FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Pullmann, R Abdelmohsen, K Lal, A Martindale, JL Ladner, RD Gorospe, M AF Pullmann, Rudolf, Jr. Abdelmohsen, Kotb Lal, Ashish Martindale, Jennifer L. Ladner, Robert D. Gorospe, Myriam TI Differential stability of thymidylate synthase 3 '-untranslated region polymorphic variants regulated by AUF1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA TURNOVER; BINDING-PROTEINS; COMMON POLYMORPHISM; GENE-EXPRESSION; LUNG-CANCER; HUR; CLONING; RISK; 5-FLUOROURACIL; IDENTIFICATION AB A 6-nucleotide insertion (I)/deletion (D) polymorphism in the 3'-untranslated region of the thymidylate synthase gene was shown to influence mRNA stability, but the molecular basis of this effect has not been elucidated. Here, studies of both endogenous and ectopically expressed thymidylate synthase alleles revealed that the mRNA-binding, decay-promoting protein AUF1 has higher affinity for allele D mRNA. AUF1 overexpression preferentially suppressed D allele mRNA levels, whereas AUF1 silencing selectively elevated D allele mRNA levels. Our results illustrate the functional consequences of ribonucleoprotein associations involving a polymorphic RNA sequence and uncover a novel mechanism of action for non-coding RNA polymorphisms. C1 NIA, Cellular & Mol Biol Lab, IRP, NIH, Baltimore, MD 21224 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. RP Pullmann, R (reprint author), NIA, Cellular & Mol Biol Lab, IRP, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM pullmannru@nih.gov OI abdelmohsen, Kotb/0000-0001-6240-5810 FU Intramural NIH HHS NR 38 TC 34 Z9 39 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 2006 VL 281 IS 33 BP 23456 EP 23463 DI 10.1074/jbc.M600282200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 072WE UT WOS:000239702900020 PM 16787927 ER PT J AU Lin, Y Yang, QF Wang, X Liu, ZG AF Lin, Yong Yang, Qingfeng Wang, Xia Liu, Zheng-gang TI The essential role of the death domain kinase receptor-interacting protein in insulin growth factor-I-induced c-Jun N-terminal kinase activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B ACTIVATION; TNF-INDUCED APOPTOSIS; NECROSIS-FACTOR-ALPHA; CELL-DEATH; DNA-DAMAGE; NH2-TERMINAL KINASE; MEDIATED APOPTOSIS; GENE-EXPRESSION; IGF-1 RECEPTOR; JNK ACTIVATION AB Insulin-like growth factor I (IGF-I) plays an important role in cell survival, proliferation, and differentiation. Diverse kinases, including AKT/ protein kinase B, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK), can be activated by IGF-I. Here, we show that the receptor-interacting protein (RIP), a key mediator of tumor necrosis factor-induced NF-kappa B and JNK activation, plays a key role in IGF-I receptor signaling. IGF-I induced a robust JNK activation in wild type but not RIP null (RIP-/-) mouse embryonic fibroblast cells. Reconstitution of RIP expression in the RIP-/- cells restored the induction of JNK by IGF-I, suggesting that RIP is essential in IGF-I-induced JNK activation. Reconstitution experiments with different RIP mutants further revealed that the death domain and the kinase activity of RIP are not required for IGF-I-induced JNK activation. Interestingly, the AKT and ERK activation by IGF-I was normal in RIP-/- cells. The phosphatidylinositol 3-kinase inhibitor, wortmannin, did not affect IGF-I-induced JNK activation. These results agree with previous studies showing that the IGF-I-induced JNK activation pathway is distinct from that of ERK and AKT activation. Additionally, physical interaction of ectopically expressed RIP and IGF-IR beta was detected by co-immunoprecipitation assays. More importantly, RIP was recruited to the IGF-I receptor complex during IGF-I-induced signaling. Furthermore, we found that IGF-I-induced cell proliferation was impaired in RIP-/- cells. Taken together, our results indicate that RIP, a key factor in tumor necrosis factor signaling, also plays a pivotal role in IGF-I-induced JNK activation and cell proliferation. C1 Lovelace Fdn Med Educ & Res, Mol Biol & Lung Canc Program, Albuquerque, NM 87108 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Lin, Y (reprint author), Lovelace Fdn Med Educ & Res, Mol Biol & Lung Canc Program, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM ylin@lrri.org NR 53 TC 15 Z9 17 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 2006 VL 281 IS 33 BP 23525 EP 23532 DI 10.1074/jbc.M601487200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 072WE UT WOS:000239702900027 PM 16793775 ER PT J AU Kristof, AS Fielhaber, J Triantafillopoulos, A Nemoto, S Moss, J AF Kristof, Arnold S. Fielhaber, Jill Triantafillopoulos, Alexandra Nemoto, Shino Moss, Joel TI Phosphatidylinositol 3-kinase-dependent suppression of the human inducible nitric-oxide synthase promoter is mediated by FKHRL1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORKHEAD TRANSCRIPTION FACTOR; NF-KAPPA-B; PROTEIN-KINASE B; RAW 264.7 CELLS; GENE-EXPRESSION; SIGNALING PATHWAYS; 3-KINASE ACTIVITY; INTERFERON-GAMMA; FACTOR FKHR-L1; ACTIVATION AB The synthesis of nitric oxide by inducible nitric-oxide synthase (iNOS) plays an important role in the innate immune response by promoting microbial killing and cell damage. In response to inflammatory cytokines and bacterial products, the human iNOS (hiNOS) gene undergoes rapid transcriptional activation via binding of stimulatory transcription factors (e. g. AP-1 and NF-kappa B) to its 5 '-flanking region. However, maximal hiNOS promoter induction was suppressed via an unknown phosphatidylinositol 3-kinase (PI3K)-dependent mechanism. We hypothesized that inhibition of the transcription factor FKHRL1 by the PI3K/protein kinase B pathway attenuates hiNOS promoter induction by bacterial lipopolysaccharide and interferon-gamma (LPS/IFN-gamma). Human lung epithelial adenocarcinoma (A549) cells were transiently transfected with an 8.3-kb hiNOS promoter luciferase reporter construct. Co-expression of dominant-negative protein kinase B potentiated LPS/IFN-gamma-stimulated hiNOS promoter activity. In response to LPS/IFN-gamma FKHRL1 was phosphorylated in a PI3K- and time-dependent fashion. Co-expression of constitutively active FKHRL1 increased hiNOS promoter activity and mRNA levels. Dominant-negative siRNA expression showed that FKHRL1 was necessary for the inhibitory effects of PI3K on hiNOS induction. The same effect was observed upon mutation of a consensus FKHRL1-binding site in the hiNOS promoter. By gel-shift analysis, the corresponding oligonucleotide probe bound endogenous FKHRL1 in an LPS/IFN-gamma- and PI3K-sensitive fashion. Regulation of the hiNOS promoter by FKHRL1 represents a potentially important molecular mechanism by which the PI3K pathway might suppress pro-inflammatory and proapoptotic responses to cytokines and bacterial products. C1 McGill Univ, Royal Victoria Hosp, Crit Care Div, Montreal, PQ H3A 1A1, Canada. McGill Univ, Royal Victoria Hosp, Resp Div, Montreal, PQ H3A 1A1, Canada. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. McGill Univ, Meakins Christie Labs, Montreal, PQ H3A 1A1, Canada. RP Kristof, AS (reprint author), McGill Univ, Royal Victoria Hosp, Crit Care Div, 687 Pine Ave W,Rm L3-05, Montreal, PQ H3A 1A1, Canada. EM arnold.kristof@muhc.mcgill.ca FU Canadian Institutes of Health Research [69007]; Intramural NIH HHS NR 55 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 18 PY 2006 VL 281 IS 33 BP 23958 EP 23968 DI 10.1074/jbc.M513918200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 072WE UT WOS:000239702900070 PM 16687394 ER PT J AU Hanna, M Calkins, D AF Hanna, Michael C. Calkins, David J. TI Expression and sequences of genes encoding glutamate receptors and transporters in primate retina determined using 3'-end amplification polymerase chain reaction SO MOLECULAR VISION LA English DT Article ID AMINO-ACID TRANSPORTER; GATED CHLORIDE CHANNEL; INNER PLEXIFORM LAYER; CONE BIPOLAR CELLS; RAT RETINA; CAT RETINA; DIFFERENTIAL EXPRESSION; KAINATE RECEPTORS; VERTEBRATE RETINA; MAMMALIAN RETINA AB PURPOSE: Our long-term goal is to compare how expression of glutamate receptor and non-vesicular transporter subunits differs between single neurons in the primate retina. Here we set out to ascertain general expression in the retina of Macaca fascicularis using a robust technique suitable for both levels of analysis. We constructed full-complement cDNAs from whole retina RNA using a protocol optimized for detection of even low-abundance transcripts and for transcripts of various lengths. We probed these libraries for expression of genes encoding the AMPA- (GluR1-4) and kainate-sensitive (GluR5-7, KA1-2) ionotropic glutamate receptors, the metabotropic glutamate receptors (mGluR1-8), and five non-vesicular glutamate transporters (EAAT1-5) in the macaque retina and brain and determined large portions of coding sequences for each. We also asked whether each gene can be detected in cDNA generated from a limited amount of RNA extracted from an aldehyde-fixed retinal slice, a technique useful for probing gene expression in tissue used for histological studies. METHODS: We constructed full-length cDNA from RNA harvested from the macaque retina using a modified version of the 3'-end amplification (TPEA) technique of Dixon et al. With this technique, the 3' region is amplified arbitrarily using multiple primers to produce amplified cDNA containing as diverse and complete sample of genes as possible. We probed the cDNA for expression of glutamate receptors and non-vesicular transporters using gene-specific RT-PCR and assembled sequences from the reaction products using a series of overlapping primer pairs. We also used TPEA to compare expression in a small amount of RNA extracted from a fixed retinal slice. RESULTS: Macaque retinal cDNA created using TPEA contains a high abundance of transcripts of various lengths. Gene-specific PCR using primers designed against human sequences indicates expression for all GluR, mGluR, and non-vesicular transporter subunits for which we probed. Expression patterns were similar between two different macaque retinas, but different in brain. Several differences also exist between macaque and human brain. For some subunits, this is the first demonstration of expression in the macaque retina. The expression pattern obtained probing cDNA libraries generated from fixed tissue RNA with a different primer set was similar to that for fresh tissue. We sequenced between 1865 (mGluR8a) and 3697 (mGluR1) total nucleotides for each macaque gene and obtained complete coding sequences for GluR1-7, mGluR3 and mGluR4. A comparison with the corresponding human sequences reveal that the coding region of macaque GluR6 demonstrates the highest homology with only 26 nucleotide substitutions (99% homology), while mGluR4 demonstrates the lowest with 68 substitutions (97.5%). CONCLUSIONS: Neural tissue cDNA created using TPEA contains diverse transcripts of varying size, abundance, and homology. We established using TPEA the expression of all nine AMPA- and kainate-sensitive GluRs, all eight mGluRs and all five non-vesicular glutamate transporters and found that expression differs between macaque retina, macaque brain and human brain. The nucleotide sequences for the coding regions differed moderately between the human and macaque genes. We also found a similar expression pattern in a smaller amount of RNA extracted from a fixed retinal slice. Thus, this technique could be useful for comparing gene expression in cells extracted from fixed tissue pre-labeled using specific markers. C1 Vanderbilt Univ, Med Ctr, Vanderbilt Eye Inst, Dept Ophthalmol & Visual Sci, Nashville, TN 37232 USA. Univ Rochester, Med Ctr, Interdisciplinary Program Neurosci, Rochester, NY 14642 USA. NINDS, NIH, Cellular Neurol Unit, Bethesda, MD USA. RP Calkins, D (reprint author), Vanderbilt Univ, Med Ctr, Vanderbilt Eye Inst, Dept Ophthalmol & Visual Sci, 8000 Med Ctr E, Nashville, TN 37232 USA. EM david.j.calkins@vanderbilt.edu FU NEI NIH HHS [EY12480] NR 65 TC 5 Z9 15 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD AUG 17 PY 2006 VL 12 IS 108-09 BP 961 EP 976 PG 16 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 079FN UT WOS:000240161000001 PM 16943768 ER PT J AU Androutsellis-Theotokis, A Leker, RR Soldner, F Hoeppner, DJ Ravin, R Poser, SW Rueger, MA Bae, SK Kittappa, R McKay, RDG AF Androutsellis-Theotokis, Andreas Leker, Ronen R. Soldner, Frank Hoeppner, Daniel J. Ravin, Rea Poser, Steve W. Rueger, Maria A. Bae, Soo-Kyung Kittappa, Raja McKay, Ronald D. G. TI Notch signalling regulates stem cell numbers in vitro and in vivo SO NATURE LA English DT Article ID HEDGEHOG PATHWAY; NERVOUS-SYSTEM; ADULT BRAIN; DIFFERENTIATION; ACTIVATION; NEUROGENESIS; STAT3; AKT; MEDULLOBLASTOMA; EXPRESSION AB The hope of developing new transplantation therapies for degenerative diseases is limited by inefficient stem cell growth and immunological incompatibility with the host(1,2). Here we show that Notch receptor activation induces the expression of the specific target genes hairy and enhancer of split 3 (Hes3) and Sonic hedgehog (Shh) through rapid activation of cytoplasmic signals, including the serine/threonine kinase Akt, the transcription factor STAT3 and mammalian target of rapamycin, and thereby promotes the survival of neural stem cells. In both murine somatic and human embryonic stem cells, these positive signals are opposed by a control mechanism that involves the p38 mitogen-activated protein kinase. Transient administration of Notch ligands to the brain of adult rats increases the numbers of newly generated precursor cells and improves motor skills after ischaemic injury. These data indicate that stem cell expansion in vitro and in vivo, two central goals of regenerative medicine, may be achieved by Notch ligands through a pathway that is fundamental to development and cancer(3-5). C1 Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP McKay, RDG (reprint author), Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM mckay@codon.nih.gov FU Intramural NIH HHS NR 30 TC 600 Z9 637 U1 7 U2 72 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 17 PY 2006 VL 442 IS 7104 BP 823 EP 826 DI 10.1038/nature04940 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 074DK UT WOS:000239792700048 PM 16799564 ER PT J AU Minkler, M Fuller-Thomson, E Guralnik, JM AF Minkler, Meredith Fuller-Thomson, Esme Guralnik, Jack M. TI Gradient of disability across the socioeconomic spectrum in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SELF-REPORT; HEALTH; INEQUALITIES; PERFORMANCE; DISPARITIES; DETERMINANTS; AGE AB BACKGROUND: Although the relationship between extreme poverty and poor health among older adults has long been recognized, less attention has been devoted to investigating whether a gradient in disability exists in the United States among persons with middle-class and upper-class incomes. We attempted to determine whether a gradient in functional limitation exists across the full spectrum of income among persons 55 years of age or older. METHODS: We obtained data from the Census 2000 Supplementary Survey, which used the methods and questionnaire of the American Community Survey, a nationally representative survey of 890,698 households with a response rate of 95 percent. Our sample included 149,000 men and 186,675 women who were at least 55 years of age, of whom 32,680 men and 48,111 women reported having a functional limitation (a long-lasting condition that substantially limited one or more basic physical activities, such as climbing stairs or lifting). RESULTS: A social-class gradient was observed for both men and women between the ages of 55 and 84, a gradient that held true even at the upper rungs of the socioeconomic ladder. For example, in comparison to persons between the ages of 55 and 64 who lived at 700 percent of the poverty line or above, persons of the same age but below the poverty line had six times the odds of reporting a functional limitation. With increasing income, the odds ratio declined. A significant gradient was present up to, but not beyond, the age of 85 years. CONCLUSIONS: Our findings suggest that functional limitation in Americans between the ages of 55 and 84 years is inversely related to social class across the full spectrum of the socioeconomic gradient. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Univ Toronto, Dept Family & Community Med, Toronto, ON M5S 1A1, Canada. NIA, Dept Demog & Biometry, Lab Epidmeiol, Bethesda, MD 20892 USA. RP Minkler, M (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 316 Warren Hall, Berkeley, CA 94720 USA. EM mink@berkeley.edu FU Intramural NIH HHS NR 31 TC 121 Z9 122 U1 5 U2 12 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 17 PY 2006 VL 355 IS 7 BP 695 EP 703 DI 10.1056/NEJMsa044316 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 074AN UT WOS:000239784500008 PM 16914705 ER PT J AU Gulick, RM Ribaudo, HJ Shikuma, CM Lalama, C Schackman, BR Meyer, WA Acosta, EP Schouten, J Squires, KE Pilcher, CD Murphy, RL Koletar, SL Carlson, M Reichman, RC Bastow, B Klingman, KL Kuritzkes, DR AF Gulick, Roy M. Ribaudo, Heather J. Shikuma, Cecilia M. Lalama, Christina Schackman, Bruce R. Meyer, William A., III Acosta, Edward P. Schouten, Jeffrey Squires, Kathleen E. Pilcher, Christopher D. Murphy, Robert L. Koletar, Susan L. Carlson, Margrit Reichman, Richard C. Bastow, Barbara Klingman, Karin L. Kuritzkes, Daniel R. CA ACTG A5095 Study Team TI Three- vs four-drug antiretroviral regimens for the initial treatment of HIV-1 infection - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID IMMUNODEFICIENCY-VIRUS-INFECTION; REVERSE-TRANSCRIPTASE INHIBITOR; SOCIETY-USA PANEL; NAIVE PATIENTS; ABACAVIR HYPERSENSITIVITY; PROTEASE INHIBITORS; DRUG-RESISTANCE; CLINICAL-TRIALS; PLUS INDINAVIR; THERAPY AB Context Three-drug antiretroviral regimens are standard of care for initial treatment of human immunodeficiency virus 1 (HIV-1) infection, but a 4-drug regimen could improve antiretroviral activity and be more effective than a 3-drug regimen. Objective To compare the safety/efficacy of 3-drug vs 4-drug regimens for initial treatment of HIV-1 infection. Design The AIDS Clinical Trials Group (ACTG) A5095 study, a randomized, double-blind, placebo-controlled study with enrollment and follow-up conducted from March 22, 2001, to March 1, 2005, and enrolling treatment-naive, HIV-1-infected patients with HIV-1 RNA levels of 400 copies/mL or greater from US clinical trials units of the ACTG. Interventions Zidovudine/lamivudine plus efavirenz (3-drug regimen) vs zidovudine/ lamivudine/abacavir plus efavirenz (4-drug regimen). Main Outcome Measures Time to virologic failure ( defined as time to first of 2 successive HIV-1 RNA levels >= 200 copies/mL at or after week 16), CD4 cell count changes, and grade 3 or 4 adverse events. HIV-1 RNA data were intent-to-treat, regardless of treatment changes. Results Seven hundred sixty-five patients with a baseline mean HIV-1 RNA level of 4.86 log(10) ( 72 444) copies/mL and CD4 cell count of 240 cells/mm(3) were randomized. After a median 3-year follow-up, 99 (26%) of 382 and 94 (25%) of 383 patients receiving the 3-drug and 4-drug regimens, respectively, reached protocol-defined virologic failure; time to virologic failure was not significantly different ( hazard ratio, 0.95; 97.5% confidence interval, 0.69-1.33; P=. 73). In planned subgroup analyses, increased risk for virologic failure was seen in non-Hispanic black patients ( adjusted hazard ratio, 1.66; 95% confidence interval, 1.18-2.34; P=. 003). At 3 years, the HIV-1 RNA level was less than 200 copies/mL in 152 (90%) of 169 and 143 (92%) of 156 patients receiving the 3-drug and 4-drug regimens, respectively ( P=. 59), and less than 50 copies/mL in 144 (85%) of 169 and 137 (88%) of 156 patients ( P=. 39). CD4 cell count increases and grade 3 or 4 adverse events were not significantly different. Conclusions In treatment-naive patients, there were no significant differences between the 3-drug and 4-drug antiretroviral regimens; overall, at least approximately 80% of patients had HIV-1 RNA levels less than 50 copies/mL through 3 years. These results support current guidelines recommending 2 nucleosides plus efavirenz for initial treatment of HIV-1 infection; adding abacavir as a fourth drug provided no additional benefit. C1 Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, Cornell HIV Clin Trials Unit, New York, NY 10021 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Hawaii, Honolulu, HI 96822 USA. QuestDiagnost Inc, Baltimore, MD USA. Univ Alabama, Birmingham, AL USA. Univ Washington, Seattle, WA 98195 USA. Univ So Calif, Med Ctr, Los Angeles, CA USA. Univ N Carolina, Chapel Hill, NC USA. Northwestern Univ, Chicago, IL 60611 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Rochester, Rochester, NY USA. Social & Sci Syst Inc, Silver Spring, MD USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RP Gulick, RM (reprint author), Cornell Univ, Weill Med Coll, Div Int Med & Infect Dis, Cornell HIV Clin Trials Unit, Box 566,525 E 68th St, New York, NY 10021 USA. EM rgulick@med.cornell.edu OI Murphy, Robert/0000-0003-3936-2052 FU NCRR NIH HHS [RR00044, RR00047, RR02635, RR00046, RR00096, RR00865, RR00052]; NIAID NIH HHS [AI 38858, AI 50410, AI 38855, AI 34832, AI 32775, AI 27675, AI 27664, AI 28697, AI 27661, AI 46376, AI, 27660, AI 01781, AI 42848, AI 27659, AI 27673, AI 46370, AI 46381, AI 25879, AI 46339, AI 25924, AI 25897, AI 25868, AI 46386, AI 51966, AI 42851, AI 27658, AI 39156, AI 32782, AI 25915, AI 27670, AI 27767, AI 27668, AI 25859, AI 25903] NR 41 TC 149 Z9 152 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 16 PY 2006 VL 296 IS 7 BP 769 EP 781 DI 10.1001/jama.296.7.769 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 073SR UT WOS:000239763400018 PM 16905783 ER PT J AU Swindells, S DiRienzo, AG Wilkin, T Fletcher, CV Margolis, DM Thal, GD Godfrey, C Bastow, B Ray, MG Wang, HY Coombs, RW McKinnon, J Mellors, JW AF Swindells, Susan DiRienzo, A. Gregory Wilkin, Timothy Fletcher, Courtney V. Margolis, David M. Thal, Gary D. Godfrey, Catherine Bastow, Barbara Ray, M. Graham Wang, Hongying Coombs, Robert W. McKinnon, John Mellors, John W. CA AIDS Clinical Trials Grp TI Regimen simplification to atazanavir-ritonavir alone as maintenance antiretroviral therapy after sustained virologic suppression SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HIV-INFECTION; INDUCTION THERAPY; RANDOMIZED-TRIAL; CLINICAL-TRIALS; DRUG THERAPY; RNA; LOPINAVIR/RITONAVIR; SECRETIONS; ADHERENCE; INDINAVIR AB Context The long-term adverse effects, expense, and difficulty of adherence to antiretroviral regimens have led to studies of simpler maintenance therapies. Maintenance therapy with ritonavir-boosted atazanavir alone is a possible option because of low pill burden, once-daily dosing, safety, and unique resistance profile. Objective To assess whether simplified maintenance therapy with atazanavir-ritonavir alone after virologic suppression increases the risk of virologic failure ( 2 consecutive human immunodeficiency virus type 1 [HIV-1] RNA measurements of >= 200 copies/mL). Design, Setting, and Participants Single-group, open-label, multicenter, 24-week pilot study of 36 HIV-infected adults with virologic suppression for 48 weeks or longer receiving their first protease inhibitor (PI)-based regimen. The study was conducted between September 1, 2004, and April 18, 2006, at 12 participating AIDS clinical trial units in the United States. Intervention Participants switched PIs to atazanavir-ritonavir at entry and discontinued nucleoside analog reverse transcriptase inhibitors (NRTIs) after 6 weeks. Main Outcome Measures Virologic failure within 24 weeks of discontinuing NRTIs. Other measures included HIV-1 drug resistance, plasma atazanavir concentrations, adverse events, CD4 cell counts, plasma lipid levels, and HIV-1 RNA levels in seminal plasma. Results Thirty-six participants enrolled and 2 discontinued before simplification to atazanavir-ritonavir alone. Thirty-four patients were included in the analysis of the primary end point after 24 weeks: 1 withdrew voluntarily, and 33 continued the regimen. Virologic success ( absence of failure) through 24 weeks of simplified therapy occurred in 91% ( 31 of 34 patients; lower 90% confidence interval limit = 85%). Three participants experienced virologic failure 12, 14, and 20 weeks after simplification, with plasma HIV-1 RNA levels of 4730, 1285, and 28 397 copies/mL, respectively. Resistance testing at failure did not identify PI resistance mutations. Plasma atazanavir concentrations at failure were low or below detection in 2 of 3 participants experiencing failure. There were no treatment discontinuations for adverse events after simplification; no significant changes in CD4 cell counts or plasma lipid levels; and no detectable HIV-1 RNA in seminal plasma from all 8 participants tested. Conclusions These preliminary data suggest that simplified maintenance therapy with atazanavir-ritonavir alone may be efficacious for maintaining virologic suppression in carefully selected patients with HIV infection. These findings require confirmation in larger, randomized trials of this strategy. C1 Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE 68198 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, Dept Med, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Sch Pharm, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Internal Med, Denver, CO USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. NIAID, HIV Res Branch, Div AIDS, Bethesda, MD 20892 USA. AIDS Clin Trials Grp Operat Ctr, Silver Spring, MD USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA USA. RP Swindells, S (reprint author), Univ Nebraska, Med Ctr, Dept Internal Med, 985400 Nebraska Med Ctr, Omaha, NE 68198 USA. EM sswindells@unmc.edu OI Margolis, David/0000-0001-5714-0002 FU NCATS NIH HHS [KL2 TR000146]; NIAID NIH HHS [AI46376, AI25868, AI25897, AI27661, AI27666, AI32770, AI34832, AI34853, AI38855, AI38858, AI39156, AI46383, AI46386, U01 AI38858] NR 27 TC 66 Z9 66 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 16 PY 2006 VL 296 IS 7 BP 806 EP 814 DI 10.1001/jama.296.7.806 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 073SR UT WOS:000239763400021 PM 16905786 ER PT J AU Morse, CG Kovacs, JA AF Morse, Caryn G. Kovacs, Joseph A. TI Metabolic and skeletal complications of HIV infection - The price of success SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMBINATION ANTIRETROVIRAL THERAPY; INHIBITOR-ASSOCIATED LIPODYSTROPHY; REVERSE-TRANSCRIPTASE INHIBITORS; ADIPOSE-TISSUE ALTERATIONS; LIPID-LOWERING THERAPY; BONE-MINERAL DENSITY; DISEASE RISK-FACTORS; PROTEASE INHIBITORS; INSULIN-RESISTANCE AB Over the past 10 years, in conjunction with the broad availability of potent antiretroviral regimens, the care of human immunodeficiency virus (HIV) infected patients has shifted from prevention and treatment of opportunistic infections and malignancies to management of the metabolic and related complications associated with HIV infection and its treatment. Metabolic disorders, including lipodystrophy, dyslipidemia, and insulin resistance, occur at a high rate in HIV-infected individuals receiving highly active antiretroviral therapy ( HAART). These disorders are associated with increased risk of cardiovascular disease and have become an important cause of morbidity and mortality in HIV-infected patients. Herein, we present the case of a patient with HIV infection who responded well to HAART but developed multiple complications potentially related to this therapy. This article reviews the clinical characteristics of the metabolic and skeletal disturbances observed in HIV infection and discusses strategies for their management. C1 NIAID, Ctr Clin, HIV AIDS Program, Crit Care Med Dept,NIH, Bethesda, MD 20892 USA. RP Kovacs, JA (reprint author), NIAID, Ctr Clin, HIV AIDS Program, Crit Care Med Dept,NIH, Bldg 10,Room 2C145,MSC 1662, Bethesda, MD 20892 USA. EM jkovacs@nih.gov OI Morse, Caryn/0000-0002-1177-4365 FU Intramural NIH HHS NR 95 TC 52 Z9 55 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 16 PY 2006 VL 296 IS 7 BP 844 EP 854 DI 10.1001/jama.296.7.844 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 073SR UT WOS:000239763400024 PM 16905789 ER PT J AU Thompson, IM Chi, C Ankerst, DP Goodman, PJ Tangen, CM Lippman, SM Lucia, MS Parnes, HL Coltman, CA AF Thompson, Ian M. Chi, Chen Ankerst, Donna Pauler Goodman, Phyllis J. Tangen, Catherine M. Lippman, Scott M. Lucia, M. Scott Parnes, Howard L. Coltman, Charles A., Jr. TI Effect of finasteride on the sensitivity of PSA for detecting prostate cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANTIGEN; MEN; PREVENTION; TRIAL; NG/ML AB Background. In the Prostate Cancer Prevention Trial (PCPT), men receiving finasteride had a 24.8% lower risk of prostate cancer than men receiving placebo but a higher risk of high-grade cancer. We examined the impact of finasteride on the sensitivity and area under the receiver operating characteristic curve (AUC) of prostate-specific antigen (PSA) for detecting prostate cancer. Methods: We studied men in the placebo and finasteride groups of the PCPT who had a prostate biopsy and concurrent PSA tests during the 7-year study. We compared the placebo and finasteride groups for sensitivity and AUC of PSA for the detection of all prostate cancer, of Gleason grade 7 or higher prostate cancer, and of Gleason grade 8 or higher prostate cancer. All statistical tests were two-sided. Results: Of 5112 men in the placebo group, prostate cancer was detected in 1111. Gleason tumor grade was available for 1100 men, of whom 240 had grade 7 or higher and 55 had grade 8 or higher. Of 4579 men in the finasteride group, 695 had prostate cancer. Gleason grade was available for 686 men, of whom 264 had grade 7 or higher and 81 had grade 8 or higher. The AUC of PSA for all outcomes was greater for the finasteride group than the placebo group. For detecting prostate cancer versus no cancer, the AUCs were 0.757 and 0.681, respectively (P <.001); for detecting Gleason grade >= 7 versus <= 6 or no cancer, the AUCs were 0.838 and 0.781 , respectively (P=.003); and for detecting Gleason grade :8 versus :57 or no cancer, the AUCs were 0.886 and 0.824, respectively (P=.071). The sensitivity of PSA was higher for men in the finasteride group than in the placebo group at all PSA cutoffs matched by specificity. Conclusions: PSA had statistically significantly better sensitivity and AUC for detecting prostate cancer in the finasteride arm of the PCPT than in the placebo arm. This bias would be expected to contribute to greater detection of all grades of prostate cancer with finasteride. C1 Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX 78229 USA. Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin & Canc Prevent, Houston, TX 77030 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. SW Oncol Grp, San Antonio, TX USA. RP Thompson, IM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Urol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM thompsoni@uthscsa.edu FU NCI NIH HHS [CA37429, CA45808, CA35178]; PHS HHS [U01 86402] NR 10 TC 171 Z9 176 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 AUG 16 PY 2006 VL 98 IS 16 BP 1128 EP 1133 DI 10.1093/jnci/djj307 PG 6 WC Oncology SC Oncology GA 101ED UT WOS:000241720800010 PM 16912265 ER PT J AU Basso, O Wilcox, AJ Weinberg, CR AF Basso, Olga Wilcox, Allen J. Weinberg, Clarice R. TI Birth weight and mortality: Causality or confounding? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE confounding factors (epidemiology); fetal growth retardation; infant, small for gestational age; mortality ID INTRAUTERINE GROWTH-RETARDATION; PERINATAL-MORTALITY; GESTATIONAL-AGE; FETAL-GROWTH AB The association between birth weight and mortality is among the strongest seen in epidemiology. While preterm delivery causes both small babies and high mortality, it does not explain this association. Fetal growth restriction has also been proposed, although its features are unclear because it lacks a definition independent of weight. If, as some postulate, birth weight is not itself on the causal path to mortality, its relation with mortality would have to be explained by confounding factors that decrease birth weight and increase mortality. In this paper, the authors explore the characteristics such confounders would require in order to achieve the observed association between birth weight and mortality. Through a simple simulation, they found that the observed steep gradient of risk for small babies at term can be produced by a rare condition or conditions (with a total prevalence of 0.5%) having profound effects on both fetal growth (-1.7 standard deviations) and mortality (relative risk = 160). Candidate conditions might include malformations, fetal or placental aneuploidy, infections, or imprinting disorders. If such rare factors underlie the association of birth weight with mortality, it would have broad implications for the study of fetal growth restriction and birth weight, and for the prevention of infant mortality. C1 NIEHS, Epidemiol Branch, NIH, HHS,US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), NIEHS, Epidemiol Branch, NIH, HHS,US Dept Hlth & Human Serv, MD A3-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 24 TC 68 Z9 68 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2006 VL 164 IS 4 BP 303 EP 311 DI 10.1093/aje/kwj237 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 073SL UT WOS:000239762800002 PM 16847040 ER PT J AU Schisterman, EF Hernandez-Diaz, S AF Schisterman, Enrique F. Hernandez-Diaz, Sonia TI Invited commentary: Simple models for a complicated reality SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. RP Schisterman, EF (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X NR 2 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2006 VL 164 IS 4 BP 312 EP 314 DI 10.1093/aje/kwj238 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 073SL UT WOS:000239762800003 PM 16847041 ER PT J AU Basso, O Wilcox, AJ Weinberg, CR AF Basso, Olga Wilcox, Allen J. Weinberg, Clarice R. TI Basso et al. Respond to "Simple models for a complicated reality" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 NIEHS, Epidemiol Branch, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, US Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), NIEHS, Epidemiol Branch, NIH, US Dept Hlth & Human Serv, MD A3-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 15 PY 2006 VL 164 IS 4 BP 315 EP 316 DI 10.1093/aje/kwj239 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 073SL UT WOS:000239762800004 ER PT J AU Croxton, TL Bailey, WC AF Croxton, Thomas L. Bailey, William C. CA NHLBI Workin Grp Long-term Oxygen TI Long-term oxygen treatment in chronic obstructive pulmonary disease: Recommendations for future research - An NHLBI workshop report SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE chronic bronchitis; hypoxia; therapy; lung diseases; obstructive; oxygen inhalation therapy; pulmonary emphysema ID CHRONIC RESPIRATORY-FAILURE; CHRONIC LUNG-DISEASE; QUALITY-OF-LIFE; DOMICILIARY OXYGEN; COPD PATIENTS; HYPOXEMIC PATIENTS; SEVERE RETINOPATHY; OXIDATIVE STRESS; RANDOMIZED-TRIAL; PROGNOSTIC VALUE AB Long-term oxygen treatment (LTOT) prolongs life in patients with chronic obstructive pulmonary disease (COPD) and severe resting hypoxemia. Although this benefit is proven by clinical trials, scientific research has not provided definitive guidance regarding who should receive LTOT and how it should be delivered. Deficiencies in knowledge and in current research activity related to LTOT are especially striking in comparison to the importance of LTOT in the management of COPD and the associated costs. The National Heart, Lung, and Blood Institute, in collaboration with the Centers for Medicare and Medicaid Services, convened a working group to discuss research on LTOT. Participants in this meeting identified specific areas in which further investigation would likely lead to improvements in the care of patients with COPD or reductions in the cost of their care. The group recommended four clinical trials in subjects with COPD: (1) efficacy of ambulatory O-2 supplementation in subjects who experience oxyhemoglobin desaturation during physical activity but are not severely hypoxemic at rest; (2) efficacy of LTOT in subjects with severe COPD and only moderate hypoxemia; (3) efficacy of nocturnal O-2 supplementation in subjects who show episodic desaturation during sleep that is not attributable to obstructive sleep apnea; and (4) effectiveness of an activity-dependent prescription for O-2 flow rate that is based on clinical tests performed at rest, during exercise, and during sleep. C1 NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Pulm Allergy & Crit Care Med, Birmingham, AL 35294 USA. RP Croxton, TL (reprint author), NHLBI, Div Lung Dis, NIH, Room 10208,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM croxtont@nhlbi.nih.gov NR 44 TC 81 Z9 86 U1 2 U2 9 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 15 PY 2006 VL 174 IS 4 BP 373 EP 378 DI 10.1164/rccm.200507-1161WS PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 074FG UT WOS:000239797500005 PM 16614349 ER PT J AU Wang, GH Wu, WW Pisitkun, T Hoffert, JD Knepper, MA Shen, RF AF Wang, Guanghui Wu, Wells W. Pisitkun, Trairak Hoffert, Jason D. Knepper, Mark A. Shen, Rong-Fong TI Automated quantification tool for high-throughput proteomics using stable isotope labeling and LC-MSn SO ANALYTICAL CHEMISTRY LA English DT Article ID PROTEIN IDENTIFICATION TECHNOLOGY; TANDEM MASS-SPECTROMETRY; 2-DIMENSIONAL GEL-ELECTROPHORESIS; CODED AFFINITY TAGS; LIQUID-CHROMATOGRAPHY; QUANTITATIVE-ANALYSIS; MIXTURES; EXPRESSION; PEPTIDES; CICAT AB LC-MSn has become a popular option for high-throughput quantitative proteomics, thanks to the availability of stable-isotope labeling reagents. However, the vast quantity of data generated from LC-MSn continues to make the postacquisition quantification analyses challenging, especially in experiments involving multiple samples per experimental condition. To facilitate data analysis, we developed a computer program, QUIL, for automated protein quantification. QUIL accounts for the dynamic nature of spectral background and subtracts this background accordingly during ion chromatogram reconstruction. For elution profile identification, QUIL minimizes the inclusion of coeluted neighbor peaks, yet tolerates imperfect peak shapes. Outlier-resistant methods have been implemented for better protein ratio estimation. The utility of QUIL was validated by quantitative analyses of a standard protein as well as complex protein mixtures, which were labeled with cICAT or O-18 and analyzed using LCQ, LTQ, or FT-ICR instruments. For samples that no prior knowledge of relative protein quantities was available, Western blotting was performed for confirmation. For the standard protein, the coefficient of variation ( CV) of peptide ratio estimation was 6%. For complex mixtures, the median CV for protein ratio calculations was less than 10%. Computed protein abundance ratios exhibited a relatively high degree of correlation with those obtained from Western blot analyses. Compared with a widely used commercial software tool, QUIL showed improvement in ion chromatogram construction and peak integration and significantly reduced relative errors in abundance ratio assessment. C1 NHLBI, Proteom Core Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Shen, RF (reprint author), NHLBI, Proteom Core Facil, NIH, Bldg 10, Bethesda, MD 20892 USA. EM ShenR@nhlbi.nih.gov OI Pisitkun, Trairak/0000-0001-6677-2271 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 40 TC 33 Z9 34 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 15 PY 2006 VL 78 IS 16 BP 5752 EP 5761 DI 10.1021/ac060611v PG 10 WC Chemistry, Analytical SC Chemistry GA 073DO UT WOS:000239723200017 PM 16906720 ER PT J AU Levey, AS Coresh, J Greene, T Stevens, LA Zhang, YP Hendriksen, S Kusek, JW Van Lente, F AF Levey, Andrew S. Coresh, Josef Greene, Tom Stevens, Lesley A. Lucy Zhang, Yaping Hendriksen, Stephen Kusek, John W. Van Lente, Frederick CA Chronic Kidney Dis Epidemiology Co TI Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CHRONIC KIDNEY-DISEASE; COCKCROFT-GAULT EQUATIONS; BODY-MASS INDEX; PREDICTIVE PERFORMANCE; POSITION STATEMENT; GFR; FORMULA; CLEARANCE; TRANSPLANTATION; CLASSIFICATION AB Background: Glomerular filtration rate (GFR) estimates facilitate detection of chronic kidney disease but require calibration of the serum creatinine assay to the laboratory that developed the equation. The 4-variable equation from the Modification of Diet in Renal Disease (MDRD) Study has been reexpressed for use with a standardized assay. Objective: To describe the performance of the revised 4-variable MDRD Study equation and compare it with the performance of the 6-variable MDRD Study and Cockcroft-Gault equations. Design: Comparison of estimated and measured GFR. Setting: 15 clinical centers participating in a randomized, controlled trial. Patients: 1628 patients with chronic kidney disease participating in the MDRD Study. Measurements: Serum creatinine levels were calibrated to an assay traceable to isotope-dilution mass spectrometry. Glomerular filtraton rate was measured as urinary clearance of I-125-iothalamate. Results: Mean measured GFR was 39.8 mL/min per 1.73 m(2) (SD, 21.2). Accuracy and precision of the revised 4-variable equation were similar to those of the original 6-variable equation and better than in the Cockcroft-Gault equation, even when the latter was corrected for bias, with 90%, 91%, 60%, and 83% of estimates within 30% of measured GFR, respectively. Differences between measured and estimated GFR were greater for all equations when the estimated GFR was 60 mL/min per 1.73 m(2) or greater. Limitations: The MDRD Study included few patients with a GFR greater than 90 mL/min per 1.73 m(2). Equations were not compared in a separate study sample. Conclusions: The 4-variable MDRD Study equation provides reasonably accurate GFR estimates in patients with chronic kidney disease and a measured GFR of less than 90 mL/min per 1.73 m(2). By using the reexpressed MDRD Study equation with the standardized serum creatinine assay, clinical laboratories can report more accurate GFR estimates. C1 Tufts Univ, New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIDDK, Bethesda, MD USA. RP Levey, AS (reprint author), Tufts Univ, New England Med Ctr, Div Nephrol, 750 Washington St,Box 391, Boston, MA 02111 USA. FU NIDDK NIH HHS [UO1 DK 053869, UO1 DK 067651, UO1 DK 35073] NR 45 TC 2311 Z9 2365 U1 4 U2 40 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 15 PY 2006 VL 145 IS 4 BP 247 EP 254 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 075CC UT WOS:000239858800002 PM 16908915 ER PT J AU Lee, JS Tucker, MA AF Lee, Jennifer S. Tucker, Margaret A. TI Making sense of puzzling genetic association studies: A team approach SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID D-RECEPTOR GENE; CDX-2 POLYMORPHISM; BONE-DENSITY; OSTEOPOROSIS; WOMEN; FRACTURE; EPIDEMIOLOGY; RISK; BMD C1 NCI, Div Canc Epidmeiol & Genet, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, San Francisco, CA 94110 USA. RP Tucker, MA (reprint author), NCI, Div Canc Epidmeiol & Genet, Genet Epidemiol Branch, NIH, 6120 Execut Blvd,EPS 7122, Bethesda, MD 20892 USA. EM tuckerp@exchange.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS NR 20 TC 2 Z9 2 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 15 PY 2006 VL 145 IS 4 BP 302 EP 304 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 075CC UT WOS:000239858800009 PM 16908922 ER PT J AU Inoue, K Borchers, CH Negishi, M AF Inoue, Kaoru Borchers, Christoph H. Negishi, Masahiko TI Cohesin protein SMC1 represses the nuclear receptor CAR-mediated synergistic activation of a human P450 gene by xenobiotics SO BIOCHEMICAL JOURNAL LA English DT Article DE affinity chromatography; constitutive active/androstane receptor (CAR); cytochrome P450 (CYP); phenobarbital-responsive enhancer module; structural maintenance of chromosomes 1 (SMC1); xenobiotic ID CONSTITUTIVE ANDROSTANE RECEPTOR; THYROID-HORMONE METABOLISM; HEPG2 CELLS; CYP2B GENE; INDUCTION; CONDENSIN; ELEMENTS; MICE; DNA AB CAR (constitutive active/androstane receptor) regulates both the distal enhancer PBREM (phenobarbital-responsive enhancer module) and the proximal element OARE [OA (okadaic acid) response element] to synergistically up-regulate the endogenous CYP2B6 (where CYP is cytochrome P450) gene in HepG2 cells. In this up-regulation, CAR acts as both a transcription factor and a co-regulator, directly binding to and enhancing PBREM upon activation by xenobiotics such as TCPOBOP {1,4-bis-[2 -(3,5-dichloropyridyloxy)]benzene} and indirectly associating with the OARE in response to OA [Swales, Kakizaki, Yamamoto, Inoue, Kobayashi and Negishi (2005) J. Biol. Chem. 280, 34583466]. We have now identified the cohesin protein SMC1 (structural maintenance of chromosomes 1) as a CAR-binding protein and characterized it as a negative regulator of OARE activity, thus repressing synergy. Treatment with SMC1 small interfering RNA augmented the synergistic up-regulation of CYP2B6 expression 20-fold in HepG2 cells, while transient co-expression of spliced form of SMC1 abrogated the synergistic activation of a 1.8 kb CYP2B6 promoter. SMC1 indirectly binds to a 19 bp sequence (-236/-217) immediately downstream from the OARE in the CYP2B6 promoter. Both DNA affinity and chromatin immunoprecipitation assays showed that OA treatment dissociates SMC1 from the CYP2B6 promoter, reciprocating the indirect binding of CAR to OARE. These results are consistent with the conclusion that SMC1 binding represses OARE activity and its dissociation allows the recruitment of CAR to the OARE, synergizing PBREM activity and the expression of the CYP2B6 gene. C1 NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biophys & Biochem, Chapel Hill, NC 27816 USA. RP Negishi, M (reprint author), NIEHS, Reprod & Dev Toxicol Lab, Pharmacogenet Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 28 TC 13 Z9 14 U1 1 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 15 PY 2006 VL 398 BP 125 EP 133 DI 10.1042/BJ20060109 PN 1 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074UA UT WOS:000239836100013 PM 16623664 ER PT J AU Wang, ZL Stalcup, LD Harvey, BJ Weber, J Chloupkova, M Dumont, ME Dean, M Urbatsch, IL AF Wang, Zhanling Stalcup, Lindsay D. Harvey, Brandy J. Weber, Joachim Chloupkova, Maja Dumont, Mark E. Dean, Michael Urbatsch, Ina L. TI Purification and ATP hydrolysis of the putative cholesterol transporters ABCG5 and ABCG8 SO BIOCHEMISTRY LA English DT Article ID PLANT STEROL ABSORPTION; PICHIA-PASTORIS CELLS; P-GLYCOPROTEIN; DIETARY-CHOLESTEROL; CATALYTIC SITES; SACCHAROMYCES-CEREVISIAE; SER RESIDUES; BINDING; SITOSTEROLEMIA; NUCLEOTIDE AB Mutations in the ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 lead to sitosterolemia, a disorder characterized by sterol accumulation and premature atherosclerosis. ABCG5 and ABCG8 are both half-size transporters that have been proposed to function as heterodimers in vivo. We have expressed the recombinant human ABCG5 and ABCG8 genes in the yeast Pichia pastoris and purified the proteins to near homogeneity. Purified ABCG5 and ABCG8 had very low ATPase activities (< 5 nmol min(-1) mg(-1)), suggesting that expression of ABCG5 or ABCG8 alone yielded nonfunctional transporters. Coexpression of the two genes in P. pastoris greatly increased the yield of pure proteins, indicating that the two transporters stabilize each other during expression and purification. Copurified ABCG5/G8 displayed low but significant ATPase activity with a V-max of similar to 15 nmol min(-1) mg(-1). The ATPase activity was not stimulated by sterols. The catalytic activity of copurified ABCG5/G8 was characterized in detail, demonstrating low affinity for MgATP, a preference for Mg as a metal cofactor and ATP as a hydrolyzed substrate, and a pH optimum near 8.0. AlFx and BeFx inhibited MgATP hydrolysis by specific trapping of nucleotides in the ABCG5/G8 proteins. Furthermore, ABCG5/G8 eluted as a dimer on gel filtration columns. The data suggest that the hetero-dimer is the catalytically active species, and likely the active species in vivo. C1 Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79430 USA. Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97239 USA. Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Urbatsch, IL (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Biochem & Cell Biol, Lubbock, TX 79430 USA. EM ina.urbatsch@ttuhsc.edu RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 52 TC 21 Z9 24 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 15 PY 2006 VL 45 IS 32 BP 9929 EP 9939 DI 10.1021/bi0608055 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 071JD UT WOS:000239596600029 PM 16893193 ER PT J AU Anderson, KC Insel, BR AF Anderson, Kathleen C. Insel, Thomas R. TI The promise of extinction research for the prevention and treatment of anxiety disorders SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID FEAR EXTINCTION; D-CYCLOSERINE; CAENORHABDITIS-ELEGANS; PREFRONTAL CORTEX; MEMORY; AMYGDALA; ACQUISITION; CONTEXT C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Anderson, KC (reprint author), NIMH, NIH, Dept Hlth & Human Serv, 6001 Execut Blvd,Room 7172,MSC 9637, Bethesda, MD 20892 USA. EM kanders1@mail.nih.gov FU Intramural NIH HHS [001-1364-225, Z99 MH999999] NR 22 TC 42 Z9 43 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 2006 VL 60 IS 4 BP 319 EP 321 DI 10.1016/j.biopsych.2006.06.022 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 074UK UT WOS:000239837100002 PM 16919521 ER PT J AU Stagliano, KW Emadi, A Lu, ZH Malinakova, HC Twenter, B Yu, M Holland, LE Rom, AM Harwood, JS Amin, R Johnson, AA Pommier, Y AF Stagliano, Kenneth W. Emadi, Ashkan Lu, Zhenhai Malinakova, Helena C. Twenter, Barry Yu, Min Holland, Louis E. Rom, Amanda M. Harwood, John S. Amin, Ronak Johnson, Allison A. Pommier, Yves TI Regiocontrolled synthesis and HIV inhibitory activity of unsymmetrical binaphthoquinone and trimeric naphthoquinone derivatives of conocurvone SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE biquinones and trimeric quinones; HIV-1 integrase inhibitor; regiocontrolled synthesis; conocurvone ID IMMUNODEFICIENCY-VIRUS TYPE-1; INTEGRASE INHIBITORS; GENE-EXPRESSION; DNA INTEGRATION; STRAND TRANSFER; IN-VITRO; DISCOVERY; PRODUCTS; PROTEIN; CELLS AB Unsymmetrical biquinone and trimeric quinone derivatives were synthesized using halotriflate-biselectrophilic naphthoquinones through stepwise regioselective quinone substitution chemistry and evaluated for their ability to inhibit the cytopathogenic effects of HIV-1 using an MTT colorimetric assay. Compounds were also screened for their ability to inhibit the activity of HIV-1 integrase in vitro. Pyranylated trimeric quinones and biquinones exhibited both antiviral activity and integrase inhibitory activity. Conocurvone 1 and trimeric quinone 21 were the most potent HIV integrase inhibitors in the series. All of the biquinones showed HIV inhibitory activity. Simple methoxy substituted biquinones did not inhibit HIV-1 integrase. Published by Elsevier Ltd. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. IIT, Res Inst, Chicago, IL 60616 USA. Univ Illinois, Dept Chem, Chicago, IL 60607 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI43687] NR 56 TC 27 Z9 28 U1 0 U2 6 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 AUG 15 PY 2006 VL 14 IS 16 BP 5651 EP 5665 DI 10.1016/j.bmc.2006.04.034 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 069UB UT WOS:000239472700025 PM 16737818 ER PT J AU George, TG Johnsamuel, J Delfin, DA Yakovich, A Mukherjee, M Phelps, MA Dalton, JT Sackett, DL Kaiser, M Brun, R Werbovetz, KA AF George, Tesmol G. Johnsamuel, Jayaseharan Delfin, Dawn A. Yakovich, Adam Mukherjee, Mitali Phelps, Mitch A. Dalton, James T. Sackett, Dan L. Kaiser, Marcel Brun, Reto Werbovetz, Karl A. TI Antikinetoplastid antimitotic activity and metabolic stability of dinitroaniline sulfonamides and benzamides SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Leishmania; trypanosome; chemotherapy; tubulin; dinitroaniline ID DIHYDROFOLATE-REDUCTASE; TRYPANOSOMA-CRUZI; TUBULIN; LEISHMANIA; HERBICIDES; TRIFLURALIN; INHIBITORS; PURIFICATION; PLASMODIUM; PARASITES AB N-1-Phenyl-3,5-dinitro-N-4,N-4-di-n-propylsulfanilamide (1) and N-1-phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (2) show potent in vitro antimitotic activity against kinetoplastid parasites but display poor in vivo activity. Seventeen new dinitroaniline sulfonamide and eleven new benzamide analogs of these leads are reported here. Nine of the sulfonamides display in vitro IC50 values under 500 nM against African trypanosomes, and the most active antikinetoplastid compounds also inhibit the in vitro assembly of purified leishmanial tubulin with potencies similar to that of 2. While several of the potent compounds are rapidly degraded by rat liver S9 fractions in vitro, N-1-(3-hydroxy)phenyl-3,5-dinitro-N-4,N-4-di-n-butylsulfanilamide (21) displays an IC50 value of 260 nM against African trypanosomes in vitro and is more stable than 2 in the in vitro metabolism assay. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Swiss Trop Inst, CH-4002 Basel, Switzerland. RP Werbovetz, KA (reprint author), Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, 500 W 12th Ave, Columbus, OH 43210 USA. EM werbovetz.l@osu.edu RI Werbovetz, Karl/E-4290-2011; Phelps, Mitch/H-3941-2013; OI Phelps, Mitch/0000-0002-1615-5280; dalton, James T/0000-0002-3915-7326; Kaiser, Marcel/0000-0003-1785-7302 FU NIAID NIH HHS [AI061021] NR 26 TC 17 Z9 17 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD AUG 15 PY 2006 VL 14 IS 16 BP 5699 EP 5710 DI 10.1016/j.bmc.2006.04.017 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 069UB UT WOS:000239472700031 PM 16675220 ER PT J AU Uto, Y Ae, S Koyama, D Sakakibara, M Otomo, N Otsuki, M Nagasawa, H Kirk, KL Hori, H AF Uto, Yoshihiro Ae, Shutaro Koyama, Daisuke Sakakibara, Mitsutoshi Otomo, Naoki Otsuki, Mamoru Nagasawa, Hideko Kirk, Kenneth L. Hori, Hitoshi TI Artepillin C isoprenomics: Design and synthesis of artepillin C isoprene analogues as lipid peroxidation inhibitor having low mitochondrial toxicity SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE artepillin C isoprene analogue; isoprenomics; lipid peroxidation inhibitor; rat liver mitochondria ID BRAZILIAN PROPOLIS; ANTIOXIDANT ACTIVITY; ACIDS AB We designed and synthesized isoprene analogues of artepillin C, a major component of Brazilian propolis, and investigated the inhibitory activity on lipid peroxidation of rat liver mitochondria (RLM) and RLM toxicity based on isoprenomics. We succeeded in the synthesis of artepillin C isoprene analogues using regioselective prenylation within the range from 22% to 53% total yield. Reactivity of artepillin C and its isoprene analogues with ABTS (2,2'-Azinobis(3-ethylbenzothiazoline-6-sulfonate)) radical cations showed only a slight difference among the molecules. The isoprene side-chain elongation analogues of artepillin C showed almost the same inhibitory activity against RLM lipid peroxidation as artepillin C. Artepillin C and its isoprene analogues had very weak RLM uncoupling activity. Moreover, artepillin C and its isoprene analogues exhibited a lower inhibitory activity against adenosine 5'-triphosphate (ATP) synthesis by about two orders of magnitude than the effective inhibitory activity against RLM lipid peroxidation. From these results we conclude that artepillin C isoprene analogues could be potent lipid peroxidation inhibitors having low mitochondrial toxicity. We also conclude that elongation of the isoprene side chain of artepillin C to increase lipophilicity had little influence on the inhibitory activity toward RLM lipid peroxidation. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Tokushima, Fac Engn, Dept Biol Sci & Technol, Tokushima 7708506, Japan. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hori, H (reprint author), Univ Tokushima, Fac Engn, Dept Biol Sci & Technol, Minamijosanjimacho 2, Tokushima 7708506, Japan. EM hori@bio.tokushima-u.ac.jp FU Intramural NIH HHS NR 28 TC 13 Z9 14 U1 3 U2 9 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 AUG 15 PY 2006 VL 14 IS 16 BP 5721 EP 5728 DI 10.1016/j.bmc.2006.04.015 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 069UB UT WOS:000239472700033 PM 16697207 ER PT J AU Morrell, A Jayaraman, M Nagarajan, M Fox, BM Meckley, MR Ioanoviciu, A Pommier, Y Antony, S Hollineshead, M Cushman, M AF Morrell, Andrew Jayaraman, Muthusamy Nagarajan, Murakaman Fox, Brian M. Meckley, Marintha Rae Ioanoviciu, Alexandra Pommier, Yves Antony, Smitha Hollineshead, Melinda Cushman, Mark TI Evaluation of indenoisoquinoline topoisomerase I inhibitors using a hollow fiber assay SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE indenoisoquinoline; topoisomerase I inhibitor; anticancer; hollow fiber assay ID BIOLOGICAL EVALUATION; ANTICANCER ACTIVITY; VIVO; MODEL; NCI; POISONS; COMPLEX; DESIGN; TARGET; VITRO AB The indenoisoquinolines are a novel class of non-camptothecin topoisomerase I (Top1) inhibitors whose mechanism of action involves trapping the covalent complex formed between DNA and Top I during cellular processes. As an ongoing evaluation of the indenoisoquitiolines for Top1 inhibition and anticancer activity, indenoisoquinoline analogs have been screened in the National Cancer Institute's hollow fiber assay (HFA). Some of the derivatives demonstrated significant activity at intraperitoneal and subcutaneous fiber placement sites, along with net cancer cell kill in one or more cell lines. (c) 2006 Elsevier Ltd. All rights reserved. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Sch Pharm & Pharmaceut Sci, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH,Fairview Ctr, Frederick, MD 21701 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [N01-CO-56000, ST32 CA09634-12, U01 CA89566] NR 27 TC 14 Z9 15 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD AUG 15 PY 2006 VL 16 IS 16 BP 4395 EP 4399 DI 10.1016/j.bmcl.2006.05.048 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 068CI UT WOS:000239349000047 PM 16750365 ER PT J AU Sprague, BL Muller, F Pego, RL Bungay, PM Stavreva, DA McNally, JG AF Sprague, Brian L. Muller, Florian Pego, Robert L. Bungay, Peter M. Stavreva, Diana A. McNally, James G. TI Analysis of binding at a single spatially localized cluster of binding sites by fluorescence recovery after photobleaching SO BIOPHYSICAL JOURNAL LA English DT Article ID LIVING CELLS; IN-VIVO; GLUCOCORTICOID-RECEPTOR; NUCLEAR PROTEINS; FRAP ANALYSIS; DYNAMICS; EXCHANGE; QUANTIFICATION; PARAMETERS; TRANSPORT AB Cells contain many subcellular structures in which specialized proteins locally cluster. Binding interactions within such clusters may be analyzed in live cells using models for fluorescence recovery after photobleaching ( FRAP). Here we analyze a three-dimensional FRAP model that accounts for a single spatially localized cluster of binding sites in the presence of both diffusion and impermeable boundaries. We demonstrate that models completely ignoring the spatial localization of binding yield poor estimates for the binding parameters within the binding site cluster. In contrast, we find that ignoring only the restricted axial height of the binding-site cluster is far less detrimental, thereby enabling the use of computationally less expensive models. We also identify simplified solutions to the FRAP model for limiting behaviors where either diffusion or binding dominate. We show how ignoring a role for diffusion can sometimes produce serious errors in binding parameter estimation. We illustrate application of the method by analyzing binding of a transcription factor, the glucocorticoid receptor, to a tandem array of mouse mammary tumor virus promoter sites in live cells, obtaining an estimate for an in vivo binding constant (10(-7) M), and a first approximation of an upper bound on the transcription-factor residence time at the promoter (similar to 170 ms). These FRAP analysis tools will be important for measuring key cellular binding parameters necessary for a complete and accurate description of the networks that regulate cellular behavior. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD USA. ORS, Div Bioengn & Phys Sci, NIH, Bethesda, MD USA. Carnegie Mellon Univ, Dept Math Sci, Pittsburgh, PA USA. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD USA. EM mcnallyj@exchange.nih.gov RI Sprague, Brian/A-8923-2009; Mueller, Florian/C-9075-2012; Pego, Robert/A-7641-2017 OI Mueller, Florian/0000-0002-9622-4396; Pego, Robert/0000-0001-8502-2820 FU Intramural NIH HHS NR 25 TC 56 Z9 57 U1 1 U2 11 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG 15 PY 2006 VL 91 IS 4 BP 1169 EP 1191 DI 10.1529/biophysj.105.073676 PG 23 WC Biophysics SC Biophysics GA 066PK UT WOS:000239242000007 PM 16679358 ER PT J AU Schlucker, S Liang, C Strehle, KR DiGiovanna, JJ Kraemer, KH Levin, IW AF Schlucker, S. Liang, C. Strehle, K. R. DiGiovanna, J. J. Kraemer, K. H. Levin, I. W. TI Conformational differences in protein disulfide linkages between normal hair and hair from subjects with trichothiodystrophy: A quantitative analysis by Raman microspectroscopy SO BIOPOLYMERS LA English DT Article DE trichothiodystrophy; human hair; hair proteins; disulfide conformers; Raman microspectroscopy; quantitative analysis; density junctional calculations ID FOURIER-TRANSFORM RAMAN; WOOL FIBER KERATIN; DEFICIENT BRITTLE HAIR; CS STRETCH FREQUENCIES; FT-RAMAN; STRUCTURAL-CHANGES; MOLECULAR-CONFORMATIONS; DIALKYL DISULFIDES; SPECTROSCOPY FTR; INFRARED FTIR AB Raman spectra of normal hair shafts and hair shafts from patients exhibiting trichothiodystrophy (TTD) were obtained using line focus laser illumination. Because hair from TTD patients has a significant decrease in the content of the sulfur-containing amino acids in comparison to normal hair, the 550-500 cm(-1) disulfide stretching mode region of the Raman spectrum was examined in detail. A quantitative spectral analysis demonstrates significant increases in the two energetically less favored gauche-gauche-trans (g-g-t) and trans-gauche-trans (t-g-t) forms. These observations suggest that the increased amounts of these less stable disulfide conformers are contributing factors to or associated with the hair brittleness observed for this congenital disorder. Structure-spectra correlations for the three dominant disulfide conformers are confirmed by quantum chemical calculations using modern density functional theory (DFT). (c) 2006 Wiley Periodicals, Inc. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Inst Chem Phys, D-97074 Wurzburg, Germany. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02912 USA. RP Levin, IW (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM uwl@helix.nih.gov RI Schlucker, Sebastian/D-1031-2010 OI Schlucker, Sebastian/0000-0003-4790-4616 FU Intramural NIH HHS [Z01 BC004517-31] NR 48 TC 30 Z9 31 U1 0 U2 19 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD AUG 15 PY 2006 VL 82 IS 6 BP 615 EP 622 DI 10.1002/bip.20515 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 065ZJ UT WOS:000239198700008 PM 16557500 ER PT J AU Rezvani, K Mielke, S Ahmadzadeh, M Kilical, Y Savani, BN Zeilah, J Keyvanfar, K Montero, A Hensel, N Kurlander, R Barrett, AJ AF Rezvani, Katayoun Mielke, Stephan Ahmadzadeh, Mojgan Kilical, Yasemin Savani, Bipin N. Zeilah, Josette Keyvanfar, Keyvan Montero, Aldemar Hensel, Nancy Kurlander, Roger Barrett, A. John TI High donor FOXP3-positive regulatory T-cell (T-reg) content is associated with a low risk of GVHD following HLA-matched allogeneic SCT SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; PERIPHERAL-BLOOD; IN-VITRO; CYCLOSPORINE-A; CUTTING EDGE; TOLERANCE; CD4(+); FOXP3 AB Regulatory T cells (TregS) that constitutively express FOXP3 are instrumental to the maintenance of tolerance and may suppress graft-versus-host disease (GVHD) in humans. To determine whether regulatory T cells in allogeneic stem cell transplants (SCTS) ameliorate GVHD after transplantation, we quantitated the coexpression of FOXP3 on CD4(+) T cells in 32 donor SCTs infused into HLA-matched siblings and examined GVHD incidence in respective recipients. High CD4(+)FOXP3(+) T-cell count in the donor was associated with a reduced risk of GVHD. We monitored T(reg)s during immune reconstitution in 21 patients with leukemia undergoing a T-cell-depleted allogeneic SCT. Early after SCT, there was a significant expansion in the CD4(+)FOXP3(+) T-cell compartment. A low CD4(+)FOXP3(+) T-cell count early after SCT, (day 30) was associated with an increased risk of GVHD, and the ratio of CD4(+)FOXP3(+) T cells to CD4(+)CD25(+)FOXP3(-) T cells was significantly reduced in patients with GVHD, suggesting diminished control of effector T cells. Our findings suggest that graft T-reg content may predict for risk of GVHD after SCT Determining the T-reg levels in the donor and manipulating T-regs early after transplantation may provide a new approach to controlling GVHD. C1 NHLBI, Stem Cell Allogenec Transplant Sect, Hematol Branch, DIR,NIH, Bethesda, MD 20892 USA. NCI, Dept Surg, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Rezvani, K (reprint author), NHLBI, Stem Cell Allogenec Transplant Sect, Hematol Branch, DIR,NIH, Bldg 10 CRC Rm 3-5288,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM rezvanik@nhlbi.nih.gov NR 47 TC 209 Z9 232 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 AUG 15 PY 2006 VL 108 IS 4 BP 1291 EP 1297 DI 10.1182/blood-2006-02-003996 PG 7 WC Hematology SC Hematology GA 072UP UT WOS:000239698800032 PM 16627754 ER PT J AU Lobito, AA Kimberley, FC Muppidi, JR Komarow, H Jackson, AJ Hull, KM Kastner, DL Screaton, GR Siegel, RM AF Lobito, Adrian A. Kimberley, Fiona C. Muppidi, Jagan R. Komarow, Hirsh Jackson, Adrianna J. Hull, Keith M. Kastner, Daniel L. Screaton, Gavin R. Siegel, Richard M. TI Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in TNFR1-associated periodic fever syndrome (TRAPS) SO BLOOD LA English DT Article ID NF-KAPPA-B; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; FACTOR RECEPTOR-I; ENDOPLASMIC-RETICULUM; AUTOINFLAMMATORY DISORDER; MISFOLDED PROTEINS; SURFACE EXPRESSION; CYSTIC-FIBROSIS; CELL-DEATH; ACTIVATION AB Tumor necrosis factor (TNF) receptor-associated periodic syndrome (TRAPS) is an autosomal dominant systemic autoinflammatory disease associated with heterozygous mutations in TNF receptor 1 (TNFR1). Here we examined the structural and functional alterations caused by 9 distinct TRAPS-associated TNFR1 mutations in transfected cells and a mouse "knock-in" model of TRAPS. We found that these TNFR1 mutants did not generate soluble versions of the receptor, either through membrane cleavage or in exosomes. Mutant receptors did not bind TNF and failed to function as dominant-negative inhibitors of TNFR1-induced apoptosis. Instead, TRAPS mutant TNFR1 formed abnormal disulfide-linked oilgomers that failed to interact with wildtype TNFR1 molecules through the preligand assembly domain (PLAD) that normally governs receptor self-association. TRAPS mutant TNFR1 molecules were retained intracellularly and colocalized with endoplasmic reticulum (ER) markers. The capacity of mutant receptors to spontaneously induce both apoptosis and nuclear factor kappa B (NF-kappa B) activity was reduced. In contrast, the R920 variant of TNFR1 behaved like the wild-type receptor in all of these assays. The inflammatory phenotype of TRAPS may be due to consequences of mutant TNFR1 protein misfolding and ER retention. C1 NIAMS, Autoimmun Branch, Immunoregulat Unit, NIH, Bethesda, MD 20892 USA. NIAMS, Inflammatory Biol Sect, Genet & Gen Branch, NIH, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England. RP Siegel, RM (reprint author), NIAMS, Autoimmun Branch, Immunoregulat Unit, NIH, Bldg 10,Rm 9N238, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 NR 38 TC 120 Z9 124 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 AUG 15 PY 2006 VL 108 IS 4 BP 1320 EP 1327 DI 10.1182/blood-200511-006783 PG 8 WC Hematology SC Hematology GA 072UP UT WOS:000239698800036 PM 16684962 ER PT J AU Chiu, BCH Dave, BJ Blair, A Gapstur, SM Zahm, SH Weisenburger, DD AF Chiu, Brian C. -H. Dave, Bhavana J. Blair, Aaron Gapstur, Susan M. Zahm, Shelia Hoar Weisenburger, Dennis D. TI Agricultural pesticide use and risk of t(14;18)-defined subtypes of non-Hodgkin lymphoma SO BLOOD LA English DT Article ID HEALTHY-INDIVIDUALS; BCL-2 GENE; EXPOSURE; CANCER; TRANSLOCATION; GENOTOXICITY; EPIDEMIOLOGY; MORTALITY; APPLIERS; LEUKEMIA AB Pesticides have been specifically associated with the t(14;18)(q32;q21) chromosomal translocation. To investigate whether the association between pesticides and risk of non-Hodgkin lymphoma (NHL) differs for molecular subtypes of NHL defined by t(14; 18) status, we obtained 175 tumor blocks from case subjects in a population-based case-control study conducted in Nebraska between 1983 and 1986. The t(14;18) was determined by interphase fluorescence in situ hybridization in 172 of 175 tumor blocks. We compared exposures to insecticides, herbicides, fungicides, and fumigants in 65 t(14;18)-positive and 107 t(14;18)-negative case subjects with those among 1432 control subjects. Multivariate polytomous logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Compared with farmers who never used pesticides, the risk of t(l 4;1 8)-positive NHL was significantly elevated among farmers who used animal insecticides (OR = 2.6; 95% CI, 1.0-6.9), crop insecticides (OR = 3.0; 95% CI, 1.1-8.2), herbicides (OR = 2.9; 95% CI, 1.1-7.9), and fumigants (OR = 5.0; 95% CI, 1.7-14.5). None of these pesticides were associated with t(14;18)-negative NHL. The risk of t(14;18)-positive NHL associated with insecticides and herbicides increased with longer duration of use. We conclude that insecticides, herbicides, and fumigants were associated with risk of t(14;18)-positive NHL but not t(14;18)-negative NHL. These results suggest that defining subsets of NHL according to t(14;18) status is a useful approach for etiologic research. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Nebraska Med Ctr, Munroe Meyer Inst Genet & Rehabil, Omaha, NE 68198 USA. Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chiu, BCH (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Ste 1102, Chicago, IL 60611 USA. EM bchiu@northwestern.edu RI Zahm, Shelia/B-5025-2015 FU Intramural NIH HHS; NCI NIH HHS [R03 CA094770-01, Z01 CP010120-10, CA94770] NR 43 TC 52 Z9 53 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2006 VL 108 IS 4 BP 1363 EP 1369 DI 10.1182/blood-2005-12-008755 PG 7 WC Hematology SC Hematology GA 072UP UT WOS:000239698800042 PM 16621961 ER PT J AU Sambrook, JG Bashirova, A Andersen, H Piatak, M Vernikos, GS Coggill, P Lifson, JD Carrington, M Beck, S AF Sambrook, Jennifer G. Bashirova, Arman Andersen, Hanne Piatak, Mike Vernikos, George S. Coggill, Penny Lifson, Jeff D. Carrington, Mary Beck, Stephan TI Identification of the ancestral killer immunoglobulin-like receptor gene in primates SO BMC GENOMICS LA English DT Article ID IG-LIKE RECEPTORS; RAPID EVOLUTION; CELL RECEPTORS; MOUSE; KIR; ORGANIZATION; DIVERSITY; MOLECULES; SOFTWARE; FAMILIES AB Background: Killer Immunoglobulin-like Receptors (KIR) are essential immuno- surveillance molecules. They are expressed on natural killer and T cells, and interact with human leukocyte antigens. KIR genes are highly polymorphic and contribute vital variability to our immune system. Numerous KIR genes, belonging to five distinct lineages, have been identified in all primates examined thus far and shown to be rapidly evolving. Since few KIR remain orthologous between species, with only one of them, KIR2DL4, shown to be common to human, apes and monkeys, the evolution of the KIR gene family in primates remains unclear. Results: Using comparative analyses, we have identified the ancestral KIR lineage ( provisionally named KIR3DL0) in primates. We show KIR3DL0 to be highly conserved with the identification of orthologues in human ( Homo sapiens), common chimpanzee ( Pan troglodytes), gorilla ( Gorilla gorilla), rhesus monkey ( Macaca mulatta) and common marmoset ( Callithrix jacchus). We predict KIR3DL0 to encode a functional molecule in all primates by demonstrating expression in human, chimpanzee and rhesus monkey. Using the rhesus monkey as a model, we further show the expression profile to be typical of KIR by quantitative measurement of KIR3DL0 from an enriched population of natural killer cells. Conclusion: One reason why KIR3DL0 may have escaped discovery for so long is that, in human, it maps in between two related leukocyte immunoglobulin-like receptor clusters outside the known KIR gene cluster on Chromosome 19. Based on genomic, cDNA, expression and phylogenetic data, we report a novel lineage of immunoglobulin receptors belonging to the KIR family, which is highly conserved throughout 50 million years of primate evolution. C1 Wellcome Trust Sanger Inst, Immunogenom Lab, Cambridge CB10 1SA, England. SAIC Frederick, Natl Canc Inst, Lab Genom Divers, Frederick, MD 21702 USA. SAIC Frederick, Retroviral Pathogenesis Lab, AIDS Vaccine Program, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Lab Genom, Frederick, MD 21702 USA. RP Beck, S (reprint author), Wellcome Trust Sanger Inst, Immunogenom Lab, Genome Campus, Cambridge CB10 1SA, England. EM js8@sanger.ac.uk; bashirovaa@ncifcrf.gov; handersen@bioqual.com; piatakm@ncifcrf.gov; gsv@sanger.ac.uk; pcc@sanger.ac.uk; lifson@ncifcrf.gov; carringt@ncifcrf.gov; beck@sanger.ac.uk FU NCI NIH HHS [N01CO12400, N01-CO-12400]; Wellcome Trust NR 32 TC 36 Z9 37 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD AUG 15 PY 2006 VL 7 AR 209 DI 10.1186/1471-2164-7-209 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 083BA UT WOS:000240429700001 PM 16911775 ER PT J AU Conley, BA Wright, JJ Kummar, S AF Conley, Barbara A. Wright, John J. Kummar, Shivaani TI Targeting epigenetic abnormalities with histone deacetylase inhibitors SO CANCER LA English DT Article DE histone deacetylase inhibitors; epigenetics; drug development; targeted therapeutics ID SUBEROYLANILIDE HYDROXAMIC ACID; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ESTROGEN-RECEPTOR-ALPHA; TRANS-RETINOIC ACID; BREAST-CANCER CELLS; PHASE-I; DEPSIPEPTIDE FR901228; CARCINOMA-CELLS; ANTITUMOR-ACTIVITY AB BACKGROUND. Alterations in chromosome structure play critical roles in the control of gene transcription. These "epigenetic" alterations include modification of histones and other proteins by acetylation and/or phosphorylation. Normally, these modifications are balanced finely and are highly reversible in normal tissues, but they may be imbalanced and heritable in tumor cells. Histone deacetylase inhibitors increase histone acetylation, thereby modulating the expression of a subset of genes in a coordinated fashion. Several tumor suppressor genes associated with the malignant phenotype are repressed by epigenetic mechanisms in sporadic cancers. Thus, therapy with histone deacetylase inhibitors may alter tumor phenotype to inhibit growth in such tumors. METHODS. The authors reviewed the rationale for histone deacetylase inhibitors as potential anticancer agents and reviewed some preclinical and early clinical trial data with various classes of histone deacetylase inhibitors. RESULTS. Preclinical and clinical antitumor activity has been observed. Toxicities include fatigue, myelosuppression, and cardiac abnormalities. CONCLUSIONS. Histone deacetylase inhibitors have shown promising activity in some solid tumors and hematologic malignancies. C1 Michigan State Univ, Div Hematol Oncol, Dept Med, Coll Human Med,Clin Ctr B414, E Lansing, MI 48824 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Conley, BA (reprint author), Michigan State Univ, Div Hematol Oncol, Dept Med, Coll Human Med,Clin Ctr B414, E Lansing, MI 48824 USA. EM barbara.conley@hc.msu.edu NR 68 TC 30 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2006 VL 107 IS 4 BP 832 EP 840 DI 10.1002/cncr.22064 PG 9 WC Oncology SC Oncology GA 076II UT WOS:000239950000021 PM 16826577 ER PT J AU Aziz, NM Oeffinger, KC Brooks, S Turoff, AJ AF Aziz, Noreen M. Oeffinger, Kevin C. Brooks, Sandra Turoff, Alicia J. TI Comprehensive long-term follow-up programs for pediatric cancer survivors SO CANCER LA English DT Article DE barriers to care; long-term risk; pediatric oncology; risk-based screening; survivorship; late effects ID YOUNG-ADULT SURVIVORS; CHILDHOOD-CANCER; ADOLESCENT CANCER; HEALTH-CARE AB BACKGROUND. The objective of this study was to provide a detailed description of comprehensive long-term follow-up (LTFU) programs for pediatric cancer survivors. METHODS. Program directors from 24 comprehensive LTFU programs in the U.S. and Canada completed a 6-page survey that provided details in 5 categories: description of the program, perceived benefits and strengths of the program, barriers to the development and use of the program, methods to improve the program, and an ideal model of care for pediatric cancer survivors. RESULTS. Participants identified the following primary benefits to health care delivered to survivors through LTFU programs: health care delivered by clinicians familiar with long-term risks of survivors, provision of risk-based screening and surveillance for late effects, and targeted education for risk reduction and healthy lifestyles. Key barriers to the functioning of LTFU programs included system-driven and patient/survivor-driven factors. System-driven factors included inadequate resources and finances to sustain programs, low institutional commitment toward the provision of survivorship care, lack of capacity to care for the growing population of survivors, and difficulties with ongoing communication with community physicians. Survivor-driven barriers included lack of interest and lack of awareness of cancer-related risks. CONCLUSIONS. This report describes the frequency, content, and setting of follow-up care delivered by pediatric comprehensive LTFU programs. Critical challenges as survivorship care evolves will include integrating a structured process of program evaluation and building capacity for care. C1 Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Family & Community Med, Dallas, TX USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. EM oeffingk@mskcc.org NR 18 TC 58 Z9 59 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD AUG 15 PY 2006 VL 107 IS 4 BP 841 EP 848 DI 10.1002/cncr.22096 PG 8 WC Oncology SC Oncology GA 076II UT WOS:000239950000022 PM 16886175 ER PT J AU Ramiro, AR Nussenzweig, MC Nussenzweig, A AF Ramiro, Almudena R. Nussenzweig, Michel C. Nussenzweig, Andre TI Switching on chromosomal translocations SO CANCER RESEARCH LA English DT Review ID CYTIDINE DEAMINASE AID; CENTER B-CELLS; H2AX; RECOMBINATION; HYPERMUTATION; EXPRESSION; MYC; P53 AB Activation-induced deaminase initiates three different antibody diversification reactions: class switch recombination, somatic hypermutation (SHM), and gene conversion. We have shown that, in addition to antibody diversification, activation-induced deaminase can also initiate Burkitt's lymphoma-like c-myc/IgH translocations. However, distinct DNA damage- and oncogene-induced checkpoints operate in B cells to produce a normal intrachromosomal class switch recombination event or an aberrant interchromosomal fusion. These findings open the way to study the molecular pathways taking place at the early stages of malignant transformation. C1 Spanish Natl Canc Ctr, DNA Hypermutat Grp, E-28029 Madrid, Spain. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Ramiro, AR (reprint author), Spanish Natl Canc Ctr, DNA Hypermutat Grp, E-28029 Madrid, Spain. EM arodriguezr@cnio.es RI Ramiro, Almudena/H-6037-2015 OI Ramiro, Almudena/0000-0002-7539-3844 NR 16 TC 12 Z9 13 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 7837 EP 7839 DI 10.1158/0008-5472.CAN-06-0863 PG 3 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200002 PM 16912154 ER PT J AU Sengupta, S den Boon, JA Chen, IH Newton, MA Dahl, DB Chen, M Cheng, YJ Westra, WH Chen, CJ Hildesheim, A Sugden, B Ahlquist, P AF Sengupta, Srikumar den Boon, Johan A. Chen, I-How Newton, Michael A. Dahl, David B. Chen, Meng Cheng, Yu-Juen Westra, William H. Chen, Chien-Jen Hildesheim, Allan Sugden, Bill Ahlquist, Paul TI Genome-wide expression profiling reveals EBV-associated inhibition of MHC class I expression in nasopharyngeal carcinoma SO CANCER RESEARCH LA English DT Article ID EPSTEIN-BARR-VIRUS; COMPLEX CLASS-I; SARCOMA-ASSOCIATED HERPESVIRUS; ANTIGEN-PROCESSING FUNCTION; HLA CLASS-I; GENE-EXPRESSION; DOWN-REGULATION; MATRIX METALLOPROTEINASE-1; MOLECULAR CHARACTERIZATION; LATENT MEMBRANE-PROTEIN-1 AB To identify the molecular mechanisms by which EBV-associated epithelial cancers are maintained, we measured the expression of essentially all human genes and all latent EBV genes in a collection of 31 laser-captured, microdissected nasopharyngeal. carcinoma (NPC) tissue samples and 10 normal nasopharyngeal tissues. Global gene expression profiles clearly distinguished tumors from normal healthy epithelium. Expression levels of six viral genes (EBNA], EBNA2, EBNA3A, EBNA3B, LMP1, and LMP2A) were correlated among themselves and strongly inversely correlated with the expression of a large subset of host genes. Among the human genes whose inhibition was most strongly correlated with increased EBV gene expression were multiple MHC class I HLA genes involved in regulating immune response via antigen presentation. The association between EBV gene expression and inhibition of MHC class I HLA expression implies that antigen display is either directly inhibited by EBV, facilitating immune evasion by tumor cells, and/or that tumor cells with inhibited presentation are selected for their ability to sustain higher levels of EBV to take maximum advantage of EBV oncogene-mediated tumor-promoting actions. Our data clearly reflect such tumor promotion, showing that deregulation of key proteins involved in apoptosis (BCL2-related protein A1 and Fas apoptotic inhibitory molecule), cell cycle checkpoints (AKIP, SCYL1, and NIN), and metastasis (matrix metalloproteinase 1) is closely correlated with the levels of EBV gene expression in NPC. C1 Univ Wisconsin, Inst Mol Virol, Madison, WI 53706 USA. Univ Wisconsin, Howard Hughes Med Inst, Madison, WI 53706 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI 53706 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77834 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. Natl Taiwan Univ, Taipei 10764, Taiwan. MacKay Mem Hosp, Taipei 10764, Taiwan. RP Ahlquist, P (reprint author), Univ Wisconsin, Inst Mol Virol, 1525 Linden Dr, Madison, WI 53706 USA. EM ahlquist@wisc.edu RI Chen, Chien-Jen/C-6976-2008 FU Intramural NIH HHS; NCI NIH HHS [CA22443, CA64364, CA97944] NR 65 TC 98 Z9 103 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 7999 EP 8006 DI 10.1158/0008-5472.CAN-05-4399 PG 8 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200024 PM 16912175 ER PT J AU Zhang, ML Yao, ZS Zhang, Z Garmestani, K Talanov, VS Plascjak, PS Yu, S Kim, HS Goldman, CK Paik, CH Brechbiel, MW Carrasquillo, JA Waldmann, TA AF Zhang, Meili Yao, Zhengsheng Zhang, Zhuo Garmestani, Kayhan Talanov, Vladimir S. Plascjak, Paul S. Yu, Sarah Kim, Hyung-Sik Goldman, Carolyn K. Paik, Chang H. Brechbiel, Martin W. Carrasquillo, Jorge A. Waldmann, Thomas A. TI The anti-CD25 monoclonal antibody 7G7/B6, armed with the alpha-emitter At-211, provides effective radioimmunotherapy for a murine model of leukemia SO CANCER RESEARCH LA English DT Article ID T-CELL LEUKEMIA; THERAPY; LYMPHOMA; IMMUNOTHERAPY; TAC; INTERLEUKIN-2-RECEPTOR; FLAVOPIRIDOL; XENOGRAFTS; RECEPTOR AB Radioimmunotherapy of cancer with radiolabeled antibodies has shown promise. alpha-Particles are very attractive for cancer therapy, especially for isolated malignant cells, as is observed in leukemia, because of their high linear energy transfer and short effective path length. We evaluated an anti-CD25 [interleukin-2 receptor alpha (IL-2R alpha)] monoclonal antibody, 7G7/B6, armed with At-211 as a potential radioinummotherapeutic agent for CD25-expressing leukemias and lymphomas. Therapeutic studies were done in severe combined immunodeficient/nonobese diabetic mice bearing the karpas299 leukemia and in nude mice bearing the SUDHL-1 lymphoma. The results from a pharmacokinetic study showed that the clearance of At-211-7G7/B6 from the circulation was virtually identical to I-125-7G7/B6. The biodistributions of At-211-7G7/B6 and I-125-7G7/B6 were also similar with the exception of a higher stomach uptake of radioactivity with At-211-7G7/B6. Therapy using 15 mu Ci of At-211-7G7/B6 prolonged survival of the karpas299 leukemia-bearing mice significantly when compared with untreated mice and mice treated with At-211- 111711, a radiolabeled nonspecific control antibody (P < 0.01). All of the mice in the control and At-211-11F11 groups died by day 46 whereas > 70% of the mice in the At-211-7G7/B6 group still survived at that time. In summary, At-211-7G7/B6 could serve as an effective therapeutic agent for patients with CD25-expressing leukemias. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, PET & Nucl Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov RI Carrasquillo, Jorge/E-7120-2010 FU Intramural NIH HHS NR 29 TC 26 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 8227 EP 8232 DI 10.1158/0008-5472.CAN-06-1189 PG 6 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200051 PM 16912202 ER PT J AU Malone, KE Daling, JR Doody, DR Hsu, L Bernstein, L Coates, RJ Marchbanks, PA Simon, MS McDonald, JA Norman, SA Strom, BL Burkman, RT Ursin, G Deapen, D Weiss, LK Folger, S Madeoy, JJ Friedrichsen, DM Suter, NM Humphrey, MC Spirtas, R Ostrander, EA AF Malone, Kathleen E. Daling, Janet R. Doody, David R. Hsu, Li Bernstein, Leslie Coates, Ralph J. Marchbanks, Polly A. Simon, Michael S. McDonald, Jill A. Norman, Sandra A. Strom, Brian L. Burkman, Ronald T. Ursin, Giske Deapen, Dennis Weiss, Linda K. Folger, Suzanne Madeoy, Jennifer J. Friedrichsen, Danielle M. Suter, Nicola M. Humphrey, Mariela C. Spirtas, Robert Ostrander, Elaine A. TI Prevalence and predictors of BRCA1 and BRCA2 mutations in a population-based study of breast cancer in white and black American women ages 35 to 64 years SO CANCER RESEARCH LA English DT Article ID OVARIAN-CANCER; AFRICAN-AMERICAN; FAMILY-HISTORY; GERMLINE MUTATIONS; INHERITED MUTATIONS; ASHKENAZI JEWS; GENE-MUTATIONS; CASE SERIES; RISK; PENETRANCE AB Although well studied in families at high-risk, the roles of mutations in the BRCA-1 and BRCA2 genes are poorly understood in breast cancers in the general population, particularly in Black women and in age groups outside of the very young. We examined the prevalence and predictors of BRCA-1 and BRCA2 mutations in 1,628 women with breast cancer and 674 women without breast cancer who participated in a multicenter population-based case-control study of Black and White women, 35 to 64 years of age. Among cases, 2.4% and 2.3% carried deleterious mutations in BRCA1 and BRCA2, respectively. BRCA1 mutations were significantly more common in White (2.9%) versus Black (1.4%) cases and in Jewish (10.2%) versus non-Jewish (2.0%) cases; BRCA2 mutations were slightly more frequent in Black (2.6%) versus White (2.1%) cases. Numerous familial and demographic factors were significantly associated with BRCA1 and, to a lesser extent, BRCA2 carrier status, when examined individually. In models considering all predictors together, early onset ages in cases and in relatives, family history of ovarian cancer, and Jewish ancestry remained strongly and significantly predictive of BRCA-1 carrier status, whereas BRCA2 predictors were fewer and more modest in magnitude. Both the combinations of predictors and effect sizes varied across racial/ethnic and age groups. These results provide first-time prevalence estimates for BRCA1/BRCA2 in breast cancer cases among understudied racial and age groups and show key predictors of mutation carrier status for both White and Black women and women of a wide age spectrum with breast cancer in the general population. C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Seattle, WA 98109 USA. Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Wayne State Univ, Div Hematol & Oncol, Karmanos Canc Inst, Detroit, MI USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Bay State Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. Univ Oslo, Dept Nutr, N-0316 Oslo, Norway. Natl Canc Inst, Canc Ctr Branch, Bethesda, MD USA. NICHHD, Contracept & Reprod Branch, Ctr Populat Biol, DHHS,NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Malone, KE (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, POB 19024,Mailstop M4-C308, Seattle, WA 98109 USA. EM kmalone@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [N01-CN-0532, N01-CN-65064, N01-CN-67010, N01-PC-67006, T32 CA080416]; NICHD NIH HHS [N01 HD 3-3175, N01 HD 2-3166, N01 HD 3-3168, N01 HD 3-3174, N01 HD 3-3176, Y01 HD 7022] NR 50 TC 110 Z9 114 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 8297 EP 8308 DI 10.1158/0008-5472.CAN-06-0503 PG 12 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200061 PM 16912212 ER PT J AU Hagiwara, N Mechanic, LE Trivers, GE Cawley, HL Taga, M Bowman, ED Kumamoto, K He, P Bernard, M Doja, S Miyashita, M Tajiri, T Sasajima, K Nomura, T Makino, H Takahashi, K Hussain, SP Harris, CC AF Hagiwara, Nobutoshi Mechanic, Leah E. Trivers, Glenwood E. Cawley, Helen L. Taga, Masataka Bowman, Elise D. Kumamoto, Kensuke He, Peijun Bernard, Mark Doja, Saira Miyashita, Masao Tajiri, Takashi Sasajima, Koji Nomura, Tsutomu Makino, Hiroshi Takahashi, Ken Hussain, S. Perwez Harris, Curtis C. TI Quantitative detection of p53 mutations in plasma DNA from tobacco smokers SO CANCER RESEARCH LA English DT Article ID LUNG-CANCER PATIENTS; HEPATOCELLULAR-CARCINOMA PATIENTS; TUMOR-SUPPRESSOR GENE; COLORECTAL-CANCER; BREAST-CANCER; FOLLOW-UP; SERUM DNA; K-RAS; CLINICOPATHOLOGICAL FEATURES; MICROSATELLITE ALTERATIONS AB In lung tumors, the p53 tumor suppressor gene is commonly mutated with a characteristic mutation spectrum. The amount of and alterations in plasma DNA, such as mutations in p53, were associated with several cancers. Few studies used quantitative methods of high sensitivity. Previously, we observed p53 mutations in the noncancerous tissue that differed from those in lung tumors using the highly sensitive p53 mutation load assay. Based on our observation of an increased p53 mutation load in nontumorous lung tissue in smokers, we hypothesized that plasma DNA may contain mutant p53 indicative of tobacco smoke exposure and will be an effective biomarker of lung cancer or smoking exposure. We modified the p53 mutation load assay to detect mutations at p53 codons 248 and 249, common mutations in lung cancer, in plasma DNA samples with a sensitivity of 1:5,000. The assay was applied to a set of lung cancer cases (n = 39), hospital controls (n = 21), and population controls (n = 20) from a larger study. Controls were selected to consist of equal numbers of both ever and never smokers. The p53 mutation load (mutated p53 copies per total number of p53 copies) was associated with smoking (P = 0.06), but not with lung cancer (P = 0.59). Most of the individuals with p53 mutations observed in plasma DNA were ever smokers and the p53 mutation load was higher in those who smoked for longer durations (P = 0.04). In summary, we were able to detect p53 mutations in plasma DNA from healthy individuals and our data suggest that p53 mutations in plasma DNA may be a marker of carcinogen exposure from tobacco smoke. C1 NCI, Ctr Canc Res, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA. Nippon Med Coll Hosp, Dept Surg 1, Tokyo, Japan. Radiat Effects Res Fdn, Dept Radiobiol Mol Epidemiol, Hiroshima, Japan. RP Harris, CC (reprint author), NCI, Ctr Canc Res, Lab Human Carcinogenesis, NIH, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU Intramural NIH HHS NR 60 TC 21 Z9 24 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 15 PY 2006 VL 66 IS 16 BP 8309 EP 8317 DI 10.1158/0008-5472.CAN-06-0991 PG 9 WC Oncology SC Oncology GA 074QZ UT WOS:000239828200062 PM 16912213 ER PT J AU Park, EJ Kong, D Fisher, R Cardellina, J Shoemaker, RH Melillo, G AF Park, Eun Jung Kong, Dehe Fisher, Robert Cardellina, John Shoemaker, Robert H. Melillo, Giovanni TI Targeting the PAS-A domain of HIF-1 alpha for development of small molecule inhibitors of HIF-1 SO CELL CYCLE LA English DT Article DE HIF-1 alpha; PAS-A domain; screening; small molecule inhibitors; protein-protein interaction ID HYPOXIA-INDUCIBLE FACTOR-1; PROTEIN-PROTEIN INTERACTION; TRANSCRIPTION FACTORS; STRUCTURAL BASIS; TOPOISOMERASE-I; TUMOR-GROWTH; ANTAGONISTS; PATHWAY; IDENTIFICATION; BINDING AB Hypoxia inducible factor-1 (HIF-1) is a master regulator of cellular adaptation to oxygen deprivation and activates transcription of genes involved in tumor metabolism, angiogenesis, invasion and metastasis, all of which are implicated in cancer progression. Several domains of HIF-1 alpha mediate protein- protein interaction, which is essential for the formation of the active heterodimer with HIF-1 beta. Targeting specific domains of HIF-1 alpha might lead to the identification of more selective inhibitors. HIF-1 alpha and HIF-1 beta contain two Per-Arnt-Sim (PAS) domains, A and B, both of which appear to be important for heterodimer formation. In an attempt to identify small molecule inhibitors of the PAS-A domain of HIF-1 we expressed proteins containing amino acids 86-165 of HIF-1 alpha and amino acids 159-240 of HIF-1 beta fused to a His or FLAG tag, respectively. Expressed proteins retained functional activity as indicated by in vitro immunoprecipitation experiments and activation of luciferase expression in a mammalian two-hybrid system. Interestingly, over-expression of HIF-1 alpha-PAS-A domain was sufficient to abrogate hypoxic induction of HIF-1-dependent luciferase expression, supporting its potential role as drug target. An ELISA based on the interaction between FLAG-HIF-1 beta-PAS-A and HIF-1 alpha-PAS-A-His was developed and used to screen libraries of synthetic compounds. NSC 50352 specifically inhibited PAS-A-dependent interaction between HIF-1 alpha and HIF-1 beta, but not the interaction mediated by unrelated domains. However, NSC 50352 was devoid of activity in cell-based assays. Our results provide proof-of-principle that the PAS-A domain of HIF-1 alpha is a valid target for development of small molecule inhibitors. C1 NCI, Tumor Hypoxia Lab, SAIC Frederick, Ft Detrick, MD 21702 USA. NCI, Dev Therapeut Program, Ft Detrick, MD 21702 USA. RP Melillo, G (reprint author), NCI, Tumor Hypoxia Lab, SAIC Frederick, Bldg 432,Room 218, Ft Detrick, MD 21702 USA. EM melillog@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 44 TC 35 Z9 35 U1 2 U2 6 PU LANDES BIOSCIENCE PI AUSTIN PA 1002 WEST AVENUE, 2ND FLOOR, AUSTIN, TX 78701 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 15 PY 2006 VL 5 IS 16 BP 1847 EP 1853 PG 7 WC Cell Biology SC Cell Biology GA 086UN UT WOS:000240698600017 PM 16861921 ER PT J AU Fox, E Maris, JM Widemann, BC Meek, K Goodwin, A Goodspeed, W Kromplewski, M Fouts, ME Medina, D Cho, SY Cohn, SL Krivoshik, A Hagey, AE Adamson, PC Balis, FM AF Fox, Elizabeth Maris, John M. Widemann, Brigitte C. Meek, Kysa Goodwin, Anne Goodspeed, Wendy Kromplewski, Marie Fouts, Molly E. Medina, Diane Cho, Steve Y. Cohn, Susan L. Krivoshik, Andrew Hagey, Anne E. Adamson, Peter C. Balis, Frank M. TI A phase 1 study of ABT-751, an orally bioavailable tubulin inhibitor, administered daily for 7 days every 21 days in pediatric patients with solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID I TRIAL; CHILDREN; SULFONAMIDE; E7010 AB Purpose: To determine the toxicity profile, dose-limiting toxicities, and maximum tolerated dose of ABT-751 administered orally once daily for 7 days, repeated every 21 days. Experimental Design: Patients who were <= 18 years of age, with relapsed or refractory solid tumors, and who were able to swallow capsules were eligible. The starting dose was 100 mg/m(2) /d (n = 3) and was escalated to 130 mg/m(2) /d (n = 6), 16 5 mg/m(2) /d (n = 6), 200 mg/m(2) /d (n = 6), and 250 mg/m(2) /d (n = 2) in cohorts of three to six patients. The maximum tolerated dose was determined from dose-limiting toxicities occurring during the first treatment cycle. Results: Twenty-four children (median age, 13 years; range, 4-18 years) were enrolled; 23 were evaluable for toxicity. Diagnoses included neuroblastoma (n = 8), sarcomas (n = 8), primary brain tumors (n = 2), Wilms' tumor (n = 2), and other solid tumors (n = 3). Dose-limiting toxicities (grade 3 sensory and motor neuropathy, grade 3 hypertension, and grade 3 fatigue) were observed in patients enrolled at the 250 mg/m(2) /d dose level. The maximum tolerated dose of ABT-751 administered daily for 7 days every 21 days was 200 mg/m(2) /d. Non-dose-limiting toxicities at the maximum tolerated dose included anemia, fatigue, peripheral sensory neuropathy, abdominal pain, nausea, constipation, anorexia, fever, and weight loss. Myelosuppression was minimal at the maximum tolerated dose. The median number of cycles administered is 2 (range, 1-50). No significant ABT-751-related cumulative toxicities were observed. Conclusion: ABT-751 is well tolerated in children. The recommended dose for phase 2 trials in solid tumors is 200 mg/m(2) /d administered orally, daily for 7 days every 21 days. This dose is >40% higher than the maximum tolerated dose in adults receiving the same dosing schedule. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Mem Med Ctr, Chicago, IL USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, Room 1-5750,Bldg 10 CRC,10 Ctr Dr, Bethesda, MD 20892 USA. EM foxb@mail.nih.gov OI Cohn, Susan/0000-0001-5749-7650 FU Intramural NIH HHS NR 14 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2006 VL 12 IS 16 BP 4882 EP 4887 DI 10.1158/1078-0432.CCR-06-0534 PG 6 WC Oncology SC Oncology GA 074TJ UT WOS:000239834400015 PM 16914576 ER PT J AU Wen, PY Yung, WKA Lamborn, KR Dahia, PL Wang, YF Peng, B Abrey, LE Raizer, J Cloughesy, TF Fink, K Gilbert, M Chang, S Junck, L Schiff, D Lieberman, F Fine, HA Mehta, M Robins, HI DeAngelis, LM Groves, MD Puduvalli, VK Levin, V Conrad, C Maher, EA Aldape, K Hayes, M Letvak, L Egorin, MJ Capdeville, R Kaplan, R Murgo, AJ Stiles, C Prados, MD AF Wen, Patrick Y. Yung, W. K. Alfred Lamborn, Kathleen R. Dahia, Patricia L. Wang, Yanfeng Peng, Bin Abrey, Lauren E. Raizer, Jeffrey Cloughesy, Timothy F. Fink, Karen Gilbert, Mark Chang, Susan Junck, Larry Schiff, David Lieberman, Frank Fine, Howard A. Mehta, Minesh Robins, H. Ian DeAngelis, Lisa M. Groves, Morris D. Puduvalli, Vinay K. Levin, Victor Conrad, Charles Maher, Elizabeth A. Aldape, Kenneth Hayes, Michael Letvak, Laurie Egorin, Merrill J. Capdeville, Renaud Kaplan, Richard Murgo, Anthony J. Stiles, Charles Prados, Michael D. TI Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08 SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR EXPRESSION; PDGF-RECEPTOR GENES; TRANSFORMED PHENOTYPE; HUMAN ASTROCYTOMAS; HUMAN MENINGIOMAS; KINASE INHIBITOR; TYROSINE KINASE; CELL-GROWTH; DRUG; GLIOBLASTOMA AB Purpose: Phase I: To determine the maximum tolerated doses, toxicities, and pharmacokinetics of imatinib mesylate (Gleevec) in patients with malignant gliomas taking enzyme-inducing antiepileptic drugs (EIAED) or not taking EIAED. Phase II: To determine the therapeutic efficacy of imatinib. Experimental Design: Phase I component used an interpatient dose escalation scheme. End points of the phase II component were 6-month progression-free survival and response. Results: Fifty patients enrolled in the phase I component (27 EIAED and 23 non-EIAED). The maximum tolerated dose for non-EIAED patients was 800 mg/d. Dose-limiting toxicities were neutropenia, rash, and elevated alanine aminotransferase. EIAED patients received up to 1,200 mg/d imatinib without developing dose-limiting toxicity. Plasma exposure of imatinib was reduced by similar to 68% in EIAED patients compared with non-EIAED patients. Fifty-five non-EIAED patients (34 glioblastoma multiforme and 21 anaplastic glioma) enrolled in the phase II component. Patients initially received 800 mg/d imatinib; 15 anaplastic glioma patients received 600 mg/d after hemorrhages were observed. There were 2 partial response and 6 stable disease among glioblastoma multiforme patients and 0 partial response and 5 stable disease among anaplastic glioma patients. Six-month progression-free survival was 3% for glioblastoma multiforme and 10% for anaplastic glioma patients. Five phase II patients developed intratumoral hemorrhages. Conclusions: Single-agent imatinib has minimal activity in malignant gliomas. CYP3A4 inducers, such as EIAEDs, substantially decreased plasma exposure of imatinib and should be avoided in patients receiving imatinib for chronic myelogenous leukemia and gastrointestinal stromal tumors. The evaluation of the activity of combination regimens incorporating imatinib is under way in phase II trials. C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. Novartis Pharmaceut, Florham Pk, NJ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIH, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Wen, PY (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM pwen@partners.org RI Puduvalli, Vinay/A-2411-2016; OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [R03CA102974-02] NR 42 TC 270 Z9 274 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2006 VL 12 IS 16 BP 4899 EP 4907 DI 10.1158/1078-0432.CCR-06-0773 PG 9 WC Oncology SC Oncology GA 074TJ UT WOS:000239834400017 PM 16914578 ER PT J AU Hassan, R Williams-Gould, J Steinberg, SM Liewehr, DJ Yokokawa, J Tsang, KY Surawski, RJ Scott, T Camphausen, K AF Hassan, Raffit Williams-Gould, Juanita Steinberg, Seth M. Liewehr, David J. Yokokawa, Junko Tsang, Kwong Y. Surawski, Robert J. Scott, Tamalee Camphausen, Kevin TI Tumor-directed radiation and the immunotoxin SS1P in the treatment of mesothelin-expressing tumor xenografts SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODY; PANCREATIC-CANCER; DNA-DAMAGE; CELLS; THERAPY; RADIOSENSITIVITY; ADENOCARCINOMAS; 5-FLUOROURACIL; IDENTIFICATION; ENHANCEMENT AB Purpose: Mesothelin is a cell surface protein overexpressed in mesotheliomas and pancreatic and ovarian cancers. The goal of this study was to determine if radiation therapy in combination with the antimesothelin immunotoxin SS1 (dsFv)PE38 (SS1P) would result in enhanced antitumor activity against mesothelin-expressing xenografts in nude mice. Experimental Design: Female athymic nude mice bearing s.c. mesothelin-expressing xenografts were treated with SS1P alone, tumor-focused radiation alone, or the combination of the two. Two different regimens of the combination therapy were tested. In the low-dose combination schedule, mice were treated with either 5 Gy radiation alone, 0.2 mg/kg SS1P alone, or the same doses of radiation and SS1P in combination. In the high-dose combination experiments, mice were treated,with either 15 Gy radiation alone, 0.3 mg/kg SS1P alone, or the combination of radiation and SS1P. Results: In the low-dose radiation and SS1P combination studies, mice treated with the combination of radiation and SS1P had a statistically significant prolongation in time to tumor doubling or tripling compared with control, SS1P, or radiation alone. A similar increase in time to tumor doubling or tripling was seen in mice treated with high-dose radiation and SS1P combination. Conclusions: Combination of SS1P with tumor-directed radiation results in enhanced antitumor activity against mesothelin-expressing tumor xenografts. This effect was seen when either low or high doses of radiation were used. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5116, Bethesda, MD 20892 USA. EM hassanr@mail.nih.gov FU Intramural NIH HHS NR 27 TC 21 Z9 25 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2006 VL 12 IS 16 BP 4983 EP 4988 DI 10.1158/1078-0432.CCR-06-0441 PG 6 WC Oncology SC Oncology GA 074TJ UT WOS:000239834400027 PM 16914588 ER PT J AU Lee, GD Ingram, DK Longo, DL AF Lee, Garrick D. Ingram, Donald K. Longo, Dan L. TI Cancer chemotherapy and cognitive function in rodent models: Memory impairment induced by cyclophosphamide in mice - Response SO CLINICAL CANCER RESEARCH LA English DT Letter C1 NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Immunol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lee, GD (reprint author), NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 15 PY 2006 VL 12 IS 16 BP 5000 EP 5001 PG 2 WC Oncology SC Oncology GA 074TJ UT WOS:000239834400030 ER PT J AU Jiao, ZX Zhang, ZG Hornyak, TJ Hozeska, A Zhang, RL Wang, Y Wang, L Roberts, C Strickland, FM Chopp, M AF Jiao, Zhongxian Zhang, Zheng Gang Hornyak, Thomas J. Hozeska, Ann Zhang, Rui Lan Wang, Ying Wang, Lei Roberts, Cynthia Strickland, Faith M. Chopp, Michael TI Dopachrome tautomerase (Dct) regulates neural progenitor cell proliferation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE dopachrome tautomerase; neurogenesis; cortical neural progenitor cell; SVZ progenitor; brain; mouse ID ADULT MAMMALIAN FOREBRAIN; STEM-CELLS; TRANSCRIPTION FACTOR; SUBVENTRICULAR ZONE; GROWTH-FACTOR; MELANOCYTE DEVELOPMENT; FUNCTIONAL-ANALYSIS; NEURONAL MIGRATION; SUBEPENDYMAL CELLS; MOLECULAR-CLONING AB DOPAchrome tautomerase (Dct) functions downstream of tyrosinase in the biosynthetic pathway of eumelanin by catalyzing the conversion of dopachrome to 5,5-dihydroxyindole-2-carboxylic acid (DHICA) in pigment cells. Dct transcription is regulated directly or synergistically by Pax3, Sox10 and microphthalmia transcription factor (MITF). Using Dct-lacZ transgenic mice, we measured the spatial and temporal pattern of Dct expression in vivo during neocortical neurogenesis in the brain. Dct was expressed in all layers of the dorsal telencephalon in E10.5. At E15.5 and E17.5 when cortical neurogenesis occurs, expression of Dct was primarily localized to the ventricular zone (VZ) where neuronal stem cells reside. Blocking endogenous Dct by RNAi decreased proliferation of embryonic cortical neural progenitor cells (by 48%, P < 0.05), as determined by BrdU incorporation. In adult brain, Dct/Dct expression decreased in the subventricular zone (SVZ), dentate gyrus and olfactory bulb (OB). However, strong expression of Dct was observed in rostral migratory stream (RMS) and septum. Overexpression of Det in SVZ cells derived from the adult mice significantly increased the number of cells by 260%, whereas silencing Dct by RNAi decreased cell numbers by 25.8% at 48 It post-nucleofection (P < 0.05). The results of RT-PCR analysis revealed that Dct in the brain lacks exon 7 and is identical to the form of Lict found in neural-crest-derived melanocytes. Our data indicate that Dct, previously known as a melanoblast marker, regulates neural progenitor cell proliferation. (c) 2006 Elsevier Inc. All rights reserved. C1 Henry Ford Hosp, Dept Neurol, Hlth Sci Ctr, Detroit, MI 48202 USA. Henry Ford Hosp, Dept Dermatol, Hlth Sci Ctr, Detroit, MI 48202 USA. NCI, Dermatol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Oakland Univ, Dept Phys, Rochester, MI 48063 USA. RP Chopp, M (reprint author), Henry Ford Hosp, Dept Neurol, Hlth Sci Ctr, 2799 W Grand Blvd, Detroit, MI 48202 USA. EM chopp@neuro.hfh.edu FU Intramural NIH HHS; NIAMS NIH HHS [K08 AR 01992]; NINDS NIH HHS [P01 NS 23393, R01 NS 38292] NR 49 TC 23 Z9 24 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD AUG 15 PY 2006 VL 296 IS 2 BP 396 EP 408 DI 10.1016/j.ydbio.2006.06.006 PG 13 WC Developmental Biology SC Developmental Biology GA 076TI UT WOS:000239980200010 PM 16857183 ER PT J AU Pelletier, MM Kleinbongard, P Ringwood, L Hito, R Hunter, CJ Schechter, AN Gladwin, MT Dejain, A AF Pelletier, Mildred M. Kleinbongard, Petra Ringwood, Lorna Hito, Rania Hunter, Christian J. Schechter, Alan N. Gladwin, Mark T. Dejain, Andre TI The measurement of blood and plasma nitrite by chemiluminescence: Pitfalls and solutions SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE nitrite; plasma; erythrocytes; nitric oxide; chemiluminescence; free radicals ID OXIDE SYNTHASE ACTIVITY; NO IN-VIVO; ISCHEMIA-REPERFUSION; BIOLOGICAL SAMPLES; S-NITROSOTHIOLS; NITRATE; CELLS; REDUCTION; DEOXYHEMOGLOBIN; VASODILATION AB There are a number of difficulties involved in the quantification of nitrite in biological systems. These difficulties result from oxidation of nitrite (within minutes) by heme proteins, such as hemoglobin, myoglobin, cytoglobin, and neuroglobin; its low levels in vivo; and its ubiquitous presence in laboratory buffers and glassware. The goal of this review is to present an assay suitable for the sensitive and specific measurement of intravascular nitrite in mammals using the chemiluminescence-based nitric oxide analyzer and to inform the reader on how to evade the pitfalls pertinent to nitrite determination in biological matrices. Published by Elsevier Inc. C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, Dept Cardiol, D-4000 Dusseldorf, Germany. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Schechter, AN (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM aschecht@helix.nih.gov; mgladwin@mail.nih.gov RI Hunter, Christian/G-4344-2010; OI Schechter, Alan N/0000-0002-5235-9408 NR 33 TC 85 Z9 86 U1 2 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 15 PY 2006 VL 41 IS 4 BP 541 EP 548 DI 10.1016/j.freeradbiomed.2006.05.001 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 071NF UT WOS:000239608200003 PM 16863986 ER PT J AU Gladwin, MT Wang, XD Hogg, N AF Gladwin, Mark T. Wang, Xunde Hogg, Neil TI Methodological vexation about thiol oxidation versus S-nitrosation - A commentary on "An ascorbate-dependent artifact that interferes with the interpretation of the biotin-switch assay" SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Editorial Material ID CHROMATOGRAPHY MASS-SPECTROMETRY; CYSTEINE-SULFINIC ACID; REGIONAL BLOOD-FLOW; NITRIC-OXIDE; HUMAN PLASMA; IN-VIVO; PREECLAMPSIA PLASMA; SERUM-ALBUMIN; NITROSOTHIOLS; NITROSOALBUMIN C1 NHLBI, Vasc Med Branch, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, Dept Crit Care Med, NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM mgladwin@nih.gov NR 58 TC 28 Z9 28 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 15 PY 2006 VL 41 IS 4 BP 557 EP 561 DI 10.1016/j.freeradbiomed.2006.05.025 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 071NF UT WOS:000239608200005 PM 16863988 ER PT J AU Kyrmizi, I Hatzis, P Katrakili, N Tronche, F Gonzalez, FJ Talianidis, I AF Kyrmizi, Irene Hatzis, Pantelis Katrakili, Nitsa Tronche, Francois Gonzalez, Frank J. Talianidis, Iannis TI Plasticity and expanding complexity of the hepatic transcription factor network during liver development SO GENES & DEVELOPMENT LA English DT Article DE hepatocyte development; transcription factor; regulatory network ID HEPATOCYTE NUCLEAR FACTOR-1; INDUCED GENE ACTIVATION; CELL LINEAGE; EXPRESSION; DIFFERENTIATION; METABOLISM; CHROMATIN; PROMOTER; HNF1; MORPHOGENESIS AB Cross-regulatory cascades between hepatic transcription factors have been implicated in the determination of the hepatic phenotype. Analysis of recruitments to regulatory regions and the temporal and spatial expression pattern of the main hepatic regulators during liver development revealed a gradual increase in complexity of autoregulatory and cross-regulatory circuits. Within these circuits we identified a core group of six transcription factors, which regulate the expression of each other and the expression of other downstream hepatic regulators. Changes in the promoter occupancy patterns during development included new recruitments, release, and exchange of specific factors. We also identified promoter and developmental stage-specific dual regulatory functions of certain factors as an important feature of the network. Inactivation of HNF-4 alpha in embryonic, but not in adult, liver resulted in the diminished expression of most hepatic factors, demonstrating that the stability of the network correlates with its complexity. The results illustrate the remarkable flexibility of a self-sustaining transcription factor network, built up by complex dominant and redundant regulatory motifs in developing hepatocytes. C1 Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Greece. Inst Biol, CNRS, UMR7148, F-75231 Paris, France. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Talianidis, I (reprint author), Fdn Res & Technol Hellas, Inst Mol Biol & Biotechnol, Iraklion, Greece. EM talianid@imbb.forth.gr RI TRONCHE, Francois/F-3895-2011; Talianidis, Iannis/F-7556-2016 OI Talianidis, Iannis/0000-0002-1209-3609 NR 42 TC 146 Z9 154 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 2006 VL 20 IS 16 BP 2293 EP 2305 DI 10.1101/gad.390906 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 074CR UT WOS:000239790600012 PM 16912278 ER PT J AU Talbott, JF Cao, QL Enzmann, GU Benton, RL Achim, V Cheng, XX Mills, MD Rao, MS Whittemore, SR AF Talbott, Jason F. Cao, Qilin Enzmann, Gaby U. Benton, Richard L. Achim, Virginie Cheng, Xiao X. Mills, Michael D. Rao, Mahendra S. Whittemore, Scott R. TI Schwann cell-like differentiation by adult oligodendrocyte precursor cells following engraftment into the demyelinated spinal cord is BMP-dependent SO GLIA LA English DT Article DE demyelination; remyelination; noggin; adult oligodendrocyte precursor cell; astrocyte; spinal cord ID BONE MORPHOGENETIC PROTEINS; CENTRAL-NERVOUS-SYSTEM; BROMIDE-INDUCED DEMYELINATION; GLIAL PROGENITOR CELLS; CNS STEM-CELLS; ETHIDIUM-BROMIDE; RAT CNS; AXONAL REGENERATION; TYPE-1 ASTROCYTES; WHITE-MATTER AB The development of remyelinating strategies designed to enhance recruitment and differentiation of endogenous precursor cells available to a site of demyelination in the adult spinal cord will require a fundamental understanding of the potential for adult spinal cord precursor cells to remyelinate as well as an insight into epigenetic cues that regulate their mobilization and differentiation. The ability of embryonic and postnatal neural precursor cell transplants to remyelinate the adult central nervous system is well documented, while no transplantation studies to date have examined the remyelinating potential of adult spinal-cord-derived oligodendrocyte precursor cells (adult OPCs). In the present study, we demonstrate that, when transplanted subacutely into spinal ethidium bromide/X-irradiated (EBX) lesions, adult OPCs display a limited capacity for oligodendrocyte remyelination. Interestingly, the glia-free environment of EB lesions promotes engrafted adult OPCs to differentiate primarily into cells with immunophenotypic and ultrastructural characteristics of myelinating Schwann cells (SCs). Astrocytes modulate this potential, as evidenced by the demonstration that SC-like differentiation is blocked when adult OPCs are co-transplanted with astrocytes. We further show that inhibition of bone morphogenetic protein (BMP) signaling through noggin overexpression by engrafted adult OPCs is sufficient to block SC-like differentiation within EB-X lesions. Present data suggest that the macroglial-free environment of acute EB lesions in the ventrolateral funiculus is inhibitory to adult spinal cord-derived OPC differentiation into remyelinating oligodendrocytes, while the presence of BMPs and absence of noggin promotes SC-like differentiation, thereby unmasking a surprising lineage fate for these cells. (c) 2006 Wiley-Liss, Inc. C1 Univ Louisville, Sch Med, Dept Neurol Surg, Kentucky Spinal Cord Injury Res Ctr, Louisville, KY 40202 USA. Univ Louisville, Sch Med, MD PhD Program, Louisville, KY USA. Univ Louisville, Sch Med, Dept Anat Sci & Neurobiol, Louisville, KY USA. Univ Louisville, Sch Med, Dept Neurol Surg, Louisville, KY USA. Univ Louisville, Sch Med, Dept Radiat Oncol, Louisville, KY USA. NIA, Lab Neurosci, Baltimore, MD USA. RP Whittemore, SR (reprint author), Univ Louisville, Sch Med, Dept Neurol Surg, Kentucky Spinal Cord Injury Res Ctr, 511 S Floyd St, Louisville, KY 40202 USA. EM swhittemore@louisville.edu FU NCRR NIH HHS [P20 RR015576, P20 RR015576-07, RR15576]; NINDS NIH HHS [NS38665, P01 NS038665] NR 61 TC 36 Z9 38 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 AUG 15 PY 2006 VL 54 IS 3 BP 147 EP 159 DI 10.1002/glia.20369 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 068DF UT WOS:000239351600001 PM 16921543 ER PT J AU Nemukhin, AV Grigorenko, BL Topol, IA Burt, SK AF Nemukhin, AV Grigorenko, BL Topol, IA Burt, SK TI Modeling dioxygen binding to the non-heme iron-containing enzymes SO INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the V-A-Fock-School on Quantum and Computational Chemistry CY MAY 10-15, 2005 CL Novgorod, RUSSIA SP V A Fock Sch DE DFT; QM/MM modeling; CASSCF; non-heme iron enzymes; biomimetic complexes ID CYTOCHROME-P450 ENZYMES; MECHANICAL METHOD; OXYGENASES; CHEMISTRY; POTENTIALS; COMPLEXES; MOLECULES; CLEAVAGE AB The structures and properties of the complexes formed upon binding the oxygen molecule to the iron sites in non-heme 2-oxoglutarate-dependent enzymes are characterized by QM(CASSCF)/MM and density functional theory (DFT) calculations. Molecular models for the calculations are constructed following the crystal structure of hypoxia-inducible factor asparaginyl hydroxylase (FIH-1). DFT calculations for the 37-atomic cluster have been carried out at the B3LYP(LANL2DZdp) level. The flexible effective fragment potential method is used as a combined quantum mechanical-molecular mechanical (QM/MM) technique to characterize the fragment of the enzymatic system, including 1,758 atoms in the MM part and 27 atoms in the QM part. In these calculations, the CASSCF(LANL2DZdp) approach is applied in the QM subsystem, and AMBER force field parameters are used in the MM subsystem. With both approaches, equilibrium geometry configurations have been located for different spin states of the system. In DFT calculations, the order of the states is as follows: septet, triplet (+7.7 kcal/mol), quintet (+10.7 kcal/mol). Geometry configurations correspond to the end-on structures with no evidences of electron transfer from Fe(II) to molecular oxygen. In contrast, QM(CASSCF)/MM calculations predict the quintet state as the lowest one, while the septet structure has slightly (< 2 kcal/mol) higher energy, and the triplet state is considerably more energetic. In QM/MM calculations, in both quintet and septet states, the electronic configurations show considerable electron charge transfer from iron to oxygen, and the oxidation state of iron in the metal binding site can be characterized as Fe(III). (c) 2006 Wiley Periodicals, Inc. C1 Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. Russian Acad Sci, Inst Biochem Phys, Moscow 119997, Russia. Natl Canc Inst, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Nemukhin, AV (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. EM anem@lcc.chem.msu.ru RI Nemukhin, Alexander/P-9662-2015 NR 31 TC 12 Z9 12 U1 2 U2 16 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7608 J9 INT J QUANTUM CHEM JI Int. J. Quantum Chem. PD AUG 15 PY 2006 VL 106 IS 10 BP 2184 EP 2190 DI 10.1002/qua.20910 PG 7 WC Chemistry, Physical; Mathematics, Interdisciplinary Applications; Physics, Atomic, Molecular & Chemical SC Chemistry; Mathematics; Physics GA 052OT UT WOS:000238243700003 ER PT J AU Read, SW Higgins, J Metcalf, JA Stevens, RA Rupert, A Nason, MC Lane, HC Sereti, I AF Read, Sarah W. Higgins, Jeanette Metcalf, Julia A. Stevens, Randy A. Rupert, Adam Nason, Martha C. Lane, H. Clifford Sereti, Irini TI Decreased CD127 expression on T cells in HIV-1-infected adults receiving antiretroviral therapy with or without intermittent IL-2 therapy SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 12th Conference on Retroviruses and Opportunistic Infections CY FEB 22-25, 2005 CL Boston, MA DE interleukin-7; interleukin-2; CD25; immune activation; HAART ID HIV-INFECTED PATIENTS; SUBCUTANEOUS INTERLEUKIN-2; RECEPTOR EXPRESSION; POSITIVE PATIENTS; RANDOMIZED-TRIAL; MEMORY CELLS; SURVIVAL; LYMPHOCYTES; HOMEOSTASIS; EXPANSION AB Background: The interleukin-7 (IL-7)/IL-7 receptor a (IL-7R alpha) system is an important regulator of T-cell homeostasis. We evaluated the IL-7/IL-7R alpha system in a large cohort of HIV-infected patients, including a subset treated with intermittent IL-2. Methods: IL-7 serum levels and CD127 (IL-7R alpha) expression on T cells were evaluated in a cross-sectional study of 36 healthy volunteers, 151 HIV-infected patients, and 83 HIV-infected patients who had received IL-2 therapy. Multivariate regression models were used to determine predictors of CD127 expression. Results: HIV-infected patients had higher IL-7 levels compared with healthy volunteers (P = 0.022) and IL-2-treated patients (P = 0.012). CD 127 expression was significantly lower on CD4 and CD8 T cells of HIV-infected patients compared with healthy volunteers (P = 0.008 and P < 0.001, respectively), and CD127 median fluorescence intensity was lowest on CD4 T cells in IL-2-treated patients (P < 0.001 compared with HIV-infected patients). The proportion of naive and effector memory/effector T cells were significant predictors of CD127 expression on T cells. IL-2 immunotherapy led to the expansion of a CD25(+)/CD127-low subset of CD4 T cells. Conclusions: CD127 expression on T cells remains low in HIV-infected patients despite antiretroviral therapy, reflecting persistent aberration in the subset composition of the T-cell pool. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, AIDS Monitoring Lab, Clin Serv Program, Frederick, MD USA. RP Read, SW (reprint author), NIAID, Immunoregulat Lab, NIH, Rm 11B05,Bldg 10,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM readsa@niaid.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 34 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2006 VL 42 IS 5 BP 537 EP 544 DI 10.1097/01.qai.0000223027.47456.d0 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 069KF UT WOS:000239444100003 PM 16837861 ER PT J AU Levine, AM Vigen, C Gravink, J Mack, W Watts, CH Liebman, HA AF Levine, Alexandra M. Vigen, Cheryl Gravink, Jay Mack, Wendy Watts, C. Heather Liebman, Howard A. TI Progressive prothrombotic state in women with advancing HIV disease SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE coagulation abnormalities in HIV disease ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-S DEFICIENCY; LUPUS ANTICOAGULANT; ANTICARDIOLIPIN ANTIBODIES; VENOUS THROMBOEMBOLISM; INFECTED PATIENTS; THROMBOSIS; ASSAY; RISK; PLASMA AB Background: HIV-infected patients are at increased risk for venous thrombotic events (VTEs). We sought to determine if advancing stages of HIV were associated with coagulation abnormalities that could predispose to VTE. Methods: Functional protein S, factor VIII activity, and lupus anticoagulant were assayed in 144 participants of the Women's Interagency HIV Study. Women with conditions associated with VTE (cancer, pregnancy, hormone use, acute infection, cancer, and autoimmune disease) were excluded. Subjects included 34 women with history of clinical AIDS, 11 with immunologic AIDS (CD4 count, < 200 cells/dL), 49 with asymptomatic HIV, and 50 HIV-negative comparators. Results: We found progressive decreases in protein S, when comparing HIV-negative women (median, 76%) to women with asymptomatic HIV (median, 67%), immunologic AIDS (median, 62%), or clinical AIDS (median, 46%; P < 0.0001). Similarly, advancing HIV was associated with stepwise increases in factor VIII, from a median of 116% in HIV-negative women to 149% in those with asymptornatic HIV, 196% in those with immunologic AIDS, and 211% in those with clinical AIDS (P < 0.0001). No subject had lupus anticoagulant. Conclusions: Advancing HIV is associated with progressive abnormalities of protein S and factor VIII, both of which are associated with increased risk for VTE, thus providing a biologic mechanism for the increased prevalence of VTE in HIV. C1 Univ So Calif, Keck Sch Med, Dept Med, Div Hematol, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NICHHD, Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. RP Levine, AM (reprint author), Univ So Calif, Norris Canc Hosp, 1441 Eastlake Ave, Los Angeles, CA 90033 USA. EM alevine@usc.edu FU NIAID NIH HHS [N01-AI-35161, U01-AI-35004, U01-AI-42590, U01-AI-34989, U01-AI-31834, U01-AI-34994]; NICHD NIH HHS [U01-HD-32632] NR 27 TC 22 Z9 22 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 AUG 15 PY 2006 VL 42 IS 5 BP 572 EP 577 DI 10.1097/01.qai.0000230320.78288.79 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 069KF UT WOS:000239444100007 PM 16837864 ER PT J AU French, AL Evans, CT Anastos, K Greenblatt, RM Hershow, R Huebner, R Augenbraun, M Young, M Lopez-Gatell, H Passaro, DJ AF French, Audrey L. Evans, Charlesnika T. Anastos, Kathryn Greenblatt, Ruth M. Hershow, Ronald Huebner, Robin Augenbraun, Michael Young, Mary Lopez-Gatell, Hugo Passaro, Douglas J. TI Incidence of tuberculin skin test conversion among HIV-infected and -uninfected women: Results of a 6-year study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE tuberculosis; screening; purified protein derivative; latent TB infection; tuberculin skin test ID ANTIRETROVIRAL THERAPY; LATENT TUBERCULOSIS AB Objective: To define the incidence of tuberculin skin test (TST) conversion and to evaluate the yield of annual testing in an era of declining tuberculosis incidence in the United States. Methods: Annual TSTs were performed on initially TST-negative women (HIV infected, 995; uninfected, 260) from October 1995 through March 2002. Results: A total of 4622 repeat TSTs were performed during 5530 person-years. The incidence of TST conversion was 0.8 case per 100 person-years for HIV-infected and 1.0 case per 100 person-years for uninfected women. Non-Hispanic blacks, women younger than 40 years of age, and HIV-infected women who had recently initiated active therapy were more likely to experience TST conversion. The incidence of conversion decreased over the course of the study from a peak of 21 cases per 937 tests in 1996 to I case per 179 tests in 2002 (P = 0.046 for trend). Twenty-one of 47 conversions occurred on the second TST, implying that boosting accounted for a number of conversions. Conclusions: The yield of annual skin testing diminished from 1996 to 2002. Our data suggest that repeating testing after initiation of HIV therapy, regardless of CD4 cell change, is warranted. If serial testing is undertaken, initial 2-step testing should be performed to allow for accurate interpretation of subsequent tests and earlier identification of persons with latent Mycobacterium tuberculosis infection. C1 Stroger Hosp Cook Cty, CORE, Chicago, IL 60612 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Lincoln Med Ctr, Bronx, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. NIAID, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP French, AL (reprint author), Stroger Hosp Cook Cty, Div Infect Dis, Durand 115,1901 W Harrison St, Chicago, IL 60612 USA. EM audrey_french@rush.edu FU NCRR NIH HHS [M01-RR-00079, M01-RR-00083, M01-RR-00071]; NIAID NIH HHS [U01-AI-34989, U01-AI-34994, U01-AI-42590, U01-AI-35004, U01-AI-31834, U01-AI-34993]; OID CDC HHS [U01-CH-32632] NR 14 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 15 PY 2006 VL 42 IS 5 BP 592 EP 596 DI 10.1097/01.qai.0000229995.25493.8b PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 069KF UT WOS:000239444100011 PM 16837868 ER PT J AU Larsen, M Wei, C Yamada, KM AF Larsen, Melinda Wei, Cindy Yamada, Kenneth M. TI Cell and fibronectin dynamics during branching morphogenesis SO JOURNAL OF CELL SCIENCE LA English DT Article DE branching morphogenesis; migration; salivary gland; fibronectin ID SUBMANDIBULAR-GLAND DEVELOPMENT; URETERAL BUD; IN-VITRO; BASEMENT-MEMBRANE; EXPRESSION; MECHANISMS; INTEGRITY; FGF AB Branching morphogenesis is a dynamic developmental process shared by many organs, but the mechanisms that reorganize cells during branching morphogenesis are not well understood. We hypothesized that extensive cell rearrangements are involved, and investigated cell migration using two-color confocal time-lapse microscopy to image cell and extracellular-matrix dynamics in developing salivary glands. We labeled submandibular salivary gland (SMG) epithelial cells with green fluorescent protein and matrix with fluorescent fibronectin. Surprisingly, we observed substantial, rapid and relatively random migration of individual epithelial cells during branching morphogenesis. We predicted that cell migration would decrease after formation of acini and, indeed, found that rapid cell movements do not occur in SMG from newborn mice. However, in embryonic SMG epithelial cells, we observed an absence of choreographed cell migration, indicating that patterned cell migration alone cannot explain the highly ordered process of branching morphogenesis. We therefore hypothesized a role for directional fibronection assembly in branching. Washout and pulse-chase experiments revealed that older fibronectin accumulates at the base of the clefts and translocates inwards as a wedge, with newer fibronectin assembling behind it. These findings identify a new mechanism for branching morphogenesis involving directional fibronectin translocation superimposed on individual cell dynamics. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Yamada, KM (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, 30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM kenneth.yamada@nih.gov OI Yamada, Kenneth/0000-0003-1512-6805 FU Intramural NIH HHS NR 32 TC 118 Z9 119 U1 1 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 15 PY 2006 VL 119 IS 16 BP 3376 EP 3384 DI 10.1242/jcs.03079 PG 9 WC Cell Biology SC Cell Biology GA 082IZ UT WOS:000240381300012 PM 16882689 ER PT J AU Hiragun, T Peng, Z Beaven, MA AF Hiragun, Takaaki Peng, Ze Beaven, Michael A. TI Cutting edge: Dexamethasone negatively regulates Syk in mast cells by up-regulating Src-like adaptor protein SO JOURNAL OF IMMUNOLOGY LA English DT Article ID KINASE MAPK PHOSPHATASE-1; RECEPTOR; GLUCOCORTICOIDS; ACTIVATION; TRANSCRIPTION; INHIBITION; EXOCYTOSIS; EXPRESSION; RESPONSES; SLAP-2 AB We have identified Src-like adaptor protein (SLAP) as one of several dexamethasone-inducible inhibitory regulators in mast cells. SLAP is a known inhibitor of T cell signaling and interacts with the tyrosine kinase, Zap70. Exposure of RBL-2H3 mast cells to dexamethasone markedly increased expression of SLAP. Cells so exposed or made to overexpress SLAP exhibited reduced Ag-stimulated phosphorylation of Syk (a cognate of Zap70), linker for activation of T cells, phospholipase C gamma, and ERK. Ca2+ mobilization, Ca2+-dependent degranulation, and ERK-dependent release of arachidonic acid were suppressed as well. Small interfering RNA directed against SLAP blocked the induction of SLAP and reversed the inhibitory effects of dexamethasone on Phosphorylation of Syk, linker for activation of T cells, and phospholipase C gamma, but not downstream events, which are likely suppressed by up-regulation of downstream of tyrosine kinase-1 and MAPK phosphatase-1. The induction of these inhibitory regulators may contribute to the immunosuppressive activity of dexamethasone in mast cells. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Lab Mol Immunol, NIH, Room 8N 109,Bldg 10, Bethesda, MD 20892 USA. EM beavenm@nhlbi.nih.gov FU Intramural NIH HHS NR 25 TC 32 Z9 32 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2047 EP 2050 PG 4 WC Immunology SC Immunology GA 073LU UT WOS:000239745300008 PM 16887961 ER PT J AU Oida, T Xu, LL Weiner, HL Kitahi, A Strober, W AF Oida, Takatoku Xu, Lili Weiner, Howard L. Kitahi, Atsushi Strober, Warren TI TGF-beta-mediated suppression by CD4(+)CD25(+) T cells is facilitated by CTLA-4 signaling SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; REGULATORY CELLS; CUTTING EDGE; ANTIGEN 4; IN-VITRO; ACTIVATION; PHENOTYPE; FURIN; RESPONSIVENESS; STIMULATION AB CD4(+)CD25(+) T cells play a pivotal role in immunological homeostasis by their capacity to exert immunosuppressive activity. However, the mechanism by which these cells function is still a subject for debate. We previously reported that surface (membrane) TGF-beta produced by CD4(+)CD25(+) T cells was an effector molecule mediating suppressor function. We now support this finding by imaging surface TGF-beta on Foxp3(+)CD4(+)CD25(+) T cells in confocal fluorescence microscopy. Then, using a TGF-beta-sensitive mink lung epithelial cell (luciferase) reporter system, we show that surface TGF-beta can be activated to signal upon cell-cell contact. Moreover, if such TGF-beta signaling is blocked in an in vitro assay of CD4(+)CD25(+) T cell suppression by a specific inhibitor of TGF-beta RI, suppressor function is also blocked. Finally, we address the role of CTLA-4 in CD4(+)CD25(+) T cell suppression, showing first that whereas anti-CTLA-4 does not block in vitro suppressor function, it does complement the blocking activity of anti-TGF-beta. We then show with confocal fluorescence microscopy that incubation of CD4(+)CD25(+) T cells with anti-CTLA-4- and rB7-1/Fc-coated beads results in accumulation of TGF-beta at the cell-bead contact site. This suggests that CTLA-4 signaling facilitates TGF-beta-mediated suppression by intensifying the TGF-beta signal at the point of suppressor cell-target cell interaction. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Ctr Neurol Dis, Boston, MA 02115 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH,Clin Res Ctr, Room 5W3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 38 TC 95 Z9 107 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2331 EP 2339 PG 9 WC Immunology SC Immunology GA 073LU UT WOS:000239745300041 PM 16887994 ER PT J AU Heraud, JM Edghill-Smith, Y Ayala, V Kalisz, I Parrino, J Kalyanaraman, VS Manischewitz, J King, LR Hryniewicz, A Trindade, CJ Hassett, M Tsai, WP Venzon, D Nalca, A Vaccari, M Silvera, P Bray, M Graham, BS Golding, H Hooper, JW Franchini, G AF Heraud, Jean-Michel Edghill-Smith, Yvette Ayala, Victor Kalisz, Irene Parrino, Janie Kalyanaraman, Vaniambadi S. Manischewitz, Jody King, Lisa R. Hryniewicz, Anna Trindade, Christopher J. Hassett, Meredith Tsai, Wen-Po Venzon, David Nalca, Aysegul Vaccari, Monica Silvera, Peter Bray, Mike Graham, Barney S. Golding, Hana Hooper, Jay W. Franchini, Genoveffa TI Subunit recombinant vaccine protects against monkeypox SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SMALLPOX VACCINE; VIRUS CHALLENGE; NONHUMAN-PRIMATES; LETHAL MONKEYPOX; MICE; NEUTRALIZATION; INFECTION; IMMUNIZATION; EXPRESSION; ANTIBODIES AB The smallpox vaccine Dryvax, a live vaccinia virus (VACV), protects against smallpox and monkeypox, but is contraindicated in immunocompromised individuals. Because Abs to VACV mediate protection, a live virus vaccine could be substituted by a safe subunit protein-based vaccine able to induce a protective Ab response. We immunized rhesus macaques with plasmid DNA encoding the monkeypox orthologs of the VACV L1R, A27L, A33R, and B5R proteins by the intradermal and i.m. routes, either alone or in combination with the equivalent recombinant proteins produced in Escherichia coli. Animals that received only DNA failed to produce high titer Abs, developed innumerable skin lesions after challenge, and died in a manner similar to placebo controls. By contrast, the animals vaccinated with proteins developed moderate to severe disease (20-155 skin lesions) but survived. Importantly, those immunized with DNA and boosted with proteins had mild disease with 15 or fewer lesions that resolved within days. DNA/protein immunization elicited Th responses and binding Ab titers to all four proteins that correlated negatively with the total lesion number. The sera of the immunized macaques recognized a limited number of linear B cell epitopes that are highly conserved among orthopoxviruses. Their identification may guide future efforts to develop simpler, safer, and more effective vaccines for monkeypox and smallpox. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD 21701 USA. Adv BioSci Labs, Kensington, MD 20895 USA. NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Med Univ Bialystok, Dept Gen & Expt Pathol, Bialystok, Poland. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. NIAID, Biodef Clin Res Branch, Bethesda, MD 20892 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Bldg 41,Room D-804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI HERAUD, Jean-Michel/O-1464-2013; OI HERAUD, Jean-Michel/0000-0003-1107-0859; Hooper, Jay/0000-0002-4475-0415 FU Intramural NIH HHS; NIAID NIH HHS [N01 AI 15451] NR 35 TC 71 Z9 73 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2552 EP 2564 PG 13 WC Immunology SC Immunology GA 073LU UT WOS:000239745300064 PM 16888017 ER PT J AU Foulds, KE Rotte, MJ Seder, RA AF Foulds, Kathryn E. Rotte, Masashi J. Seder, Robert A. TI IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; CYTOKINE PRODUCTION; LEISHMANIA-MAJOR; FACTOR-ALPHA; IFN-GAMMA; INTERLEUKIN-10-DEFICIENT MICE; ACTIVATED MACROPHAGES; TOXOPLASMA-GONDII; TRYPANOSOMA-CRUZI AB IL-10 is an important immunoregulatory cytokine that plays a central role in maintaining a balance between protective immunity against infection and limiting proinflammatory responses to self or cross-reactive Ags. We examined the full effects of IL-10 deficiency on the establishment and quality of T cell memory using murine listeriosis as a model system. IL-10(-/-) mice had reduced bacterial loads and a shorter duration of primary infection than did wild-type mice. However, the number of Ag-specific T cells in secondary lymphoid and nonlymphoid organs was diminished in IL-10(-/-) mice, compared with wild-type mice, at the peak of the effector response. Moreover, the frequency and protective capacity of memory T cells also were reduced in IL-10(-/-) mice when assessed up to 100 days postinfection. Remarkably, this effect was more pronounced for CD8 T cells than CD4 T cells. To address whether differences in the number of bacteria and duration of primary infection could explain these findings, both strains of mice were treated with ampicillin 24 hours after primary infection. Despite there being more comparable bacterial loads during primary infection, IL-10(-/-) mice still generated fewer memory CD8 T cells and were less protected against secondary infection than were wild-type mice. Finally, the adoptive transfer of purified CD8 T cells from previously infected wild-type mice into naive recipients conferred better protection than the transfer of CD8 T cells from immune IL-10(-/-) mice. Overall, these data show that IL-10 plays an unexpected role in promoting and/or sustaining CD8 T cell memory following Listeria monocytogenes infection. C1 NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 3512, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov NR 61 TC 54 Z9 56 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2565 EP 2574 PG 10 WC Immunology SC Immunology GA 073LU UT WOS:000239745300065 PM 16888018 ER PT J AU Abdool, K Cretney, E Brooks, AD Kelly, JM Swann, J Shanker, A Bere, EW Yokoyama, WM Ortaldo, JR Smyth, MJ Sayers, TJ AF Abdool, Karen Cretney, Erika Brooks, Alan D. Kelly, Janice M. Swann, Jeremy Shanker, Anil Bere, Earl W., Jr. Yokoyama, Wayne M. Ortaldo, John R. Smyth, Mark J. Sayers, Thomas J. TI NK cells use NKG2D to recognize a mouse renal cancer (Renca), yet require intercellular adhesion molecule-1 expression on the tumor cells for optimal perforin-dependent effector function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID APOPTOSIS-INDUCING LIGAND; NATURAL-KILLER-CELLS; FAS LIGAND; IN-VIVO; T-CELLS; MEDIATED CYTOTOXICITY; CUTTING EDGE; IFN-GAMMA; RECEPTOR; METASTASIS AB The NKG2D receptor on NK cells can recognize a variety of ligands on the tumor cell surface. Using a mouse renal cancer (Renca), we show that NKG2D recognition by NK cells was crucial for their ability to limit tumor metastases in vivo in both liver and lungs using perforin-dependent effector mechanisms. However, for the R331 cell line established from Renca, NKG2D recognition and perforin-dependent lysis played no role in controlling liver metastases. R331 cells were also more resistant to perforin-dependent lysis by NK cells in vitro. We therefore used these phenotypic differences between Renca and R331 to further investigate the crucial receptor:ligand interactions required for triggering lytic effector functions of NK cells. Reconstitution of R331 cells with ICAM-1, but not Rae-1 gamma, restored NKG2D-mediated, perforin-dependent lysis. Interestingly, R331 cells were efficiently lysed by NK cells using death ligand-mediated apoptosis. This death ligand-mediated killing did not depend on NKG2D recognition of its ligands on tumor cells. This result suggests that the intracellular signaling in NK cells required for perforin and death ligand-mediated lysis of tumor target cell are quite distinct, and activation of both of these antitumor lytic effector functions of NK cells could improve therapeutic benefits for certain tumors. C1 NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. Howard Univ, Coll Med, Dept Microbiol, Washington, DC USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Peter MacCallum Canc Ctr, Canc Immunol Program, Trescowthick Labs, Melbourne, Vic, Australia. RP Sayers, TJ (reprint author), NCI, SAIC Frederick, Basic Res Program, Ctr Canc Res, POB B,Bldg 560,Room 31-67, Frederick, MD 21702 USA. EM Sayerst@mail.nih.gov RI Sayers, Thomas/G-4859-2015; Smyth, Mark/H-8709-2014; OI Smyth, Mark/0000-0001-7098-7240; Shanker, Anil/0000-0001-6372-3669 FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 44 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2575 EP 2583 PG 9 WC Immunology SC Immunology GA 073LU UT WOS:000239745300066 PM 16888019 ER PT J AU Garcia, CS Curiel, RE Mwatibo, JM Pestka, S Li, HF Espinoza-Delgado, I AF Garcia, Carmen S. Curiel, Rafael E. Mwatibo, James M. Pestka, Sidney Li, Huifen Espinoza-Delgado, Igor TI The antineoplastic agent bryostatin-1 differentially regulates IFN-gamma receptor Subunits in monocytic cells: Transcriptional and posttranscriptional control of IFN-gamma R2 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; MESSENGER-RNA DEGRADATION; INTERFERON-GAMMA; GENE-EXPRESSION; ACCESSORY FACTOR; T-CELLS; ACTIVATOR BRYOSTATIN-1; EXTRACELLULAR DOMAIN AB .Bryostatin-1 (Bryo-1) is a potent ligand and modulator of protein kinase C that exerts antineophistic and immunomodulatory activities both in vitro and in vivo. We have previously reported that Bryo-1 synergized with IFN-gamma to induce NO synthase and NO by macrophages. To determine whether this effect was associated with changes in levels of IFN-gamma R, we investigated the effects of Bryo-1 on the expression and regulation of IFN-gamma R chains in monocytic cells. Northern blot analysis revealed that Bryo-1 treatment of the human monocytic cell lines MonoMac6 and THP-1 and human monocytes enhanced the expression of IFN-gamma R2 mRNA but did not affect IFN-gamma R1 mRNA expression. Bryo-1 increased IFN-gamma R2 mRNA in a dose-dependent manner as early as 3 h posttreatment. Bryo-1-induced up-regulation of IFN-gamma R2 mRNA levels is not dependent on de novo protein synthesis as shown by cell treatment with the protein-synthesis inhibitor cycloheximide. Bryo-1 treatment increased the IFN-gamma R2 mRNA half-life by 2 h. EMSA analysis from Bryo-1-treated MonoMac6 cells showed an increased nuclear protein binding to the NF-kappa B motif present in the 5' flanking region of the human IFN-gamma R2 promoter that was markedly decreased by-pretreatment with the NF-kappa B inhibitor SN50. These results show for the first time that Bryo-1 up-regulates IFN-gamma R2 expression in monocytic cells. Given the pivotal role that IFN-gamma exerts on monocyte activation and in the initiation and outcome of the immune response, the induction of IFN-gamma R2 by Bryo-1 has significant implications in immunomodulation and could overcome some of the immune defects observed in cancer patients. C1 NIA, Hematol Oncol Sect, Gerontol Res Ctr, Baltimore, MD 21224 USA. Louisiana State Univ, Med Ctr, Dept Med, New Orleans, LA 70112 USA. Louisiana State Univ, Med Ctr, Stanley S Scott Canc Ctr, New Orleans, LA 70112 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. RP Espinoza-Delgado, I (reprint author), NIA, Hematol Oncol Sect, Gerontol Res Ctr, 5600 Nathan Shock Dr,Room 4C10, Baltimore, MD 21224 USA. EM espinozaig@grc.nia.nih.gov FU Intramural NIH HHS; NCI NIH HHS [R01 CA 46465]; NIAID NIH HHS [R01 AI 43369, R01 AI 59465, R01 AI 36450, P01 AI 57596] NR 58 TC 7 Z9 8 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2006 VL 177 IS 4 BP 2707 EP 2716 PG 10 WC Immunology SC Immunology GA 073LU UT WOS:000239745300080 PM 16888033 ER PT J AU Castellucci, L Menezes, E Oliveira, J Magalhaes, A Guimaraes, LH Lessa, M Ribeiro, S Reale, J Noronha, EF Wilson, ME Duggal, P Beaty, TH Jeronimo, S Jamieson, SE Bales, A Blackwell, JM de Jesus, AR Carvalho, EM AF Castellucci, Lea Menezes, Eliane Oliveira, Joyce Magalhaes, Andrea Guimaraes, Luiz Henrique Lessa, Marcus Ribeiro, Silvana Reale, Jeancarlo Noronha, Elza Ferreira Wilson, Mary E. Duggal, Priya Beaty, Terri H. Jeronimo, Selma Jamieson, Sarra E. Bales, Ashlee Blackwell, Jenefer M. Ribeiro de Jesus, Amelia Carvalho, Edgar M. TI IL6-174 G/C promoter polymorphism influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID REGULATORY T-CELLS; MUCOCUTANEOUS LEISHMANIASIS; TRES-BRACOS; IL-6; DIFFERENTIATION; ASSOCIATION; MACROPHAGES; GENOTYPE; IMMUNITY; IDENTIFICATION AB Background. Mucosal leishmaniasis (ML) is associated with exaggerated tumor necrosis factor-alpha and interferon-gamma responses and tissue destruction. ML follows localized cutaneous leishmaniasis (CL) caused by Leishmania braziliensis infection. Interleukin (IL)-6 down-regulates T helper (Th) cell type 1 differentiation and drives Th2 cell differentiation. The IL6 -174 G/C polymorphism is associated with proinflammatory diseases and IL-6 regulation. Methods. The -174 G/C polymorphism was genotyped in population samples and families with CL and ML from Brazil. Genotype frequencies were compared among patients with ML, patients with CL, and 2 control groups by logistic regression and family-based association test (FBAT) analysis. IL-6 levels were measured in macrophages. Results. The C allele was more common in patients with ML than in patients with CL (odds ratio [OR], 2.55 [95% confidence interval {CI}, 1.32-4.91]; P = .005), than in patients who were leishmanin skin-test positive (OR, 2.23 [95% CI, 1.23-4.05]; P = .009), and than in neighborhood control subjects (OR, 2.47 [95% CI, 1.24-4.90]; P = .01). FBAT analysis confirmed an association between allele C and ML under both additive (P = .000017) and dominant (z = 4.325; P = .000015) models. Significantly lower levels of IL-6 were measured in unstimulated macrophages from CC individuals than from GG individuals (P = .003) as well as after stimulation with soluble leishmania antigen (P = .009). Conclusions. IL-6 may regulate type 1 proinflammatory responses, putting individuals with low macrophage IL-6 levels at increased risk for ML. C1 Univ Fed Bahia, HUPES, Serv Imunol, Salvador, BA, Brazil. Univ Fed Rio Grande Norte, Dept Bioquim, Ctr Biociencias, BR-59072970 Natal, RN, Brazil. Univ Brasilia, BR-70910900 Brasilia, DF, Brazil. Univ Iowa, Iowa City, IA 52242 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD USA. Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge CB2 1TN, England. RP de Jesus, AR (reprint author), Univ Fed Bahia, HUPES, Serv Imunol, 5o Andar,Rua Joao Botas S-N, Salvador, BA, Brazil. EM imuno@ufba.br RI Blackwell, Jenefer/H-3015-2015 FU FIC NIH HHS [1 D43 TW007127-01]; Intramural NIH HHS; NIAID NIH HHS [AI-30639, AI-48822, R01 AI048822]; Wellcome Trust NR 39 TC 55 Z9 56 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 15 PY 2006 VL 194 IS 4 BP 519 EP 527 DI 10.1086/505504 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 064WO UT WOS:000239121000016 PM 16845637 ER PT J AU Gsell, W Burke, M Wiedermann, D Bonvento, G Silva, AC Dauphin, F Buhrle, C Hoehn, M Schwindt, W AF Gsell, Willy Burke, Michael Wiedermann, Dirk Bonvento, Gilles Silva, Afonso C. Dauphin, Francois Buehrle, Christian Hoehn, Mathias Schwindt, Wolfram TI Differential effects of NMDA and AMPA glutamate receptors on functional magnetic resonance imaging signals and evoked neuronal activity during forepaw stimulation of the rat SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate; AMPA receptors; NMDA receptors; functional magnetic resonance imaging; evoked potentials; somatosensory cortex; rat ID NITRIC-OXIDE SYNTHASE; CEREBRAL-BLOOD-FLOW; CHLORALOSE ANESTHETIZED RATS; ACTIVITY-DEPENDENT INCREASES; MOUSE SOMATOSENSORY CORTEX; ALPHA-CHLORALOSE; IN-VIVO; GLUCOSE-UTILIZATION; VENTRAL POSTERIOR; BRAIN-FUNCTION AB Most of the currently used methods for functional brain imaging do not visualize neuronal activity directly but rather rely on the elicited hemodynamic and/or metabolic responses. Glutamate, the major excitatory neurotransmitter, plays an important role in the neurovascular/neurometabolic coupling, but the specific mechanisms are still poorly understood. To investigate the role of the two major ionotropic glutamate receptors [NMDA receptors (NMDA-Rs) and AMPA receptors (AMPA-Rs)] for the generation of functional magnetic resonance imaging (fMRI) signals, we used fMRI [measurements of blood oxygenation level-dependent (BOLD), perfusion-weighted imaging (PWI), and cerebral blood volume (CBV)] together with recordings of somatosensory evoked potentials (SEPs) during electrical forepaw stimulation in the alpha-chloralose anesthetized rat. Intravenous injection of theNMDA-Rantagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a, d] cyclohepten-5,10-imine maleate] (0.06 mg/kg plus 3.6 mu g (.) kg(-1) (.) h(-1)) significantly decreased BOLD (-51 +/- 19%; n = 5) and PWI (- 57 +/- 26%; n = 5) responses but reduced the SEPs only mildly (approximately - 10%). Systemic application of the AMPA-R antagonist GYKI-53655 [1-(4-aminophenyl)-3-methylcarbamyl-4-methyl7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine] significantly decreased both the hemodynamic response (BOLD, -49 +/- 13 and -65 +/- 15%; PWI, -22 +/- 48 and -68 +/- 4% for 5 and 7 mg/kg, i. v., respectively; CBV, -80 +/- 7% for 7 mg/kg; n = 4) and the SEPs (up to -60%). These data indicate that the interaction of glutamate with its postsynaptic and/or glial receptors is necessary for the generation of blood flow and BOLD responses and illustrate the differential role of NMDA-Rs and AMPA-Rs in the signaling chain leading from increased neuronal activity to the hemodynamic response in the somatosensory cortex. C1 Univ Hosp Munster, Dept Clin Radiol, D-48129 Munster, Germany. Max Planck Inst Neurol Res, D-50931 Cologne, Germany. Univ Caen, CNRS, UMR 6551, F-14032 Caen, France. Univ Glasgow, Wellcome Surg Inst, MR Facil 7T, Glasgow 6G1 1QH, Lanark, Scotland. Univ Marburg, Sect Expt & Biol Psychol, Fac Psychol, D-35032 Marburg, Germany. Serv Hosp Frederic Joliot, CNRS, URA 2210, CEA, F-91401 Orsay, France. NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. Univ Caen, Ctr Etud Rech Medicament Normandie, F-14032 Caen, France. Univ Cologne, Dept Stereotact & Funct Neurosurg, D-50923 Cologne, Germany. RP Schwindt, W (reprint author), Univ Hosp Munster, Dept Clin Radiol, D-48129 Munster, Germany. EM wschwindt@uni-muenster.de RI Silva, Afonso/A-7129-2009; Gsell, Willy/D-6545-2012; Bonvento, Gilles/F-6023-2013; Dauphin, Francois/B-1642-2012 OI Bonvento, Gilles/0000-0002-2886-4228; FU Intramural NIH HHS NR 71 TC 44 Z9 47 U1 0 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 AUG 15 PY 2006 VL 26 IS 33 BP 8409 EP 8416 DI 10.1523/JNEUROSCI.4615-05.2006 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 074MY UT WOS:000239817700001 PM 16914666 ER PT J AU Xi, ZX Gilbert, JG Peng, XQ Pak, AC Li, X Gardner, EL AF Xi, Zheng-Xiong Gilbert, Jeremy G. Peng, Xiao-Qing Pak, Arlene C. Li, Xia Gardner, Eliot L. TI Cannabinoid CB1 receptor antagonist AM251 inhibits cocaine-primed relapse in rats: Role of glutamate in the nucleus accumbens SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cocaine; dopamine; glutamate; mGluR2/3; AM251; cannabinoid; relapse ID DRUG-SEEKING BEHAVIOR; PRIMING-INDUCED REINSTATEMENT; MU-OPIOID RECEPTORS; SYNAPTIC TRANSMISSION; DOPAMINE; HEROIN; SHELL; CB1; REINFORCEMENT; SENSITIZATION AB Blockade of cannabinoid CB1 receptors has been reported to inhibit cocaine- or cocaine cue-induced reinstatement of drug seeking. However, the mechanisms underlying this action are poorly understood. Given the importance of dopamine, glutamate, and GABA in cocaine reward and relapse, we studied the effects of AM251 [N-(piperidin-1-yl)-5-(4-iodophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3- carboxamide], a novel highly selective CB1 receptor antagonist, on cocaine- primed reinstatement of drug-seeking behavior and on cocaine- induced changes in extracellular DA, glutamate, and GABA in the nucleus accumbens (NAc) under reinstatement conditions. We found that systemic administration of AM251 selectively inhibited cocaine- induced, but not sucrose plus sucrose cue-induced, reinstatement of reward-seeking behavior. AM251 alone did not trigger reinstatement. Local perfusion of AM251 into the NAc or the dorsal striatum also inhibited cocaine- triggered reinstatement. AM251 alone dose dependently elevated NAc glutamate in a voltage-dependent Na+ channel-dependent manner. AM251 did not affect NAc DA or GABA. Pretreatment with AM251 dose dependently inhibited cocaine- induced increases in NAc glutamate but not in DA. Blockade of NAc metabotropic glutamate mGluR2/3 receptors by LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] slightly facilitated cocaine-enhanced glutamate release but blocked the antagonism of cocaine- induced reinstatement by AM251. These data suggest the following: (1) CB1 receptors exert tonic inhibition over NAc glutamate release under cocaine- extinction conditions; (2) blockade of CB1 receptors by AM251 inhibits cocaine- enhanced NAc glutamate release and cocaine- triggered reinstatement; and (3) these effects appear to be mediated by activation of presynaptic mGluR2/3 autoreceptors secondary to AM251-induced increase (disinhibition) of NAc glutamate release. C1 NIDA, Neuropsychopharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept HHS, Baltimore, MD 21224 USA. RP Xi, ZX (reprint author), NIDA, Neuropsychopharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept HHS, POB 5180, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov OI PENG, XIAOQING/0000-0002-7272-5428 FU Intramural NIH HHS NR 34 TC 103 Z9 103 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 2006 VL 26 IS 33 BP 8531 EP 8536 DI 10.1523/JNEUROSCI.0726-06.2006 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 074MY UT WOS:000239817700014 PM 16914679 ER PT J AU Matsusue, K Miyoshi, A Yamano, S Gonzalez, FJ AF Matsusue, Kimihiko Miyoshi, Aya Yamano, Shigeru Gonzalez, Frank J. TI Ligand-activated PPAR beta efficiently represses the induction of LXR-dependent promoter activity through competition with RXR SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE PPAR; PPAR beta/8; triglyceride; angiopoietin; LXR; RXR ID RETINOID-X-RECEPTOR; FATTY-ACID-METABOLISM; THYROID-HORMONE; NUCLEAR RECEPTORS; CROSS-TALK; TRANSCRIPTIONAL ACTIVATION; NUTRITIONAL REGULATION; LIPID-METABOLISM; PROLIFERATOR; GENE AB Angiopoietin-like protein 3 (angptl3), a member of the vascular endothelial growth factor family, was shown to play an important role in regulating lipid metabolism. To elucidate the mechanism by which PPAR beta represses angptl3 promoter activity, reporter constructs were prepared and transfection analysis carried out. PPAR beta repressed angptl3-Luc promoter activity and activation of PPAR beta by L-165041, a PPAR beta-specific ligand, increased the extent of repression. The repression by L-I 65041 was lost in angptl3-Lucplasmids having a deleted or mutated LXR alpha binding site (DR4). PPAR beta L405R, deficient in RXR alpha binding, had no effect on angptl3-Luc promoter activity. PPAR beta did not repress the activity of GAL4-LXR alpha which activates of GAL4DBD TK-Luc independent of RXR. Addition of RXRa completely abolished the repression of angptl3-Lue activity by PPAR beta. Mammalian two-hybrid analysis revealed that PPAR beta ligand binding enhanced the dissociation of the LXR alpha-RXR alpha heterodimer. Gel shift assays also indicated that PPAR beta ligand binding increased dissociation of LXR alpha/RXR alpha binding to a DR4 oligonucleotide probe; addition of RXR alpha restored the binding lost by addition of PPAR beta. Collectively, these results suggest that the binding of PPAR beta-specific ligand enhances the affinity between RXR alpha and activated PPAR beta and thus may regulate angptl3 gene expression through a DR4 element by competing with LXR alpha for RXR alpha. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, Fukuoka 8140180, Japan. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005708-14] NR 46 TC 21 Z9 26 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD AUG 15 PY 2006 VL 256 IS 1-2 BP 23 EP 33 DI 10.1016/j.mce.2006.05.005 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 085VO UT WOS:000240632700004 PM 16806672 ER PT J AU Hutchinson, EB Stefanovic, B Koretsky, AP Silva, AC AF Hutchinson, Elizabeth B. Stefanovic, Bojana Koretsky, Alan P. Silva, Afonso C. TI Spatial flow-volume dissociation of the cerebral microcirculatory response to mild hypercapnia SO NEUROIMAGE LA English DT Article DE cerebral blood flow; brain; red blood cell velocity; hypercapnia; two-photon microscopy ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; RAT-BRAIN; WHISKER STIMULATION; IN-VIVO; SOMATOSENSORY STIMULATION; CONFOCAL MICROSCOPY; NEURONAL-ACTIVITY; PLASMA PERFUSION; LASER AB The spatial and temporal response of the cerebral microcirculation to mild hypercapnia was investigated via two-photon laser-scanning microscopy. Cortical vessels, traversing the top 200 mu m of somatosensory cortex, were visualized in alpha-chloralose-anesthetized Sprague-Dawley rats equipped with a cranial window. Intraluminal vessel diameters, transit times of fluorescent dextrans and red blood cells (RBC) velocities in individual capillaries were measured under normocapnic (PaCO2 = 32.6 +/- 2.6 mm Hg) and slightly hypercapnic (PaCO2 = 45 7 mm Hg) conditions. This gentle increase in PaCO2 was sufficient to produce robust and significant increases in both arterial and venous vessel diameters, concomitant to decreases in transit times of a bolus of dye from artery to venule (14%, P < 0.05) and from artery to vein (27%, P < 0.05). On the whole, capillaries exhibited a significant increase in diameter (16 +/- 33%, P < 0.001, n = 393) and a substantial increase in RBC velocities (75 +/- 114%, P < 0.001, n = 46) with hypercapnia. However, the response of the cerebral microvasculature to modest increases in PaCO2 was spatially heterogeneous. The maximal relative dilatation (range: 5-77%; mean SD: 25 +/- 34%, P < 0.001, n = 271) occurred in the smallest capillaries (1.6 mu m-4.0 mu m resting diameter), while medium and larger capillaries (4.4 mu m-6.8 mu m resting diameter) showed no significant changes in diameter (P > 0.08, n = 122). In contrast, on average, RBC velocities increased less in the smaller capillaries (39 +/- 5%, P < 0.002, n = 22) than in the medium and larger capillaries (107 +/- 142%, P < 0.003, n = 24). Thus, the changes in capillary RBC velocities were spatially distinct from the observed volumetric changes and occurred to homogenize cerebral blood flow along capillaries of all diameters. Published by Elsevier Inc. C1 NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Silva, AC (reprint author), NINDS, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Room B1D114, Bethesda, MD 20892 USA. EM Silvaa@ninds.nih.gov RI Silva, Afonso/A-7129-2009; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS002989-08] NR 60 TC 71 Z9 71 U1 0 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2006 VL 32 IS 2 BP 520 EP 530 DI 10.1016/j.neuroimage.2006.03.033 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 074YO UT WOS:000239848700005 PM 16713717 ER PT J AU Hahn, B Ross, TJ Stein, EA AF Hahn, Britta Ross, Thomas J. Stein, Elliot A. TI Neuroanatomical dissociation between bottom-up and top-down processes of visuospatial selective attention SO NEUROIMAGE LA English DT Article ID ANTERIOR CINGULATE CORTEX; LATERAL INTRAPARIETAL AREA; OVERLAPPING NEURAL SYSTEMS; POSTERIOR PARIETAL CORTEX; COVERT SPATIAL ATTENTION; FRONTAL EYE-FIELD; VISUAL-ATTENTION; HUMAN BRAIN; NETWORK; MECHANISMS AB Allocation of attentional resources to portions of the available sensory input can be regulated by bottom-up processes, i.e., spontaneous orientation towards an oncoming stimulus (stimulus-driven attention), and by top-down processes, i.e., intentionally and driven by knowledge, expectation and goals. The present study aimed at advancing the understanding of brain networks mediating bottom-up and top-down control of visuospatial attention by employing a paradigm that parametrically varied demands on these two processes. Spatial predictability of peripheral targets was parametrically varied by centrally cueing one, two, three or four of four possible locations. Reaction time decreased linearly with more precise valid cueing of the target location and increased with more precise invalid cueing. Event-related functional magnetic resonance imaging (fMRI) enabled measurement of blood oxygenation level-dependent (BOLD) responses to cues and to targets. A mostly left-hemispheric network consisting of left intraparietal sulcus, inferior and superior parietal lobule, bilateral precuneus, middle frontal gyri including superior frontal sulci, and middle occipital gyri displayed BOLD responses to cues that increased linearly with more precise spatial cueing, indicating engagement by top-down spatial selective attention. In contrast, bilateral temporoparietal junction, cingulate gyrus, right precentral gyrus and anterior and posterior insula, bilateral fusiform gyri, lingual gyri and caucus displayed BOLD responses to targets that increased with their spatial unpredictability, indicating engagement by stimulus-driven orienting. The results suggest two largely dissociated neural networks mediating top - down and bottom - up control of visuospatial selective attention. (c) 2006 Elsevier Inc. All rights reserved. C1 NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Hahn, B (reprint author), NIDA, Intramural Res Program, Neuroimaging Res Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bhahn@intra.nida.nih.gov RI Ross, Thomas/B-7469-2008; Stein, Elliot/C-7349-2008; Frank, David/E-8213-2012; Hahn, Britta/G-4593-2012 OI Ross, Thomas/0000-0002-7745-3572; FU Intramural NIH HHS [Z99 DA999999] NR 48 TC 113 Z9 114 U1 3 U2 26 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD AUG 15 PY 2006 VL 32 IS 2 BP 842 EP 853 DI 10.1016/j.neuroimage.2006.04.177 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 074YO UT WOS:000239848700036 PM 16757180 ER PT J AU Overholtzer, M Zhang, J Smolen, GA Muir, B Li, W Sgroi, DC Deng, CX Brugge, JS Haber, DA AF Overholtzer, Michael Zhang, Jianmin Smolen, Gromoslaw A. Muir, Beth Li, Wenmei Sgroi, Dennis C. Deng, Chu-Xia Brugge, Joan S. Haber, Daniel A. TI Transforming properties of YAP, a candidate oncogene on the chromosome 11q22 amplicon SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE breast; mammary; transformation; Yorkie ID YES-ASSOCIATED PROTEIN; COMPARATIVE GENOMIC HYBRIDIZATION; SQUAMOUS-CELL CARCINOMA; MAMMARY EPITHELIAL-CELLS; AMINO-ACID CHANGE; TUMOR-SUPPRESSOR; PROMOTES APOPTOSIS; BREAST-CANCER; TRANSCRIPTIONAL COACTIVATOR; PROLIFERATION ARREST AB In a screen for gene copy-number changes in mouse mammary tumors, we identified a tumor with a small 350-kb amplicon from a region that is syntenic to a much larger locus amplified in human cancers at chromosome 11c122. The mouse amplicon contains only one known gene, Yap, encoding the mammalian ortholog of Drosophila Yorkie (Yki), a downstream effector of the Hippo(Hpo)Salvador(Sav)-Warts(Wts) signaling cascade, recently identified in flies as a critical regulator of cellular proliferation and apoptosis. In nontransformed mammary epithelial cells, overexpression of human YAP induces epithelial-to-mesenchymal transition, suppression of apoptosis, growth factor-independent proliferation, and anchorage-independent growth in soft agar. Together, these observations point to a potential oncogenic role for YAP in 11q22amplified human cancers, and they suggest that this highly conserved signaling pathway identified in Drosophila regulates both cellular proliferation and apoptosis in mammalian epithelial cells. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Pathol Res Unit,Dept Pathol, Charlestown, MA 02129 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Brugge, JS (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM joan_brugge@hms.harvard.edu RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [F32 CA117737, CA080111, CA089393, P01 CA080111, P01 CA95281, P50 CA089393, T32 CA009361, T32CA09361] NR 54 TC 423 Z9 439 U1 4 U2 46 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 15 PY 2006 VL 103 IS 33 BP 12405 EP 12410 DI 10.1073/pnas.0605579103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 075EW UT WOS:000239867500038 PM 16894141 ER PT J AU Mehler, EL Hassan, SA Kortagere, S Weinstein, H AF Mehler, Ernest L. Hassan, Sergio A. Kortagere, Sandhya Weinstein, Harel TI Ab initio computational modeling of loops in G-protein-coupled receptors: Lessons from the crystal structure of rhodopsin SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE calculation of loop structures in GPCRs; loops in rhodopsin; continuum solvent model; biased scaled collective variables; Monte Carlo simulations ID SOLVENT-INDUCED FORCES; SCREENED COULOMB POTENTIALS; SIDE-CHAIN INTERACTIONS; MOLECULAR-DYNAMICS; POLYPEPTIDE FRAGMENTS; SURFACE LOOPS; ENERGY; SIMULATION; PREDICTION; CONFORMATIONS AB With the help of the crystal structure of rhodopsin an ab initio method has been developed to calculate the three-dimensional structure of the loops that connect the transmembrane helices (TMHs). The goal of this procedure is to calculate the loop structures in other G-protein coupled receptors (GPCRs) for which only model coordinates of the TMHs are available. To mimic this situation a construct of rhodopsin was used that only includes the experimental coordinates of the TMHs while the rest of the structure, including the terminal domains, has been removed. To calculate the structure of the loops a method was designed based on Monte Carlo (MC) simulations which use a temperature annealing protocol, and a scaled collective variables (SCV) technique with proper structural constraints. Because only part of the protein is used in the calculations the usual approach of modeling loops, which consists of finding a single, lowest energy conformation of the system, is abandoned because such a single structure may not be a representative member of the native ensemble. Instead, the method was designed to generate structural ensembles from which the single lowest free energy ensemble is identified as representative of the native folding of the loop. To find the native ensemble a successive series of SCV-MC simulations are carried out to allow the loops to undergo structural changes in a controlled manner. To increase the chances of finding the native funnel for the loop, some of the SCV-MC simulations are carried out at elevated temperatures. The native ensemble can be identified by an MC search starting from any conformation already in the native funnel. The hypothesis is that native structures are trapped in the conformational space because of the high-energy barriers that surround the native funnel. The existence of such ensembles is demonstrated by generating multiple copies of the loops from their crystal structures in rhodopsin and carrying out an extended SCV-MC search. For the extracellular loops e1 and e3, and the intracellular loop i1 that were used in this work, the procedure resulted in dense clusters of structures with C alpha-RMSD similar to 0.5 angstrom. To test the predictive power of the method the crystal structure of each loop was replaced by its extended conformations. For e1 and i1 the procedure identifies native clusters with C alpha-RMSD similar to 0.5 angstrom and good structural overlap of the side chains; for e3, two clusters were found with C alpha-RMSD similar to 1.1 angstrom each, but with poor overlap of the side chains. Further searching led to a single cluster with lower C alpha-RMSD but higher energy than the two previous clusters. This discrepancy was found to be due to the missing elements in the constructs available from experiment for use in the calculations. Because this problem will likely appear whenever parts of the structural information are missing, possible solutions are discussed. C1 Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. NIH, Ctr Mol Modeling, Div Computat Biosci, DHHS, Bethesda, MD USA. RP Mehler, EL (reprint author), Cornell Univ, Weill Med Coll, Dept Physiol & Biophys, New York, NY 10021 USA. EM elm2020@med.cornell.edu FU NIDA NIH HHS [P01 DA12923, DA00060, R01 DA15170] NR 66 TC 32 Z9 32 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD AUG 15 PY 2006 VL 64 IS 3 BP 673 EP 690 DI 10.1002/prot.21022 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 064QI UT WOS:000239103800010 PM 16729264 ER PT J AU Garner, CE Sumner, SCJ Davis, JG Burgess, JP Yueh, Y Demeter, J Zhan, Q Valentine, J Jeffcoat, AR Burka, LT Mathews, JM AF Garner, C. E. Sumner, S. C. J. Davis, J. G. Burgess, J. P. Yueh, Y. Demeter, J. Zhan, Q. Valentine, J. Jeffcoat, A. R. Burka, L. T. Mathews, J. M. TI Metabolism and disposition of 1-bromopropane in rats and mice following inhalation or intravenous administration SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE 1-bomopropane; metabolism; (CNMR)-C-13; bromoacetone ID NUCLEAR-MAGNETIC-RESONANCE; GLUTATHIONE-S-TRANSFERASE; LAYER DEPLETING SOLVENTS; URINARY METABOLITES; TOXIC AGENTS; SPECTROSCOPY; EXPOSURE; IDENTIFICATION; BIOSYNTHESIS; HOMONUCLEAR AB Workplace exposure to 1-bromopropane (1-BrP) can potentially occur during its use in spray adhesives, fats, waxes, and resins. 1-BrP may be used to replace ozone depleting solvents, resulting in an increase in its annual production in the US, which currently exceeds I million pounds. The potential for human exposure to 1-BrP and the reports of adverse effects associated with potential occupational exposure to high levels of 1-BrP have increased the need for the development of biomarkers of exposure and an improved understanding of 1-BrP metabolism and disposition. In this study, the factors influencing the disposition and biotransformation of 1-BrP were examined in mate F344 rats and B6C3F1 mice following inhalation exposure (800 ppm) or intravenous administration (5, 20, and 100 mg/kg). [1,2,3-C-13] 1-BrP and [1-C-14] 1-BrP were administered to enable characterization of urinary metabolites using NMR spectroscopy, LC-MS/MS, and HPLC coupled radiochromatography. Exhaled breath volatile organic chemicals (VOC), exhaled CO2, urine, feces, and tissues were collected for up to 48 h post-administration for determination of radioactivity distribution. Rats and mice exhaled a majority of the administered dose as either VOC (40-72%) or (CO2)-C-14 (10-30%). For rats, but not mice, the percentage of the dose exhaled as VOC increased between the mid (similar to 50%) and high (similar to 71%) dose groups; while the percentage of the dose exhaled as (CO2)-C-14 decreased (19 to 10%). The molar ratio of exhaled (CO2)-C-14 to total released bromide, which decreased as dose increased, demonstrated that the proportion of 1-BrP metabolized via oxidation relative to pathways dependent on glutathione conjugation is inversely proportional to dose in the rat. [C-14] 1-BrP equivalents were recovered in urine (13-17%, rats; 14-23% mice), feces (< 2%), or retained in the tissues and carcass (< 6%) of rats and mice administered i.v. 5 to 100 mg/kg [C-14] 1-BrP. Metabolites characterized in urine of rats and mice include N-acetyl-S-propylcysteine, N-acetyl-3-(propylsulfinyl)alanine, N-acetyl-S-(2-hydroxypropyl)cysteine, 1-bromo-2-hydroxypropane-O-glucuronide, N-acetyl-S-(2-oxopropyl)cysteine, and N-acetyl-3-[(2-oxopropyl)sulfinyl]alanine. These metabolites may be formed following oxidation of 1-bromopropane to 1-bromo-2-propanol and bromoacetone and following subsequent glutathione conjugation with either of these compounds. Rats pretreated with I-aminobenzotriazole (ABT), a potent inhibitor of P450 excreted less in urine (130%), exhaled as (14)CO2 (180%), or retained in liver (190%), with a concomitant increase in radioactivity expired as VOC (up arrow 52%). Following ABT pretreatment, rat urinary metabolites were reduced in number from 10 to 1, N-acetyl-S-propylcysteine, which accounted for > 90% of the total urinary radioactivity in ABT pretreated rats. Together, these data demonstrate a role for cytochrome P450 and glutathione in the dose-dependent metabolism and disposition of 1-BrP in the rat. Published by Elsevier Inc. C1 RTI Int, Dept Drug Metab & Disposit, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Garner, CE (reprint author), RTI Int, Dept Drug Metab & Disposit, Res Triangle Pk, NC 27709 USA. EM cegarner@rti.org FU NIEHS NIH HHS [N01 ES 25482] NR 41 TC 24 Z9 34 U1 1 U2 11 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 AUG 15 PY 2006 VL 215 IS 1 BP 23 EP 36 DI 10.1016/j.tapp.2006.01.010 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 072BV UT WOS:000239648500004 PM 16513153 ER PT J AU Van Cleve, W Amaro-Carambot, E Surman, SR Bekisz, J Collins, PL Zoon, KC Murphy, BR Skiadopoulos, MH Bartlett, EJ AF Van Cleve, William Amaro-Carambot, Emerito Surman, Sonja R. Bekisz, Joseph Collins, Peter L. Zoon, Kathryn C. Murphy, Brian R. Skiadopoulos, Mario H. Bartlett, Emmalene J. TI Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1 SO VIROLOGY LA English DT Article DE human parainfluenza virus; interferon antagonist; attenuating mutation; vaccine candidate ID RESPIRATORY SYNCYTIAL VIRUS; NF-KAPPA-B; NONSTRUCTURAL PROTEINS NS1; DOUBLE-STRANDED-RNA; ACUTE OTITIS-MEDIA; SENDAI-VIRUS; C-PROTEINS; V-PROTEIN; REGULATORY FACTOR-3; ANTIVIRAL RESPONSES AB Recombinant human parainfluenza virus type I (HPIV1) and mutants containing point and deletion (A) mutations in the P/C gene (r-C Delta(10-15HNT553A), r-C-R84G, r-C-F170S and r-C-Delta 170), which have previously been evaluated as HPIV I vaccine candidates, were evaluated for their effect on the type I interferon (IFN) response in vitro. HPIV1 wt infection inhibited the IFN response by inhibiting IFN regulatory factor-3 (IRF-3) activation and IFN production in A549 cells and IFN signaling in Vero cells. In contrast, r-C-R84G, r-C-F170S and r-C-Delta 170 were defective for inhibition of IRF-3 activation and IFN production and r-C-F170S and r-C-Delta 170 did not inhibit IFN signaling. Thus, HPIV I antagonizes the IFN response at both the level of induction and signaling, and antagonism at both levels was disrupted by mutations in the P/C gene. Because C-F170S affects C and not P, the anti-IFN function can be attributed to the C proteins. These data, in the context of previous in vivo studies, suggest that the loss of antagonism of the IFN response at both the level of induction and signaling, observed with the P/C mutants, r-C-F170S and r-C-Delta 170, was necessary for significant attenuation in African green monkeys (AGMs). Published by Elsevier Inc. C1 NIH, Infect Dis Lab, Resp Viruses Sect, Bethesda, MD 20892 USA. NIAID, Cytokine Biol Sect, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Bartlett, EJ (reprint author), NIH, Infect Dis Lab, Resp Viruses Sect, Bldg 50,Room 6511,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. EM EBartlett@niaid.nih.gov OI Van Cleve, William/0000-0001-5637-4966 FU Intramural NIH HHS NR 86 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2006 VL 352 IS 1 BP 61 EP 73 DI 10.1016/j.virol.2006.04.011 PG 13 WC Virology SC Virology GA 074IV UT WOS:000239806800007 PM 16750233 ER PT J AU Ellenberger, D Otten, RA Li, B Aidoo, M Rodriguez, IV Sariol, CA Martinez, M Monsour, M Wyatt, L Hudgens, MG Edmundo, K Bernard, M Robinson, H Thomas, F Butera, S AF Ellenberger, Dennis Otten, Ronald A. Li, Bin Aidoo, Michael Rodriguez, I. Vanessa Sariol, Carlos A. Martinez, Melween Monsour, Michael Wyatt, Linda Hudgens, Michael G. Edmundo, Kraiselburd Bernard, Moss Robinson, Harriet Thomas, Folks Butera, Salvatore TI HIV-1 DNA/MVA vaccination reduces the per exposure probability of infection during repeated mucosal SHIV challenges SO VIROLOGY LA English DT Article DE repetitive virus challenge; mucosal challenge; vaccine; DNA/MVA; non-human primate model; human sexual transmission; SHIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; IMMUNE-RESPONSES; RHESUS MACAQUES; AIDS VACCINE; SEXUAL TRANSMISSION; NONHUMAN-PRIMATES; GASTROINTESTINAL-TRACT; CD8(+) LYMPHOCYTES; HUMORAL IMMUNITY AB Historically, HIV vaccines specifically designed to raise cellular immunity resulted in protection from disease progression but not infection when tested in monkeys challenged with a single high virus exposure. An alternative approach, more analogous to human sexual exposures, is to repetitively challenge immunized monkeys with a much lower dose of virus until systemic infection is documented. Using these conditions to mimic human sexual transmission, we found that a multi-protein DNA/MVA HIV-1 vaccine is indeed capable of protecting rhesus monkeys against systemic infection when repeatedly challenged with a highly heterologous immunodeficiency virus (SHIV). Furthermore, this repetitive challenge approach allowed us to calculate per-exposure probability of infection, an observed vaccine efficacy of 64%, and undertake a systematic analysis for correlates of protection based on exposures needed to achieve infection. Therefore, improved non-human primate models for vaccine efficacy can provide novel insight and perhaps renew expectations for positive outcomes of human HIV clinical trials. (c) 2006 Elsevier Inc. All rights reserved. C1 Ctr Dis Control & Prevent, Lab Branch, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Stat & Data Management Branch, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Caribbean Primate Res Ctr, Unit Comparat Med, San Juan, PR 00936 USA. Caribbean Primate Res Ctr, Dept Microbiol & Med Zool, San Juan, PR 00936 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Emory Univ, Yerkes Reg Primate Res Ctr, Atlanta, GA 30322 USA. RP Ellenberger, D (reprint author), Ctr Dis Control & Prevent, Lab Branch, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Mail Stop G-19,1600 Clifton Rd, Atlanta, GA 30333 USA. EM dellenberger@cdc.gov; ROtten@cdc.gov; BLi@cdc.gov; MAidoo@cdc.gov; irodriguez@rcm.upr.edu; csariol@rcm.upr.edu; mimartinez@rcm.upr.edu; MMonsour@cdc.gov; LWYATT@niaid.nih.gov; mhudgens@bios.unc.edu; ekraiselburd@rcm.upr.edu; BMOSS@niaid.nih.gov; hrobins@rmy.emory.edu; TFolks@cdc.gov; SButera@cdc.gov NR 50 TC 38 Z9 41 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD AUG 15 PY 2006 VL 352 IS 1 BP 216 EP 225 DI 10.1016/j.virol.2006.04.005 PG 10 WC Virology SC Virology GA 074IV UT WOS:000239806800021 PM 16725169 ER PT J AU Maher, JM Slitt, AL Callaghan, TN Cheny, X Cheung, C Gonzalez, FJ Klaassen, CD AF Maher, J. M. Slitt, A. L. Callaghan, T. N. Cheny, X. Cheung, C. Gonzalez, F. J. Klaassen, C. D. TI Alterations in trans porter expression in liver, kidney, and duodenum after targeted disruption of the transcription factor HNF1 alpha SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE hepatocyte nuclear factor 1 alpha; gene expression; transcription factor; transporter; ABC; SLC; gene regulation ID HEPATOCYTE NUCLEAR FACTOR-1-ALPHA; ORGANIC ANION TRANSPORTER; GENE-EXPRESSION; BILE-ACID; OBSTRUCTIVE CHOLESTASIS; TISSUE DISTRIBUTION; PROXIMAL TUBULES; UP-REGULATION; NTCP GENE; RAT AB The transcription factor hepatocyte nuclear factor 1 alpha (HNF1 alpha) is involved in regulation of glucose metabolism and transport, and in the expression of several drug and bile acid metabolizing enzymes. Targeted disruption of the HNF1 alpha gene results in decreased Cyp1a2, and Cyp2e1 expression, and increased Cyp4a1 and Cyp7a1 expression, suggesting these enzymes are HNI'lo target genes. Since hepatic metabolism can be coordinately linked with drug and metabolite transport, this study aims to demonstrate whether HNF1 alpha regulates expression of a variety of organic anion and cation transporters through utilization of an HNF1 alpha-null mouse model. Expression of 32 transporters, including members of the Oat, Oatp, Oct, Mrp, Mdr, bile acid and sterolin families, was quantified in three different tissues: liver, kidney, and duodenum. The expression of 17 of 32 transporters was altered in liver, 21 of 32 in kidney, and 6 of 32 in duodenum of HNF1 alpha-null mice. This includes many novel observations, including marked downregulation of Oats in kidney, as well as upregulation of many Mrp and Mdr family members in all three tissues. These data indicate that disruption of HNF1 alpha causes a marked attenuation of several Oat and Oatp uptake transporters in liver and kidney, and increased expression of efflux transporters such as Mdrs and Mrps, thus suggesting that HNF1 alpha is a central mediator in regulating hepatic, renal, and intestinal transporters. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Kansas, Ctr Med, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. Lab Metab, NIH, Bethesda, MD 20892 USA. RP Klaassen, CD (reprint author), Univ Kansas, Ctr Med, Dept Pharmacol Toxicol & Therapeut, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM cklaasse@kumc.edu FU NIEHS NIH HHS [F32 ES011239-02, F32 ES011239-01, F32 ES011239, ES-07079, ES-09716] NR 42 TC 53 Z9 59 U1 0 U2 1 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 AUG 14 PY 2006 VL 72 IS 4 BP 512 EP 522 DI 10.1016/j.bcp.2006.03.016 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 071ZE UT WOS:000239641600012 PM 16806085 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate? SO BIOLOGY DIRECT LA English DT Review ID MESSENGER-RNA DECAY; SPLICEOSOMAL INTRONS; EUKARYOTIC EVOLUTION; EXON THEORY; MOLECULAR EVOLUTION; PROTEIN-DEGRADATION; BACTERIAL-VIRUSES; UBIQUITIN SYSTEM; GENOME EVOLUTION; ANCIENT INTRONS AB Background: Ever since the discovery of 'genes in pieces' and mRNA splicing in eukaryotes, origin and evolution of spliceosomal introns have been considered within the conceptual framework of the 'introns early' versus 'introns late' debate. The 'introns early' hypothesis, which is closely linked to the so-called exon theory of gene evolution, posits that protein-coding genes were interrupted by numerous introns even at the earliest stages of life's evolution and that introns played a major role in the origin of proteins by facilitating recombination of sequences coding for small protein/peptide modules. Under this scenario, the absence of spliceosomal introns in prokaryotes is considered to be a result of "genome streamlining". The 'introns late' hypothesis counters that spliceosomal introns emerged only in eukaryotes, and moreover, have been inserted into protein-coding genes continuously throughout the evolution of eukaryotes. Beyond the formal dilemma, the more substantial side of this debate has to do with possible roles of introns in the evolution of eukaryotes. Results: I argue that several lines of evidence now suggest a coherent solution to the introns-early versus introns-late debate, and the emerging picture of intron evolution integrates aspects of both views although, formally, there seems to be no support for the original version of introns-early. Firstly, there is growing evidence that spliceosomal introns evolved from group II self-splicing introns which are present, usually, in small numbers, in many bacteria, and probably, moved into the evolving eukaryotic genome from the alpha-proteobacterial progenitor of the mitochondria. Secondly, the concept of a primordial pool of 'virus-like' genetic elements implies that self-splicing introns are among the most ancient genetic entities. Thirdly, reconstructions of the ancestral state of eukaryotic genes suggest that the last common ancestor of extant eukaryotes had an intron-rich genome. Thus, it appears that ancestors of spliceosomal introns, indeed, have existed since the earliest stages of life's evolution, in a formal agreement with the introns-early scenario. However, there is no evidence that these ancient introns ever became widespread before the emergence of eukaryotes, hence, the central tenet of introns-early, the role of introns in early evolution of proteins, has no support. However, the demonstration that numerous introns invaded eukaryotic genes at the outset of eukaryotic evolution and that subsequent intron gain has been limited in many eukaryotic lineages implicates introns as an ancestral feature of eukaryotic genomes and refutes radical versions of introns-late. Perhaps, most importantly, I argue that the intron invasion triggered other pivotal events of eukaryogenesis, including the emergence of the spliceosome, the nucleus, the linear chromosomes, the telomerase, and the ubiquitin signaling system. This concept of eukaryogenesis, in a sense, revives some tenets of the exon hypothesis, by assigning to introns crucial roles in eukaryotic evolutionary innovation. Conclusion: The scenario of the origin and evolution of introns that is best compatible with the results of comparative genomics and theoretical considerations goes as follows: self-splicing introns since the earliest stages of life's evolution numerous spliceosomal introns invading genes of the emerging eukaryote during eukaryogenesis-subsequent lineage-specific loss and gain of introns. The intron invasion, probably, spawned by the mitochondrial endosymbiont, might have critically contributed to the emergence of the principal features of the eukaryotic cell. This scenario combines aspects of the introns-early and introns-late views. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 123 TC 117 Z9 120 U1 1 U2 26 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD AUG 14 PY 2006 VL 1 AR 22 DI 10.1186/1745-6150-1-22 PG 23 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 133SY UT WOS:000244034900001 PM 16907971 ER PT J AU Pardo, J Urban, C Galvez, EM Ekert, PG Muller, U Kwon-Chung, J Lobigs, M Mullbacher, A Wallich, R Borner, C Simon, MM AF Pardo, Julian Urban, Christin Galvez, Eva M. Ekert, Paul G. Mueller, Uwe Kwon-Chung, June Lobigs, Mario Muellbacher, Arno Wallich, Reinhard Borner, Christoph Simon, Markus M. TI The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PERMEABILITY TRANSITION PORE; CYTOCHROME-C RELEASE; IMMUNOMODULATING AGENT GLIOTOXIN; CELL-DEATH; BH3-ONLY PROTEINS; MEDIATED APOPTOSIS; OXIDATIVE STRESS; FUNGAL TOXINS; CHANNEL VDAC; BH3 DOMAINS AB A spergillus fumigatus infections cause high levels of morbidity and mortality in immunocompromised patients. Gliotoxin (GT), a secondary metabolite, is cytotoxic for mammalian cells, but the molecular basis and biological relevance of this toxicity remain speculative. We show that GT induces apoptotic cell death by activating the proapoptotic Bcl-2 family member Bak, but not Bax, to elicit the generation of reactive oxygen species, the mitochondrial release of apoptogenic factors, and caspase-3 activation. Activation of Bak by GT is direct, as GT triggers in vitro a dose-dependent release of cytochrome c from purified mitochondria isolated from wild-type and Bax- but not Bak-deficient cells. Resistance to A. fumigatus of mice lacking Bak compared to wild-type mice demonstrates the in vivo relevance of this GT-induced apoptotic pathway involving Bak and suggests a correlation between GT production and virulence. The elucidation of the molecular basis opens new strategies for the development of therapeutic regimens to combat A. fumigatus and related fungal infections. C1 Max Planck Inst Immunbiol, Metschnikoff Lab, D-79108 Freiburg, Germany. Ctr Biochem & Mol Res, Inst Mol Med & Cell Res, D-79104 Freiburg, Germany. Univ Freiburg, Inst Phys Chem, D-79104 Freiburg, Germany. Royal Childrens Hosp, Childrens Canc Ctr, Parkville, Vic 3052, Australia. Univ Leipzig, Mol Pathogenesis Biotechnol & Biomed Ctr, D-04103 Leipzig, Germany. NIAID, Mol Microbiol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Australian Natl Univ, John Curtin Sch Med Res, Canberra, ACT 2601, Australia. Univ Klinikum Heidelberg, Inst Immunol, D-69120 Heidelberg, Germany. RP Simon, MM (reprint author), Max Planck Inst Immunbiol, Metschnikoff Lab, Stubeweg 51, D-79108 Freiburg, Germany. EM simon@immunbio.mpg.de RI Ekert, Paul/C-7247-2013; Galvez, Eva/K-6751-2014; Pardo, Julian/K-6764-2014; Ekert, Paul/Q-1842-2015 OI Ekert, Paul/0000-0002-2976-8617; Galvez, Eva/0000-0001-6928-5516; Pardo, Julian/0000-0003-0154-0730; Ekert, Paul/0000-0002-2976-8617 FU Intramural NIH HHS NR 79 TC 58 Z9 62 U1 1 U2 9 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 AUG 14 PY 2006 VL 174 IS 4 BP 509 EP 519 DI 10.1083/jcb.200604044 PG 11 WC Cell Biology SC Cell Biology GA 076VQ UT WOS:000239986600010 PM 16893972 ER PT J AU Eblan, MJ Scholz, S Stubblefield, B Gutti, U Goker-Alpan, O Hruska, KS Singleton, AB Sidransky, E AF Eblan, Michael J. Scholz, Sonja Stubblefield, Barbara Gutti, Usha Goker-Alpan, Ozlern Hruska, Kathleen S. Singleton, Andrew B. Sidransky, Ellen TI Glucocerebrosidase mutations are not found in association with LRRK2 G2019S in subjects with parkinsonism SO NEUROSCIENCE LETTERS LA English DT Article DE Gaucher disease; Parkinson disease; risk factor; dardarin; Lewy bodies ID GAUCHER-DISEASE; ASHKENAZI JEWS; GENETICS AB Alteration G2019S in the leucine-rich repeat kinase 2 gene (LRRK2) has been identified in several populations of patients with parkinsonism, including Ashkenazi Jewish subjects with Parkinson disease. Mutations in glucocerebrosidase (GBA), the enzyme deficient in Gaucher disease, are also identified at an increased frequency among Parkinson probands, including those of Ashkenazi Jewish ancestry. A Taqman Assay-by-Design SNP genotyping strategy was utilized to establish whether G2019S was found in association with GBA mutations. Among 37 subjects with parkinsonism who were heterozygous for a GBA mutation, none carried G2019S. Furthermore, G2019S was not found in 18 patients with Gaucher disease who developed parkinsonian manifestations and 11 other Gaucher probands with parkinsonism in a first degree relative. Among 45 patients with Gaucher disease without a history of parkinsonism, one G2019S carrier was found. These findings suggest that GBA and LRRK2 mutations are discrete risk factors for parkinsonism in both Ashkenazi Jewish and non-Jewish subjects. Published by Elsevier Ireland Ltd. C1 NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIA, Mol Genet Unit, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov RI Singleton, Andrew/C-3010-2009; OI Gutti, Usha/0000-0003-0927-0923; Scholz, Sonja/0000-0002-6623-0429 FU Intramural NIH HHS NR 17 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 14 PY 2006 VL 404 IS 1-2 BP 163 EP 165 DI 10.1016/j.neulet.2006.05.032 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 073SZ UT WOS:000239764200033 PM 16781064 ER PT J AU Fang, J Iwasa, KH AF Fang, Jie Iwasa, K. H. TI Effects of tarantula toxin GsMTx4 on the membrane motor of outer hair cells SO NEUROSCIENCE LETTERS LA English DT Article DE membrane capacitance; operating point; prestin ID COCHLEAR AMPLIFIER; SHAPE CHANGES; ELECTROMOTILITY; CAPACITANCE; INHIBITION; MOTILITY; CHANNELS; PRESTIN AB GsMTx4, a cationic hydrophobic peptide isolated from tarantula venom, is a specific inhibitor of stretch-activated channels (SACs). Here, we show that the toxin also affects the membrane motor of outer hair cells at low doses. The membrane motor of outer hair cells is based on prestin, a member of the SLC26 family of membrane proteins, and directly uses electrical energy available at the plasma membrane. It is considered to be an essential part of the "cochlear amplifier," which increases the sensitivity, tuning, and dynamic range of the mammalian ear. The toxin shifts the operating point of the motor. The saturating value of the voltage shift is (26 +/- 1) mV, capable of significantly reducing the performance of the cochlear amplifier. The dissociation constant is (3.1 +/- 0.6) mu M, about five-fold higher than that for SACs. Published by Elsevier Ireland Ltd. C1 NIDCD, LCB, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), NIDCD, LCB, Biophys Sect, NIH, Bethesda, MD 20892 USA. EM kiwasa@helix.nih.gov OI Iwasa, Kuni/0000-0002-9397-7704 FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000010-14] NR 17 TC 4 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 14 PY 2006 VL 404 IS 1-2 BP 213 EP 216 DI 10.1016/j.neulet.2006.05.059 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 073SZ UT WOS:000239764200043 PM 16797839 ER PT J AU Friedberg, EC Aguilera, A Gellert, M Hanawalt, PC Hays, JB Lehmann, AR Lindahl, T Lowndes, N Sarasin, A Wood, RD AF Friedberg, Errol C. Aguilera, Andres Gellert, Martin Hanawalt, Philip C. Hays, John B. Lehmann, Alan R. Lindahl, Tomas Lowndes, Noel Sarasin, Alain Wood, Richard D. TI DNA repair: From molecular mechanism to human disease SO DNA REPAIR LA English DT Editorial Material AB A comprehensive meeting on biological responses to DNA damage organized by Alan Lehmann, Deborah Barnes, Wouter Ferro, Robert Fuchs, Jan Hoeijmakers, Roland Kanaar, Leon Mullenders and Bert van Zeeland, was convened at Noordwijkerhout, The Netherlands, from April 2 to 7, 2006. This article summarizes information presented by speakers at the seven plenary sessions. Poster sessions with organized discussions constituted a fundamental aspect of the meeting - as did a marvelous evening of musical entertainment by a talented group of conferees. C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Sevilla, Dept Genet, Seville 41013, Spain. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA. Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. Univ Sussex, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. Natl Univ Ireland Univ Coll Galway, Dept Biochem, Galway, Ireland. RP Friedberg, EC (reprint author), Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. EM errol.friedberg@utsouthwestern.edu RI Wood, Richard/E-7855-2011; OI Wood, Richard/0000-0002-9495-6892; Lowndes, Noel/0000-0002-3216-4427; Aguilera, Andres/0000-0003-4782-1714 NR 0 TC 92 Z9 94 U1 1 U2 20 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD AUG 13 PY 2006 VL 5 IS 8 BP 986 EP 996 DI 10.1016/j.dnarep.2006.05.005 PG 11 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 074ZJ UT WOS:000239851100012 PM 16955546 ER PT J AU Zhang, XG Tanaka, N Nakajuna, T Kamijo, Y Gonzalez, FJ Aoyama, T AF Zhang, Xiuguo Tanaka, Naoki Nakajuna, Takero Kamijo, Yuji Gonzalez, Frank J. Aoyama, Toshifumi TI Peroxisome proliferator-activated receptor alpha-independent peroxisome proliferation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peroxisome proliferator-activated receptor alpha; peroxisome proliferation; morphometry; dynamin-like protein 1 ID PPAR-ALPHA; NULL MICE; RAT-LIVER; EXPRESSION; ACID; GENE; RETICULUM; WY-14,643; AGONIST; ENZYMES AB Hepatic peroxisome proliferation, increases in the numerical and volume density of peroxisomes, is believed to be closely related to peroxisome proliferator-activated receptor alpha (PPAR alpha) activation; however, it remains unknown whether peroxisome proliferation depends absolutely on this activation. To verify occurrence of PPAR alpha-independent peroxisome proliferation, fenofibrate treatment was used. which was expected to significantly enhance PPAR alpha dependence in the assay system. Surprisingly, a novel type of PPAR alpha-independent peroxisome proliferation and enlargement was uncovered in PPAR alpha-null mice. The increased expression of dynamin-like protein 1, but not peroxisome biogenesis factor 11 alpha, might be associated with the PPAR alpha-independent peroxisome proliferation at least in part. (c) 2006 Elsevier Inc. All rights reserved. C1 Shinshu Univ, Dept Metab Regulat, Grad Sch Med, Matsumoto, Nagano 3908621, Japan. Shinshu Univ, Dept Internal Med, Grad Sch Med, Matsumoto, Nagano 3908621, Japan. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Tanaka, N (reprint author), Shinshu Univ, Dept Metab Regulat, Grad Sch Med, 3-1-1 Asahi, Matsumoto, Nagano 3908621, Japan. EM naopi@hsp.md.shinshu-u.ac.jp NR 25 TC 18 Z9 18 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 11 PY 2006 VL 346 IS 4 BP 1307 EP 1311 DI 10.1016/j.bbrc.2006.06.042 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 063KH UT WOS:000239016600027 PM 16806075 ER PT J AU Vonholdt, BM Ostrander, EA AF vonHoldt, Bridgett M. Ostrander, Elaine A. TI The singular history of a canine transmissible tumor SO CELL LA English DT Editorial Material ID VENEREAL TUMOR; HOST AB In this issue of Cell, Murgia et al. (2006) confirm that the infectious agent of canine transmissible venereal tumor is the cancer cell itself and that the tumor is clonal in origin. Their findings have implications for understanding the relationship between genome instability and transmissible cancer and for conservation biology, canine genomics, and companion animal medicine. C1 Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 9 TC 12 Z9 14 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 11 PY 2006 VL 126 IS 3 BP 445 EP 447 DI 10.1016/j.cell.2006.07.016 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 075KI UT WOS:000239883400004 PM 16901777 ER PT J AU Baker, DL Fujiwara, Y Pigg, KR Tsukahara, R Kobayashi, S Murofushi, H Uchiyama, A Murakami-Murofushi, K Koh, E Bandle, RW Byun, HS Bittman, R Fan, D Murph, M Mills, GB Tigyi, G AF Baker, Daniel L. Fujiwara, Yuko Pigg, Kathryn R. Tsukahara, Ryoko Kobayashi, Susumu Murofushi, Hiromu Uchiyama, Ayako Murakami-Murofushi, Kimiko Koh, Eunjin Bandle, Russell W. Byun, Hoe-Sup Bittman, Robert Fan, Dominic Murph, Mandi Mills, Gordon B. Tigyi, Gabor TI Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOTILITY-STIMULATING PROTEIN; FATTY ALCOHOL PHOSPHATES; DNA-POLYMERASE-ALPHA; LYSOPHOSPHATIDIC ACID; LYSOPHOSPHOLIPASE-D; SPHINGOSINE 1-PHOSPHATE; PHYSARUM-POLYCEPHALUM; MELANOMA-CELLS; OVARIAN-CANCER; PPAR-GAMMA AB Autotaxin (ATX, nucleotide pyrophosphate/phosphodiesterase-2) is an autocrine motility factor initially characterized from A2058 melanoma cell-conditioned medium. ATX is known to contribute to cancer cell survival, growth, and invasion. Recently ATX was shown to be responsible for the lysophospholipase D activity that generates lysophosphatidic acid (LPA). Production of LPA is sufficient to explain the effects of ATX on tumor cells. Cyclic phosphatidic acid (cPA) is a naturally occurring analog of LPA in which the sn-2 hydroxy group forms a 5-membered ring with the sn-3 phosphate. Cellular responses to cPA generally oppose those of LPA despite activation of apparently overlapping receptor populations, suggesting that cPA also activates cellular targets distinct from LPA receptors. cPA has previously been shown to inhibit tumor cell invasion in vitro and cancer cell metastasis in vivo. However, the mechanism governing this effect remains unresolved. Here we show that 3-carba analogs of cPA lack significant agonist activity at LPA receptors yet are potent inhibitors of ATX activity, LPA production, and A2058 melanoma cell invasion in vitro and B16F10 melanoma cell metastasis in vivo. C1 Univ Tennessee, Ctr Hlth Sci, Dept Physiol, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Med, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Vasc Biol, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Dept Genom, Memphis, TN 38163 USA. Univ Tennessee, Ctr Hlth Sci, Bioinformat Ctr Excellence, Memphis, TN 38163 USA. Tokyo Univ Sci, Fac Pharmaceut, Dept Med Chem, Chiba 2788510, Japan. Yamaguchi Univ, Fac Nat Sci, Dept Biol Sci, Yamaguchi 7538511, Japan. Ochanomizu Univ, Fac Sci, Dept Biol, Tokyo 1128610, Japan. NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. City Univ New York, Queens Coll, Dept Chem & Biochem, Flushing, NY 11367 USA. Univ Texas, Dept Canc Biol, Houston, TX 77030 USA. Univ Texas, Dept Mol Therapeut, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Tigyi, G (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Physiol, 894 Union Ave, Memphis, TN 38163 USA. EM gtigyi@physio1.utmem.edu FU Intramural NIH HHS; NCI NIH HHS [CA92160, P01 CA064602, P01 CA64602, R01 CA092160, R01 CA092160-08]; NHLBI NIH HHS [HL61469, HL79004, R01 HL061469] NR 54 TC 110 Z9 113 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 11 PY 2006 VL 281 IS 32 BP 22786 EP 22793 DI 10.1074/jbc.M512486200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 070RY UT WOS:000239542600039 PM 16782709 ER PT J AU Radichev, I Kwon, SW Zhao, YM DePamphilis, ML Vassilev, A AF Radichev, Ilian Kwon, Sung Won Zhao, Yingming DePamphilis, Melvin L. Vassilev, Alex TI Genetic analysis of human ORC2 reveals specific domains that are required in vivo for assembly and nuclear localization of the origin recognition complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPSTEIN-BARR-VIRUS; DNA-REPLICATION; CELL-CYCLE; MAMMALIAN-CELLS; CHROMATIN ASSOCIATION; PROTEINS; INITIATION; BINDING; SUBUNITS; CDC6 AB Eukaryotic DNA replication begins with the binding of a six subunit origin recognition complex (ORC) to DNA. To study the assembly and function of mammalian ORC proteins in their native environment, HeLa cells were constructed that constitutively expressed an epitope-tagged, recombinant human Orc2 subunit that had been genetically altered. Analysis of these cell lines revealed that Orc2 contains a single ORC assembly domain that is required in vivo for interaction with all other ORC subunits, as well as two nuclear localization signals (NLSs) that are required for ORC accumulation in the nucleus. The recombinant Orc2 existed in the nucleus either as an ORC-(2-5) or ORC-(1-5) complex; no other combinations of ORC subunits were detected. Moreover, only ORC-(1-5) was bound to the chromatin fraction, suggesting that Orc1 is required in vivo to load ORC-(2-5) onto chromatin. Surprisingly, recombinant Orc2 suppressed expression of endogenous Orc2, revealing that mammalian cells limit the intracellular level of Orc2, and thereby limit the amount of ORC-(2-5) in the nucleus. Because this suppression required only the ORC assembly and NLS domains, these domains appear to constitute the functional domain of Orc2. C1 NICHD, Natl Inst Hlth, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. RP Vassilev, A (reprint author), NICHD, Natl Inst Hlth, Bldg 6-3A-02,9000 Rockville Pike, Bethesda, MD 20892 USA. EM vassilev@mail.nih.gov NR 31 TC 12 Z9 12 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 AUG 11 PY 2006 VL 281 IS 32 BP 23264 EP 23273 DI 10.1074/jbc.M603873200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 070RY UT WOS:000239542600089 PM 16762929 ER PT J AU Rau, DC AF Rau, Donald C. TI Sequestered water and binding energy are coupled in complexes of lambda Cro repressor with non-consensus binding sequences SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE recognition; DNA-protein complex; osmotic pressure; dissociation rate; hydration ID PROTEIN-DNA INTERACTIONS; OSMOTIC-STRESS; NONSPECIFIC DNA; LAC REPRESSOR; MACROMOLECULAR HYDRATION; PREFERENTIAL HYDRATION; CRYSTAL-STRUCTURE; OPERATOR DNA; ECORI; SITE AB We use the osmotic pressure dependence of dissociation rates and relative binding constants to infer differences in sequestered water among complexes of lambda Cro repressor with varied DNA recognition sequences. For over a 1000-fold change in association constant, the number of water molecules sequestered by non-cognate complexes varies linearly with binding free energy. One extra bound water molecule is coupled with the loss of similar to 150 cal/mol complex in binding free energy. Equivalently, every tenfold decrease in binding constant at constant salt and temperature is associated with eight to nine additional water molecules sequestered in the non-cognate complex. The relative insensitivity of the difference in water molecules to the nature of the osmolyte used to probe the reaction suggests that the water is sterically sequestered. If the previously measured changes in heat capacity for lambda Cro binding to different non-cognate sequences are attributed solely to this change in water, then the heat capacity change per incorporated water is almost the same as the difference between ice and water. The associated changes in enthalpies and entropies, however, indicate that the change in complex structure involves more than a simple incorporation of fixed water molecules that act as adaptors between noncomplementary surfaces. Published by Elsevier Ltd. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Rau, DC (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM raud@mail.nih.gov FU Intramural NIH HHS NR 61 TC 13 Z9 14 U1 0 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 11 PY 2006 VL 361 IS 2 BP 352 EP 361 DI 10.1016/j.jmb.2006.06.036 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 074WP UT WOS:000239842800012 PM 16828799 ER PT J AU Emanuel, EJ Wertheimer, A AF Emanuel, Ezekiel J. Wertheimer, Alan TI The ethics of influenza vaccination - Response SO SCIENCE LA English DT Letter C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD AUG 11 PY 2006 VL 313 IS 5788 BP 759 EP 760 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072KC UT WOS:000239671300020 ER PT J AU Izquierdo, A Wiedholz, LM Millstein, RA Yang, RJ Bussey, TJ Saksida, LM Holmes, A AF Izquierdo, Alicia Wiedholz, Lisa M. Millstein, Rachel A. Yang, Rebecca J. Bussey, Timothy J. Saksida, Lisa M. Holmes, Andrew TI Genetic and dopaminergic modulation of reversal learning in a touchscreen-based operant procedure for mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE mouse; discrimination; reversal; cognition; strain; gene; dopamine; SKF81297; D1 receptor ID COMPUTER-GRAPHIC STIMULI; INBRED MOUSE STRAINS; PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; PARKINSONS-DISEASE; REFERENCE MEMORY; WORKING-MEMORY; FRONTAL-CORTEX; DEFICIENT MICE; C57BL/6 MICE AB Mice are uniquely suited as experimental subjects for various approaches to the study of the molecular and genetic basis of behavior, and there has been a corresponding explosion in the use of mice in behavioral neuroscience. Rats and monkeys, however, remain the preferred species for high-order cognitive models largely due to the unavailability of valid, reliable and translatable endpoint measures of behavior in the mouse. Here we present further development and validation of a touchscreen-based operant method for measuring cognition that is comparable to methods used in other species and human patients. C57BL/6J mice were found to show good performance on visual discrimination and reversal learning using this method. Demonstrating the sensitivity of the paradigm to genetic factors, C57BL/6J and DBA/2J mice exhibited marked differences in discrimination and reversal learning. Systemic treatment with the selective D1-like agonist, SKF81297, produced an impairment in the early phase of reversal learning, but did not alter visual discrimination, in C57BL/6J mice. The same treatment impaired spatial working memory on the T-maze delayed alternation task, but did not alter control measures of behavior including motivation and locomotor activity. These data demonstrate the sensitivity of visual discrimination and reversal learning measured by this method to genetic factors and pharmacological challenge, and thereby provide an extension and further validation of the method for measuring cognition in mice. When combined with emerging molecular techniques uniquely suited to this species such as genetic engineering and RNA modification this paradigm could provide a powerful new tool for behavioral neuroscience. (c) 2006 Elsevier B.V. All rights reserved. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. RP Izquierdo, A (reprint author), Calif State Univ Los Angeles, Coll Nat & Social Sci, Dept Psychol, 5151 State Univ Dr, Los Angeles, CA 90032 USA. EM AIzquie@calstatela.edu RI Bussey, Timothy/M-2758-2016; Saksida, Lisa/M-2753-2016 OI Bussey, Timothy/0000-0001-7518-4041; Saksida, Lisa/0000-0002-8416-8171 FU Intramural NIH HHS; Medical Research Council [G0001354] NR 50 TC 66 Z9 66 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD AUG 10 PY 2006 VL 171 IS 2 BP 181 EP 188 DI 10.1016/j.bbr.2006.03.029 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 065YY UT WOS:000239197500001 PM 16713639 ER PT J AU Swain, SM AF Swain, Sandra M. TI A step in the right direction SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID GENE-EXPRESSION SIGNATURE; BREAST-CANCER; SURVIVAL; CHEMOTHERAPY; RECURRENCE; TAMOXIFEN; THERAPY; TRIALS C1 NCI, NIH, Bethesda, MD 20892 USA. RP Swain, SM (reprint author), NCI, NIH, Bethesda, MD 20892 USA. OI Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 23 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 10 PY 2006 VL 24 IS 23 BP 3717 EP 3718 DI 10.1200/JCO.2006.06.7025 PG 2 WC Oncology SC Oncology GA 075TG UT WOS:000239907500001 PM 16720679 ER PT J AU Lopez-Lemus, J Romero-Bastida, M Darden, TA Alejandre, J AF Lopez-Lemus, J. Romero-Bastida, M. Darden, T. A. Alejandre, J. TI Liquid-vapour equilibrium of n-alkanes using interface simulations SO MOLECULAR PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; SURFACE-TENSION; PHASE-EQUILIBRIA; LATTICE SUMS; FORCE-FIELD; ENSEMBLE; FLUIDS; POTENTIALS; DENSITIES; MIXTURES AB Dynamics simulations were performed to calculate liquid-vapour coexisting properties of n-alkane chains up to 16 carbon atoms using interface simulations. The lattice sum or Ewald method on the dispersion forces of the Lennard-Jones potential was applied to calculate the full interaction. The liquid and vapour coexisting densities were obtained for two flexible force field models, NERD and TraPPE-UA, where the intermolecular interactions are of the Lennard - Jones type. We have recently shown [ P. Orea, J. Lopez- Lemus, and J. Alejandre, J. Chem. Phys. 123, 114702 ( 2005)] that the liquid - vapour densities for simple fluids do not depend on interfacial area and therefore it is possible to use a small number of molecules in a simulation. We show that the same trend is found on the simulation of these hydrocarbon molecules. The phase diagram of ethane/n-decane binary mixtures is also obtained at 410.95K for the NERD model. The simulation results from this work were compared with those obtained using methods with interfaces using large cut-off distances and with methods without interfaces for the same potential model. In both comparisons, excellent agreement was found. The results of liquid density from the TraPPE-UA model are in good agreement with experimental data while those from the NERD model are underestimated at low temperatures. Our findings are consistent with results published by other authors for small hydrocarbons. C1 Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Mexico City 09340, DF, Mexico. Univ Autonoma Estado Mexico, Fac Ciencias, Toluca 50000, Mexico. Ctr Invest Polimeros, Grp COMEX, Tepexpan 55885, Mexico. NIEHS, Res Triangle Pk, NC 27709 USA. RP Alejandre, J (reprint author), Univ Autonoma Metropolitana Iztapalapa, Dept Quim, Av San Rafael Atlixco 186,Colonia Vicentina, Mexico City 09340, DF, Mexico. EM jra@xanum.uam.mx RI Alejandre, Jose/B-3191-2015; Lopez, Jorge/A-3328-2016 OI Alejandre, Jose/0000-0003-3158-6027; Lopez, Jorge/0000-0002-9486-6942 NR 34 TC 32 Z9 32 U1 2 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0026-8976 J9 MOL PHYS JI Mol. Phys. PD AUG 10 PY 2006 VL 104 IS 15 BP 2413 EP 2421 DI 10.1080/00268970600691274 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 078MW UT WOS:000240108900001 ER PT J AU Goldbach-Mansky, R Dailey, NJ Canna, SW Gelabert, A Jones, J Rubin, BI Kim, HJ Brewer, C Zalewski, C Wiggs, E Hill, S Turner, ML Karp, BI Aksentijevich, I Pucino, F Penzak, SR Haverkamp, MH Stein, L Adams, BS Moore, TL Fuhlbrigge, RC Shaham, B Jarvis, JN O'Neil, K Vehe, RK Beitz, LO Gardner, G Hannan, WP Warren, RW Horn, W Cole, JL Paul, SM Hawkins, PN Pham, TH Snyder, C Wesley, RA Hoffmann, SC Holland, SM Butman, JA Kastner, DL AF Goldbach-Mansky, Raphaela Dailey, Natalie J. Canna, Scott W. Gelabert, Ana Jones, Janet Rubin, Benjamin I. Kim, H. Jeffrey Brewer, Carmen Zalewski, Christopher Wiggs, Edythe Hill, Suvimol Turner, Maria L. Karp, Barbara I. Aksentijevich, Ivona Pucino, Frank Penzak, Scott R. Haverkamp, Margje H. Stein, Leonard Adams, Barbara S. Moore, Terry L. Fuhlbrigge, Robert C. Shaham, Bracha Jarvis, James N. O'Neil, Kathleen Vehe, Richard K. Beitz, Laurie O. Gardner, Gregory Hannan, William P. Warren, Robert W. Horn, William Cole, Joe L. Paul, Scott M. Hawkins, Philip N. Pham, Tuyet Hang Snyder, Christopher Wesley, Robert A. Hoffmann, Steven C. Holland, Steven M. Butman, John A. Kastner, Daniel L. TI Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NF-KAPPA-B; MUCKLE-WELLS-SYNDROME; AUTOINFLAMMATORY DISEASES; ACTIVATE CASPASE-1; FEBRILE RESPONSE; ANAKINRA; MUTATIONS; CYTOKINES; GENE; ASC AB BACKGROUND: Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation. METHODS: We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare. RESULTS: All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events. CONCLUSIONS: Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD 20892 USA. NINDS, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Michigan, Ann Arbor, MI 48109 USA. St Louis Univ, St Louis, MO 63103 USA. Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp, Los Angeles, CA 90027 USA. Univ Oklahoma Coll, Oklahoma City, OK USA. Univ Minnesota, Minneapolis, MN USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Univ Washington, Ctr Bone & Joint, Seattle, WA 98195 USA. SUNY Hosp, Syracuse, NY USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Watauga Med Ctr, Boone, NC USA. Adult & Pediat Rheumatol, San Antonio, TX USA. UCL Royal Free Univ Coll Med Sch, London, England. RP Goldbach-Mansky, R (reprint author), NIAMS, Bldg 10,Rm 9S-205,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldbacr@mail.nih.gov RI Hawkins, Philip/C-5573-2008; Butman, John/A-2694-2008; OI Paul, Scott/0000-0003-1274-6670; Canna, Scott/0000-0003-3837-5337 FU Intramural NIH HHS [ZIA AR041138-11]; Medical Research Council [G7900510] NR 37 TC 459 Z9 479 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 10 PY 2006 VL 355 IS 6 BP 581 EP 592 DI 10.1056/NEJMoa055137 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 071QM UT WOS:000239616700008 PM 16899778 ER PT J AU Nguyen-Khac, F Della Valle, V Lopez, RG Ravet, E Mauchauffe, M Friedman, AD Huang, LE Fichelson, S Ghysdael, J Bernard, OA AF Nguyen-Khac, F. Della Valle, V. Lopez, R. G. Ravet, E. Mauchauffe, M. Friedman, A. D. Huang, L. E. Fichelson, S. Ghysdael, J. Bernard, O. A. TI Functional analyses of the TEL-ARNT fusion protein underscores a role for oxygen tension in hematopoietic cellular differentiation SO ONCOGENE LA English DT Article DE TEL/ETV6; ARNT; transcription factor; leukemia; differentiation block ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ACUTE MYELOID-LEUKEMIA; ENDOTHELIAL-CELLS; TUMOR-SUPPRESSOR; FACTOR 1-ALPHA; TRANSCRIPTION; GROWTH; TRANSLOCATION; METABOLISM; ACTIVATION AB The transcription factor hypoxia inducible factor 1 (HIF1), an HIF1 alpha-aryl hydrocarbon receptor nuclear translocator ( ARNT) dimeric factor, is essential to the cellular response to hypoxia. We described a t(1;12)(q21;p13) chromosomal translocation in human acute myeloblastic leukemia that involves the translocated Ets leukemia (TEL/ETV6) and the ARNT genes and results in the expression of a TEL-ARNT fusion protein. Functional studies show that TEL-ARNT interacts with HIF1 alpha and the complex binds to consensus hypoxia response element. In low oxygen tension conditions, the HIF1 alpha/TEL-ARNT complex does not activate transcription but exerts a dominant-negative effect on normal HIF1 activity. Differentiation of normal human CD34+ progenitors cells along all the erythrocytic, megakaryocytic and granulocytic pathways was accelerated in low versus high oxygen tension conditions. Murine 32Dcl3 myeloid cells also show accelerated granulocytic differentiation in low oxygen tension in response to granulocyte colony-stimulating factor. Interestingly, stable expression of the TEL-ARNT in 32Dcl3 subclones resulted in impaired HIF1-mediated transcriptional response and inhibition of differentiation enhancement in hypoxic conditions. Taken together, our results underscore the role of oxygen tension in the modulation of normal hematopoietic differentiation, whose targeting can participate in human malignancies. C1 Grp Hosp Pitie Salpetriere, Serv Hematol Biol, F-75013 Paris, France. Univ Paris 05, INSERM, Hop Necker Enfants Malad, IRNEM, Paris, France. CNRS, Inst Curie, UMR 146, F-91405 Orsay, France. CNRS, Inst Cochin Genet Mol, Dept Hematol, INSERM,U567,UMR 8104, Paris, France. INSERM, U674, Paris, France. Johns Hopkins Oncol Ctr, Div Pediat Oncol, Baltimore, MD USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Nguyen-Khac, F (reprint author), Grp Hosp Pitie Salpetriere, Serv Hematol Biol, Pavillon Laveran 47-83 Bd Hop, F-75013 Paris, France. EM florence.nguyen@psl.aphp.fr RI GHYSDAEL, Jacques/F-3377-2013; Bernard, Olivier/E-5721-2016 NR 45 TC 16 Z9 18 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 AUG 10 PY 2006 VL 25 IS 35 BP 4840 EP 4847 DI 10.1038/sj.onc.1209503 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 072QE UT WOS:000239687100002 PM 16547490 ER PT J AU Grishaev, A Ying, JF Bax, A AF Grishaev, Alexander Ying, Jinfa Bax, Ad TI Pseudo-CSA restraints for NMR refinement of nucleic acid structure SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID RESIDUAL DIPOLAR COUPLINGS; CHEMICAL-SHIFT ANISOTROPY; RNA; ALIGNMENT; PROTEINS; RESOLUTION; TENSORS; GELS C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov FU Intramural NIH HHS NR 22 TC 13 Z9 13 U1 0 U2 2 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 AUG 9 PY 2006 VL 128 IS 31 BP 10010 EP 10011 AR JA0633058 DI 10.1021/ja0633058 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 069NI UT WOS:000239454800014 PM 16881619 ER PT J AU Wang, B Sayer, JM Yagi, H Frank, H Seidel, A Jerina, DM AF Wang, Ben Sayer, Jane M. Yagi, Haruhiko Frank, Heinrich Seidel, Albrecht Jerina, Donald M. TI Facile interstrand migration of the hydrocarbon moiety of a dibenzo[a,l]pyrene 11,12-diol 13,14-epoxide adduct at N-2 of deoxyguanosine in a duplex oligonucleotide SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; TUMOR-INITIATING ACTIVITY; DIOL EPOXIDE ADDUCTS; MOUSE SKIN; DNA; DIGESTION; RESISTANCE; DEOXYADENOSINE; CONFORMATION AB When a synthesized deoxyribonucleotide duplex, 5'-CCATCG*CTACC-3'center dot 5'-GGTAGCGATGG-3', containing a trans 14R dibenzo[a,l] pyrene (DB[a,l]P) adduct, corresponding to trans opening of the (+)-(11S, 12R)-diol (13R,14S)-epoxide by N-2 of the central G* residue, was allowed to stand for 2-6 days at ambient temperature in neutral aqueous solution, three new products were observed on denaturing HPLC. One of these corresponded to loss of the DB[ a, l] P moiety from the original adducted strand to give an 11-mer with an unmodified central dG. The other two products resulted from a highly unexpected migration of the hydrocarbon moiety to either dG(5) or dG(7) of the complementary strand, 5'-GGTAG(5)CG(7)ATGG-3'. Enzymatic hydrolysis of the two 11-mer migration products followed by CD spectroscopy of the isolated adducted nucleosides indicated that, in both cases, the hydrocarbon moiety had undergone configurational inversion at C14 to give the cis 14 S DB[a,l]P dG adduct. MS/MS and partial enzymatic hydrolysis showed that the major 11-mer had the hydrocarbon at dG(7). Two 11-mer oligonucleotides were synthesized with a single cis 14S DB[a,l]P dG adduct either at G(7) or at G(5) and were found to be chromatographically identical to the major and minor migration products, respectively. Although HPLC evidence suggested that a small extent of hydrocarbon migration from the trans 14 S DB[ a, l] P dG diastereomer also occurred, the very small amount of presumed migration products from this isomer precluded their detailed characterization. This interstrand migration appears unique to DB[a,l]P adducts and has not been observed for their fjord-region benzo[c] phenanthrene or bay-region benzo[a]pyrene analogues. C1 NIDDK, Lab Bioorgan Chem, NIH, DHHS, Bethesda, MD 20892 USA. Grimmer Fdn, Biochem Inst Environm Carcinogens, D-22927 Grosshansdorf, Germany. RP Sayer, JM (reprint author), NIDDK, Lab Bioorgan Chem, NIH, DHHS, Bethesda, MD 20892 USA. EM jmsayer@helix.nih.gov FU Intramural NIH HHS NR 21 TC 9 Z9 9 U1 1 U2 1 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 AUG 9 PY 2006 VL 128 IS 31 BP 10079 EP 10084 AR JA0608038 DI 10.1021/ja0608038 PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 069NI UT WOS:000239454800031 PM 16881636 ER PT J AU Hamel, DJ Zhou, HJ Starich, MR Byrd, RA Dahlquist, FW AF Hamel, Damon J. Zhou, Hongjun Starich, Mary R. Byrd, R. Andrew Dahlquist, Frederick W. TI Chemical-shift-perturbation mapping of the phosphotransfer and catalytic domain interaction in the histidine autokinase CheA from Thermotoga maritima SO BIOCHEMISTRY LA English DT Article ID KINASE CHEA; SIGNAL-TRANSDUCTION; BACTERIAL CHEMOTAXIS; ESCHERICHIA-COLI; PROTEIN; NMR; BINDING; PHOSPHORYLATION; PORTION AB Regulating the activity of the histidine autokinase CheA is a central step in bacterial chemotaxis. The CheA autophosphorylation reaction minimally involves two CheA domains, denoted P1 and P4. The kinase domain (P4) binds adenosine triphosphate (ATP) and orients the phosphate for phosphotransfer to a reactive histidine on the phosphoacceptor domain (P1). Three-dimensional triple-resonance experiments allowed sequential assignments of backbone nuclei from P1 and P4 domains as well as the P4 assignments within a larger construct, P3P4, which includes the dimerization domain P3. We have used nuclear magnetic resonance chemical-shift-perturbation mapping to define the interaction of P1 and P3P4 from the hyperthermophile Thermotoga maritima. The observed chemical-shift changes in P1 upon binding suggest that the P1 domain is bound by interactions on the side opposite the histidine that is phosphorylated. The observed shifts in P3P4 upon P1 binding suggest that P1 is bound at a site distinct from the catalytic site on P4. These results argue that the P1 domain is not bound in a mode that leads to productive phosphate transfer from ATP at the catalytic site and imply the presence of multiple binding modes. The binding mode observed may be regulatory or it may reflect the binding mode needed for effective transfer of the histidyl phosphate of P1 to the substrate proteins CheY and CheB. In either case, this work describes the first direct observation of the interaction between P1 and P4 in CheA. C1 Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. NCI, Struct Biophys Lab, Frederick, MD 21701 USA. RP Dahlquist, FW (reprint author), Univ Calif Santa Barbara, Dept Chem & Biochem, Santa Barbara, CA 93106 USA. EM dahlquist@chem.ucsb.edu RI Byrd, R. Andrew/F-8042-2015 OI Byrd, R. Andrew/0000-0003-3625-4232 FU NIGMS NIH HHS [5R01GM059544-25] NR 28 TC 15 Z9 15 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 AUG 8 PY 2006 VL 45 IS 31 BP 9509 EP 9517 DI 10.1021/bi060798K PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069CJ UT WOS:000239422400015 PM 16878985 ER PT J AU Nordstrom, LJ Clark, CA Andersen, B Champlin, SM Schwinefus, JJ AF Nordstrom, Larisa J. Clark, Chris A. Andersen, Brian Champlin, Sara M. Schwinefus, Jeffrey J. TI Effect of ethylene glycol, urea, and N-methylated glycines on DNA thermal stability: The role of DNA base pair composition and hydration SO BIOCHEMISTRY LA English DT Article ID CALF-THYMUS DNA; GAMMA-AMINOBUTYRIC ACID; AQUEOUS-SOLUTIONS; PREFERENTIAL INTERACTIONS; OSMOTIC-STRESS; THERMODYNAMIC PROPERTIES; CONFORMATIONAL STATE; TRANSITION ENTHALPY; BETA-ALANINE; AMINO-ACIDS AB The accumulation of the cosolutes ethylene glycol, urea, glycine, sarcosine, and glycine betaine at the single-stranded DNA surface exposed upon melting the double helix has been quantified for DNA samples of different guanine-cytosine (GC) content using the local-bulk partitioning model [Record, M. T., Jr., Zhang, W., and Anderson, C. F. (1998) AdV. Protein Chem. 51, 281-353]. Urea and ethylene glycol are both locally accumulated at single-stranded DNA relative to bulk solution. Urea exhibits a stronger affinity for adenine ( A) and thymine ( T) bases, leading to a greater net dehydration of these bases upon DNA melting; ethylene glycol local accumulation is practically independent of base composition. However, glycine, sarcosine, and glycine betaine are not necessarily locally accumulated at single strands after melting relative to bulk solution, although they are locally accumulated relative to double-stranded DNA. The local accumulation of glycine, sarcosine, and glycine betaine at single strands relative to double-stranded DNA decreases with bulk cosolute molality and increases with GC content for all N-methylated glycines, demonstrating a stronger affinity for G and C bases. Glycine also shows a minimum in melting temperature T-m at 1-2 m for DNA samples of 50% GC content or less. Increasing ionic strength attenuates the local accumulation of urea, glycine, sarcosine, and glycine betaine and removes the minimum in Tm with glycine. This attenuation in local accumulation results in counterion release during the melting transition that is dependent on water activity and, hence, cosolute molality. C1 St Olaf Coll, Dept Chem, Northfield, MN 55057 USA. Natl Alcohol Abuse & Alcoholism, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. RP Schwinefus, JJ (reprint author), St Olaf Coll, Dept Chem, Northfield, MN 55057 USA. EM schwinef@stolaf.edu NR 47 TC 25 Z9 25 U1 4 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 8 PY 2006 VL 45 IS 31 BP 9604 EP 9614 DI 10.1021/bi052469i PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069CJ UT WOS:000239422400025 PM 16878995 ER PT J AU Mazumdar, M Lee, JH Sengupta, K Ried, T Rane, S Misteli, T AF Mazumdar, Manjari Lee, Ji-Hyeon Sengupta, Kundan Ried, Thomas Rane, Sushil Misteli, Tom TI Tumor formation via loss of a molecular motor protein SO CURRENT BIOLOGY LA English DT Article ID MITOTIC CHECKPOINT; CHROMOSOME INSTABILITY; GENOMIC INSTABILITY; CENTROSOME AMPLIFICATION; CELL-DEATH; CANCER; ANEUPLOIDY; TUMORIGENESIS; INHIBITION; ACTIVATION AB Aneuploidy has long been suggested to be causal in tumor formation. Direct testing of this hypothesis has been difficult because of the absence of methods to specifically induce aneuploidy. The chromosome-associated kinesin motor KIF4 plays multiple roles in mitosis, and its loss leads to multiple mitotic defects including aneuploidy [1-5]. Here, we have taken advantage of the direct formation of aneuploidy in the absence of KIF4 to determine whether loss of a molecular motor and generation of aneuploidy during mitosis can trigger tumorigenesis. We find that embryonic stem cells genetically depleted of KIF4 support anchorage-independent growth and form tumors in nude mice. In cells lacking KIF4, mitotic spindle checkpoints and DNA-damage response pathways are activated. Down regulation or loss of KIF4 is physiologically relevant because reduced KIF4 levels are present in 35% of human cancers from several tissues. Our results support the notion that loss of a molecular motor leads to tumor formation and that aneuploidy can act as a primary trigger of tumorigenesis. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Mazumdar, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mazumdam@mail.nih.gov; mistelit@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010309-07] NR 30 TC 34 Z9 37 U1 2 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD AUG 8 PY 2006 VL 16 IS 15 BP 1559 EP 1564 DI 10.1016/j.cub.2006.06.029 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 075GM UT WOS:000239872400032 PM 16890532 ER PT J AU Elkins, JS Longstreth, WT Manolio, TA Newman, AB Bhadelia, RA Johnston, SC AF Elkins, J. S. Longstreth, W. T., Jr. Manolio, T. A. Newman, A. B. Bhadelia, R. A. Johnston, S. C. TI Education and the cognitive decline associated with MRI-defined brain infarct SO NEUROLOGY LA English DT Article ID MINI-MENTAL-STATE; CARDIOVASCULAR-HEALTH; ELDERLY-PEOPLE; WHITE-MATTER; ALZHEIMER-DISEASE; DEMENTIA; MANIFESTATIONS; PERFORMANCE; PREDICTORS; DIAGNOSIS AB Objective: To assess whether educational attainment, a correlate of cognitive reserve, predicts the amount of cognitive decline associated with a new brain infarct. Methods: The Cardiovascular Health Study is a population-based, longitudinal study of people aged 65 years and older. Cognitive function was measured annually using the Modified Mini-Mental State Examination (3MS) and the Digit-Symbol Substitution Test (DSST). The authors tested whether education level modified 1) the cross-sectional association between cognitive performance and MRI-defined infarct and 2) the change in cognitive function associated with an incident infarct at a follow-up MRI. Results: In cross-sectional analysis (n = 3,660), MRI-defined infarct was associated with a greater impact on 3MS performance in the lowest education quartile when compared with others ( p for heterogeneity = 0.012). Among those with a follow-up MRI who had no infarct on initial MRI (n = 1,433), education level was not associated with the incidence, size, or location of new brain infarct. However, a new MRI- defined infarct predicted substantially greater decline in 3MS scores in the lowest education group compared with the others ( 6.3, 95% CI 4.4- to 8.2- point decline vs 1.7, 95% CI 0.7- to 2.7- point decline; p for heterogeneity < 0.001). Higher education was not associated with smaller declines in DSST performance in the setting of MRI- defined infarct. Conclusions: Education seems to modify an individual's decline on a test of general cognitive function when there is incident brain infarct. These findings are consistent with the hypothesis that cognitive reserve influences the impact of vascular injury in the brain. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Washington, Seattle, WA 98195 USA. NHLBI, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Tufts New England Med Ctr, Boston, MA USA. RP Elkins, JS (reprint author), Univ Calif San Francisco, Dept Neurol, 505 Parnassus Ave,Box 0114, San Francisco, CA 94143 USA. EM jacob.elkins@ucsfmedctr.org RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-85086, N01 HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085]; NINDS NIH HHS [K23 NS046302] NR 35 TC 50 Z9 54 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 8 PY 2006 VL 67 IS 3 BP 435 EP 440 DI 10.1212/01.wnl.0000228246.89109.98 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 071LK UT WOS:000239603500015 PM 16894104 ER PT J AU Wilhelm, B Jordan, M Birbaumer, N AF Wilhelm, B. Jordan, M. Birbaumer, N. TI Communication in locked-in syndrome: Effects of imagery on salivary pH SO NEUROLOGY LA English DT Editorial Material ID DEVICE C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. NIH, Human Cort Physiol Unit, Bethesda, MD 20892 USA. RP Birbaumer, N (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM niels.birbaumer@uni-tuebingen.de FU NIBIB NIH HHS [EB00856]; NICHD NIH HHS [HD30146] NR 6 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 8 PY 2006 VL 67 IS 3 BP 534 EP 535 DI 10.1212/01.wnl.0000228226.86382.5f PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 071LK UT WOS:000239603500042 PM 16894126 ER PT J AU Forsythe, ME Love, DC Lazarus, BD Kim, EJ Prinz, WA Ashwell, G Krause, MW Hanover, JA AF Forsythe, Michele E. Love, Dona C. Lazarus, Brooke D. Kim, Eun Ju Prinz, William A. Ashwell, Gilbert Krause, Michael W. Hanover, John A. TI Caenorhabditis elegans ortholog of a diabetes susceptibility locus: oga-1 (O-GlcNAcase) knockout impacts O-GlcNAc cycling, metabolism, and dauer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hexosamine; insulin signaling; nutrients; obesity ID GLUCOSE-INDUCED DESENSITIZATION; LINKED N-ACETYLGLUCOSAMINE; GLYCOGEN-SYNTHASE KINASE-3; INSULIN-RESISTANCE; HEXOSAMINE BIOSYNTHESIS; C-ELEGANS; LIFE-SPAN; SIGNAL-TRANSDUCTION; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; POSTTRANSLATIONAL MODIFICATION AB A dynamic cycle of O-linked N-acetylglucosamine (O-GlcNAc) addition and removal acts on nuclear pore proteins, transcription factors, and kinases to modulate cellular signaling cascades. Two highly conserved enzymes (O-GlcNAc transferase and O-GlcNAcase) catalyze the final steps in this nutrient-driven "hexosamine-signaling pathway." A single nucleotide polymorphism in the human O-GlcNAcase gene is linked to type 2 diabetes. Here, we show that Caenorhabditis elegans oga-1 encodes an active O-GlcNAcase. We also describe a knockout allele, oga-1(ok1207), that is viable and fertile yet accumulates OGlcNAc on nuclear pores and other cellular proteins. Interfering with O-GlcNAc cycling with either oga-1(ok1207) or the O-GlcNAc transferase-null ogt-1(ok430) altered Ser- and Thr-phosphoprotein profiles and increased glycogen synthase kinase 3 beta (GSK-3 beta) levels. Both the oga-1(ok1207) and ogt-1(ok430) strains showed elevated stores of glycogen and trehalose, and decreased lipid storage. These striking metabolic changes prompted us to examine the insulin-like signaling pathway controlling nutrient storage, longevity, and dauer formation in the C elegans O-GlcNAc cycling mutants. Indeed, we found that the oga-1(ok1207) knockout augmented dauer formation induced by a temperature sensitive insulin-like receptor (daf-2) mutant under conditions in which the ogt-1(ok430)-null diminished dauer formation. Our findings suggest that the enzymes of O-GlcNAc cycling "finetune" insulin-like signaling in response to nutrient flux. The knockout of O-GlcNAcase (oga-1) in C elegans mimics many of the metabolic and signaling changes associated with human insulin resistance and provides a genetically amenable model of non-insulin-dependent diabetes. C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, G (reprint author), NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM ga15u@nih.gov; jah@helix.nih.gov OI Krause, Michael/0000-0001-6127-3940 FU Intramural NIH HHS NR 80 TC 86 Z9 92 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 8 PY 2006 VL 103 IS 32 BP 11952 EP 11957 DI 10.1073/pnas.0601931103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072VU UT WOS:000239701900025 PM 16882729 ER PT J AU Venkova-Canova, T Srivastava, P Chattoraj, DK AF Venkova-Canova, Tatiana Srivastava, Preeti Chattoraj, Dhruba K. TI Transcriptional inactivation of a regulatory site for replication of Vibrio cholerae chromosome II SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE checkpoint control; DNA-protein interactions; homeostasis; replication control ID P1 PLASMID REPLICATION; ESCHERICHIA-COLI; DNA-REPLICATION; INITIATOR PROTEIN; ORIGIN; SEGREGATION; CYCLE; GENE; REQUIREMENTS; PROKARYOTES AB The bacterium Vibrio cholerae has two chromosomes. The origin of replication of chromosome I is similar to that of Escherichia coli. The origin-containing region of chromosome II (oriCII) resembles replicons of plasmids such as P1, except for the presence of an additional gene, rctA [Egan, E. S. & Waldor, M. K. (2003) Cell 114, 521-530]. The oriCII region that includes the initiator gene, rctB, can function as a plasmid in E. coli. Here we show that RctB suffices for the oriCII-based plasmid replication, and rctA in cis or trans reduces the plasmid copy number, thereby serving as a negative regulator. The inhibitory activity could be overcome by increasing the concentration of RctB, suggesting that rctA titrates the initiator. Purified RctB bound to a DNA fragment carrying rctA, confirming that the two can interact. Although rctA apparently works as a titrating site, it is nonetheless transcribed. We find that the transcription attenuates the inhibitory activity of the gene, presumably by interfering with RctB binding. RctB, in turn, repressed the rctA promoter and, thereby, could control its own titration by modulating the transcription of rctA. This control circuit appears to be a putative novel mechanism for homeostasis of initiator availability. C1 NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM chattoraj@nih.gov NR 38 TC 22 Z9 22 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 8 PY 2006 VL 103 IS 32 BP 12051 EP 12056 DI 10.1073/pnas.0605120103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072VU UT WOS:000239701900042 PM 16873545 ER PT J AU Dubois, S Waldmann, TA Muller, JR AF Dubois, Sigrid Waldmann, Thomas A. Mueller, Juergen R. TI ITK and IL-15 support two distinct subsets of CD8(+) T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE thymic development; T cell activation; NK receptors ID TEC FAMILY KINASES; POSITIVE SELECTION; CELIAC-DISEASE; NATURAL-KILLER; LYMPHOCYTES-T; MEMORY; PROLIFERATION; HOMEOSTASIS; INTERLEUKIN-15; IMMUNOTHERAPY AB CD8(+) T cells are commonly divided into naive CD44(lo)CD122(lo) and "memory phenotype" CD44(hi)CD122(hi) cells. Here we show data suggesting that these two cell populations represent independent CD8(+) T cell subsets. Whereas IL-15(-/-) mice lack CD44(hi)CD122(hi) CD8(+) T cells, mice deficient in the kinase ITK lack CD44(lo)CD122(lo) cells among CD8(+) T cells. The same defects were observed during thymus development. CD44(hi)CD122(hi) cells were found among double-positive thymocytes and increased in frequency during CD8 development in wild-type mice. At the mature stage, IL-15(-/-) mice harbored virtually no CD44(hi)CD122(hi) CD8(+) thymocytes. In contrast, ITK-/- mice lacked CD44(lo)CD122(lo) CD8(+) cells at this stage. We generated mice with genetic deletions in both IL-15 and ITK and observed a severe reduction of all CD8(+) T cells. The two CD44(lo)CD122(lo) and CD44(hi)CD122(hi) CD8(+) T cell subsets differed in the periphery in that natural killer (NK) receptor expression was found only on CD44(hi)CD122(hi) CD8(+) T cells. This expression was paralleled by their ability to respond to both T cell receptor and NK receptor engagements. In contrast, CD44(lo)CD122(lo) CD8(+) T cells mounted stronger responses to T cell receptor stimulation but failed to recognize NK receptor ligands. Thus, whereas ITK-dependent CD44(lo)CD122(lo) CD8(+) T cells appear to represent conventional CD8(+) T cells, IL-15-dependent CD44(hi)CD122(hi) CD8(+) T cells may have functions in both adaptive and innate immunity. C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov; muellerj@mail.nih.gov FU Intramural NIH HHS NR 28 TC 68 Z9 68 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 8 PY 2006 VL 103 IS 32 BP 12075 EP 12080 DI 10.1073/pnas.0605212103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072VU UT WOS:000239701900046 PM 16880398 ER PT J AU Tschritter, O Preissl, H Hennige, AM Stumvoll, M Porubska, K Frost, R Marx, H Klosel, B Lutzenberger, W Birbaumer, N Haring, HU Fritsche, A AF Tschritter, Otto Preissl, Hubert Hennige, Anita M. Stumvoll, Michael Porubska, Katarina Frost, Rebekka Marx, Hannah Kloesel, Benjamin Lutzenberger, Werner Birbaumer, Niels Haering, Hans-Ulrich Fritsche, Andreas TI The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: A magnetoencephalographic study SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glucose metabolism; insulin resistance; magnetoencephalography; mismatch negativity; type 2 diabetes ID INSULIN-RECEPTOR SUBSTRATE-1; CENTRAL-NERVOUS-SYSTEM; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; BRAIN GLUCOSE-METABOLISM; WORKING-MEMORY TASK; ALZHEIMERS-DISEASE; DIABETES-MELLITUS; BODY-WEIGHT; FOOD-INTAKE AB Animal studies have shown that the brain is an insulin-responsive organ and that central nervous insulin resistance induces obesity and disturbances in glucose metabolism. In humans, insulin effects in the brain are poorly characterized. We used a magnetoencephalography approach during a two-step hyperinsulinemic euglycemic clamp to (i) assess cerebrocortical insulin effects in humans, (ii) compare these effects between 10 lean and 15 obese subjects, and (iii) test whether the insulin receptor substrate (IRS)-1 Gly972Arg polymorphism in the insulin-signaling cascade modifies these effects. Both spontaneous and stimulated (mismatch negativity) cortical activity were assessed. In lean humans, stimulated cortical activity (P = 0.046) and the beta and theta band of spontaneous cortical activity (P = 0.01 and 0.04) increased with insulin infusion relative to saline. In obese humans, these effects were suppressed. Moreover, the insulin effect on spontaneous cortical activity correlated negatively with body mass index and percent body fat (all r < -0.4; all P < 0.05) and positively with insulin sensitivity of glucose disposal (theta band, r = 0.48, P = 0.017). Furthermore, insulin increased spontaneous cortical activity (beta band) in carriers of wild-type IRS-1, whereas, in carriers of the 972Arg allele, this insulin effect was absent (P = 0.01). We conclude that, in lean humans, insulin modulates cerebrocortical activity, and that these effects are diminished in obese individuals. Moreover, cerebrocortical insulin resistance is found in individuals with the Gly972Arg polymorphism in IRS-1, which is considered a type 2 diabetes risk gene. C1 Univ Tubingen, Med Klin, D-72076 Tubingen, Germany. Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72076 Tubingen, Germany. Univ Arkansas Med Sci, Dept Obstet & Gynecol, Coll Med, Little Rock, AR 72205 USA. Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Haring, HU (reprint author), Univ Tubingen, Med Klin, Otfried Muller Str 10, D-72076 Tubingen, Germany. EM hans-ulrich.haering@med.uni-tuebingen.de RI Lutzenberger, Werner/B-4296-2008; PreiSSl, Hubert/E-9070-2012 OI PreiSSl, Hubert/0000-0002-8859-4661 NR 43 TC 103 Z9 108 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 8 PY 2006 VL 103 IS 32 BP 12103 EP 12108 DI 10.1073/pnas.0604404103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 072VU UT WOS:000239701900051 PM 16877540 ER PT J AU Andersson, S Wallin, KL Hellstrom, AC Morrison, LE Hjerpe, A Auer, G Ried, T Larsson, C Heselmeyer-Haddad, K AF Andersson, S. Wallin, K-L Hellstroem, A-C Morrison, L. E. Hjerpe, A. Auer, G. Ried, T. Larsson, C. Heselmeyer-Haddad, K. TI Frequent gain of the human telomerase gene TERC at 3q26 in cervical adenocarcinomas SO BRITISH JOURNAL OF CANCER LA English DT Article DE cervical adenocarcinoma; human papillomavirus; interphase fluorescence in situ hybridisation; chromosome arm 3q; telomerase; early detection ID HUMAN-PAPILLOMAVIRUS TYPES; UTERINE CERVIX; CHROMOSOMAL-ABERRATIONS; GENOMIC AMPLIFICATION; RECURRENT PATTERN; CELL CARCINOMAS; CANCER; WORLDWIDE; SWEDEN; GRADE AB The level of genomic amplification of the human telomerase gene TERC, which maps to chromosome band 3q26, was determined in primary cervical adenocarcinomas. Interphase nuclei prepared from archival material of 12 primary cervical adenocarcinomas, eight of which were human papillomavirus positive, were hybridised with a triple colour probe set specific for centromeres of chromosomes 3 and 7 and the TERC gene. We observed high proportions of nuclei with increased absolute copy numbers for TERC in all tumours (mean 3.3; range 2.3-5.2). Amplification of the human telomerase gene TERC is a consistent aberration in cervical adenocarcinomas. Therefore, application of our probe set may provide an objective genetic test for the assessment of glandular cells in Pap smears and hence for the diagnosis of cervical adenocarcinomas. C1 Karolinska Univ Hosp Solna, Karolinska Inst, Dept Mol Med & Surg, SE-17176 Stockholm, Sweden. Karolinska Inst, Karolinska Hosp, Dept Clin Sci Intervent & Technol, Div Obstet & Gynecol, SE-14186 Stockholm, Sweden. Karolinska Inst, Karolinska Univ Hosp, Radiumhemmet, Dept Gynecol Oncol, SE-17176 Stockholm, Sweden. Abbott Mol, Des Plaines, IL 60018 USA. Karolinska Inst, Karolinska Univ Hosp Solna, Dept Oncol Pathol, CCK, SE-17176 Stockholm, Sweden. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Larsson, C (reprint author), Karolinska Univ Hosp Solna, Karolinska Inst, Dept Mol Med & Surg, CMM L80, SE-17176 Stockholm, Sweden. EM catharina.larsson@cmm.ki.se NR 35 TC 29 Z9 41 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 EI 1532-1827 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 7 PY 2006 VL 95 IS 3 BP 331 EP 338 DI 10.1038/sj.bjc.6603253 PG 8 WC Oncology SC Oncology GA 071JZ UT WOS:000239599400012 PM 16847471 ER PT J AU Lee, YC Zhang, ZJ Mukherjee, AB AF Lee, Yi-Ching Zhang, Zhongjian Mukherjee, Anil B. TI Mice lacking uteroglobin are highly susceptible to developing pulmonary fibrosis SO FEBS LETTERS LA English DT Article DE uteroglobin; inflammation; chemotaxis; pulmonary fibrosis ID LUNG; EXPRESSION; DISEASE; INVASION AB Uteroglobin (UG) is an anti-inflammatory protein secreted by the airway epithelia of all mammals. UG-knockout (UG-KO) mice sporadically develop focal pulmonary fibrosis (PIT), a group of complex interstitial disorders of the lung that has high mortality and morbidity; however, the molecular mechanism(s) remains unclear. We report here that UG-KO mice are extraordinarily sensitive to bleomycin, an anti-cancer agent known to induce PIT and readily develop PIT when treated with an extremely low dose of bleomycin that has virtually no effect on the wild type littermates. We further demonstrate that UG prevents PF suppressing bleomycin-induced production of proinflammatory T-helper 2 cytokines and TGF-beta, which are also pro-fibrotic. Our results define a critical role of UG in preventing the development of PIT and provide the proof of principle that recombinant UG may have therapeutic potential. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NICHHD, Hertitable Disorders Branch, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHHD, Hertitable Disorders Branch, Sect Dev Genet, NIH, Bldg 10,Rm 9D42,10 Ctr Dr, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov FU Intramural NIH HHS NR 24 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 7 PY 2006 VL 580 IS 18 BP 4515 EP 4520 DI 10.1016/j.febslet.2006.07.031 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 072JF UT WOS:000239669000035 PM 16872605 ER PT J AU Piquemal, JP Perera, L Cisneros, GA Ren, PY Pedersen, LG Darden, TA AF Piquemal, Jean-Philip Perera, Lalith Cisneros, G. Andres Ren, Pengyu Pedersen, Lee G. Darden, Thomas A. TI Towards accurate solvation dynamics of divalent cations in water using the polarizable amoeba force field: From energetics to structure SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID HYDRATED MAGNESIUM-ION; MOLECULAR-DYNAMICS; CALCIUM-ION; LIQUID WATER; SIMULATION; MECHANICS; REPRESENTATION; EXCHANGE; DENSITY; CA2+ AB Molecular dynamics simulations were performed using a modified amoeba force field to determine hydration and dynamical properties of the divalent cations Ca2+ and Mg2+. The extension of amoeba to divalent cations required the introduction of a cation specific parametrization. To accomplish this, the Thole polarization damping model parametrization was modified based on the ab initio polarization energy computed by a constrained space orbital variation energy decomposition scheme. Excellent agreement has been found with condensed phase experimental results using parameters derived from gas phase ab initio calculations. Additionally, we have observed that the coordination of the calcium cation is influenced by the size of the periodic water box, a recurrent issue in first principles molecular dynamics studies. (c) 2006 American Institute of Physics. C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. Univ Texas, Dept Biomed Engn, Austin, TX 78712 USA. RP Piquemal, JP (reprint author), Univ Paris 06, Chim Theor Lab, Case 137,4 Pl Jussieu, F-75252 Paris 05, France. EM jpp@lct.jussieu.fr; perera12@niehs.nih.gov; darden@niehs.nih.gov RI Cisneros, Gerardo/B-3128-2010; Piquemal, Jean-Philip/B-9901-2009; perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI Piquemal, Jean-Philip/0000-0001-6615-9426; perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 FU Intramural NIH HHS NR 50 TC 121 Z9 122 U1 1 U2 34 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD AUG 7 PY 2006 VL 125 IS 5 AR 054511 DI 10.1063/1.2234774 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 071BV UT WOS:000239573100035 PM 16942230 ER PT J AU Buhrow, SA Reid, JM Jia, L McGovern, RM Covey, JM Kobs, DJ Grossi, IM Ames, MM AF Buhrow, Sarah A. Reid, Joel M. Jia, Lee McGovern, Renee M. Covey, Joseph M. Kobs, Dean J. Grossi, Irma M. Ames, Matthew M. TI LC-MS/MS assay and dog pharmacokinetics of the dimeric pyrrolobenzodiazepine SJG-136 (NSC 694501) SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE LC/MS/MS; pharmacokinetics; anticancer agents; benzodiazepine ID SPECTRUM ANTITUMOR-ACTIVITY; ADVANCED SOLID TUMORS; CROSS-LINKING AGENT; PRECLINICAL PHARMACOLOGY; PHASE-I; POTENT; BIZELESIN; CC-1065 AB The dimeric pyrrolobenzodiazepine SJG-136 (NSC 694501) has potent in vitro cytotoxicity and in vivo antitumor activity. SJG-136 binds in the minor groove of DNA and produces G-G interstrand cross-links via reactive N-10-C-11/N-10-C-ll' imine/carbinolamine moieties. We have developed a sensitive, specific liquid chromatography tandem mass spectrometry (LC/MS/MS) method for the quantitative determination of SJG-136 in plasma. SJG-136 was isolated by solid phase extraction through a C8 column, reverse-phase HPLC separation was accomplished on a C18 column with isocratic elution and MS/MS detection, monitoring the m/z 557-m/z 476 transition after electrospray ionization. The linear range and lower limit of quantitation from plasma standard curves were 2.8-1800 nM, and 5 nM, respectively. SJG-136 plasma protein binding was species-dependent. Values of the unbound fraction in human, rat and mouse were 25%, 16.2% and < 1%, respectively. Protein binding was saturable in dog plasma where the unbound fraction increased from 10.8% to 22.3% over a 22-720 nM concentration range. SJG-136 pharmacokinetics after a single intravenous dose were best fit to a two-compartment open model with elimination half-life and plasma clearance values of 97 min and 6.1 mL/min/kg, respectively. SJG-136 did not accumulate in plasma following intravenous administration of 1.0 mu g/kg doses for five consecutive days. (c) 2006 Elsevier B.V. All rights reserved. C1 Mayo Clin & Mayo Fdn, Dept Oncol, Div Dev Oncol Res, Rochester, MN 55905 USA. NCI, DTP, DCTD, Rockville, MD USA. Battelle Mem Inst, Columbus, OH USA. RP Ames, MM (reprint author), Mayo Clin & Mayo Fdn, Dept Oncol, Div Dev Oncol Res, 200 1st St SW, Rochester, MN 55905 USA. EM ames.matthew@mayo.edu FU NCI NIH HHS [N01-CM-07105] NR 8 TC 10 Z9 10 U1 0 U2 1 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 AUG 7 PY 2006 VL 840 IS 1 SI SI BP 56 EP 62 DI 10.1016/j.jchromb.2006.04.031 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 072KT UT WOS:000239673000008 PM 16730244 ER PT J AU Lie, RK Emanuel, EJ Grady, C AF Lie, Reidar K. Emanuel, Ezekiel J. Grady, Christine TI Circumcision and HIV prevention research: an ethical analysis SO LANCET LA English DT Article C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Lie, RK (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM riie@cc.nih.gov FU Intramural NIH HHS NR 12 TC 14 Z9 15 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 AUG 5 PY 2006 VL 368 IS 9534 BP 522 EP 525 DI 10.1016/S0140-6736(06)69160-5 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 071AL UT WOS:000239569000035 PM 16890839 ER PT J AU Gonzalez-Iglesias, AE Kretschmannova, K Tomic, M Stojilkovic, SS AF Gonzalez-Iglesias, Arturo E. Kretschmannova, Karla Tomic, Melanija Stojilkovic, Stanko S. TI ZD7288 inhibits exocytosis in an HCN-independent manner and downstream of voltage-gated calcium influx in pituitary lactotrophs SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE hyperpolarization-activated cyclic nucleotide-gated channels; I-h; prolactin; ZD7288; pacemaking; calcium; exocytosis; pituitary; lactotrophs ID ACTIVATED CATION CURRENT; CURRENT I-H; CARDIAC-PACEMAKER CHANNELS; ADENYLATE-CYCLASE; SINOATRIAL NODE; RAT LACTOTROPHS; HYPERPOLARIZATION; NEURONS; CELLS; SECRETION AB Pituitary lactotrophs fire action potentials spontaneously and the associated voltage-gated calcium influx is sufficient to maintain high prolactin release. Here we studied the role of hyperpolarization-activated cation channels in pacemaking activity, calcium signaling, and prolactin secretion in these cells. A slowly developing and hyperpolarization-activated inward current was identified but only in a fraction of lactotrophs. The current was blocked by ZD7288, a relatively specific blocker of these channels. However, the pacemaking activity increased in ZD7288-treated cells independently of the presence of this current. This in turn facilitated voltage-gated calcium influx and transiently stimulated prolactin secretion. Sustained ZD7288 application in concentrations that are commonly used to block the hyperpolarization-activated cation channels inhibited hormone release at elevated intracellular calcium concentrations. Agonist and Bay K 8644-stimulated prolactin release was also inhibited by ZD7288, indicating that this compound attenuates the exocytotic pathway downstream of calcium influx. (c) 2006 Elsevier Inc. All rights reserved. C1 NICHHD, Sect Cellular Signaling Endocrinol & Reprod Res, NIH, Bethesda, MD 20892 USA. RP Gonzalez-Iglesias, AE (reprint author), NICHHD, Sect Cellular Signaling Endocrinol & Reprod Res, NIH, Bethesda, MD 20892 USA. EM iglesiaa@mail.nih.gov RI Tomic, Melanija/C-3371-2016 FU Intramural NIH HHS NR 36 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 4 PY 2006 VL 346 IS 3 BP 845 EP 850 DI 10.1016/j.bbrc.2006.05.194 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 061IT UT WOS:000238865900029 PM 16780797 ER PT J AU Murphy, S Larrivee, B Pollet, I Craig, KS Williams, DE Huang, XH Abbott, M Wong, F Curtis, C Conrads, TP Veenstra, T Puri, M Hsiang, Y Roberge, M Andersen, RJ Karsan, A AF Murphy, Siun Larrivee, Bruno Pollet, Ingrid Craig, Kyle S. Williams, David E. Huang, Xin-Hui Abbott, Megan Wong, Fred Curtis, Cameron Conrads, Thomas P. Veenstra, Timothy Puri, Mira Hsiang, York Roberge, Michel Andersen, Raymond J. Karsan, Aly TI Identification of sokotrasterol sulfate as a novel proangiogenic steroid SO CIRCULATION RESEARCH LA English DT Article DE angiogenesis; ischemia; endothelium ID MARINE NATURAL-PRODUCTS; NF-KAPPA-B; INTEGRIN ALPHA(V)BETA(3); ENDOTHELIAL-CELLS; IN-VITRO; ANGIOGENESIS; ARTERIOGENESIS; ACTIVATION; INHIBITION; APOPTOSIS AB The potential to promote neovascularization in ischemic tissues using exogenous agents has become an exciting area of therapeutics. In an attempt to identify novel small molecules with angiogenesis promoting activity, we screened a library of natural products and identified a sulfated steroid, sokotrasterol sulfate, that induces angiogenesis in vitro and in vivo. We show that sokotrasterol sulfate promotes endothelial sprouting in vitro, new blood vessel formation on the chick chorioallantoic membrane, and accelerates angiogenesis and reperfusion in a mouse hindlimb ischemia model. We demonstrate that sulfation of the steroid is critical for promoting angiogenesis, as the desulfated steroid exhibited no endothelial sprouting activity. We thus developed a chemically synthesized sokotrasterol sulfate analog, 2 beta,3 alpha,6 alpha-cholestanetrisulfate, that demonstrated equivalent activity in the hindlimb ischemia model and resulted in the generation of stable vessels that persisted following cessation of therapy. The function of sokotrasterol sulfate was dependent on cyclooxygenase-2 activity and vascular endothelial growth factor induction, as inhibition of either cyclooxygenase-2 or vascular endothelial growth factor blocked angiogenesis. Surface expression of alpha(v)beta(3) integrin was also necessary for function, as neutralization of alpha(v)beta(3) integrin, but not beta(1) integrin, binding abrogated endothelial sprouting and antiapoptotic activity in response to sokotrasterol sulfate. Our findings indicate that sokotrasterol sulfate and its analogs can promote angiogenesis in vitro and in vivo and could potentially be used for promoting neovascularization to relieve the sequelae of vasoocclusive diseases. C1 British Columbia Canc Agcy, Dept Med Biophys, Vancouver, BC V5Z 1L3, Canada. British Columbia Canc Agcy, Dept Pathol & Lab Med, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Dept Chem, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Surg, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Med Biophys, Toronto, ON, Canada. RP Karsan, A (reprint author), British Columbia Canc Agcy, Dept Med Biophys, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM akarsan@bccrc.ca RI Tang, Macy/B-9798-2014; Karsan, Aly/K-2067-2015 FU NCI NIH HHS [N01-CO-12400] NR 39 TC 8 Z9 8 U1 0 U2 3 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 AUG 4 PY 2006 VL 99 IS 3 BP 257 EP 265 DI 10.1161/01.RES.0000233316.17882.33 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 070DT UT WOS:000239501200009 PM 16794189 ER PT J AU Hu, XQ Sun, H Peoples, RW Hong, R Zhang, L AF Hu, Xiang-Qun Sun, Hui Peoples, Robert W. Hong, Ren Zhang, Li TI An interaction involving an arginine residue in the cytoplasmic domain of the 5-HT3A receptor contributes to receptor desensitization mechanism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SINGLE-CHANNEL CONDUCTANCE; GATED ION-CHANNEL; SEROTONIN-RECEPTOR; AMINO-ACID; 5-HYDROXYTRYPTAMINE TYPE-3; SUBUNIT; PROTEIN; ACETYLCHOLINE; AGONIST; DETERMINANTS AB A large cytoplasmic domain accounts for approximately one third of the entire protein of one superfamily of ligand-gated membrane ion channels, which includes nicotinic acetylcholine ( nACh), gamma-aminobutyric acid type A ( GABA(A)), serotonin type 3 ( 5-HT3), and glycine receptors. Desensitization is one functional feature shared by these receptors. Because most molecular studies of receptor desensitization have focused on the agonist binding and channel pore domains, relatively little is known about the role of the large cytoplasmic domain ( LCD) in this process. To address this issue, we sequentially deleted segments of the LCD of the 5-HT3A receptor and examined the function of the mutant receptors. Deletion of a small segment that contains three amino acid residues ( 425 - 427) significantly slowed the desensitization kinetics of the 5-HT3A receptor. Both deletion and point mutation of arginine 427 altered desensitization kinetics in a manner similar to that of the ( 425 - 427) deletion without significantly changing the apparent agonist affinity. The extent of receptor desensitization was positively correlated with the polarity of the amino acid residue at 427: the desensitization accelerates with increasing polarity. Whereas the R427L mutation produced the slowest desensitization, it did not significantly alter single channel conductance of 5-HT3A receptor. Thus, the arginine 427 residue in the LCD contributes to 5-HT3A receptor desensitization, possibly through forming an electrostatic interaction with its neighboring residues. Because the polarity of the amino acid residue at 427 is highly conserved, such a desensitization mechanism may occur in other members of the Cys-loop family of ligand-gated ion channels. C1 NIAAA, NIH, Lab Integrat Neurosci, Bethesda, MD 20892 USA. Marquette Univ, Dept Biomed Sci, Coll Hlth Sci, Milwaukee, WI 53201 USA. RP Zhang, L (reprint author), NIAAA, NIH, Lab Integrat Neurosci, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM lzhang@mail.nih.gov NR 31 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 4 PY 2006 VL 281 IS 31 BP 21781 EP 21788 DI 10.1074/jbc.M600676200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 068PO UT WOS:000239387100024 PM 16754678 ER PT J AU McPhie, P Ni, YS Minton, AP AF McPhie, Peter Ni, Yi-sheng Minton, Allen P. TI Macromolecular crowding stabilizes the molten globule form of apomyoglobin with respect to bath cold and heat unfolding SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein stability; molecular crowding; molten globule; excluded volume; cold denaturation ID PROTEIN STABILITY; DENATURATION; STATES AB At pH 2 apomyoglobin is extensively unfolded. Addition of increasing concentration of salts has been shown to convert the protein into molten globule form(s), which can undergo both heat-induced and cold-induced unfolding. Increasing concentrations of an inert polymer, dextran, lead to increased formation of molten globule and stabilizes the protein with respect to both heat-induced and cold-induced denaturation. The transitions were studied by circular dichroism. Two-state analysis of the data shows that the effects of salt and polymer are additive, and that stabilization by the polymer is independent of temperature, as predicted by excluded volume theory. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP McPhie, P (reprint author), NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH, Bldg 8,Room 215, Bethesda, MD 20892 USA. EM pmcphie@helix.nih.gov NR 12 TC 35 Z9 36 U1 2 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 4 PY 2006 VL 361 IS 1 BP 7 EP 10 DI 10.1016/j.jmb.2006.05.075 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 072LA UT WOS:000239673700002 PM 16824541 ER PT J AU Meng, ZJ Camalier, CE Lucas, DA Veenstra, TD Beck, GR Conrads, TP AF Meng, Zhaojing Camalier, Corinne E. Lucas, David A. Veenstra, Timothy D. Beck, George R., Jr. Conrads, Thomas P. TI Probing early growth response 1 interacting proteins at the active promoter in osteoblast cells using oligoprecipitation and mass spectrometry SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE oligoprecipitation; EGR1; DNA-protein interaction; mass spectrometry; inorganic phosphate ID GENE-EXPRESSION; INORGANIC-PHOSPHATE; GROWTH-FACTORS; C-FOS; RESPONSE GENES; RECEPTOR GENE; ANNEXIN-II; EGR-1; BINDING; TRANSCRIPTION AB Current advances in proteomics have allowed for a rapidly expanding integration of associated methodologies with more traditional molecular and biochemical approaches to the study of cell function. Recent studies on the role of inorganic phosphate have suggested this ion is a novel signaling molecule capable of altering the function of numerous cell types. Elevated inorganic phosphate generated in the extracellular microenvironment by differentiating osteoblasts has recently been determined to act through a largely uncharacterized mechanism as an important signaling molecule responsible for altering the transcription of various genes during osteoblast differentiation. The transcription factor, early growth response protein 1 (EGR1), has previously been shown to be involved in the early response of osteoblasts to inorganic phosphate. To elucidate the role of EGR1 as a potential early regulator of transcription in the inorganic phosphate response, an oligoprecipitation procedure was optimized to capture the DNA bound, transcriptionally active form of EGR1. The interacting proteins thusly captured were identified using mass spectrometry (MS). Proteins involved in transcription, RNA processing, and chromatin modification were identified by this approach. The combined oligoprecipitation-MS approach presented here is highly effective for isolating and characterizing entire transcriptional complexes in the DNA bound state and is broadly extendable to the identification of both known and unknown transcription factor protein complexes. C1 SAIC Frederick Inc, Natl Canc Inst Frederick, Mass Spectrometry Ctr, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA 30322 USA. RP Beck, GR (reprint author), SAIC Frederick Inc, Natl Canc Inst Frederick, Mass Spectrometry Ctr, Lab Proteom & Analyt Technol, POB B, Frederick, MD 21702 USA. EM george.beck@emory.edu; conrads@ncifcrf.gov FU NCI NIH HHS [CA84573, N01-CO-12400] NR 36 TC 16 Z9 18 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD AUG 4 PY 2006 VL 5 IS 8 BP 1931 EP 1939 DI 10.1021/pr060009l PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 070AW UT WOS:000239493700013 PM 16889415 ER PT J AU Hendler, RW AF Hendler, Richard W. TI Reply to "Comment on 'An apparent general solution for the kinetic models of the bacteriorhodopsin photocycle'" SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hendler, RW (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 9 TC 0 Z9 0 U1 1 U2 1 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 AUG 3 PY 2006 VL 110 IS 30 BP 15043 EP 15044 DI 10.1021/jp056537m PG 2 WC Chemistry, Physical SC Chemistry GA 067NI UT WOS:000239309500073 ER PT J AU Leopold, DA Bondar, IV Giese, MA AF Leopold, David A. Bondar, Igor V. Giese, Martin A. TI Norm-based face encoding by single neurons in the monkey inferotemporal cortex SO NATURE LA English DT Article ID INFERIOR TEMPORAL CORTEX; VISUAL-CORTEX; RECOGNITION; DISTINCTIVENESS; RESPONSES; MACAQUE; IDENTIFICATION; SELECTIVITY; CARICATURES; IDENTITY AB The rich and immediate perception of a familiar face, including its identity, expression and even intent, is one of the most impressive shared faculties of human and non-human primate brains. Many visually responsive neurons in the inferotemporal cortex of macaque monkeys respond selectively to faces(1-4), sometimes to only one or a few individuals(5-7), while showing little sensitivity to scale and other details of the retinal image(8,9). Here we show that face-responsive neurons in the macaque monkey anterior inferotemporal cortex are tuned to a fundamental dimension of face perception. Using a norm-based caricaturization framework previously developed for human psychophysics(10-12), we varied the identity information present in photo-realistic human faces(13), and found that neurons of the anterior inferotemporal cortex were most often tuned around the average, identity-ambiguous face. These observations are consistent with face-selective responses in this area being shaped by a figural comparison, reflecting structural differences between an incoming face and an internal reference or norm. As such, these findings link the tuning of neurons in the inferotemporal cortex to psychological models of face identity perception. C1 Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. Univ Clin Tubingen, Hertie Inst Clin Brain Res, Dept Cognit Neurol, Lab Act Representat & Learning, D-72072 Tubingen, Germany. RP Leopold, DA (reprint author), NIMH, Unit Cognit Neurophysiol & Imaging, Neuropsychol Lab, NIH, 49 Convent Dr,Bldg 49,MSC 4400, Bethesda, MD 20892 USA. EM leopoldd@mail.nih.gov OI Leopold, David/0000-0002-1345-6360 NR 26 TC 183 Z9 183 U1 0 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 3 PY 2006 VL 442 IS 7102 BP 572 EP 575 DI 10.1038/nature04951 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 069NQ UT WOS:000239455900045 PM 16862123 ER PT J AU Lederman, RJ AF Lederman, Robert J. TI Balloon angioplasty or nitinol stents for peripheral-artery disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NHLBI, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM lederman@nih.gov NR 1 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 AUG 3 PY 2006 VL 355 IS 5 BP 522 EP 522 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 069FT UT WOS:000239432500019 PM 16888842 ER PT J AU Dale, DC Rosenberg, PS Alter, BP AF Dale, David C. Rosenberg, Philip S. Alter, Blanche P. TI Lineage-specific hematopoietic growth factors SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Univ Washington, Seattle, WA 98195 USA. NCI, Rockville, MD 20892 USA. RP Dale, DC (reprint author), Univ Washington, Seattle, WA 98195 USA. NR 1 TC 2 Z9 2 U1 1 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD AUG 3 PY 2006 VL 355 IS 5 BP 526 EP 527 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 069FT UT WOS:000239432500027 PM 16888846 ER PT J AU Stewart, CV Plenz, D AF Stewart, Craig V. Plenz, Dietmar TI Inverted-U profile of dopamine-NMDA-mediated spontaneous avalanche recurrence in superficial layers of rat prefrontal cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article DE prefrontal cortex; spontaneous activity; dopamine; NMDA; spatiotemporal activity patterns; microelectrode array; acute slice; local field potential ID CORTICAL PYRAMIDAL NEURONS; WORKING-MEMORY PERFORMANCE; RECEPTOR MODULATION; ACTIVITY PATTERNS; CEREBRAL-CORTEX; D-1 RECEPTORS; IN-VITRO; MECHANISMS; NEOCORTEX; INHIBITION AB Prefrontal cortex (PFC) functions, such as working memory, attention selection, and memory retrieval, depend critically on dopamine and NMDA receptor activation by way of an inverted-U-shaped pharmacological profile. Although single neuron responses in the PFC have shown some aspects of this profile, a network dynamic that follows the dopamine-NMDA dependence has not been identified. We studied neuronal network activity in acute medial PFC slices of adult rats by recording local field potentials (LFPs) with microelectrode arrays. Bath application of dopamine or the dopamine D-1 agonist SKF38393 [( +/-)-1-phenyl- 2,3,4,5-tetrahydro-(1H)-3-benzazepine- 7,8-diol hydrochloride] in combination with NMDA induced spontaneous LFPs predominantly in superficial cortex layers. The LFPs at single electrodes were characterized by sharp negative peaks that were clustered in time across electrodes revealing diverse spatiotemporal patterns on the array. The pattern formation required fast GABAergic transmission, coactivation of the dopamine D-1 and NMDA receptor, and depended in an inverted-U profile on dopamine. At moderate concentrations of dopamine or the dopamine D-1 agonist, the pattern size distribution formed a power law with exponent alpha = -1.5, indicating that patterns are organized in the form of neuronal avalanches, thereby maximizing spatial correlations in the network. At lower or higher concentrations, alpha was more negative than - 1.5, indicating reduced spatial correlations. Likewise, at moderate dopamine concentrations, the avalanche rate and recurrence of specific avalanches was maximal with recurrence frequencies after a "power law"-like heavy-tail distribution with a slope of -2.4. We suggest that the dopamine-NMDA-dependent spontaneous recurrence of specific avalanches in superficial cortical layers might facilitate integrative and associative aspects of PFC functions. C1 NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Porter Neurosci Res Ctr,NIH, Bethesda, MD 20892 USA. RP Plenz, D (reprint author), NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Porter Neurosci Res Ctr,NIH, Room 3A-100,35 Convent Dr, Bethesda, MD 20892 USA. EM plenzd@mail.nih.gov FU Intramural NIH HHS NR 65 TC 61 Z9 61 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 2 PY 2006 VL 26 IS 31 BP 8148 EP 8159 DI 10.1523/JNEUROSCI.0723-06.2006 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 069VV UT WOS:000239477800016 PM 16885228 ER PT J AU Xi, LF Kiviat, NB Hildesheim, A Galloway, DA Wheeler, CM Ho, J Koutsky, LA AF Xi, Long Fu Kiviat, Nancy B. Hildesheim, Allan Galloway, Denise A. Wheeler, Cosette M. Ho, Jesse Koutsky, Laura A. TI Human papillomavirus type 16 and 18 variants: Race-related distribution and persistence SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; FEMALE UNIVERSITY-STUDENTS; NATURAL-HISTORY; MOLECULAR VARIANTS; SEQUENCE VARIATION; INFECTION; WOMEN; COEVOLUTION; ACQUISITION; PRODUCTS AB Background. Analogous to the geographic distribution of variants of human papillomavirus (HPV) types, the distribution and persistence of these variants among infected individuals may be related to the racial composition of a population living in one geographic region. Methods: We studied 1114 women in the United States participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 and/or HPV18 at enrollment. Race was self-reported. HPV samples were characterized by sequencing the E6 gene and part of the long control region and classified as variants according to established lineages. Subjects were examined for HPV every 6 months for 2 years. All statistical tests were two-sided. Results: HPV18 African variants were predominant in the 97 HPV18-infected African American women (i.e., 62 women or 63.9%, 95% confidence interval [CI] = 53.5% to 73.4%), and European variants were common in the 168 HPV18-infected white women (i.e., 91 women or 54.2%, 95% CI = 46.3% to 61.9%). HPV16 African variants accounted for 43 (26.5%, 95% CI = 19.9% to 34.0%) of the infections in the 162 HPV16-infected African American women but for only 25 (4.3%, 95% CI = 2.8% to 6.3%) in the 584 HPV16-infected white women. The likelihood of remaining HPV18 positive was statistically significantly higher in white women infected with European than in white women infected with African variants (P = .04); the reverse was observed in African American women (P = .03). A similar pattern was observed for persistence of HPV16 variants, with the likelihood of remaining positive being higher for white women, but lower for African American women, infected with an European variant than with an African variant (P = .03 and P =. 