIN; EXPRESSION; TRANSACTIVATION; IDENTIFICATION; ACTIVATION; INITIATION; GENOME; DOMAIN AB Glucocorticoids regulate diverse physiological functions ranging from mitosis to apoptosis, although only one glucocorticoid receptor (GR) gene has been discovered. We report here that one single GR mRNA species unexpectedly produces at least eight functional GR N-terminal isoforms via translational mechanisms. These GR isoforms display diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities. In human osteosarcoma cells, the transcriptional responses to glucocorticoids closely reflect the identity and abundance of the GR isoforms. In addition, each GR isoform regulates both a common and a unique set of genes in the same cell. Interestingly, the levels of these GR isoforms differ significantly among tissues. Based on these observations, we propose that cell-type specific GR isoforms generate specificity in glucocorticold control of transcription in different tissues. C1 NIEHS, Mol Endocrinol Grp, Lab Signaling Transduct, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Mol Endocrinol Grp, Lab Signaling Transduct, Dept Hlth & Human Serv,NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov NR 27 TC 210 Z9 217 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 29 PY 2005 VL 18 IS 3 BP 331 EP 342 DI 10.1016/j.molcel.2005.03.025 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 922NM UT WOS:000228844600007 PM 15866175 ER PT J AU Zhang, YJ Chen, Y Ahsan, H Lunn, RM Chen, SY Lee, PH Chen, CJ Santella, RM AF Zhang, YJ Chen, Y Ahsan, H Lunn, RM Chen, SY Lee, PH Chen, CJ Santella, RM TI Silencing of glutathione S-transferase P1 by promoter hypermethylation and its relationship to environmental chemical carcinogens in hepatocellular carcinoma SO CANCER LETTERS LA English DT Article DE epigenetic changes; hepatocellular carcinoma; hypermethylation; glutathione S-transferase P1; chemical carcinogens ID GLUTATHIONE-S-TRANSFERASE; GENE O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; ISLAND DNA HYPERMETHYLATION; GSTP1 CPG ISLAND; AFLATOXIN EXPOSURE; BREAST-CANCER; HUMAN NEOPLASIA; EXPRESSION; PI; METHYLATION AB Glutathione S-transferases (GSTs) are a family of isoenzymes that play an important role in protecting cells from cytotoxic and carcinogenic agents. GST pi is encoded by the GSTP1 gene. GSTP1 null mice show an increased risk of skin tumorigenesis induced by carcinogens. GSTP1 is transcriptionally silenced by promoter hypermethylation in several human cancers including hepatocellular carcinoma (HCC). Methylation-specific PCR (MSP) was used to analyze the GSTP1 promoter hypermethylation status of 83 hepatocellular carcinoma tissues from Taiwan. Hypermethylation was detected in 38 of 83 (46%) tumors. GSTP1 expression by immunohistochemical staining of HCC tissue samples was significantly associated with methylation status. The relationship between methylation status and clinical parameters and tumor markers including environmental exposure to aflatoxin B(1)(AFB(1)) and polycyclic aromatic hydrocarbons (PAH), measured as DNA adducts, was also investigated. A statistically significant association was found between GSTP1 promoter hypermethylation and the level of AFB(1)-DNA adducts in tumor tissue (OR 2.81, 95% CI 1.03-7.70); a marginally significant association was found for adjacent non-tumor tissue (OR 2.57, 95% CI 0.97-6.80). There was no association between GSTP1 hypermethylation and PAH-DNA adducts in tumor or adjacent non-tumor tissues. These results suggest that epigenetic inactivation of GSTP1 plays an important role in the development of HCC and exposure to environmental carcinogens may be related to altered methylation of genes involved in hepatocarcinogenesis. The mechanism by which environmental exposures induce epigenetic changes in HCC needs further analysis. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, New York, NY 10032 USA. NIEHS, Res Triangle Pk, NC USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei, Taiwan. Natl Taiwan Univ, Coll Med, Dept Surg, Taipei, Taiwan. RP Santella, RM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Environm Hlth Sci, 701 W 168th St, New York, NY 10032 USA. EM rps1@columbia.edu RI Chen, Chien-Jen/C-6976-2008; OI LEE, PO-HUANG/0000-0001-5831-035X FU NIEHS NIH HHS [ES05116, ES09098, P30 ES009089, R01 ES005116] NR 43 TC 55 Z9 57 U1 1 U2 5 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 28 PY 2005 VL 221 IS 2 BP 135 EP 143 DI 10.1016/j.canlet.2004.08.028 PG 9 WC Oncology SC Oncology GA 919GS UT WOS:000228607000003 PM 15808399 ER PT J AU Keshava, C Divi, RL Whipkey, DL Frye, BL McCanlies, E Kuo, M Poirier, MC Weston, A AF Keshava, C Divi, RL Whipkey, DL Frye, BL McCanlies, E Kuo, M Poirier, MC Weston, A TI Induction of CYP1A1 and CYP1B1 and formation of carcinogen-DNA adducts in normal human mammary epithelial cells treated with benzo[a]pyrene SO CANCER LETTERS LA English DT Article DE polycyclic aromatic hydrocarbons; chemiluminescence immunoassay; metabolic activation; cell culture; carcinogenesis; DNA damage ID BREAST-CANCER RISK; GENE-EXPRESSION; PASSIVE SMOKING; DIFFERENTIAL EXPRESSION; AROMATIC-HYDROCARBONS; METABOLIZING-ENZYMES; CIGARETTE-SMOKING; KOREAN WOMEN; POLYMORPHISMS; ASSOCIATION AB Inter-individual variation in formation of carcinogen-DNA adducts and induction of cytochrome P450 genes was measured in 23 cultured normal human mammary epithelial cell (NHMEC) strains established from reduction mammoplasty tissue. Semi-confluent cells were exposed to 4 mu M benzo[a]pyrene (BP) for 12 h and BP-DNA adduct levels were measured by chemiluminescence immunoassay using antiserum elicited against DNA modified with r7, t8-dihydroxy-t-9, 10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE). BP-DNA adduct levels for 22 of 23 different cell strains ranged from nondetectable (three samples) to about 15 adducts/10(8) nucleotides. Increases in levels of CYP1A1 and CYP1B1 were detected using both oligonucleotide arrays and reverse transcription/quantitative real-time polymerase chain reactions (RT-PCRs). For CYP1A1 and CYP1B1, the oligonucleotide array data and RT-PCR data were highly correlated (r = 0.73 and 0.70, respectively), suggesting that oligonucleotide arrays are a suitable gene discovery tool, and demonstrating that the complementary and efficient RT-PCR may be used to confirm rnicroarray data for a specific gene in a large number of samples. As measured by RT-PCR, inter-individual variation in CYP1A1 induction was 100-fold, while the variation in CYP1B1 induction was almost 40-fold. On a per-person basis, CYP1A1 and CYP1B1 induction were well-correlated (r = 0.88, P < 0.001), which is to be expected as they are under the control of a common transcriptional regulation mechanism in response to BP exposure. C1 NIOSH, Ctr Dis Control & Prevent, Mol Epidemiol Team, Toxicol & Mol Biol Branch, Morgantown, WV 26505 USA. NCI, Ctr Canc Res, Lab Cellular Carcinogenesis & Tumor Promot, Carcinogen DNA Interact Sect,NIH, Bethesda, MD 20892 USA. Natl Inst Occupat Safety & Hlth, Ctr Dis Control & Prevent, Hlth Effects Lab Div, Biostat & Epidemiol Branch, Morgantown, WV 26505 USA. RP Weston, A (reprint author), NIOSH, Ctr Dis Control & Prevent, Mol Epidemiol Team, Toxicol & Mol Biol Branch, 1095 Willowdale Rd, Morgantown, WV 26505 USA. EM agw8@cdc.gov NR 51 TC 22 Z9 24 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 28 PY 2005 VL 221 IS 2 BP 213 EP 224 DI 10.1016/j.canlet.2004.08.038 PG 12 WC Oncology SC Oncology GA 919GS UT WOS:000228607000011 PM 15808407 ER PT J AU Graziano, G Lee, B AF Graziano, G Lee, B TI On the intactness of hydrogen bonds around nonpolar solutes dissolved in water SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID HEAT-CAPACITY CHANGES; HYDROPHOBIC HYDRATION SHELL; AQUEOUS-SOLUTION; LIQUID WATER; COMPUTER-SIMULATION; MOLECULAR-DYNAMICS; TEMPERATURE-RANGE; ORGANIC-COMPOUNDS; RANDOM NETWORK; MODEL AB Angell developed a simple two-state model of hydrogen bonds with the aim to describe some properties of pure water. Muller extended the two-state model description to treat the unusual thermodynamics of hydrophobic hydration. We show here that, to correctly reproduce a qualitative feature of the temperature dependence of the hydration heat capacity change of nonpolar solutes by means of the two-state Muller's model, the hydrogen bonds in the hydration shell have to be more broken than those in bulk water. This contrasts with the suggestion in the literature that more hydrogen bonds form around a nonpolar solute in water. C1 Univ Sannio, Fac Sci, Dipartimento Sci Biol & Ambientali, I-82100 Benevento, Italy. NCI, Mol Modeling & Bioinformat Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Lee, B (reprint author), Univ Sannio, Fac Sci, Dipartimento Sci Biol & Ambientali, Via Port Arsa,11, I-82100 Benevento, Italy. EM graziano@unisannio.it; bk@nih.gov OI Graziano, Giuseppe/0000-0001-6935-8172 NR 54 TC 29 Z9 29 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 28 PY 2005 VL 109 IS 16 BP 8103 EP 8107 DI 10.1021/jp044634u PG 5 WC Chemistry, Physical SC Chemistry GA 919FM UT WOS:000228603700071 PM 16851947 ER PT J AU Mattapallil, JJ Douek, DC Hill, B Nishimura, Y Martin, M Roederer, M AF Mattapallil, JJ Douek, DC Hill, B Nishimura, Y Martin, M Roederer, M TI Massive infection and loss of memory CD4(+) T cells in multiple tissues during acute SIV infection SO NATURE LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; GASTROINTESTINAL-TRACT; HIV-1 INFECTION; RHESUS-MONKEYS; EXPRESSION; DEPLETION; DYNAMICS; TRANSMISSION; REPLICATION; LYMPHOCYTES AB It has recently been established that both acute human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections are accompanied by a dramatic and selective loss of memory CD4(+) T cells predominantly from the mucosal surfaces. The mechanism underlying this depletion of memory CD4(+) T cells (that is, T-helper cells specific to previously encountered pathogens) has not been defined. Using highly sensitive, quantitative polymerase chain reaction together with precise sorting of different subsets of CD4(+) T cells in various tissues, we show that this loss is explained by a massive infection of memory CD4(+) T cells by the virus. Specifically, 30-60% of CD4(+) memory T cells throughout the body are infected by SIV at the peak of infection, and most of these infected cells disappear within four days. Furthermore, our data demonstrate that the depletion of memory CD4(+) T cells occurs to a similar extent in all tissues. As a consequence, over one-half of all memory CD4(+) T cells in SIV-infected macaques are destroyed directly by viral infection during the acute phase-an insult that certainly heralds subsequent immunodeficiency. Our findings point to the importance of reducing the cell-associated viral load during acute infection through therapeutic or vaccination strategies. C1 NIAID, Immunotechnol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, Immunotechnol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Roederer@nih.gov RI Roederer, Mario/G-1887-2011 NR 25 TC 860 Z9 882 U1 3 U2 32 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 28 PY 2005 VL 434 IS 7037 BP 1093 EP 1097 DI 10.1038/nature03501 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 920MD UT WOS:000228693300033 PM 15793563 ER PT J AU Goldman, JM AF Goldman, JM TI A unifying mutation in chronic myeloproliferative disorders SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Goldman, JM (reprint author), NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 4 TC 26 Z9 32 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 28 PY 2005 VL 352 IS 17 BP 1744 EP 1746 DI 10.1056/NEJMp058083 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 920KY UT WOS:000228689000003 PM 15858182 ER PT J AU Falsey, AR Hennessey, PA Formica, MA Cox, C Walsh, EE AF Falsey, AR Hennessey, PA Formica, MA Cox, C Walsh, EE TI Respiratory syncytial virus infection in elderly and high-risk adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID REVERSE TRANSCRIPTION-PCR; DISEASE BURDEN; VIRAL CULTURE; UNITED-STATES; INFLUENZA; COMMUNITY; PNEUMONIA; MORTALITY; ILLNESS; VACCINATION AB BACKGROUND: Respiratory syncytial virus (RSV) is an increasingly recognized cause of illness in adults. Data on the epidemiology and clinical effects in community-dwelling elderly persons and high-risk adults can help in assessing the need for vaccine development. METHODS: During four consecutive winters, we evaluated all respiratory illnesses in prospective cohorts of healthy elderly patients (greater/equal 65 years of age) and high-risk adults (those with chronic heart or lung disease) and in patients hospitalized with acute cardiopulmonary conditions. RSV infection and influenza A were diagnosed on the basis of culture, reverse-transcriptase polymerase chain reaction, and serologic studies. RESULTS: A total of 608 healthy elderly patients and 540 high-risk adults were enrolled in prospective surveillance, and 1388 hospitalized patients were enrolled. A total of 2514 illnesses were evaluated. RSV infection was identified in 102 patients in the prospective cohorts and 142 hospitalized patients, and influenza A was diagnosed in 44 patients in the prospective cohorts and 154 hospitalized patients. RSV infection developed annually in 3 to 7 percent of healthy elderly patients and in 4 to 10 percent of high-risk adults. Among healthy elderly patients, RSV infection generated fewer office visits than influenza; however, the use of health care services by high-risk adults was similar in the two groups. In the hospitalized cohort, RSV infection and influenza A resulted in similar lengths of stay, rates of use of intensive care (15 percent and 12 percent, respectively), and mortality (8 percent and 7 percent, respectively). On the basis of the diagnostic codes of the International Classification of Diseases, 9th Revision, Clinical Modification at discharge, RSV infection accounted for 10.6 percent of hospitalizations for pneumonia, 11.4 percent for chronic obstructive pulmonary disease, 5.4 percent for congestive heart failure, and 7.2 percent for asthma. CONCLUSIONS: RSV infection is an important illness in elderly and high-risk adults, with a disease burden similar to that of nonpandemic influenza A in a population in which the prevalence of vaccination for influenza is high. An effective RSV vaccine may offer benefits for these adults. C1 Rochester Gen Hosp, Infect Dis Unit, Dept Med, Rochester, NY 14621 USA. Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Falsey, AR (reprint author), Rochester Gen Hosp, Infect Dis Unit, Dept Med, 1425 Portland Ave, Rochester, NY 14621 USA. EM ann.falsey@viahealth.org FU NIAID NIH HHS [R01-AI-45969] NR 38 TC 670 Z9 697 U1 9 U2 39 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 28 PY 2005 VL 352 IS 17 BP 1749 EP 1759 DI 10.1056/NEJMoa043951 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 920KY UT WOS:000228689000005 PM 15858184 ER PT J AU Adams, PC Reboussin, DM Barton, JC McLaren, CE Eckfeldt, JH McLaren, GD Dawkins, FW Acton, RT Harris, EL Gordeuk, VR Leiendecker-Foster, C Speechley, M Snively, BM Holup, JL Thomson, E Sholinsky, P Acton, RT Barton, JC Dixon, D Rivers, CA Tucker, D Ware, JC McLaren, CE McLaren, GD Anton-Culver, H Baca, JA Bent, TC Brunner, LC Dao, MM Jorgensen, KS Kuniyoshi, J Le, HD Masatsugu, MK Meyskens, FL Morohashi, D Nguyen, HP Panagon, SN Phung, C Raymundo, V Ton, T Walker, AP Wenzel, LB Ziogas, A Adams, PC Bloch, E Chakrabarti, S Fleischhauer, A Harrison, H Jia, K Larson, S Lin, E Lopez, M Nguyen, L Pepper, C Power, T Speechley, M Sun, D Woelfle, D Jordan, J Hogan, B Moses, G Harris, EL Aickin, M Baker, E Erwin, M Holup, J Lloyd, C Press, N Press, RD Reiss, J Ritenbaugh, C Uchida, A Vogt, T Yim, D Gordeuk, VR Dawkins, FW Fadojutimi-Akinsiku, M Castro, O White-Coleman, D Gerald, M Harrison, BW Lewis-Jack, O Murray, RF McDonald-Pinkett, S Romagoza, J Williams, R Eckfeldt, JH Leiendecker-Foster, C McGlennen, RC Rynders, G Tsai, MY Reboussin, DM Snively, BM Anderson, R Bostic, E Craven, BL Ellis, S Furberg, C Griffin, J Hall, M Harris, D Henkin, L Jackson, S Jewett, T King, MD Lohman, K Lovato, L Michaleckyj, J Palla, S Parks, T Passmore, L Phatak, PD Rich, S Ruggiero, A Vitolins, M Wolgast, G Zaccaro, D Sholinsky, P Bookman, E Chang, H Fabsitz, R Jaquish, C Manolio, T O'Neill, L Thomson, E AF Adams, PC Reboussin, DM Barton, JC McLaren, CE Eckfeldt, JH McLaren, GD Dawkins, FW Acton, RT Harris, EL Gordeuk, VR Leiendecker-Foster, C Speechley, M Snively, BM Holup, JL Thomson, E Sholinsky, P Acton, RT Barton, JC Dixon, D Rivers, CA Tucker, D Ware, JC McLaren, CE McLaren, GD Anton-Culver, H Baca, JA Bent, TC Brunner, LC Dao, MM Jorgensen, KS Kuniyoshi, J Le, HD Masatsugu, MK Meyskens, FL Morohashi, D Nguyen, HP Panagon, SN Phung, C Raymundo, V Ton, T Walker, AP Wenzel, LB Ziogas, A Adams, PC Bloch, E Chakrabarti, S Fleischhauer, A Harrison, H Jia, K Larson, S Lin, E Lopez, M Nguyen, L Pepper, C Power, T Speechley, M Sun, D Woelfle, D Jordan, J Hogan, B Moses, G Harris, EL Aickin, M Baker, E Erwin, M Holup, J Lloyd, C Press, N Press, RD Reiss, J Ritenbaugh, C Uchida, A Vogt, T Yim, D Gordeuk, VR Dawkins, FW Fadojutimi-Akinsiku, M Castro, O White-Coleman, D Gerald, M Harrison, BW Lewis-Jack, O Murray, RF McDonald-Pinkett, S Romagoza, J Williams, R Eckfeldt, JH Leiendecker-Foster, C McGlennen, RC Rynders, G Tsai, MY Reboussin, DM Snively, BM Anderson, R Bostic, E Craven, BL Ellis, S Furberg, C Griffin, J Hall, M Harris, D Henkin, L Jackson, S Jewett, T King, MD Lohman, K Lovato, L Michaleckyj, J Palla, S Parks, T Passmore, L Phatak, PD Rich, S Ruggiero, A Vitolins, M Wolgast, G Zaccaro, D Sholinsky, P Bookman, E Chang, H Fabsitz, R Jaquish, C Manolio, T O'Neill, L Thomson, E CA HEIRS Study Res Investigators TI Hemochromatosis and iron-overload screening in a racially diverse population SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; AFRICAN-AMERICANS; HFE MUTATIONS; PREVALENCE; GENE; HEPATITIS; FIBROSIS; DISEASE; ORIGIN; COMMON AB BACKGROUND: Iron overload and hemochromatosis are common, treatable conditions. HFE genotypes, levels of serum ferritin, transferrin saturation values, and self-reported medical history were studied in a multiethnic primary care population. METHODS: Participants were recruited from primary care practices and blood-drawing laboratories. Blood samples were tested for transferrin saturation, serum ferritin, and C282Y and H63D mutations of the HFE gene. Before genetic screening, participants were asked whether they had a history of medical conditions related to iron overload. RESULTS: Of the 99,711 participants, 299 were homozygous for the C282Y mutation. The estimated prevalence of C282Y homozygotes was higher in non-Hispanic whites (0.44 percent) than in Native Americans (0.11 percent), Hispanics (0.027 percent), blacks (0.014 percent), Pacific Islanders (0.012 percent), or Asians (0.000039 percent). Among participants who were homozygous for the C282Y mutation but in whom iron overload had not been diagnosed (227 participants), serum ferritin levels were greater than 300 microg per liter in 78 of 89 men (88 percent) and greater than 200 microg per liter in 79 of 138 women (57 percent). Pacific Islanders and Asians had the highest geometric mean levels of serum ferritin and mean transferrin saturation despite having the lowest prevalence of C282Y homozygotes. There were 364 participants in whom iron overload had not been diagnosed (29 C282Y homozygotes) who had a serum ferritin level greater than 1000 microg per liter. Among men, C282Y homozygotes and compound heterozygotes were more likely to report a history of liver disease than were participants without HFE mutations. CONCLUSIONS: The C282Y mutation is most common in whites, and most C282Y homozygotes have elevations in serum ferritin levels and transferrin saturation. The C282Y mutation does not account for high mean serum ferritin levels and transferrin saturation values in nonwhites. C1 London Hlth Sci Ctr, Dept Med, London, ON N6A 5A5, Canada. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Calif Irvine, Dept Med, Div Hematol & Oncol, Irvine, CA 92717 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA. Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA. Howard Univ, Dept Med, Washington, DC 20059 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. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Univ Western Ontario, Dept Epidemiol & Biostat, London, ON, Canada. Kaiser Permanente Ctr Hlth Res, Honolulu, HI USA. NHGRI, Bethesda, MD 20892 USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. RP Adams, PC (reprint author), London Hlth Sci Ctr, Dept Med, 339 Windermere Rd, London, ON N6A 5A5, Canada. EM padams@uwo.ca RI Ellis, Shellie/I-4811-2015 OI Ellis, Shellie/0000-0002-3599-0804 FU NCRR NIH HHS [M01-RR10284, M01-RR00032, M01-RR00827]; NHLBI NIH HHS [N01-HC-05185, N01-HC-05186, N01-HC-05188, N01-HC-05189, N01-HC-05190, N01-HC-05191, N01-HC-05192, UH1-HL03679-05] NR 34 TC 379 Z9 388 U1 1 U2 18 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 28 PY 2005 VL 352 IS 17 BP 1769 EP 1778 DI 10.1056/NEJMoa041534 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 920KY UT WOS:000228689000007 PM 15858186 ER PT J AU Sugarman, J Getz, K Speckman, JL Byrne, MM Gerson, J Emanuel, EJ AF Sugarman, J Getz, K Speckman, JL Byrne, MM Gerson, J Emanuel, EJ CA Consortium Evaluate Clin Res Ethic TI he cost of institutional review boards in academic medical centers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. Tufts Univ, Boston, MA 02111 USA. Boston Univ, Boston, MA 02118 USA. Univ Miami, Miami, FL 33136 USA. NIH, Bethesda, MD 20892 USA. RP Sugarman, J (reprint author), Johns Hopkins Univ, Baltimore, MD 21205 USA. NR 5 TC 39 Z9 39 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 28 PY 2005 VL 352 IS 17 BP 1825 EP 1827 DI 10.1056/NEJM200504283521723 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 920KY UT WOS:000228689000033 PM 15858200 ER PT J AU Wang, TJ Parise, H Sullivan, LM Levy, D Wolf, PA AF Wang, TJ Parise, H Sullivan, LM Levy, D Wolf, PA TI Obesity and the risk of new-onset atrial fibrillation - In reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID C-REACTIVE PROTEIN; ELEVATION C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Framingham Heart Study, Sch Med, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. EM emelia@bu.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 27 PY 2005 VL 293 IS 16 BP 1975 EP 1975 DI 10.1001/jama.293.16.1975-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 919XS UT WOS:000228651500013 ER PT J AU Lindor, NM Rabe, K Petersen, GM Haile, R Casey, G Baron, J Gallinger, S Bapat, B Aronson, M Hopper, J Jass, J LeMarchand, L Grove, J Potter, J Newcomb, P Terdiman, JP Conrad, P Moslein, G Goldberg, R Ziogas, A Anton-Culver, H de Andrade, M Siegmund, K Thibodeau, SN Boardman, LA Seminara, D AF Lindor, NM Rabe, K Petersen, GM Haile, R Casey, G Baron, J Gallinger, S Bapat, B Aronson, M Hopper, J Jass, J LeMarchand, L Grove, J Potter, J Newcomb, P Terdiman, JP Conrad, P Moslein, G Goldberg, R Ziogas, A Anton-Culver, H de Andrade, M Siegmund, K Thibodeau, SN Boardman, LA Seminara, D TI Lower cancer incidence in Amsterdam-I criteria families without mismatch repair deficiency - Familial colorectal cancer type X SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MICROSATELLITE INSTABILITY; MUTATION CARRIERS; KINDREDS; GENES AB Context Approximately 60% of families that meet the Amsterdam-I criteria (AC-I) for hereditary nonpolyposis colorectal cancer (HNPCC) have a hereditary abnormality in a DNA mismatch repair (MMR) gene. Cancer incidence in AC-I families with MMR gene mutations is reported to be very high, but cancer incidence for individuals in AC-I families with no evidence of an MMR defect is unknown. Objective To determine if cancer risks in AC-I families with no apparent deficiency in DNA MMR are different from cancer risks in AC-I families with DNA MMR abnormalities. Design, Setting, and Participants Identification (1997-2001) of 161 AC-I pedigrees from multiple population- and clinic-based sources,in North America and Germany, with families grouped into those with (group A) or without (group B) MMR deficiency by tumor testing. A total of 3422 relatives were included in the analyses. Main Outcome Measures Cancer incidence in groups A and B (excluding the 3 affected members used to define each pedigree as AC-I) and computed age- and sex-adjusted standardized incidence ratios (SIRs) using Surveillance, Epidemiology, and End Results data. Results Group A families from both population- and clinic-based series showed increased incidence of the HNPCC-related cancers. Group B families showed increased incidence only for colorectal cancer (SIR, 2.3; 95% confidence interval,. 1.7-3.0) and to a lesser extent than group A (SIR, 6.1; 95% confidence interval, 5.2-7.2) (P<.001). Conclusions Families who fulfill AC-I criteria but who have no evidence of a DNA MMR defect do not share the same cancer incidence as families with HNPCC-Lynch syndrome (ie, hereditary MMR deficiency). Relatives in such families have a lower incidence of colorectal cancer than those in families with HNPCC-Lynch syndrome, and incidence may not be increased for other cancers. These families should not be described or counseled as having HNPCC-Lynch syndrome. To facilitate distinguishing these entities, the designation of "familial colorectal cancer type V is suggested to describe this type of familial aggregation of colorectal cancer. C1 Mayo Clin & Mayo Fdn, Dept Med Genet, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Gastroenterol, Rochester, MN 55905 USA. Univ So Calif, Los Angeles, CA USA. Cleveland Clin, Cleveland, OH 44106 USA. Dartmouth Coll Sch Med, Hanover, NH USA. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Univ Melbourne, Melbourne, Vic, Australia. McGill Univ, Montreal, PQ, Canada. Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. Univ San Francisco, Dept Canc Biol, San Francisco, CA 94117 USA. Univ Dusseldorf, Dept Surg, D-4000 Dusseldorf, Germany. Univ N Carolina, Chapel Hill, NC USA. Univ Calif Irvine, Irvine, CA USA. NCI, Div Canc Control & Populat Sci, Clin & Genet Epidemiol Res Branch, NIH, Bethesda, MD 20892 USA. RP Lindor, NM (reprint author), Mayo Clin & Mayo Fdn, Dept Med Genet, 200 1st St SW, Rochester, MN 55905 USA. EM nlindor@mayo.edu RI Gallinger, Steven/E-4575-2013; Bapat, Bharati/B-5839-2014; OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [UO1 CA074783, CA-95-011, U01 CA074783, U01 CA074794, U01 CA074799, U01 CA074800, U01 CA074806, U01 CA078296, U01 CA097735, U24 CA074800, U24 CA074800-13, UO1 CA074794, UO1 CA074799, UO1 CA074800, UO1 CA074806, UO1 CA078296, UO1 CA097735] NR 18 TC 310 Z9 320 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 27 PY 2005 VL 293 IS 16 BP 1979 EP 1985 DI 10.1001/jama.293.16.1979 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 919XS UT WOS:000228651500023 PM 15855431 ER PT J AU Toth, A Boczan, J Kedei, N Lizanecz, E Bagi, Z Papp, Z Edes, I Csiba, L Blumberg, PM AF Toth, A Boczan, J Kedei, N Lizanecz, E Bagi, Z Papp, Z Edes, I Csiba, L Blumberg, PM TI Expression and distribution of vanilloid receptor 1 (TRPV1) in the adult rat brain SO MOLECULAR BRAIN RESEARCH LA English DT Article DE vanilloid receptor 1(VR1 or TRPV1); immunohistochemistry; astrocyte; synapses; brain; central nervous system ID SPINOTHALAMIC TRACT NEURONS; INTRADERMAL INJECTION; DORSAL-HORN; GASTROINTESTINAL-TRACT; CAPSAICIN RECEPTORS; TRIGEMINAL GANGLION; VR1; ANANDAMIDE; PHOSPHORYLATION; IMMUNOREACTIVITY AB The vanilloid receptor (TRPV1 or VR1) is a molecular integrator of various painful stimuli, including capsaicin, acid, and high temperature. It can also be activated by endogenous ligands, like the cannabinoid 1 receptor (CBI) agonist anandamide. TRPV1 is well characterized at the terminals of sensory nerves involved in the pain pathway. There is also evidence that TRPV1 is expressed in the brain but little is known about its function. Here, using commercially available specific antibodies to investigate the localization of TRPV1 in the brain of the rat, we report that TRPV1 was expressed in hippocampus, cortex, cerebellum, olfactory bulb, mesencephalon and hindbrain. Immunohistochemical analyses showed high expression in the cell bodies and dendrites of neurons in the hippocampus and in the cortex. To address the question of subcellular localization, immunoelectronmicroscopy was used. TRPV1-like staining was detected in the synapses (mostly, but not exclusively in post-synaptic dendritic spines), on the end feet of astrocytes and in pericytes. In summary, TRPV1 expression shows wide distribution in the brain of the rat, being found in astrocytes and pericytes as well as in neurons. Its localization is consistent with multiple functions within the central nervous system, including the regulation of brain vasculature. Published by Elsevier B.V. C1 Univ Debrecen, Inst Cardiol, Div Clin Physiol, H-4004 Debrecen, Hungary. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Mol Mech Tumor Promot Sect, NIH, Bethesda, MD 20892 USA. Univ Debrecen, Dept Neurol, H-4012 Debrecen, Hungary. RP Toth, A (reprint author), Univ Debrecen, Inst Cardiol, Div Clin Physiol, Moricz Zs Krt 22,POB 1, H-4004 Debrecen, Hungary. EM atitoth@jaguar.unideb.hu RI Edes, Istvan/B-8795-2011; Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 NR 29 TC 115 Z9 124 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 27 PY 2005 VL 135 IS 1-2 BP 162 EP 168 DI 10.1016/j.molbrainres.2004.12.003 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 927PN UT WOS:000229206100017 PM 15857679 ER PT J AU Smith, A Bourdeau, I Wang, J Bondy, CA AF Smith, A Bourdeau, I Wang, J Bondy, CA TI Expression of Catenin family members CTNNA1, CTNNA2, CTNNB1 and JUP in the primate prefrontal cortex and hippocampus SO MOLECULAR BRAIN RESEARCH LA English DT Article DE prefrontal cortex; hippocampus; pyramidal neuron; rhesus monkey ID ALPHA-N-CATENIN; WNT-SIGNALING PATHWAY; BETA-CATENIN; E-CADHERIN; DIFFERENTIAL EXPRESSION; ALZHEIMERS-DISEASE; MOLECULAR-CLONING; TUMOR-DEVELOPMENT; NERVOUS-SYSTEM; BRAIN AB Members of the catenin family of proteins are thought to play a major role in the folding and lamination of the cerebral cortex. We have used in situ hybridization to determine the cellular expression patterns of four members of this family, Alpha-E-, Alpha-N-, Beta-, and Gamma-catenins (CTNNA1, CTNNA2, CTNNB1, and JUP respectively) in the adult primate dorsolateral prefrontal cortex (DLPFC) and hippocampus. CTNNA2, CTNNB1, and JUP mRNAs were detected in all layers of the DLPFC and in all neuronal subregions of the hippocampal formation, however CTNNA1 mRNA, coding for an 'epithelial' specific catenin, was not detected in any region of the cortex or hippocampus. CTNNA2, a 'neuronal-specific' catenin, and CTNNB1 mRNAs were abundant in both DLPFC and hippocampus, with a distinct neuronal localization. CTNNA2 mRNA was concentrated in both granular/stellate cells and large pyramidal cell bodies, while CTNNB1 expression was more strongly associated with granular cell bodies throughout the DLPFC, with expression in pyramidal cells confined mainly to cortical Layers III and VI. CTNNA2 and CTNNB1 mRNAs were also abundant in the granule cells of the dentate gyrus and pyramidal cells of Ammon's horn, apparently co-expressed in the same neurons. JUP mRNA was rather diffusely localized in the DLPFC without the distinct laminar patterns seen for CTNNA2 and CTNNB1 but was distinctly localized in the granule cells of the dentate gyrus and pyramidal cells of Ammon's horn. These studies demonstrate a distinct neuronal pattern of gene expression for catenin family members in primate brain structures characterized by high degrees of folding and strong lamination. The high level expression of these transcripts supports the notion of a major role for catenins even in the adult brain. Such an understanding is also important in view of the multiple interactions that catenins have with many other proteins in the adult and ageing brain. This may also have implications for understanding the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, as well as emerging neuronal stem cell therapies. Published by Elsevier B.V. C1 Natl Inst Child Hlth, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), Natl Inst Child Hlth, Dev Endocrinol Branch, NIH, Bldg 10-10N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov NR 39 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD APR 27 PY 2005 VL 135 IS 1-2 BP 225 EP 231 DI 10.1016/j.molbrainres.2004.12.025 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 927PN UT WOS:000229206100023 ER PT J AU Saul, A AF Saul, A TI Models of Phase 1 vaccine trials: optimization of trial design to minimize risks of multiple serious adverse events SO VACCINE LA English DT Article DE trial design; serious adverse event; dose; computer simulation; mathematical model ID PLASMODIUM-FALCIPARUM MALARIA; I TRIAL AB A mathematical model of Phase 1 vaccine trial design was used to investigate strategies for minimizing the number of serious adverse events (SAES) that could be encountered in the first Phase 1 trials of new vaccine formulations. For a relatively standard dose escalation trial with three dose groups each with 10 subjects, an optimal balanced between risk of more than one serious adverse event and trial design is achieved by splitting each dose group into two subgroups of three and seven. Based on the modeling, for a two vaccination, dose-escalating Phase 1 trial, a design where all subjects receive the first vaccination before any subject receives a second vaccination generally carries a lower risk of multiple serious adverse events than other designs. (c) 2004 Elsevier Ltd. All rights reserved. C1 NIAID, NIH, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. RP Saul, A (reprint author), NIAID, NIH, Malaria Vaccine Dev Branch, 5460 Fishers Lane,Room 1113,Twinbrook 1, Rockville, MD 20852 USA. EM asaul@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 8 TC 4 Z9 4 U1 0 U2 0 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 APR 27 PY 2005 VL 23 IS 23 BP 3068 EP 3075 DI 10.1016/j.vaccine.2004.10.048 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 920KK UT WOS:000228687600017 PM 15811654 ER PT J AU Saul, A Lawrence, G Allworth, A Elliott, S Anderson, K Rzepczyk, C Martin, LB Taylor, D Eisen, DP Irving, DO Pye, D Crewther, PE Hodder, AN Murphy, VJ Anders, RF AF Saul, A Lawrence, G Allworth, A Elliott, S Anderson, K Rzepczyk, C Martin, LB Taylor, D Eisen, DP Irving, DO Pye, D Crewther, PE Hodder, AN Murphy, VJ Anders, RF TI A human phase 1 vaccine clinical trial of the Plasmodium falciparum malaria vaccine candidate apical membrane antigen 1 in Montanide ISA720 adjuvant SO VACCINE LA English DT Article DE AMA1; P. falciparum; phase 1 vaccine trial ID APICAL MEMBRANE ANTIGEN-1; BLOOD-STAGE MALARIA; PAPUA-NEW-GUINEA; AMA-1; IMMUNOGENICITY; LOCALIZATION; IMMUNIZATION; EXPRESSION; DIVERSITY; INFECTION AB A dose escalating, placebo-controlled phase 1 trial was conducted to test the safety and immunogenicity of a vaccine containing recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) formulated in Montanide ISA720. Three groups of volunteers were vaccinated intramuscularly with 5 mu g, 20 mu g or 80 mu g of AMA1, respectively, in 0.5 mL of formulation at 0, 3 and 6 months. Anti-AMA1 antibody levels and T cell stimulation indices were measured before and after each vaccination. No vaccine-related serious adverse events were recorded. Most subjects generated a mild to moderate, transient local reaction after the first vaccination. Three subjects developed a local reaction approximately 10 days following vaccination. Six of the 29 subjects seroconverted. Only one of these developed a high antibody titre. However, the interpretation of this trial was compromised by a loss of potency of the formulated vaccine during the course of the study. (c) 2005 Published by Elsevier Ltd. C1 Cooperat Res Ctr Vaccine Technol, Brisbane, Qld, Australia. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. Vaccine Solut Pty Ltd, Brisbane, Qld 4029, Australia. Biotech Australia Pty Ltd, Sydney, NSW, Australia. CSL Ltd, Melbourne, Vic, Australia. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. La Trobe Univ, Melbourne, Vic, Australia. RP Saul, A (reprint author), NIH, Malaria Vaccine Dev Unit, 5640 Fishers Lane,Twinbrook 1,Room 1113, Rockville, MD 20852 USA. EM asaul@niaid.nih.gov RI Allworth, Anthony/G-3143-2011; Saul, Allan/I-6968-2013; Martin, Laura/N-1789-2013 OI Saul, Allan/0000-0003-0665-4091; Martin, Laura/0000-0002-4431-4381 NR 28 TC 82 Z9 84 U1 1 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 APR 27 PY 2005 VL 23 IS 23 BP 3076 EP 3083 DI 10.1016/j.vaccine.2004.09.040 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 920KK UT WOS:000228687600018 PM 15811655 ER PT J AU Sciarretta, KL Gordon, DJ Petkova, AT Tycko, R Meredith, SC AF Sciarretta, KL Gordon, DJ Petkova, AT Tycko, R Meredith, SC TI A beta 40-Lactam(D23/K28) models a conformation highly favorable for nucleation of amyloid SO BIOCHEMISTRY LA English DT Article ID SOLID-STATE NMR; PARALLEL BETA-SHEET; ALZHEIMERS-DISEASE; SECONDARY STRUCTURE; MAGNETIC-RESONANCE; STRUCTURAL MODEL; FIBRIL FORMATION; CHEMICAL-SHIFTS; THIOFLAVINE-T; AMINO-ACIDS AB Recent solid-state NMR data (1) demonstrate that A beta(1-40) adopts a conformation in amyloid fibrils with two in-register, parallel P-sheets, connected by a bend structure encompassing residues D(23)VGSNKG(29), with a close contact between the side chains of Asp23 and Lys28. We hypothesized that forming this bend structure might be rate-limiting in fibril formation, as indicated by the lag period typically observed in the kinetics of A beta(1-40) fibrillogenesis. We synthesized A beta(1-40)-Lactam(D23/K28), a congener A beta(1-40) peptide that contains a lactam bridge between the side chains of Asp23 and Lys28. A beta(1-40)-Lactam(D23/K28) forms fibrils similar to those formed by A beta(1-40). The kinetics of fibrillogenesis, however, occur without the typical lag period, and at a rate; approximate to 1000-fold greater than is seen with A beta(1-40) fibrillogenesis. The strong tendency toward self-association is also shown by size exclusion chromatography in which A beta(1-40)-Lactam(D23/K28) forms oligomers even at concentrations of approximate to 1-5 mu M. Under the same conditions, A beta(1-40) shows no detectable oligomers by size exclusion chromatography. Our data suggest that A beta(1-40)-Lactam(D23/K28) could bypass an unfavorable folding step in fibrillogenesis, because the lactam linkage "preforms" a bendlike structure in the peptide. Consistent with this view A beta(1-40) growth is efficiently nucleated by A beta(1-40)-Lactam(D23/K28) fibril seeds. C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Chicago, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem, Chicago, IL 60637 USA. Univ Chicago, Dept Mol Biol, Chicago, IL 60637 USA. NIDDK, NIH, Phys Chem Lab, Bethesda, MD 20892 USA. RP Meredith, SC (reprint author), Univ Chicago, Dept Pathol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM scmeredi@uchicago.edu FU NIGMS NIH HHS [5 T32 GM07281, T32 GM07183]; NINDS NIH HHS [R01 NS042852] NR 60 TC 159 Z9 161 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 26 PY 2005 VL 44 IS 16 BP 6003 EP 6014 DI 10.1016/bi0474867 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 920HB UT WOS:000228678900006 PM 15835889 ER PT J AU Jung, HJ Lee, JY Kim, SH Eu, YJ Shin, SY Milescu, M Swartz, KJ Kim, JI AF Jung, HJ Lee, JY Kim, SH Eu, YJ Shin, SY Milescu, M Swartz, KJ Kim, JI TI Solution structure and lipid membrane partitioning of VSTx1, an inhibitor of the KvAP potassium channel SO BIOCHEMISTRY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; DEPENDENT K+ CHANNEL; 3-DIMENSIONAL SOLUTION STRUCTURE; RELAXATION MATRIX ANALYSIS; VOLTAGE-SENSING DOMAINS; GATING MODIFIER TOXINS; DISTANCE GEOMETRY; PROTEIN STRUCTURES; CHARYBDOTOXIN BLOCK; NMR-SPECTROSCOPY AB VSTx1 is a voltage sensor toxin from the spider Grammostola spatulata that inhibits KvAP, an archeabacterial voltage-activated K+ channel whose X-ray structure has been reported. Although the receptor for VSTx1 and the mechanism of inhibition are unknown, the sequence of the toxin is related to hanatoxin (HaTx) and SGTx, two toxins that inhibit eukaryotic voltage-activated K+ channels by binding to voltage sensors. VSTx1 has been recently shown to interact equally well with lipid membranes that contain zwitterionic or acidic phospholipids, and it has been proposed that the toxin receptor is located within a region of the channel that is submerged in the membrane. As a first step toward understanding the inhibitory mechanism of VSTx1, we determined the three-dimensional solution structure of the toxin using NMR. Although the structure of VSTx1 is similar to HaTx and SGTx in terms of molecular fold and amphipathic character, the detailed positions of hydrophobic and surrounding charged residues in VSTx1 are very different than what is seen in the other toxins. The amphipathic character of VSTx1, notably the close apposition of basic and hydrophobic residues on one face of the toxin, raises the possibility that the toxin interacts with interfacial regions of the membrane. We reinvestigated the partitioning of VSTx1 into lipid membranes and find that VSTx1 partitioning requires negatively charged phospholipids. Intrinsic tryptophan fluorescence and acrylamide quenching experiments suggest that tryptophan residues on the hydrophobic surface of VSTx1 have a diminished exposure to water when the toxin interacts with membranes. The present results suggest that if membrane partitioning is involved in the mechanism by which VSTx1 inhibits voltage-activated K+ channels, then binding of the toxin to the channel would likely occur at the interface between the polar headgroups and the hydrophobic phase of the membrane. C1 Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. Chosun Univ, Grad Sch, Dept Biomat, Kwangju 501759, South Korea. Chosun Univ, Res Ctr Prot Mat, Kwangju 501759, South Korea. Natl Inst Neurol Disorders & Stroke, Mol Physiol & Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Kim, JI (reprint author), Gwangju Inst Sci & Technol, Dept Life Sci, Kwangju 500712, South Korea. EM jikim@gist.ac.kr FU Intramural NIH HHS [ZIA NS002945-13] NR 56 TC 67 Z9 69 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 26 PY 2005 VL 44 IS 16 BP 6015 EP 6023 DI 10.1021/bi0477034 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 920HB UT WOS:000228678900007 PM 15835890 ER PT J AU Dalley, JW Laane, K Theobald, DEH Armstrong, HC Corlett, PR Chudasama, Y Robbins, TW AF Dalley, JW Laane, K Theobald, DEH Armstrong, HC Corlett, PR Chudasama, Y Robbins, TW TI Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE consolidation; dopamine; learning; autoshaping; glutamate ID ANTERIOR CINGULATE CORTEX; D-AMPHETAMINE; WATER MAZE; DIFFERENTIAL INVOLVEMENT; COINCIDENT ACTIVATION; BASOLATERAL AMYGDALA; SYNAPTIC PLASTICITY; DOPAMINE AGONISTS; APPROACH BEHAVIOR; FRONTAL-CORTEX AB Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. in addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as D-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Addenbrookes Hosp, Dept Psychiat, Brain Mapping Unit, Cambridge CB2 2QQ, England. NIMH, NIH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Dalley, JW (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM jwd20@cam.ac.uk NR 39 TC 141 Z9 140 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 26 PY 2005 VL 102 IS 17 BP 6189 EP 6194 DI 10.1073/pnas.0502080102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 921BI UT WOS:000228738800054 PM 15833811 ER PT J AU Rahman, M Pressel, S Davis, BR Nwachuku, C Wright, JT Whelton, PK Barzilay, J Batuman, V Eckfeldt, JH Farber, M Henriquez, M Kopyt, N Louis, GT Saklayen, M Stanford, C Walworth, C Ward, H Wiegmann, T AF Rahman, M Pressel, S Davis, BR Nwachuku, C Wright, JT Whelton, PK Barzilay, J Batuman, V Eckfeldt, JH Farber, M Henriquez, M Kopyt, N Louis, GT Saklayen, M Stanford, C Walworth, C Ward, H Wiegmann, T CA ALLHAT Grp TI Renal outcomes in high-risk hypertensive patients treated with an angiotensin-converting enzyme inhibitor or a calcium channel blocker vs a diuretic - A report from the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 02-06, 2003 CL DALLAS, TX SP Natl Kidney Fdn ID GLOMERULAR-FILTRATION-RATE; BLOOD-PRESSURE CONTROL; DIABETIC-NEPHROPATHY; KIDNEY-FUNCTION; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR OUTCOMES; ALBUMIN EXCRETION; RANDOMIZED-TRIAL; II BLOCKADE; DISEASE AB Background: This study was performed to determine whether, in high-risk hypertensive patients with a reduced glomerular filtration rate (GFR), treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor lowers the incidence of renal disease outcomes compared with treatment with a diuretic. Methods: We conducted post hoc analyses of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertensive participants 55 years or older with at least 1 other coronary heart disease risk factor were randomized to receive chlorthalidone, amlodipine, or lisinopril for a mean of 4.9 years. Renal outcomes were incidence of end-stage renal disease (ESRD) and/or a decrement in GFR of 50% or more from baseline. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into normal or increased (>= 90 mL/min per 1.73 m(2), n=8126), mild reduction (60-89 mL/min per 1.73 m(2), n = 18 109), or moderate-severe reduction (< 60 mL/min per 1.73 m(2), n=5662) in GFR. Each stratum was analyzed for effects of the treatments on outcomes. Results: In 448 participants, ESRD developed. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking amlodipine in the mild (relative risk [RR], 1.47; 95% confidence interval [CI], 0.97-2.23) or moderate-severe (RR,0.92; 95% CI, 0.68-1.24) reduction in GFZ groups. Compared with patients taking chlorthalidone, no significant differences occurred in the incidence of ESRD in patients taking lisinopril in the mild (RR, 1.34; 95% CI, 0.87-2.06) or moderate-severe (RR,0.98-195% CI, 0.73-1.31) reduction in GFRgroups. In patients with mild and moderate-severe reduction in GFR, the incidence of ESRD or 50% or greater decrement in GFR was not significantly different in patients treated with chlorthalidone compared with those treated with amlodipine (odds ratios, 0.96 [P=.74] and 0.85 [P=.231, respectively) and lisinopril (odds ratios, 1.13 [P=.31] and 1.00 [P=.98], respectively). No difference in treatment effects occurred for either end point for patients taking amlodipine or lisinopril compared with those taking chlorthalidone across the 3 GFR subgroups, either for the total group or for participants with diabetes at baseline. At 4 years of follow-up, estimated GFR was 3 to 6 mL/min per 1.73 m(2) higher in patients assigned to receive amlodipine compared with chlorthalidone, depending on baseline GFR stratum. Conclusions: In hypertensive patients with reduced GFR, neither amlodipine nor lisinopril was superior to chlorthalidone in reducing the rate of development of ESRD or a 50% or greater decrement in GFR. Participants assigned to receive amlodipine had a higher GFR than those assigned to receive chlorthalidone, but rates of development of ESRD were not different between the groups. C1 Univ Texas, Sch Publ Hlth, Hlth Sci Ctr, Houston, TX 77030 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland Vet Affairs Med Ctr, Div Nephrol & Hypertens, Cleveland, OH 44106 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Gen Clin Res Ctr, Cleveland, OH 44106 USA. Tulane Univ, Ctr Hlth Sci, New Orleans, LA 70118 USA. Kaiser Permanente, Tucker, GA USA. Vet Affairs Med Ctr, New Orleans, LA 70146 USA. Tulane Univ, Sch Med, New Orleans, LA 70118 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Pitman Internal Med Associates, Pitman, NJ USA. Bronx Nephrol Hypertens PC, Bronx, NY USA. Lehigh Valley Hosp Ctr, Div Nephrol, Allentown, PA 18102 USA. Vet Affairs Med Ctr, Dayton, OH USA. Univ Missouri, Sch Med, Kansas City, MO 64110 USA. Androscoggin Clin Associates, Lewiston, ME USA. King Drew Med Ctr, Los Angeles, CA 90059 USA. Dept Vet Affairs Med Ctr, Kansas City, MO USA. RP Davis, BR (reprint author), Univ Texas, Sch Publ Hlth, Hlth Sci Ctr, 1200 Herman Pressler St,Suite E-801, Houston, TX 77030 USA. EM barry.r.davis@uth.tmc.edu NR 42 TC 184 Z9 192 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 25 PY 2005 VL 165 IS 8 BP 936 EP 946 DI 10.1001/archinte.165.8.936 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 919DT UT WOS:000228599200017 PM 15851647 ER PT J AU Smith, WW Norton, DD Gorospe, M Jiang, HB Nemoto, S Holbrook, NJ Finkel, T Kusiak, JW AF Smith, WW Norton, DD Gorospe, M Jiang, HB Nemoto, S Holbrook, NJ Finkel, T Kusiak, JW TI Phosphorylation of p66Shc and forkhead proteins mediates A beta toxicity SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FKHR-L1; STRESS-INDUCED APOPTOSIS; ALZHEIMERS-DISEASE; CELL-DEATH; C-JUN; SIGNALING PATHWAY; OXIDATIVE STRESS; KINASE-B; CAENORHABDITIS-ELEGANS; HYDROGEN-PEROXIDE AB Excessive accumulation of amyloid beta-peptide (A beta) plays an early and critical role in synapse and neuronal loss in Alzheimer's Disease ( AD). Increased oxidative stress is one of the mechanisms whereby A beta induces neuronal death. Given the lessened susceptibility to oxidative stress exhibited by mice lacking p66Shc, we investigated the role of p66Shc in A beta toxicity. Treatment of cells and primary neuronal cultures with A beta caused apoptotic death and induced p66Shc phosphorylation at Ser36. Ectopic expression of a dominant-negative SEK1 mutant or chemical JNK inhibition reduced A beta-induced JNK activation and p66Shc phosphorylation ( Ser36), suggesting that JNK phosphorylates p66Shc. A beta induced the phosphorylation and hence inactivation of forkhead transcription factors in a p66Shc-dependent manner. Ectopic expression of p66ShcS36A or antioxidant treatment protected cells against A beta-induced death and reduced forkhead phosphorylation, suggesting that p66Shc phosphorylation critically influences the redox regulation of forkhead proteins and underlies A beta toxicity. These findings underscore the potential usefulness of JNK, p66Shc, and forkhead proteins as therapeutic targets for AD. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21205 USA. NIA, Mol Neurobiol Unit, Cellular & Mol Biol Lab, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol & Cellular Neurobiol Program, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. RP Smith, WW (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat, Div Neurobiol, Baltimore, MD 21205 USA. EM wsmith60@jhmi.edu NR 69 TC 68 Z9 72 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR 25 PY 2005 VL 169 IS 2 BP 331 EP 339 DI 10.1083/jcb.200410041 PG 9 WC Cell Biology SC Cell Biology GA 919YJ UT WOS:000228653300014 PM 15837797 ER PT J AU Moaddel, R Yamaguchi, R Ho, PC Patel, S Hsu, CP Subrahmanyam, V Wainer, IW AF Moaddel, R Yamaguchi, R Ho, PC Patel, S Hsu, CP Subrahmanyam, V Wainer, IW TI Development and characterization of an immobilized human organic cation transporter based liquid chromatographic stationary phase SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE hOCT1; drug transporters; affinity chromatography; MDCK cells ID P-GLYCOPROTEIN; SUBSTRATE-BINDING; AFFINITIES; HOCT1 AB Membranes from a stably transfected cell line that expresses the human organic cation 1 transporter (hOCT1) have been immobilized on the immobilized artificial membrane (IAM) liquid chromatographic stationary phase to form the hOCT1 (+)-IAM stationary phase. Membranes from the parent cell line that does not express the hOCT1 were also immobilized to create the hOCT1 (-)-IAM stationary phase. Columns were created using both stationary phases, and frontal displacement chromatography experiments were conducted using [H-3]-methyl phenyl pyridinium ([H-1]-MPP+) as the marker ligand and MPP+, verapamil, quinidine, quinine, nicotine, dopamine and vinblastin as the displacers. The K-d values calculated from the chromatographic studies correlated with previously reported K-i values (r(2) = 0.9987; p < 0.001). The data indicate that the hOCT1(+)-IAM column can be used for the on-line determination of binding affinities to the hOCT1 and that these affinities are comparable to those obtained using cellular uptake studies. In addition, the chromatographic method was able to identify a previously undetected high affinity binding site for MPP+ and to determine that hOCT1 bound (R)-verapamil to a greater extent than (S)-verapamil. Published by Elsevier B.V. C1 NIA, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Natl Univ Singapore, Dept Pharm, Singapore 117543, Singapore. Johnson & Johnson Pharmaceut Res & Dev, Preclin Pharmacokinet, Raritan, NJ 08869 USA. RP Moaddel, R (reprint author), NIA, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov RI Ho, Paul/O-9652-2014 OI Ho, Paul/0000-0001-9213-7116 NR 14 TC 21 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 25 PY 2005 VL 818 IS 2 BP 263 EP 268 DI 10.1016/j.jchromb.2005.01.015 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 906GQ UT WOS:000227629200020 PM 15734168 ER PT J AU Horton, JK Stefanick, DF Naron, JM Kedar, PS Wilson, SH AF Horton, JK Stefanick, DF Naron, JM Kedar, PS Wilson, SH TI Poly(ADP-ribose) polymerase activity prevents signaling pathways for cell cycle arrest after DNA methylating agent exposure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; S-PHASE; MAMMALIAN-CELLS; INDUCED CYTOTOXICITY; DAMAGE CHECKPOINT; ATR; REPLICATION; BETA; CHK1; ACTIVATION AB Mouse fibroblasts, deficient in DNA polymerase beta, are hypersensitive to monofunctional DNA methylating agents such as methyl methanesulfonate ( MMS). Both wild- type and, in particular, repair- deficient DNA polymerase beta null cells are highly sensitized to the cytotoxic effects of MMS by 4- amino- 1,8- naphthalimide ( 4-AN), an inhibitor of poly( ADP- ribose) polymerase ( PARP) activity. Experiments with synchronized cells suggest that exposure during S- phase of the cell cycle is required for the 4- AN effect. 4- AN elicits a similar extreme sensitization to the thymidine analog, 5- hydroxymethyl-2' -deoxyuridine, implicating the requirement for an intermediate of DNA repair. In PARP- 1- expressing fibroblasts treated with a combination of MMS and 4- AN, a complete inhibition of DNA synthesis is apparent after 4 h, and by 24 h, all cells are arrested in S- phase of the cell cycle. Continuous incubation with 4- AN is required to maintain the cell cycle arrest. Caffeine, an inhibitor of the upstream checkpoint kinases ATM ( ataxia telangiectasia-mutated) and ATR ( ATM and Rad3- related), has no effect on the early inhibition of DNA synthesis, but cells are no longer able to maintain the block after 8 h. Instead, the addition of caffeine leads to arrest of cells in G(2)/ M rather than S- phase after 24 h. Analysis of signaling pathways in cell extracts reveals an activation of Chk1 after treatment with MMS and 4- AN, which can be suppressed by caffeine. Our results suggest that inhibition of PARP activity results in sensitization to MMS through maintenance of an ATR and Chk1- dependent S- phase checkpoint. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov NR 57 TC 53 Z9 54 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 22 PY 2005 VL 280 IS 16 BP 15773 EP 15785 DI 10.1074/jbc.M413841200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800040 PM 15701627 ER PT J AU Dolman, NJ Gerasimenko, JV Gerasimenko, OV Voronina, SG Petersen, OH Tepikin, AV AF Dolman, NJ Gerasimenko, JV Gerasimenko, OV Voronina, SG Petersen, OH Tepikin, AV TI Stable Golgi-mitochondria complexes and formation of Golgi Ca2+ gradients in pancreatic acinar cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOPLASMIC-RETICULUM; INOSITOL TRISPHOSPHATE; EXOCRINE CELLS; BREFELDIN-A; CALCIUM; TRANSPORT; SIGNALS; OSCILLATIONS; APPARATUS; STORES AB We have determined the localization of the Golgi with respect to other organelles in living pancreatic acinar cells and the importance of this localization to the establishment of Ca2+ gradients over the Golgi. Using confocal microscopy and the Golgi- specific fluorescent probe 6-(( N-( 7- nitrobenz- 2- oxa- 1,3- diazol- 4- yl) amino) hexanoyl) sphingosine, we found Golgi structures localizing to the outer edge of the secretory granular region of individual acinar cells. We also assessed Golgi positioning in acinar cells located within intact pancreatic tissue using two- photon microscopy and found a similar localization. The mitochondria segregate the Golgi from lateral regions of the plasma membrane, the nucleus, and the basal part of the cytoplasm. The Golgi is therefore placed between the principal Ca2+ release sites in the apical region of the cell and the important Ca2+ sink formed by the peri- granular mitochondria. During acetylcholine-induced cytosolic Ca2+ signals in the apical region, large Ca2+ gradients form over the Golgi ( decreasing from trans- to cis- Golgi). We further describe a novel, close interaction of the peri- granular mitochondria and the Golgi apparatus. The mitochondria and the Golgi structures form very close contacts, and these contacts remain stable over time. When the cell is forced to swell, the Golgi and mitochondria remain juxtaposed up to the point of cell lysis. The strategic position of the Golgi ( closer to release sites than the bulk of the mitochondrial belt) makes this organelle receptive to local apical Ca2+ transients. In addition the Golgi is ideally placed to be preferentially supplied by ATP from adjacent mitochondria. C1 Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. RP Tepikin, AV (reprint author), Natl Inst Neurol Disorders & Stroke, Synapt Physiol Unit, NIH, Bldg 35,35 Convent Dr, Bethesda, MD 20892 USA. EM a.tepikin@liv.ac.uk RI Petersen, Ole/E-8708-2010; Gerasimenko, Julia/A-7688-2010; Gerasimenko, Oleg/A-6622-2010; OI Gerasimenko, Julia/0000-0002-2262-2543; Gerasimenko, Oleg/0000-0003-2573-8258 NR 44 TC 46 Z9 48 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 APR 22 PY 2005 VL 280 IS 16 BP 15794 EP 15799 DI 10.1074/jbc.M412694200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800042 PM 15722348 ER PT J AU Ouyang, K Wu, CH Cheng, HP AF Ouyang, K Wu, CH Cheng, HP TI Ca2+-induced Ca2+ release in sensory neurons - Low gain amplification confers intrinsic stability SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEART-MUSCLE; SARCOPLASMIC-RETICULUM; RYANODINE RECEPTORS; CALCIUM-RELEASE; LOCAL-CONTROL; CARDIAC MYOCYTES; SKELETAL-MUSCLE; CELLS; SPARKS; ADAPTATION AB Ca2+-induced Ca2+ release (CICR) is a ubiquitous mechanism by which Ca2+ release from the endoplasmic reticulum amplifies the trigger Ca2+ entry and generates propagating Ca2+ waves. To elucidate the mechanisms that control this positive feedback, we investigated the spatial and temporal kinetics and measured the gain function of CICR in small sensory neurons from mammalian dorsal root ganglions ( DRGs). We found that subsurface Ca2+ release units (CRUs) are under tight local control by Ca2+ entry, whereas medullar CRUs as a "common pool" system are recruited by inwardly propagating CICR. Active CRUs often displayed repetitive Ca2+ sparks, conferring the ability to encode a "memory" of neuronal activity well beyond the duration of an action potential. Store Ca2+ reserve was able to support all CRUs each to fire similar to 15 sparks, excluding use-dependent inactivation or store depletion as the major CICR termination mechanism. Importantly, CICR in DRG neurons operated in a low gain, linear regime ( gain = 0.54), which conferred intrinsic stability to CICR. Combined with high Ca2+ current density ( - 156 pA/pF at - 10 mV), such a low gain CICR system generated large intracellular Ca2+ transients without jeopardizing the stability. These findings provide the first demonstration that CICR operating in a low gain regime can be harnessed to provide a robust and graded amplification of Ca2+ signal in the absence of counteracting inhibitory mechanism. C1 Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. Peking Univ, Coll Life Sci, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA. RP Cheng, HP (reprint author), Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. EM chengp@grc.nia.nih.gov RI ouyang, kunfu/B-3073-2011 OI ouyang, kunfu/0000-0003-0292-375X NR 32 TC 14 Z9 15 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 APR 22 PY 2005 VL 280 IS 16 BP 15898 EP 15902 DI 10.1074/jbc.C500026200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800055 PM 15749692 ER PT J AU Liu, MZ Durfee, T Cabrera, JE Zhao, K Jin, DJ Blattner, FR AF Liu, MZ Durfee, T Cabrera, JE Zhao, K Jin, DJ Blattner, FR TI Global transcriptional programs reveal a carbon source foraging strategy by Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLUORESCENCE LIFETIME IMAGES; RATE-DEPENDENT REGULATION; LAC OPERON EXPRESSION; GROWTH-RATE; RNA-POLYMERASE; CATABOLITE REPRESSION; SALMONELLA-TYPHIMURIUM; REGULATORY MECHANISMS; SIGMA(S) SUBUNIT; TEXTURE ANALYSIS AB By exploring global gene expression of Escherichia coli growing on six different carbon sources, we discovered a striking genome transcription pattern: as carbon substrate quality declines, cells systematically increase the number of genes expressed. Gene induction occurs in a hierarchical manner and includes many factors for uptake and metabolism of better but currently unavailable carbon sources. Concomitantly, cells also increase their motility. Thus, as the growth potential of the environment decreases, cells appear to devote progressively more energy on the mere possibility of improving conditions. This adaptation is not what would be predicated by classic regulatory models alone. We also observe an inverse correlation between gene activation and rRNA synthesis suggesting that reapportioning RNA polymerase ( RNAP) contributes to the expanded genome activation. Significant differences in RNAP distribution in vivo, monitored using an RNAP-green fluorescent protein fusion, from energy-rich and energy-poor carbon source cultures support this hypothesis. Together, these findings represent the integration of both substrate-specific and global regulatory systems, and may be a bacterial approximation to metazoan risk-prone foraging behavior. C1 Univ Wisconsin, Dept Genet, Madison, WI 53706 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. NCI, Transcript Control Sect, Gene Regulat & Crhomosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA. RP Blattner, FR (reprint author), Univ Wisconsin, Dept Genet, 445 Henry Mall, Madison, WI 53706 USA. EM fred@genome.wisc.edu FU NIGMS NIH HHS [GM35682-17S1] NR 51 TC 113 Z9 117 U1 4 U2 16 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 APR 22 PY 2005 VL 280 IS 16 BP 15921 EP 15927 DI 10.1074/jbc.M414050200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800058 PM 15705577 ER PT J AU Nemoto, S Fergusson, MM Finkel, T AF Nemoto, S Fergusson, MM Finkel, T TI SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1 alpha SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LIFE-SPAN EXTENSION; CALORIE RESTRICTION; SACCHAROMYCES-CEREVISIAE; CELL-SURVIVAL; NAD(+)-DEPENDENT DEACETYLASES; MITOCHONDRIAL BIOGENESIS; PROTEIN DEACETYLASES; GAMMA COACTIVATOR-1; NAD; LONGEVITY AB In lower organisms, increased expression of the NAD-dependent deacetylase Sir2 augments lifespan. The mechanism through which this life extension is mediated remains incompletely understood. Here we have examined the cellular effects of overexpression of SIRT1, the closest mammalian ortholog of Sir2. In PC12 cells, increased expression of the NAD-dependent deacetylase SIRT1 reduces cellular oxygen consumption by similar to 25%. We further demonstrate that SIRT1 expression can alter the transcriptional activity of the mitochondrial biogenesis coactivator PGC-1 alpha. In addition, SIRT1 and PGC-1 alpha directly interact and can be co-immunoprecipitated as a molecular complex. A single amino acid mutation in the putative ADP-ribosyltransferase domain of SIRT1 inhibits the interaction of SIRT1 with PGC-1 alpha but does not effect the interaction of SIRT1 with either p53 or Foxo3a. We further show that PGC-1 alpha is acetylated in vivo. This acetylation is augmented by treatment with the SIRT1 inhibitor nicotinamide or by expression of the transcriptional coactivator p300. Finally we demonstrate that SIRT1 catalyzes PGC-1 alpha deacetylation both in vitro and in vivo. These results provide a direct link between the sirtuins, a family of proteins linked to lifespan determination and PGC-1 alpha, a coactivator that regulates cellular metabolism. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10 CRC,Rm 5-3330, Bethesda, MD 20892 USA. EM Finkelt@nih.gov NR 37 TC 500 Z9 522 U1 3 U2 30 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 APR 22 PY 2005 VL 280 IS 16 BP 16456 EP 16460 DI 10.1074/jbc.M501485200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800119 PM 15716268 ER PT J AU Sattlegger, E Hinnebusch, AG AF Sattlegger, E Hinnebusch, AG TI Polyribosome binding by GCN1 is required for full activation of eukaryotic translation initiation factor 2 alpha kinase GCN2 during amino acid starvation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; SACCHAROMYCES-CEREVISIAE; STARVED CELLS; N-TERMINUS; RNA; ASSOCIATION; RIBOSOMES; YEAST; GENE; PHOSPHORYLATION AB The protein kinase GCN2 mediates translational control of gene expression in amino acid-starved cells by phosphorylating eukaryotic translation initiation factor 2 alpha. In Saccharomyces cerevisiae, activation of GCN2 by uncharged tRNAs in starved cells requires its direct interaction with both the GCN1 center dot GCN20 regulatory complex and ribosomes. GCN1 also interacts with ribosomes in cell extracts, but it was unknown whether this activity is crucial for its ability to stimulate GCN2 function in starved cells. We describe point mutations in two conserved, noncontiguous segments of GCN1 that lead to reduced polyribosome association by GCN1 center dot GCN20 in living cells without reducing GCN1 expression or its interaction with GCN20. Mutating both segments simultaneously produced a greater reduction in polyribosome binding by GCN1 center dot GCN20 and a stronger decrease in eukaryotic translation initiation factor 2 alpha phosphorylation than did mutating in one segment alone. These findings provide strong evidence that ribosome binding by GCN1 is required for its role as a positive regulator of GCN2. A particular mutation in the GCN1 domain, related in sequence to translation elongation factor 3 (eEF3), decreased GCN2 activation much more than it reduced ribosome binding by GCN1. Hence, the eEF3-like domain appears to have an effector function in GCN2 activation. This conclusion supports the model that an eEF3-related activity of GCN1 influences occupancy of the ribosomal decoding site by uncharged tRNA in starved cells. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 6A,Rm B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 21 TC 24 Z9 26 U1 0 U2 7 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 APR 22 PY 2005 VL 280 IS 16 BP 16514 EP 16521 DI 10.1074/jbc.M414566200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917GO UT WOS:000228444800126 PM 15722345 ER PT J AU Yingling, YG Shapiro, BA AF Yingling, YG Shapiro, BA TI Dynamic behavior of the telomerase RNA hairpin structure and its relationship to dyskeratosis congenita SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE telomerase; RNA; molecular dynamics simulations; dyskeratosis congenita; pseudoknot ID GENERALIZED BORN MODELS; MOLECULAR-DYNAMICS; NUCLEIC-ACIDS; BASE-PAIRS; SIMULATIONS; CANCER; PSEUDOKNOT; TETRALOOP; BINDING; RIBONUCLEOPROTEIN AB In this paper, we present the results from a comprehensive study of nanosecond-scale implicit and explicit solvent molecular dynamics simulations of the wild-type telomerase RNA hairpin. The effects of various mutations on telomerase RNA dynamics are also investigated. Overall, we found that the human telomerase hairpin is a very flexible molecule. In particular, periodically the molecule exhibits dramatic structural fluctuations represented by the opening and closing of a non-canonical base-pair region. These structural deviations correspond to significant disruptions of the direct hydrogen bonding network in the helix, widening of the major groove of the hairpin structure, and causing several U and C nucleotides to protrude into the major groove from the helix permitting them to hydrogen bond with, for example, the P3 domain of the telomerase RNA. We suggest that these structural fluctuations expose a nucleation point for pseudoknot formation. We also found that mutations in the pentaloop and non-canonical region stabilize the hairpin. Moreover, our results show that the hairpin with dyskeratosis congenita mutations is more stable and less flexible than the wild-type hairpin due to base stacking in the pentaloop. The results from our molecular dynamics simulations are in agreement with experimental observations. In addition, they suggest a possible mechanism for pseudoknot formation based on the dynamics of the hairpin structure and also may explain the mutational aspects of dyskeratosis congenita. Published by Elsevier Ltd. C1 NCI, Ctr Canc Res, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res, Lab Expt & Computat Biol, NIH, Bldg 469,Room 150, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 NR 46 TC 23 Z9 25 U1 1 U2 6 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 APR 22 PY 2005 VL 348 IS 1 BP 27 EP 42 DI 10.1016/j.jmb.2005.02.015 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 915KG UT WOS:000228302500003 PM 15808851 ER PT J AU Li, YY Conway, JF Cheng, NQ Steven, AC Hendrix, RW Duda, RL AF Li, YY Conway, JF Cheng, NQ Steven, AC Hendrix, RW Duda, RL TI Control of virus assembly: HK97 "Whiffleball" mutant capsids without pentons SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE bacteriophage; HK97; capsid structure; virus assembly; subunit oligomerization ID LAMBDA HEAD SHELL; BACTERIOPHAGE-LAMBDA; SCAFFOLDING SUBUNITS; STRUCTURAL PROTEINS; GEL ELECTROPHORESIS; INHERENT PROPERTIES; MATURATION; COAT; RESOLUTION; PETITE AB The capsid of Escherichia coli bacteriophage HK97 assembles as a 420 subunit icosahedral shell called Prohead I which undergoes a series of maturation steps, including proteolytic cleavage, conformational rearrangements, and covalent cross-linking among all the subunits to yield the highly stable mature Head II shell. Prohead I have been shown to assemble from pre-formed hexamers and pentamers of the capsid protein subunit. We report here the properties of a mutant of the capsid protein, E219K, which illuminate the assembly of Prohead I. The mutant capsid protein is capable of going through all of the biochemically and morphologically defined steps of capsid maturation, and when it is expressed by itself from a plasmid it assembles efficiently into a Prohead I that is morphologically indistinguishable from the wild-type Prohead I, with a full complement of both hexamers and pentamers. Unlike the wildtype Prohead I, when the mutant structure is dissociated into capsomers in vitro, only hexamers are found. When such preparations are put under assembly conditions, these mutant hexamers assemble into "Whiffleballs", particles that are identical with Prohead I except that they are missing the 12 pentamers. These Whiffleballs can even be converted to Prohead I by specifically binding wild-type pentamers. We argue that the ability of the mutant hexamers to assemble in the absence of pentamers implies that they retain a memory of their earlier assembled state, most likely as a conformational difference relative to assembly-naive hexamers. The data therefore favor a model in which Prohead I assembly is regulated by conformational switching of the hexamer. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Inst Biol Struct JP Ebel, Grenoble, France. NIAMS, NIH, Struct Biol Lab, Bethesda, MD 20892 USA. RP Duda, RL (reprint author), Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. EM duda@pitt.edu RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 FU NIGMS NIH HHS [R01 GM47795] NR 45 TC 22 Z9 22 U1 0 U2 2 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 APR 22 PY 2005 VL 348 IS 1 BP 167 EP 182 DI 10.1016/j.jmb.2005.02.045 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 915KG UT WOS:000228302500013 PM 15808861 ER PT J AU Bichot, NP Rossi, AF Desimone, R AF Bichot, NP Rossi, AF Desimone, R TI Parallel and serial neural mechanisms for visual search in macaque area V4 SO SCIENCE LA English DT Article ID FRONTAL EYE FIELD; PARIETAL CORTEX; SELECTIVE ATTENTION; PREFRONTAL CORTEX; WORKING-MEMORY; SALIENCE MAP; RESPONSES; SYNCHRONIZATION; NEURONS; SPACE AB To find a target object in a crowded scene, a face in a crowd for example, the visual system might turn the neural representation of each object on and off in a serial fashion, testing each representation against a template of the target item. Alternatively, it might allow the processing of all objects in parallel but bias activity in favor of those neurons that represent critical features of the target, until the target emerges from the background. To test these possibilities, we recorded neurons in area V4 of monkeys freely scanning a complex array to find a target defined by color, shape, or both. Throughout the period of searching, neurons gave enhanced responses and synchronized their activity in the gamma range whenever a preferred stimulus in their receptive field matched a feature of the target, as predicted by parallel models. Neurons also gave enhanced responses to candidate targets that were selected for saccades, or foveation, reflecting a serial component of visual search. Thus, serial and parallel mechanisms of response enhancement and neural synchrony work together to identify objects in a scene. C1 NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Psychol, Nashville, TN 37203 USA. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Bichot, NP (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 9, Bethesda, MD 20892 USA. EM bichotn@mail.nih.gov NR 27 TC 332 Z9 336 U1 1 U2 27 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 APR 22 PY 2005 VL 308 IS 5721 BP 529 EP 534 DI 10.1126/science.1109676 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922BK UT WOS:000228810500046 PM 15845848 ER PT J AU Best, RB Hummer, G AF Best, RB Hummer, G TI Comment on "Force-clamp spectroscopy monitors the folding trajectory of a single protein" SO SCIENCE LA English DT Editorial Material C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; Best, Robert/H-7588-2016 OI Hummer, Gerhard/0000-0001-7768-746X; Best, Robert/0000-0002-7893-3543 NR 7 TC 2 Z9 2 U1 0 U2 8 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 APR 22 PY 2005 VL 308 IS 5721 DI 10.1126/science.1106969 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 922BK UT WOS:000228810500031 ER PT J AU Reali, E Canter, D Zeytin, H Schlom, J Greiner, JW AF Reali, E Canter, D Zeytin, H Schlom, J Greiner, JW TI Comparative studies of Avipox-GM-CSF versus recombinant GM-CSF protein as immune adjuvants with different vaccine platforms SO VACCINE LA English DT Article DE Avipox-GM-CSF; immune adjuvant ID COLONY-STIMULATING FACTOR; EPIDERMAL LANGERHANS CELLS; DENDRITIC CELLS; ANTITUMOR IMMUNITY; IN-VIVO; PHASE-I; ANTIGEN; CANCER; VIRUS; IMMUNOTHERAPY AB Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent immune stimulant when administered with different vaccines. Optimal use of GM-CSF resides in its ability to act locally to stimulate the proliferation and maturation of professional antigen-presenting cells (APCs) (i.e., Langerhans' cells) at the injection site. GM-CSF was engineered into a replication-incompetent recombinant avian (fowlpox) virus (rF-GM-CSF) and a single subcutaneous injection resulted in a sustained enrichment of activated dendritic cells within the regional draining lymph nodes. Those changes were attributed to local GM-CSF production at the injection site by rF-GM-CSF-infected cells. Studies were carried out in which mice were administered different types of beta-galactosidase (beta-gal)-based vaccines - whole protein, peptide, recombinant poxviruses - and GM-CSF was administered either as a single injection of rF-GM-CSF or four daily bolus injections of the recombinant protein. The use of rF-GM-CSF either improved the immune adjuvant effect, as observed for poxvirus-based vaccines, or was equivalent to rGM-CSF, as observed with the beta-gal protein vaccine. It is important to note that with either the replication-competent (vaccinia) or replicalion-incompetent (fowlpox) vaccines expressing LacZ, strong CTL responses directed against beta-gal were induced only when rF-GM-CSF was used as the immune adjuvant. Engineering GM-CSF into a recombinant fowlpox virus offers an excellent vehicle for the delivery of this cytokine as an immune adjuvant with specific vaccine platforms. In particular, delivery of GM-CSF via the rF-GM-CSF construct would be preferred over bolus injections of rGM-CSF when used as an immune adjuvant with whole protein or recombinant poxvirus-based vaccines. The study underscores the importance of defining the appropriate delivery form of an immune adjuvant, such as GM-CSF, relative to the immunization strategy to maximize the host immune responses against a specific antigen. Published by Elsevier Ltd. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. EM jg117s@nih.gov RI Reali, Eva/Q-1161-2016 OI Reali, Eva/0000-0003-1900-1356 NR 30 TC 24 Z9 24 U1 1 U2 4 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 APR 22 PY 2005 VL 23 IS 22 BP 2909 EP 2921 DI 10.1016/j.vaccine.2004.11.060 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 915QL UT WOS:000228318800011 PM 15780740 ER PT J AU Jenkins, LMM Byrd, JC Hara, T Srivastava, P Mazur, SJ Stahl, SJ Inman, JK Appella, E Omichinski, JG Legault, P AF Jenkins, LMM Byrd, JC Hara, T Srivastava, P Mazur, SJ Stahl, SJ Inman, JK Appella, E Omichinski, JG Legault, P TI Studies on the mechanism of inactivation of the HIV-1 nucleocapsid protein NCp7 with 2-mercaptobenzamide thioesters SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TERMINAL ZINC-FINGER; ANTI-HIV; IN-VITRO; PYRIDINIOALKANOYL THIOESTERS; ANTIRETROVIRAL THERAPY; BIOLOGICAL-PROPERTIES; DISULFIDE BENZAMIDES; IMPROVED SENSITIVITY; NMR-SPECTROSCOPY AB The HIV-1 nucleocapsid protein (NCp7) is a small basic protein with two CysCysHisCys zinc-binding domains that specifically recognizes the psi-site of the viral RNA. NCp7 plays a number of crucial roles in the viral lifecycle, including reverse transcription and RNA encapsidation. Several classes of potential anti-HIV compounds have been designed to inactivate NCp7 through zinc ejection, including a special class of thioester compounds. We have investigated the mechanism of action of two N-substituted-S-acyl-2-mercaptobenzamide compounds (compounds I and 2) that target NCp7. UV/Visible spectroscopy studies demonstrated that both thioesters were able to eject metal from NCp7. NMR and mass spectroscopy studies showed that the thioester compounds specifically ejected zinc from the carboxyl-terminal zinc-binding domain of NCp7 by covalent modification of Cys(39). Exposure of NCp7 to compounds 1 and 2 destroyed its ability to specifically bind RNA, whereas NCp7 already bound to RNA was protected from zinc ejection by the thioesters. The thiol component of the thioesters (compound 3, 2-mercaptobenzoyl-beta-alaninamide) did not eject zinc from NCp7, but when compound 3 was incubated with acetyl CoA prior to incubation with NCp7, we observed extensive metal ejection. Thus, the thiol released by the reaction of compounds 1 and 2 could be re-acylated in vivo by acyl CoA to form a new thioester compound that is able to react with NCp7. These studies provide a better understanding of the mechanism of action of thioester compounds, which is important for future design of anti-HIV-1 compounds that target NCp7. C1 Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. NCI, Cell Biol Lab, NCI, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Georgia, Dept Chem, Athens, GA 30602 USA. RP Omichinski, JG (reprint author), Univ Montreal, Dept Biochem, CP 6128,Succirsale Ctr Ville, Montreal, PQ H3C 3J7, Canada. EM jg.omichinski@umontreal.ca; pascale.legault@umontreal.ca FU NIGMS NIH HHS [R01 GM60298-01] NR 56 TC 29 Z9 33 U1 0 U2 10 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 APR 21 PY 2005 VL 48 IS 8 BP 2847 EP 2858 DI 10.1021/jm0492195 PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 917DH UT WOS:000228435700014 PM 15828823 ER PT J AU Gustchina, E Hummer, G Bewley, CA Clore, GM AF Gustchina, E Hummer, G Bewley, CA Clore, GM TI Differential inhibition of HIV-1 and SIV envelope-mediated cell fusion by C34 peptides derived from the C-terminal heptad repeat of gp41 from diverse strains of HIV-1, HIV-2, and SIV SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TRIMERIC COILED-COIL; POTENT INHIBITORS; ACTIVE CONFORMATION; MAJOR DETERMINANT; ATOMIC-STRUCTURE; VIRUS-INFECTION; TYPE-1 GP41; ENTRY; PROTEIN; DESIGN AB The spectrum of inhibition of human (HIV) and simian (SIV) immunodeficiency virus envelope (Env)-mediated cell fusion by C34, a 34 residue peptide corresponding to the C-heptad repeat of gp41 (residues 628-661 of HIV-1 Env), has been examined using a panel of five envelope glycoproteins, three from HIV-1 (LAV, SF162 and 89.6) and two from SIV (mac239 and mac316), and six C34 peptides derived from three strains of HIV-1 (LAV, N CM, and 0 CM), two strains of HIV-2 (EHO and ALI), and one strain of SIV (African Green Monkey, AGM). A quantitative vaccinia-based reporter gene cell fusion assay was employed. The inhibition data from the panel of 30 C34/envelope glycoprotein combinations, which can be fit to a simple activity relationship with IC50 values spanning a range of over 4 orders of magnitude from 4 nM to 70 mu M, permits one to rationalize both the potency and broadness of the inhibitory properties of the C34 peptides in terms of computed interaction free energies between the C34 peptides and the N-helical trimeric coiled-coil of gp41 and the helical propensities of the free C34 peptides. Of particular interest is the finding that the C34 peptide derived from the EHO strain of HIV-2 is a broad spectrum, highly potent inhibitor of Env-mediated cell fusion with IC50 values spanning a very narrow range from only 4 to 25 nM over the entire panel of HIV-1 and SIV envelope glycoproteins tested. This result suggests that C34 from HIV-2 EHO may present a potentially useful therapeutic agent against diverse and/or resistant strains of HIV-1. C1 NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, Bldg 8, Bethesda, MD 20892 USA. EM caroleb@intra.niddk.nih.gov; mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008; Hummer, Gerhard/A-2546-2013 OI Clore, G. Marius/0000-0003-3809-1027; Hummer, Gerhard/0000-0001-7768-746X NR 44 TC 25 Z9 25 U1 1 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 APR 21 PY 2005 VL 48 IS 8 BP 3036 EP 3044 DI 10.1021/jm049026h PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 917DH UT WOS:000228435700033 PM 15828842 ER PT J AU Koenig, BW Gawrisch, K AF Koenig, BW Gawrisch, K TI Lipid-ethanol interaction studied by NMR on bicelles SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID DIPOLAR COUPLINGS; PROTON NMR; BILAYERS; BRAIN; WATER; FIELD; MACROMOLECULES; SPECTROSCOPY; CONSTANTS; MEMBRANES AB The interaction of ethanol with phospholipids was studied in bicelles at a physiologically relevant ethanol concentration of 20 mM and a lipid content of 14 wt% by high-resolution NMR. Transient association of ethanol with magnetically aligned bicelles imparts a small degree of anisotropy to the solute. This anisotropy allows detection of residual H-1-H-1 and H-1-C-13 dipolar couplings, which are superimposed on scalar couplings. Residual 2 H NMR quadrupole splittings of isotope-labeled ethanol were measured as well. The analysis of residual tensorial interactions yielded information on the orientation and motions of ethanol in the membrane-bound state. The fraction of phosphatidylcholine-bound ethanol was determined independently by gas chromatography and NMR. About 4% of ethanol is bound to phosphatidylcholine at a bicelle concentration of 14 wt% at 40 degrees C. Free and bound ethanol are in rapid exchange. The lifetime of ethanol association with phosphatidylcholine membranes is of the order of a few nanoseconds. C1 Res Ctr Julich, Inst Biol Struct, D-52425 Julich, Germany. Univ Dusseldorf, Inst Biol Phys, D-40225 Dusseldorf, Germany. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Koenig, BW (reprint author), Forschungszentrum Julich, IBI-2-NMR, D-53425 Julich, Germany. EM b.koenig@fz-juelich.de RI Koenig, Bernd/B-4315-2008 OI Koenig, Bernd/0000-0002-5300-6276 NR 29 TC 22 Z9 22 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 21 PY 2005 VL 109 IS 15 BP 7540 EP 7547 DI 10.1021/jp044980b PG 8 WC Chemistry, Physical SC Chemistry GA 916XE UT WOS:000228419100088 PM 16851866 ER PT J AU Tycko, R AF Tycko, R TI Techniques - NMR on a chip SO NATURE LA English DT Editorial Material ID SOLIDS C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM robertty@mail.nih.gov NR 9 TC 8 Z9 9 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 21 PY 2005 VL 434 IS 7036 BP 966 EP 967 DI 10.1038/434966b PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 918EH UT WOS:000228524600022 PM 15846328 ER PT J AU Grayston, JT Kronmal, RA Jackson, LA Parisi, AF Muhlestein, JB Cohen, JD Rogers, WJ Crouse, JR Borrowdale, SL Schron, E Knirsch, C AF Grayston, JT Kronmal, RA Jackson, LA Parisi, AF Muhlestein, JB Cohen, JD Rogers, WJ Crouse, JR Borrowdale, SL Schron, E Knirsch, C CA ACES Investigators TI Azithromycin for the secondary prevention of coronary events SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Meeting of the European-Society-for-Chlamydia-Research CY SEP 02, 2004 CL Budapest, HUNGARY SP European Soc Chlamydia Res ID CHLAMYDIA-PNEUMONIAE INFECTION; MYCOBACTERIUM-AVIUM COMPLEX; CONTROLLED-TRIAL; DOUBLE-BLIND; ATHEROSCLEROTIC LESIONS; CARDIOVASCULAR-DISEASE; ANTIBIOTIC-TREATMENT; HEART-DISEASE; RABBIT MODEL; CLARITHROMYCIN AB BACKGROUND: Epidemiologic, laboratory, animal, and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis. We evaluated the efficacy of one year of azithromycin treatment for the secondary prevention of coronary events. METHODS: In this randomized, prospective trial, we assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year. The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States. RESULTS: The primary end point, a composite of death due to coronary heart disease, nonfatal myocardial infarction, coronary revascularization, or hospitalization for unstable angina, occurred in 446 of the participants who had been randomly assigned to receive azithromycin and 449 of those who had been randomly assigned to receive placebo. There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point (risk reduction, 1 percent [95 percent confidence interval, -13 to 13 percent]). There were also no significant risk reductions with regard to any of the components of the primary end point, death from any cause, or stroke. The results did not differ when the participants were stratified according to sex, age, smoking status, presence or absence of diabetes mellitus, or C. pneumoniae serologic status at baseline. CONCLUSIONS: A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Miriam Hosp, Providence, RI 02906 USA. Latter Day St Hosp, Salt Lake City, UT 84143 USA. St Louis Univ, Med Ctr, St Louis, MO 63103 USA. Univ Alabama, Birmingham, AL USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Axio Res, Seattle, WA USA. NHLBI, Bethesda, MD 20892 USA. Pfizer, New York, NY USA. RP Grayston, JT (reprint author), Univ Washington, Dept Epidemiol, Box 357236, Seattle, WA 98195 USA. NR 25 TC 207 Z9 218 U1 2 U2 6 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 2005 VL 352 IS 16 BP 1637 EP 1645 DI 10.1056/NEJMoa043526 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 918CE UT WOS:000228515200005 PM 15843666 ER PT J AU Landon, MB Leindecker, S Spong, CY AF Landon, MB Leindecker, S Spong, CY TI Outcomes associated with a trial of labor after prior cesarean delivery - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID UTERINE RUPTURE C1 Ohio State Univ, Coll Med, Columbus, OH 43210 USA. George Washington Univ, Ctr Biostat, Rockville, MD 20852 USA. NICHHD, Bethesda, MD 20892 USA. RP Landon, MB (reprint author), Ohio State Univ, Coll Med, Columbus, OH 43210 USA. EM landon.1@osu.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 21 PY 2005 VL 352 IS 16 BP 1720 EP 1720 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 918CE UT WOS:000228515200024 ER PT J AU Wang, YA Zhang, ZQ Lubet, R You, M AF Wang, YA Zhang, ZQ Lubet, R You, M TI Tobacco smoke-induced lung tumorigenesis in mutant A/J mice with alterations in K-ras, p53, or Ink4a/Arf SO ONCOGENE LA English DT Article DE tobacco smoke; A/J mice; transgene; lung tumorigenesis; K-ras; p53; Ink4a/Arf ID CIGARETTE-SMOKE; P16(INK4A) INACTIVATION; PROTEIN ACCUMULATION; ONCOGENE ACTIVATION; CANCER; TUMORS; MUTATIONS; MOUSE; GENE; 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE AB A/J mice with genetic alterations in K-ras, p53, or Ink4a/Arf were employed to investigate whether mice carrying these germline mutations would be susceptible to tobacco smoke-induced lung tumorigenesis. Transgenic mice of both genders and their wild-type littermates were exposed to environmental cigarette smoke for 6 months, followed by recovery in air for 5 months. A significant increase of lung tumor multiplicity was observed in K-ras, p53, or Ink4a/Arf mutant mice when compared with wild-type mice. Furthermore, an additive effect was observed between the mice with a mutant p53 transgene and an Ink4A/Arf deletion during tobacco smoke-induced lung tumorigenesis. Sequence analysis of the K-ras gene indicated that the mutations had occurred at either codon 12/13 or 61 in both spontaneously occurring (air control) and tobacco smoke-induced lung tumors. K-ras mutations were found in 62% of the tumors from air-control animals and 83% in those exposed to tobacco smoke. The mutation spectrum found in tumors from mice exposed to tobacco smoke is somewhat similar to that in tumors from air-control mice. In addition, we identified three novel mutations at codon 12: GGT (Gly)-> TTT (Phe), ATT (Ile), and CTT (Leu). These findings provide evidence that K-ras, p53, and Ink4a/Arf mutations play a role in tobacco smoke-related lung carcinogenesis. The similarity of the mutation spectra in the K-ras oncogene observed in tobacco smoke-induced tumors, as compared to spontaneous tumors, suggests that tobacco smoke enhances lung tumorigenesis primarily through promoting spontaneously occurring K-ras mutations. C1 Washington Univ, Sch Med, Dept Surg, Siteman Canc Ctr, St Louis, MO 63110 USA. NCI, Rockville, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, Siteman Canc Ctr, 660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [R01CA58554, N01CN-35117] NR 46 TC 26 Z9 26 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 APR 21 PY 2005 VL 24 IS 18 BP 3042 EP 3049 DI 10.1038/sj.onc.1208390 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 919WY UT WOS:000228649500013 PM 15846305 ER PT J AU Guarne, A Brendler, T Zhao, QH Ghirlando, R Austin, S Yang, W AF Guarne, A Brendler, T Zhao, QH Ghirlando, R Austin, S Yang, W TI Crystal structure of a SeqA-N filament: implications for DNA replication and chromosome organization SO EMBO JOURNAL LA English DT Article DE chromosome segregation; filament; oriC sequestration; SeqA; SeqA-DNA superhelix ID ESCHERICHIA-COLI; GATC SEQUENCES; ORIGIN SEQUESTRATION; PROMOTER ACTIVITY; PROTEIN; INITIATION; BINDING; COMPLEX; GENE; LOCALIZATION AB Escherichia coli SeqA binds clusters of transiently hemimethylated GATC sequences and sequesters the origin of replication, oriC, from methylation and premature reinitiation. Besides oriC, SeqA binds and organizes newly synthesized DNA at replication forks. Binding to multiple GATC sites is crucial for the formation of stable SeqA-DNA complexes. Here we report the crystal structure of the oligomerization domain of SeqA (SeqA-N). The structural unit of SeqA-N is a dimer, which oligomerizes to form a filament. Mutations that disrupt filament formation lead to asynchronous DNA replication, but the resulting SeqA dimer can still bind two GATC sites separated from 5 to 34 base pairs. Truncation of the linker between the oligomerization and DNA-binding domains restricts SeqA to bind two GATC sites separated by one or two full turns. We propose a model of a SeqA filament interacting with multiple GATC sites that accounts for both origin sequestration and chromosome organization. C1 McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Gene Regulat & Chromosome Biol Lab, Div Basic Sci, Ctr Canc Res, Frederick, MD 21701 USA. RP Guarne, A (reprint author), McMaster Univ, Dept Biochem & Biomed Sci, HSC-4N16,1200 Main St W, Hamilton, ON L8N 3Z5, Canada. EM guarnea@mcmaster.ca RI Ghirlando, Rodolfo/A-8880-2009; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 43 TC 29 Z9 31 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 20 PY 2005 VL 24 IS 8 BP 1502 EP 1511 DI 10.1038/sj.emboj.7600634 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923XW UT WOS:000228943900002 PM 15933720 ER PT J AU Hassan, SA Mehler, EL AF Hassan, SA Mehler, EL TI From quantum chemistry and the classical theory of polar liquids to continuum approximations in molecular mechanics calculations SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article DE continuum solvent; molecular mechanics; QM/MM; quantum chemistry ID DISTRIBUTED MULTIPOLE ANALYSIS; EFFECTIVE DIELECTRIC FUNCTION; SCREENED COULOMB POTENTIALS; DENSITY-FUNCTIONAL THEORY; IMPLICIT SOLVENT MODEL; POPULATION ANALYSIS; FORCE-FIELD; DYNAMICS SIMULATIONS; CARBONYL-COMPOUNDS; SOLVATION MODELS AB Biological macromolecules and other polymers belong to the class of mesoscopic systems, with characteristic length scale of the order of a nanometer. Although microscopic models would be the preferred choice in theoretical calculations, their use in computer simulations becomes prohibitive for large systems or long simulation times. On the other hand, the use of purely macroscopic models in the mesoscopic domain may introduce artifacts, with effects that are difficult to assess and that may compromise the reliability of the calculations. Here is proposed an approach with the aim of minimizing the empirical nature of continuum approximations of solvent effects within the scope of molecular mechanics (MM) approximations in mesoscopic systems. Using quantum chemical methods, the potential generated by the molecular electron density is first decomposed in a multicenter-multipole expansion around predetermined centers. The monopole and dipole terms of the expansion at each site create electric fields that polarize the surrounding aqueous medium whose dielectric properties can be described by the classical theory of polar liquids. Debye's theory allows a derivation of the dielectric profiles created around isolated point charges and dipoles that can incorporate Onsager reaction field corrections. A superposition of screened Coulomb potentials obtained from this theory makes possible a simple derivation of a formal expression for the total electrostatic energy and the polar component of the solvation energy of the system. A discussion is presented on the physical meaning of the model parameters, their transferability, and their convergence to calculable quantities in the limit of simple systems. The performance of this continuum approximation in computer calculations of amino acids in the context of an atomistic force field is discussed. Applications of a continuum model based on screened Coulomb potentials in multinanosecond simulations of peptides and proteins are briefly reviewed. (c) 2005 Wiley Periodicals, Inc. C1 Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. US Dept HHS, NIH, CIT, DCB,CMM, Bethesda, MD 20892 USA. RP Hassan, SA (reprint author), Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. EM mago@helix.nih.gov; elm2020@med.cornell.edu NR 72 TC 16 Z9 17 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7608 J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD APR 20 PY 2005 VL 102 IS 5 BP 986 EP 1001 DI 10.1002/qua.20526 PG 16 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA 914KY UT WOS:000228227700051 ER PT J AU Levine, RJ Epstein, FH Karumanchi, SA AF Levine, RJ Epstein, FH Karumanchi, SA TI Urinary placental growth factor and preeclampsia - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Nephrol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA 02215 USA. RP Levine, RJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. EM sananth@bidmc.harvard.edu NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 20 PY 2005 VL 293 IS 15 BP 1857 EP 1858 DI 10.1001/jama.293.15.1857-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 916QW UT WOS:000228401700019 ER PT J AU Flegal, KM Graubard, BI Williamson, DF Gail, MH AF Flegal, KM Graubard, BI Williamson, DF Gail, MH TI Excess deaths associated with underweight, overweight, and obesity SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-MASS INDEX; UNITED-STATES; FOLLOW-UP; BREAST-CANCER; US ADULTS; ALL-CAUSE; MORTALITY; WOMEN; GUIDELINES; SMOKING AB Context As the prevalence of obesity increases in the United States, concern over the association of body weight with excess mortality has also increased. Objective To estimate deaths associated with underweight (body mass index [BMI] <18.5), overweight (BMI 25 to <30), and obesity (BMI >= 30) in the United States in 2000. Design, Setting, and Participants We estimated relative risks of mortality associated with different levels of BMI (calculated as weight in kilograms divided by the square of height in meters) from the nationally representative National Health and Nutrition Examination Survey (NHANES) 1 (1971-1975) and NHANES II (1976-1980), with follow-up through 1992, and from NHANES 111 (1988-1994), with follow-up through 2000. These relative risks were applied to the distribution of BMI and other covariates from NHANES 1999-2002 to estimate attributable fractions and number of excess deaths, adjusted for confounding factors and for effect modification by age. Main Outcome Measures Number of excess deaths in 2000 associated with given BMI levels. Results Relative to the normal weight category (BMI 18.5 to <25), obesity (BMI >= 30) was associated with 111 909 excess deaths (95% confidence interval [CI], 53 754170064) and underweight with 33 746 excess deaths (95% Cl, 15726-51766). Overweight was not associated with excess mortality (-86094 deaths; 95% Cl, -161223 to -10966). The relative risks of mortality associated with obesity were lower in NHANES 11 and NHANES III than in NHANES I. Conclusions Underweight and obesity, particularly higher levels of obesity, were associated with increased mortality relative to the normal weight category. The impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. These findings are consistent with the increases in life expectancy in the United States and the declining mortality rates from ischemic heart disease. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Calif Berkeley, Ctr Weight & Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. RP Flegal, KM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4311, Hyattsville, MD 20782 USA. EM kflegal@cdc.gov RI Flegal, Katherine/A-4608-2013; OI Flegal, Katherine/0000-0002-0838-469X NR 41 TC 3474 Z9 3532 U1 34 U2 255 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 20 PY 2005 VL 293 IS 15 BP 1861 EP 1867 DI 10.1001/jama.293.15.1861 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 916QW UT WOS:000228401700024 PM 15840860 ER PT J AU Mamounas, EP Brown, A Anderson, S Smith, R Julian, T Miller, B Bear, HD Caldwell, CB Walker, AP Mikkelson, WM Stauffer, JS Robidoux, A Theoret, H Sovan, A Fisher, B Wickerham, DL Wolmark, N AF Mamounas, EP Brown, A Anderson, S Smith, R Julian, T Miller, B Bear, HD Caldwell, CB Walker, AP Mikkelson, WM Stauffer, JS Robidoux, A Theoret, H Sovan, A Fisher, B Wickerham, DL Wolmark, N TI Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: Results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ROUTINE AXILLARY DISSECTION; LYMPH-NODE; PREOPERATIVE CHEMOTHERAPY; GAMMA-PROBE; LYMPHADENECTOMY; CARCINOMA; TUMORS; WOMEN; TRIAL AB Purpose Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. Patients and Methods During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). Results Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. Conclusion These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy. C1 Aultman Hlth Fdn, Canton, OH 44710 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15212 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Genesee Hosp, Rochester, NY 14607 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Texas, Hlth Sci Ctr, Fredericksburg, TX USA. Univ Montreal, Ctr Hosp, Montreal, PQ, Canada. RP Mamounas, EP (reprint author), Aultman Hlth Fdn, 2600 6th St SW, Canton, OH 44710 USA. EM tmamounas@aultman.com OI Anderson, Stewart/0000-0001-8948-0650 FU NCI NIH HHS [U10CA-69651, U10CA-37377, U10CA-69974] NR 37 TC 231 Z9 253 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2005 VL 23 IS 12 BP 2694 EP 2702 DI 10.1200/JCO.2005.05.188 PG 9 WC Oncology SC Oncology GA 918QV UT WOS:000228563600017 PM 15837984 ER PT J AU Low, JA Wedam, SB Lee, JJ Berman, AW Brufsky, A Yang, SX Poruchynsky, MS Steinberg, SM Mannan, N Fojo, T Swain, SM AF Low, JA Wedam, SB Lee, JJ Berman, AW Brufsky, A Yang, SX Poruchynsky, MS Steinberg, SM Mannan, N Fojo, T Swain, SM TI Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 05-08, 2004 CL New Orleans, LA SP Amer Soc Clin Oncol ID MICROTUBULE-STABILIZING AGENTS; SOLID TUMORS; PATIENTS PTS; PACLITAXEL; DOCETAXEL AB Purpose (BMS-247550) is an epothilone B analog that stabilizes microtubules and has antitumor activity in taxane-refractory patients in phase I studies. In a phase II trial, we evaluated the efficacy and safety of ixabepilone in women with metastatic and locally advanced breast cancer. Patients and Methods Breast cancer patients with measurable disease who had paclitaxel and/or docetaxel as prior neoadjuvant, adjuvant, or metastatic therapy were treated with ixabepilone at 6 mg/m(2)/d intravenously on days 1 through 5 every 3 weeks. Levels of glutamate (glu)-terminated and acetylated alpha-tubulin, markers of microtubule stabilization, were detected by Western blot and by immunohistochemistry in a subset of matched pre- and post-treatment tumor biopsies. Results Thirty-seven patients received 153 cycles of ixabepilone. The best responses were a complete response in one patient (3%), partial responses in seven patients (19%), and stable disease in 13 patients (35%). Grade 3 and 4 toxicities included neutropenia (35%), febrile neutropenia (14%), fatigue (14%), diarrhea (11%), nausea/vomiting (5%), myalgia/arthralgia (3%), and sensory neuropathy (3%). Two patients were removed from study because of prolonged grade 2 or 3 neurotoxicity, and three patients were removed from study for other grade 3 and 4 nonhematologic toxicities. Compared with baseline levels, levels of both glu-terminated and acetylated alpha-tubulin were increased in tumor biopsies performed after ixabepilone therapy. Conclusion An objective response was seen in 22% of the patients in a population who had been previously treated with a taxane. Sensory neuropathy was mild with grade 3 neurotoxicity rarely seen. Microtubule stabilization occurred in tumor biopsies after treatment with ixabepilone. C1 Natl Canc Inst, Canc Res Ctr, Canc Therapeut Branch, NIH,Med Oncol Clin Res Unit, Bethesda, MD 20889 USA. Natl Canc Inst, Canc Res Ctr, Canc Therapeut Branch, NIH,Biostat & Data Management Sect, Bethesda, MD 20889 USA. Univ Pittsburgh, Magee Womens Hosp, Inst Canc, Pittsburgh, PA 15213 USA. RP Swain, SM (reprint author), Natl Canc Inst, Canc Res Ctr, Canc Therapeut Branch, NIH,Med Oncol Clin Res Unit, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 NR 26 TC 158 Z9 162 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 20 PY 2005 VL 23 IS 12 BP 2726 EP 2734 DI 10.1200/JCO.2005.10.024 PG 9 WC Oncology SC Oncology GA 918QV UT WOS:000228563600020 PM 15837987 ER PT J AU Cortes, J Faderl, S Estey, E Kurzrock, R Thomas, D Beran, M Garcia-Manero, G Ferrajoli, A Giles, F Koller, C O'Brien, S Wright, J Bai, SA Kantarjian, H AF Cortes, J Faderl, S Estey, E Kurzrock, R Thomas, D Beran, M Garcia-Manero, G Ferrajoli, A Giles, F Koller, C O'Brien, S Wright, J Bai, SA Kantarjian, H TI Phase I study of BMS-214662, a farnesyl transferase inhibitor in patients with acute leukemias and high-risk myelodysplastic syndromes SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FL SP Amer Soc Hematol ID CHRONIC MYELOID-LEUKEMIA; ADVANCED SOLID TUMORS; PRECLINICAL ANTITUMOR-ACTIVITY; ORAL LONAFARNIB SARASAR(TM); INTERNATIONAL WORKING GROUP; RAS TRANSGENIC MICE; FARNESYLTRANSFERASE INHIBITOR; HEMATOLOGIC MALIGNANCIES; PROTEIN TRANSFERASE; RESPONSE CRITERIA AB Purpose To investigate the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of BMS-214662, a farnesyl transferase (FTase) inhibitor, in patients with acute leukemias and high-risk myelodysplastic syndromes (MDS). Patients and Methods Patients with relapsed or refractory acute leukemias or MDS, or previously untreated but poor candidates for chemotherapy, were included in this phase I study with a 3 + 3 dose escalation design. BMS-214662 was administered as a 1-hour bolus once weekly at doses of 42 to 157 mg/m(2). Once the MTD was identified, the schedule was changed to a 24-hour continuous infusion once weekly (starting dose, 300 mg/m(2)). Results Thirty patients were treated at a dose of 42 (n = 1), 56 (n = 3), 84 (n = 3), 118 (n = 13), 157 (n = 6) or 300 mg/m(2) (n = 4). DLT occurred in 3 patients at 157 mg/m(2), including nausea, vomiting, diarrhea, hypokalemia and cardiovascular problems. No DLT occurred with 24-hour MTD with a 1-hour infusion was 118 mg/m(2), with no MTD identified continuous infusion. with the 24-hour infusion. Plasma concentrations of BMS-214662 correlated with the dose. Inhibition of FTase activity of approximately 60 % occurred after the infusion with recovery to near baseline after 24 hours. Five patients had evidence of antileukemia activity, including two with complete remission with incomplete platelet recovery, one with hematologic improvement, and two with morphologic leukemia-free state. Conclusion 118 mg/m(2) BMS-214662 is well tolerated at doses of up to as a 1-hour infusion. The toxicity profile and efficacy may be improved with prolonged exposure. Further investigation of this agent in leukemia is warranted. C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, Houston, TX 77030 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Bristol Myers Squibb Co, Princeton, NJ 08543 USA. RP Cortes, J (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Unit 428, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM jcortes@mdanderson.org NR 38 TC 38 Z9 41 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 APR 20 PY 2005 VL 23 IS 12 BP 2805 EP 2812 PG 8 WC Oncology SC Oncology GA 918QV UT WOS:000228563600029 PM 15728224 ER PT J AU Shepard, JD Liu, Y Sassone-Corsi, P Aguilera, G AF Shepard, JD Liu, Y Sassone-Corsi, P Aguilera, G TI Role of glucocorticoids and cAMP-mediated repression in limiting corticotropin-releasing hormone transcription during stress SO JOURNAL OF NEUROSCIENCE LA English DT Article DE corticotropin-releasing hormone; transcription; glucocorticoids; CREM; ICER; phospho-CREB ID LONG-TERM DESENSITIZATION; MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; GENE-EXPRESSION; CREM GENE; VASOPRESSIN TRANSCRIPTION; DIFFERENTIAL REGULATION; NEUROSECRETORY NEURONS; ADRENERGIC-RECEPTORS; RESPONSIVE ELEMENT AB The role of glucocorticoids and the repressor isoform of cAMP response element ( CRE) modulator ( CREM), inducible cAMP early repressor ( ICER), in limiting corticotropin-releasing hormone (CRH) transcription during restraint stress were examined in both intact and adrenalectomized rats receiving glucocorticoid replacement. CRH primary transcript, measured by intronic in situ hybridization, increased after 30 min of restraint and returned to basal levels by 90 min, despite the persistent stressor. The decline was independent of circulating glucocorticoids, because adrenalectomized rats displayed an identical pattern. ICER mRNA in the hypothalamic paraventricular nucleus (PVN) increased after 30 min and remained elevated for up to 4 h inaglucocorticoid-independent manner. Western blot and electrophoretic mobility shift assay analyses showed increases in endogenous ICER in the PVN of rats subjected to restraint stress for 3 h. Chromatin immunoprecipitation assays showed the recruitment of CREM by the CRH CRE in conjunction with decreases in RNA polymerase II (Pol II) binding in the PVN region of rats restrained for 3 h. These data show that stress-induced glucocorticoids do not mediate the limitation of CRH transcription. Furthermore, the ability of CREM to bind the CRH CRE and the time relationship between elevated CREM and reduced Pol II recruitment by the CRH promoter suggest that inhibitory isoforms of CREM induced during stress contribute to the decline in CRH gene transcription during persistent stimulation. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20891 USA. Univ Strasbourg 1, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM, F-67404 Illkirch Graffenstaden, France. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262, Bethesda, MD 20892 USA. EM Greti_Aguilera@nih.gov RI Sassone-Corsi, Paolo/H-6182-2011 NR 54 TC 47 Z9 48 U1 1 U2 6 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 APR 20 PY 2005 VL 25 IS 16 BP 4073 EP 4081 DI 10.1523/JNEUROSCI.0122-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 918LF UT WOS:000228542600009 PM 15843609 ER PT J AU Wang, YN Bohle, DS Bonifant, CL Chmurny, GN Collins, JR Davies, KM Deschamps, J Flippen-Anderson, JL Keefer, LK Klose, JR Saavedra, JE Waterhouse, DJ Ivanic, J AF Wang, YN Bohle, DS Bonifant, CL Chmurny, GN Collins, JR Davies, KM Deschamps, J Flippen-Anderson, JL Keefer, LK Klose, JR Saavedra, JE Waterhouse, DJ Ivanic, J TI Chemistry of the diazeniumdiolates: Z reversible arrow E isomerism SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID POLARIZABLE CONTINUUM MODEL; WAVE-FUNCTIONS; AB-INITIO; DENSITY; ENERGY; OXIDE; GEOMETRY; SYSTEMS; ATOMS; ION AB Here, we explore the chemistry of the previously undocumented E form of diazeniumdiolates having the structure R(1)R(2)NN(O)=NOR(3). Reported crystallographic studies have uniformly revealed the Z configuration, and our attempts to observe a Z -> E conversion through thermal equilibration or photochemical means have, until now, consistently failed to reveal a significant amount of a second conformer. As a typical example, the NMR spectrum of trimethyl derivative Me(2)NN(O)=NOMe revealed no evidence for a second configuration. Electronic structure calculations attribute this finding to a prohibitively high interconversion barrier of similar to 40 kcal/mol. A similar result was obtained when we considered the case of R(1) = Me = R(3) and R(2) = H at the same levels of theory. However, when MeHNN(O)=NOMe was ionized by dissociating the N-H bond, the barrier was calculated to be lower by approximately 20 kcal/mol, with the E form of the anion being favored over Z This circumstance suggested that an E isomer might be isolable if a Z anion were formed and given sufficient time to assume the E configuration, then quenched by reaction with an electrophile to trap and neutralize the E form and restore the putatively high interconversion barrier. Consistent with this prediction, basifying iPrHNN(O)=NOCH(2)CH(2)Br rapidly led to a six-membered heterocycle that was crystallographically characterized as containing the -N(O)=NO- functional group in the E configuration. The results suggest an approach for generating pairs of Z and E diazeniumdiolates for systematic comparison of the rates at which the individual isomers release bioactive NO and of other physicochemical determinants of their biomedical utility. C1 NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. McGill Univ, Dept Chem, Montreal, PQ H3A 2K6, Canada. NCI, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. NCI, Lab Proteom & Analyt Technol, SAIC Frederick, Frederick, MD 21702 USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. USN, Res Lab, Lab Struct Matter, Washington, DC 20375 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. RP Ivanic, J (reprint author), NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. EM jivanic@ncifcrf.gov RI Keefer, Larry/N-3247-2014; OI Keefer, Larry/0000-0001-7489-9555; Deschamps, Jeffrey/0000-0001-5845-0010 FU NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [Y1-DA1002] NR 32 TC 15 Z9 15 U1 0 U2 3 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 APR 20 PY 2005 VL 127 IS 15 BP 5388 EP 5395 DI 10.1021/ja0422581 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 916TE UT WOS:000228408300041 PM 15826177 ER PT J AU Strickler, HD Burk, RD Fazzari, M Anastos, K Minkoff, H Massad, LS Hall, C Bacon, M Levine, AM Watts, DH Silverberg, MJ Xue, XN Schlecht, NF Melnick, S Palefsky, JM AF Strickler, HD Burk, RD Fazzari, M Anastos, K Minkoff, H Massad, LS Hall, C Bacon, M Levine, AM Watts, DH Silverberg, MJ Xue, XN Schlecht, NF Melnick, S Palefsky, JM TI Natural history and possible reactivation of human papillomavirus in human immunodeficiency virus-positive women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SQUAMOUS INTRAEPITHELIAL LESIONS; ACTIVE ANTIRETROVIRAL THERAPY; CD4 CELL COUNTS; OPPORTUNISTIC INFECTIONS; CERVICAL-CANCER; RISK-FACTORS; VIRAL LOAD; SEROPOSITIVE WOMEN; SERONEGATIVE WOMEN; ADOLESCENT GIRLS AB Little is known in human immunodeficiency virus (HIV)-positive women about how the combination of plasma HIV RNA level and CD4(+) T-cell count is associated with the natural history of human papillomavirus (HPV) infection or about HPV reactivation-whether it occurs and with what frequency in HIV-positive women. Methods: HIV-positive (n = 1848) and -negative (n = 514) women were assessed at semiannual visits (total person-years = 5661) for cervicovaginal HPV with polymerase chain reaction assays and for squamous intraepithelial lesions (SILs) by Pap smear. We studied the prevalent detection of HPV and SILs with generalized estimating equations and the incident detection and persistence of HPV and SILs with multivariable Cox models. All statistical tests were two-sided. Results: We observed a strong interaction between the associations of CD4+ and plasma HIV RNA strata with both prevalent (P-interaction =.002) and incident (P-interaction =.001) detection of HPV. Indeed, the hazard ratio for incident HPV detection peaked between 4.0 and 5.0, with either a CD4(+) count of less than 200 cells per mm(3) or an HIV RNA level of more than 100 000 copies per mL. Although incident HPV detection in all women was associated with the number of recent sex partners (P-trend <.001), 22% of sexually inactive HIV-positive women with a CD4(+) count of less than 200 cells/mm(3) also had at least one incidently detected HPV type. The association between CD4'/HIV RNA strata and HPV persistence was statistically significantly smaller (P <.001) than for incident HPV detection. SIL prevalence, incident detection, and persistence had similar associations with CD4(+)/HIV RNA strata as HPV (above). Conclusion: In HIV-positive women, plasma HIV RNA level and CD4(+) count in combination appear to have a strong and statistically interactive association with incident detection of HPV, some of which may reflect HPV reactivation (e.g., in sexually inactive women). The more moderate association between HIV coinfection and HPV persistence could partly explain why cervical cancer rates have not reached more epidemic proportions in HIV-positive women. C1 Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Maimonides Hosp, Brooklyn, NY 11219 USA. So Illinois Univ, Sch Med, Springfield, IL USA. Georgetown Univ, Ctr Med, Washington, DC USA. Univ So Calif, Los Angeles, CA USA. NICHHD, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Strickler, HD (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1308, Bronx, NY 10461 USA. EM strickle@aecom.yu.edu FU NCI NIH HHS [CA85178-01]; NCRR NIH HHS [5 M01-RR-00079, M01-RR-00079, M01-RR-00083]; NIAID NIH HHS [U01 AI-35004, U01-AI-31834, U01-AI-34994]; NICHD NIH HHS [U01-HD-32632] NR 53 TC 245 Z9 259 U1 0 U2 6 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 APR 20 PY 2005 VL 97 IS 8 BP 577 EP 586 DI 10.1093/jnci/dji073 PG 10 WC Oncology SC Oncology GA 916VA UT WOS:000228413200012 PM 15840880 ER PT J AU Ron, E Ikeda, T Preston, DL Tokuoka, S AF Ron, E Ikeda, T Preston, DL Tokuoka, S TI Male breast cancer incidence among atomic bomb survivors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES; MORTALITY; RADIATION; MEN AB To learn more about the role of ionizing radiation in the development of male breast cancer, we evaluated male breast cancer incidence among 45880 male members of the Life Span Study cohort of Japanese atomic bomb survivors. Male breast cancers, diagnosed between January 1, 1958, and December 31, 1998, were identified through the Hiroshima and Nagasaki Tumor Registries. Nine male breast cancers were diagnosed among exposed Life Span Study members (crude rate = 1.8 per 100000 person-years), and three were diagnosed among nonexposed cohort members (crude rate = 0.5 per 100000 person-years). A statistically significant dose-response relation was observed (excess relative risk per sievert = 8, 95% confidence interval = 0.8 to 48; P =.01). Our finding of a statistically significant association between ionizing radiation and male breast cancer incidence adds to the very limited information that shows an association between radiation exposure and an increased risk of male breast cancer. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Radiat Effects Res Fdn, Nagasaki, Japan. Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan. Radiat Effects Res Fdn, Hiroshima, Japan. RP Ron, E (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Executive Blvd,MSC 7362, Bethesda, MD 20892 USA. EM eron@mail.nih.gov FU PHS HHS [4893-8-001] NR 17 TC 30 Z9 34 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 APR 20 PY 2005 VL 97 IS 8 BP 603 EP 605 DI 10.1093/jnci/dji097 PG 3 WC Oncology SC Oncology GA 916VA UT WOS:000228413200015 PM 15840883 ER PT J AU Widemann, BC Balis, FM Adamson, PC AF Widemann, BC Balis, FM Adamson, PC TI Re: Treatment of accidental intrathecal methotrexate overdose - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID MANAGEMENT C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Widemann, BC (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10 CRC Room 1-5750 MSC 1101, Bethesda, MD 20892 USA. EM bw42y@nih.gov NR 7 TC 1 Z9 1 U1 1 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 APR 20 PY 2005 VL 97 IS 8 BP 610 EP 611 DI 10.1093/jnci/dji109 PG 2 WC Oncology SC Oncology GA 916VA UT WOS:000228413200021 ER PT J AU Srinivasan, R Filie, A Reynolds, J Chang, R Chow, C Schrump, DS Takahashi, Y Suffredini, AF Childs, RW AF Srinivasan, R Filie, A Reynolds, J Chang, R Chow, C Schrump, DS Takahashi, Y Suffredini, AF Childs, RW TI Positron emission tomography for lymphoma staging: Tissue remains the issue SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID PET C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), NHLBI, Hematol Branch, 10 Ctr Dr,Bldg 10,CRC-3-5330, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov RI Takahashi, Yoshiyuki/I-1929-2012 NR 7 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 20 PY 2005 VL 97 IS 8 BP 611 EP 613 DI 10.1093/jnci/dji110 PG 3 WC Oncology SC Oncology GA 916VA UT WOS:000228413200022 PM 15840888 ER PT J AU Thompson, JR Bell, JK Bratt, J Grant, GA Banaszak, LJ AF Thompson, JR Bell, JK Bratt, J Grant, GA Banaszak, LJ TI V-max regulation through domain and subunit changes. The active form of phosphoglycerate dehydrogenase SO BIOCHEMISTRY LA English DT Article ID COLI D-3-PHOSPHOGLYCERATE DEHYDROGENASE; ESCHERICHIA-COLI; EFFECTOR-BINDING; 3-PHOSPHOGLYCERATE DEHYDROGENASE; SERA GENE; PROTEINS; INHIBITION; MOTIONS; MODEL; COOPERATIVITY AB An active conformation of phosphoglycerate dehydrogenase (PGDH) from Escherichia coli has been obtained using X-ray crystallography. The X-ray crystal structure is used to examine the potential intermediates for V-max regulation, for the redox reaction, and for cooperative effects of serine binding. The crystal structure at 2.2 angstrom resolution contains bound NAD(+) cofactor, either sulfate or phosphate anions, and a-ketoglutarate, a nonphysiological substrate. A PGDH subunit is formed from three distinct domains: regulatory (RBD), substrate (SBD), and nucleotide binding (NBD). The crystal conformation of the homotetramer points to the fact that, in the absence of serine, coordinated movement of the RBD-SBD domains occurs relative to the NBD. The result is a conformational change involving the steric relationships of both the domains and the subunits. Within the active site of each subunit is a bound molecule of alpha-ketoglutarate and the coenzyme, NAD. The catalytic or active site cleft is changed slightly although it is still solvent exposed; therefore, the catalytic reaction probably involves additional conformational changes. By comparing the inhibited with the uninhibited complex, it is possible to describe changes in conformation that are involved in the inhibitory signal transduction of serine. C1 Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Washington Univ, Dept Med, St Louis, MO 63110 USA. Washington Univ, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. RP Banaszak, LJ (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. EM banas001@umn.edu FU NIGMS NIH HHS [GM13925, GM56671] NR 31 TC 30 Z9 32 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 19 PY 2005 VL 44 IS 15 BP 5763 EP 5773 DI 10.1021/bi047944b PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916ZN UT WOS:000228425600022 PM 15823035 ER PT J AU Morrison, JP Read, JA Coleman, WG Tanner, ME AF Morrison, JP Read, JA Coleman, WG Tanner, ME TI Dismutase activity of ADP-L-glycero-D-manno-heptose 6-epimerase: Evidence for a direct oxidation/reduction mechanism SO BIOCHEMISTRY LA English DT Article ID D-MANNOHEPTOSE 6-EPIMERASE; UDP-GALACTOSE 4-EPIMERASE; LIVER ALCOHOL-DEHYDROGENASE; DROSOPHILA-MELANOGASTER; ESCHERICHIA-COLI; ALDEHYDE DEHYDROGENASE; GLUCOSE DEHYDROGENASE; SITE RESIDUES; EPIMERIZATION; ACID AB The first positive evidence for the utilization of a direct C-6" oxidation/reduction mechanism by ADP-L-glycero-D-manno-heptose 6-epimerase is reported here. The epimerase (HldD or AGME, formerly RfaD) operates in the biosynthetic pathway Of L-glycero-D-manno-heptose, which is a conserved sugar in the core region of lipopolysaccharide (LPS) of Gram-negative bacteria. The stereochemical inversion catalyzed by the epimerase is interesting as it occurs at an "unactivated" stereocenter that lacks an acidic C-H bond, and therefore, a direct deprotonation/reprotonation mechanism cannot be employed. Instead, the epimerase employs a transient oxidation strategy involving a tightly bound NADP(+) cofactor. A recent study ruled out mechanisms involving transient oxidation at C-4 '' and C-7 '' and supported a mechanism that involves an initial oxidation directly at the C-6 '' position to generate a 6"-keto intermediate (Read, J. A., Ahmed, R. A., Morrison, J. P., Coleman, W. G., Jr., Tanner, M. E. (2004) J. Am. Chem. Soc. 126, 8878-8879). A subsequent nonstereospecific reduction of the ketone intermediate can generate either epimer of the ADP-heptose. In this work, an intermediate analogue containing an aldehyde functionality at C-6 '', ADP-beta-D-manno-hexodialdose, is prepared in order to probe the ability of the enzyme to catalyze redox chemistry at this position. It is found that incubation of the aldehyde with a catalytic amount of the epimerase leads to a dismutation process in which one-half of the material is oxidized to ADP-beta-D-mannuronic acid and the other half is reduced to ADP-beta-D-mannose. Transient reduction of the enzyme-bound NADP(+) was monitored by UV spectroscopy and implicates the cofactor's involvement during catalysis. C1 Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20817 USA. RP Tanner, ME (reprint author), Univ British Columbia, Dept Chem, 2036 Main Mall, Vancouver, BC V6T 1Z1, Canada. EM mtanner@chem.ubc.ca NR 33 TC 17 Z9 17 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 19 PY 2005 VL 44 IS 15 BP 5907 EP 5915 DI 10.1021/bi050106c PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 916ZN UT WOS:000228425600037 PM 15823050 ER PT J AU Beilina, A Van Der Brug, M Ahmad, R Kesavapanyt, S Miller, DW Petsko, GA Cookson, MR AF Beilina, A Van Der Brug, M Ahmad, R Kesavapanyt, S Miller, DW Petsko, GA Cookson, MR TI Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitochondria; PARK6; Parkinson's disease ID EARLY-ONSET PARKINSONISM; PARK6-LINKED PARKINSONISM; DOPAMINERGIC DYSFUNCTION; CELL LINES; DISEASE; PINK1; DJ-1; GENE; MITOCHONDRIA; PET AB Several mutations in PTEN-induced putative kinase 1 (PINK1) gene have been reported to be associated with recessive parkinsonism. The encoded protein is predicted to be a Ser/Thr protein kinase targeted to mitochondria. In this study, we have investigated the effects of mutations on PINK1 kinase activity in vitro and on expression levels and localization in mammalian cells. We chose to examine two point mutations: G309D, which was originally reported to be stable and properly localized in cells and L347P, which is of interest because it is present at an appreciable carrier frequency in the Philippines. We were able to confirm kinase activity and produce artificial "kinase-dead" mutants that are stable but lack activity. The L347P mutation grossly destabilizes PINK1 and drastically reduces kinase activity, whereas G309D has much more modest effects on these parameters in vitro. This finding is in line with predictions based on homology modeling. We also examined the localization of PINK1 in transfected mammalian cells by using constructs that were tagged with myc or GFP at either end of the protein. These results show that PINK1 is processed at the IN terminus in a manner consistent with mitochondrial import, but the mature protein also exists in the cytosol. The physiological relevance of this observation is not yet clear, but it implies that a portion of PINK1 may be exported after processing in the mitochondria. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. NINDS, Neurochem Lab, Bethesda, MD 20892 USA. Brandeis Univ, Dept Biochem, Waltham, MA 02454 USA. Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, 35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov NR 29 TC 236 Z9 237 U1 2 U2 10 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 APR 19 PY 2005 VL 102 IS 16 BP 5703 EP 5708 DI 10.1073/pnas.0500617102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 918RL UT WOS:000228565200015 PM 15824318 ER PT J AU Zhao, HT Joseph, J Fales, HM Sokoloski, EA Levine, RL Vasquez-Vivar, J Kalyanaraman, B AF Zhao, HT Joseph, J Fales, HM Sokoloski, EA Levine, RL Vasquez-Vivar, J Kalyanaraman, B TI Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE free radical; reactive oxygen species; 2-hydroxyethidium; EPR; spin trapping ID SPONTANEOUSLY HYPERTENSIVE RATS; IN-VIVO EVIDENCE; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; DISMUTASE DEFICIENCY; NEURONS; INJURY; MICE; ATHEROSCLEROSIS; EXPRESSION AB Here we report the structural characterization of the product formed from the reaction between hydroethidine (HE) and superoxide (O-2(center dot-)). By using mass spectral and NMR techniques, the chemical structure of this product was determined as 2-hydroxyethidium (2-OH-E+). By using an authentic standard, we developed an HPLC approach to detect and quantitate the reaction product of HE and O-2(center dot-) formed in bovine aortic endothelial cells after treatment with menadione or antimycin A to induce intracellular reactive oxygen species. Concomitantly, we used a spin trap, 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), to detect and identify the structure of reactive oxygen species formed. BMPO trapped the O-2(center dot-) that formed extracellularly and was detected as the BMPO-OH adduct during use of the EPR technique. BMPO, being cell-permeable, inhibited the intracellular formation of 2-OH-E+. However, the intracellular BMPO spin adduct was not detected. The definitive characterization of the reaction product of O-2(center dot-) with HE described here forms the basis of an unambiguous assay for intracellular detection and quantitation of O-2(center dot-). Analysis of the fluorescence characteristics of ethidium (E+) and 2-OH-E+ strongly suggests that the currently available fluorescence methodology is not suitable for quantitating intracellular O-2(center dot-). We conclude that the HPLC/fluorescence assay using HE as a probe is more suitable reactive oxygen species for detecting intracellular O-2(center dot-). C1 Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Kalyanaraman, B (reprint author), Med Coll Wisconsin, Dept Biophys, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM balarama@mcw.edu RI Levine, Rodney/D-9885-2011 FU NCI NIH HHS [R01 CA077822, 5R01 CA 77822]; NHLBI NIH HHS [5P01 HL 68769-01, 5R01 HL 067244, P01 HL068769, R01 HL067244]; NINDS NIH HHS [2R01 NS 39958, R01 NS039958] NR 25 TC 347 Z9 348 U1 1 U2 45 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 APR 19 PY 2005 VL 102 IS 16 BP 5727 EP 5732 DI 10.1073/pnas.0501719102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 918RL UT WOS:000228565200019 PM 15824309 ER PT J AU Harper, SQ Staber, PD He, XH Eliason, SL Martins, IH Mao, QW Yang, L Kotin, RM Paulson, HL Davidson, BL AF Harper, SQ Staber, PD He, XH Eliason, SL Martins, IH Mao, QW Yang, L Kotin, RM Paulson, HL Davidson, BL TI RNA interference improves motor and neuropathological abnormalities in a Huntington's disease mouse model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE short hairpin RNAs; triplet repeat diseases; gene therapy; nanomedicine ID EXPANDED CAG REPEAT; TRANSGENIC MICE; NEURODEGENERATIVE DISEASE; NEURONAL LOSS; WEIGHT-LOSS; IN-VIVO; GENE; INACTIVATION; HDH; DEGENERATION AB Huntington's disease (HD) is a fatal, dominant neurogenetic disorder. HD results from polyglutamine repeat expansion (CAG codon, Q) in exon 1 of HD, conferring a toxic gain of function on the protein huntingtin (htt). Currently, no preventative treatment exists for HID. RNA interference (RNAi) has emerged as a potential therapeutic tool for treating dominant diseases by directly reducing disease gene expression. Here, we show that RNAi directed against mutant human htt reduced htt mRNA and protein expression in cell culture and in HD mouse brain. Importantly, htt gene silencing improved behavioral and neuropathological abnormalities associated with HID. Our data provide support for the further development of RNAi for HD therapy. C1 Univ Iowa, Program Gene Therapy, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Program Gene Therapy, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Program Gene Therapy, Dept Physiol & Biophys, Iowa City, IA 52242 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Davidson, BL (reprint author), Univ Iowa, Program Gene Therapy, Dept Internal Med, Iowa City, IA 52242 USA. EM beverly-davidson@uiowa.edu RI kotin, robert/B-8954-2008; Harper, Scott/E-3205-2011 NR 43 TC 377 Z9 393 U1 3 U2 30 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 APR 19 PY 2005 VL 102 IS 16 BP 5820 EP 5825 DI 10.1073/pnas.0501507102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 918RL UT WOS:000228565200035 PM 15811941 ER PT J AU Lilly, MA Duronio, RJ AF Lilly, MA Duronio, RJ TI New insights into cell cycle control from the Drosophila endocycle SO ONCOGENE LA English DT Review DE endocycle; Drosophila; cyclin E; DNA replication; E2F; notch ID DEPENDENT KINASE INHIBITOR; MINICHROMOSOME MAINTENANCE PROTEINS; TROPHOBLAST GIANT-CELLS; DNA-REPLICATION; S-PHASE; FOLLICLE CELLS; POLYTENE CHROMOSOMES; ENDOREDUPLICATION CYCLES; TRANSCRIPTION FACTOR; DISTINCT ROLES AB During metazoan development, the organization of the cell cycle is often modified in response to developmental signals. The endocycle provides a dramatic example of this phenomenon. In the endocycle, also referred to as the endoreplicative cycle, cells undergo successive rounds of DNA replication without an intervening mitosis. Often the endocycle is used to expand the genome of a group of specialized cells that are highly biosynthetically active. In these circumstances, large polyploid cells are produced in organisms that are primarily comprised of diploid cells. However, many organisms achieve growth by increasing cell size, rather than cell number. This strategy is more generally exploited in insects and plants. For instance, in the insect Drosophila melanogaster, the majority of the larval tissues, as well as many adult tissues, enter the endocycle and become polyploid. Therefore, Drosophila has been a rich source for studies on endocycle regulation. Recent work from Drosophila is beginning to reveal how developmental signals promote the transition from the mitotic cycle to the endocycle, as well as what drives endocycle progression. In addition, studies on the endocycle have provided insight into the regulatory principles underlying the once per cell cycle replication of the genome, as well as the relationship between S phase and mitosis. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Program Mol Biol & Biotechnol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA. RP Lilly, MA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM mlilly@helix.nih.gov; duronio@med.unc.edu OI Lilly, Mary/0000-0003-1564-619X NR 105 TC 73 Z9 74 U1 0 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 18 PY 2005 VL 24 IS 17 BP 2765 EP 2775 DI 10.1038/sj.onc.1208610 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 917MI UT WOS:000228465800003 PM 15838513 ER PT J AU Hougaku, H Fleg, JL Lakatta, EG Scuteri, A Earley, CJ Najjar, S Deb, S Metter, EJ AF Hougaku, H Fleg, JL Lakatta, EG Scuteri, A Earley, CJ Najjar, S Deb, S Metter, EJ TI Effect of light-to-moderate alcohol consumption on age-associated arterial stiffening SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIOVASCULAR-DISEASE; AORTIC STIFFNESS; MEDIA THICKNESS; WOMEN; RISK; STROKE; INTIMA; WALL; MEN AB Increased thickness and stiffness of large arteries may contribute to why aging is the most important risk for cardiovascular diseases. Arterial stiffness, intimal medial thickness, and alcohol intake were measured in 563 subjects. A U-shaped relation was found between alcohol intake and a stiffness index, with the lowest index in moderate drinkers, which may partially explain the relation between alcohol and. cardiovascular disease. (c) 2005 by Excerpta Medica Inc. C1 NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. Osaka Univ, Grad Sch Med, Osaka, Japan. INRCA, Dipartimento Cardiogeriatr, Rome, Italy. Univ Toronto, MD Program, Toronto, ON, Canada. RP Metter, EJ (reprint author), Harbor Hosp, Clin Res Branch, Intramural Res Program, NIA,ASTRA, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM metterj@mail.nih.gov NR 20 TC 6 Z9 6 U1 0 U2 3 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 15 PY 2005 VL 95 IS 8 BP 1006 EP 1010 DI 10.1016/j.amjcard.2004.12.051 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 915WX UT WOS:000228343200024 PM 15820179 ER PT J AU Klein, AP Duggal, P Lee, KE O'Neill, JA Klein, R Bailey-Wilson, JE Klein, BEK AF Klein, AP Duggal, P Lee, KE O'Neill, JA Klein, R Bailey-Wilson, JE Klein, BEK TI Polygenic effects and cigarette smoking account for a portion of the familial aggregation of nuclear sclerosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cataract; eye diseases; family; genes; genetic predisposition to disease; heredity; smoking ID BEAVER DAM EYE; BLUE MOUNTAINS EYE; LENS OPACITIES; RISK-FACTORS; MAJOR GENE; CATARACT; POPULATION; PREVALENCE; TRAITS; MODELS AB Cataract is the most common cause of blindness worldwide. Nuclear cataract, an advanced stage of nuclear sclerosis, is the most common type of age-related cataract. The authors assessed data from 2,089 persons within 620 extended pedigrees who participated in the 1988-1990 Beaver Dam Eye Study in Wisconsin to determine whether the observed familial aggregation of nuclear sclerosis could be explained by inheritance of a major gene. Familial correlations were examined and segregation analyses were performed on nuclear sclerosis measurements adjusted for age, sex, and pack-years of cigarette smoking. There was modest correlation among close family members after adjustment for age, sex, and pack-years of cigarette smoking: 0.084 between parents and offspring, and 0.198 between sibling pairs. Although results do not support involvement of a single major locus in the etiology of nuclear sclerosis, models that allowed for familial correlation, attributable in part to polygenic effects, did provide a better fit to the observed data than models without a polygenic effect. This finding suggests that several genes of modest effect may influence development of nuclear lens opacity, possibly in conjunction with environmental factors. Cigarette smoking was an important covariate in these analyses. Overall, results highlight the complex etiology of nuclear sclerosis. C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA. NHGRI, Stat Genet Sect, Inherited Dis Res Branch, Baltimore, MD USA. RP Klein, BEK (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 610 N Walnut St,Room 409, Madison, WI 53726 USA. EM kleinb@epi.ophth.wisc.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [RR03655]; NEI NIH HHS [EY 06594, R03 EY13438] NR 27 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 2005 VL 161 IS 8 BP 707 EP 713 DI 10.1093/aje/kwi102 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 912MA UT WOS:000228081300001 PM 15800262 ER PT J AU McBride, KL Pignatelli, R Lewin, M Ho, T Fernbach, S Menesses, A Lam, W Leal, SM Kaplan, N Schliekelman, P Towbin, JA Belmont, JW AF McBride, KL Pignatelli, R Lewin, M Ho, T Fernbach, S Menesses, A Lam, W Leal, SM Kaplan, N Schliekelman, P Towbin, JA Belmont, JW TI Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: Segregation, multiplex relative risk, and heritability SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital heart defects; hypoplastic left heart syndrome; bicuspid aortic valve; cardiac development; echocardiography; genetics ID HYPOPLASTIC-LEFT-HEART; BICUSPID AORTIC-VALVE; CARDIOVASCULAR MALFORMATIONS; FAMILIAL AGGREGATION; CARDIAC MALFORMATION; AMERICAN-INDIANS; LINKAGE ANALYSIS; DEFECTS; DISEASES; COARCTATION AB The left ventricular outflow tract (LVOTO) malformations, aortic valve stenosis (AVS), coaretation of the aorta (COA), and hypoplastic left heart (HLH) constitute a mechanistically defined subgroup of congenital heart defects that have substantial evidence for a genetic component. Evidence from echocardiography studies has shown that bicuspid aortic valve (BAV) is found frequently in relatives of children with LVOTO defects. However, formal inheritance analysis has not been performed. We ascertained 124 families by an index case with AVS, COA, or HLH. A total of 413 relatives were enrolled in the study, of which 351 had detailed echocardiography exams for structural heart defects and measurements of a variety of aortic arch, left ventricle, and valve structures. LVOTO malformations were noted in 30 relatives (18 BAV, 5 HLH, 3 COA, and 3 AVS), along with significant congenital heart defects (CHD) in 2 others (32/413; 7.7%). Relative risk for first-degree relatives in this group was 36.9, with a heritability of 0.71-0.90. Formal segregation analysis suggests that one or more minor loci with rare dominant alleles may be operative in a subset of families. Multiplex relative risk analysis, which estimates number of loci, had the highest maximum likelihood score in a model with 2 loci (range of 1-6 in the lod-1 support interval). Heritability of several aortic arch measurements and aortic valve was significant. These data support a complex but most likely oligogenic pattern of inheritance. A combination of linkage and association study designs is likely to enable LVOTO risk gene identification. This data can also provide families with important information for screening asymptomatic relatives for potentially harmful cardiac defects. (c) 2005 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. Univ Georgia, Dept Stat, Athens, GA 30602 USA. RP Belmont, JW (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM jbelmont@bcm.tmc.edu RI McBride, Kim/A-5879-2008; OI McBride, Kim/0000-0002-8407-8942; Belmont, John/0000-0001-7409-3578 FU NCRR NIH HHS [P41 RR003655, RR03655]; NHLBI NIH HHS [K23 HL070823, K23 HL70823]; NICHD NIH HHS [K12 HD041648, K12 HD41648, R01 HD039056, R01 HD39056] NR 53 TC 85 Z9 89 U1 2 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR 15 PY 2005 VL 134A IS 2 BP 180 EP 186 DI 10.1002/ajmg.a.30602 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 911WN UT WOS:000228037500009 PM 15690347 ER PT J AU Yitzhaki, S Shneyvays, V Jacobson, KA Shainberg, A AF Yitzhaki, S Shneyvays, V Jacobson, KA Shainberg, A TI Involvement of uracil nucleotides in protection of cardiomyocytes from hypoxic stress SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE P2Y(2) nucleotide receptor; G protein-coupled receptor; pyrimidines; cardioprotection; ischemia; preconditioning ID PROTEIN-KINASE-C; ADENOSINE RECEPTOR; CARDIAC MYOCYTES; RAT CARDIOMYOCYTES; DRUG TARGETS; ACTIVATION; HEART; MYOCARDIUM; AGONIST; CARDIOPROTECTION AB Cardiomyocytes express one or more subtypes of P2 receptors for extracellular nucleotides. P2 purinoceptors, which are activated by nucleotides, are classified as P2X or P2Y. P2X receptors are ligand-gated intrinsic ion channels, and P2Y receptors are G protein-coupled receptors. Extracellular pyrimidine and purine nucleotides are released from the heart during hypoxia. Although the cardioprotective effects of purines acting via purinoceptors were studied intensively, the physiological role of uracil nucleotide-responsive P2Y(2), P2Y(4), P2Y(6), and P2Y(14) receptors is still unclear, especially in the cardiovascular system. This study revealed that uridine-5'-triphosphate (UTP) protected cultured rat cardiomyocytes during hypoxia and explored the UTP signaling pathway leading to this cardioprotection. We found that UTP, but not UDP or uridine, significantly reduced cardiomyocyte death induced by hypoxia. Incubation with UTP for 1 h, before exposure to hypoxic conditions, protected the cells 24 h later. The cardioprotective effect of UTP was reduced in the presence of the P2 antagonist suramin. In addition, UTP caused a transient increase of [Ca2+](i) in cardiomyocytes. Pyridoxal-5-phosphate-6-azophenyl-2,4-disulfonate (PPADS) or Reactive blue 2 (RB-2), other antagonists of P2 receptors, abolished the [Ca2+](i) elevation caused by UTP. We used various inhibitors of the Ca2+ signaling pathway to show that UTP elevated levels of [Ca2+](i), originating from intracellular sources, via activation of phospholipase C and the IP3 receptor. Interestingly, these inhibitors of the Ca2+ signaling pathway did not prevent the immediate protective effect caused by UTR Although mitochondrial K-ATP channels are involved in other preconditioning mediator pathways, the involvement of these channels in the cardioprotective effect induced by UTP was ruled out, because 5-hydroxydecanoic acid (5-HD), a specific inhibitor of these channels, did not prevent the protection. (c) 2005 Elsevier Inc. All rights reserved. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shainberg, A (reprint author), Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. EM shaina@mail.biu.ac.il RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20] NR 38 TC 40 Z9 41 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD APR 15 PY 2005 VL 69 IS 8 BP 1215 EP 1223 DI 10.1016/j.bcp.2005.01.018 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916ZU UT WOS:000228426400010 PM 15794942 ER PT J AU Kann, MG Thiessen, PA Panchenko, AR Schaffer, AA Altschul, SF Bryant, SH AF Kann, MG Thiessen, PA Panchenko, AR Schaffer, AA Altschul, SF Bryant, SH TI A structure-based method for protein sequence alignment SO BIOINFORMATICS LA English DT Article ID HIDDEN MARKOV-MODELS; PSI-BLAST; DATABASE; IDENTIFICATION; SIMILARITIES; INFORMATION; SENSITIVITY; SELECTIVITY; ACCURACY; SEARCHES AB Motivation: With the continuing rapid growth of protein sequence data, protein sequence comparison methods have become the most widely used tools of bioinformatics. Among these methods are those that use position-specific scoring matrices (PSSMs) to describe protein families. PSSMs can capture information about conserved patterns within families, which can be used to increase the sensitivity of searches for related sequences. Certain types of structural information, however, are not generally captured by PSSM search methods. Here we introduce a program, Structure-based ALignment TOol (SALTO), that aligns protein query sequences to PSSMs using rules for placing and scoring gaps that are consistent with the conserved regions of domain alignments from NCBI's Conserved Domain Database. Results: In most cases, the alignment scores obtained using the local alignment version follow an extreme value distribution. SALTO's performance in finding related sequences and producing accurate alignments is similar to or better than that of IMPALA; one advantage of SALTO is that it imposes an explicit gapping model on each protein family. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov RI Kann, Maricel/E-5701-2012; Schaffer, Alejandro/F-2902-2012 NR 44 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2005 VL 21 IS 8 BP 1451 EP 1456 DI 10.1093/bioinformatics/bti233 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 916QX UT WOS:000228401800026 PM 15613392 ER PT J AU Pal, R Datta, A Fornace, AJ Bittner, ML Dougherty, ER AF Pal, R Datta, A Fornace, AJ Bittner, ML Dougherty, ER TI Boolean relationships among genes responsive to ionizing radiation in the NCI 60 ACDS SO BIOINFORMATICS LA English DT Article ID REGULATORY NETWORKS; CELL-LINES; PATHWAY AB Motivation: An early use of gene-expression data coming from microarrays was to discover non-linear multivariate intergene relationships. Pursuing this direction, the motivation for this paper is 2-fold: (1) to discover and elucidate multivariate logical predictive relations among gene expressions in a dataset arising from radiation studies using the NCI 60 Anti-Cancer Drug Screen (ACDS) cell lines; and (2) to demonstrate how these logical relations based on coarse quantization reflect corresponding relations in the continuous data. Results: Using the coefficient of determination, a large number of logical relationships have been discovered among genes in the NCI 60 ACDS cell lines. Moreover, these relationships can be seen directly in the original continuous data, and many are robust relative to the thresholds used to obtain the logical data from the continuous data. A key observation is that a number of intergene relationships appear to be considerably stronger when p53 is functional as compared to when it is not, which is consistent with earlier findings in the literature. C1 Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. NCI, NIH, Bethesda, MD 20892 USA. Translat Genom Res Inst, Phoenix, AZ 85004 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Dougherty, ER (reprint author), Texas A&M Univ, Dept Elect Engn, College Stn, TX 77843 USA. EM edward@ee.tamu.edu RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 17 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2005 VL 21 IS 8 BP 1542 EP 1549 DI 10.1093/bioinformatics/bti214 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 916QX UT WOS:000228401800038 PM 15598836 ER PT J AU Harrison, PJ Arango, V Vawter, MP Kleinman, JE AF Harrison, PJ Arango, V Vawter, MP Kleinman, JE TI Postmortem brain collections for neuropsychiatric disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Warneford Hosp, Oxford OX3 7JX, England. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Calif Irvine, Irvine, CA USA. NIMH, Sect Neuropathol, CBDB, NIH,IRP,Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Arango, Victoria/K-9377-2015 OI Arango, Victoria/0000-0001-8811-400X NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 7 BP 2S EP 3S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600009 ER PT J AU Bachmann, RF Yuan, PX Zhou, RL Manji, HK AF Bachmann, RF Yuan, PX Zhou, RL Manji, HK TI Chronic mood stabilizer treatment attenuates both methamphetamine-induced increases of proapoptotic and decreases of antiapoptotic Bcl-2 family members in mitochondria SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 24 BP 7S EP 8S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600026 ER PT J AU Gold, PW Martinez, P Haim, A Eskandari, F Cizza, G Alesci, S Kling, MA Quon, M AF Gold, PW Martinez, P Haim, A Eskandari, F Cizza, G Alesci, S Kling, MA Quon, M TI Decreased insulin sensitivity and increased plasma insulin, glucose, and triglyceride concentrations and their interactions in remitted patients with major depression: Evidence for an incipient metabolic syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Intramural Program, Bethesda, MD 20892 USA. NCCAM, Metab Sect, Intramural 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 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 23 BP 7S EP 7S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600025 ER PT J AU Egan, MF AF Egan, MF TI Molecular genetic studies of cognitive dysfunction in schizophrenia: Implications for treatment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, CBDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 45 BP 13S EP 13S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600047 ER PT J AU Chen, G AF Chen, G TI Evidence for the involvement of the ERK pathway in mood-regulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, LMP, MAP, NIH, Bethesda, MD 20892 USA. RI Chen, Guang/A-2570-2017 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 47 BP 14S EP 14S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600049 ER PT J AU Chuang, DM AF Chuang, DM TI Robust neuroprotective effects of the mood stabilizers lithium and valproate: Can these drugs be used to treat neurodegenerative diseases? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 48 BP 14S EP 14S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600050 ER PT J AU Higley, JD AF Higley, JD TI Studies of gene X environment interactions using a nonhuman primate model of alcohol abuse SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Sect Primate Models Psychopathol, LCTS, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 57 BP 16S EP 16S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600059 ER PT J AU Drevets, WC AF Drevets, WC TI Putative neuroimaging endophenotypes in bipolar disorder: Similarities with familial unipolar depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 61 BP 17S EP 17S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600063 ER PT J AU Hasler, G AF Hasler, G TI The endophenotype concept in psychiatry: Utilizing brain reward pathways as possible endophenotypes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 59 BP 17S EP 17S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600061 ER PT J AU Hu, XZ Zhu, GS Lipsky, RH Greenberg, BD Murphy, DL Goldman, D AF Hu, XZ Zhu, GS Lipsky, RH Greenberg, BD Murphy, DL Goldman, D TI Association of specific haplotypes of serotonin transporter gene with obsessive-compulsive disorder in caucasians SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Butler Hosp, Providence, RI 02906 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 70 BP 19S EP 20S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600072 ER PT J AU Szabo, S Einat, H Du, J Wu, JF Chen, WX Falke, C Manji, HK AF Szabo, S Einat, H Du, J Wu, JF Chen, WX Falke, C Manji, HK TI Neurogranin: A critical molecule at the nexus of signaling pathways involved in mood regulation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 69 BP 19S EP 19S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600071 ER PT J AU Du, J Gray, N Falke, C Wei, YL Chen, WX Zhang, L Manji, HK AF Du, J Gray, N Falke, C Wei, YL Chen, WX Zhang, L Manji, HK TI Regulation of synaptic localization and trafficking of AMPA glutamate receptor subunit GluR2 by mood stabilizers and antidepressants: Avenues for the development of novel therapeutics SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. USHUS, Dept Psychiat, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 74 BP 21S EP 21S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600076 ER PT J AU Lopez, VA Detera-Wadleigh, S Cardona, I McMahon, FJ McMahon, FJ AF Lopez, VA Detera-Wadleigh, S Cardona, I McMahon, FJ McMahon, FJ TI Genetic variation in tryptophan hydroxylase II is associated with suicidal behavior in bipolar affective disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIH, Bethesda, MD 20892 USA. RI McMahon, Francis/A-7290-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 79 BP 22S EP 22S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600081 ER PT J AU Rao, U Parker, A Ernst, M AF Rao, U Parker, A Ernst, M TI Decision-making in the context of risk-taking and vulnerability for addictive disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 85 BP 24S EP 24S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600087 ER PT J AU Beltaifa, S Law, AJ Hyde, TM McClintock, B Herman, MM Harrison, PJ Kleinman, JE Shannon-Weickert, C AF Beltaifa, S Law, AJ Hyde, TM McClintock, B Herman, MM Harrison, PJ Kleinman, JE Shannon-Weickert, C TI Altered ErbB3 receptor mRNA in the dorsolateral prefrontal cortex in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, MiNDS Unit, CBDB, Bethesda, MD 20892 USA. Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. RI Law, Amanda/G-6372-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 88 BP 25S EP 25S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600090 ER PT J AU Grillon, C Baas, JMP Pine, DS Ievine, J Lawley, M Ellis, V AF Grillon, C Baas, JMP Pine, DS Ievine, J Lawley, M Ellis, V TI The benzodiazepine alprazolam reduces contextual fear but not cued fear-potentiated startle in humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Utrecht, Dept Psychon, Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 89 BP 25S EP 25S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600091 ER PT J AU Grillon, C Baas, JMP Pine, DS Lawley, M Ellis, V Levine, J Charney, DS AF Grillon, C Baas, JMP Pine, DS Lawley, M Ellis, V Levine, J Charney, DS TI Relationship among plasma DHEAS and cortisol levels, and startle during aversive conditioning in humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Utrecht, Dept Psychon, Utrecht, Netherlands. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 90 BP 25S EP 26S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600092 ER PT J AU McCormack, KM Newman, TK Fulks, R Graff, A Maestripieri, D Higley, JD Sanchez, MM AF McCormack, KM Newman, TK Fulks, R Graff, A Maestripieri, D Higley, JD Sanchez, MM TI Hypothalamic-pituitary-adrenal (HPA) axis function in 12 month old rhesus macaques: The effects of serotonin transporter gene variation and early adverse experience SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Emory Univ, Yerkes Natl Primate Ctr, Atlanta, GA 30322 USA. NIAAA, Clin Studies Lab, NIH, Poolesville, MD USA. Univ Chicago, Inst Mind & Biol, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 92 BP 26S EP 26S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600094 ER PT J AU Buzas, B Hodgkinson, CA Jaeger, J Petrides, G McKnight, C Goldman, D Malhotra, AK AF Buzas, B Hodgkinson, CA Jaeger, J Petrides, G McKnight, C Goldman, D Malhotra, AK TI Single locus and haplotype analysis of AKT1 in schizophrenia and bipolar disorder in Caucasian and African-American populations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIDCR, Pain & Nuerosensory Mech Branch, NIH, Bethesda, MD USA. Zucker Hillside Hosp, Glen Oaks, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 101 BP 29S EP 29S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600103 ER PT J AU Frank, GK Bailer, UF Henry, SE Drevets, WC Meltzer, CC Price, JC Mathis, CA Wagner, A Kaye, WH AF Frank, GK Bailer, UF Henry, SE Drevets, WC Meltzer, CC Price, JC Mathis, CA Wagner, A Kaye, WH TI Increased dopamine D2/D3 receptor binding after recovery from anorexia nervosa SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Calif San Diego, San Diego, CA 92103 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA. Med Univ Vienna, Dept Gen Psychiat, Vienna, Austria. NIH, Neuroimaging Sect, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Presbyterian Univ Hosp, Sch Med, Dept Radiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Presbyterian Univ Hosp, Sch Med, Dept Neurol, Pittsburgh, PA 15213 USA. RI Mathis, Chester/A-8607-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 150 BP 43S EP 43S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600152 ER PT J AU Casanova, MF Christensen, JD Giedd, J Rumsey, JM Garver, DL Postel, GC AF Casanova, MF Christensen, JD Giedd, J Rumsey, JM Garver, DL Postel, GC TI A magnetic resonance study of brain asymmetries in dyslexic patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Louisville, Louisville, KY 40292 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Clin Neurosci Branch, Bethesda, MD 20892 USA. 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 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 172 BP 49S EP 49S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600174 ER PT J AU Moreno, FA Garriock, HA Delgado, PL Kling, MA Carpenter, LL Burke, M Burke, W Schwartz, T Marangell, L Husain, M Erickson, R AF Moreno, FA Garriock, HA Delgado, PL Kling, MA Carpenter, LL Burke, M Burke, W Schwartz, T Marangell, L Husain, M Erickson, R TI Monoamine-related genes and association with major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Arizona, Tucson, AZ USA. Case Western Reserve Univ, Univ Hosp Cleveland, Cleveland, OH 44106 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Butler Hosp, Providence, RI 02912 USA. Univ Kansas, Topeka, KS USA. Univ Nebraska, Omaha, NE 68182 USA. New York Upstate Psychiat Inst, Syracuse, NY USA. Baylor Univ, Sch Med, Houston, TX 77030 USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. RI Kling, Mitchel/F-4152-2010 OI Kling, Mitchel/0000-0002-2232-1409 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 179 BP 51S EP 51S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600180 ER PT J AU Perlman, WR Webster, M Kleinman, JE Weickert, CS AF Perlman, WR Webster, M Kleinman, JE Weickert, CS TI Expression of estrogen receptor alpha exon-deleted mRNA variants in the frontal cortex of patients with major mental illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders branch, DHHS, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 193 BP 54S EP 55S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600193 ER PT J AU Lauderdale, SG McClintock, B Saunders, R Webster, M Weickert, CS AF Lauderdale, SG McClintock, B Saunders, R Webster, M Weickert, CS TI Widespread expression of ErbB2, 3 and 4 mRNA in the juvenile and adult monkey brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 196 BP 55S EP 55S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600196 ER PT J AU Sanchez, MM Lyon, CK Noble, PL Crawford, JL Boudreau, M Higley, JD Nemeroff, CB Plotsky, PM Newman, TK Winslow, JT AF Sanchez, MM Lyon, CK Noble, PL Crawford, JL Boudreau, M Higley, JD Nemeroff, CB Plotsky, PM Newman, TK Winslow, JT TI Maternal separation alters hypothalamic-pituitary-adrenal (HPA) axis function in rhesus macaques: Effects of sex and serotonin transporter gene variation SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Emory Univ, Decatur, GA USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. NIMH, IRP Neurobiol Primate Core, NIH, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 204 BP 57S EP 58S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600204 ER PT J AU Gold, PW Wong, ML Goldstein, D Esler, M Alesci, S Charney, DS Perini, J Vgontzes, A DeBellis, M Geracioti, T Ronsaville, DS Kling, MA AF Gold, PW Wong, ML Goldstein, D Esler, M Alesci, S Charney, DS Perini, J Vgontzes, A DeBellis, M Geracioti, T Ronsaville, DS Kling, MA TI Increased total body norepinephrine spillover and ECT-reversible, around-the-clock indices of central noradrenergic, sympathomedullary, and adrenocortical hyperactivity in major depression: Potential mechanisms for increased mortality in patients with chronic heart failure complicated by depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH Intramural, Clin Neuroendocrinol, Bethesda, MD USA. Univ Calif Los Angeles, Los Angeles, CA USA. NIMH Intramural, Nincds, Bethesda, MD USA. Baker Heart Inst, Bethesda, MD USA. NIMH, Intramural Program, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Off Dean, New York, NY USA. Univ Padua, Padua, Italy. Penn State Coll Med, Hershey, PA USA. Duke Univ, Durham, NC USA. Univ Cincinnati, Cincinnati, OH USA. RI Kling, Mitchel/F-4152-2010; Wong, Ma-Li/D-7903-2011 OI Kling, Mitchel/0000-0002-2232-1409; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 218 BP 61S EP 61S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600218 ER PT J AU Radulescu, E Goldberg, TE Callicott, JH Egan, MF Munoz, KE Drabant, E Hariri, AS Mattay, VS Weinberger, DR AF Radulescu, E Goldberg, TE Callicott, JH Egan, MF Munoz, KE Drabant, E Hariri, AS Mattay, VS Weinberger, DR TI Sex differences in brain activation during episodic memory for aversive visual stimuli SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 221 BP 62S EP 62S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600221 ER PT J AU Sartorius, LJ Ren-Patterson, R Li, Z Lipska, BK Egan, MF Harrison, PJ Sei, Y Weinberger, DR AF Sartorius, LJ Ren-Patterson, R Li, Z Lipska, BK Egan, MF Harrison, PJ Sei, Y Weinberger, DR TI Expression of human metabotropic glutamate receptor 3 (GRM3) isoforms in B lymphoblasts from healthy and schizophrenic subjects SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. Univ Oxford, Dept Psychiat, Oxford, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 222 BP 62S EP 63S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600222 ER PT J AU Krain, AL Milham, MP Hefton, S Ernst, M Iwamoto, H Pine, DS Klein, RG Castellanos, X AF Krain, AL Milham, MP Hefton, S Ernst, M Iwamoto, H Pine, DS Klein, RG Castellanos, X TI A functional magnetic resonance imaging (fMRI)study of decision-making in anxiety-disordered adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NYU, Sch Med, NYU Child Study Ctr, New York, NY USA. NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 229 BP 64S EP 64S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600229 ER PT J AU Reist, C Ozdemir, V Goldman, D Mee, S Hashemzadeh, M AF Reist, C Ozdemir, V Goldman, D Mee, S Hashemzadeh, M TI A genetic association study of impulsivity and functional polymorphisms in dopamine D4 receptor (DRD4) and serotonin transporter (SLC6A4) genes SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 VA Long Beach Healthcare Syst, Psychiat, Long Beach, CA USA. VA Long Beach Healthcare Syst, Res Serv, Long Beach, CA USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 228 BP 64S EP 64S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600228 ER PT J AU Newman, TK Barr, CS Suomi, SJ Higley, JD AF Newman, TK Barr, CS Suomi, SJ Higley, JD TI Impulsive and aggressive behavior is influenced by MAOA genotype in male rhesus macaques (Macaca mulatta) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Clin Studies Lab, Rockville, MD 20852 USA. NIAAA, Clin Studies Lab, Poolesville, MD USA. NICHD, Lab Comparat Ecol, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 235 BP 66S EP 66S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600234 ER PT J AU Ducci, F Shen, PH Virkkunen, M Albaugh, B Goldman, D AF Ducci, F Shen, PH Virkkunen, M Albaugh, B Goldman, D TI Association between temperament traits and alcoholism in diverse populations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Helsinki, NIH, Helsinki, Finland. NIAAA, Neurogenet Lab, NIAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 240 BP 67S EP 67S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600239 ER PT J AU Enoch, MA Schwartz, LS Albaugh, B Virkkunen, M Goldman, D AF Enoch, MA Schwartz, LS Albaugh, B Virkkunen, M Goldman, D TI Anxious temperament mediates linkage of GABRA2 haplotypes with alcoholism SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 239 BP 67S EP 67S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600238 ER PT J AU Schwartz, LS White, KV Albaugh, B Goldman, D Enoch, MA AF Schwartz, LS White, KV Albaugh, B Goldman, D Enoch, MA TI Linkage of GABRB1 to alcoholism and low voltage alpha EEG in two independent populations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 241 BP 67S EP 68S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600240 ER PT J AU Holmes, A AF Holmes, A TI Genetic modulation or early life stress in mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Sect Behav Sci & Genet, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 274 BP 76S EP 76S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600272 ER PT J AU Warner, V Grillon, C AF Warner, V Grillon, C TI Families at high risk for depression: Anxiety and startle response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 New York State Psychiat Inst & Hosp, New York, NY 10032 USA. NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 275 BP 76S EP 77S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600273 ER PT J AU Keefe, R Bilder, RM Palmer, B Harvey, PD Davis, S McEvoy, J Golberg, T Gold, J Green, MF Swartz, MS Stroup, S Rosenheck, R Perkins, D Meltzer, H Lieberman, JA AF Keefe, R Bilder, RM Palmer, B Harvey, PD Davis, S McEvoy, J Golberg, T Gold, J Green, MF Swartz, MS Stroup, S Rosenheck, R Perkins, D Meltzer, H Lieberman, JA TI Baseline neurocognitive assessment of 1364 patients with schizophrenia in the clinical antipsychotic trials for intervention effectiveness (CATIE) project SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Duke Univ, Med Ctr, Durham, NC USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Mt Sinai Med Ctr, New York, NY USA. Quintilies Inc, Biostat, Res Triangle Pk, NC USA. NIMH, Bethesda, MD 20892 USA. Maryland Psychiat Res Ctr, Baltimore, MD 21228 USA. Univ N Carolina, Chapel Hill, NC USA. Yale Univ, New Haven, CT USA. Vanderbilt Univ, Nashville, TN USA. Columbia Univ, New York, NY USA. RI Bilder, Robert/A-8894-2008; Meltzer, Herbert/E-8131-2013 OI Bilder, Robert/0000-0001-5085-7852; NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 289 BP 79S EP 79S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600281 ER PT J AU Bertolino, A Caforio, G Petruzzella, V Latorre, V Rubino, V Dimalta, S De Candia, M Torraco, A Kolachana, B Papa, S Nardini, M Weinberger, DR Scarabino, T AF Bertolino, A Caforio, G Petruzzella, V Latorre, V Rubino, V Dimalta, S De Candia, M Torraco, A Kolachana, B Papa, S Nardini, M Weinberger, DR Scarabino, T TI GRM3 genotype and olanzapine treatment: Differential effects on prefrontal cortical function during working memory in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Bari, Dept Neurol & Psychiat, Bari, Italy. NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. IRCCSS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 293 BP 80S EP 80S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600285 ER PT J AU Du, J AF Du, J TI Modulation of AMPA glutamate receptor synaptic expression by antimanic agents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 306 BP 83S EP 84S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600298 ER PT J AU Grillon, C AF Grillon, C TI Integration of clinical and basic studies of fear and anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorder Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 320 BP 87S EP 87S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600312 ER PT J AU Merikangas, KR AF Merikangas, KR TI Gene-environment interaction in mental disorders: Choosing samples and research strategies SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 322 BP 88S EP 88S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600314 ER PT J AU Quiroz, JA Zarate, CA Singh, J Denicoff, KD Charney, DS Manji, HK AF Quiroz, JA Zarate, CA Singh, J Denicoff, KD Charney, DS Manji, HK TI N-acetyl-aspartate (NAA) and NAA-glutamate (NAAG) levels differs across brain regions in acutely depressed patients with mood disorders when compared with healthy volunteers: A proton magnetic resonance spectroscopy study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Deans Off, New York, NY USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 335 BP 91S EP 92S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600327 ER PT J AU Apud, JA Mattay, VS Das, S Alce, G Iudicello, J Akbar, N Egan, MF Goldberg, TE Weinberger, DR AF Apud, JA Mattay, VS Das, S Alce, G Iudicello, J Akbar, N Egan, MF Goldberg, TE Weinberger, DR TI COMT genotype and prefrontal function: Effects of tolcapone on cognition and fMRI in normal volunteers SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Genes Cognit & Psychosis Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 340 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600332 ER PT J AU Lawson, WB Hipolito, MM Wambulwa, CC Brisbane, E Barnes, DM AF Lawson, WB Hipolito, MM Wambulwa, CC Brisbane, E Barnes, DM TI Rapid cycling in African Americans with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Howard Univ, Washington, DC 20059 USA. NIMH, Genet Initiat Bipolar Grp, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 343 BP 94S EP 94S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600335 ER PT J AU Rich, BA Vinton, DT Hommer, RE Dickstein, DP McClure, EB Monk, CS Ernst, M Pine, DS Leibenluft, E AF Rich, BA Vinton, DT Hommer, RE Dickstein, DP McClure, EB Monk, CS Ernst, M Pine, DS Leibenluft, E TI The pathophysiology of social cognition deficits in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 351 BP 96S EP 97S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600343 ER PT J AU Brody, A Mandelkern, MA London, ED Olmestead, R Scheibal, D Jou, J Allen, V Tiongson, N Chefer, S Mukhin, A AF Brody, A Mandelkern, MA London, ED Olmestead, R Scheibal, D Jou, J Allen, V Tiongson, N Chefer, S Mukhin, A TI Effect of variable levels of cigarette smoking on nicotinic acetylcholine receptor availability during early smoking abstinence SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Psychiat, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Nucl Med, Los Angeles, CA USA. Univ Calif Irvine, Irvine, CA USA. NIDA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 357 BP 98S EP 98S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600349 ER PT J AU Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Sullivan, LK Hamner, MB Bohning, DE Arana, GW George, MS AF Kose, S Lorberbaum, JP Dubno, JR Horwitz, AR Newman, JD Sullivan, LK Hamner, MB Bohning, DE Arana, GW George, MS TI Regional brain activity in mothers and fathers listening to infant cries SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Mental Hlth Clin, Charleston, SC USA. Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA. NICHHD, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 369 BP 102S EP 102S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600361 ER PT J AU Vythilingam, M Scaramozza, M Nelson, EE Hazlett, G Waldeck, T Hadd, K Agarwal, R Drevets, WC Pine, DS Charney, DS Ernst, M AF Vythilingam, M Scaramozza, M Nelson, EE Hazlett, G Waldeck, T Hadd, K Agarwal, R Drevets, WC Pine, DS Charney, DS Ernst, M TI Resilient special forces soldiers have enhanced activation of reward related circuits SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. John F Kennedy Special Warfare Training & Sch, Psychol Applicat Directorate, Ft Bragg, NC USA. Mt Sinai Sch Med, Deans Off, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 375 BP 103S EP 104S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600366 ER PT J AU Osuch, E Willis, M Ursano, R Drevets, WC AF Osuch, E Willis, M Ursano, R Drevets, WC TI Regional cerebral blood flow changes with symptom provocation in the acute aftermath of motor vehicle accidents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIMH, Mood Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 402 BP 110S EP 110S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338600393 ER PT J AU Cornwell, BR Johnson, L Berardi, L Moak, Z Grillon, C AF Cornwell, BR Johnson, L Berardi, L Moak, Z Grillon, C TI Public speaking to a virtual audience: Startle reactivity and subjective experience SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 414 BP 113S EP 114S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601012 ER PT J AU Gould, NF Holmes, MK Pine, DS Burgess, N Manji, HK Zarate, CA AF Gould, NF Holmes, MK Pine, DS Burgess, N Manji, HK Zarate, CA TI Duke Nukem 3-D: Video games, virtual reality and spatial memory in patients with mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Rockville, MD 20857 USA. UCL, Dept Anat, London, England. UCL, Inst Cognit Neurosci, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 432 BP 118S EP 118S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601030 ER PT J AU Iloreta, SF Yokley, JL Hommer, D Weinberger, DR Egan, MF AF Iloreta, SF Yokley, JL Hommer, D Weinberger, DR Egan, MF TI Impaired smooth pursuit eye movement in schizophrenia: Heritability, reliability, and relation to cognitive dysfunction SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 447 BP 122S EP 123S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601045 ER PT J AU Alesci, S Martinez, PE Kelkar, S Ilias, I Ronsaville, DS Listwak, SJ Ayala, AR Masood, A Licinio, J Gold, HK Chrousos, GP Gold, PW Kling, MA AF Alesci, S Martinez, PE Kelkar, S Ilias, I Ronsaville, DS Listwak, SJ Ayala, AR Masood, A Licinio, J Gold, HK Chrousos, GP Gold, PW Kling, MA TI Major depression is associated with significant diurnal elevations in plasma IL-6 levels, a shift of its circadian rhythm, and loss of physiologic complexity in its secretion: Clinical implications SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD USA. Univ Calif Los Angeles, Lab Pharmacogenom, Los Angeles, CA USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. RI Kling, Mitchel/F-4152-2010; Licinio, Julio/L-4244-2013 OI Kling, Mitchel/0000-0002-2232-1409; Licinio, Julio/0000-0001-6905-5884 NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 454 BP 124S EP 124S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601052 ER PT J AU Cadet, JL Better, W Tate, K Herning, RI AF Cadet, JL Better, W Tate, K Herning, RI TI Cerebral blood flow and EEG alterations in MDMA users SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIDA, Mol Neuropsychiat Branch, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 493 BP 136S EP 136S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601091 ER PT J AU Ernst, M AF Ernst, M TI Ventral striatum in psychopathology: Neuroimaging perspective SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 501 BP 138S EP 138S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601099 ER PT J AU Insel, TR AF Insel, TR TI How do neurodevelopmental disorders develop? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, NIH, DHHS, Bethesda, MD 20892 USA. NIMH, Off Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 518 BP 142S EP 142S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601115 ER PT J AU Gould, TD Einat, H Picchini, AM Eberhart, CG Bhat, R Kempermann, G Manji, HK AF Gould, TD Einat, H Picchini, AM Eberhart, CG Bhat, R Kempermann, G Manji, HK TI Behavioral analysis of alternate GSK-3 inhibitors and b-catenin transgenic mice reveal mood stabilizer-like behaviors SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. Univ Minnesota, Dept Pharmacol, Duluth, MN 55812 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. AstraZeneca, R&D, Sodertalje, Sweden. Max Delbruck Ctr Mol Med, Dept Expt Neurol, Berlin, Germany. 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Dept Vet Affairs, New Jersey Healthcare Syst, Psychiat Serv 116A, E Orange, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 537 BP 147S EP 148S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601134 ER PT J AU Burdick, KE Hodgkinson, CA Ekholm, JM Szeszko, PR Lencz, T Kane, JM Goldman, D Malhotra, AK AF Burdick, KE Hodgkinson, CA Ekholm, JM Szeszko, PR Lencz, T Kane, JM Goldman, D Malhotra, AK TI DISC-1 genetic variation and neurocognitive function in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Zucker Hillside Long Isl Jewish Med Ctr, Glen Oaks, NY USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. 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NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 539 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601136 ER PT J AU Fanous, AH Gardner, CO Neale, MC Riley, BP Straub, RE O'Neill, AF Walsh, D Kendler, KS AF Fanous, AH Gardner, CO Neale, MC Riley, BP Straub, RE O'Neill, AF Walsh, D Kendler, KS TI A genome-wide scan of schizotypy in 270 Irish multiplex schizophrenia families reveals a significant genetic correlation with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Washington VA Med Ctr, Washington, DC USA. Georgetown Univ, Sch Med, Washington, DC USA. Virginia Commonwealth Univ, Richmond, VA USA. 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Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 542 BP 149S EP 149S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601139 ER PT J AU Zarate, CA AF Zarate, CA TI Modulation of glutamatergic activity with inhibitors of glutamate release and low-to-moderate affinity NMDA antagonists in patients with mood disorders: Results from recent clinical trials and future directions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 551 BP 152S EP 152S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601148 ER PT J AU Callicott, JH AF Callicott, JH TI Working memory: Genetic influences on prefrontal information processing as revealed by BOLD fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 555 BP 153S EP 153S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601152 ER PT J AU Rapoport, JL AF Rapoport, JL TI Structural and functional changes during late childhood and adolescence: Relevance to schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 559 BP 154S EP 154S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601156 ER PT J AU McClure, EB AF McClure, EB TI Effects of treatment on attention-modulated brain activation to emotional faces in youth with anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 572 BP 157S EP 157S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601169 ER PT J AU Monk, CS AF Monk, CS TI Attention-related brain activation to emotional facial expressions in adolescents at risk for psychopathology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 571 BP 157S EP 157S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601168 ER PT J AU Singh, J Zarate, CA Quiroz, JA De Jesus, G Lukenbaugh, D Denicoff, KD Manji, HK Charney, DS AF Singh, J Zarate, CA Quiroz, JA De Jesus, G Lukenbaugh, D Denicoff, KD Manji, HK Charney, DS TI A double-blind, placebo-controlled study of memantine in the treatment of major depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 590 BP 162S EP 162S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601187 ER PT J AU Hardin, MG Jazbec, S Pine, DS Ernst, M AF Hardin, MG Jazbec, S Pine, DS Ernst, M TI Influence of reward on saccadic eye movements in anxious and depressed adolescents SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 602 BP 165S EP 165S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601199 ER PT J AU Di Martino, A Graber, HL Hyde, C Schmitz, C Babour, RL Walters, JR Castellanos, X AF Di Martino, A Graber, HL Hyde, C Schmitz, C Babour, RL Walters, JR Castellanos, X TI Low frequency oscillations of oxy-Hemoglobin in brain are decreased during a cognitive task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NYU, Ctr Child Study, Inst Pediat Neurosci, New York, NY USA. SUNY Downstate Med Ctr, Dept Pathol, New York, NY USA. Na Bioassessments LLC, Elkton, MD USA. NINDS, Neurophysiol Pharmacol Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 610 BP 167S EP 168S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601207 ER PT J AU Moates, AF Avila, MT Hong, LE Wonodi, I Pickworth, WB Thaker, GK AF Moates, AF Avila, MT Hong, LE Wonodi, I Pickworth, WB Thaker, GK TI Smoking, nicotine dependence, and schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. NIDA, Clin Pharmacol Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 626 BP 172S EP 172S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601223 ER PT J AU Gogtay, N Nugent, TF Herman, D Hayashi, KM Greenstein, D Clasen, L Sporn, A Ordonez, A Giedd, J Thompson, PM Rapoport, JL AF Gogtay, N Nugent, TF Herman, D Hayashi, KM Greenstein, D Clasen, L Sporn, A Ordonez, A Giedd, J Thompson, PM Rapoport, JL TI Dynamic mapping of cortical brain development in early onset bipolar illness SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Lab Neuroimaging, Los Angeles, CA 90024 USA. RI Gogtay, Nitin/A-3035-2008; 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 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 633 BP 174S EP 174S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601230 ER PT J AU Oroszi, G Enoch, MA Chun, J Virkkunen, M Goldman, D AF Oroszi, G Enoch, MA Chun, J Virkkunen, M Goldman, D TI Thr105Ile, a functional polymorphism of histamine N-methyltransferase (HNMT), is associated with alcoholism in two independent populations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 641 BP 176S EP 176S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601238 ER PT J AU Tan, HY Mattay, VS Sust, S Buckholtz, JW Egan, MF Weinberger, DR Callicott, JH AF Tan, HY Mattay, VS Sust, S Buckholtz, JW Egan, MF Weinberger, DR Callicott, JH TI Prefrontal activation and behavioral performance across varying working memory loads in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIH, Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 652 BP 179S EP 179S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601249 ER PT J AU Guyer, AE Monk, CS McClure, EB Nelson, EE Roberson-Nay, R Adler, AD Zarahn, E Pine, DS Ernst, M AF Guyer, AE Monk, CS McClure, EB Nelson, EE Roberson-Nay, R Adler, AD Zarahn, E Pine, DS Ernst, M TI Developmental differences in attention-related amygdala response to emotional facial expressions SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Columbia Univ, Dept Psychiat, New York, NY USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 654 BP 180S EP 180S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601251 ER PT J AU Thompson, MJ McClintock, B Saunders, R Webster, M Weickert, CS AF Thompson, MJ McClintock, B Saunders, R Webster, M Weickert, CS TI Expression of ErbB 2, 3 and 4 protein in the frontal cortex rhesus macaque monkey SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Fdn Lab Brain Res, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 663 BP 182S EP 183S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601260 ER PT J AU Genderson, MR Diaz-Asper, CM Egan, MF Weinberger, DR Goldberg, TE AF Genderson, MR Diaz-Asper, CM Egan, MF Weinberger, DR Goldberg, TE TI Factor analysis of neurocognitive tests in a large mixed sample of schizophrenic probands, their siblings, and healthy controls SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 685 BP 188S EP 189S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601282 ER PT J AU Flory, JD Xu, K Mitropoulou, V Finch, T New, AS Goldman, D Siever, LJ AF Flory, JD Xu, K Mitropoulou, V Finch, T New, AS Goldman, D Siever, LJ TI Irritable assault, suicide history and variation in the COMT gene among people with Axis II disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Mt Sinai Sch Med, New York, NY USA. NIAAA, Neurogenet Lab, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 697 BP 192S EP 192S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601294 ER PT J AU Lissek, S Dvir, S McDowell, DJ Baas, JM Pine, DS Shaywitz, JE Grillon, C AF Lissek, S Dvir, S McDowell, DJ Baas, JM Pine, DS Shaywitz, JE Grillon, C TI Trait anxiety and retention of aversive conditioning SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Utrecht, Inst Helminthol, Psychol Lab, Utrecht, Netherlands. RI Lissek, Shmuel/B-6577-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 701 BP 193S EP 193S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601298 ER PT J AU Lissek, S Dvir, S Baas, JM McDowell, DJ Johnson, LL Pine, DS Shaywitz, JE Grillon, C AF Lissek, S Dvir, S Baas, JM McDowell, DJ Johnson, LL Pine, DS Shaywitz, JE Grillon, C TI Pathological anxiety is associated with sustained anxiety to an unpredictably stressful context, but not with phasic fear reactions to an explicit threat cue SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Utrecht, Inst Helminthol, Psychol Lab, Utrecht, Netherlands. RI Lissek, Shmuel/B-6577-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 700 BP 193S EP 193S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601297 ER PT J AU Sokolov, BP Cadet, JL AF Sokolov, BP Cadet, JL TI Methamphetamine-induced aggressiveness in mice is associated with complex changes in MAP kinase pathways SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIDA, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 711 BP 196S EP 196S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601308 ER PT J AU Belfer, I Hipp, H McKnight, C Scully, M Buzas, B Bollettino, A Schwartz, LS Max, MB Goldman, D Enoch, MA AF Belfer, I Hipp, H McKnight, C Scully, M Buzas, B Bollettino, A Schwartz, LS Max, MB Goldman, D Enoch, MA TI Linkage of galanin haplotypes with alcoholism is mediated by anxiety in two populations SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIDCR, Pnmb, NIH, Bethesda, MD USA. NIAAA, Lng, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 732 BP 202S EP 202S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601329 ER PT J AU Neumeister, A Belfer, I Drevets, WC Luckenbaugh, DA Goldman, D Charney, DS AF Neumeister, A Belfer, I Drevets, WC Luckenbaugh, DA Goldman, D Charney, DS TI Genetic influences on neural processing of emotionally valenced stimuli in depression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Yale Univ, Sch Med, Dept Psychiat, West Haven, CT 06516 USA. NIAAA, NIH, Bethesda, MD USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 733 BP 202S EP 202S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601330 ER PT J AU Marx, CE Yuan, PX Shampine, LJ Manji, HK AF Marx, CE Yuan, PX Shampine, LJ Manji, HK TI Neuroactive steroids, mood stabilizers, and neuroplasticity: Alterations following lithium and changes in Bcl-2 knockout mice SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Duke Univ, Med Ctr, Durham, NC USA. Durham VA, Durham, NC USA. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 741 BP 205S EP 205S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601338 ER PT J AU Baas, JM Grillon, C Pine, DS Lissek, S Drevets, WC Furey, M AF Baas, JM Grillon, C Pine, DS Lissek, S Drevets, WC Furey, M TI Prefrontal cortex activation during phasic fear and sustained anxiety, an FMRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 Univ Utrecht, Psychol Lab, Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Lissek, Shmuel/B-6577-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 744 BP 206S EP 206S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601341 ER PT J AU Lipsky, RH Lapteva, L Oroszi, G Hodgkinson, CA Davis, E Roebuck-Spencer, TM Yarboro, CH Jacobs, G Weickert, T Bleiberg, J Goldman, D Illei, GG AF Lipsky, RH Lapteva, L Oroszi, G Hodgkinson, CA Davis, E Roebuck-Spencer, TM Yarboro, CH Jacobs, G Weickert, T Bleiberg, J Goldman, D Illei, GG TI The Met66 variant of a common, functional Va166Met polymorphism in brain-derived neurotrophic factor (BDNF) confers protection against neurocognitive dysfunction in systemic lupus erythematosus (SLE) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Natl Rehabil Hosp, Washington, DC USA. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 755 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601352 ER PT J AU Tian, F Jiang, XY Anderson, T Neyer, K Marini, AM Lipsky, RH AF Tian, F Jiang, XY Anderson, T Neyer, K Marini, AM Lipsky, RH TI BDNF isoforms are expressed by transfected HEK cells SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIAAA, NIH, Bethesda, MD USA. USUHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 754 BP 209S EP 209S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601351 ER PT J AU McClure, EB Nelson, EE Easter, J Parrish, J Thorne, JF Monk, CS Rilling, JK Charney, DS Ernst, M Pine, DS AF McClure, EB Nelson, EE Easter, J Parrish, J Thorne, JF Monk, CS Rilling, JK Charney, DS Ernst, M Pine, DS TI A novel method for studying responses to social conflict in youth with mood and anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NIMH, Sect Dev & Affect Neurosci, NIH, MAP, Bethesda, MD 20892 USA. NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Durham, NC USA. Univ Chicago, Dept Psychol, Chicago, IL 60637 USA. Emory Univ, Dept Anthropol, Atlanta, GA 30322 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 765 BP 211S EP 212S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601361 ER PT J AU Bergen, AW AF Bergen, AW TI DRD2 and anorexia nervosa SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat C1 NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 SU S MA 766 BP 212S EP 212S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915VE UT WOS:000228338601362 ER PT J AU Neumeister, A Wood, S Bonne, O Nugent, AC Luckenbaugh, DA Young, T Bain, EE Charney, DS Drevets, WC AF Neumeister, A Wood, S Bonne, O Nugent, AC Luckenbaugh, DA Young, T Bain, EE Charney, DS Drevets, WC TI Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects SO BIOLOGICAL PSYCHIATRY LA English DT Article DE major depression; morphometry; hippocampal volume; high resolution MRI imaging ID IMPAIRMENT AB Background: Hippocampal volumes obtained from a group of medication-free, remitted subjects with, recurrent major depressive disorder (MDD) were compared against corresponding measures from healthy controls. Methods. Thirty-one subjects with, recurrent MDD in full remission, and 57 healthy controls underwent high resolution magnetic resonance imaging (MRI) on a GE 3T scanner. Eight patients with MDD were medication-naive, and twenty-three MDD patients were off antidepressant medications for a mean of 30 months at the time of the MRI study. Results. Patients showed smaller total and posterior hippocampal volume relative to controls. Anterior hippocampal volume did not differ between patients and controls. Conclusions. Recurrent depression is associated with smaller hippocampal volume which is most prominent in the posterior hippocampus. Smaller hippocampal volume appears to be a trait characteristic for MDD. C1 Yale Univ, Sch Med, Clin Neurosci Div,VA CT Healthcare Syst, VA Natl Ctr PTSD 116 A,Dept Psychiat, West Haven, CT 06516 USA. NIMH, Mood & Anxiety Disorders Program, Sect Expt Therapeut & Pathophysiol, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Sect Neuroimaging Mood & Antiety Disorders, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Neumeister, A (reprint author), Yale Univ, Sch Med, Clin Neurosci Div,VA CT Healthcare Syst, VA Natl Ctr PTSD 116 A,Dept Psychiat, 950 Campbell Ave, West Haven, CT 06516 USA. EM alexander.neumeister@yale.edu OI Nugent, Allison/0000-0003-2569-2480 NR 14 TC 168 Z9 178 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2005 VL 57 IS 8 BP 935 EP 937 DI 10.1016/j.biopsych.2005.01.016 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 915EM UT WOS:000228280700015 PM 15820716 ER PT J AU Malolanarasimhan, K Lai, CC Kelley, JA Iaccarino, L Reynolds, D Young, HA Marquez, VE AF Malolanarasimhan, K Lai, CC Kelley, JA Iaccarino, L Reynolds, D Young, HA Marquez, VE TI Synthesis and biological study of a flavone acetic acid analogue containing an azido reporting group designed as a multifunctional binding site probe SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE immunomodulatory small molecules; flavone acetic acid; azide-modified flavone acetic acid; affinity label; Staudinger reaction ID KILLER CELL-ACTIVITY; MURINE RENAL-CANCER; FLAVONE-8-ACETIC ACID; ANTITUMOR-ACTIVITY; NSC-347512; TUMOR; MICE; EXPRESSION; INDUCTION; MECHANISM AB Flavone-8-acetic acid (FAA) is a potent immunomodulatory small molecule that is uniquely characterized as being active on mouse but not human cells. Although FAA is a potent inducer of murine cytokine, chemokine and interferon gene expression, its mode of action remains unknown. In this report, we describe the synthesis of a new flavone acetic acid (FAA) analogue, (2-[2-(4-azidophenyl)-4-oxochromen-8-yl-]acetic acid (compound 2). We demonstrate that compound 2 is equally active as the parent FAA in inducing chemokine gene expression and that the azide functional group is capable of reacting with a reporter molecule, such as the FLAG peptide-phosphine, under mild conditions. This reaction will be useful for detecting the drug-bound protein active complex utilizing an anti-FLAG antibody. Published by Elsevier Ltd. C1 Frederick Ctr Canc Res, Ctr Canc Res, Lab Med Chem, NCI, Ft Detrick, MD 21702 USA. Ctr Canc Res, Lab Expt Immunol, NCI, Ft Detrick, MD 21702 USA. RP Marquez, VE (reprint author), Frederick Ctr Canc Res, Ctr Canc Res, Lab Med Chem, NCI, Ft Detrick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 30 TC 10 Z9 10 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD APR 15 PY 2005 VL 13 IS 8 BP 2717 EP 2722 DI 10.1016/j.bmc.2005.02.035 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 914US UT WOS:000228254000002 PM 15781383 ER PT J AU Sayers, TJ AF Sayers, TJ TI Mcl-1 reduction: releasing a death brake? SO BLOOD LA English DT Editorial Material C1 NCI, Expt Immunol Lab, Bethesda, MD 20892 USA. RP Sayers, TJ (reprint author), NCI, Expt Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2005 VL 105 IS 8 BP 3005 EP 3005 DI 10.1182/blood-2005-01-0290 PG 1 WC Hematology SC Hematology GA 915XK UT WOS:000228344500005 ER PT J AU Zhou, J Tagaya, Y Tolouei-Semnani, R Schlom, J Sabzevari, H AF Zhou, J Tagaya, Y Tolouei-Semnani, R Schlom, J Sabzevari, H TI Physiological relevance of antigen presentasome (APS), an acquired MHC/costimulatory complex, in the sustained activation of CD4(+) T cells in the absence of APCs SO BLOOD LA English DT Article ID HIV-INFECTED INDIVIDUALS; COSTIMULATORY MOLECULES; CD80; STIMULATION; EXPRESSION; RECEPTOR; CD28; ACQUISITION AB T-cell interaction with antigen-presenting cells (APCs) results in activation and clonal expansion of naive T cells. CD80 expression/acquisition in T cells has been implicated in disease processes in patients with rheumatoid arthritis and multiple myeloma and patients infected with HIV. Our previous data indicate that antigen-specific activation of naive T cells results in T-cell acquisition of CD80 molecules from APCs. However, the functional relevance of the acquired CD80 by T cells in signal pathways has remained unresolved. This study aims to define for the first time the role of acquired CD80 in T-cell clonal expansion. We demonstrate the following: (1) T cells, upon CD80 acquisition, sustain their proliferative response in the absence of APCs; (2) T cells that acquire CD80 sustain the activity of transcriptional factors such as nuclear factor-kappa B (NF kappa B) and activator protein-1 (AP1) for 24 hours after separation from APCs and up-regulate signal transducer and activator of transcription-5 (Stat5) in the absence of APCs or exogenous signal 1; and (3) maintenance of these signals results in unique cytokine production. Collectively, our data support the unique concept that naive T cells sustain their activation by removing '' antigen presentasome '' (APS; eg, antigen-presenting complex) from APCs, thereby releasing the constraint of APC requirement for further activation. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bldg 10,Rm 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov NR 19 TC 26 Z9 28 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2005 VL 105 IS 8 BP 3238 EP 3246 DI 10.1182/blood-2004-08-3236 PG 9 WC Hematology SC Hematology GA 915XK UT WOS:000228344500042 PM 15637136 ER PT J AU Wen, J Huang, SM Rogers, H Dickinson, LA Kohwi-Shigematsu, T Noguchi, CT AF Wen, J Huang, SM Rogers, H Dickinson, LA Kohwi-Shigematsu, T Noguchi, CT TI SATB1 family protein expressed during early erythroid differentiation modifies globin gene expression SO BLOOD LA English DT Article ID LOCUS-CONTROL REGION; DNA-BINDING PROTEIN; TRANSCRIPTION FACTOR GATA-1; NUCLEAR-MATRIX; HISTONE ACETYLTRANSFERASES; ERYTHROLEUKEMIA-CELLS; K562 CELLS; IN-VIVO; ACETYLATION; ACTIVATION AB Special AT-rich binding protein 1 (SATB1) nuclear protein, expressed predominantly in T cells, regulates genes through targeting chromatin remodeling during T-cell maturation. Here We show SATB1 family protein induction during early human adult erythroid progenitor cell differentiation concomitant with epsilon-globin expression. Erythroid differentiation of human erythroleukemia K562 cells by hemin simultaneously increases gamma-globin and down-regulates SATB1 family protein and epsilon-globin gene expression. Chromatin immunoprecipitation using ariti-SATB1 anti- body shows selective binding in vivo in the beta-globin cluster to the hypersensitive site 2 (HS2) in the locus control region (LCR) and to the epsilon-globin promoter. SATB1 overexpression increases epsilon-globin and decreases gamma-globin gene expression accompanied by histone hyperacetylation and hypomethylation in chromatin from the epsilon-globin promoter and HS2, and histone hypoacetylation and hypermethylation associated with the gamma-globin promoter. In K562 cells SATB1 family protein forms a complex with CREB-binding protein (CBP) important in transcriptional activation. In cotransfection experiments, increase in epsilon-promoter activity by SATB1 was amplified by CBP and blocked by E1A, a CBP inhibitor. Our results suggest that SATB1 can up-regulate the E-globin gene by interaction with specific sites in the beta-globin cluster and imply that SATB1 family protein expressed in the erythroid progenitor cells may have a role in globin gene expression during early erythroid differentiation. C1 NIDDKD, Mol Med Branch, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Med Branch, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Lawrence Berkeley Natl Lab, Dept Cell & Mol Biol, Berkeley, CA USA. RP Noguchi, CT (reprint author), NIDDKD, Mol Med Branch, Biol Chem Lab, NIH, Bldg 10,Rm 9N307,10 Ctr Dr,MSC 1822, Bethesda, MD 20892 USA. EM cnoguchi@helix.nih.gov NR 51 TC 59 Z9 66 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2005 VL 105 IS 8 BP 3330 EP 3339 DI 10.1182/blood-2004-08-2988 PG 10 WC Hematology SC Hematology GA 915XK UT WOS:000228344500054 PM 15618465 ER PT J AU Elam, C Hesson, L Vos, MD Eckfeld, K Ellis, CA Bell, A Krex, D Birrer, NJ Latif, F Clark, GJ AF Elam, C Hesson, L Vos, MD Eckfeld, K Ellis, CA Bell, A Krex, D Birrer, NJ Latif, F Clark, GJ TI RRP22 is a farnesylated, nucleolar, ras-related protein with tumor suppressor potential SO CANCER RESEARCH LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; GENE; GTP; ACTIVATION; EFFECTOR; OVARIAN; CANCER; ARHI; COMPLEMENTARY; PRENYLATION AB Ras proteins are members of a superfamily of related small GTPases. Some members, such as Ras, are oncogenic. However, other members seem to serve as tumor suppressors, such as Rig and Noey2. We now identify and characterize a novel member of the Ras superfamily, RRP22. Like Ras, RRP22 can be posttranslationally modified by farnesyl. Unlike Ras, RRP22 inhibits cell growth and promotes caspase-independent cell death. Examination of human tumor cells shows that RRP22 is frequently down-regulated due to promoter methylation. Moreover, reexpression of RRP22 in an RRP22-negative neural tumor cell line impairs its growth in soft agar. Unusually for a Ras-related protein, RRP22 localizes to the nucleolus in a GTP-dependent manner, suggesting a novel mechanism of action. Thus, we identify a new member of the Ras superfamily that can serve as a potential tumor suppressor. C1 NCI, Dept Cell & Canc Biol, NIH, Rockville, MD 20820 USA. Univ Birmingham, Div Reprod & Child Hlth, Sect Med & Mol Genet, Birmingham, W Midlands, England. Tech Univ Dresden, Klinikum Carl Gustav Carus, Dept Neurosurg, D-8027 Dresden, Germany. RP Clark, GJ (reprint author), NCI, Dept Cell & Canc Biol, NIH, Room 307,9610 Med Ctr Dr, Rockville, MD 20820 USA. EM gclark@mad.nih.gov RI Krex, Dietmar/E-6833-2014 NR 38 TC 23 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2005 VL 65 IS 8 BP 3117 EP 3125 PG 9 WC Oncology SC Oncology GA 916ZF UT WOS:000228424800023 PM 15833841 ER PT J AU Wang, V Davis, DA Haque, M Huang, LE Yarchoan, R AF Wang, V Davis, DA Haque, M Huang, LE Yarchoan, R TI Differential gene up-regulation by hypoxia-inducible factor-1 alpha and hypoxia-inducible factor-2 alpha in HEK293T cells SO CANCER RESEARCH LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; TUMOR-SUPPRESSOR PROTEIN; EPISODIC ATAXIA TYPE-2; TRANSCRIPTION FACTOR; HEMIPLEGIC MIGRAINE; ANDROGEN RECEPTOR; ENDOTHELIAL-CELLS; FACTOR 1-ALPHA; DNA-BINDING; FACTOR-I AB Cells exposed to hypoxia respond by increasing the level of hypoxia-inducible factor-1 (HIF-1). This factor then activates a number of genes by binding to hypoxia response elements in their promoter regions. A second hypoxia-responsive factor, HIF-2, can activate many of the same genes as HIF-1. Overexpression of HIFs accompanies the pathogenesis of many tumors. It is unclear, however, as to the respective role of these factors in responsiveness to hypoxia and other stresses. To address this issue, we used microarray technology to study the genes activated in HEK293T cells by hypoxia or transfection with the alpha chain of HIF-1 (or mutant HIF-1 resistant to degradation) or HIF-2. Fifty-six genes were found to be upregulated at least 3-fold by either hypoxia or transfection. Of these, 21 were elevated both by transfection with HIF-1 alpha and with HIF-2 alpha, and 14 were preferentially activated by HIF-1 alpha including several involved in glycolysis. Ten genes were preferentially activated by HIF-2 alpha, including two (CACNA1A and PTPRZ1) implicated in neurologic diseases. Interestingly, most HIF-2 alpha-responsive genes were not substantially activated by hypoxia. An additional 10 genes were up-regulated by hypoxia but minimally activated by HIF-1 alpha or HIF-2 alpha transfection. Ten of the genes were studied by quantitative real-time PCR and/or by Northern blot and the results paralleled those found with microarray technology. Although confirmation in other systems will be necessary, these results indicate that whereas some genes are robustly activated by both HIF-1 and HIF-2, others can be preferentially activated by one or the other factor. C1 NCI, Canc Res Ctr, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Yarchoan, R (reprint author), NCI, Canc Res Ctr, HIV & AIDS Malignancy Branch, NIH, 10 Ctr Dr,Bldg 10,Room 10S255,MSC 1868, Bethesda, MD 20892 USA. EM yarchoan@helix.nih.gov NR 51 TC 175 Z9 182 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2005 VL 65 IS 8 BP 3299 EP 3306 PG 8 WC Oncology SC Oncology GA 916ZF UT WOS:000228424800045 PM 15833863 ER EF