16, respectively). Conclusions: Variants of HPV16 and HPV18 appear to persist longer in a host whose race indicates an ancestral geographic distribution that was once shared with that of the variant-i.e., European variants persist longer in white women, and African variants persist longer in African American women. C1 Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ New Mexico, Sch Med, Dept Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Mol Genet, Albuquerque, NM USA. RP Xi, LF (reprint author), 1914 N 34th St,Suite 300, Seattle, WA 98103 USA. EM longfu@u.washington.edu FU NCI NIH HHS [CA 84396] NR 27 TC 87 Z9 88 U1 1 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 AUG 2 PY 2006 VL 98 IS 15 BP 1045 EP 1052 DI 10.1093/jnci/djj297 PG 8 WC Oncology SC Oncology GA 070CL UT WOS:000239497800008 PM 16882941 ER PT J AU Tung, JY Rosen, MP Nelson, LM Turek, PJ Witte, JS Cramer, DW Cedars, MI Reijo-Pera, RA AF Tung, Joyce Y. Rosen, Mitchell P. Nelson, Lawrence M. Turek, Paul J. Witte, John S. Cramer, Daniel W. Cedars, Marcelle I. Reijo-Pera, Renee A. TI Novel missense mutations of the Deleted-in-AZoospermia-Like (DAZL) gene in infertile women and men SO REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY LA English DT Article ID MESSENGER-RNA LOCALIZATION; EMBRYONIC STEM-CELLS; GERM-CELLS; BINDING PROTEINS; HUMAN PUMILIO-2; Y-CHROMOSOME; IDENTIFICATION; EXPRESSION; CANDIDATE; HOMOLOG AB Background: The Deleted-in-AZoospermia-Like (DAZL) gene has homologs required for germ cell development in many organisms. Recently, we showed that there are several common polymorphisms within the DAZL gene that are associated with age at ovarian failure/menopause and sperm count. Methods: Here we sought to identify rare mutations in DAZL and examine their phenotypes in men and women. We sequenced the DAZL gene in 519 individuals; sequences spanned the entire coding region of the gene. Results: We report the identification of four putative missense mutations in DAZL. Three individuals that were heterozygous for a DAZL mutation reported having children, while two individuals that were homozygous reported no children. These mutations were found only in infertile men and women. Conclusion: Given the strong data associating DAZL polymorphisms and deletions with fertility in humans and model organisms, we suggest that these mutations may be associated with age at menopause and/or sperm count and warrant further biochemical and genetic investigation. C1 Univ Calif San Francisco, Human Embryon Stem Cell Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Natl Inst Child Hlth & Human Dev, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Epidemiol Ctr, Boston, MA 02115 USA. RP Reijo-Pera, RA (reprint author), Univ Calif San Francisco, Human Embryon Stem Cell Ctr, San Francisco, CA 94143 USA. EM joyce.tung@stanford.edu; rosenm@obgyn.ucsf.edu; Lawrence_Nelson@nih.gov; pturek@urol.ucsf.edu; wittej@humgen.ucsf.edu; dcramer@partners.org; marcelle.cedars@ucsfmedctr.org; reijoperar@obgyn.ucsf.edu OI Reijo Pera, Renee/0000-0002-6487-1329 FU Intramural NIH HHS; NICHD NIH HHS [R01 HD037095, R01 HD044876, R01 HD047721, R01 HD37095] NR 42 TC 24 Z9 27 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1477-7827 J9 REPROD BIOL ENDOCRIN JI Reprod. Biol. Endocrinol. PD AUG 2 PY 2006 VL 4 AR 40 DI 10.1186/1477-7827-4-40 PG 6 WC Endocrinology & Metabolism; Reproductive Biology SC Endocrinology & Metabolism; Reproductive Biology GA 079AC UT WOS:000240146900001 PM 16884537 ER PT J AU Ji, XH AF Ji, Xinhua TI Structural basis for non-catalytic and catalytic activities of ribonuclease III SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID DOUBLE-STRANDED-RNA; ESCHERICHIA-COLI; BACTERIOPHAGE-LAMBDA; BINDING DOMAIN; SUBSTRATE-SPECIFICITY; PROCESSING ACTIVITY; GENE-EXPRESSION; NUCLEASE DOMAIN; DSRNA-BINDING; CLEAVAGE AB Ribonuclease III ( RNase III) represents a highly conserved family of double- stranded ( ds) RNA- specific endoribonucleases, exemplified by bacterial RNase III and eukaryotic Rnt1p, Drosha and Dicer. Bacterial RNase III, containing an endonuclease domain followed by a dsRNA- binding domain, is the most extensively studied member of the family. It can affect RNA structure and gene expression in either of two ways: as a processing enzyme that cleaves dsRNA or as a binding protein that binds but does not cleave dsRNA. The available biochemical and structural data support the existence of two distinct forms of the RNase III - dsRNA complex which reflect the dual activities of the protein. The information revealed by the structures of bacterial RNase III provides insight into the mechanism of dsRNA processing by all members of the family. C1 Natl Canc Inst, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. RP Ji, XH (reprint author), Natl Canc Inst, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU Intramural NIH HHS NR 43 TC 20 Z9 21 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD AUG PY 2006 VL 62 BP 933 EP 940 DI 10.1107/S090744490601153X PN 8 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 064WE UT WOS:000239119800013 PM 16855311 ER PT J AU Collins, CC Moolchan, ET AF Collins, Charles C. Moolchan, Eric T. TI Shorter time to first cigarette of the day in menthol adolescent cigarette smokers SO ADDICTIVE BEHAVIORS LA English DT Article DE adolescent; tobacco; nicotine; TTF; addiction ID NICOTINE DEPENDENCE; EXPOSURE; SMOKING AB Menthol smoking is thought to contribute to the addictiveness of smoking. Given the high prevalence of menthol smoking among youth, the aim of the current analysis was to examine differences in consumption and tobacco dependence, including smoking urgency among menthol and non-menthol adolescent smokers. Data for the current analysis were collected from telephone interviews with adolescent smokers applying to a cessation treatment study. Of 572 adolescent smokers (mean age= 15.6 1.6 years; 55.1% female; 46.9% African American, 48.2% European American), 531 smoked menthol cigarettes and 41 smoked non-menthol as their usual brand. Analysis using Fisher's Exact (one-tailed) Test revealed that menthol smokers had a significantly shorter time to first (TTF) cigarette of the day compared to non-menthol smokers (smoking within the first 5 min of the day, 45% vs. 29%, respectively; p < 0.04). Independent t tests revealed no significant difference in number of cigarettes per day (CPD) (mean= 12.2 +/- 8.5 vs. 11.4 +/- 8.8; p < 0.28) or Fagerstrom Test for Nicotine Dependence (FTND) scores (3.4 +/- 1.4 vs. 3.2 +/- 1.3; p < 0.23). While preliminary, our findings suggest greater smoking urgency among menthol compared to non-menthol adolescent cessation-treatment seekers. Further study in a broader sample of adolescent smokers is warranted to elucidate the mechanisms underlying the effects of menthol smoking for youths. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Treatment Res Clin, Clin Pharmacol & Therapeut Res Branch, DHHS,NIH,IRP, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov FU Intramural NIH HHS NR 11 TC 39 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD AUG PY 2006 VL 31 IS 8 BP 1460 EP 1464 DI 10.1016/j.addbeh.2005.10.001 PG 5 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 072YI UT WOS:000239708700016 PM 16303257 ER PT J AU Cutler, RG Mattson, MP AF Cutler, Roy G. Mattson, Mark P. TI Introduction: The adversities of aging SO AGEING RESEARCH REVIEWS LA English DT Editorial Material DE aging process; oxidative stress; healthspan ID LIFE-SPAN; CAENORHABDITIS-ELEGANS; EXCEPTIONAL LONGEVITY; OXIDATIVE STRESS; SLEEP DURATION; AGE; PERFORMANCE; GENE; DROSOPHILA; EXERCISE AB The aging process is evolutionarily conserved and subject to quantitative modification by both genetic and environmental factors. Fundamental mechanisms of aging result in progressive deficits in the function of cells and organs, often leading to diseases that ultimately kill the organism such as cancers, cardiovascular disease and neurodegenerative disorders. Oxidative stress and damage to all of the major classes of molecules in cells are involved in aging and age-related diseases. The widely pursued approach of targeting disease-specific processes to develop therapeutic interventions has not had a major impact on healthspan. A more productive approach would be to target the fundamental mechanisms of aging throughout adult life so as to extend healthspan. Caloric restriction and regular exercise are two such approaches. Published by Elsevier Ireland Ltd. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Cutler, RG (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM cutlerro@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 70 TC 31 Z9 32 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD AUG PY 2006 VL 5 IS 3 BP 221 EP 238 DI 10.1016/j.arr.2006.05.002 PG 18 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 092FQ UT WOS:000241082800001 PM 16950665 ER PT J AU Martin, B Mattson, MP Maudsley, S AF Martin, Bronwen Mattson, Mark P. Maudsley, Stuart TI Caloric restriction and intermittent fasting: Two potential diets for successful brain aging SO AGEING RESEARCH REVIEWS LA English DT Review DE caloric restriction; intermittent fasting; aging ID ACTIVATED-RECEPTOR-ALPHA; EXTENDS LIFE-SPAN; FORKHEAD TRANSCRIPTION FACTORS; AMYLOID-PRECURSOR PROTEIN; FATTY-ACID OXIDATION; GENE-EXPRESSION; CAENORHABDITIS-ELEGANS; INSULIN-RECEPTOR; SKELETAL-MUSCLE; SACCHAROMYCES-CEREVISIAE AB The vulnerability of the nervous system to advancing age is all too often manifest in neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. In this review article we describe evidence suggesting that two dietary interventions, caloric restriction (CR) and intermittent fasting (IF), can prolong the health-span of the nervous system by impinging upon fundamental metabolic and cellular signaling pathways that regulate life-span. CR and IF affect energy and oxygen radical metabolism, and cellular stress response systems, in ways that protect neurons against genetic and environmental factors to which they would otherwise succumb during aging. There are multiple interactive pathways and molecular mechanisms by which CR and IF benefit neurons including those involving insulin-like signaling, FoxO transcription factors, sirtuins and peroxisome proliferator-activated receptors. These pathways stimulate the production of protein chaperones, neurotrophic factors and antioxidant enzymes, all of which help cells cope with stress and resist disease. A better understanding of the impact of CR and IF on the aging nervous system will likely lead to novel approaches for preventing and treating neurodegenerative disorders. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Harbor Hosp, Medstar Res Inst, Baltimore, MD 21225 USA. RP Martin, B (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM martinbro@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000318-01] NR 147 TC 156 Z9 159 U1 16 U2 57 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD AUG PY 2006 VL 5 IS 3 BP 332 EP 353 DI 10.1016/j.arr.2006.04.002 PG 22 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 092FQ UT WOS:000241082800006 PM 16899414 ER PT J AU Demissie, S Levy, D Benjamin, EJ Cupples, LA Gardner, JP Herbert, A Kimura, M Larson, MG Meigs, JB Keaney, JF Aviv, A AF Demissie, S. Levy, D. Benjamin, E. J. Cupples, L. A. Gardner, J. P. Herbert, A. Kimura, M. Larson, M. G. Meigs, J. B. Keaney, J. F. Aviv, A. TI Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study SO AGING CELL LA English DT Article DE accelerated aging; disease; insulin/IGF-1 signalling; life span; oxidative stress; telomeres ID HOMEOSTASIS MODEL ASSESSMENT; CARDIOVASCULAR-DISEASE; GLUCOSE-TOLERANCE; HUMAN FIBROBLASTS; PULSE PRESSURE; BLOOD-PRESSURE; INFLAMMATION; ATHEROSCLEROSIS; ASSOCIATION; SENSITIVITY AB Insulin resistance and oxidative stress are associated with accelerated telomere attrition in leukocytes. Both are also implicated in the biology of aging and in aging-related disorders, including hypertension. We explored the relations of leukocyte telomere length, expressed by terminal restriction fragment (TRF) length, with insulin resistance, oxidative stress and hypertension. We measured leukocyte TRF length in 327 Caucasian men with a mean age of 62.2 years (range 40-89 years) from the Offspring cohort of the Framingham Heart Study. TRF length was inversely correlated with age (r = -0.41, P < 0.0001) and age-adjusted TRF length was inversely correlated with the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (r = -0.16, P = 0.007) and urinary 8-epi-PGF(2 alpha) (r = -0.16, P = 0.005) - an index of systemic oxidative stress. Compared with their normotensive peers, hypertensive subjects exhibited shorter age-adjusted TRF length (hypertensives = 5.93 +/- 0.042 kb, normotensives = 6.07 +/- 0.040 kb, P = 0.025). Collectively, these observations suggest that hypertension, increased insulin resistance and oxidative stress are associated with shorter leukocyte telomere length and that shorter leukocyte telomere length in hypertensives is largely due to insulin resistance. C1 Univ Med & Dent New Jersey, Ctr Human Dev & Aging, MSB, Newark, NJ 07103 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. Evans Mem Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Aviv, A (reprint author), Univ Med & Dent New Jersey, Ctr Human Dev & Aging, MSB, Room F-464,185 S Orange Ave, Newark, NJ 07103 USA. EM avivab@umdnj.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01 HL64753, N01-HC 25195, R01 HL076784]; NIA NIH HHS [AG021593] NR 37 TC 247 Z9 261 U1 0 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1474-9718 J9 AGING CELL JI Aging Cell PD AUG PY 2006 VL 5 IS 4 BP 325 EP 330 DI 10.1111/j.1474-9726.2006.00224.x PG 6 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 064WP UT WOS:000239121100006 PM 16913878 ER PT J AU Valenti, G Denti, L Sacco, M Ceresini, G Bossoni, S Giustina, A Maugeri, D Vigna, GB Fellin, R Paolisso, G Barbagallo, M Maggio, M Strollo, F Bollanti, L Romanelli, F Latini, M AF Valenti, Giorgio Denti, Licia Sacco, Marcella Ceresini, Graziano Bossoni, Simonetta Giustina, Andrea Maugeri, Domenico Vigna, Giovanni B. Fellin, Renato Paolisso, Giuseppe Barbagallo, Mario Maggio, Marcello Strollo, Felice Bollanti, Lucilla Romanelli, Francesco Latini, Maurizio CA GISEG TI Consensus Document on substitution therapy with DHEA in the elderly SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Consensus Document; elderly; adrenal insufficiency; adrenopause; DHEA; DHEAS; DHEA substitution therapy ID SERUM DEHYDROEPIANDROSTERONE-SULFATE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; PLACEBO-CONTROLLED TRIAL; CARDIOVASCULAR RISK-FACTORS; SUBJECTIVE HEALTH-STATUS; INSULIN-RESISTANT OBESE; BLOOD-PRESSURE LEVELS; BODY-FAT DISTRIBUTION; BONE-MINERAL DENSITY; EYE-MOVEMENT SLEEP C1 Univ Parma, Dipartimento Med Interna & Sci Biomed, Sez Geriatria, I-43100 Parma, Italy. Univ Brescia, I-25121 Brescia, Italy. Univ Catania, I-95124 Catania, Italy. Univ Ferrara, I-44100 Ferrara, Italy. Univ Naples, I-80138 Naples, Italy. Univ Palermo, I-90133 Palermo, Italy. NIA, Baltimore, MD 21224 USA. INRCA, Rome, Italy. Univ Roma, Rome, Italy. Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Div Epidemiol, Philadelphia, PA 19104 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Valenti, G (reprint author), Univ Parma, Dipartimento Med Interna & Sci Biomed, Sez Geriatria, Via Gramsci 14, I-43100 Parma, Italy. EM geriat@unipr.it RI Romanelli, Francesco/A-7925-2012; Vigna, Giovanni/H-2826-2015; OI Vigna, Giovanni/0000-0001-8640-7052; BARBAGALLO, MARIO/0000-0002-1349-6530; Paolisso, Giuseppe/0000-0002-2137-455X NR 201 TC 13 Z9 14 U1 2 U2 4 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD AUG PY 2006 VL 18 IS 4 BP 277 EP 300 PG 24 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 102LH UT WOS:000241812000003 ER PT J AU Cohen-Mansfield, J Marx, MS Guralnik, JM AF Cohen-Mansfield, Jiska Marx, Marcia S. Guralnik, Jack M. TI Comparison of exercise models in an elderly population SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE models of exercise behavior; physical activity; self-efficacy; two-stage model ID PHYSICAL-ACTIVITY; OLDER-ADULTS; PERCEIVED BARRIERS; PLANNED BEHAVIOR; ADHERENCE; EFFICACY; SCALE; PARTICIPATION; INTERVENTION; MAINTENANCE AB Background and aims: Two different models of exercise behavior in an older population have been previously published (Schuster et al., 1995 and Resnick et al., 2000). We aimed to validate the models with data from a different sample, and to examine whether any of these models explained a greater proportion of the variance in exercise behavior in this population. Methods: Participants were 324 community-dwelling persons aged 74-85 years who completed a mailed questionnaire. The questionnaire included questions about demographics, current exercise habits, health, activities of daily living, depressed affect, living arrangement, attitudes about exercise, self-efficacy, barriers to exercise, and enjoyment of exercise. Results: While our data explained some of the variance of the two previously published models of exercise behavior, the percentage of variance explained was less impressive than that reported by those authors. A path analysis of demographic and psychological constructs, which have been used in both models, demonstrated that physical health, mental health, gender, and past enjoyment of exercise affect self-efficacy, attitudes/outcome expectancy, and reported barriers to exercise. These psychological constructs in turn affect exercise habits. Conclusions: The relatively low percentage of variance explained by the models may imply that other factors contribute to exercise behavior in older adults that the constructs are very sensitive to measurement differences, or that these factors are not as important as previously thought. Our results are consistent with the models of both Schuster et al. and Resnick et al., but suggest that a combined model may better represent the data. Future investigations of exercise behavior in older persons should examine this possibility. C1 Hebrew Home Greater Washington, Res Inst Aging, Rockville, MD 20852 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Cohen-Mansfield, J (reprint author), Hebrew Home Greater Washington, Res Inst Aging, 6121 Montrose Rd, Rockville, MD 20852 USA. EM cohen-mansfield@hebrew-home.org NR 31 TC 5 Z9 5 U1 1 U2 5 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD AUG PY 2006 VL 18 IS 4 BP 312 EP 319 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 102LH UT WOS:000241812000006 PM 17063066 ER PT J AU Shao, WS Lazaryan, A Dorak, MT Penman-Aguilar, A Wilson, CM Margolick, JB Goedert, JJ Prins, M Tang, JM Kaslow, RA AF Shao, Wenshuo Lazaryan, Aleksandr Dorak, M. Tevfik Penman-Aguilar, Ana Wilson, Craig M. Margolick, Joseph B. Goedert, James J. Prins, Maria Tang, Jianming Kaslow, Richard A. TI Cohort- and time-specific associations of CTLA4 genotypes with HIV-1 disease progression SO AIDS LA English DT Article DE AIDS; CTLA4; genetics; HIV; virus load ID VIRUS TYPE-1 INFECTION; T-CELL-ACTIVATION; GENE POLYMORPHISMS; IMMUNE ACTIVATION; RNA CONCENTRATION; CCR5 GENOTYPES; HOMOSEXUAL-MEN; VIRAL LOAD; SUSCEPTIBILITY; CD28 AB Background: CTLA4 in the chromosome 2q33 region encodes cytotoxic T-lymphocyte (CTL) associated antigen 4, which clownregulates CTL responses. We examined the relationships between common CTLA4 variants and several outcomes of HIV-1 infection in adults and adolescents. Methods: We studied 765 HIV-1-infected persons: 558 Caucasian seroconverters from three cohorts (MACS, ACS, and DCG) and 207 infected adolescents (mostly female) from another cohort (REACH) of mixed ethnicity. Single nucleoticle polymorphisms in CTLA4 promoter (-1147C/T, -658C/T, -318C/T), coding sequence (49A/G) and the 3' untranslated region (CT60A/G) were resolved by PCR-based techniques. Repeated measures and survival analyses were used to test allelic and haplotypic associations with HIV-1 viral load (VL) and time to AIDS, respectively. Results: Individuals carrying -318T or the (-1147) T-(-318) T haplotype had elevated HIV-1 VL in MACS and REACH but reduced VL in DCG and ACS participants. Time-dependent associations of CTLA4-318T with VL were observed in MACS and REACH (P = 0.03-0.09). In Cox regression models adjusted for age and established contributory markers in CCR5 and HLA class I genes, CTLA4-318T was associated with rapid progression to AIDS in MACS (relative hazard 1.69; 95% confidence interval, 1.15-2.49; P < 0.01) as opposed to a non-significant slower disease progression in ACS and no appreciable association in DCG. Conclusions: Association of CTLA4 genotypes with clinical and virological outcomes following HIV-1 infection appeared to vary with time and among the cohorts. Further analyses in conjunction with other biologically and positionally related genes, such as CD28 and ICOS, may help explain the disparate findings. (c) 2006 Lippincott Williams & Wilkins. C1 Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. NCI, Rockville, MD USA. Hlth Serv, Amsterdam, Netherlands. RP Kaslow, RA (reprint author), Univ Alabama, Dept Epidemiol, 1665 Univ Blvd,RPHB Room 220, Birmingham, AL 35294 USA. EM rkaslow@uab.edu OI Tang, Jianming/0000-0003-0137-7486 FU Intramural NIH HHS; NIAID NIH HHS [AI41951]; NICHD NIH HHS [U01 HD32830] NR 50 TC 5 Z9 6 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 AUG 1 PY 2006 VL 20 IS 12 BP 1583 EP 1590 DI 10.1097/01.aids.0000238403.08497.3f PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 076VI UT WOS:000239985800002 PM 16868438 ER PT J AU Engels, EA Pfeiffer, RM Goedert, JJ Virgo, P McNeel, TS Scoppa, SM Biggar, RJ AF Engels, Eric A. Pfeiffer, Ruth M. Goedert, James J. Virgo, Phillip McNeel, Timothy S. Scoppa, Steven M. Biggar, Robert J. CA HIVAIDS Canc Match Study TI Trends in cancer risk among people with AIDS in the United States 1980-2002 SO AIDS LA English DT Article DE cancer risk; AIDS; United States; HAART ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS-INFECTION; SWISS HIV COHORT; HUMAN-PAPILLOMAVIRUS; LUNG-CANCER; MORTALITY; PREVALENCE; INITIATION; EUROPE; ADULTS AB Background: People with AIDS have heightened cancer risk from immunosuppression. HAART has been available since 1996 and has reduced AIDS-related mortality, but there are few large-scale studies on cancer trends. Methods: AIDS and cancer registries in 11 US regions (1980-2002) were used to identify cancers in 375 933 people with AIDS. Cancer risk relative to the general population was measured using the standardized incidence ratio (SIR), focusing on the 2 years after AIDS onset for those with AIDS in 1990-1995 and 1996-2002 (HAARTera). Time trends were assessed with Poisson regression. Results: Between 1990-1995 and 1996-2002, risk declined for the two major AIDS-defining cancers: Kaposi sarcoma [(KS) n = 5131; SIR, 22 100 and 3640, respectively; P < 0.0001] and non-Hodgkin lymphoma [(NHL) n=3412; SIR, 53.2 and 22.6, respectively; P < 0.00011. Declines began in the 1980s, but risk fell sharply in 1996 and was stable thereafter. Risk of cervical cancer did not change (n = 64; SIR, 4.2 and 5.3, respectively; P = 0.33). Among non-AIDS malignancies, lung cancer was most common, but risk declined between 1990-1995 and 1996-2002 (n = 344; SIR, 3.3 and 2.6, respectively; P = 0.02). Risk of Hodgkin lymphoma increased substantially over the 1990-2002 period (n = 149; SIR, 8.1 and 13.6, respectively; P = 0.003). Conclusions: Dramatic declines in KS and NHL were temporally related to improving therapies, especially introduction of HAART, but those with AIDS remain at marked risk. Among non-AIDS-related cancers, a recent increase in Hodgkin lymphoma was observed. (c) 2006 Lippincott Williams & Wilkins. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. Informat Management Serv Inc, Silver Spring, MD USA. Comp Sci Corp, Rockville, MD USA. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7076, Rockville, MD 20852 USA. EM engelse@exchange.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU Intramural NIH HHS NR 32 TC 406 Z9 409 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 1 PY 2006 VL 20 IS 12 BP 1645 EP 1654 DI 10.1097/01.aids.0000238411.75324.59 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 076VI UT WOS:000239985800010 PM 16868446 ER PT J AU Lovinger, DM AF Lovinger, David M. TI Mixing proteomics and alcohol SO ALCOHOL LA English DT Editorial Material ID PROTEIN EXPRESSION; ETHANOL; BRAIN; MICROARRAY; RATS AB Techniques for high-throughput measurement of protein expression and posuranslational modification are just beginning to be applied to alcohol research. Studies using this proteomic approach to examine tissue from alcoholic humans and alcohol-exposed nonhuman primates have appeared in the last year. In the present issue of Alcohol, Bell et al. present the first such analysis of brain protein expression in relation to alcohol drinking in rodents. This study found changes in several interesting classes of proteins, including molecules involved in vesicular neurotransmitter release, cellular metabolism, and cell structure. These new and exciting findings are discussed in relation to the proteomics studies in primates, and the future of proteomics in the alcohol research field. (c) 2006 Elsevier Inc. All rights reserved. C1 NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, Rockville, MD 20852 USA. EM lovindav@mail.nih.gov NR 13 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD AUG PY 2006 VL 40 IS 1 BP 1 EP 2 DI 10.1016/j.alcohol.2006.11.002 PG 2 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 120DW UT WOS:000243064900001 PM 17157715 ER PT J AU Dominguez, LJ Barbagallo, M Lauretani, F Bandinelli, S Bos, A Corsi, AM Simonsick, EM Ferrucci, L AF Dominguez, Ligia J. Barbagallo, Mario Lauretani, Fulvio Bandinelli, Steania Bos, Angelo Corsi, Anna Maria Simonsick, Eleanor M. Ferrucci, Luigi TI Magnesium and muscle performance in older persons: the InCHIANTI study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE magnesium; aging; sarcopenia; muscle performance; muscle strength ID DIETARY MAGNESIUM; PHYSICAL PERFORMANCE; HANDGRIP STRENGTH; SKELETAL-MUSCLE; WOMENS HEALTH; DEFICIENCY; DISABILITY; AGE; SUPPLEMENTATION; FEASIBILITY AB Background: The role of magnesium in maintaining muscle integrity and function in older adults is largely unknown. Objective: We aimed to investigate the relation between serum magnesium concentrations and muscle performance in older subjects. Design: Data are from the baseline examination conducted between September 1998 and March 2000 of the InCHIANTI (aging in the Chianti area) study, a prospective epidentiologic survey of risk factors for late-life disability. From among 1453 randomly selected community residents completing a home interview, 1138 men (46%) and women (aged 66.7 +/- 15.2; (x) over bar +/- SD) with complete data on muscle performance and serum magnesium who were not severely cognitively compromised and had no evidence of kidney disease or hypercalcemia were included in the analysis. Muscle performance was evaluated by grip strength, lower-leg muscle power, knee extension torque, and ankle extension isometric strength and was normalized for age and body mass index (BMI) within each sex. Results: After adjustment for age, sex, BMI, laboratory variables, presence of chronic diseases, muscle area, muscle density, and physical activity level, serum magnesium concentrations were significantly associated with indexes of muscle performance, including grip strength (ss = 2.0 +/- 0.5. P = 0.0002), lower-leg muscle power (ss = 8.8 +/- 2.7, P = 0.001). knee extension torque (ss = 31.2 +/- 7.9, P < 0.0001), and ankle extension strength (ss = 3.8 +/- 0.5, P < 0.0001). Conclusions: The serum magnesium concentration is an independent correlate of muscle performance in older persons. Whether magnesium supplementation improves muscle function remains to be shown. C1 Univ Palermo, Dept Internal Med & Geriatr, Geriatr Unit, I-90144 Palermo, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. Tuscany Hlth Reg Agcy, Florence, Italy. ASF, Geriatr Rehabil Unit, Florence, Italy. RP Dominguez, LJ (reprint author), Univ Palermo, Dept Internal Med & Geriatr, Geriatr Unit, Viale F Scaduto 6-C, I-90144 Palermo, Italy. EM mabar@unipa.it RI Lauretani, Fulvio/K-5115-2016 OI dominguez, ligia j/0000-0003-1466-8610; BARBAGALLO, MARIO/0000-0002-1349-6530; Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-916413, N01-AG-821336]; NIMHD NIH HHS [R01 MD009164, 263 MD 821336, 263 MD 9164 13] NR 40 TC 51 Z9 51 U1 8 U2 22 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD AUG PY 2006 VL 84 IS 2 BP 419 EP 426 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 072LG UT WOS:000239674300023 PM 16895893 ER PT J AU Ayache, S Panelli, M Marincola, FM Stroncek, DF AF Ayache, Saleh Panelli, Monica Marincola, Francesco M. Stroncek, David F. TI Effects of storage time and exogenous protease inhibitors on plasma protein levels SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE plasma; proteases; protease inhibitors ID METALLOPROTEINASE; INFLAMMATION; PROTEOMICS; STABILITY; ANALYTES; DISEASE; SERUM AB Plasma biomarker analysis requires intact unbiased starting material. We analyzed the effects on plasma protein profiles of protease inhibitor cocktails and preprocessing storage. Plasma from 12 healthy subjects collected with and without protease inhibitors was prepared immediately and after 2 hours of room temperature storage. The samples were analyzed by a multiplexed enzyme-linked immunosorbent assay that captured 99 chemokines and cytokines. Unsupervised hierarchical analysis clustered the samples into 4 groups: one composed predominantly of samples processed immediately, another of samples processed after 2 hours, and the remaining two a mix of immediate and 2-hour samples. The mixed and immediate group protein profiles were similar However, among the immediate and 2-hour samples, the levels of 37 factors differed significantly: all were greater after 2 hours. The dramatic changes in protein levels during storage were independent of protease inhibitors and are likely due to cytokine production and/or release by leukocytes and platelets. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Immunogenet Lab, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Immunogenet Lab, Bldg 10,Room 1C711,10 Ctr Dr MSC-1184, Bethesda, MD 20892 USA. NR 16 TC 39 Z9 39 U1 1 U2 5 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD AUG PY 2006 VL 126 IS 2 BP 174 EP 184 DI 10.1039/3WM7XJ7RD8BCLNKX PG 11 WC Pathology SC Pathology GA 066FV UT WOS:000239216000002 PM 16891190 ER PT J AU Ward, MH Wartenberg, D AF Ward, Mary H. Wartenberg, Daniel TI Invited commentary: On the road to improved exposure assessment using geographic information systems SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID CANCER MORTALITY; ENVIRONMENTAL EPIDEMIOLOGY; POSITIONAL ACCURACY; SPATIAL-ANALYSIS; RISK-ASSESSMENT; AIR-POLLUTION; LUNG-CANCER; HEALTH; TAIWAN; POPULATION C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Div Environm Epidemiol, Dept Environm & Occupat Med, Piscataway, NJ 08854 USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. EM wardm@exchange.nih.gov NR 39 TC 6 Z9 6 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD AUG 1 PY 2006 VL 164 IS 3 BP 208 EP 211 DI 10.1093/ajekwj183 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 068QX UT WOS:000239390600003 PM 16707652 ER PT J AU Ahmed, B Merz, CNB McClure, C Johnson, BD Reis, SE Bittner, V Pepine, CJ Sharaf, BL Sopko, G Kelsey, SF Shaw, L AF Ahmed, Bina Merz, C. Noel Bairey McClure, Candace Johnson, B. Delia Reis, Steve E. Bittner, Vera Pepine, Carl J. Sharaf, Barry L. Sopko, George Kelsey, Sheryl F. Shaw, Leslee CA WISE Study Grp TI Migraines, angiographic coronary artery disease and cardiovascular outcomes in women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE migraines; coronary artery disease; cardiovascular events ID SYNDROME EVALUATION WISE; HEART-DISEASE; ATHEROSCLEROSIS RISK; ISCHEMIA; HEADACHES; ANGINA; EPIDEMIOLOGY; ASSOCIATIONS; COMMUNITIES; PREVALENCE AB PURPOSE: There are conflicting data regarding the association between migraines and cardiovascular events. We evaluated the relationship between migraine headaches, angiographic coronary artery disease, and cardiovascular events in women. SUBJECTS AND METHODS: The Women's Ischemia Syndrome Evaluation (WISE) study is a National Heart, Lung and Blood Institute (NHLBI)-sponsored prospective, multicenter study aiming to improve ischemia evaluation in women. A total of 944 women presenting with chest pain or symptoms suggestive of myocardial ischemia were enrolled and underwent complete demographic, medical, and psychosocial history, physical examination, and coronary angiography testing. A smaller subset of 905 women, representing a mean age of 58 years, answered questions regarding a history of migraines. We prospectively followed 873 women for 4.4 years for cardiovascular events and all-cause mortality. RESULTS: Women reporting a history of migraines (n = 220) had lower angiographic coronary severity scores, and less severe (>= 70% luminal stenosis) angiographic coronary artery disease compared to women without a history of migraines (n = 685). These differences remained statistically significant after adjustment for age and other important cardiac risk factors. On prospective follow- up of a median of 4.4 years, women with a history of migraines were not more likely to have a cardiovascular event (hazard ratio [HR] 1.2; 95% confidence interal [CI], 0.93-1.58) and migraines did not predict all-cause mortality (HR 0.96; 95% CI, 0.49-1.99). CONCLUSION: Among women undergoing coronary angiography for suspected ischemia, those reporting migraines had less severe angiographic coronary artery disease. We could not support an association between migraines and cardiovascular events or death. Further research studying the common pathophysiology underlying migraines and cardiovascular disease is warranted. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, WISW Coordinating Ctr, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Med, Div Cardiol, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. Rhode Isl Hosp, Providence, RI USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Merz, CNB (reprint author), Univ Pittsburgh, WISW Coordinating Ctr, Grad Sch Publ Hlth, Dept Epidemiol, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM noel.merz@cshs.org RI Reis, Steven/J-3957-2014; OI Bittner, Vera/0000-0001-9456-850X FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68163, N01-HV-68161, N01-HV-68164, N01-HV-68162] NR 25 TC 28 Z9 28 U1 0 U2 2 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD AUG PY 2006 VL 119 IS 8 BP 670 EP 675 DI 10.1016/j.amjmed.2006.03.023 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 070UH UT WOS:000239549900011 PM 16887413 ER PT J AU Biega, TJ Lonser, RR Butman, JA AF Biega, T. J. Lonser, R. R. Butman, J. A. TI Differential cortical thickness across the central across the central sulcus: A method for identifying the central sulcus in the presence of mass effect and vasogenic edema SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Neuroradiology CY MAY 21-27, 2005 CL Toronto, CANADA SP Amer Soc Neuroradiol ID LOCALIZATION; MOTOR AB BACKGROUND AND PURPOSE: Identification of the motor strip on MR imaging studies is difficult in the presence of mass effect and vasogenic edema because sulcal landmarks are obscured. We hypothesize that a difference in cortical thickness between the motor and sensory strips is readily apparent on T2-weighted images in the presence of vasogenic edema and reliably identifies the central sulcus. METHODS: Thirteen patients with brain tumors resulting in vasogenic edema near the central sulcus were identified. The cortical thickness of the anterior and posterior banks of the central sulcus as well as the neighboring sulci in the frontal and parietal lobes were measured from T2-weighted images. Similar measures were obtained from neighboring sulci in the frontal and parietal lobes. Location of the central sulcus was confirmed with standard anatomic landmarks in all patients and by intraoperative cortical mapping in 2 patients. RESULTS: A twofold difference in cortical thickness between the anterior and posterior banks of the central sulcus uniquely identified the central sulcus on T2-weighted images in the presence of vasogenic edema, despite the marked distortion of sulcal anatomy as a result of mass effect. This relationship was not present in neighboring sulci. CONCLUSION: Cytoarchitectonic differences in the motor and sensory cortices result in a markedly thicker posterior than anterior bank of the central sulcus that is readily visible on routine T2-weighted images in the presence of vasogenic edema. Therefore, the cortical thickness can serve as a complementary method in identification of the motor strip in patients with mass effect. C1 George Washington Univ, Med Ctr, Dept Neuroradiol, Washington, DC 20052 USA. Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Diagnost Radiol Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Butman, JA (reprint author), Bldg 10,Rm 1C635,9000 Rockville Pike, Bethesda, MD 20817 USA. EM jbutman@nih.gov RI Butman, John/A-2694-2008 NR 8 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD AUG PY 2006 VL 27 IS 7 BP 1450 EP 1453 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 076JF UT WOS:000239952500017 PM 16908556 ER PT J AU Walker, JL Wang, SS Schiffman, M Solomon, D AF Walker, Joan L. Wang, Sophia S. Schiffman, Mark Solomon, Diane CA ALTS Grp TI Predicting absolute risk of CIN3 during post-colposcopic follow-up: Results from the ASCUS-LSIL Triage Study (ALTS) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE loop electrosurgical excisional procedure; atypical squamous cells of undetermined significance; ASCUS/LSIL Triage Study; cervical intraepithelial neoplasia; Hybrid capture 2; human papillomavirus; high grade squamous intraepithelial lesion; low grade squamous intraepithelial lesion ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ELECTROSURGICAL EXCISION PROCEDURE; LOOP; MANAGEMENT; BIOPSY; VISIT; WOMEN AB Objective: At present, clinical management of women referred to colposcopy but found to have < CIN2 remains unclear. Using data from the ASCUS-LSIL Triage Study (ALTS) to inform clinical management, we calculated the absolute risk for developing CIN3 within 2 years of referral to an enrollment colposcopy. Study design: Women included in the analyses: (1) were initially referred to ALTS with a community cytologic interpretation of atypical squamous cell of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesions (LSIL); (2) had a colposcopic evaluation and biopsy, if indicated, resulting in a diagnosis < CIN2; and, therefore (3) were followed without treatment. Results from subsequent human papillomavirus (HPV) testing, liquid-based cytology interpretations, and a second colposcopic evaluation at least 6 months after and within 2 years of the first colposcopic evaluation were used to calculate absolute risks for CIN3. Results: Women with HPV-negative test results were at low risk for CIN3 regardless of other test results. Among HPV-positive women, increasing absolute risks of CIN3 were observed with increasing cytology severity: 7% (normal), 11% (ASCUS and LSIL), and 45% (HSIL). The highest absolute risk for CIN3 (67%) was observed for HPV-positive women with HSIL and a colposcopic impression of high-grade/cancer on the second colposcopy. Conclusion: In the ALTS population, after the first colposcopic diagnosis of < CIN2, clear risk stratification for CIN3 outcomes was obtained among women with a subsequent HPV-positive test. Because absolute risk for histologic CIN3 outcomes was high for women with HPV positive tests, HSIL cytology, and a high-grade impression at second colposcopy, it is worth considering whether this combination of findings might warrant immediate excisional therapy in some circumstances. (c) 2006 Mosby, Inc. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Walker, JL (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. EM Joan-walker@ouhsc.edu FU NCI NIH HHS [CN-55105, CN-55153, CN-55156, CN-55159, CN-55155, CN-55158, CN-55154, CN-55157] NR 16 TC 34 Z9 36 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 341 EP 348 DI 10.1016/j.ajog.2006.02.047 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000002 PM 16890545 ER PT J AU Jeronimo, J Schiffman, M AF Jeronimo, Jose Schiffman, Mark TI Colposcopy at a crossroads SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE colposcopy; visual inspection; cervical cancer ID CERVICAL INTRAEPITHELIAL NEOPLASIA; ATYPICAL SQUAMOUS-CELLS; UNDETERMINED SIGNIFICANCE; HUMAN-PAPILLOMAVIRUS; RANDOMIZED-TRIAL; CYTOLOGICAL ABNORMALITIES; CANCER; MANAGEMENT; BIOPSY; RISK AB New cervical cancer prevention strategies are arising from rapidly improving insight into human papillomavirus (HPV) natural history and cervical carcinogenesis, challenging the coventional roles of cytology and colposcopically directed biopsy as the reference standards of screening and diagnosis, respectively. HPV testing has high sensitivity but mediocre specificity and positive predictive value, making the role of colposcopy for the accurate identification of patients requiring treatment even more important. We believe that deficiencies of the colposcopically guided biopsy must be addressed, in particular, the inaccuracy of biopsy placement leading to low sensitivity for detection of CIN3. This opinion outlines our concerns and summarizes new data, suggesting posssible steps that may lead to improvement in colposcopic accuracy. (c) 2006 Mosby, Inc. All rights reserved. C1 NCI, Hormona & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Resources, Bethesda, MD 20892 USA. RP Jeronimo, J (reprint author), NCI, Hormona & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Resources, Bethesda, MD 20892 USA. NR 31 TC 110 Z9 114 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 349 EP 353 DI 10.1016/j.ajog.2006.01.091 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000003 PM 16677597 ER PT J AU Romero, R Tromp, G AF Romero, Roberto Tromp, Gerard TI High-dimensional biology in obstetrics and gynecology: Functional genomics in microarray studies SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article ID HUMAN CHORIONIC-GONADOTROPIN; GENE-EXPRESSION SIGNATURE; SYSTEMS BIOLOGY; HUMAN MYOMETRIUM; SAMPLE-SIZE; DNA MICROARRAY; BREAST-CANCER; PURIFICATION; LABOR; DISCOVERY C1 Hutzels Womens Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Romero, R (reprint author), Hutzels Womens Hosp, Perinatol Res Branch, NICHD, NIH,DHHS, Box 4,3990 John R, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 FU Intramural NIH HHS NR 71 TC 26 Z9 26 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 360 EP 363 DI 10.1016/j.ajog.2006.06.077 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000005 PM 16890547 ER PT J AU Tarca, AL Romero, R Draghici, S AF Tarca, Adi L. Romero, Roberto Draghici, Sorin TI Analysis of microarray experiments of gene expression profiling SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Review DE expression profiling; data preprocessing; differential expression; prediction; clustering; reliability; functional profiling ID CDNA MICROARRAY; FUNCTIONAL GENOMICS; DNA MICROARRAY; HUMAN MYOMETRIUM; REGULATED GENES; ONTO-TOOLS; COMPUTATIONAL GENOMICS; STATISTICAL-INFERENCE; PREDICT SURVIVAL; HIGH-THROUGHPUT AB The study of gene expression profiling of cells and tissue has become a major too] for discovery in medicine. Microarray experiments allow description of genome-wide expression changes in health and disease. The results of such experiments are expected to change the methods employed in the diagnosis and prognosis of disease in obstetrics and gynecology. Moreover, an unbiased and systematic study of gene expression profiling should allow the establishment of a new taxonomy of disease for obstetric and gynecologic syndromes. Thus, a new era is emerging in which reproductive processes and disorders could be characterized using molecular tools and fingerprinting. The design, analysis, and interpretation of microarray experiments require specialized knowledge that is not part of the standard curriculum of our discipline. This article describes the types of studies that can be conducted with microarray experiments (class comparison, class prediction, class discovery). We discuss key issues pertaining to experimental design, data preprocessing, and gene selection methods. Common types of data representation are illustrated. Potential pitfalls in the interpretation of microarray experiments, as well as the strengths and limitations of this technology, are highlighted. This article is intended to assist clinicians in appraising the quality of the scientific evidence now reported in the obstetric and gynecologic literature. (c) 2006 Mosby, Inc. All rights reserved. C1 Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. Karmanos Canc Inst, Detroit, MI USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Detroit, MI USA. RP Draghici, S (reprint author), Wayne State Univ, Dept Comp Sci, 408 State Hall, Detroit, MI 48202 USA. EM sorin@wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU Intramural NIH HHS; NCI NIH HHS [1R21CA10074001, R21 CA100740, R21 CA100740-01]; NHGRI NIH HHS [R01 HG003491, 1R01HG003491, R01 HG003491-01A1]; NIBIB NIH HHS [IR21 EB00990-01, R21 EB000990, R21 EB000990-01]; NINDS NIH HHS [1R01 NS045207-01, R01 NS045207, R01 NS045207-01] NR 155 TC 68 Z9 69 U1 4 U2 17 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 373 EP 388 DI 10.1016/j.ajog.2006.07.001 PG 16 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000007 PM 16890548 ER PT J AU Catherino, WH Leppert, PC Segars, JH AF Catherino, William H. Leppert, Phyllis C. Segars, James H. TI The promise and perils of microarray analysis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE microarray; leiomyoma; reverse transcriptase; polymerase chain; reaction; affymetrix; gene confirmation ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE ARRAYS; PROBES; ADENOCARCINOMA; TUMOR; LUNG; SETS; WNT AB Microarray analysis has provided a novel means of identifying clues into the mechanisms of disease development. As a methodology, microarray analysis holds the promise for genome-wide screening in which 2 tissues (diseased and normal) are compared, and molecular pathways that defined the phenotype of the disease could be precisely defined. Alternatively, microarray experiments can be used to differentially compare pathologically similar diseased tissues to predict response to chemotherapy and risk of recurrence. However, the clinician should be aware that various sources of error can influence microarray analysis results. Sources of error can be minimized but not eliminated, explaining why meticulously conducted experiments in different laboratories or using different platforms result in different lists of genes. Confirmation and validation of genome-wide microarray results using ancillary methods remains a critical step. With proper confirmatory studies and cautious interpretation, microarray analysis represents a powerful tool for molecular discovery. (c) 2006 Mosby, Inc. All rights reserved. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20892 USA. EM catheriw@mail.nih.gov FU Intramural NIH HHS NR 26 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 389 EP 393 DI 10.1016/j.ajog.2006.02.035 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000008 PM 16643826 ER PT J AU Haddad, R Tromp, G Kuivaniemi, H Chaiworapongsa, T Kim, YM Mazor, M Romero, R AF Haddad, Ramsi Tromp, Gerard Kuivaniemi, Helena Chaiworapongsa, Tinnakorn Kim, Yeon Mee Mazor, Moshe Romero, Roberto TI Human spontaneous labor without histologic chorioamnionitis is characterized by an acute inflammation gene expression signature SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE chorioamniotic membrane; blood; transcriptional profile; microarray acute inflammation; parturition; chorioamnionitis; chemokines; cytokines ID HUMAN FETAL MEMBRANES; COLONY-ENHANCING FACTOR; TOLL-LIKE RECEPTORS; PRETERM PARTURITION; GESTATIONAL MEMBRANES; CHEMOKINE RECEPTORS; PREMATURE RUPTURE; LINKING INNATE; TERM; CYTOKINE AB Objective: The purpose of this study was to identify which biological processes may be involved in normal labor. Study design: Transcriptional profiles for chorioamniotic membranes (n = 24) and blood (n = 20) were generated from patients at term with no labor (TNL) and in labor (TIL). Results: Expression of 197 transcripts (P <= .02) differentiated TIL and TNL chorioamniotic membrane samples. Gene Ontology analysis indicated that TIL samples had increased expression of multiple chemokines and transcripts associated with neutrophil and monocyte recruitment. Microarray results were verified using quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) with independent samples. Transcriptional profiles from blood RNA revealed no Gene Ontology category enrichment of discriminant probe sets. Conclusion: Labor induces gene expression changes consistent with localized inflammation, despite the absence of histologically detectable inflammation. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Surg, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Tromp, Gerard/B-2677-2017 OI Tromp, Gerard/0000-0002-7761-0806 NR 38 TC 84 Z9 85 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 394 EP 405 DI 10.1016/j.ajog.2005.08.0557 PG 12 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000009 ER PT J AU Leppert, PC Catherino, WH Segars, JH AF Leppert, Phyllis C. Catherino, William H. Segars, James H. TI A new hypothesis about the origin of uterine fibroids based on gene expression profiting with microarrays SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE leiomyoma; fibroids; keloid; microarray; extracellular matrix; collagen ID TRANSFORMING GROWTH FACTOR-BETA-3; SMOOTH-MUSCLE-CELLS; DERMATOPONTIN EXPRESSION; TGF-BETA; LEIOMYOMA; PIRFENIDONE; PATHOGENESIS; MYOMETRIUM; COLLAGEN; WOMEN AB This article will discuss some recent insights based on our microarray studies that have emphasized the role the extracellular matrix, transforming growth factor beta, and collagen structure in fibroid formation. These studies led to appreciation of molecular similarities between fibroids and keloids. Collectively, these observations suggest a model of fibroid development based on an abnormal response to tissue repair, resulting in disordered healing and formation of an altered extracellular matrix. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. RP Leppert, PC (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 HD999999] NR 37 TC 82 Z9 84 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 415 EP 420 DI 10.1016/j.ajog.2005.12.059 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000011 PM 16635466 ER PT J AU Toso, L Roberson, R Woodard, J Abebe, D Spong, CY AF Toso, Laura Roberson, Robin Woodard, Jade Abebe, Daniel Spong, Catherine Y. TI Prenatal alcohol exposure alters GABA(A)alpha(5) expression: A mechanism of alcohol-induced learning dysfunction SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fetal alcohol syndrome; GABA; NMDA; mouse; learning ID MOUSE MODEL; GABA(A) RECEPTOR; MICE; SUBUNIT; HIPPOCAMPUS; MEMORY; BRAIN; RAT AB Objective: In a model for fetal alcohol syndrome (FAS), we have previously found an alteration in NMDA receptors suggesting mediation, at least in part, of alcohol-related learning deficit. NMDA and GABA receptors interact in a multisynaptic circuit for the regulation of the inhibitory tone through the CNS. The GABA receptor subunit GABA(A)alpha(5) is involved in learning and is developmentally regulated, as it is excitatory in the perinatal brain and inhibitory in the adult. We were interested to evaluate alcohol's effect on GABA(A)alpha(5) expression to further understand alcohol-induced learning dysfunction. Study design: Timed, pregnant C57B16/Jmice were treated on gestational day 8 with alcohol (25% alcohol, 0.03 mL/kg ip) or control (saline). Embryos and brains were harvested 10 days after treatment, and brains from adult offspring were collected after evaluation in the Morris Water Maze, a well-established test for spatial learning. Gene expression included samples from at least 3 litters per timepoint, and calibrator-normalized relative real-time polymerase chain reaction (PCR) was performed to quantify GABA(A)alpha(5) with GAPDH standardization. Statistical analysis included analysis of variance (ANOVA). Results: Prenatal alcohol exposure significantly decreased GABAAa5 expression in the embryo (P < .02) and fetal brains (P < .01) 10 days after therapy. However, in adult brains GABAAa5 expression was increased versus controls (P < .01). As previously demonstrated, prenatal alcohol exposure resulted in deficits in adults learning the Morris Water Maze with controls learning faster (P < .05). Conclusion: Prenatal alcohol exposure alters developmental GABAAa5 expression. This may further explain the long-lasting damage of alcohol on learning skills. Both the alcohol-induced reduction in the GABAAa5 subunit during development and up-regulation in adult brain may be related to learning deficits resulting in decreased learning potential caused by the developmental defect and an increased inhibition of learning resulting from increased expression as an adult. In combination with our previous findings, these suggest that alcohol-induced learning impairment is likely the result of alterations of both NMDA and GABA expression and function. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHD, UPDN, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD 20892 USA. RP Toso, L (reprint author), NICHD, UPDN, NIH, Blg 9 Room 1W125,9 Mem Dr MSC 0925, Bethesda, MD 20892 USA. EM laura_toso@hotmail.com FU Intramural NIH HHS NR 18 TC 15 Z9 16 U1 2 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD AUG PY 2006 VL 195 IS 2 BP 522 EP 527 DI 10.1016/j.ajog.2006.01.098 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 071XU UT WOS:000239638000028 PM 16643827 ER PT J AU Furuichi, K Gao, JL Murphy, PM AF Furuichi, Kengo Gao, Ji-Liang Murphy, Philip M. TI Chemokine receptor CX3CR1 regulates renal interstitial fibrosis after ischemia-reperfusion injury SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; GROWTH-FACTOR-BETA; EXPERIMENTAL GLOMERULONEPHRITIS; TUBULOINTERSTITIAL INJURY; KNOCKOUT MICE; P-SELECTIN; FRACTALKINE; EXPRESSION; CX(3)CR1; ADHESION AB Transient renal ischemia induces both inflammatory and fibrotic processes and is a major cause of acute and chronic renal insufficiency. Study of ischemia-reperfusion injury in gene-targeted mice has identified multiple factors responsible for inflammation, whereas mechanisms underlying fibrosis remain poorly defined. Here we demonstrate by both gene inactivation and target protein blockade that a single chemokine receptor subtype, the fractalkine receptor CX3CR1, is able to reduce both inflammation and fibrosis after ischemia-reperfusion injury in the mouse, leading to partially preserved renal function after injury. The mechanism involves selective effects in the outer medulla, including reduced accumulation of macrophages and reduced expression of the macrophage and platelet-derived fibrogenic protein platelet-derived growth factor-B. CX3CR1 is the first chemokine receptor shown to contribute to fibrogenesis in renal ischemia-reperfusion injury. C1 NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Intramural NIH HHS NR 49 TC 72 Z9 78 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2006 VL 169 IS 2 BP 372 EP 387 DI 10.2353/ajpath.2006.060043 PG 16 WC Pathology SC Pathology GA 069TM UT WOS:000239471100006 PM 16877340 ER PT J AU Tormo, D Ferrer, A Gaffal, E Wenzel, J Basner-Tschakarjan, E Steitz, J Heukamp, LC Gutgemann, I Buettner, R Malumbres, M Barbacid, M Merlino, G Tuting, T AF Tormo, Damia Ferrer, Aleix Gaffal, Evelyn Wenzel, Joerg Basner-Tschakarjan, Etiena Steitz, Julia Heukamp, Lukas C. Guetgemann, Ines Buettner, Reinhard Malumbres, Marcos Barbacid, Mariano Merlino, Glenn Tueting, Thomas TI Rapid growth of invasive metastatic melanoma in carcinogen-treated hepatocyte growth factor/scatter factor-transgenic mice carrying an oncogenic CDK4 mutation SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID MALIGNANT-MELANOMA; GENETIC IMMUNIZATION; CUTANEOUS MELANOMA; HA-RAS; MOUSE; P16(INK4A); ACTIVATION; EXPRESSION; MET; SUSCEPTIBILITY AB Currently, novel mouse models of melanoma are being generated that recapitulate the histopathology and molecular pathogenesis observed in human disease. Impaired cell-cycle control, which is a hallmark of both familial and sporadic melanoma, promotes slowly growing carcinogen-induced melanomas in the skin of mice carrying a mutated cyclin-dependent kinase 4 (CDK4(R24C)). Deregulated receptor tyrosine kinase signaling, which is another important feature of human melanoma, leads to spontaneous development of metastatic melanoma after a long latency period in mice overexpressing hepatocyte growth factor/scatter factor (HGF/SF mice). Here we report that treatment with 7,12-dimethylbenz[a]anthracene and 12-O-tetradecanoylphorbol-13-acetate induced metastatic melanomas in all HGF/SF mice on the C57BL/6 background, which histologically resemble human melanoma. importantly, mutant CDK4 dramatically increased the number and the growth kinetics of carcinogen-induced primary melanomas in the skin and promoted the growth of spontaneous metastases in lymph nodes and lungs in all HGF/SF mice within the first 3 months of life. Apart from very few skin papillomas, we did not observe tumors of other histology in carcinogen-treated HGF/SF X CDK4(R24C) mice. This new experimental mouse model can now be exploited to study further the biology of melanoma and evaluate new treatment modalities. C1 Univ Bonn, Dept Dermatol, Lab Expt Dermatol, D-53105 Bonn, Germany. Univ Bonn, Inst Pathol, D-5300 Bonn, Germany. Ctr Nacl Invest Oncol, Madrid, Spain. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Tuting, T (reprint author), Univ Bonn, Dept Dermatol, Lab Expt Dermatol, Sigmund Freud Str 25, D-53105 Bonn, Germany. EM thomas.tueting@ukb.uni-bonn.de RI Malumbres, Marcos/E-8834-2011; Heukamp, Lukas/A-8338-2013; OI Malumbres, Marcos/0000-0002-0829-6315; Wenzel, Joerg/0000-0002-4744-5993 NR 37 TC 26 Z9 28 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD AUG PY 2006 VL 169 IS 2 BP 665 EP 672 DI 10.2353/ajpath.2006.060017 PG 8 WC Pathology SC Pathology GA 069TM UT WOS:000239471100030 PM 16877364 ER PT J AU Santolaya-Forgas, J Romero, R Wildman, DE Kim, CJ Mahoney, M Mehendale, R Burd, L AF Santolaya-Forgas, Joaquin Romero, Roberto Wildman, Derek E. Kim, Chong Jai Mahoney, Michael Mehendale, Ramakrishna Burd, Laurence TI Relationship between maternal and fetal plasma glucose and insulin concentrations during graded maternal hyperglycemic states in primates SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE diabetes in pregnancy; fetal surgery; fetal glucose homeostasis ID GROWTH-RETARDATION; SOMATOMEDIN AB Our goal was to conduct a controlled study using an established timed-pregnant baboon model to describe the maternal and fetal plasma glucose and insulin concentrations during graded increases in maternal circulating glucose levels. Timed-pregnant baboons were operated on during the second half of pregnancy, and after recovery from surgery, maternal glucose infusions were started. To determine changes in plasma glucose and insulin concentrations, maternal and fetal blood samples were obtained before glucose infusion and at 30-minute intervals to include 30 minutes postinfusion. Maternal plasma glucose concentrations ranged from 97 to 392 mg/dL and fetal plasma glucose concentrations from 78 to 278 mg/dL. Maternal plasma insulin concentrations ranged from 123 to 1384 U/mL, and the fetal plasma insulin concentrations from 76 to 260 U/mL. Significant correlations were noted between maternal plasma glucose and insulin concentrations (N =10; R-2, 80%; p < 0.001), as well as maternal and fetal plasma glucose concentrations (N =10; R2, 97%; p < 0.001). Maternal-to-fetal glucose gradient ranged from 16 to 34% (mean, 23%) and did not correlate with maternal plasma glucose concentration. No correlation was found between fetal plasma glucose and insulin concentration. Maternal-to-fetal insulin gradient ranged from 31 to 87% (mean, 70.7%) and was significantly different from the glucose gradient (p < 0.0001). Results from this study suggests that (1) there is a relatively steady transplacental glucose transfer during the second half of pregnancy at maternal plasma glucose concentrations ranging from 97 to 392 mg/dL; and (2) there is also a relative incapacity of the fetal pancreas, compared with the maternal pancreas, to respond to graded increases of hyperglycemia. Studies aimed at determining whether particular thresholds of maternal hyperglycemia at different gestational ages can lead to transitory hyperosmolar and polyuric fetal states could provide further insights into the mechanisms leading to idiopathic polyhydramnios. C1 Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. Univ Illinois, Sch Med, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chicago, IL USA. RP Santolaya-Forgas, J (reprint author), Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, 3990 John R Rd,7 Brush N, Detroit, MI 48201 USA. FU Intramural NIH HHS NR 16 TC 3 Z9 3 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD AUG PY 2006 VL 23 IS 6 BP 369 EP 375 DI 10.1055/s-2006-947725 PG 7 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 076MM UT WOS:000239962400008 PM 16841274 ER PT J AU Kim, CH Pennisi, P Zhao, H Yakar, S Kaufman, JB Iganaki, K Shiloach, J Scherer, PE Quon, MJ LeRoith, D AF Kim, Chul-Hee Pennisi, Patricia Zhao, Hong Yakar, Shoshana Kaufman, Jeanne B. Iganaki, Kenjiro Shiloach, Joseph Scherer, Philipp E. Quon, Michael J. LeRoith, Derek TI MKR mice are resistant to the metabolic actions of both insulin and adiponectin: discordance between insulin resistance and adiponectin responsiveness SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE adiponectin resistance; muscle insulin-like growth factor-I receptor-lysine-arginine mouse ID ACTIVATED PROTEIN-KINASE; FATTY-ACID OXIDATION; SKELETAL-MUSCLE; PLASMA-CONCENTRATIONS; GLOBULAR DOMAIN; IGF-I; RECEPTORS; GLUCOSE; EXPRESSION; SENSITIVITY AB Most rodent models of insulin resistance are accompanied by decreased circulating adiponectin levels. Adiponectin treatment improves the metabolic phenotype by increasing fatty acid oxidation in skeletal muscle and suppressing hepatic glucose production. Muscle IGF-I receptor (IGF-IR)-lysine-arginine (MKR) mice expressing dominant-negative mutant IGF-IRs in skeletal muscle are diabetic with insulin resistance in muscle, liver, and adipose tissue. Adiponectin levels are elevated in MKR mice, suggesting an unusual discordance between insulin resistance and adiponectin responsiveness. Therefore, we investigated the metabolic actions of adiponectin in MKR mice. MKR and ob/ob mice were treated both acutely (28 mu g/g) and chronically (for 2 wk) with full-length adiponectin. Acute hypoglycemic effects of adiponectin were evident only in ob/ob mice but not in MKR mice. Chronic adiponectin treatment significantly improved both insulin sensitivity and glucose tolerance in ob/ob but not in MKR mice. Adiponectin receptor mRNA levels and adiponectin-stimulated phosphorylation of AMPK in skeletal muscle and liver were similar among MKR, wild-type, and ob/ob mice. Thus MKR mice are adiponectin resistant despite normal expression of adiponectin receptors and normal AMPK phosphorylation in muscle and liver. MKR mice may be a useful model for dissecting relationships between insulin resistance and adiponectin action in regulation of glucose homeostasis. C1 NIDDK, Diabet Branch, Bethesda, MD USA. NIDDK, Biotechnol Unit, Bethesda, MD USA. NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. RP LeRoith, D (reprint author), Mt Sinai Sch Med, Div Endocrinol Diabet & Bone Dis, 1 Gustave L Levy Pl,Box 1055, New York, NY 10029 USA. EM derek.leroith@mssm.edu RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS; NIDDK NIH HHS [R01-DK-55758-0, R24-DK-071030-01] NR 35 TC 23 Z9 26 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD AUG PY 2006 VL 291 IS 2 BP E298 EP E305 DI 10.1152/ajpendo.00319.2005 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 060ZO UT WOS:000238841200013 PM 16507604 ER PT J AU Yin, Z Gonzales, L Kolla, V Rath, N Zhang, YZ Lu, MM Kimura, S Ballard, PL Beers, MF Epstein, JA Morrisey, EE AF Yin, Zhan Gonzales, Linda Kolla, Venkatadri Rath, Nibedita Zhang, Yuzhen Lu, Min Min Kimura, Shioko Ballard, Philip L. Beers, Michael F. Epstein, Jonathan A. Morrisey, Edward E. TI Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE homeodomain only protein; histone deacetylase ID RESPIRATORY EPITHELIAL-CELLS; HEART TUBE FORMATION; TRANSCRIPTION FACTOR; HISTONE DEACETYLASE; VENTRAL MORPHOGENESIS; CARDIAC-HYPERTROPHY; HOMEODOMAIN PROTEIN; LUNG EPITHELIUM; DIFFERENTIATION; SURFACTANT AB Hop is an unusual homeodomain protein that was first identified in the developing heart where it functions downstream of Nkx2.5 to modulate cardiac gene expression. Hop functions through interactions with histone deacetylase (HDAC) 2 to mediate repression of cardiac-specific genes, and recent studies show that HDAC activity and HDAC2 expression are decreased in people with chronic obstructive pulmonary disease. Here, we show that Hop is expressed in airway epithelium coincident with HDAC2, and expression is induced by the combination of dexamethasone and cAMP in parallel with induction of surfactant protein gene expression. Hop functions in the developing pulmonary airway, acting downstream of Nkx2.1 and GATA6, to negatively regulate surfactant protein expression. Loss of Hop expression in vivo results in defective type 2 pneumocyte development with increased surfactant production and disrupted alveolar formation. Thus Hop represents a novel regulator of pulmonary maturation that is induced by glucocorticoids to mediate functionally important HDAC-dependent negative feedback regulation. C1 Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. NCI, Met Lab, NIH, Bethesda, MD 20892 USA. RP Morrisey, EE (reprint author), Univ Penn, Dept Med, 956 BRB 2-3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM emorrise@mail.med.upenn.edu FU NHLBI NIH HHS [HL-019737, HL-064632, HL-071546, HL-075215] NR 36 TC 45 Z9 45 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD AUG PY 2006 VL 291 IS 2 BP L191 EP L199 DI 10.1152/ajplung.00385.2005 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 060ZL UT WOS:000238840900008 PM 16510470 ER PT J AU Baehr, CH Fricker, G Miller, DS AF Baehr, Carsten H. Fricker, Gert Miller, David S. TI Fluorescein-methotrexate transport in dogfish shark (Squalus acanthias) choroid plexus SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE image analysis; organic anion transport; xenobiotic transport ID ORGANIC ANION TRANSPORT; EXPRESSION CLONING; RESISTANCE; TUBULES; MICE AB The vertebrate choroid plexus removes potentially toxic metabolites and xenobiotics from cerebrospinal fluid (CSF) to blood for subsequent excretion in urine and bile. We used confocal microscopy and quantitative image analysis to characterize the mechanisms driving transport of the large organic anion, fluorescein-methotrexate (FLMTX), from bath (CSF-side) to blood vessels in intact lateral choroid plexus from dogfish shark, Squalus acanthias, an evolutionarily ancient vertebrate. With 2 mu M FL-MTX in the bath, steady-state fluorescence in the subepithelium/vascular space exceeded bath levels by 5- to 10-fold, and fluorescence in the epithelial cells was slightly below bath levels. FL-MTX accumulation in both tissue compartments was reduced by NaCN, Na removal, and ouabain, but not by a 10-fold increase in medium K. Certain organic anions, e. g., probenecid, MTX, and taurocholate, reduced FL-MTX accumulation in both tissue compartments; p-aminohippurate and estrone sulfate reduced subepithelial/vascular accumulation, but not cellular accumulation. At low concentrations, digoxin, leukotriene C-4, and MK-571 reduced fluorescence in the subepithelium/vascular space while increasing cellular fluorescence, indicating preferential inhibition of efflux over uptake. In the presence of 10 mu M digoxin ( reduced efflux, enhanced cellular accumulation), cellular FL-MTX accumulation was specific, concentrative, and Na dependent. Thus transepithelial FL-MTX transport involved the following two carrier-mediated steps: electroneutral, Na-dependent uptake at the apical membrane and electroneutral efflux at the basolateral membrane. Finally, FL-MTX accumulation in both tissue compartments was reduced by phorbol ester and increased by forskolin, indicating antagonistic modulation by protein kinase C and protein kinase A. C1 Natl Inst Environm Hlth Sci, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. RP Miller, DS (reprint author), Natl Inst Environm Hlth Sci, NIH, Lab Pharmacol & Chem, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM miller@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [ES-03828] NR 18 TC 7 Z9 7 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 2006 VL 291 IS 2 BP R464 EP R472 DI 10.1152/ajpregu.00814.2005 PG 9 WC Physiology SC Physiology GA 060LF UT WOS:000238803000028 PM 16914433 ER PT J AU Ponzio, TA Wang, YF Hatton, GI AF Ponzio, Todd A. Wang, Yu-Feng Hatton, Glenn I. TI Activation of adenosine A(2A) receptors alters postsynaptic currents and depolarizes neurons of the supraoptic nucleus SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE magnocellular; astrocytes; oxytocin; vasopressin; neuroendocrine; glutamate; immunocytochemistry; 5 ' nucleotidase ID CENTRAL-NERVOUS-SYSTEM; IN-VITRO; GLUTAMATE RELEASE; CALCIUM-CHANNELS; MGLU5 RECEPTORS; GLIAL-CELLS; RAT; MODULATION; VASOPRESSIN; INHIBITION AB Supraoptic nucleus (SON) neurons secrete oxytocin or vasopressin in response to various physiological stimuli (e. g., lactation/suckling, dehydration). Released near fenestrated capillaries of the neurohypophysis, these peptides enter the blood and travel to peripheral target organs. The pervasive neuromodulator adenosine, acting at A(1) receptors, is an important inhibitory regulator of magnocellular neuroendocrine cell activity. Another high-affinity adenosine receptor exists in this system, however. We examined the physiological effects of adenosine A(2A) receptor activation and determined its localization among various cell types within the SON. In whole cell patch-clamp recordings from rat brain slices, application of the selective adenosine A(2A) receptor agonist CGS-21680 caused membrane depolarizations in SON neurons, often leading to increased firing activity. Membrane potential changes were persistent (> 10 min) and could be blocked by the selective A(2A) receptor antagonist ZM-241385, or GDP-beta-S, the latter suggesting postsynaptic sites of action. However, +/--alpha-methyl-(4-carboxyphenyl) glycine or TTX also blocked CGS-21680 effects, indicating secondary actions on postsynaptic neurons. In voltage-clamp mode, application of CGS-21680 caused a slight increase (similar to 8%) in high-frequency clusters of excitatory postsynaptic currents. With the use of specific antibodies, adenosine A(2A) receptors were immunocytochemically localized to both the magnocellular neurons and astrocytes of the SON. Ecto-5' nucleotidase, an enzyme involved in the metabolism of ATP to adenosine, was also localized to astrocytes of the SON. These results demonstrate that adenosine acting at A(2A) receptors can enhance the excitability of SON neurons and modulate transmitter release from glutamatergic afferents projecting to the nucleus. We suggest that adenosine A(2A) receptors may function in neuroendocrine regulation through both direct neuronal mechanisms and via actions involving glia. C1 Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. RP Ponzio, TA (reprint author), NIH, Neurochem Lab, Bldg 49-5C68, Bethesda, MD 20892 USA. EM ponziot@mail.nih.gov FU NINDS NIH HHS [NS-009140] NR 42 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD AUG PY 2006 VL 291 IS 2 BP R359 EP R366 DI 10.1152/ajpregu.00747.2005 PG 8 WC Physiology SC Physiology GA 060LF UT WOS:000238803000015 PM 16644907 ER PT J AU Cai, Q Dmitrieva, NI Ferraris, JD Michea, LF Salvador, JM Hollander, MC Fornace, AJ Fenton, RA Burg, MB AF Cai, Qi Dmitrieva, Natalia I. Ferraris, Joan D. Michea, Luis F. Salvador, Jesus M. Hollander, M. Christine Fornace, Albert J., Jr. Fenton, Robert A. Burg, Maurice B. TI Effects of expression of p53 and Gadd45 on osmotic tolerance of renal inner medullary cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE high NaCl; high urea; cell survival ID P38 ACTIVATION PATHWAY; MURINE KIDNEY-CELLS; HYPERTONIC STRESS; EPITHELIAL-CELLS; DNA-DAMAGE; KINASE-ACTIVITY; GROWTH ARREST; HIGH NACL; IN-VIVO; APOPTOSIS AB The response of renal inner medullary (IM) collecting duct cells (mIMCD3) to high NaCl involves increased expression of Gadd45 and p53, both of which have important effects on growth and survival of the cells. However, mIMCD3 cells, being immortalized by SV40, proliferate rapidly, which is known to sensitize cells to high NaCl, whereas IM cells in situ proliferate very slowly and survive much higher levels of NaCl. In the present studies, we have examined the importance of Gadd45 and p53 for survival of normal IM cells in their usual high-NaCl environment by using more slowly proliferating second-passage mouse inner medullary epithelial (p2mIME) cells and comparing cells from wild-type and gene knockout mice. Acutely elevating NaCl (and/or urea) reduces Gadd45a, but increases Gadd45b and Gadd45g mRNA, depending on the mix of NaCl and urea and the rate of increase of osmolality. Nevertheless, p2mIME cells from Gadd45b(-/-), Gadd45g(-/-), and Gadd45bg(-/-) mice survive elevation of NaCl (or urea) essentially the same as do wild-type cells. p53(-/-) Cells do not tolerate as high a concentration of NaCl (or urea) as p53(+/+) cells, but urinary concentrating ability of p53(-/-) mice is normal, as is the histology of inner medullas from p53(-/-) and Gadd45abg(-/-) mice. Thus although Gadd45 and p53 may play roles in osmotically stressed mIMCD3 cells, we do not find that their expression makes an important difference, either for Gadd45 in slower proliferating p2mIME cells or for Gadd45 or p53 in normal inner medullary epithelial cells in situ. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NCI, Gene Response Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. EM maurice_burg@nih.gov RI Fornace, Albert/A-7407-2008; Dmitrieva, Natalia/A-2924-2013 OI Fornace, Albert/0000-0001-9695-085X; Dmitrieva, Natalia/0000-0001-8074-6950 FU Intramural NIH HHS NR 40 TC 10 Z9 10 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD AUG PY 2006 VL 291 IS 2 BP F341 EP F349 DI 10.1152/ajprenal.00518.2005 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 060LD UT WOS:000238802800010 PM 16597604 ER PT J AU Skoumbourdis, EK Weed, JL AF Skoumbourdis, E. K. Weed, J. L. TI Occurrence of floating limb behavior in pigtail macaques (Macaca nemestrina) during the overnight hours SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 SoBran Inc, Bethesda, MD 20892 USA. NIH, DHHS, ORS, DVR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 13 BP 37 EP 37 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400014 ER PT J AU Novak, MS Dettmer, A AF Novak, M. S. Dettmer, A. TI Gerry Ruppenthal symposium: A tribute to the gadgets, lives and ideas of "The unsung hero" SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 22 BP 41 EP 41 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400023 ER PT J AU Suomi, SJ AF Suomi, S. J. TI Gerald C. Ruppenthal's motherless mothers research SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 26 BP 43 EP 43 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400027 ER PT J AU Kenney, C Ruppenthal, G Novak, M AF Kenney, C. Ruppenthal, G. Novak, M. TI Ruppenthal symposium, gadgets from the past: Where are they now? The "Ruperch" SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 30 BP 45 EP 45 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400031 ER PT J AU Unkefer, MK AF Unkefer, M. K. TI Ruppenthal symposium, gadgets from the past: Where are they now? Nuclear family caging SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 33 BP 46 EP 46 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400034 ER PT J AU Unkefer, MK Kenney, CI Sidhu, HK Ruggiero, AM Lutz, CK Suomi, SJ Novak, MS AF Unkefer, M. K. Kenney, C. I. Sidhu, H. K. Ruggiero, A. M. Lutz, C. K. Suomi, S. J. Novak, M. S. TI Handling and emotionality during cognitive testing on infant rhesus monkeys (Macaca mulatta): Object permanence and the Wisconsin General Testing Apparatus (wgta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 49 BP 53 EP 54 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400050 ER PT J AU Iba, KE Schwandt, ML Tolbert, S Suomi, SJ Higley, JD AF Iba, K. E. Schwandt, M. L. Tolbert, S. Suomi, S. J. Higley, J. D. TI Comparison of alcohol consumption between younger and older adolescent rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, Lab Comparat & Translat Studies, NIH, Poolesville, MD 20837 USA. NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 57 BP 57 EP 57 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400058 ER PT J AU Davis, EB Suomi, SJ AF Davis, E. B. Suomi, S. J. TI Hair loss and replacement cycles in socially housed, pregnant, rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Res Anim Management Branch, Anim Ctr, NIH, Poolesville, MD 20837 USA. NICHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 0 TC 7 Z9 7 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 59 BP 58 EP 58 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400060 ER PT J AU Abney, DM Weed, JL AF Abney, D. M. Weed, J. L. TI Methods for successfully pair housing adult male rhesus macaques (macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 SoBran Inc, Bethesda, MD 20892 USA. NIH, Off Res Serv, Div Vet Resources, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 61 BP 59 EP 59 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400062 ER PT J AU Kenney, C Ruppenthal, G Novak, M Suomi, S AF Kenney, C. Ruppenthal, G. Novak, M. Suomi, S. TI Animal-operated foldable perch usage in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 63 BP 60 EP 60 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400064 ER PT J AU Spinelli, S Schwandt, M Erickson, K Lindell, SG Schulkin, J Gold, P Suomi, SJ Higley, JD AF Spinelli, S. Schwandt, M. Erickson, K. Lindell, S. G. Schulkin, J. Gold, P. Suomi, S. J. Higley, J. D. TI Relationship between behavior and neurochemical changes in rhesus macaques during a separation paradigm SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, Sect Primate Models Psychopathol, Anim Ctr, NIH, Poolesville, MD 20837 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. NICHD, Comparat Ethol Lab, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 75 BP 66 EP 66 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400076 ER PT J AU Milligan, LA Rapoport, SI Bazinet, RP AF Milligan, L. A. Rapoport, S. I. Bazinet, R. P. TI Fatty acid profiles of anthropoid primate milk SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Arizona, Dept Anthropol, Tucson, AZ 85721 USA. Smithsonian Natl Zool Pk, Natl Lab, Dept Conservat Biol, Washington, DC 20008 USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 79 BP 68 EP 68 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400080 ER PT J AU Sackett, G Novak, M Kenney, C AF Sackett, G. Novak, M. Kenney, C. TI Maternal-fetal correlation: Circadian, pharmacological, and environmental effects SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Natl Primate Res Ctr, Seattle, WA 98195 USA. NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 80 BP 68 EP 69 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400081 ER PT J AU Ruggiero, AM Roma, PG Schwandt, ML Higley, JD Suomi, SJ AF Ruggiero, A. M. Roma, P. G. Schwandt, M. L. Higley, J. D. Suomi, S. J. TI Maternal behavioral interactions and stress reactivity in infants of differentially reared rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Comparat Ethol Lab, Poolesville, MD USA. American Univ, Dept Psychol, Washington, DC 20016 USA. NIAAA, Primate Unit, Lab Clin & Translat Studies, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 81 BP 69 EP 69 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400082 ER PT J AU Miller, ML Novak, MS Kenney, CI Sackett, GP Woodward, RA Bacher, J Suomi, SJ AF Miller, M. L. Novak, M. S. Kenney, C. I. Sackett, G. P. Woodward, R. A. Bacher, J. Suomi, S. J. TI Psychological challenges during pregnancy alters the autocorrelation structure of cardiovascular rhythms in both the mother and fetus in macaque monkeys (Macaca) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. Univ Washington, Natl Primate Res Ctr, Infant Primate Res Lab, Seattle, WA USA. NICHD, RAMB, Anim Ctr, NIH, Bethesda, MD USA. ORS, DVR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 83 BP 70 EP 71 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400084 ER PT J AU Sidhu, HK Unkefer, MK Kenney, CI Ruggiero, A Suomi, SJ Novak, MS AF Sidhu, H. K. Unkefer, M. K. Kenney, C. I. Ruggiero, A. Suomi, S. J. Novak, M. S. TI Individual differences in performance across object permanence and discrimination learning testing in infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 82 BP 70 EP 70 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400083 ER PT J AU Snyder, ML Kenney, CI Unkefer, MK Ruggiero, AM Suomi, SJ Novak, MS AF Snyder, M. L. Kenney, C. I. Unkefer, M. K. Ruggiero, A. M. Suomi, S. J. Novak, M. S. TI Young rhesus monkeys (macaca mulatta) learn about cognitive tasks before they can perform them SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 89 BP 73 EP 74 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400090 ER PT J AU Flint, WW Chen, SA Iba, KE Davis, EB Suomi, SJ Higley, JD AF Flint, W. W. Chen, S. A. Iba, K. E. Davis, E. B. Suomi, S. J. Higley, J. D. TI Concurrent environmental enrichment and ethanol consumption in socially-housed rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, LCTS, Anim Ctr, NIH, Poolesville, MD 20837 USA. NICHD, RAMB, NIH, Bethesda, MD 20892 USA. NICHD, LCE, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 97 BP 77 EP 78 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400098 ER PT J AU McCarty, PJ AF McCarty, P. J. TI The National Institutes of Health (NIH) experience: A decade of diligence SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 ORS, Div Occupat Hlth & Safety, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 104 BP 80 EP 80 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400105 ER PT J AU Powell, DA AF Powell, D. A. TI Zoonoses of nonhuman primates used in research SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIHAC, DVR, ORS, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 103 BP 80 EP 80 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400104 ER PT J AU Schwandt, ML Suomi, SJ Higley, JD AF Schwandt, M. L. Suomi, S. J. Higley, J. D. TI Social support modulates the behavioral and hypothalamic-pituitary-adrenal axis response to maternal separation in infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD 20837 USA. NICHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 111 BP 83 EP 83 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400111 ER PT J AU Gerald, MS Accamando, A Weiss, A Seelig, D Ayala, J AF Gerald, M. S. Accamando, A. Weiss, A. Seelig, D. Ayala, J. TI Can face color look nice? Face coloration and heterosexual interactions in free-ranging male rhesus macaques (Macaca mulatta) in the mating season SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 CPRC, Caribbean Primate Res Ctr, Punta Santiago, PR 00741 USA. Univ Puerto Rico, San Juan, PR 00936 USA. NICHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. Univ Edinburgh, Sch Philos Psychol & Language Sci, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurosci, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. RP Gerald, MS (reprint author), CPRC, Caribbean Primate Res Ctr, POB 906, Punta Santiago, PR 00741 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 115 BP 85 EP 86 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400115 ER PT J AU Higley, J Rogers, J AF Higley, J. Rogers, J. TI The use of molecular genetics in behavior studies SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 125 BP 90 EP 90 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400125 ER PT J AU Newman, TK Wendland, JR Barr, CS Higley, JD Goldman, D AF Newman, T. K. Wendland, J. R. Barr, C. S. Higley, J. D. Goldman, D. TI Multiple novel DRD4 and TPH2 polymorphisms in the rhesus macaque: Association with impulsive and aggressive behavior? SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 127 BP 91 EP 91 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400127 ER PT J AU Suomi, SJ AF Suomi, S. J. TI Gene x environment interactions and biobehavioral development in rhesus monkeys and other macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 129 BP 92 EP 92 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400129 ER PT J AU Cameron, JL Higley, JD Rogers, J Abbott, K Oostman, H Williamson, DE AF Cameron, J. L. Higley, J. D. Rogers, J. Abbott, K. Oostman, H. Williamson, D. E. TI Genetic links to alcoholism in nonhuman primates SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 130 BP 93 EP 93 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400130 ER PT J AU McCormack, K Grand, AP Newman, TK Maestripieri, D Higley, JD Sanchez, MM AF McCormack, K. Grand, A. P. Newman, T. K. Maestripieri, D. Higley, J. D. Sanchez, M. M. TI The role of genetic polymorphisms in understanding the behavioral and hypothalamic-pituitary-adrenal (HPA) axis responses of abused and non-abused rhesus monkeys (Macaca mulatta) to novel stimuli SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Spelman Coll, Atlanta, GA 30314 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Univ Georgia, Athens, GA 30602 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 131 BP 93 EP 94 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400131 ER PT J AU Barr, CS Gupte, M Newman, TK Lindell, SG Suomi, SJ Goldman, D Higley, JD AF Barr, C. S. Gupte, M. Newman, T. K. Lindell, S. G. Suomi, S. J. Goldman, D. Higley, J. D. TI Polymorphisms in stress pathway genes that influence alcohol consumption in stress- and alcohol-exposed rhesus macaques (Macaca mulatta): Evidence for an allostatic shift? SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Poolesville, MD 20837 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 133 BP 94 EP 95 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400133 ER PT J AU Sanchez, MM Newman, TK Higley, JD Plotsky, PM Nemeroff, CB Winslow, JT AF Sanchez, M. M. Newman, T. K. Higley, J. D. Plotsky, P. M. Nemeroff, C. B. Winslow, J. T. TI Early adverse experience alters hypothalamic-pituitary-adrenal (HPA) function of rhesus macaques: Effects of serotonin transporter gene variation and sex SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIMH, IRP Neurobiol Primate Core, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 132 BP 94 EP 94 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400132 ER PT J AU Ionica, C Berman, C Li, J AF Ionica, C. Berman, C. Li, J. TI Ritualized affiliation associated with provisioning in Tibetan macaques (Macaca thibetana) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, LCE, Poolesville, MD 20837 USA. SUNY Buffalo, Dept Anthropol, Buffalo, NY 14216 USA. Anhui Univ, Sch Life Sci, Hefei 230039, Anhui Province, Peoples R China. RI Ionica, Consuel/A-5186-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 138 BP 97 EP 97 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400138 ER PT J AU Laszlo, K Miller, KE Suomi, SJ AF Laszlo, K. Miller, K. E. Suomi, S. J. TI Influence of female social hierarchy during introduction and assimilation of a new male in captive tufted capuchins (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, Anim Ctr, NIH, Poolesville, MD USA. Montgomery Coll, Dept Biol, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 143 BP 99 EP 100 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400143 ER PT J AU Robbins, KL Gerald, MS Lambides, AR Accamando, AA Suomi, SJ AF Robbins, K. L. Gerald, M. S. Lambides, A. Ruiz Accamando, A. A. Suomi, S. J. TI The development of sexual behavior and first conception in free-ranging adolescent female rhesus monkeys SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Comparat Ethol Lab, Anim Ctr, NIH, Poolesville, MD 20837 USA. Univ Puerto Rico, Caribbean Primate Res Ctr, San Juan, PR 00936 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 144 BP 100 EP 100 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400144 ER PT J AU Lutz, CK Davis, EB Ruggiero, AM Wang, N Suomi, SJ AF Lutz, C. K. Davis, E. B. Ruggiero, A. M. Wang, N. Suomi, S. J. TI Early predictors of self-biting in socially-housed rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Comparat Ethol Lab, Anim Ctr, NIH, Poolesville, MD 20837 USA. NICHD, Res Anim Management Branch, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 161 BP 108 EP 108 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400161 ER PT J AU Roma, PG Ruggiero, AM Schwandt, ML Higley, JD Suomi, SJ AF Roma, P. G. Ruggiero, A. M. Schwandt, M. L. Higley, J. D. Suomi, S. J. TI Does practice make perfect? Maternal behavioral interactions and stress reactivity in infants of primiparous and multiparous rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 American Univ, Dept Psychol, Washington, DC 20016 USA. NICHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. NIAAA, Clin Studies Lab, Primate Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 177 BP 116 EP 117 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400177 ER PT J AU Huntsberry, ME Ruggiero, AM Christensen, CJ Roma, PG Silberberg, A Suomi, SJ AF Huntsberry, M. E. Ruggiero, A. M. Christensen, C. J. Roma, P. G. Silberberg, A. Suomi, S. J. TI Operant conditioning fails to facilitate mirror self-recognition in capuchin monkeys (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 American Univ, Dept Psychol, Washington, DC 20016 USA. NICHD, Lab Comparat Ethol, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 184 BP 119 EP 120 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400184 ER PT J AU Ionica, C Berman, C Li, J AF Ionica, C. Berman, C. Li, J. TI Data collection using voice recording and speech recognition in demanding environments SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, LCE, NIH, Poolesville, MD 20837 USA. SUNY Coll Buffalo, Dept Anthropol, Buffalo, NY 14216 USA. Anhui Univ, Sch Life Sci, Hefei 230039, Peoples R China. RI Ionica, Consuel/A-5186-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 188 BP 121 EP 122 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400188 ER PT J AU Aronoff, EC Ladd, KR Newman, JD AF Aronoff, E. C. Ladd, K. R. Newman, J. D. TI Vocalizations of common marmosets as behavioral phenotypes SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Lab Comparat Ethol, DHHS, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 190 BP 122 EP 123 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400190 ER PT J AU Corcoran, CA Christenson, JL Suomi, SJ Bennett, AJ AF Corcoran, C. A. Christenson, J. L. Suomi, S. J. Bennett, A. J. TI Longevity of effects of early rearing experience on behavioral response to social separation in adult rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Wake Forest Univ, Winston Salem, NC USA. NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 195 BP 125 EP 125 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400195 ER PT J AU Higley, J AF Higley, J. TI Variables affecting nonhuman primate alcohol intake: Twenty years of experience with alcohol-consuming monkeys SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 198 BP 126 EP 127 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400198 ER PT J AU Howell, S Westergaard, GC Higley, JD AF Howell, S. Westergaard, G. C. Higley, J. D. TI Non-human primate alcohol research: Current studies and new directions SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Alpha Genesis Inc, NIH, Yemassee, SC 29945 USA. NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 197 BP 126 EP 126 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400197 ER PT J AU Barr, CS Lindell, SG Schwandt, ML Dvoskin, RL Gupte, M Newman, TK Suomi, SJ Higley, JD AF Barr, C. S. Lindell, S. G. Schwandt, M. L. Dvoskin, R. L. Gupte, M. Newman, T. K. Suomi, S. J. Higley, J. D. TI Functional variants in the CRH and NPY genes increase stress reactivity among infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Poolesville, MD 20837 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 200 BP 127 EP 128 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400200 ER PT J AU Chen, SA Flint, WW Iba, KE Suomi, SJ Higley, JD AF Chen, S. A. Flint, W. W. Iba, K. E. Suomi, S. J. Higley, J. D. TI Social drinking in female rhesus macaques: A profile of voluntary oral ethanol consumption, rearing history, and dominance ranking SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, LCTS, Anim Ctr, NIH, Poolesville, MD 20837 USA. NICHD, LCE, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 202 BP 128 EP 129 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400202 ER PT J AU Howell, S Westergaard, GC Higley, JD AF Howell, S. Westergaard, G. C. Higley, J. D. TI Alcohol consumption across multiple non-human primate species SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Alpha Genesis Inc, NIH, Yemassee, SC 29945 USA. NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 203 BP 129 EP 129 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400203 ER PT J AU Schwandt, ML Barr, CS Suomi, SJ Higley, JD AF Schwandt, M. L. Barr, C. S. Suomi, S. J. Higley, J. D. TI Age-dependent variation in behavior following acute alcohol administration in male and female adolescent rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, Lab Clin & Translat Studies, NIH, Poolesville, MD 20837 USA. NICHD, Comparat Ethol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 204 BP 129 EP 130 PG 2 WC Zoology SC Zoology GA 069NV UT WOS:000239456400204 ER PT J AU Dettmer, AM Ruggiero, AM Novak, MA Suomi, SJ AF Dettmer, A. M. Ruggiero, A. M. Novak, M. A. Suomi, S. J. TI The neurobehavioral development of infant rhesus macaques (Macaca mulatta) reared on two types of inanimate surrogate mothers SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. NICHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2006 VL 68 SU 1 MA 218 BP 137 EP 137 PG 1 WC Zoology SC Zoology GA 069NV UT WOS:000239456400218 ER PT J AU Viswanath, K Steele, WR Finnegan, JR AF Viswanath, Kasisomayajula Steele, Whitney Randolph Finnegan, John R., Jr. TI Social capital and health: Civic engagement, community size, and recall of health messages SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SELF-RATED HEALTH; INCOME INEQUALITY; CARDIOVASCULAR-DISEASE; WIDE PREVENTION; PUBLIC-HEALTH; COMMUNICATION; STRATEGIES; PROGRAM; DISCRIMINATION; INFORMATION AB Objectives. We explored the effects of community integration and pluralism on recall of cardiovascular disease health information messages. Methods. With 1980-1983 data from the Minnesota Heart Health Program, we examined whether ties to community groups were associated with recall of health messages, and whether this relation was modified by size and degree of differentiation of the community. Results. A higher level of civic engagement through ties to community groups was associated with better recall of health messages. Ties to community groups independently contributed to better message recall even after control for gender, education, and other variables. The moderating role of community size was nonsignificant but intriguing. Conclusions. Community group membership could increase exposure to health messages, providing a critical pathway for social capital to influence health promotion and, thus, public health outcomes. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. RP Viswanath, K (reprint author), Dana Farber Canc Inst, Dept Med Oncol, SM 251,44 Binney St, Boston, MA 02115 USA. EM vish_viswanath@dfci.harvard.edu NR 51 TC 61 Z9 61 U1 0 U2 9 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD AUG PY 2006 VL 96 IS 8 BP 1456 EP 1461 DI 10.2105/AJPH.2003.029793 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 070NR UT WOS:000239530000026 PM 16809608 ER PT J AU Yao, L Magalnick, M Wilson, M Lipsky, P Goldbach-Mansky, R AF Yao, Lawrence Magalnick, Michael Wilson, Mildred Lipsky, Peter Goldbach-Mansky, Raphaela TI Periarticular bone findings in rheumatoid arthritis: T2-weighted versus contrast-enhanced TI-weighted MRI SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE arthritis; MRI; MR technique; musculoskeletal system; rheumatoid arthritis; wrist ID DISEASE-ACTIVITY; EROSIONS; WRIST; REVEALS; PANNUS; VOLUME; HANDS AB OBJECTIVE. The purpose of this study was to establish the relative predictive value of T2-weighted and contrast-enhanced T1-weighted MRI techniques for bone erosions that are evident on CT. Because it is known that MRI depicts abnormalities in the periarticular bone of patients with rheumatoid arthritis, we wanted to compare the outcomes of T2-weighted versus contrast-enhanced T1-weighted MRI techniques. MATERIALS AND METHODS. Eleven patients with rheumatoid arthritis underwent CT imaging of their most affected wrist. Fast spin-echo T2-weighted MR images were then acquired with spectral fat saturation. Enhanced T1-weighted spin-echo images acquired before and after IV administration of gadopentetate dimeglumine were used to determine the percent enhancement. Imaging examinations were scored for 15 anatomic zones. The CT score was based on cortical bone erosion. The MR score was based on periarticular bone marrow signal alteration. RESULTS. Both T2-weighted MR images with spectral fat saturation and enhanced T1-weighted images were concordant for the presence or absence of bone abnormalities in 122 of 165 zones (74%). Of the 43 zones that were discordant for an abnormality by the two MR techniques, the T2-weighted images were positive in five zones, and enhanced T1-weighted images were positive in 38 zones (p < 0.001). Of the 43 zones that were discordant by the two MR techniques, enhanced T1-weighted images were concordant with CT in 20 zones, whereas the T2-weighted images were concordant with CT in 23 zones (p = 0.76). A greater proportion of lesions detected by the T2-weighted images were "edema-like" signal patterns. CONCLUSION. In rheumatoid arthritis, contrast-enhanced T1-weighted MRI depicts more periarticular bone abnormalities than fat-suppressed T2-weighted MRI. These MR techniques are equally predictive of frank, erosive disease that is evident on CT. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Yao, L (reprint author), NIH, Dept Diagnost Radiol, 10 Ctr Dr,Room 1C640, Bethesda, MD 20892 USA. NR 14 TC 9 Z9 9 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2006 VL 187 IS 2 BP 358 EP 363 DI 10.2214/AJR.05.0098 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 068FX UT WOS:000239359200016 PM 16861538 ER PT J AU Garcia-Eulate, R Hussain, N Heller, T Kleiner, D Malech, H Holland, S Choyke, PL AF Garcia-Eulate, Reyes Hussain, Nadeem Heller, Theo Kleiner, David Malech, Harry Holland, Steven Choyke, Peter L. TI CT and MRI of hepatic abscess in patients with chronic granulomatous disease SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; genetics; infectious diseases; liver disease; MRI ID LIVER-ABSCESS; FEATURES AB OBJECTIVE. We describe the spectrum of radiologic appearances of hepatic abscesses in patients with chronic granulomatous disease (CGD), a hereditary immunodeficiency presenting in childhood that occurs at a rate of 1 in 200,000-250,000 live births and predisposes patients to infection with catalase-positive organisms. CONCLUSION. Hepatic abscesses in patients with CGD show an atypical radiologic appearance compared with sporadic hepatic abscesses, and they are characterized by homogeneous enhancement and multiseptal enhancement. In the appropriate clinical setting, the appearance of an enhancing mass should suggest the possibility of a CGD-related hepatic abscess. C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. NIDDK, Liver Dis Branch, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIAID, Host Def Lab, Bethesda, MD 20892 USA. Lab Clin Infect Dis, Bethesda, MD USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Rm B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pchoyke@nih.gov OI Malech, Harry/0000-0001-5874-5775; Kleiner, David/0000-0003-3442-4453 NR 13 TC 15 Z9 17 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD AUG PY 2006 VL 187 IS 2 BP 482 EP 490 DI 10.2214/AJR.05.1386 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 068FX UT WOS:000239359200032 PM 16861554 ER PT J AU Pinedo-Cancino, V Sheen, P Tarazona-Santos, E Oswald, WE Jeri, C Vittor, AY Patz, JA Gilman, RH AF Pinedo-Cancino, Viviana Sheen, Patricia Tarazona-Santos, Eduardo Oswald, William E. Jeri, Cesar Vittor, Amy Yomiko Patz, Jonathan A. Gilman, Robert H. TI Limited diversity of Anopheles darlingi in the peruvian Amazon region of Iquitos SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID AMPLIFIED POLYMORPHIC DNA; MALARIA VECTOR; POPULATION-STRUCTURE; SOUTH-AMERICA; NUNEZTOVARI DIPTERA; MITOCHONDRIAL-DNA; CULICIDAE; BRAZIL; NYSSORHYNCHUS; MARKERS AB Anopheles darlingi is the most important malaria vector in the Amazon basin of South America, and is capable of transmitting both Plasmodium falciparum and P. vivax. To understand the genetic structure of this vector in the Amazonian region of Peru, a simple polymerase chain reaction (PCR)-based test to identify this species of mosquito was used. A random amplified polymorphic DNA-PCR was used to study genetic variation at the micro-geographic level in nine geographically separate populations of An. darlingi collected in areas with different degrees of deforestation surrounding the city of Iquitos. Within-population genetic diversity in nine populations, as quantified by the expected heterozygosity (H,), ranged from 0.27 to 0.32. Average genetic distance (F-ST) among these populations was 0.017. These results show that the nine studied populations are highly homogeneous, suggesting that strategies can be developed to combat this malaria vector as a single epidemiologic unit. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Dept Int Hlth, Baltimore, MD 21205 USA. Univ Peruana Cayetano Heredia, Infect Dis Lab, Dept Microbiol, Fac Sci, Lima, Peru. Asociac Benefica PRISMA, Biomed Res Unit, Lima, Peru. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Fed Minas Gerais, Dept Gen Biol, Belo Horizonte, MG, Brazil. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Wisconsin, Nelson Inst Environm Studies, Madison, WI USA. RP Gilman, RH (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, 615 N Wolfe St,Room 5515, Baltimore, MD 21205 USA. EM rgilman@jhsph.edu RI Oswald, William/A-4061-2013 FU FIC NIH HHS [D43 TW006581, 3D43TW006581]; NIAID NIH HHS [T35 AI007646, Y35AI07646] NR 40 TC 16 Z9 17 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD AUG PY 2006 VL 75 IS 2 BP 238 EP 245 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 072ND UT WOS:000239679200010 PM 16896125 ER PT J AU Finkel, JC Besch, VG Hergen, A Kakareka, J Pohida, T Melzer, JM Koziol, D Wesley, R Quezado, ZMN AF Finkel, Julia C. Besch, Virginia G. Hergen, Adrienne Kakareka, John Pohida, Thomas Melzer, Jonathan M. Koziol, Deloris Wesley, Robert Quezado, Zenaide M. N. TI Effects of aging on current vocalization threshold in mice measured by a novel nociception assay SO ANESTHESIOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Anesthesiologists CY OCT 22-26, 2005 CL Atlanta, GA SP Amer Soc Anesthesiologists ID AGE-RELATED DIFFERENCES; CURRENT PERCEPTION THRESHOLD; PERIPHERAL-NERVE; PAIN PERCEPTION; THERMAL PAIN; TEMPORAL SUMMATION; NEURONS INVITRO; YOUNGER ADULTS; HEALTHY OLDER; RATS AB Background: Age-related changes in nociception have been extensively studied in the past decades. However, it remains unclear whether in addition to the increased incidence of chronic illness, age-related changes in nociception contribute to increased prevalence of pain in the elderly. Although a great deal of evidence suggests that nociception thresholds increase with aging, other studies yield disparate results. The aim of this investigation was to longitudinally determine the effect of aging on nociception. Methods: The authors developed a nociception assay for mice using electrical stimuli at 2,000, 250, and 5 Hz; that reportedly stimulate A beta, A delta, and C sensory nerve fibers, respectively. A system was designed to automate a method that elicits and detects pain-avoiding behavior in mice. Using a Latin square design, the authors measured current vocalization thresholds serially over the course of mice's life span. Results: For 2,000-Hz (A beta), 250-Hz (A delta), and 5-Hz (C) electrical stimuli, current vocalization thresholds first decreases and then increases with aging following a U-shaped pattern (P < 0.001). In addition, average current vocalization thresholds at youth and senescence are significantly higher than those at middle age for the 250-Hz (A delta) and 5-Hz (C fiber) electrical stimulus (P < 0.05). Conclusions: Using a novel and noninjurious nociception assay, the authors showed that over the life span of mice, current vocalization threshold to electrical stimuli changes in a U-shaped pattern. The findings support the notion that age-related changes in nociception are curvilinear, and to properly study and treat pain, the age of subjects should be considered. C1 NIH, Dept Anesthesia & Surg Serv, Biostat & Clin Epidemiol Sect, Off Director,Clin Ctr, Bethesda, MD 20892 USA. NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), NIH, Dept Anesthesia & Surg Serv, Biostat & Clin Epidemiol Sect, Off Director,Clin Ctr, 10 Ctr Dr,MSC-1512,Bldg 10,Room 2C624, Bethesda, MD 20892 USA. EM zquezado@nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [Z99 CT999999] NR 60 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD AUG PY 2006 VL 105 IS 2 BP 360 EP 369 DI 10.1097/00000542-200608000-00020 PG 10 WC Anesthesiology SC Anesthesiology GA 068YP UT WOS:000239411600019 PM 16871071 ER PT J AU Foxman, B Camargo, CA Lilienfeld, D Linet, M Mays, VM McKeown, R Ness, R Rothenberg, R AF Foxman, Betsy Camargo, Carlos A., Jr. Lilienfeld, David Linet, Martha Mays, Vickie M. McKeown, Robert Ness, Roberta Rothenberg, Richard TI Looking back at hurricane Katrina: lessons for 2006 and beyond SO ANNALS OF EPIDEMIOLOGY LA English DT Letter C1 Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Amer Coll Epidemiol, Raleigh, NC 27607 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. InterMune Inc, Brisbane, CA 94005 USA. NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ S Carolina, Columbia, SC 29208 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. RP Foxman, B (reprint author), Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. RI Foxman, Betsy/E-1836-2015; OI McKeown, Robert/0000-0002-8829-5784; Foxman, Betsy/0000-0001-6682-238X FU NIMHD NIH HHS [P60 MD000508, P60 MD000508-03] NR 0 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD AUG PY 2006 VL 16 IS 8 BP 652 EP 653 DI 10.1016/j.annepidem.2005.11.013 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 072LU UT WOS:000239675700010 PM 16820304 ER PT J AU Arnlov, J Pencina, MJ Amin, S Nam, BH Benjamin, EJ Murabito, JM Wang, TJ Knapp, PE D'Agostino, RB Bhasin, S Vasan, RS AF Arnlov, Johan Pencina, Michael J. Amin, Shreyasee Nam, Byung-Ho Benjamin, Emelia J. Murabito, Joanne M. Wang, Thomas J. Knapp, Philip E. D'Agostino, Ralph B., Sr. Bhasin, Shalendar Vasan, Ramachandran S. TI Endogenous sex hormones and cardiovascular disease incidence in men SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-ARTERY-DISEASE; ISCHEMIC-HEART-DISEASE; ALPHA GENE VARIATION; MIDDLE-AGED MEN; DEHYDROEPIANDROSTERONE-SULFATE; MYOCARDIAL-INFARCTION; ELDERLY-MEN; RISK-FACTORS; FREE TESTOSTERONE; ESTROGEN AB Background: Data suggest that endogenous sex hormones (testosterone, dehydroepiandrosterone sulfate [DHEA-S], and estradiol) influence cardiovascular disease (CVD) risk factors and vascular function. Yet, prospective studies relating sex hormones to CVD incidence in men have yielded inconsistent results. Objective: To examine the association of circulating sex hormone levels and CVD risk in men. Design: Prospective cohort study. Setting: Community-based study in Framingham, Massachusetts. Participants: 2084 middle-aged white men without CVD at baseline. Measurements: The authors used multivariable Cox regression to relate baseline levels of testosterone, DHEA-S, and estradiol to the incidence of CVD (coronary, cerebrovascular, or peripheral vascular disease or heart failure) during 10 years of follow-up. Results: During follow-up, 386 men (18.5%) experienced a first CVD event. After adjustment for baseline standard CVD risk factors, higher estradiol level was associated with lower risk for CVD (hazard ratio per SD increment in log estradiol, 0.90 [95% Cl, 0.82 to 0.99]; P = 0.035). The authors observed effect modification by age: Higher estradiol levels were associated with lower CVD risk in older (median age > 56 years) men (hazard ratio per SD increment, 0.86 [Cl, 0.78 to 0.96]; P = 0.005) but not in younger (median age <= 56 years) men (hazard ratio per SD increment, 1.11 [Cl, 0.89 to 1.38]; P = 0.36). The association of higher estradiol level with lower CVD incidence remained robust in time-dependent Cox models (updating standard CVD risk factors during follow-up). Serum testosterone and DHEA-S levels were not statistically significantly associated with incident CVD. Limitations: Sex hormone levels were measured only at baseline, and the findings may not be generalizable to women and nonwhite people. Conclusions: In the community-based sample, a higher serum estradiol level was associated with lower risk for CVD events in older men. The findings are consistent with the hypothesis that endogenous estrogen has vasculoprotective influences in men. C1 Boston Univ, Sch Med, Framingham Heart Study, Massachusetts Gen Hosp, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin, Coll Med, Rochester, MN USA. Uppsala Univ, Uppsala, Sweden. NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Boston Univ, Sch Med, Framingham Heart Study, Massachusetts Gen Hosp, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Arnlov, Johan/N-9886-2013; OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24 HL04334, K23 HL074077, N01-HC-25195]; NINDS NIH HHS [6R01-NS 17950] NR 60 TC 119 Z9 123 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 1 PY 2006 VL 145 IS 3 BP 176 EP 184 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 070MN UT WOS:000239526800003 PM 16880459 ER PT J AU Ascherio, A Chen, HP Weisskopf, MG O'Reilly, E McCullough, ML Calle, EE Schwarzschild, MA Thun, MJ AF Ascherio, Alberto Chen, HonPei Weisskopf, Marc G. O'Reilly, Eilis McCullough, Marjorie L. Calle, Eugenia E. Schwarzschild, Michael A. Thun, Michael J. TI Pesticide exposure and risk for Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID AMERICAN-CANCER-SOCIETY; DOPAMINERGIC NEUROTOXICITY; SUBSTANTIA-NIGRA; PARAQUAT; POPULATION; ETIOLOGY; MANEB; ONSET; DEGENERATION; PREVALENCE AB Objective: Chronic, low-dose exposure to pesticides is suspected to increase the risk for Parkinson's disease (PD), but data are inconclusive. Methods: We prospectively examined whether individuals exposed to pesticides have higher risk for PD than those not exposed. The study population comprised participants in the Cancer Prevention Study II Nutrition Cohort, a longitudinal investigation of US men and women initiated in 1992 by the American Cancer Society. Follow-up surveys were conducted in 1997, 1999, and 2001. The 143,325 individuals who returned the 2001 survey and did not have a diagnosis or symptoms of PD at baseline (1992) were included in the analyses. Results: Exposure to pesticides was reported by 7,864 participants (5.7%), including 1,956 farmers, ranchers, or fishermen. Individuals exposed to pesticides had a 70% higher incidence of PD than those not exposed (adjusted relative risk, 1.7; 95% confidence interval, 1.2-2.3; p = 0.002). The relative risk for pesticide exposure was similar in farmers and nonfarmers. No relation was found between risk for PD and exposure to asbestos, chemical/acids/solvents, coal or stone dust, or eight other occupational exposures. Interpretation: These data support the hypothesis that exposure to pesticides may increase risk for PD. Future studies should seek to identify the specific chemicals responsible for this association. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Ascherio, A (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02215 USA. EM aascheri@hsph.harvard.edu OI Chen, Honglei/0000-0003-3446-7779 FU NIEHS NIH HHS [ES10804] NR 51 TC 191 Z9 195 U1 1 U2 17 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD AUG PY 2006 VL 60 IS 2 BP 197 EP 203 DI 10.1002/ana.20904 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 070PX UT WOS:000239536600008 PM 16802290 ER PT J AU Landgren, O Axdorph, U Fears, TR Porwit-MacDonald, A Wedelin, C Bjorkholm, M AF Landgren, O. Axdorph, U. Fears, T. R. Porwit-MacDonald, A. Wedelin, C. Bjorkholm, M. TI A population-based cohort study on early-stage Hodgkin lymphoma treated with radiotherapy alone: with special reference to older patients SO ANNALS OF ONCOLOGY LA English DT Article DE elderly; Hodgkin lymphoma; late complications; radiotherapy; relapse ID PROGNOSTIC-FACTORS; RANDOMIZED-TRIALS; ELDERLY-PATIENTS; DISEASE; ABVD; CLASSIFICATION; CHEMOTHERAPY; IRRADIATION; NEOPLASMS; RADIATION AB Background: Combined modality treatment has reduced the risk of relapse among younger early-stage Hodgkin lymphoma (HL) patients. Older HL patients may not tolerate chemotherapy and their prognosis is less favorable. We conducted a population-based study to evaluate long-term follow-up outcome in older early-stage HL patients initially treated with radiotherapy (RT) alone. Patients and methods: We included 308 consecutive patients (22% were >= 60 years) diagnosed 1972-1999 (median follow-up 20 years; range 1-28). Using Cox regression models we defined risk of relapse and survival in relation to clinical factors. Results: 272/308 (88%) patients obtained complete remission following first-line RT alone. Among these, 42% relapsed within a median of 21 months. The relapse rate was independent of gender and age at diagnosis (median age 32 years, range 14-85); however, lymphocyte-predominant HL was associated with borderline (P = 0.049) 56% decreased risk of relapse. Among patients < 60 years and >= 60 years, we observed 29 (median latency 10 years, range 2-25) and 11 (median latency 3 years, range 1-10) second tumors, respectively. Conclusions: Older age (>= 60 years) was not associated with an increased risk of relapse following RT alone. Given the risks of iatrogenic morbidity/mortality of chemotherapy in older patients, RT alone could be an alternative first-line therapy in early-stage older HL patients. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Univ Hosp & Inst, Dept Med, Hematol Ctr, Stockholm, Sweden. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Karolinska Univ Hosp & Inst, Dept Pathol, Stockholm, Sweden. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Bldg EPS,Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.mih.gov NR 26 TC 5 Z9 5 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD AUG PY 2006 VL 17 IS 8 BP 1290 EP 1295 DI 10.1093/annonc/mdl094 PG 6 WC Oncology SC Oncology GA 075QA UT WOS:000239899100016 PM 16740597 ER PT J AU Gelber, AC Pillemer, SR Baum, BJ Wigley, FM Hummers, LK Morris, S Rosen, A Casciola-Rosen, L AF Gelber, A. C. Pillemer, S. R. Baum, B. J. Wigley, F. M. Hummers, L. K. Morris, S. Rosen, A. Casciola-Rosen, L. TI Distinct recognition of antibodies to centromere proteins in primary Sjogren's syndrome compared with limited scleroderma SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID PROGRESSIVE SYSTEMIC-SCLEROSIS; ANTICENTROMERE ANTIBODIES; CLINICAL-SIGNIFICANCE; RAYNAUDS-PHENOMENON; CREST SYNDROME; CENP-C; CLASSIFICATION; AUTOANTIGEN; AUTOANTIBODIES; KINETOCHORE AB Background: Anticentromere antibodies are characteristically observed in scleroderma but have recently been reported in other autoimmune rheumatic disorders, including Sjogren's syndrome. It is not known whether distinct centromere proteins ( CENP) are targeted in primary Sjogren's syndrome ( pSS) and scleroderma. Objective: To determine whether antibodies to CENP-B and CENP-C are present in these two disorders. Methods: Sera from 45 patients with pSS and 33 with limited scleroderma were studied. All patients met classification criteria for pSS and scleroderma, respectively. Sera were used to immunoprecipitate in vitro translated CENP-B and CENP-C. The proportions recognising CENP-B or CENP-C were compared. Results: 10 of 45 patients ( 22%) with pSS and 18 of 33 ( 55%) with scleroderma had antibodies recognising CENPs ( p = 0.004). Seven of 10 ( 70%) CENP positive patients with pSS recognised CENP-C alone, compared with one of 18 ( 6%) CENP positive patients with scleroderma ( odds ratio ( OR) = 40 ( 95% confidence interval ( CI), 3.5 to 450) ( p = 0.003). In contrast, the majority ( 15 of 18 ( 83%)) of CENP positive scleroderma sera recognised both CENP-B and CENP-C, compared with none of 10 pSS sera ( OR = 93 ( 95% CI, 4.4 to 1979) ( p = 0.0001). Conclusions: The pattern of CENP recognition differs markedly in pSS and limited scleroderma. While patients with pSS predominantly recognise CENP-C alone, dual recognition of CENP-B and CENP-C is most frequent in scleroderma. These findings suggest that obtaining antibodies to specific centromere antigens is useful diagnostically, and imply that distinct mechanisms underlie the unique patterns of centromere autoreactivity in pSS and scleroderma. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. Natl Inst Dent & Craniofacial Res, Dept Gene Therapy, NIH, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Therapeut Branch, NIH, Bethesda, MD USA. RP Gelber, AC (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 5200 Eastern Ave,Mason F Lord Bldg Ctr Tower, Baltimore, MD 21224 USA. EM agelber@jhmi.edu OI Hummers, Laura/0000-0002-4864-4011 FU Intramural NIH HHS; NIAMS NIH HHS [AR 44684, R01 AR044684]; NIDCR NIH HHS [DE 12354, R01 DE012354, R01 DE 12354-05] NR 30 TC 23 Z9 25 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD AUG PY 2006 VL 65 IS 8 BP 1028 EP 1032 DI 10.1136/ard.2005.046003 PG 5 WC Rheumatology SC Rheumatology GA 063GJ UT WOS:000239006000008 PM 16414973 ER PT J AU Lenfant, C AF Lenfant, Claude TI Will lung volume reduction surgery be widely applied? SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material ID EMPHYSEMA; TRIAL C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), POB 83027, Gaithersburg, MD 20883 USA. EM lenfantc@prodigy.net NR 8 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2006 VL 82 IS 2 BP 385 EP 387 DI 10.1016/j.athoracsur.2006.06.049 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 070UM UT WOS:000239550600001 PM 16863733 ER PT J AU Horvath, KA AF Horvath, Keith A. TI Light and ice cream SO ANNALS OF THORACIC SURGERY LA English DT Letter ID TRANSMYOCARDIAL LASER REVASCULARIZATION C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Horvath, KA (reprint author), NHLBI, NIH, Bldg 10,CRC,Rm 6-5140, Bethesda, MD 20892 USA. EM khorvath@nih.gov NR 3 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 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD AUG PY 2006 VL 82 IS 2 BP 771 EP 771 DI 10.1016/j.athoracsur.2005.11.022 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 070UM UT WOS:000239550600089 PM 16863827 ER PT J AU Moayeri, M Wiggins, JF Lindeman, RE Leppla, SH AF Moayeri, Mahtab Wiggins, Jason F. Lindeman, Robin E. Leppla, Stephen H. TI Cisplatin inhibition of anthrax lethal toxin SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TUMOR-BEARING MICE; PROTECTIVE ANTIGEN; COMPARATIVE PHARMACOKINETICS; MACROPHAGE SENSITIVITY; ANTITUMOR-ACTIVITY; MAMMALIAN-CELLS; L1210 LEUKEMIA; KINASE-KINASE; N-TERMINUS; GLUTATHIONE AB Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages derived from certain inbred strains. LT is comprised of a receptor binding component, protective antigen (PA), which delivers the enzymatic component, lethal factor (LIT), into cells. We found that mouse macrophages were protected from toxin by the antitumor drug cis-diammineplatinum (II) dichloride (cisplatin). Cisplatin was shown to inhibit LT-mediated cleavage of cellular mitogen-activated protein kinases (MEKs) without inhibiting LF's in vitro proteolytic activity. Cisplatin-treated PA lost 100% of its ability to function in toxicity assays when paired with untreated LF, despite maintaining the ability to bind to cells. Cisplatin-treated PA was unable to form heptameric oligomers required for LF binding and translocation. The drug was shown to modify PA in a reversible noncovalent manner. Not surprisingly, cisplatin also blocked the actions of anthrax edema toxin and of LF-Pseudomonas aeruginosa exotoxin A fusion peptide (FP59), both of which require PA for translocation. Treatment of BALB/cJ mice or Fischer F344 rats with cisplatin at biologically relevant concentrations completely protected the animals from a coadministered lethal dose of LT. However, treatment with cisplatin 2 hours before or after animals received a lethal bolus of toxin did not protect them. C1 NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bldg 30,Room 303, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov FU Intramural NIH HHS NR 42 TC 25 Z9 27 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD AUG PY 2006 VL 50 IS 8 BP 2658 EP 2665 DI 10.1128/AAC.01412-05 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 071YS UT WOS:000239640400009 PM 16870755 ER PT J AU Anderson, JM Norris, DE AF Anderson, Jennifer M. Norris, Douglas E. TI Genetic diversity of Borrelia burgdorferi sensu stricto, in Peromyscus leucopus, the primary reservoir of Lyme disease in a region of endemicity in southern Maryland SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SURFACE PROTEIN-C; FRAGMENT-LENGTH-POLYMORPHISM; NORTHEASTERN UNITED-STATES; OSPC GENE; IXODES-SCAPULARIS; SEQUENCE-ANALYSIS; MITOCHONDRIAL-DNA; FLAGELLIN GENE; ENZOOTIC SITE; INFECTED MICE AB In the north central and northeastern United States, Borrelia burgdorferi sensu stricto, the etiologic agent of Lyme disease (LD), is maintained in an enzootic cycle between the vector, Ixodes scapularis, and the primary reservoir host, Peromyscus leucopus. Genetic diversity of the pathogen based on sequencing of two plasmid-located genes, those for outer surface protein A (ospA) and outer surface protein C (ospC), has been examined in both tick and human specimens at local, regional, and worldwide population scales. Additionally, previous studies have only been conducted with tick or human specimens at the local population level in areas with high LD transmission rates. This study examined the genetic diversity of circulating borreliae in the reservoir population from a large region of the western coastal plains of southern Maryland, where moderate numbers of human LD cases are reported. Six ospA mobility classes, including two that were not previously described, and eight ospC groups were found among the P. leucopus samples. Twenty-five percent of all specimens were infected with more than one ospA or ospC variant. The frequency distribution of variants was homogeneous, both locally and spatially. The spirochete diversity found in Maryland was not as high as that observed among northern tick populations, yet similar genotypes were observed in both populations. These results also show that mice are important for maintaining Borrelia variants, even rare variants, and that reservoir populations should therefore be considered when assessing the diversity of B. burgdorferi. C1 Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. RP Anderson, JM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy,Rm 2E-22, Rockville, MD 20852 USA. EM jenanderson@niaid.nih.gov FU NIEHS NIH HHS [T32 ES007141, T32ES07141]; PHS HHS [U50/CCU319554] NR 78 TC 27 Z9 28 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD AUG PY 2006 VL 72 IS 8 BP 5331 EP 5341 DI 10.1128/AEM.00014-06 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 073ZC UT WOS:000239780400027 PM 16885284 ER PT J AU Nordlind, K Thorslund, K Lonne-Rahm, S Mohabbati, S Berki, T Morales, M Azmitia, EC AF Nordlind, Klas Thorslund, Kristoffer Lonne-Rahm, Solbritt Mohabbati, Sheila Berki, Timea Morales, Marisela Azmitia, Efrain C. TI Expression of serotonergic receptors in psoriatic skin SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE psoriasis; receptors; serotonin ID 5-HT1A RECEPTOR; TRYPTOPHAN-HYDROXYLASE; MAST-CELLS; APOPTOSIS; RAT; PROLIFERATION; AGONIST; PROTEIN; HYPERSENSITIVITY; ANTAGONISTS AB Psoriasis appears to be influenced by stress, which causes release of adrenal hormones. Serotonin, or hormonal actions on serotonin and serotonin receptors, may have a role in psoriasis. Distribution of serotonin receptors was studied in involved and noninvolved skin in patients with psoriasis and compared to normal skin, by using immunohistochemistry and antibodies to 5-HT1A, 5-HT2A and 5-HT3 receptors (R). There was a decreased (P < 0.001) number of 5-HT1AR positive cells, the majority being tryptase positive, in involved and noninvolved psoriatic papillary dermis, compared to normal skin. 5-HT1AR expression was also found in the upper part of the epidermis, on vessel walls and on melanocytes. 5-HT2AR expressing papillary mononuclear cells, CD3 positive, were increased (P < 0.001 and P < 0.01, respectively) in involved and noninvolved psoriatic skin, compared to normal skin, an increase (P < 0.01) also being found in the involved compared to noninvolved skin. Expression of 5-HT3R could be found in the basal epidermal layer of noninvolved but not in the involved skin of psoriasis, where it was only found in the acrosyringium. The present findings are compatible with the 5-HT1A and 5-HT2A receptors having antagonistic functions, and raise the possibility of using receptor specific drugs in the treatment of psoriasis. C1 Karolinska Univ Hosp, Dept Med, Unit Dermatol & Venereol, S-17176 Stockholm, Sweden. Acad Hosp, Unit Dermatol & Venereol, Dept Med Sci, Uppsala, Sweden. Univ Pecs, Dept Immunol & Biotechnol, Pecs, Hungary. Natl Inst Drug Abuse, Baltimore, MD USA. NYU, Dept Biol & Psychiat, New York, NY USA. RP Nordlind, K (reprint author), Karolinska Univ Hosp, Dept Med, Unit Dermatol & Venereol, S-17176 Stockholm, Sweden. EM Klas.Nordlind@karolinska.se OI azmitia, efrain/0000-0002-8806-1064 NR 38 TC 22 Z9 23 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD AUG PY 2006 VL 298 IS 3 BP 99 EP 106 DI 10.1007/s00403-006-0652-6 PG 8 WC Dermatology SC Dermatology GA 081HI UT WOS:000240307500001 PM 16794822 ER PT J AU Gurling, HMD Critchley, H Datta, SR McQuillin, A Blaveri, E Thirumalai, S Pimm, J Krasucki, R Kalsi, G Quested, D Lawrence, J Bass, N Choudhury, K Puri, V O'Daly, O Curtis, D Blackwood, D Muir, W Malhotra, AK Buchanan, RW Good, CD Frackowiak, RSJ Dolan, RJ AF Gurling, Hugh M. D. Critchley, Hugo Datta, Susmita R. McQuillin, Andrew Blaveri, Ekaterina Thirumalai, Srinivasa Pimm, Jonathan Krasucki, Robert Kalsi, Gursharan Quested, Digby Lawrence, Jacob Bass, Nicholas Choudhury, Khalid Puri, Vinay O'Daly, Owen Curtis, David Blackwood, Douglas Muir, Walter Malhotra, Anil K. Buchanan, Robert W. Good, Catriona D. Frackowiak, Richard S. J. Dolan, Raymond J. TI Genetic association and brain morphology studies and the chromosome 8p22 pericentriolar material 1 (PCM1) gene in susceptibility to schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID VOXEL-BASED MORPHOMETRY; NEUREGULIN-1; LINKAGE; LOCI; HAPLOTYPE; FAMILIES; SUBUNIT; 8P21-22; VOLUME; IRISH AB Context: There is evidence of linkage to a schizophrenia susceptibility locus on chromosome 8p21-22 found by several family linkage studies. Objectives: To fine map and identify a susceptibility gene for schizophrenia on chromosome 8p22 and to investigate the effect of this genetic susceptibility on an endophenotype of abnormal brain structure using magnetic resonance imaging. Design: Fine mapping and identification of a chromosome 8p22 susceptibility gene was carried out by finding linkage disequilibrium between genetic markers and schizophrenia in multiply affected families, a case-control sample, and a trio sample. Variation in brain morphology associated with pericentriolar material 1 (PCM1) alleles was examined using voxel-based morphometry and statistical parametric mapping with magnetic resonance imaging. Setting and Patients: A family sample of 13 large families multiply affected with schizophrenia, 2 schizophrenia case-control samples from the United Kingdom and Scotland, and a sample of schizophrenic trios from the United States containing parents and 1 affected child with schizophrenia. Main Outcome Measures: Tests of transmission disequilibrium between PCM1 locus polymorphisms and schizophrenia using a family sample and tests of allelic association in case-control and trio samples. Voxel-based morphometry using statistical parametric mapping. Results: The family and trio samples both showed significant transmission disequilibrium between marker D85261 in the PCM1 gene locus and schizophrenia. The case-control sample from the United Kingdom also found significant allelic association between PCM1 gene markers and schizophrenia. Voxel-based morphometry of cases who had inherited a PCM1 genetic susceptibility showed a significant relative reduction in the volume of orbitofrontal cortex gray matter in comparison with patients with non-PCM1-associated schizophrenia, who, by contrast, showed gray matter volume reduction in the temporal pole, hippocampus, and inferior temporal cortex. Conclusions: The PCM1 gene is implicated in susceptibility to schizophrenia and is associated with orbitofrontal gray matter volumetric deficits. C1 UCL, Mol Psychol Lab, Dept Mental Hlth Sci, Windeyer Inst Med Sci, London W1T 4JF, England. UCL, Funct Imaging Lab, Wellcome Dept Cognit Neurol, Neurol Inst, London W1T 4JF, England. Berkshire Healthcare Natl Hlth Serv Trust, Reading, Berks, England. St Pancras Hosp, Camden & Islington Mental Hlth & Social Care Trus, London, England. St Bernards Hosp, W London Ment Hlth Trust, Hammersmith & Fulham Mental Hlth Unit, London, England. Univ London, Queen Mary Coll, London, England. Royal London Hosp, E London & City Mental Hlth Trust, London E1 1BB, England. Univ Edinburgh, Dept Psychiat, Royal Edinburgh Hosp, Edinburgh EH8 9YL, Midlothian, Scotland. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Ecole Normale Super, Dept Etud Cognit, F-75231 Paris, France. RP Gurling, HMD (reprint author), UCL, Mol Psychol Lab, Dept Mental Hlth Sci, Windeyer Inst Med Sci, 46 Cleveland St, London W1T 4JF, England. EM h.gurling@ucl.ac.uk RI critchley, hugo/G-9267-2011; O'Daly, Owen/A-2369-2013; Gurling, Hugh/A-5029-2010; Frackowiak, Richard/I-1809-2013; Frackowiak, Richard/H-4383-2011; McQuillin, Andrew/C-1623-2008; OI Frackowiak, Richard/0000-0002-3151-822X; McQuillin, Andrew/0000-0003-1567-2240; Dolan, Ray/0000-0001-9356-761X FU Wellcome Trust [, 078865] NR 38 TC 59 Z9 64 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2006 VL 63 IS 8 BP 844 EP 854 DI 10.1001/archpsyc.63.8.844 PG 11 WC Psychiatry SC Psychiatry GA 071BW UT WOS:000239573200002 PM 16894060 ER PT J AU Zarate, CA Singh, JB Carlson, PJ Brutsche, NE Ameli, R Luckenbaugh, DA Charney, DS Manji, HK AF Zarate, Carlos A., Jr. Singh, Jaskaran B. Carlson, Paul J. Brutsche, Nancy E. Ameli, Rezvan Luckenbaugh, David A. Charney, Dennis S. Manji, Husseini K. TI A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID SEROTONIN REUPTAKE INHIBITORS; NMDA RECEPTOR SUBUNIT; OPEN-LABEL TRIAL; DOUBLE-BLIND; RATING-SCALE; REMISSION RATES; KETAMINE; ANTIDEPRESSANT; GLUTAMATE; DISORDER AB Context: Existing therapies for major depression have a lag of onset of action of several weeks, resulting in considerable morbidity. Exploring pharmacological strategies that have rapid onset of antidepressant effects within a few days and that are sustained would have an enormous impact on patient care. Converging lines of evidence suggest the role of the glutamatergic system in the pathophysiology and treatment of mood disorders. Objective: To determine whether a rapid antidepressant effect can be achieved with an antagonist at the N-methyl-D-aspartate receptor in subjects with major depression. Design: A randomized, placebo-controlled, double-blind crossover study from November 2004 to September 2005. Setting: Mood Disorders Research Unit at the National Institute of Mental Health. Patients: Eighteen subjects with DSM-IV major depression (treatment resistant). Interventions: After a 2-week drug-free period, subjects were given an intravenous infusion of either ketamine hydrochloride (0.5 mg/kg) or placebo on 2 test days, a week apart. Subjects were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days postinfusion. Main Outcome Measure: Changes in scores on the primary efficacy measure, the 21-item Hamilton Depression Rating Scale. Results: Subjects receiving ketamine showed significant improvement in depression compared with subjects receiving placebo within 110 minutes after injection, which remained significant throughout the following week. The effect size for the drug difference was very large (d = 1.46 [95% confidence interval, 0.91-2.01]) after 24 hours and moderate to large (d = 0.68 [95% confidence interval, 0.13-1.23]) after 1 week. Of the 17 subjects treated with ketamine, 71% met response and 29% met remission criteria the day following ketamine infusion. Thirty-five percent of subjects maintained response for at least 1 week. Conclusions: Robust and rapid antidepressant effects resulted from a single intravenous dose of an N-methyl-D-aspartate antagonist; onset occurred within 2 hours postinfusion and continued to remain significant for 1 week. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Bethesda, MD USA. RP Zarate, CA (reprint author), CRC, 10 Ctr Dr,Unit 7 SE,Room 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov FU Intramural NIH HHS NR 59 TC 1159 Z9 1195 U1 35 U2 150 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2006 VL 63 IS 8 BP 856 EP 864 DI 10.1001/archpsyc.63.8.856 PG 9 WC Psychiatry SC Psychiatry GA 071BW UT WOS:000239573200003 PM 16894061 ER PT J AU Rutledge, T Reis, SE Olson, MB Owens, J Kelsey, SF Pepine, CJ Mankad, S Rogers, WJ Merz, NB Sopko, G Cornell, CE Sharaf, B Matthews, KA Vaccarino, V AF Rutledge, Thomas Reis, Steven E. Olson, Marian B. Owens, Jane Kelsey, Sheryl F. Pepine, Carl J. Mankad, Sunil Rogers, William J. Merz, Noel Bairey Sopko, George Cornell, Carol E. Sharaf, Barry Matthews, Karen A. Vaccarino, Viola TI Depression symptom severity and reported treatment history in the prediction of cardiac risk in women with suspected myocardial ischemia - The NHLBI-sponsored WISE study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; MAJOR DEPRESSION; ASSOCIATION; MORTALITY; INFARCTION; DISORDERS; HEALTH; METAANALYSIS; ANXIETY AB Background: Depression is associated with clinical events and premature mortality among patients with established coronary artery disease (CAD). Typically, however, studies in this area focus only on baseline symptom severity and lack any data concerning symptom duration or symptom history. Objectives: To describe and compare the relationships between 2 measures of depression-assessed in the form of depression symptom severity and reported treatment history-with atherosclerosis risk factors and major clinical events in a sample of women with suspected myocardial ischemia. Design: Follow-up study of women who completed a diagnostic CAD protocol, including cardiac symptoms, coronary angiography, ischemic testing, and assessments of depression symptom severity and reported treatment history. Setting: The Women's Ischemia Syndrome Evaluation (WISE), a National Heart, Lung, and Blood Institute (NHLBI)-sponsored multicenter study assessing cardiovascular function using state-of-the-art techniques in women referred for coronary angiography to evaluate chest pain or suspected myocardial ischemia. Participants: Five hundred five women (mean age, 53.4 years) enrolled in WISE and followed up for a mean of 4.9 years. Main Outcome Measures: Incidence of cardiac events, including myocardial infarction, stroke, and heart failure, and total mortality. Results: Relative to those with no or less stable depression symptoms, women with elevated depression symptoms and a reported treatment history showed higher rates of smoking, hypertension, and poorer education and an increased incidence of deathandcardiac events (multivariate-adjusted risk ratio, 3.1; 95% confidence interval, 1.5-6.3; P = .001). Conclusions: Among women with suspected myocardial ischemia, a combination of depressive symptom severity and treatment history was a strong predictor of an elevated CAD risk profile and increased risk of cardiac events compared with those without depression or with only 1 of the 2 measured depression markers. These findings reinforce the importance of assessing mental health factors in women at elevated CAD risk. Focusing only on baseline depression symptom severity may provide an incomplete picture of CAD risk. C1 VA San Diego Healthcare Syst, Med Ctr, Psychol Serv, Dept Psychiat, La Jolla, CA 92161 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Florida, Dept Med, Gainesville, FL USA. Allegheny Gen Hosp, Birmingham, AL USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NHLBI, Bethesda, MD 20892 USA. Rhode Isl Hosp, Providence, RI USA. Emory Univ, Atlanta, GA 30322 USA. Univ Arkansas Med Sci, Dept Psychol, Little Rock, AR 72205 USA. RP Rutledge, T (reprint author), VA San Diego Healthcare Syst, Med Ctr, Psychol Serv, Dept Psychiat, Mail Code 116B,3350 La Jolla Village Dr, La Jolla, CA 92161 USA. EM Thomas.Rutledge@med.va.gov RI Reis, Steven/J-3957-2014 FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68164, N01-HV-68163, N01-HV-68161, N01-HV-68162] NR 26 TC 45 Z9 46 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2006 VL 63 IS 8 BP 874 EP 880 DI 10.1001/archpsyc.63.8.874 PG 7 WC Psychiatry SC Psychiatry GA 071BW UT WOS:000239573200005 PM 16894063 ER PT J AU Brody, AL Mandelkern, MA London, ED Olmstead, RE Farahi, J Scheibal, D Jou, J Allen, V Tiongson, E Chefer, SI Koren, AO Mukhin, AG AF Brody, Arthur L. Mandelkern, Mark A. London, Edythe D. Olmstead, Richard E. Farahi, Judah Scheibal, David Jou, Jennifer Allen, Valerie Tiongson, Emmanuelle Chefer, Svetlana I. Koren, Andrei O. Mukhin, Alexey G. TI Cigarette smoking saturates brain alpha(4)beta(2) nicotinic acetylcholine receptors SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; INDUCED DOPAMINE RELEASE; WITHDRAWAL SYMPTOMS; NUCLEUS-ACCUMBENS; TOBACCO SMOKING; BINDING-SITES; PET; REWARD; DRUGS; QUANTIFICATION AB Context: 2-[F-18]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2-F-A-85380, abbreviated as 2-FA) is a recently developed radioligand that allows for visualization of brain alpha(4)beta(2)* nicotinic acetylcholine receptors (nAChRs) with positron emission tomography (PET) scanning in humans. Objective: To determine the effect of cigarette smoking on alpha(4)beta(2)* nAChR occupancy in tobacco-dependent smokers. Design: Fourteen 2- FA PET scanning sessions were performed. During the PET scanning sessions, subjects smoked 1 of 5 amounts (none, 1 puff, 3 puffs, 1 full cigarette, or to satiety [2(2)/(1) to 3 cigarettes]). Setting: Academic brain imaging center. Participants: Eleven tobacco-dependent smokers (paid volunteers). Main Outcome Measure: Dose-dependent effect of smoking on occupancy of alpha(4)beta(2)* nAChRs, as measured with 2-FA and PET in nAChR-rich brain regions. Results: Smoking 0.13 (1 to 2 puffs) of a cigarette resulted in 50% occupancy of alpha(4)beta(2)* nAChRs for 3.1 hours after smoking. Smoking a full cigarette (or more) resulted in more than 88% receptor occupancy and was accompanied by a reduction in cigarette craving. A venous plasma nicotine concentration of 0.87 ng/mL (roughly (25)/(1)th of the level achieved in typical daily smokers) was associated with 50% occupancy of alpha(4)beta(2)* nAChRs. Conclusions: Cigarette smoking in amounts used by typical daily smokers leads to nearly complete occupancy of alpha(4)beta(2)* nAChRs, indicating that tobacco-dependent smokers maintain alpha(4)beta(2)* nAChR saturation throughout the day. Because prolonged binding of nicotine to alpha(4)beta(2)* nAChRs is associated with desensitization of these receptors, the extent of receptor occupancy found herein suggests that smoking may lead to withdrawal alleviation by maintaining nAChRs in the desensitized state. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Greater Los Angeles Vet Affairs Healthcare Syst P, Healthcare Syst Positron Emiss Tomog Ctr, Los Angeles, CA USA. Univ Calif Irvine, Dept Phys, Irvine, CA USA. Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Rockville, MD USA. Inst Neurodegenerat Disorders, New Haven, CT USA. RP Brody, AL (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, 300 Med Pl,Suite 2200, Los Angeles, CA 90095 USA. EM abrody@ucla.edu FU NIDA NIH HHS [R01 DA015059, R01 DA014093, DA20872, R01 DA015059-04, R01 DA020872, R01 DA020872-02, R01 DA14093, R01 DA15059] NR 69 TC 195 Z9 196 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2006 VL 63 IS 8 BP 907 EP 915 DI 10.1001/archpsyc.63.8.907 PG 9 WC Psychiatry SC Psychiatry GA 071BW UT WOS:000239573200009 PM 16894067 ER PT J AU Xu, K Lichtermann, D Lipsky, RH Franke, P Liu, XH Hu, Y Cao, LP Schwab, SG Wildenauer, DB Bau, CHD Ferro, E Astor, W Finch, T Terry, J Taubman, J Maier, W Goldman, D AF Xu, Ke Lichtermann, Dirk Lipsky, Robert H. Franke, Petra Liu, Xiehe Hu, Ying Cao, Liping Schwab, Sibylle G. Wildenauer, Dieter B. Bau, Claiton H. D. Ferro, Erica Astor, Will Finch, Thembi Terry, Jeanietta Taubman, Julie Maier, Wolfgang Goldman, David TI Estimation of haplotypes at DRD2 may have produced misleading results - In reply SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Letter C1 NIAAA, Lab Neurogenet, Rockville, MD USA. RP Xu, K (reprint author), NIAAA, Lab Neurogenet, Rockville, MD USA. EM ke@mail.nih.gov RI Bau, Claiton/C-9980-2013; Goldman, David/F-9772-2010 OI Bau, Claiton/0000-0001-5644-3845; Goldman, David/0000-0002-1724-5405 NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD AUG PY 2006 VL 63 IS 8 BP 939 EP 940 DI 10.1001/archpsyc.63.8.939-b PG 8 WC Psychiatry SC Psychiatry GA 071BW UT WOS:000239573200015 ER PT J AU Pao, M Ballard, ED Rosenstein, DL Wiener, L Wayne, AS AF Pao, Maryland Ballard, Elizabeth D. Rosenstein, Donald L. Wiener, Lori Wayne, Alan S. TI Psychotropic medication use in pediatric patients with cancer SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID MEDICALLY ILL CHILDREN; DEPRESSION; SYMPTOMS; PSYCHOPHARMACOLOGY; ADOLESCENTS; ONCOLOGY; PERSPECTIVE; MANAGEMENT; DISORDERS; MECHANISM AB Background: Use of psychotropic medication in medically ill adults, in particular, patients with cancer, is common. While increased use of psychotropic medications in children and adolescents in the general population has been reported, little is known about the prescribing practices for these medications in medically ill children. Objective: To examine the frequency and types of psychotropic medications used in a population of children and adolescents with cancer. Design: Retrospective review of the National Institutes of Health Medical Information System. Setting: Pediatric Oncology Branch of the National Cancer Institute, National Institutes of Health. Participants: Three hundred forty-seven patients aged 1 to 21 years who were enrolled in clinical research trials at the Pediatric Oncology Branch between January 2000 and December 2003. Main Outcome Measures: Psychotropic medication use was analyzed according to cancer diagnosis and patient age. Results: Fourteen percent of identified patients had been prescribed at least 1 psychotropic medication at the time of National Cancer Institute clinical trial enrollment. The most commonly used medications were anticonvulsant agents (8%) and antidepressant medications (7%), in particular, selective serotonin reuptake inhibitors. Anxiolytic medications could not be accurately assessed because of their frequent use as antiemetic agents in many chemotherapy regimens. Psychostimulant use was rare. Conclusions: This study suggests that psychotropic medications are commonly prescribed to children and adolescents with cancer. Clinical safety and efficacy trials are needed in medically ill children at high risk for mood and anxiety symptoms. C1 NIMH, Clin Res Ctr, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Pao, M (reprint author), NIMH, Clin Res Ctr, 5-5340, Bethesda, MD 20892 USA. EM paom@mail.nih.gov FU Intramural NIH HHS NR 35 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2006 VL 160 IS 8 BP 818 EP 822 DI 10.1001/archpedi.160.8.818 PG 5 WC Pediatrics SC Pediatrics GA 071BX UT WOS:000239573400009 PM 16894081 ER PT J AU Stout, JW Visness, CM Enright, P Lamm, C Shapiro, G Gan, VN Adams, GK Mitchell, HE AF Stout, James W. Visness, Cynthia M. Enright, Paul Lamm, Carin Shapiro, Gail Gan, Vanthaya N. Adams, G. Kenneth, III Mitchell, Herman E. TI Classification of asthma severity in children - The contribution of pulmonary function testing SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PEAK EXPIRATORY FLOW; INNER-CITY ASTHMA; QUALITY-OF-LIFE; NATIONAL GUIDELINES; ENVIRONMENTAL INTERVENTION; CLASSIFYING ASTHMA; AIRWAY-OBSTRUCTION; MANAGED CARE; POPULATION; SYMPTOMS AB Background: Despite increasing awareness of the National Asthma Education and Prevention Program guidelines, the relative contribution of symptom frequency or pulmonary function to the recommended asthma severity levels remains poorly understood. Objective: To determine whether adding lung function measurements to clinical history substantially changes the asthma severity classification, thereby influencing treatment decisions. Design: Baseline data were studied from children enrolled in 2 multicenter studies: phase 1 of the National Cooperative Inner-City Asthma Study (1992-1994) (cohort 1) and the Inner-City Asthma Study (1998-2001) (cohort 2). Setting: Fifteen (8 for cohort 1 and 7 for cohort 2) major metropolitan inner-city areas in the United States. Participants: Inner-city children aged 8 through 11 years with asthma. Main Outcome Measures: Proportion of children reclassified from less severe asthma categories based on symptom frequency into more severe categories because of lung function. Results: Of children with symptoms of mild intermittent asthma, 22.8% in cohort 1 and 27.7% in cohort 2 would be reclassified as having either moderate or severe persistent asthma. Of children with symptoms of mild persistent asthma, 31.2% in cohort 1 and 33.3% in cohort 2 would be similarly reclassified. Conclusions: In 2 different studies of inner-city children with asthma, approximately one third of the participants were reclassified into higher National Asthma Education and Prevention Program asthma severity categories when pulmonary function was considered in addition to symptom frequency. This may have direct implications for the undertreatment of asthma. C1 Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Rho Fed Syst Div Inc, Chapel Hill, NC USA. Univ Arizona, Resp Sci Ctr, Tucson, AZ USA. Mt Sinai Sch Med, Dept Pediat, New York, NY USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. NIAID, Bethesda, MD 20892 USA. RP Stout, JW (reprint author), Univ Washington, Sch Med, Dept Pediat, Box 354920, Seattle, WA 98195 USA. EM jstout@u.washington.edu FU NCRR NIH HHS [M01 RR00533]; NIAID NIH HHS [AI-39901, AI-39769, AI-39776, AI-39789, AI-39900, AI-39761, AI-39902]; PHS HHS [A--39785] NR 36 TC 44 Z9 46 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD AUG PY 2006 VL 160 IS 8 BP 844 EP 850 DI 10.1001/archpedi.160.8.844 PG 7 WC Pediatrics SC Pediatrics GA 071BX UT WOS:000239573400013 PM 16894085 ER PT J AU Lapteva, L Nowak, M Yarboro, CH Takada, K Roebuck-Spencer, T Weickert, T Bleiberg, J Rosenstein, D Pao, M Patronas, N Steele, S Manzano, M van der Veen, JWC Lipsky, PE Marenco, S Wesley, R Volpe, B Diamond, B Illei, GG AF Lapteva, Larissa Nowak, Miroslawa Yarboro, Cheryl H. Takada, Kazuki Roebuck-Spencer, Tresa Weickert, Thomas Bleiberg, Joseph Rosenstein, Donald Pao, Maryland Patronas, Nicholas Steele, Sonya Manzano, Melissa van der Veen, Jan Willem C. Lipsky, Peter E. Marenco, Stefano Wesley, Robert Volpe, Bruce Diamond, Betty Illei, Gabor G. TI Anti-N-methyl-D-aspartate receptor antibodies, cognitive dysfunction, and depression in systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; PROTON MR SPECTROSCOPY; NEUROPSYCHIATRIC MANIFESTATIONS; PREMORBID INTELLIGENCE; GLUTAMATE RECEPTORS; REVISED CRITERIA; BRAIN-INJURY; IMPAIRMENT; PREVALENCE; CLASSIFICATION AB Objective. To assess the association of cognitive dysfunction and depression with serum antibodies to N-methyl-D-aspartate (NMDA) receptor (anti-NR2) and analyze clinical and neuroimaging correlates in patients with systemic lupus erythematosus (SLE). Methods. Sixty patients underwent neurocognitive assessment, evaluation for depression with the Beck Depression Inventory II (BDI-II) and psychiatric interview (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition [DSM-IV] criteria), brain magnetic resonance imaging, and proton magnetic resonance spectroscopy imaging (H-1-MRSI). Cognition was assessed in 5 domains: memory, attention/executive, visuospatial, motor, and psychomotor, and adjusted to each individual's best level of prior cognitive functioning estimated from the reading subtest of the Wide Range Achievement Test-3 (WRAT-3). Serum anti-NR2 antibodies were measured by enzyme-linked immunosorbent assay using a pentapeptide from the human NMDA receptor. Results. Cognitive dysfunction was found in 28 of 60 patients (mild in 8, moderate in 20) before adjustment for WRAT-3 and in 35 of 60 patients (mild in 15, moderate in 11, and severe in 9) after adjustment for WRAT-3. The changes were most pronounced in the memory and visuospatial domains. There was no significant association between anti-NR2 antibody levels and cognition. On H-1-MRSI, patients with moderate or severe cognitive dysfunction had significantly higher choline:creatine ratios in the dorsolateral prefrontal cortex and the white matter, compared with patients with mild or absent cognitive dysfunction. Anti-NR2 antibodies were significantly correlated with BDI scores; patients with BDI-II scores of >= 14 had higher serum levels of anti-NR2 antibodies (P = 0.005, 95% confidence interval 0.83, 4.31), and there was a trend toward higher anti-NR2 antibody levels among patients who fulfilled the DSM-IV criteria for major depression. Conclusion. Serum anti-NR2 antibodies are associated with depressive mood but not with cognitive dysfunction in SLE at a given time point. Larger longitudinal studies are needed to address the possible association between anti-NR2 antibodies and depression in SLE. C1 Natl Inst Dent & Craniofacial Res, NIH, Sjogrens Syndrome Clin, Bethesda, MD 20892 USA. Natl Rehabil Hosp, Washington, DC USA. Cornell Univ, Weill Coll Med, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Lapteva, L (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Sjogrens Syndrome Clin, 10 Ctr Dr,Bldg 10,R 1N114,MSC1190, Bethesda, MD 20892 USA. EM lapteva1@mail.nih.gov RI Marenco, Stefano/A-2409-2008; OI Marenco, Stefano/0000-0002-2488-2365; Volpe, Bruce/0000-0002-1098-1848; Bleiberg, Joseph/0000-0003-0867-5494 FU Intramural NIH HHS NR 56 TC 125 Z9 132 U1 1 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2006 VL 54 IS 8 BP 2505 EP 2514 DI 10.1002/art.22031 PG 10 WC Rheumatology SC Rheumatology GA 071ZC UT WOS:000239641400019 PM 16868971 ER PT J AU Shi, T Giannakopoulos, B Yan, XK Yu, P Berndt, MC Andrews, RK Rivera, J Iverson, GM Cockerill, KA Linnik, MD Krilis, SA AF Shi, Tong Giannakopoulos, Bill Yan, Xiaokai Yu, Pei Berndt, Michael C. Andrews, Robert K. Rivera, Juan Iverson, G. Michael Cockerill, Keith A. Linnik, Matthew D. Krilis, Steven A. TI Anti-beta(2)-glycoprotein I antibodies in complex with beta(2)-glycoprotein I can activate platelets in a dysregulated manner via glycoprotein Ib-IX-V SO ARTHRITIS AND RHEUMATISM LA English DT Article ID LEUCINE-RICH REPEATS; ANTIPHOSPHOLIPID ANTIBODIES; BINDING-SITE; FACTOR-XI; ANTICARDIOLIPIN ANTIBODIES; DOMAIN-V; ALPHA; AUTOANTIBODIES; THROMBIN; EPITOPE AB Objective. Results of previous studies suggest that anti-beta(2)-glycoprotein I (anti-beta(2)GPI) antibodies in complex with beta(2)GPI activate platelets in a dysregulated manner, potentially contributing to the prothrombotic tendency associated with the antiphospholipid syndrome (APS). We undertook this study to investigate the possible contribution of the GPIb-IX-V receptor to platelet activation mediated by the anti-beta(2)GPI antibody-beta(2)GPI complex. Methods. In vitro methods were used in the present study. The interaction between beta(2)GPI and the GPIb alpha subunit of the GPIb-IX-V receptor was delineated using direct binding and competitive inhibition assays. The interaction between the anti-beta(2)GPI antibody-beta(2)GPI complex and platelets was studied using a novel method in which the Fc portion of the antibody was immobilized using protein A coated onto a microtiter plate. Platelet activation was assessed by two. methods; one involved measuring thromboxane B-2 production and the other involved assessment of the activation of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3 beta intracellular signaling pathway. The contribution of the GPIb alpha receptor to platelet activation induced by the anti-beta(2)GPI antibody-beta(2)GPI complex was assessed by observing the influence of 2 anti-GPIb alpha antibodies (AK2 and SZ2) directed against distinct epitopes. Results. This study showed that beta(2)GPI could bind to the GPIba receptor. The anti-beta(2)GPI antibody-beta(2)GPI complex was able to activate platelets, and this effect was inhibited by anti-GPIb alpha antibody directed against epitope Leu-36-Gln-59, but not by anti-GPIb alpha antibody directed against residues Tyr-276-Glu-282. Conclusion. Our findings show that inappropriate platelet activation by the anti-beta(2)GPI antibody-beta(2)GPI complex via the GPIb alpha receptor may contribute to the prothrombotic tendency associated with APS. C1 Univ New S Wales, St George Hosp, Kensington, NSW 2033, Australia. Monash Univ, Clayton, Vic 3168, Australia. NIAMSD, NIH, Bethesda, MD 20892 USA. La Jolla Pharmaceut Co, San Diego, CA USA. RP Krilis, SA (reprint author), Dept Immunol Allergy & Infect Dis, 2 South St, Sydney, NSW 2217, Australia. EM s.krilis@unsw.edu.au RI Berndt, Michael/D-5580-2012 NR 41 TC 84 Z9 88 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2006 VL 54 IS 8 BP 2558 EP 2567 DI 10.1002/art.21968 PG 10 WC Rheumatology SC Rheumatology GA 071ZC UT WOS:000239641400025 PM 16868978 ER PT J AU Aksentijevich, I Remmers, EF Goldbach-Mansky, R Reiff, A Kastner, DL AF Aksentijevich, Ivona Remmers, Elaine F. Goldbach-Mansky, Raphaela Reiff, Andreas Kastner, Daniel L. TI Mutational analysis in neonatal-onset multisystem innammatory disease: comment on the articles by Frenkel et al and Saito et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID ARTICULAR SYNDROME; AUTOINFLAMMATORY DISEASES; CIAS1 MUTATIONS; GENE C1 NIH, Bethesda, MD 20892 USA. Univ So Calif, Childrens Hosp, Los Angeles, CA 90027 USA. RP Aksentijevich, I (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD AUG PY 2006 VL 54 IS 8 BP 2703 EP 2704 DI 10.1002/art.22022 PG 2 WC Rheumatology SC Rheumatology GA 071ZC UT WOS:000239641400043 PM 16871551 ER PT J AU Cao, JJ Barzilay, JI Peterson, D Manolio, TA Psaty, BM Kuller, L Wexler, J Bleyer, AJ Cushman, M AF Cao, Jie J. Barzilay, Joshua I. Peterson, Do Manolio, Teri A. Psaty, Bruce M. Kuller, Lewis Wexler, Jason Bleyer, Anthony J. Cushman, Mary TI The association of microalbuminuria with clinical cardiovascular disease and subclinical atherosclerosis in the elderly: The Cardiovascular Health Study SO ATHEROSCLEROSIS LA English DT Article DE microalbuminuria; cardiovascular disease; hypertension; diabetes mellitus ID URINARY ALBUMIN EXCRETION; INTIMA-MEDIA THICKNESS; INSULIN-RESISTANCE ATHEROSCLEROSIS; ACUTE MYOCARDIAL-INFARCTION; RISK-FACTORS; DIABETES-MELLITUS; CAROTID-ARTERY; POPULATION; MORTALITY; PROTEINURIA AB Purpose: Microalbuminuria (MA) is a risk factor for cardiovascular disease (CVD). It is not known whether this association is due to the effect of MA on the development of subclinical atherosclerosis or whether MA destabilizes subclinical atherosclerosis, leading to clinical events. Methods: In a cross-sectional analysis we evaluated 3312 Cardiovascular Health Study participants, age >= 65 years, who had MA testing. Participants were divided into three groups: those without diabetes or hypertension (33%), those with hypertension (52%) and those with diabetes, with or without hypertension (15%). Clinical CVD was defined as presence of coronary heart disease (angina, MI, CABG, PTCA), cerebrovascular disease (stroke, TIA) and peripheral arterial disease (requiring intervention). Among those without clinical disease, subclinical atherosclerosis was defined as increased carotid artery intima-media thickness, decreased ankle arm index or increased left ventricular mass. Results: In each of the three groups of participants, the adjusted odds of prevalent clinical CVD in the presence of MA was 1.70-1.80-fold increased, independent of other risk factors. MA was not associated with risk of subclinical atherosclerosis in those without hypertension or diabetes (OR 1.14 [95% CI 0.59, 2.23]), whereas it was associated with subclinical atherosclerosis in those with hypertension (OR 1.58 [95% CI 1.08, 2.30]) or diabetes (OR 2.51 [95% CI 1.27, 4.94]). Conclusion: In the absence of hypertension or diabetes, MA was associated with clinical CVD but not with subclinical atherosclerosis. Thus, a hypothesis may be made that the mechanism of association of MA with clinical vascular disease involves destabilization of the vasculature, leading to clinical disease. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Vermont, Coll Med, Dept Pathol & Med, Colchester, VT 05446 USA. NHLBI, Nihon Univ, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Kaiser Permanente Georgia, Atlanta, GA USA. Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif Davis, Dept Med, Davis, CA 95616 USA. Wake Forest Univ, Dept Med, Winston Salem, NC 27109 USA. RP Cushman, M (reprint author), Univ Vermont, Coll Med, Dept Pathol & Med, 208 S Pk Dr,Suite 2, Colchester, VT 05446 USA. EM mary.cushman@uvm.edu FU NHLBI NIH HHS [N01 HC-15103, N01-HC-85081, N01-HC-85085, N01-HC-85079, N01-HC-35129, N01-HC-85086, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85080] NR 27 TC 38 Z9 43 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD AUG PY 2006 VL 187 IS 2 BP 372 EP 377 DI 10.1016/j.atherosclerosis.2005.09.015 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 068IV UT WOS:000239368000018 PM 16242696 ER PT J AU Venkataraman, K Thangada, S Michaud, J Oo, ML Ai, YX Lee, YM Wu, MT Parikh, NS Khan, F Proia, RL Hla, T AF Venkataraman, Krishnan Thangada, Shobha Michaud, Jason Oo, Myat Lin Ai, Youxi Lee, Yong-Moon Wu, Mingtao Parikh, Nehal S. Khan, Faraz Proia, Richard L. Hla, Timothy TI Extracellular export of sphingosine kinase-1a contributes to the vascular S1P gradient SO BIOCHEMICAL JOURNAL LA English DT Article DE extracellular export; platelet-poor plasma; platelet-rich plasma; sphingosine kinase; sphingosine 1-phosphate; sphingosine 1-phosphate (S1P) gradient ID CELL-GROWTH; FUNCTIONAL-CHARACTERIZATION; ACID SPHINGOMYELINASE; QUANTITATIVE-ANALYSIS; NEUTRAL CERAMIDASE; BIOLOGICAL SAMPLES; MOLECULAR-CLONING; 1-PHOSPHATE; FTY720; PHOSPHORYLATION AB Sphingosine 1-phosphate (S1P), produced by Sphk (sphingosine kinases), is a multifunctional lipid mediator that regulates immune cell trafficking and vascular development. Mammals maintain a large concentration gradient of SIP between vascular and extravascular compartments. Mechanisms by which SIP is released from cells and concentrated in the plasma are poorly understood. We recently demonstrated [Ancellin, Colmont, Su, Li, Mittereder, Chare, Stefansson, Liau and Hla (2002) J. Biol. Chem. 277, 6667-6675] that Sphk1 activity is constitutively secreted by vascular endothelial cells. In the present study, we show that among the five Sphk isoforms, expressed in endothelial cells, the Sphk-1a isoform is selectively secreted in HEK-293 cells (human embryonic kidney cells) and human umbilical-vein endothelial cells. In sharp contrast, Sphk2 is not secreted. The exported Sphk-1a isoform is enzymatically active and produced sufficient SIP to induce SIP receptor internalization. Wild-type mouse plasma contains significant Sphk activity (179 pmol (.) min(-1) (.) g(-1)). In contrast, Sphk1(-/-) mouse plasma has undetectable Sphk activity and approx. 65% reduction in S1P levels. Moreover, human plasma contains enzymatically active Sphk1 (46 pmol (.) min(-1) (.) g(-1)). These results suggest that export of Sphk-1a occurs under physiological conditions and may contribute to the establishment of the vascular S1P gradient. C1 Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA. Connecticut Childrens Med Ctr, Div Hematol & Oncol, Hartford, CT 06106 USA. NIDDK, Genet Dis & Dev Branch, NIH, Bethesda, MD 20892 USA. RP Hla, T (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Ctr Vasc Biol, Farmington, CT 06030 USA. EM hla@nso2.uchc.edu RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012 OI Hla, Timothy/0000-0001-8355-4065 FU NHLBI NIH HHS [HL70694, HL67330, P01 HL070694, R01 HL067330, R37 HL067330] NR 38 TC 121 Z9 124 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD AUG 1 PY 2006 VL 397 BP 461 EP 471 DI 10.1042/BJ20060251 PN 3 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 069UO UT WOS:000239474100009 PM 16623665 ER PT J AU Guo, HB Wlodawer, A Nakayama, T Xu, Q Guo, H AF Guo, Haobo Wlodawer, Alexander Nakayama, Toru Xu, Qin Guo, Hong TI Catalytic role of proton transfers in the formation of a tetrahedral adduct in a serine carboxyl peptidase SO BIOCHEMISTRY LA English DT Article ID FREE-ENERGY CALCULATIONS; HISTOGRAM ANALYSIS METHOD; MOLECULAR-DYNAMICS; HYDROGEN-BONDS; ACTIVE-SITE; PROTEINASE; ENZYMES; STABILIZATION; PURIFICATION; SPECIFICITY AB Quantum mechanical/molecular mechanical molecular dynamics and 2D free energy simulations are performed to study the formation of a tetrahedral adduct by an inhibitor N-acetyl-isoleucyl-prolylphenylalaninal (AcIPF) in a serine-carboxyl peptidase (kumamolisin-As) and elucidate the role of proton transfers during the nucleophilic attack by the Ser278 catalytic residue. It is shown that although the serine-carboxyl peptidases have a fold resembling that of subtilisin, the proton transfer processes during the nucleophilic attack by the Ser residue are likely to be more complex for these enzymes compared to the case in classical serine proteases. The computer simulations demonstrate that both general base and acid catalysts are required for the formation and stabilization of the tetrahedral adduct. The 2D free energy maps further demonstrate that the proton transfer from Ser278 to Glu78 (the general base catalyst) is synchronous with the nucleophilic attack, whereas the proton transfer from Asp164 (the general acid catalyst) to the inhibitor is not. The dynamics of the protons at the active site in different stages of the nucleophilic attack as well as the motions of the corresponding functional groups are also studied. It is found that the side chain of Glu78 is generally rather flexible, consistent with its possible multifunctional role during catalysis. The effects of proton shuffling from Asp82 to Glu78 and from Glu32 to Asp82 are examined, and the results indicate that such proton shuffling may not play an important role in the stabilization of the tetrahedral intermediate analogue. C1 Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. Natl Canc Inst, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. Tohoku Univ, Grad Sch Engn, Dept Biomol Engn, Sendai, Miyagi 9808579, Japan. RP Guo, H (reprint author), Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. EM hguo1@utk.edu RI Guo, Hao-Bo/B-7486-2009; Guo, Hong/E-6357-2010; Xu, Qin/O-7310-2015 OI Guo, Hao-Bo/0000-0003-1321-1758; Xu, Qin/0000-0002-8346-9431 FU Intramural NIH HHS NR 43 TC 17 Z9 18 U1 0 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 AUG 1 PY 2006 VL 45 IS 30 BP 9129 EP 9137 DI 10.1021/bi060461i PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 066OF UT WOS:000239238500014 PM 16866358 ER PT J AU Lima, LMTR Cordeiro, Y Tinoco, LW Marques, AF Oliveira, CLP Sampath, S Kodali, R Choi, G Foguel, D Torriani, I Caughey, B Silva, JL AF Trambaioli da Rocha e Lima, Luis Mauricio Cordeiro, Yraima Tinoco, Luzineide W. Marques, Adriana F. Oliveira, Cristiano L. P. Sampath, Srisailam Kodali, Ravindra Choi, Gildon Foguel, Debora Torriani, Iris Caughey, Byron Silva, Jerson L. TI Structural insights into the interaction between prion protein and nucleic acid SO BIOCHEMISTRY LA English DT Article ID SMALL-ANGLE SCATTERING; BETA-SHEET CONVERSION; CELL-FREE FORMATION; BIOLOGICAL MACROMOLECULES; HIGH-PRESSURE; SCRAPIE; BINDING; SPECTROSCOPY; AGGREGATION; HYDRATION AB The infectious agent of transmissible spongiform encephalopathies (TSE) is believed to comprise, at least in part, the prion protein (PrP). Other molecules can modulate the conversion of the normal PrPC into the pathological conformer ( PrPSc), but the identity and mechanisms of action of the key physiological factors remain unclear. PrP can bind to nucleic acids with relatively high affinity. Here, we report small-angle X-ray scattering (SAXS) and nuclear magnetic resonance spectroscopy measurements of the tight complex of PrP with an 18 bp DNA sequence. This double-stranded DNA sequence (E2DBS) binds with nanomolar affinity to the full-length recombinant mouse PrP. The SAXS data show that formation of the rPrP-DNA complex leads to larger values of the maximum dimension and radius of gyration. In addition, the SAXS studies reveal that the globular domain of PrP participates importantly in the formation of the complex. The changes in NMR HSQC spectra were clustered in two major regions: one in the disordered portion of the PrP and the other in the globular domain. Although interaction is mediated mainly through the PrP globular domain, the unstructured region is also recruited to the complex. This visualization of the complex provides insight into how oligonucleotides bind to PrP and opens new avenues to the design of compounds against prion diseases. C1 Univ Fed Rio de Janeiro, Fac Farm, Ctr Nacl Ressonancia Magnet Nucl, Inst Bioquim Med, BR-21941590 Rio De Janeiro, Brazil. Univ Estadual Campinas, Inst Fis Gleb Wataghin, BR-13084971 Campinas, SP, Brazil. NIAID, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Silva, JL (reprint author), Univ Fed Rio de Janeiro, Fac Farm, Ctr Nacl Ressonancia Magnet Nucl, Inst Bioquim Med, BR-21941590 Rio De Janeiro, Brazil. EM jerson@bioqmed.ufrj.br RI kodali, ravindra/D-1543-2010; Marques, Alexandre/F-9935-2012; Torriani, Iris/E-5686-2010; Cordeiro, Yraima/J-7619-2012; Tinoco, Luzineide/G-3630-2014; Silva, Jerson/J-8984-2014; Marques, Alexandre/K-3678-2013; Inst. of Physics, Gleb Wataghin/A-9780-2017; Oliveira, Cristiano/B-4403-2008 OI Marques, Alexandre/0000-0001-9416-3465; Cordeiro, Yraima/0000-0003-4278-212X; Tinoco, Luzineide/0000-0002-1299-6242; Silva, Jerson/0000-0001-9523-9441; Marques, Alexandre/0000-0001-9416-3465; Oliveira, Cristiano/0000-0002-3426-6507 NR 44 TC 53 Z9 54 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD AUG 1 PY 2006 VL 45 IS 30 BP 9180 EP 9187 DI 10.1021/bi060532d PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 066OF UT WOS:000239238500020 PM 16866364 ER PT J AU Zhang, TQ Rubtsov, IV Nakajima, H Aono, S Yoshihara, K AF Zhang, Tieqiao Rubtsov, Igor V. Nakajima, Hiroshi Aono, Shigetoshi Yoshihara, Keitaro TI Effect of mutation on the dissociation and recombination dynamics of CO in transcriptional regulator CooA: A picosecond infrared transient absorption study SO BIOCHEMISTRY LA English DT Article ID RHODOSPIRILLUM-RUBRUM; ACTIVATOR COOA; CARBON-MONOXIDE; HEME-PROTEINS; RESONANCE RAMAN; FLASH-PHOTOLYSIS; GENE-EXPRESSION; LIGAND-BINDING; AXIAL LIGAND; HISTIDINE 77 AB The CO ligation process in a mutant (H77G) of CooA, the CO-sensing transcriptional regulator in Rhodospirillum rubrum, is studied with femtosecond time-resolved transient absorption spectroscopy in the mid-infrared region. Following photolyzing excitation, a transient bleach in the vibrational region of bound CO due to the CO photodissociation is detected. In contrast to the spectra of the wild-type ( WT) CooA, the transient bleach spectra of H77G CooA show a bimodal shape with peaks shifting to the lower frequency during spectral evolution. The CO recombination dynamics show single-exponential behavior, and the CO escaping yield is higher than that of the WT CooA. A reorientation process of CO relative to the heme plane during recombination is revealed by anisotropy measurements. These phenomena indicate changes in the protein response to the CO ligation and suggest an alteration to the CO environment caused by the mutation. On the basis of these results, the role of His77 in the CO-dependent activation of CooA and a possible activation mechanism involving collaborative movement of the heme and the amino residues at both sides of the heme plane are discussed. C1 Japan Adv Inst Sci & Technol, Sch Mat Sci, Tatsunokuchi, Ishikawa 9231292, Japan. RP Zhang, TQ (reprint author), Natl Inst Hlth, Imaging Sci Program, Ctr Clin, Bethesda, MD 20892 USA. EM zhangti@mail.nih.gov; Riken-Yoshihara@mosk.tytlabs.co.jp NR 46 TC 3 Z9 3 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 AUG 1 PY 2006 VL 45 IS 30 BP 9246 EP 9253 DI 10.1021/bi0603672 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 066OF UT WOS:000239238500027 PM 16866371 ER PT J AU Brown, DT Izard, T Misteli, T AF Brown, D. T. Izard, Tina Misteli, Tom TI Mapping the interaction surface of the linker histone H1(circle) with the nucleosome of native chromatin in vivo SO BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE LA English DT Meeting Abstract C1 Univ Mississippi, Med Ctr, Dept Biochem, Jackson, MS 39216 USA. St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0829-8211 J9 BIOCHEM CELL BIOL JI Biochem. Cell Biol. PD AUG PY 2006 VL 84 IS 4 BP 660 EP 660 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 077TL UT WOS:000240053100029 ER PT J AU Baum, BJ Zheng, CY Cotrim, AP Goldsmith, CM Atkinson, JC Brahim, JS Chiorini, JA Voutetakis, A Leakan, RA Van Waes, C Mitchell, JB Delporte, C Wang, SL Kaminsky, SM Illei, GG AF Baum, Bruce J. Zheng, Changyu Cotrim, Ana P. Goldsmith, Corinne M. Atkinson, Jane C. Brahim, Jaime S. Chiorini, John A. Voutetakis, Antonis Leakan, Rose Anne Van Waes, Carter Mitchell, James B. Delporte, Christine Wang, Songlin Kaminsky, Stephen M. Illei, Gabor G. TI Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article; Proceedings Paper CT 4th International Conference on Aquaporins CY SEP 10-13, 2005 CL Genval, BELGIUM DE gene therapy; adenoviral vector; aquaporin-1; salivary gland; radiation damage; animal model; clinical trial ID HUMAN AQUAPORIN-1 CDNA; GENE-TRANSFER VECTORS; QUALITY-OF-LIFE; NECK-CANCER; MEDIATED TRANSFER; IN-VIVO; RECOMBINANT ADENOVIRUS; EPITHELIAL-CELLS; FLUID MOVEMENT; PAROTID-GLANDS AB The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C. Delporte, B.C. O'Connell, X. He, H.E. Lancaster, A.C. O'Connell, P. Agre, B.J. Baum, Increased fluid secretion after adenoviral -mediated transfer of the aquaporin-1 cDNA to irradiated rat salivary glands. Proc. Nail. Acad. Sci. U S A. 94 (1997) 3268-3273] and miniature pig [Z. Shan, J. Li, C. Zheng, X. Liu, Z. Fan, C. Zhang, C.M. Goldsmith, R.B. Wellner, B.J Baum, S. Wang. Increased fluid secretion after adenoviral-mediated transfer of the human aquaporin-1 cDNA to irradiated miniature pig parotid glands. Mol. Ther. 11 (2005) 444-451] salivary glands 16 weeks following IR resulted in a dose-dependent increase in salivary flow to >= 80% control levels on day 3. A control Ad vector was without any significant effect on salivary flow. Additionally, after administration of Ad vectors to salivary glands, no significant lasting effects were observed in multiple measured clinical chemistry and hematology values. Taken together, the findings show that localized delivery of AdhAQP1 to IR-damaged salivary glands is useful in transiently increasing salivary secretion in both small and large animal models, without significant general adverse events. Based on these results, we are developing a clinical trial to test if the hAQP1 cDNA transfer strategy will be clinically effective in restoring salivary flow in patients with IR-induced parotid hypofunction. Published by Elsevier B.V. C1 Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Clin Res Core, Bethesda, MD 20892 USA. Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Libre Bruxelles, Lab Biol Chem & Nutr, Fac Med, Brussels, Belgium. Capital Univ Med Sci, Fac Stomatol, Mol Lab Gene Therapy, Salivary Gland Dis Ctr, Beijing, Peoples R China. Cornell Univ, Weill Coll Med, Belfer Gene Therapy Vector Core, New York, NY 10021 USA. RP Baum, BJ (reprint author), Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov RI Kaminsky, Stephen/J-5141-2016 OI Kaminsky, Stephen/0000-0003-1869-834X NR 39 TC 28 Z9 30 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD AUG PY 2006 VL 1758 IS 8 BP 1071 EP 1077 DI 10.1016/j.bbamem.2005.11.006 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 094XP UT WOS:000241272900013 PM 16368071 ER PT J AU Hurley, JH AF Hurley, James H. TI Membrane binding domains SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE protein kinase C; diacylglycerol; phosphoinositide; signal transduction; membrane trafficking ID PROTEIN-KINASE-C; PLECKSTRIN HOMOLOGY DOMAINS; HIGH-AFFINITY BINDING; PHORBOL ESTER BINDING; GENOME-WIDE ANALYSIS; CRYSTAL-STRUCTURE; PHOSPHATIDYLINOSITOL 3-PHOSPHATE; FYVE DOMAINS; PX DOMAINS; PHOSPHOLIPASE C-DELTA(1) AB Eukaryotic signaling and trafficking proteins are rich in modular domains that bind cell membranes. These binding events are tightly regulated in space and time. The structural, biochemical, and biophysical mechanisms for targeting have been worked out for many families of membrane binding domains. This review takes a comparative view of seven major classes of membrane binding domains, the C1, C2, PH, FYVE, PX, ENTH, and BAR domains. These domains use a combination of specific headgroup interactions, hydrophobic membrane penetration, electrostatic surface interactions, and shape complementarity to bind to specific subcellular membranes. Published by Elsevier B.V. C1 NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov FU Intramural NIH HHS [Z01 DK036118-14] NR 79 TC 97 Z9 100 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD AUG PY 2006 VL 1761 IS 8 BP 805 EP 811 DI 10.1016/j.bbalip.2006.02.020 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 092XL UT WOS:000241130800002 PM 16616874 ER PT J AU Varnai, P Balla, T AF Varnai, Peter Balla, Tamas TI Live cell imaging of phosphoinositide dynamics with fluorescent protein domains SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE green fluorescent protein; phosphoinositide; pleckstrin homology domain; InsP3; calcium; phospholipase C ID PLECKSTRIN-HOMOLOGY-DOMAIN; RESONANCE ENERGY-TRANSFER; OXYSTEROL-BINDING-PROTEIN; BRUTONS TYROSINE KINASE; INOSITOL-LIPID-BINDING; SINGLE LIVING CELLS; PLASMA-MEMBRANE; PHOSPHOLIPASE-C; PH DOMAIN; PHOSPHATIDYLINOSITOL 4-PHOSPHATE AB Phosphoinositides make up only a small fraction of membrane phospholipids yet they are of outmost significance in regulating membrane-associated signaling processes. A large number of inositol lipid kinases and phosphatases have evolved to control the rapid production and elimination of these lipids at specific cellular membrane compartments. For a long period of time, the only information about the spatial aspect of inositol lipid metabolism relied upon the immunostaining of enzymes or cell fractionation of the enzyme activities that acted upon these lipids. Recent advances in the understanding of the nature of protein-inositol lipid interactions permitted the design of fluorescent molecular probes that can interact with inositol lipids in a specific manner allowing imaging of phosphoinositide dynamics in live cells. This approach has rapidly gained high popularity, but also provoked criticisms and debate about its limitations. In this review, we will summarize our experience with using these molecular tools and address some issues that most often come up in discussions concerning the usefulness and drawbacks of this technique. The most important value of these debates is that they also challenge our preconceived views of how phosphoinositides regulate cellular functions. Published by Elsevier B.V. C1 NICHD, Endocrinol & Reprod Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Dept Physiol, Fac Med, Budapest, Hungary. RP Balla, T (reprint author), NICHD, Endocrinol & Reprod Branch, NIH, Bldg 49,Rm 6A35,49 Convent Dr, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov OI Balla, Tamas/0000-0002-9077-3335 FU Intramural NIH HHS NR 83 TC 87 Z9 88 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD AUG PY 2006 VL 1761 IS 8 BP 957 EP 967 DI 10.1016/j.bbalip.2006.03.019 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 092XL UT WOS:000241130800013 PM 16702024 ER PT J AU Saltz, J Oster, S Hastings, S Langella, S Kurc, T Sanchez, W Kher, M Manisundaram, A Shanbhag, K Covitz, P AF Saltz, Joel Oster, Scott Hastings, Shannon Langella, Stephen Kurc, Tahsin Sanchez, William Kher, Manav Manisundaram, Arumani Shanbhag, Krishnakant Covitz, Peter TI caGrid: design and implementation of the core architecture of the cancer biomedical informatics grid SO BIOINFORMATICS LA English DT Article AB Motivation: The complexity of cancer is prompting researchers to find new ways to synthesize information from diverse data sources and to carry out coordinated research efforts that span multiple institutions. There is a need for standard applications, common data models, and software infrastructure to enable more efficient access to and sharing of distributed computational resources in cancer research. To address this need the National Cancer Institute (NCI) has initiated a national-scale effort, called the cancer Biomedical Informatics Grid (caBIG (TM)), to develop a federation of interoperable research information systems. Results: At the heart of the caBIG approach to federated interoperability effort is a Grid middleware infrastructure, called caGrid. In this paper we describe the caGrid framework and its current implementation, caGrid version 0.5. caGrid is a model-driven and service-oriented architecture that synthesizes and extends a number of technologies to provide a standardized framework for the advertising, discovery, and invocation of data and analytical resources. We expect caGrid to greatly facilitate the launch and ongoing management of coordinated cancer research studies involving multiple institutions, to provide the ability to manage and securely share information and analytic resources, and to spur a new generation of research applications that empower researchers to take a more integrative, trans-domain approach to data mining and analysis. C1 Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA. Sci Applicat Int Corp, Annapolis, MD USA. Booz Allen & Hamilton Inc, Rockville, MD USA. NCI, Ctr Bioinformat, Rockville, MD USA. RP Saltz, J (reprint author), Ohio State Univ, Dept Biomed Informat, 3184 Graves Hall,333 W 10th Ave, Columbus, OH 43210 USA. EM joel.saltz@osumc.edu FU NIBIB NIH HHS [P20EB000591] NR 16 TC 99 Z9 99 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 1 PY 2006 VL 22 IS 15 BP 1910 EP 1916 DI 10.1093/bioinformatics/btl272 PG 7 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 075QG UT WOS:000239899700014 PM 16766552 ER PT J AU O'Brien, SJ Troyer, JL Roelke, M Marker, L Pecon-Slattery, J AF O'Brien, Stephen J. Troyer, Jennifer L. Roelke, Melody Marker, Laurie Pecon-Slattery, Jill TI Plagues and adaptation: Lessons from the Felidae models for SARS and AIDS SO BIOLOGICAL CONSERVATION LA English DT Article DE FIV; SARS; AIDS; CDV ID FELINE IMMUNODEFICIENCY VIRUS; ACUTE RESPIRATORY SYNDROME; LIONS PANTHERA-LEO; TRANSMISSIBLE GASTROENTERITIS CORONAVIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; COMPARATIVE GENOME ORGANIZATION; CANINE-DISTEMPER VIRUS; PUMA PUMA-CONCOLOR; FREE-RANGING LIONS; GENETIC DIVERSITY AB Research studies of infectious disease outbreaks in wild species of the cat family Felidae have revealed unusual details regarding forces that shape population survival and genetic resistance in these species. A highly virulent feline coronavirus epidemic in African cheetahs, a disease model for human SARS, illustrates the critical role of ancestral population genetic variation. Widespread prevalence of species specific feline immunodeficiency virus (FM, a relative of HIV-AIDS, occurs with little pathogenesis in felid species, except in domestic cats, suggesting immunological adaptation in species where FIV is endemic. Resolving the interaction of host and pathogen genomes can shed new light on the process of disease outbreak in wildlife and in humankind. The role of disease in endangered populations and species is difficult to access as opportunities to monitor outbreaks in natural populations are limited. Conservation management may benefit greatly from advances in molecular genetic tools developed for human biomedical research to assay the biodiversity of both host species and emerging pathogen. As these examples illustrate, strong parallels exist between disease in human and endangered wildlife and argue for an integration of the research fields of comparative genomics, infectious disease, epidemiology, molecular genetics and population biology for an effective proactive conservation approach. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. NCI, Lab Genom Divers, SAIC Frederick, Frederick, MD USA. RP O'Brien, SJ (reprint author), Natl Canc Inst, Lab Genom Divers, Bldg 560,Room 21-105, Ft Detrick, MD 21702 USA. EM obrien@ncifcrf.gov RI Troyer, Jennifer/B-8415-2012 NR 83 TC 10 Z9 10 U1 2 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0006-3207 J9 BIOL CONSERV JI Biol. Conserv. PD AUG PY 2006 VL 131 IS 2 BP 255 EP 267 DI 10.1016/j.biocon.2006.05.001 PG 13 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 064DP UT WOS:000239069700010 ER PT J AU Cannon, DM Ichise, M Fromm, SJ Nugent, AC Rollis, D Gandhi, SK Klaver, JM Charney, DS Manji, HK Drevets, WC AF Cannon, Dara M. Ichise, Masanori Fromm, Stephen J. Nugent, Allison C. Rollis, Denise Gandhi, Shilpa K. Klaver, Jacqueline M. Charney, Dennis S. Manji, Husseini K. Drevets, Wayne C. TI Serotonin transporter binding in bipolar disorder assessed using [C-11]DASB and positron emission tomography SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; positron emission tomography; serotonin transporter; [C-11]DASB ID 5-HT UPTAKE SITES; TRITIATED IMIPRAMINE BINDING; AGE-RELATED DECLINE; HUMAN-BRAIN; MAJOR DEPRESSION; SUICIDE VICTIMS; FRONTAL-CORTEX; MESSENGER-RNA; PREFRONTAL CORTEX; IN-VITRO AB Background. Evidence from neuroimaging post-mortem, and genetic studies suggests that bipolar disorder (BD) is associated with abnormalities of the serotonin-transporter (5-HTT) system. Because of various limitations of these studies, however, it has remained unclear whether 5-HTT binding is abnormal in unmedicated BD-subjects. This study used PET and [C-11]DASB, a radioligand that afforded higher sensitivity and specificity for the 5-HTT than previously available radioligands, to compare 5-HTT binding between BD and control subjects. Methods: The 5-HTT binding-potential (BP) was assessed in 18 currently-depressed, unmedicated BD-subjects and 3 7 healthy controls using PET and [C-11]DASB. Results. In BD, the mean 5-HTTBP was increased in thalamus, dorsal cingulate cortex (DCC) medial prefrontal cortex and insula and decreased in the brainstem at the level of the pontine raphe-nuclei. Anxiety ratings correlated positively with 5-HTTBP in insula and DCC, and BP in these regions was higher in subjects manifesting pathological obsessions and compulsions relative to BD-subjects lacking such symptoms. Subjects with a history of suicide attempts showed reduced 5-HTT binding in the midbrain and increased binding in anterior cingulate cortex versus controls and to BD-subjects without attempts. Conclusions: This is the first study to report abnormalities in 5-HTT binding in unmedicated BD-subjects. The direction of abnormality in the brainstem was opposite to that found in the cortex, thalamus, and striatum. Elevated 5-HTT binding in the cortex may be related to anxiety symptoms and syndromes associated with BD. C1 Brigham & Womens Hosp, Div Nucl Med, Bethesda, MD USA. NIMH, Mol Imaging Branch, Bethesda, MD USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. RP Cannon, DM (reprint author), NIH, 15K-202 North Dr, Bethesda, MD 20892 USA. EM daracannon@mail.nih.gov RI Cannon, Dara/C-1323-2009; OI Cannon, Dara/0000-0001-7378-3411; Nugent, Allison/0000-0003-2569-2480 FU Intramural NIH HHS NR 89 TC 95 Z9 100 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 1 PY 2006 VL 60 IS 3 BP 207 EP 217 DI 10.1016/j.biopsych.2006.05.005 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 070SI UT WOS:000239543800001 PM 16875929 ER PT J AU Blair, KS Richell, RA Mitchell, DGV Leonard, A Morton, J Blair, RJR AF Blair, K. S. Richell, R. A. Mitchell, D. G. V. Leonard, A. Morton, J. Blair, R. J. R. TI They know the words, but not the music: Affective and semantic priming in individuals with psychopathy SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE psychopathy; affective priming; semantic priming ID SPREADING ACTIVATION THEORY; AMYGDALA; MODULATION; EMOTION; MEMORY; REWARD; PERSONALITY; MECHANISMS; OFFENDERS; BEHAVIOR AB Previous work has indicated dysfunctional affect-language interactions in individuals with psychopathy through use of the lexical decision task. However, it has been uncertain as to whether these deficits actually reflect impaired affect-language interactions or a more fundamental deficit in general semantic processing. In this study, we examined affective priming and semantic priming (dependent measures were reaction times and error rates) in individuals with psychopathy and comparison individuals, classified according to the psychopathy checklist revised (PCL-R) [Hare, R.D., 1991. The Hare Psychopathy Checklist-Revised. Multi-Health Systems, Toronto, Ont.]. Individuals with psychopathy showed significantly less affective priming relative to comparison individuals. In contrast, the two groups showed comparable levels of semantic priming. The results are discussed with reference to current models of psychopathy. Published by Elsevier B.V. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London, England. HM Prison Wormwood Scrubs, Dept Psychol, London, England. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, NIH,Dept Hlth & Human Serv, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov FU Intramural NIH HHS NR 52 TC 34 Z9 36 U1 11 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD AUG PY 2006 VL 73 IS 2 BP 114 EP 123 DI 10.1016/j.biopsycho.2005.12.006 PG 10 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 082OK UT WOS:000240396000002 PM 16574302 ER PT J AU Semba, RD Ferrucci, L Cappola, AR Ricks, MO Ray, AL Xue, QL Guralnik, JM Fried, LP AF Semba, Richard D. Ferrucci, Luigi Cappola, Anne R. Ricks, Michelle O. Ray, Amanda L. Xue, Qian-Li Guralnik, Jack M. Fried, Linda P. TI Low serum selenium is associated with anemia among older women living in the community SO BIOLOGICAL TRACE ELEMENT RESEARCH LA English DT Article DE aging; anemia; hemoglobin; selenium; women ID OXIDATIVE DAMAGE; PHYSICAL PERFORMANCE; RAT ERYTHROCYTES; DIETARY SELENIUM; MUSCLE STRENGTH; DISEASE; AGE; SUSCEPTIBILITY; REQUIREMENTS; PREVALENCE AB Anemia is common among older adults, and a substantial proportion of anemia in the older population is of indeterminate cause. Low selenium levels have been associated with anemia in animals, but this relationship has not been well characterized in humans. The objective was to determine whether low serum selenium concentrations are associated with anemia among older women. We conducted a cross-sectional analysis of participants in the Women's Health and Aging Studies, a population-based sample of women living in the community in Baltimore, MD, USA. Of 632 women, aged 70-79 yr, 14.1% of women were anemic (hemoglobin < 120 g/L). The prevalence of anemia among women in the lowest to highest quartile of serum selenium was 22.4%, 14.6%, 11.9% and 6.6%, respectively (p < 0.0001). An increase in loge selenium was associated with a reduced risk of anemia (odds ratio per 1 SD increase = 0.63, 95% confidence interval = 0.47-0.84), adjusting for age, education, chronic diseases, iron status, and serum interleukin-6. We conclude that low serum selenium is independently associated with anemia among older women living in the community. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Clin Res Branch, Longitudinal Studies Sect, Bethesda, MD USA. NIA, Epidemiol Demog & Biometry Branch, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Med, Div Endocrinol Diabet & Metab, Philadelphia, PA 19104 USA. RP Semba, RD (reprint author), Johns Hopkins Med Inst, Baltimore, MD 21205 USA. FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000722]; NIA NIH HHS [N01 AG012112, N01-AG12112, R01 AG011703, R01 AG027012, R01 AG11703-01A1]; NIAID NIH HHS [R01 AI41956, R01 AI041956] NR 40 TC 13 Z9 13 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0163-4984 J9 BIOL TRACE ELEM RES JI Biol. Trace Elem. Res. PD AUG PY 2006 VL 112 IS 2 BP 97 EP 107 DI 10.1385/BTER:112:2:97 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 203KL UT WOS:000248973400001 PM 17028376 ER PT J AU Proschan, MA Hunsberger, SA AF Proschan, Michael A. Hunsberger, Sally A. TI Combining treatment selection and definitive testing SO BIOMETRICAL JOURNAL LA English DT Editorial Material DE adaptive design; adaptive hierarchical test; adaptive methods; comparisons with control; conditional error function; critical value; dropping treatments; Dunnett's procedure; interim look; many-one comparison; multiple comparisons; optimal design; reallocation of sample size; safety data; safety monitoring rules; treatment selection AB This is a discussion of the following two papers appearing in this special issue on adaptive designs: 'An adaptive hierarchical test procedure for selecting safe and efficient treatments' by Franz Konig, Peter Bauer and Wertier Brannath, and 'An adaptive two-stage design with treatment selection using the conditional error function approach' by Jixian Wang. C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NIAID, Biostat Res Branch, 6700A Rockledge Dr, Bethesda, MD 20892 USA. EM proscham@niaid.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2006 VL 48 IS 4 BP 690 EP 692 DI 10.1002/bimj.200610247 PG 3 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 080TE UT WOS:000240270500026 PM 16972721 ER PT J AU Vexler, A Liu, AY Schisterman, EE AF Vexler, Albert Liu, Aiyi Schisterman, Enrique E. TI Efficient design and analysis of biospecimens with measurements subject to detection limit SO BIOMETRICAL JOURNAL LA English DT Article DE detection limit; information matrix; pooling design; random sampling; truncated/censored data ID DEFECTIVE MEMBERS; LARGE POPULATIONS; PARAMETERS; SAMPLES; DISTRIBUTIONS; ESTIMATORS AB Pooling biospecimens is a well accepted sampling strategy in biomedical research to reduce study cost of measuring biomarkers, and has been shown in the case of normally distributed data to yield more efficient estimation. In this paper we examine the efficiency of pooling, in the context of information matrix related to estimators of unknown parameters, when the biospecimens being pooled yield incomplete observations due to the instruments' limit of detection. Our investigation of three sampling strategies shows that, for a range of values of the detection limit, pooling is the most efficient sampling procedure. For certain other values of the detection limit, pooling can perform poorly. C1 DHHS, Div Epidemiol Stat & Prevent Res, Natl Inst Child Hlth & Human Dev, NIH, Rockville, MD 20852 USA. RP Vexler, A (reprint author), DHHS, Div Epidemiol Stat & Prevent Res, Natl Inst Child Hlth & Human Dev, NIH, 6100 Execut Blvd, Rockville, MD 20852 USA. EM vexlera@mail.nih.gov OI Liu, Aiyi/0000-0002-6618-5082; Schisterman, Enrique/0000-0003-3757-641X NR 17 TC 16 Z9 16 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD AUG PY 2006 VL 48 IS 5 BP 780 EP 791 DI 10.1002/bimj.200610266 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 099YD UT WOS:000241632800004 PM 17094343 ER PT J AU Zheng, J Ma, BY Tsai, CJ Nussinov, R AF Zheng, Jie Ma, Buyong Tsai, Chung-Jung Nussinov, Ruth TI Structural stability and dynamics of an amyloid-forming peptide GNNQQNY from the yeast prion sup-35 SO BIOPHYSICAL JOURNAL LA English DT Article ID BETA-PROTEIN; FIBRIL FORMATION; COMMON MECHANISM; HUMAN CALCITONIN; MOLECULAR-BASIS; AGGREGATION; SIMULATIONS; OLIGOMERIZATION; SUP35; REORGANIZATION AB A seven amino acid yeast prion sup-35 fragment (GNNQQNY) forms amyloid fibrils. The availability of its detailed atomic oligomeric structure makes it a good model for studying the early stage of aggregation. Here we perform long all-atom explicit solvent molecular simulations of various sizes and arrangements of oligomer seeds of the wild-type and its mutants to study its stability and dynamics. Previous studies have suggested that the early stage rate-limiting step of oligomer formation occurs in high-order oligomers. Our simulations show that with the increase in the number of strands even from a dimer to a trimer, oligomer stability increases dramatically. This suggests that the minimal nucleus seed for GNNQQNY fibril formation could be small and is likely three or four peptides, in agreement with experiment, and that higher-order oligomers do not dissociate quickly since they have small diffusion coefficients and thus slow kinetics. Further, for the hydrophilic polar GNNQQNY, there are no hydrogen bonds and no hydrophobic interactions between adjacent beta-sheets. Simulations suggest that within the sheet, the driving forces to associate and stabilize are interstrand backbone-backbone and side chain-side chain hydrogen bonds, whereas between the sheets, shape-complementary by the dry polar steric zipper via the side chains of Asn-2, Gln-4, and Asn-6 holds the sheets together, as proposed in an earlier study. Since the polar side chains of Asn-2, Gln-4, and Asn-6 act as a hook to bind two neighboring sheets together, these geometric restraints reduce the conformational search for the correct side chain packing to a two-dimensional problem of intersheet side chain interactions. Mutant simulations show that substitution of Asn-2, Gln-4, or Asn-6 by Ala would disrupt this steric zipper, leading to unstable oligomers. C1 NCI, Ctr Canc Res, Nanobiol Program, Basic Res Program,SAIC Frederick, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Ctr Canc Res, Nanobiol Program, Basic Res Program,SAIC Frederick, 469-151 CCRNP, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011; Zheng, Jie/B-5057-2013 OI Ma, Buyong/0000-0002-7383-719X; Zheng, Jie/0000-0003-1547-3612 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 36 TC 96 Z9 98 U1 2 U2 17 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2006 VL 91 IS 3 BP 824 EP 833 DI 10.1529/biophysj.106.083246 PG 10 WC Biophysics SC Biophysics GA 064KA UT WOS:000239086800007 PM 16679374 ER PT J AU Stanley, C Rau, DC AF Stanley, Christopher Rau, Donald C. TI Preferential hydration of DNA: The magnitude and distance dependence of alcohol and polyol interactions SO BIOPHYSICAL JOURNAL LA English DT Article ID GLYCINE BETAINE; OSMOTIC-STRESS; HYDROPHOBIC INTERACTIONS; INTERMOLECULAR FORCES; UNCHARGED SOLUTES; DOUBLE HELICES; PROTEIN; EXCLUSION; SALTS; WATER AB The physical forces that underlie the exclusion of solutes from macromolecular surfaces can be probed in a similar way as the measurement of forces between macromolecules in condensed arrays using the osmotic stress technique and x-ray scattering. We report here the dependence of alcohol exclusion or, equivalently, the preferential hydration of DNA on the spacing between helices in condensed arrays. The actual forces describing exclusion are quite different from the commonly assumed steric crowding coupled with weak binding. For a set of 12 nonpolar alcohols, exclusion is due to repulsive hydration interactions with the charged DNA surface. Exclusion amplitudes do not depend simply on size, but rather on the balance between alkyl carbons and hydroxyl oxygens. Polyols are included at very close spacings. The distance dependence of polyol inclusion, however, is quite different from nonpolar alcohol exclusion, suggesting the underlying mechanism of interaction is different. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, NIST Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Rau, DC (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM raud@mail.nih.gov OI Stanley, Christopher/0000-0002-4226-7710 FU Intramural NIH HHS NR 36 TC 40 Z9 40 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD AUG PY 2006 VL 91 IS 3 BP 912 EP 920 DI 10.1529/biophysj.106.086579 PG 9 WC Biophysics SC Biophysics GA 064KA UT WOS:000239086800017 PM 16714350 ER PT J AU Schiffmann, DA Dikovskaya, D Appleton, PL Newton, IP Creager, DA Allan, C Nathke, IS Goldberg, IG AF Schiffmann, David A. Dikovskaya, Dina Appleton, Paul L. Newton, Ian P. Creager, Douglas A. Allan, Chris Nathke, Inke S. Goldberg, Ilya G. TI Open Microscopy Environment and FindSpots: integrating image informatics with quantitative multidimensional image analysis SO BIOTECHNIQUES LA English DT Article ID POLYPOSIS-COLI PROTEIN; SPINDLE CHECKPOINT; CHROMOSOME INSTABILITY; DYNAMICS; CELLS; KINETOCHORES; MECHANISMS; PARTICLES; CHROMATIN; MOVEMENT AB Biomedical research and drug development increasingly involve the extraction of quantitative data from digital microscope images, such as those obtained using fluorescence microscopy. Here, we describe a novel approach for both managing and analyzing such images. The Open Microscopy Environment (OME) is a sophisticated open-source scientific image management database that coordinates the organization, storage, and analysis of the large volumes of image data typically generated by modem imaging methods. We describe FindSpots, a powerful image-analysis package integrated in OME that will be of use to those who wish to identify and measure objects within microscope images or time-lapse movies. The algorithm used in FindSpots is in fact only one of many possible segmentation (object detection) algorithms, and the underlying data model used by OME to capture and store its results can also be used to store results from other segmentation algorithms. In this report, we illustrate how image segmentation can be achieved in OME using one such implementation of a segmentation algorithm, and how this output subsequently can be displayed graphically or processed numerically using a spreadsheet. C1 Univ Dundee, Sch Life Sci, Wellcome Trust Bioctr, Div Cell & Dev Biol, Dundee DD1 5EH, Scotland. MIT, Cambridge, MA 02139 USA. NIA, Image Informat & Computat Biol Unit, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Nathke, IS (reprint author), Univ Dundee, Sch Life Sci, Wellcome Trust Bioctr, Div Cell & Dev Biol, Dundee DD1 5EH, Scotland. EM inke@lifesci.dundee.ac.uk; igg@nih.gov RI Goldberg, Ilya/H-5307-2011; OI Goldberg, Ilya/0000-0001-8514-6110; Nathke, Inke/0000-0003-2420-4385 FU Wellcome Trust NR 34 TC 19 Z9 21 U1 0 U2 0 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD AUG PY 2006 VL 41 IS 2 BP 199 EP 208 DI 10.2144/000112224 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129PH UT WOS:000243740900029 PM 16925022 ER PT J AU Holmes, MK Erickson, K Luckenbaugh, DA Drevets, WC Bain, EE Cannon, DM Snow, J Sahakian, BJ Manji, HK Zarate, CA AF Holmes, M. Kathleen Erickson, Kristine Luckenbaugh, David A. Drevets, Wayne C. Bain, Earle E. Cannon, Dara M. Snow, Joseph Sahakian, Barabara J. Manji, Husseini K. Zarate, Carlos A. TI A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 2nd Biennial Conference of the International-Society-for-Bipolar-Disorders CY AUG 02-04, 2006 CL Edinburgh, SCOTLAND C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Cambridge, Dept Psychiat, Cambridge, England. RI Gallagher, Peter/B-8652-2009; Olivier, Patrick/B-2909-2011; Cannon, Dara/C-1323-2009 OI Olivier, Patrick/0000-0003-2841-7580; Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD AUG PY 2006 VL 8 SU 1 MA 175 BP 63 EP 63 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 065UV UT WOS:000239186300174 ER PT J AU Rozman, KK Bhatia, J Calafat, AM Chambers, C Culty, M Etzel, RA Flaws, JA Hansen, DK Hoyer, PB Jeffery, EH Kesner, JS Marty, S Thomas, JA Umbach, D AF Rozman, Karl K. Bhatia, Jatinder Calafat, Antonia M. Chambers, Christina Culty, Martine Etzel, Ruth A. Flaws, Jodi A. Hansen, Deborah K. Hoyer, Patricia B. Jeffery, Elizabeth H. Kesner, James S. Marty, Sue Thomas, John A. Umbach, David TI NTP-CERHR expert panel report on the reproductive and developmental toxicity of soy formula SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review ID HIGH-RISK INFANTS; BIRTH-WEIGHT INFANTS; MILK-BASED FORMULA; NONSPECIFIC MACROMOLECULAR ABSORPTION; CHROMATOGRAPHY-MASS SPECTROMETRY; PREMENOPAUSAL JAPANESE WOMEN; SMALL INTESTINAL BARRIER; PARTIAL WHEY HYDROLYSATE; SPRAGUE-DAWLEY RATS; SEX-HORMONE LEVELS C1 NIEHS, Res Triangle Pk, NC 27709 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Dow Chem Co USA, Toxicol Res Lab, Midland, MI 48674 USA. NIOSH, Cincinnati, OH 45226 USA. Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Univ Calif San Diego, Med Ctr, Dept Pediat, San Diego, CA 92103 USA. Univ Calif San Diego, Med Ctr, Dept Family & Prevent Med, San Diego, CA 92103 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Med Coll Georgia, Dept Pediat, Div Neonatol, Augusta, GA 30912 USA. Univ Kansas, Med Ctr, Dept Pharmacol & Toxicol, Kansas City, KS 66103 USA. RP Rozman, KK (reprint author), NIEHS, POB 12233,EC-32, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 ES999999] NR 227 TC 23 Z9 26 U1 3 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD AUG PY 2006 VL 77 IS 4 BP 280 EP 397 DI 10.1002/bdrb.20086 PG 118 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 086ZF UT WOS:000240711100004 PM 16998908 ER PT J AU Kim, HK Sierra, MD Williams, CK Gulino, AV Tosato, G AF Kim, Hyun Kyung Sierra, Maria De La Luz Williams, Cassin Kimmel Gulino, A. Virginia Tosato, Giovanna TI G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC PROGENITOR CELLS; BONE-MARROW; FACTOR-I; PERIPHERAL-BLOOD; CHEMOKINE RECEPTOR; MOLECULAR-CLONING; WHIM SYNDROME; STEM-CELLS; SDF-1 AB CXCR4 receptor expression is required for the retention of granulocyte precursors and mature neutrophils within the bone marrow, and disruption of the SDF1/CXCR4 axis in the bone marrow results in the mobilization of myeloid lineage cells to the peripheral circulation. We report that G-CSF down-regulates CXCR4 expression in bone marrow-derived murine and human myeloid lineage cells. When exposed to G-CSF, murine Gr1(+) bone marrow myelold cells display a timedependent reduction of cell-surface CXCR4 and respond poorly to SDF-1 in attachment and migration assays. Bone marrow-derived cells of nonmyeloid lineage display no change in surface CXCR4 expression upon exposure to G-CSF. Compared with controls, mice treated with G-CSF for mobilization of hematopoietic progenitor cells display reduced levels. of CXCR4 selectively in bone marrow Gri(+) myelold cells. Since bone marrow myeloid cells express G-CSF receptors and G-CSF rapidly reduces CXCR4 expression in purified Gr1(+) cells populations, these results provide evidence that GCSF acts directly on myeloid lineage cells to reduce CXCR4 expression. By downregulating CXCR4 expression in bone marrow myeloid cells and attenuating their responsiveness to SDF-1, G-CSF promotes their mobilization from the bone marrow to the peripheral blood. C1 NCI, Basic Res Lab, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Lab Med, Seoul 151, South Korea. Seoul Natl Univ, Coll Med, Inst Canc Res, Seoul 151, South Korea. RP Tosato, G (reprint author), NCI, Basic Res Lab, Canc Res Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. EM tosatog@mail.nih.gov RI Kim, Hyun Kyung/J-5449-2012 FU Intramural NIH HHS NR 49 TC 101 Z9 103 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2006 VL 108 IS 3 BP 812 EP 820 DI 10.1182/blood-10-4162 PG 9 WC Hematology SC Hematology GA 068NK UT WOS:000239381000015 PM 16537807 ER PT J AU Lee, JH Kim, YM Kim, NW Kim, JW Her, E Kim, BK Kim, JH Ryu, SH Park, JW Seo, DW Han, JW Beaven, MA Choi, WS AF Lee, Jun Ho Kim, Young Mi Kim, Nam Wook Kim, Jie Wan Her, Erk Kim, Bo Kyung Kim, Jong Hyun Ryu, Sung Ho Park, Jong Woo Seo, Dong Wan han, Jeung W. Han Beaven, Michael A. Choi, Wahn Soo TI Phosphiolipase D2 acts as an essential adaptor protein in the activation of Syk in antigen-stimulated mast cells SO BLOOD LA English DT Article ID PHOSPHOLIPASE-D ACTIVITY; LINKER REGION TYROSINES; ADP-RIBOSYLATION FACTOR; AFFINITY IGE RECEPTOR; KINASE-C; RBL-2H3 CELLS; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PHOSPHATIDYLCHOLINE HYDROLYSIS; PROTOONCOGENE PRODUCT; DEPENDENT ACTIVATION AB Mast cells are responsible for IgE-mediated allergic reactions. Phospholipase D1 (PLD1) and PLD2 regulate mast cell activation, but the mechanisms remain unclear. Here we show that PLD2 associates with and promotes activation of Syk, a key enzyme in mast cell activation. Antigen stimulation resulted in increased association and colocalization of Syk with PLD2 on the plasma membrane as indicated by coimmunoprecipitation and confocal microscopy. This association was dependent on tyrosine phosphorylation of Syk but not on PLD2 activity. In vitro, PLD2 interacted via its Phox homology (PX) domain with recombinant Syk to induce phosphorylation and activation of Syk. Furthermore, overexpression of PLD2 or catalytically inactive PLD2K758R enhanced antigen-induced phosphorylations of Syk and its downstream targets, the adaptor proteins LAT and SLP-76, while expression of a PLD2 siRNA blocked these phosphorylations. Apparently, the interaction of PLD2 with Syk is an early critical event in the activation of mast cells. C1 Konkuk Univ, Coll Med, Dept Immunol, Chungju 380701, South Korea. Konkuk Univ, Coll Med, Dept Physiol, Chungju 380701, South Korea. Duksung Womens Univ, Coll Pharm, Seoul, South Korea. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Choi, WS (reprint author), Konkuk Univ, Coll Med, Dept Immunol, Chungju 380701, South Korea. EM wahnchoi@kku.ac.kr FU Intramural NIH HHS NR 69 TC 19 Z9 21 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2006 VL 108 IS 3 BP 956 EP 964 DI 10.1182/blood-2005-10-009159 PG 9 WC Hematology SC Hematology GA 068NK UT WOS:000239381000034 PM 16861349 ER PT J AU Pesu, M Muul, L Kanno, Y O'Shea, JJ AF Pesu, Marko Muul, Linda Kanno, Yuka O'Shea, John J. TI Proprotein convertase furin is preferentially expressed in T helper 1 cells and regulates interferon gamma SO BLOOD LA English DT Article ID GENE-EXPRESSION; IL-12 RESPONSES; MICE; ACTIVATION; STAT4; PHOSPHORYLATION; INTERLEUKIN-12; INFECTION; RECEPTOR; LACKING AB Interleukin 12 (IL-12) is a major inducer of interleron gamma (IFN-gamma) and the principal mediator of T helper 1 (Th1) differentiation. To identify IL-12-regulated genes, which might contribute to Th1 differentiation and IFNG regulation, we employed microarray analysis. Surprisingly, a ubiquitously expressed proprotein convertase (PC), furin, was one of the most consistently IL-12-induced genes in T cells, and among PCs was the only one regulated by this cytokine. Furin was preferentially expressed in differentiated Th1 cells in a Stat4-dependent manner. Expression of furin enhanced IFN-gamma secretion, whereas inhibition of furin interfered with IFN-gamma production. Thus, we conclude that IL-12 induction of furin might represent a new aspect of IFN-gamma regulation and control of Th1 differentiation. C1 NIH, MIIB, NIAMSD, Bethesda, MD 20892 USA. RP Pesu, M (reprint author), NIH, MIIB, NIAMSD, Bldg 10,Rm 9N262,10 Ctr Dr, Bethesda, MD 20892 USA. EM pesum@mail.nih.gov RI Kanno, Yuka/B-5802-2013; Pesu, marko/L-6344-2013; OI Kanno, Yuka/0000-0001-5668-9319 FU Intramural NIH HHS NR 24 TC 32 Z9 32 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2006 VL 108 IS 3 BP 983 EP 985 DI 10.1182/blood-2005-09-3824 PG 3 WC Hematology SC Hematology GA 068NK UT WOS:000239381000037 PM 16627761 ER PT J AU Zhang, Z Zhang, ML Garmestani, K Talanov, VS Plascjak, PS Beck, B Goldman, C Brechbiel, MW Wadmann, TA AF Zhang, Zhuo Zhang, Meili Garmestani, Kayhan Talanov, Vladimir S. Plascjak, Paul S. Beck, Barbara Goldman, Carolyn Brechbiel, Martin W. Wadmann, Thomas A. TI Effective treatment of a murine model of adult T-cell leukemia using At-211-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25 SO BLOOD LA English DT Article ID MONOCLONAL-ANTIBODY; EFFECTIVE THERAPY; IL-2 RECEPTOR; RADIOIMMUNOTHERAPY; LYMPHOMA; XENOGRAFTS AB Adult T-cell leukemia (ATL) consists of an overabundance of T cells, which express CD25. Therapeutic efficacy of astatine-211 (At-211)-labeled murine monoclonal antibody 7G7/B6 alone and in combination with daclizumab was evaluated in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice given injections of MET-1 human T-cell leukemia cells. Daclizumab and 7G7/B6 are directed toward different epitopes of CD25. Either a single dose of 12 mu Ci (0.444 MBq) At-211-7G7/B6 per mouse given intravenously or receptor-saturating doses of daclizumab given at 100 mu g weekly for 4 weeks intravenously inhibited tumor growth as monitored by serum levels of human beta-2 microglobulin (beta 2 mu) and by prolonged survival of leukemia-bearing mice compared with the control groups (P < .001). The combination of 2 agents enhanced the antitumor effect when compared with groups treated with 12 mu Ci (0.444 MBq) of At-211-7G7/B6 (P < .05) or daclizumab alone (P < .05). The median survival duration of the PBS group was 62.6 days and 61.5 days in the radiolabeled nonspecific antibody At-211-11F11-treated group. In contrast, 91% of mice in the combination group survived through day 94. These results that demonstrate a significantly improved therapeutic efficacy by combining At-211-7G7/B6 with daclizumab support a clinical trial of this regimen in patients with ATL. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wadmann, TA (reprint author), NCI, Metab Branch, NIH, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov FU Intramural NIH HHS NR 32 TC 18 Z9 19 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2006 VL 108 IS 3 BP 1007 EP 1012 DI 10.1182/blood-2005-11-4757 PG 6 WC Hematology SC Hematology GA 068NK UT WOS:000239381000041 PM 16569769 ER PT J AU Datta, A Bellon, M Sinha-Datta, U Bazarbachi, A Lepelletier, Y Canioni, D Waldmann, TA Hermine, O Nicot, C AF Datta, Abh Bellon, Marcia Sinha-Datta, Uma Bazarbachi, Ali Lepelletier, Yves Canioni, Danielle Waldmann, Thomas A. Hermine, Olivier Nicot, Christophe TI Persistent inhibition of telomerase reprograms adult T-cell leukemia to p53-dependent senescence SO BLOOD LA English DT Article ID NF-KAPPA-B; VIRUS TYPE-1 TAX; CHRONIC LYMPHOCYTIC-LEUKEMIA; HTLV-I; TRANSCRIPTIONAL ACTIVITY; INTERFERON-ALPHA; EX-VIVO; EFFECTIVE THERAPY; GENE-EXPRESSION; SMAD PROTEINS AB The antiviral thymidine analog azidothymidine (AZT) is used to treat several virus-associated human cancers. However, to date. the mechanism of AZT action remains unclear and thus, reasons for treatment failure are unknown. Adult T-cell leukemia/lymphoma (ATL) is an aggressive malignancy of poor prognosis. Here, we report that enduring AZT treatment of T-cell leukemia virus I-infected cells, in vitro and in vivo in ATL patients, results in inhibition of telomerase activity, progressive telomere shortening, and increased p14(ARF) expression. In turn, this elicits stabilization and reactivation of the tumor suppressor p53-dependent transcription, increased expression of the cyclin-dependent kinase in ihibitor p21(Waf1), and accumulation of p27(kip1), thereby inducing cellular senescence and tumor cell death. While ATL patients carrying a wild-type p53 enter remission following treatment with AZT, those with a mutated p53 did not respond, and patients' disease relapse was associated with the selection of a tumor clone carrying mutated inactive p53. C1 Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. Univ Paris 05, Hop Necker, CNRS, Unite Mixte Rech 8603, Paris, France. NCI, NIH, Metab Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Nicot, C (reprint author), Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, 3025 Wahl Hall W, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM cnicot@kumc.edu FU NCI NIH HHS [R01 CA106258, R01CA106258] NR 61 TC 74 Z9 79 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2006 VL 108 IS 3 BP 1021 EP 1029 DI 10.1182/blood-2006-01-0067 PG 9 WC Hematology SC Hematology GA 068NK UT WOS:000239381000043 PM 16569765 ER PT J AU Landgren, O Gridley, G Fears, TR Caporaso, N AF Landgren, Ola Gridley, Gloria Fears, Thomas R. Caporaso, Neil TI Immune thrombocytopenic purpura does not exhibit a disparity in prevalence between African American and white veterans SO BLOOD LA English DT Letter ID SPLENECTOMY; PATIENT; ITP C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. RP Landgren, O (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, 6120 Execut Blvd,Bldg EPS,Room 7110, Bethesda, MD 20892 USA. EM landgreo@mail.nih.gov NR 11 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 1 PY 2006 VL 108 IS 3 BP 1111 EP 1112 DI 10.1182/blood-2006-03-010405 PG 2 WC Hematology SC Hematology GA 068NK UT WOS:000239381000061 PM 16861360 ER PT J AU Bohlhalter, S Goldfine, A Matteson, S Garraux, G Hanakawa, T Kansaku, K Wurzman, R Hallett, M AF Bohlhalter, S. Goldfine, A. Matteson, S. Garraux, G. Hanakawa, T. Kansaku, K. Wurzman, R. Hallett, M. TI Neural correlates of tic generation in Tourette syndrome: an event-related functional MRI study SO BRAIN LA English DT Article DE tic; Tourette syndrome; functional MRI; paralimbic areas ID POSITRON-EMISSION-TOMOGRAPHY; TRANSCRANIAL MAGNETIC STIMULATION; EXTERNALLY TRIGGERED MOVEMENTS; OBSESSIVE-COMPULSIVE DISORDER; SUPPLEMENTARY MOTOR CORTEX; CEREBRAL BLOOD-FLOW; VOLUNTARY MOVEMENT; ELECTRICAL-STIMULATION; HUMAN BRAIN; SYMPTOM PROVOCATION AB Little is known about the neural correlates of tics and associated urges. In the present study, we aimed to explore the neural basis of tics in patients with Tourette syndrome by using event-related functional MRI (fMRI). Ten patients (6 women, 4 men; age: mean +/- SD = 31 +/- 11.2) were studied while spontaneously exhibiting a variety of motor and vocal tics. On the basis of synchronized video/audio recordings, fMRI activities were analysed 2 s before and at tic onset irrespective of the clinical phenomenology. We identified a brain network of paralimbic areas such as anterior cingulate and insular cortex, supplementary motor area (SMA) and parietal operculum (PO) predominantly activated before tic onset (P < 0.05, corrected for multiple comparisons). In contrast, at the beginning of tic action, significant fMRI activities were found in sensorimotor areas including superior parietal lobule bilaterally and cerebellum. The results of this study indicate that paralimbic and sensory association areas are critically implicated in tic generation, similar to movements triggered internally by unpleasant sensations, as has been shown for pain or itching. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC-1430, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Garraux, Gaetan/G-9050-2011 NR 62 TC 158 Z9 162 U1 1 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2006 VL 129 BP 2029 EP 2037 DI 10.1093/brain/awl050 PN 8 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 075QP UT WOS:000239900600012 PM 16520330 ER PT J AU Gilbert, DL Wang, ZW Sallee, FR Ridel, KR Merhar, S Zhang, J Lipps, TD White, C Badreldin, N Wassermann, EM AF Gilbert, Donald L. Wang, Zhewu Sallee, Floyd R. Ridel, Keith R. Merhar, Stephanie Zhang, Jie Lipps, Tara D. White, Colin Badreldin, Nevert Wassermann, Eric M. TI Dopamine transporter genotype influences the physiological response to medication in ADHD SO BRAIN LA English DT Article DE ADHD; TMS; Tourette syndrome; children; motor cortex ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; TRANSCRANIAL MAGNETIC STIMULATION; HUMAN MOTOR CORTEX; NOREPINEPHRINE-REUPTAKE INHIBITOR; TRAIT LOCUS ANALYSIS; VARIABLE NUMBER; TOURETTES-SYNDROME; PREFRONTAL CORTEX; INTRACORTICAL EXCITABILITY AB Attention deficit hyperactivity disorder (ADHD) is a complex, multifactorial disorder characterized by physical hyperactivity and behavioural disinhibition. Short interval cortical inhibition (SICI), measured in motor cortex with transcranial magnetic stimulation, is reduced in ADHD and correlates with symptom severity. However, ADHD medication-induced changes in SICI vary widely among normal individuals and have not been well studied in children with ADHD. Therefore, we undertook this study to measure and compare effects of two ADHD medications, methylphenidate (MPH), a psychostimulant, and atomoxetine (ATX), a selective norepinephrine reuptake inhibitor, on SICI in children with ADHD. In addition, we wished to determine whether a genetic variation in the dopamine transporter (DAT1), a site of action of MPH, could influence the effects of MPH or ATX on SICI. We performed a randomized, double-blind, single-dose, crossover study comparing 0.5 mg/kg MPH with 1.0 mg/kg ATX in 16 children with ADHD, aged 8-17. Seven were homozygotes and 9 heterozygotes for the DAT1 variable number of tandem repeats 10-repeat allele. Medication and genotype effects on SICI were estimated with repeated measures, mixed model regression. We found that MPH and ATX had similar effects on SICI. However, medication effects differed significantly by DAT1 genotype [F(2,13) = 13.04, P = 0.0008]. Both MPH and ATX increased SICI in heterozygotes but not in 10-repeat homozygotes. In conclusion, MPH and ATX have similar effects on SICI in children with ADHD. A genetic variation in DAT1, previously linked to ADHD risk and MPH behavioural responses, influences the neurophysiological effects of both MPH and ATX. C1 Cincinnati Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. Cincinnati Childrens Hosp, Div Pediat, Cincinnati, OH 45229 USA. Univ Cincinnati, Vet Adm Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, Bethesda, MD USA. RP Gilbert, DL (reprint author), Cincinnati Childrens Hosp, Med Ctr, Div Neurol, ML 2015,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM d.gilbert@cchmc.org RI Gilbert, Donald/D-6443-2016 OI Gilbert, Donald/0000-0002-9245-6878 FU NINDS NIH HHS [K23 NS41920] NR 72 TC 52 Z9 53 U1 4 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD AUG PY 2006 VL 129 BP 2038 EP 2046 DI 10.1093/brain/awl147 PN 8 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 075QP UT WOS:000239900600013 PM 16760197 ER PT J AU Kulp, KS Montgomery, JL Nelson, DO Cutter, B Latham, ER Shattuck, DL Klotz, DM Bennett, LM AF Kulp, Kristen S. Montgomery, Jennifer L. Nelson, David O. Cutter, Beth Latham, E. Ray Shattuck, David L. Klotz, Diane M. Bennett, L. Michelle TI Essiac (R) and Flor-Essence (R) herbal tonics stimulate the in vitro growth of human breast cancer cells SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE cell growth stimulation; complementary and alternative medicine; Essiac (R) Herbal Tonic; estrogen receptor; Flor-Essence (R) Herbal Tonic; human breast cancer cells ID ESTROGEN-RECEPTOR-ALPHA; SPRAGUE-DAWLEY RATS; ANTIESTROGEN ICI-182780; ENVIRONMENTAL CHEMICALS; ENDOCRINE DISRUPTORS; MAMMARY-GLAND; RED-CLOVER; E-SCREEN; GENISTEIN; COMPLEMENTARY AB Background. People diagnosed with cancer often self-administer complementary and alternative medicines (CAMs) to supplement their conventional treatments, improve health, or prevent recurrence. Flor-Essence (R) and Essiac (R) Herbal Tonics are commercially available complex mixtures of herbal extracts sold as dietary supplements and used by cancer patients based on anecdotal evidence that they can treat or prevent disease. In this study, we evaluated Flor-Essence (R) and Essiac (R) for their effects on the growth of human tumor cells in culture. Methods. The effect of Flor-Essence (R) and Essiac (R) herbal tonics on cell proliferation was tested in MCF-7, MDA-MB-436, MDA-MB-231, and T47D cancer cells isolated from human breast tumors. Estrogen receptor (ER) dependent activation of a luciferase reporter construct was tested in MCF-7 cells. Specific binding to the ER was tested using an ICI 182,780 competition assay. Results. Flor-Essence (R) and Essiac (R) herbal tonics at 1%, 2%, 4% and 8% stimulated cell proliferation relative to untreated controls in both estrogen receptor positive (MCF-7 and T47D) and estrogen receptor negative (MDA-MB-231 and MDA-MB-436) cell lines. Exposure to the tonics also produced a dose-dependent increase in ER dependent luciferase activity in MCF-7 cells. A 10(-7) M concentration of ICI 182,780 inhibited the induction of ER dependent luciferase activity by Flor-Essence (R) and Essiac (R), but did not affect cell proliferation. Conclusion. Flor-Essence (R) and Essiac (R) Herbal Tonics can stimulate the growth of human breast cancer cells through ER mediated as well as ER independent mechanisms of action. C1 Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Res Triangle Pk, NC USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. RP Kulp, KS (reprint author), Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA USA. EM Kulp2@llnl.gov FU NCCIH NIH HHS [R21AT001730-02]; NIEHS NIH HHS [K22 ES00322-01] NR 63 TC 11 Z9 12 U1 2 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD AUG PY 2006 VL 98 IS 3 BP 249 EP 259 DI 10.1007/s10549-005-9156-x PG 11 WC Oncology SC Oncology GA 071IM UT WOS:000239593800002 PM 16541326 ER PT J AU Gerecitano, J Goy, A Wright, J MacGregor-Cortelli, B Neylon, E Gonen, M Esseltine, D Boral, A Schenkein, D Busam, K Teruya-Feldstein, J Sachs, D O'Connor, OA AF Gerecitano, John Goy, Andre Wright, John MacGregor-Cortelli, Barbara Neylon, Ellen Gonen, Mithat Esseltine, Dixie Boral, Anthony Schenkein, David Busam, Klaus Teruya-Feldstein, Julie Sachs, Dana O'Connor, Owen A. TI Drug-induced cutaneous vasculitis in patients with non-Hodgkin lymphoma treated with the novel proteasome inhibitor bortezomib: a possible surrogate marker of response? SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE cutaneous vasculitis; proteasome inhibitor; bortezomib; lymphoma; rash ID PHASE-I TRIAL; MYELOMA; CANCER; MALIGNANCIES; ERLOTINIB; RECURRENT; NECK; HEAD AB Bortezomib is the first proteasome inhibitor to be approved for use in haematological malignancies. Although a rash has been described as a common adverse event associated with the drug, it has not been well characterised. Based on three phase II studies of bortezomib in patients with non-Hodgkin lymphoma (140 assessable patients), we identified 26 patients who developed a unique erythematous maculopapular rash during treatment, six of whom underwent cutaneous biopsy. Punch biopsy in six patients revealed a perivascular lymphocytic infiltrate without evidence of lymphoma, consistent with a non-necrotising cutaneous vasculitis. The combined overall response rate was 41%. The response in the 26 patients who developed a rash was 73%, compared with 33% in patients who did not. The odds ratio for response given the development of a rash was 4.6 (95% CI, 1.7-12.4, P = 0.001). This is the first report to characterise a vasculitic rash associated with bortezomib, and to show a relationship between development of the rash and response to treatment. Unlike classic hypersensitivity type reactions, this vasculitic rash may not necessarily prompt cessation of drug. In fact, the development of an isolated cutaneous vasculitis may portend a better clinical response to bortezomib in some patients. C1 Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Lymphoma & Dev Chemotherapy Serv, New York, NY 10021 USA. Univ Hackensack, Med Ctr, Dept Med, Hackensack, NJ USA. NCI, Canc Therapeut & Evaluat Program, Bethesda, MD USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY USA. Millennium Pharmaceut Inc, Cambridge, MA USA. Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Dept Dermatol, New York, NY 10021 USA. RP O'Connor, OA (reprint author), Cornell Univ, Med Ctr, Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. EM oconnoro@mskcc.org RI Gonen, Mithat/E-4826-2012 FU NCI NIH HHS [T32 CA 09207, U01 CA 69913] NR 19 TC 34 Z9 35 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD AUG PY 2006 VL 134 IS 4 BP 391 EP 398 DI 10.1111/j.1365-2141.2006.06201.x PG 8 WC Hematology SC Hematology GA 064TI UT WOS:000239111600004 PM 16882131 ER PT J AU Post, RM Altshuler, LL Leverich, GS Frye, MA Nolen, WA Kupka, RW Suppes, T McElroy, S Keck, PE Denicoff, KD Grunze, H Kitchen, CMR Mintz, J AF Post, R. M. Altshuler, L. L. Leverich, G. S. Frye, M. A. Nolen, W. A. Kupka, R. W. Suppes, T. McElroy, S. Keck, P. E. Denicoff, K. D. Grunze, H. Kitchen, C. M. R. Mintz, J. TI Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion and sertraline SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID DOUBLE-BLIND; ANTIDEPRESSANT DISCONTINUATION; SYMPTOMATOLOGY IDS; NUCLEUS-ACCUMBENS; NATURAL-HISTORY; DISORDER; NETWORK; 1-YEAR; IMIPRAMINE; TRIAL AB Background: Few studies have examined the relative risks of switching into hypomania or mania associated with second-generation antidepressant drugs in bipolar depression. Aims: To examine the relative acute effects of bupropion, sertraline and venlafaxine as adjuncts to mood stabilisers. Method: In a 10-week trial, participants receiving out-patient treatment for bipolar disorder (stratified for rapid cycling) were randomly treated with a flexible dose of one of the antidepressants, or their respective matching placebos, as adjuncts to mood stabilisers. Results: A total of 174 adults with bipolar disorder 1, 11 or not otherwise specified, currently in the depressed phase, were included. All three antidepressants were associated with a similar range of acute response (49-53%) and remission (34-41%). There was a significantly increased risk of switches into hypomania or mania in participants treated with venlafaxine compared with bupropion or sertraline. Conclusions: More caution appears indicated in the use of venlafaxine rather than bupropion or sertraline in the adjunctive treatment of bipolar depression, especially if there is a prior history of rapid cycling. Declaration of interest: None. C1 NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. Univ Groningen Hosp, Groningen, Netherlands. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Univ Munich, Munich, Germany. Univ Calif Los Angeles, Sch Publ Hlth, Dept Biostat, Los Angeles, CA 90024 USA. RP Post, RM (reprint author), Bldg 10,Room 3S239,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. EM postr@mail.nih.gov RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 NR 37 TC 195 Z9 201 U1 1 U2 6 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD AUG PY 2006 VL 189 BP 124 EP 131 PG 8 WC Psychiatry SC Psychiatry GA 074UH UT WOS:000239836800006 PM 16880481 ER PT J AU Farhat, GN Strotmeyer, ES Newman, AB Sutton-Tyrrell, K Bauer, DC Harris, T Johnson, KC Taaffe, DR Cauley, JA AF Farhat, G. N. Strotmeyer, E. S. Newman, A. B. Sutton-Tyrrell, K. Bauer, D. C. Harris, T. Johnson, K. C. Taaffe, D. R. Cauley, J. A. CA Hlth ABC Study TI Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: The health, aging, and body composition study SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE volumetric bone mineral density; areal bone mineral density; cardiovascular disease; subclinical peripheral arterial disease; inflammatory cytokine ID HUMAN ATHEROSCLEROTIC PLAQUES; PERIPHERAL ARTERIAL-DISEASE; AORTIC CALCIFICATION; POSTMENOPAUSAL WOMEN; OSTEOPOROTIC FRACTURES; ELDERLY-WOMEN; INFLAMMATORY MARKERS; GENDER-DIFFERENCES; US ADULTS; MORTALITY AB The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index < 0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10-1.63; ORtrabecular = 1.25, 95% CI 1.02-1.53; ORcortical = 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Queensland, Sch Human Movement Studies, Brisbane, Qld 4072, Australia. RP Farhat, GN (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St,127 Parran Hall, Pittsburgh, PA 15261 USA. EM farhatg@edc.pitt.edu RI Strotmeyer, Elsa/F-3015-2014; Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Strotmeyer, Elsa/0000-0002-4093-6036 FU Intramural NIH HHS; NIA NIH HHS [5-T32-AG00181, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 57 TC 56 Z9 63 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X EI 1432-0827 J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD AUG PY 2006 VL 79 IS 2 BP 102 EP 111 DI 10.1007/s00223-006-0052-0 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 078JC UT WOS:000240097900005 PM 16927045 ER PT J AU Sharifi, N Kawasaki, BI Hurt, EM Farrar, WL AF Sharifi, Nima Kawasaki, Brian I. Hurt, Elaine M. Farrar, William L. TI Stem cells in prostate cancer - Resolving the castrate-resistant conundrum and implications for hormonal therapy SO CANCER BIOLOGY & THERAPY LA English DT Review DE prostate cancer; androgen deprivation therapy; androgen receptor; stem cells; castrate-resistance; steroid hormone; cd44 ID ANDROGEN-RECEPTOR; PROSPECTIVE IDENTIFICATION; GENE AMPLIFICATION; CONTROLLED-TRIAL; DIFFERENTIATION; SUPPRESSION; EXPRESSION; BIOLOGY; PROLIFERATION; MITOXANTRONE AB Androgen deprivation therapy (ADT) is initial systemic therapy for advanced prostate cancer and is used as an adjuvant to local therapy for high-risk disease, but responses in advanced disease are transient. Prostate cancer stem cells are a small fraction of tumor cells that give rise to malignant cells. Initial or acquired stem cell resistance to castration must therefore underlie castrate-resistant prostate cancer. We sought to review the evidence on cancer stem cells and androgen deprivation therapy to determine if prostate cancer stem cell resistance occurs from the outset, or if it is an acquired resistance. Prostate cancer stem cells do not express androgen receptor (AR) and hence should not be directly responsive to androgen deprivation therapy. However, castrate-resistant tumors that are derived from stem cells, have molecular changes such as amplification of the androgen receptor gene, or other genetic changes resulting in gain-of function changes in AR, implying an acquired resistance to androgen deprivation. The origins of castrate-resistant tumors, with Mechanisms such as androgen receptor gene amplification from androgen receptor negative prostate cancer stem cells, is an apparent conundrum. Insight into how this occurs may lead to new treatments that overcome or delay castrate-resistance. Herein, we review the evidence on cancer stem cells, the benefits of ADT, the biological basis of response to ADT, and mechanisms of castrate-resistance. We also explore the apparent conundrum of why AR-negative prostate cancer stem cells can give rise to castrate-resistant prostate cancer. We propose possible explanations that may resolve this conundrum and discuss implications for hormonal therapy. C1 NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Farrar, WL (reprint author), NCI, Cytokine Mol Mech Sect, Lab Canc Prevent, Bldg 560,Room 21-81, Frederick, MD 21702 USA. EM forrar@ncifarf.gov NR 51 TC 25 Z9 26 U1 0 U2 5 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD AUG PY 2006 VL 5 IS 8 BP 901 EP 906 PG 6 WC Oncology SC Oncology GA 110SU UT WOS:000242400700006 PM 16855379 ER PT J AU Sion, AM Figg, WD AF Sion, Amy M. Figg, William D. TI Lysyl oxidase (LOX) and hypoxia-induced metastases SO CANCER BIOLOGY & THERAPY LA English DT Article DE LOX; hypoxia; adhesion; invasion; metastases; HIF ID CANCER; CELL AB Angiogenesis is a critical process in the transition of tumors from a localized, primary site to a distant site of metastases. Hypoxic conditions within the tumor mass lead to the activation of signalling pathways which initiate tumor cell invasion, migration, adhesion and subsequent angiogenesis. Several key molecular players in hypoxia-induced tumor progression are well-described, e.g., hypoxia-inducible factor-1 (HIF-1) and angiopoietin-2; however, drug development aimed at suppressing individual members of this signalling cascade has proven to be challenging. The article by Erler et al. published in Nature (Vol. 440, April 2006) identifies lysyl oxidase (LOX) as an essential enzyme for hypoxia -induced metastases. This Journal Club reviews the findings presented by Erler and colleagues and briefly discusses the implications of LOX in cancer. C1 NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Med Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 12 TC 9 Z9 9 U1 1 U2 9 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD AUG PY 2006 VL 5 IS 8 BP 909 EP 911 PG 3 WC Oncology SC Oncology GA 110SU UT WOS:000242400700008 PM 16969095 ER PT J AU Kelly, MP Lee, FT Smyth, FE Brechbiel, MW Scott, AM AF Kelly, M. P. Lee, F. T. Smyth, F. E. Brechbiel, M. W. Scott, A. M. TI Radioimmunotherapy with alpha particle emitting (BI)-B-213-CHX-A ''-DTPA-hu3S193 SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Meeting Abstract CT 11th Conference on Cancer Therapy with Antibodies and Immunoconjugates CY OCT 12-14, 2006 CL Parsippany, NJ SP Ctr Mol Med & Immunol, Garden State Canc Ctr C1 Austin Hosp, Tumour Targeting Program, Ludwig Inst Canc Res, Heidelberg, Vic 3084, Australia. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD AUG PY 2006 VL 21 IS 4 MA 33 BP 393 EP 393 PG 1 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 089SB UT WOS:000240899900042 ER PT J AU Milenic, DE Garmestani, K Brady, ED Flynn, J Albert, PS Abdulla, A Brechbiel, MW AF Milenic, D. E. Garmestani, K. Brady, E. D. Flynn, J. Albert, P. S. Abdulla, A. Brechbiel, M. W. TI Radioinimunotherapy of intraperitoneal disseminated disease: An update on herceptin as a targeting agent for alpha-particle radiation SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Meeting Abstract CT 11th Conference on Cancer Therapy with Antibodies and Immunoconjugates CY OCT 12-14, 2006 CL Parsippany, NJ SP Ctr Mol Med & Immunol, Garden State Canc Ctr C1 NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD AUG PY 2006 VL 21 IS 4 MA 43 BP 397 EP 397 PG 1 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 089SB UT WOS:000240899900052 ER PT J AU Koralek, DO Peters, U Andriole, G Reding, D Kirsh, V Subar, A Schatzkin, A Hayes, R Leitzmann, MF AF Koralek, DO Peters, U Andriole, G Reding, D Kirsh, V Subar, A Schatzkin, A Hayes, R Leitzmann, MF TI A prospective study of dietary alpha-linolenic acid and the risk of prostate cancer (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE prostatic neoplasms; alpha-linolenic acid; epidemiology; cohort studies ID POLYUNSATURATED FATTY-ACIDS; FOOD FREQUENCY QUESTIONNAIRES; DOCOSAHEXAENOIC ACID; ADIPOSE-TISSUE; ENERGY; SERUM; CONSUMPTION; CARCINOMA; OMEGA-3; GROWTH AB Background Alpha-linolenic acid (ALA) is the most common omega-3 fatty acid in the Western diet. The relation of dietary intake of ALA to prostate cancer risk remains unresolved. Objective We prospectively evaluated total ALA and ALA from specific food sources including animal, fish, and plant sources in relation to prostate cancer risk. Design A cohort of 29,592 male participants (age 55-74 years) in the screening arm of the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial was followed for an average of 5.1 years. Results We ascertained 1,898 cases of total prostate cancer, of which 1,631 were organ-confined cases (stage T1b to T3a and N0M0) and 285 were advanced stage cases (stage >= T3b, N1, or M1). We found no association between total ALA intake and overall prostate cancer (multivariate RR comparing extreme quintiles=0.94; 95% CI=0.81-1.09; P for trend=0.76). The corresponding RRs for organ-confined and advanced prostate cancer were 0.94 (95% CI=0.80-1.10; P for trend=0.80) and 0.83 (95% CI=0.58-1.19; P for trend=0.34), respectively. In addition, no relations were observed between ALA intake from any specific food source and the risks of total, organ-confined, or advanced prostate cancer. ALA intake also showed no association with low grade (Gleason sum < 7; 1,221 cases) tumors (P for trend=0.23) or high grade (Gleason sum >= 7; n=677 cases) tumors (P for trend=0.26). Conclusions In this prospective study of predominantly Caucasian men who were screened annually for newly incident prostate cancer, dietary intake of total ALA and ALA from specific food sources was not associated with risk of total prostate cancer or prostate tumors that were defined by stage and grade. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. Marshfield Med Res & Educ Fdn, Marshfield, WI USA. NCI, Div Canc Control & Populat Sci, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Koralek, DO (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM dkoralek@unc.edu NR 50 TC 30 Z9 30 U1 0 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD AUG PY 2006 VL 17 IS 6 BP 783 EP 791 DI 10.1007/s10552-006-0014-x PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 053XR UT WOS:000238340000004 PM 16783606 ER PT J AU Budhu, A Forgues, M Ye, QH Jia, HL He, P Zanetti, KA Kammula, US Chen, YD Qin, LX Tang, ZY Wang, XW AF Budhu, Anuradha Forgues, Marshonna Ye, Qing-Hai Jia, Hu-Liong He, Ping Zanetti, Krista A. Kammula, Udai S. Chen, Yidong Qin, Lun-Xiu Tang, Zhao-You Wang, Xin Wei TI Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a unique immune response signature of the liver microenvironment SO CANCER CELL LA English DT Article ID GENE-EXPRESSION; MOLECULAR SIGNATURE; CANCER; CELLS; MACROPHAGES; PROGRESSION; SURVIVAL; VIRUS; INFLAMMATION; DISEASE AB Hepatocellular carcinoma (HCC) is an aggressive malignancy mainly due to metastases or postsurgical recurrence. We postulate that metastases are influenced by the liver microenvironment. Here, we show that a unique inflammation/immune response-related signature is associated with noncancerous hepatic tissues from metastatic HCC patients. This signature is principally different from that of the tumor. A global Th1/Th2-like cytokine shift in the venous metastasis-associated liver microenvironment coincides with elevated expression of macrophage colony-stimulating factor (CSF1). Moreover, a refined 17 gene signature was validated as a superior predictor of HCC venous metastases in an independent cohort, when compared to other clinical prognostic parameters. We suggest that a predominant humoral cytokine profile occurs in the metastatic liver milieu and that a shift toward anti-inflammatory/immune-suppressive responses may promote HCC metastases. C1 NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Fudan Univ, Liver Canc Inst, Shanghai 200032, Peoples R China. Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NCI, Mol Genet & Carcinogenesis Sect, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Canc Genet Lab, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Tang, ZY (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM zytang8@yahoo.com.cn; xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS NR 40 TC 367 Z9 393 U1 2 U2 39 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2006 VL 10 IS 2 BP 99 EP 111 DI 10.1016/j.ccr.2006.06.016 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 075NH UT WOS:000239891300005 PM 16904609 ER PT J AU Sodhi, A Chaisuparat, R Hu, JD Ramsdell, AK Manning, BD Sausville, EA Sawai, ET Molinolo, A Gutkind, JS Montaner, S AF Sodhi, Akrit Chaisuparat, Risa Hu, Jiadi Ramsdell, Amanda K. Manning, Brendan D. Sausville, Edward A. Sawai, Earl T. Molinolo, Alfredo Silvio Gutkind, J. Montaner, Silvia TI The TSC2/mTOR pathway drives endothelial cell transformation induced by the Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor SO CANCER CELL LA English DT Article ID NF-KAPPA-B; PHOSPHOINOSITIDE 3-KINASE/AKT PATHWAY; COMPLEX GENE-PRODUCTS; MAMMALIAN TARGET; CHEMOKINE RECEPTOR; HUMAN CANCER; GROWTH-FACTOR; MTOR; AKT; KINASE AB The Kaposi's sarcoma-associated herpesvirus (KSHV), the infectious causative agent of Kaposi's sarcoma (KS), encodes a G protein-coupled receptor (vGPCR) implicated in the initiation of KS. Here we demonstrate that Kaposils sarcomagenesis involves stimulation of tuberin (TSC2) phosphorylation by vGPCR, promoting the activation of mTOR through both direct and paracrine mechanisms. Pharmacologic inhibition of mTOR with rapamycin prevented vGPCR sarcomagenesis, while overactivation of this pathway was sufficient to render endothelial cells oncogenic. Moreover, mice haploinsufficient for TSC2 are predisposed to vascular sarcomas remarkably similar to KS. Collectively, these results implicate mTOR in KS initiation and suggest that the sarcomagenic potential of KSHV may be a direct consequence of the profound sensitivity of endothelial cells to vGPCR dysregulation of the TSC2/mTOR pathway. C1 Univ Maryland, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. Natl Inst Dental & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Comparat Pathol, Davis, CA 95616 USA. Harvard Univ, Dept Genet & Complex Dis, Boston, MA 02115 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Montaner, S (reprint author), Univ Maryland, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. EM smontaner@umaryland.edu RI Gutkind, J. Silvio/A-1053-2009 FU NCI NIH HHS [R01 CA122617, R01 CA122617-01] NR 65 TC 116 Z9 122 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD AUG PY 2006 VL 10 IS 2 BP 133 EP 143 DI 10.1016/j.ccr.2006.05.026 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 075NH UT WOS:000239891300008 PM 16904612 ER PT J AU Rosenberg, L Boggs, D Wise, LA Palmer, JR Roltsch, MH Makambi, KH Adams-Campbe, LL AF Rosenberg, Lynn Boggs, Deborah Wise, Lauren A. Palmer, Julie R. Roltsch, Mark H. Makambi, Kepher H. Adams-Campbe, Lucile L. TI A follow-up study of physical activity and incidence of colorectal polyps in African-American women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; HYPERPLASTIC POLYPS; RISK-FACTORS; ADENOMATOUS POLYPS; UNITED-STATES; ENERGY-INTAKE; LARGE-BOWEL; OBESITY; COLON; QUESTIONNAIRES AB Background: Physical activity is associated with a reduced risk of colon cancer, but the effect of activity on colorectal adenomas, which are precursors to colon cancer, is uncertain. The influence of physical activity on colorectal adenomas among African-American women is of particular interest because African-American women have an increased risk of colon cancer relative to other U.S. women. Methods: We prospectively assessed the relation of physical activity to the incidence of colorectal polyps among African-American women. We followed 45,400 women in the Black Women's Health Study from 1997 to 2003. Data were obtained by biennial mailed questionnaires. During 287,029 person-years of follow-up, 1,390 women reported having been diagnosed with colorectal polyps. A review of medical records of 58 women who reported colorectal polyps indicated that 59% had adenomas and 41% had hyperplastic polyps. We converted hours per week of vigorous exercise and hours per week of walking to metabolic equivalent (MET)-hours. We estimated incidence rate ratios with Cox proportional hazard models, controlling for age, body mass index, smoking, family history of colorectal cancer, and education. Results: For total MET-hours/wk spent in walking and vigorous exercise, the incidence rate ratio decreased from 0.94 for < 5 MET-hours/wk to 0.72 for >= 40 MET-hours/wk (P-trend = 0.01). The inverse association was apparent among most subgroups examined, including women who may be at higher risk of colorectal adenomas because of being obese. Conclusions: Increased physical activity is associated with a reduced incidence of colorectal polyps among African-American women. C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Howard Univ, Ctr Canc, Washington, DC 20059 USA. RP Rosenberg, L (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM lrosenberg@slone.bu.edu RI Abnet, Christian/C-4111-2015; OI Abnet, Christian/0000-0002-3008-7843; Palmer, Julie/0000-0002-6534-335X; Wise, Lauren/0000-0003-2138-3752 FU NCI NIH HHS [CA58420] NR 30 TC 14 Z9 17 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1438 EP 1442 DI 10.1158/1055-9965.EPI-06-0079 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500003 PM 16896029 ER PT J AU Foster, MC Kleinerman, RA Abramson, DH Seddon, JM Tarone, RE Tucker, MA AF Foster, Meredith C. Kleinerman, Ruth A. Abramson, David H. Seddon, Johanna M. Tarone, Robert E. Tucker, Margaret A. TI Tobacco use in adult long-term survivors of retinoblastoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHILDHOOD-CANCER SURVIVORS; FOLLOW-UP; CIGARETTE-SMOKING; LUNG-CANCER; RISK; BEHAVIORS; AGE AB A significant risk of lung cancer was identified among hereditary, but not nonhereditary, retinoblastoma (Rb) patients. Tobacco use was investigated to determine whether differences in smoking prevalence might explain the lung cancer excess and to characterize smoking patterns in adult survivors of Rb. Subjects were 441 hereditary and 395 nonhereditary 1-year survivors of Rb, age >= 18 years, who responded to a telephone survey about current health behavior, including tobacco use. Response rates were 76% for hereditary and 73% for nonhereditary survivors. We compared patterns and predictors of current tobacco use among hereditary and nonhereditary survivors with other childhood cancer survivor studies and the U.S. population. Hereditary Rb survivors currently smoke cigarettes significantly less frequently than nonhereditary survivors (16.8% versus 24.3%), although among current smokers, age at smoking initiation (17 years old) and average cigarettes (1.5 packs) smoked daily are similar. Predictors of current and ever cigarette smoking include nonhereditary Rb, older age, being female, less education, and use of other tobacco products. Rb survivors smoke cigarettes significantly less than the U.S. population (rate ratio, 0.63; 95% confidence interval, 0.5-0.8 for males; rate ratio, 0.75; 95% confidence interval, 0.6-0.9 for females), but Rb survivors have comparable smoking rates with other childhood cancer survivors. Smoking did not account for the increased risk of lung cancer among hereditary Rb patients, and this may point to an enhanced sensitivity to the carcinogenic effects of tobacco. Adult survivors of Rb should be encouraged to stop smoking. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Int Epidemiol Inst, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, Ophthalm Oncol Serv, New York, NY 10021 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kleinerman, RA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS 7044,6120 Execut Blvd, Rockville, MD 20852 USA. EM kleinerr@mail.nih.gov RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 FU Intramural NIH HHS NR 24 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1464 EP 1468 DI 10.1158/1055-9965.EPI-05-0783 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500007 PM 16896033 ER PT J AU Marshall, JR Sakr, W Wood, D Berry, D Tangen, C Parker, F Thompson, I Lippman, SM Lieberman, R Alberts, D Jarrard, D Coltman, C Greenwald, P Minasian, L Crawford, ED AF Marshall, James R. Sakr, Wael Wood, David Berry, Donna Tangen, Catherine Parker, Felicia Thompson, Ian Lippman, Scott M. Lieberman, Ronald Alberts, David Jarrard, David Coltman, Charles Greenwald, Peter Minasian, Lori Crawford, E. David TI Design and progress of a trial of selenium to prevent prostate cancer among men with high-grade prostatic intraepithelial neoplasia SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PREDIAGNOSTIC SERUM SELENIUM; MONOCLONAL-ANTIBODY KI-67; SUBSEQUENT RISK; BREAST-CANCER; TOENAIL SELENIUM; ALPHA-TOCOPHEROL; LUNG-CANCER; NUTRITIONAL PREVENTION; SEROLOGIC PRECURSORS; MALIGNANT-MELANOMA AB High-grade prostatic intraepithelial neoplasia (HGPIN) is generally regarded as a premalignant lesion that progresses toward prostate cancer. In light of the significant sequelae of prostate cancer treatment, prevention is desirable, and men with HGPIN would be suitable, high-risk subjects. There is in vitro, in vivo, epidemiologic, and human experimental evidence that selenium supplementation may protect against prostate cancer. This article introduces the rationale for, and progress to date, of a double-blind, randomized, placebo-controlled trial of selenium supplementation (200 mu g/d in the form of selenomethionine), to prevent the development of prostate cancer among men with HGPIN. The trial, Southwest Oncology Group Protocol 9917, funded by a National Cancer Institute program supporting pivotal prevention trials has registered 537 patients and has randomized > 380 to date. Subject accrual is expected to be completed by the fall of 2006, with trial completion in 2009. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Wayne State Univ, Detroit, MI USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Univ Wisconsin, Madison, WI USA. Canc Therapy & Res Ctr S Texas, San Antonio, TX 78229 USA. Univ Colorado, Hlth Sci Ctr, Aurora, CO USA. RP Marshall, JR (reprint author), Roswell Pk Canc Inst, Buffalo, NY 14263 USA. EM james.marshall@roswellpark.org NR 67 TC 28 Z9 28 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1479 EP 1484 DI 10.1158/1055-9965.EPI-05-0585 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500010 PM 16896036 ER PT J AU Palmer, JR Wise, LA Hatch, EE Troisi, R Titus-Ernstoff, L Strohsnitter, W Kaufman, R Herbst, AL Noller, KL Hyer, M Hoover, RN AF Palmer, Julie R. Wise, Lauren A. Hatch, Elizabeth E. Troisi, Rebecca Titus-Ernstoff, Linda Strohsnitter, William Kaufman, Raymond Herbst, Arthur L. Noller, Kenneth L. Hyer, Marianne Hoover, Robert N. TI Prenatal diethylstilbestrol exposure and risk of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BIRTH-WEIGHT; UNITED-STATES; YOUNG-WOMEN; IN-UTERO; ANDROGEN CONCENTRATIONS; POSTMENOPAUSAL WOMEN; PREGNANCY ESTRIOL; MAMMARY-GLAND; FOLLOW-UP; ESTROGEN AB It has been hypothesized that breast cancer risk is influenced by prenatal hormone levels. Diethylstilbestrol (DES), a synthetic estrogen, was widely used by pregnant women in the 1950s and 1960s. Women who took the drug have an increased risk of breast cancer, but whether risk is also increased in the daughters who were exposed in utero is less clear. We assessed the relation of prenatal DES exposure to risk of breast cancer in a cohort of DES-exposed and unexposed women followed since the 1970s by mailed questionnaires. Eighty percent of both exposed and unexposed women completed the most recent questionnaire. Self-reports of breast cancer were confirmed by pathology reports. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for prenatal DES exposure relative to no exposure. During follow-up, 102 incident cases of invasive breast cancer occurred, with 76 among DES-exposed women (98,591 person-years) and 26 among unexposed women (35,046 person-years). The overall age-adjusted IRR was 1.40 [95% confidence interval (95% CI), 0.89-2.22]. For breast cancer occurring at ages >= 40 years, the IRR was 1.91 (95% CI, 1.09-3.33) and for cancers occurring at ages >= 50 years, it was 3.00 (95% CI, 1.01-8.98). Control for calendar year, parity, age at first birth, and other factors did not alter the results. These results, from the first prospective study on the subject, suggest that women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years. The findings support the hypothesis that prenatal hormone levels influence breast cancer risk. C1 Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Informat Management Serv Inc, Rockville, MD USA. RP Palmer, JR (reprint author), Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM jpalmer@slone.bu.edu OI Palmer, Julie/0000-0002-6534-335X; Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 FU NCI NIH HHS [N01-CP-01289, N01-CP-21168, N01-CP-51017] NR 36 TC 159 Z9 165 U1 4 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1509 EP 1514 DI 10.1158/1055-9965.EPI-06-0109 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500015 PM 16896041 ER PT J AU Lam, S McWilliams, A leRiche, J MacAulay, C Wattenberg, L Szabo, E AF Lam, Stephen McWilliams, Annette leRiche, Jean MacAulay, Calum Wattenberg, Lee Szabo, Eva TI A phase I study of myo-inositol for lung cancer chernoprevention SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INOSITOL HEXAPHOSPHATE IP6; FEMALE A/J MICE; DOUBLE-BLIND; PULMONARY CARCINOGENESIS; DIETARY MYOINOSITOL; CROSSOVER TRIAL; PANIC DISORDER; IIB TRIAL; TUMORIGENESIS; CELLS AB Introduction: A phase 1, open-label, multiple dose, dose-escalation clinical study was conducted to assess the safety, tolerability, maximum tolerated dose, and potential chemopreventive effect of myo-inositol in smokers with bronchial dysplasia. Materials and Methods: Smokers between 40 and 74 years of age with 30 pack-years of smoking history and one or more sites of bronchial dysplasia were enrolled. A dose escalation study ranging from 12 to 30 g/d of myo-inositol for a month was first conducted in 16 subjects to determine the maximum tolerated dose. Ten new subjects were then enrolled to take the maximum tolerated dose for 3 months. The potential chemopreventive effect of myo-inositol was estimated by repeat autofluorescence bronchoscopy and biopsy. Results: The maximum tolerated dose was found to be 18 g/d. Side effects, when present, were mild and mainly gastrointestinal in nature. Using the regression rate of the placebo subjects from a recently completed clinical trial with the same inclusion/exclusion criteria as a comparison, a significant increase in the rate of regression of preexisting dysplastic lesions was observed (91% versus 48%; P = 0.014). A statistically significant reduction in the systolic and diastolic blood pressures by an average of 10 mm Hg was observed after taking 18 g/d of myo-inositol for a month or more. Conclusion: myo-Inositol in a daily dose of 18 g p.o. for 3 months is safe and well tolerated. The potential chemopreventive effect as well as other health benefits such as reduction in blood pressure should be investigated further. C1 British Columbia Canc Agcy, Dept Canc Imaging, Vancouver, BC V5Z 1L3, Canada. British Columbia Canc Agcy, Dept Pathol, Vancouver, BC V5Z 1L3, Canada. British Columbia Canc Agcy, Dept Canc Imaging, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Univ Minnesota, Minneapolis, MN 55455 USA. NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Lam, S (reprint author), British Columbia Canc Agcy, Dept Canc Imaging, 675 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. EM slam@bccancer.bc.ca RI MacAulay, Calum/K-1795-2016 FU NCI NIH HHS [N01-CN85188] NR 25 TC 52 Z9 53 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1526 EP 1531 DI 10.1158/1055-9965.EPI-06-0128 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500018 PM 16896044 ER PT J AU Howard, RA Dores, GM Curtis, RE Anderson, WF Travis, LB AF Howard, Regan A. Dores, Graqa M. Curtis, Rochelle E. Anderson, William F. Travis, Lois B. TI Merkel cell carcinoma and multiple primary cancers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CASE SERIES; CHEMOTHERAPY; TUMORS; SKIN AB Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin for which causative factors remain largely unknown. The site-specific risks of multiple primary cancers associated with MCC, which may provide insight into etiologic influences, have not been quantified in large population-based studies. We estimated the long-term risk of subsequent primary tumors after a first primary MCC (1,306 patients) and the risk of second primary MCC following other first primary cancers (2,048,739 patients) within 11 population-based cancer registries which report to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (1986-2002). Patients with first primary MCC were at significantly increased risk of developing a subsequent cancer [standardized incidence ratio (SIR), 1.22; 5% confidence intervals (95% CI), 1.01-1.45; observed (O) = 122], with significant excesses restricted to the first year after diagnosis (SIR, 1.71; 95% CI, 1.21-2.33; O = 39). Significantly elevated site-specific risks were observed for cancers of salivary gland (SIR, 11.55; 95% CI, 2.32-33.76; O = 3), biliary sites other than liver and gallbladder (SIR, 7.24; 95% CI, 1.46-21.16; O = 3), and non-Hodgkin lymphoma (SIR, 2.56; 95% CI, 1.23-4.71; O = 10). Nonsignificantly increased risks of 2-fold or higher were seen for chronic lymphocytic leukemia, and cancers of the small intestine and brain. A significantly increased 1.36-fold risk (95% CI, 1.19-1.55; O = 221) of MCC as a second primary malignancy was observed among patients with all other first primary cancers taken together. In particular, significant 3- to 7-fold excesses of MCC followed multiple myeloma (SIR, 3.70; 95% CI, 1.01-9.47; O = 4), chronic lymphocytic leukemia (SIR, 6.89; 95% CI, 3.77-11.57; O = 14), non-Hodgkin lymphoma (SIR, 3.37; 95% CI, 1.93-5.47; O = 16), and malignant melanoma (SIR, 3.05; 95% CI, 1.74-4.95; O = 16). Although enhanced medical surveillance may play a role, increased reciprocal risks suggest that MCC may share etiologic influences with other malignancies. Heightened awareness of the associations of lymphohematopoietic malignancies with MCC may facilitate early clinical recognition. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Off Prevent Oncol, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Howard, RA (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7091,MSC 7238, Bethesda, MD 20892 USA. EM reganho@mail.nih.gov FU Intramural NIH HHS NR 21 TC 63 Z9 63 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1545 EP 1549 DI 10.1158/1055-9965.EPI-05-0895 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500021 PM 16896047 ER PT J AU Sherman, ME Lacey, JV Buys, SS Reding, DJ Berg, CD Williams, C Hartge, P AF Sherman, Mark E. Lacey, James V. Buys, Saundra S. Reding, Douglas J. Berg, Christine D. Williams, Craig Hartge, Patricia TI Ovarian volume: Determinants and associations with cancer among postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-MASS INDEX; ENDOMETRIAL CANCER; REPRODUCTIVE HORMONES; STEROID-HORMONES; SCREENING TRIAL; BREAST-CANCER; COLON-CANCER; AGE; ENDOCRINE; ANDROGENS AB Clinical studies have reported associations between ovarian stromal hyperplasia and the diagnosis of hormonally related tumors such as endometrial cancer. To assess the hypothesis that characteristics of benign ovaries among postmenopausal women are related to risk for breast, endometrial, and colon cancer, we analyzed systematically collected transvaginal ultrasound data for participants enrolled in the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Among women without cancer, median ovarian volume declined with age from 1.25 cm(3) for women between ages 55 and 59 years to 1.0 cm(3) for those between ages 65 and 69 years. African American and Caucasian women had larger median ovarian volumes than Asians. Larger ovarian volume was also associated with the highest quartiles of height and weight and ever having smoked. After adjusting for race, age, parity, body mass, smoking, and hormone use, women with median ovarian volumes : >= 3.0 cm(2) were at increased risk for breast cancer [odds ratio (OR), 1.42; 95% confidence interval (95% CI), 1.11-1.70], endometrial cancer (OR, 1.97; 95% CI, 1.12-3.48), and colon cancer (OR, 2.00; 95% CI, 1.25-3.21). Significant trends of risk with increasing volume were found only for breast and endometrial cancers. We conclude that large ovaries among postmenopausal women may represent a marker of risk for hormonally related tumors. Confirmation of these findings in future studies, including analyses of serum hormone levels and tissues, may provide insights into hormonal carcinogenesis among older women. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Early Detect Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Marshfield Clin Fdn Med Res & Educ, Dept Hematol & Oncol, Marshfield, WI 54449 USA. Informat Management Serv Inc, Rockville, MD USA. RP Sherman, ME (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov FU Intramural NIH HHS NR 23 TC 8 Z9 10 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1550 EP 1554 DI 10.1158/1055-9965.EPI-05-0847 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500022 PM 16896048 ER PT J AU Pine, SR Mechanic, LE Bowman, ED Welsh, JA Chanock, SC Shields, PG Harris, CC AF Pine, Sharon R. Mechanic, Leah E. Bowman, Elise D. Welsh, Judith A. Chanock, Stephen C. Shields, Peter G. Harris, Curtis C. TI MDM2 SNP309 and SNP354 are not associated with lung cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID POLYMORPHISMS; PROMOTER; P53; POPULATION; MUTATION; TP53 AB A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been found to be associated with tumor formation. Publication of this null report is important because an association between MDM2 SNP309 and lung cancer was previously reported in two independent studies. Our findings suggest that MDM2 SNP309 is not a strong factor in lung carcinogenesis. In addition, this is the first MDM2 SNP309 report on a population consisting of Caucasians in the United States and African-Americans. A strength of the study design is that the controls consist of both population and hospital controls. C1 NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Room 3068,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov NR 12 TC 36 Z9 36 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1559 EP 1561 DI 10.1158/1055-9965.EPI-06-0217 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500024 PM 16896050 ER PT J AU Kamangar, F Qiao, YL Yu, BB Sun, XD Abnet, CC Fan, JH Mark, SD Zhao, P Dawsey, SM Taylor, PR AF Kamangar, Farin Qiao, You-Lin Yu, Binbing Sun, Xiu-Di Abnet, Christian C. Fan, Jin-Hu Mark, Steven D. Zhao, Ping Dawsey, Sanford M. Taylor, Philip R. TI Lung cancer chemoprevention: A randomized, double-blind trial in Linxian, China SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BETA-CAROTENE; CARDIOVASCULAR-DISEASE; GENERAL-POPULATION; SUPPLEMENTATION AB We examined the effect of supplementation with four different combinations of vitamins and minerals in the prevention of lung cancer mortality among 29,584 healthy adults from Linxian, China. In accord with a partial factorial design, the participants were randomly assigned to take either a vitamin/mineral combination or a placebo for 5.25 years. The combinations tested in this trial were as follows: factor A, retinol and zinc; factor B, riboflavin and niacin; factor C, ascorbic acid and molybdenum; factor D, beta-carotene, a.-tocopherol, and selenium. Lung cancer deaths (n = 147) identified during the trial period (1986-1991) and 10 years after the trial ended (1991-2001) were the study outcome. No significant differences in lung cancer death rates were found for any of the four combinations of supplements tested in this study, using log-rank tests (all P values are > 0.20) or Cox proportional hazards models adjusted for age, sex, commune, and other treatments. No significant interactions were seen for age, sex, or smoking status. Supplementation with combinations of vitamins and minerals at nutrient-repletion levels for 5.25 years did not reduce lung cancer mortality in this nutrient-inadequate population in Linxian, China. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 3034, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov; qiaoy@public.bta.net.cn RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU CCR NIH HHS [N01-RC-47701]; Intramural NIH HHS; NCI NIH HHS [N01-SC-91030] NR 6 TC 32 Z9 35 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD AUG PY 2006 VL 15 IS 8 BP 1562 EP 1564 DI 10.1158/1055-9965.EPI-06-0316 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 073YT UT WOS:000239779500025 PM 16896051 ER PT J AU Cabelof, DC Ikeno, Y Nyska, A Busuttil, RA Anyangwe, N Vijg, J Matherly, LH Tucker, JD Wilson, SH Richardson, A Heydari, AR AF Cabelof, Diane C. Ikeno, Yuji Nyska, Abraham Busuttil, Rita A. Anyangwe, Njwen Vijg, Jan Matherly, Larry H. Tucker, James D. Wilson, Samuel H. Richardson, Arlan Heydari, Ahmad R. TI Haploinsufficiency in DNA polymerase beta increases cancer risk with age and alters mortality rate SO CANCER RESEARCH LA English DT Article ID BASE EXCISION-REPAIR; CALORIC RESTRICTION; GENOME MAINTENANCE; OXIDATIVE STRESS; MICE LACKING; IN-VIVO; MOUSE; MECHANISMS; SENESCENCE; PARAMETERS AB This study uses a base excision repair (BER)-deficient model, the DNA polymerase heterozygous mouse, to investigate the effect of BER deficiency on tumorigenicity and aging. Aged beta-pol(+/-) mice express 50% less beta-pol transcripts and protein (P < 0.05) than aged beta-pol(+/+) mice, showing maintenance of the heterozygous state over the life span of the mouse. This reduction in beta-pol expression was not associated with an increase in mutation rate but was associated with a 100% increase in the onset of hypoploidy. Aged beta-pol(+/-) mice exhibited a 6.7-fold increase in developing lymphoma (P < 0.01). Accordingly, 38% of beta-pol(+/-) mice exhibited lymphoid hyperplasia, whereas none of the beta-pol(+/-) exhibited this phenotype. beta-pol(+/-) mice were also more likely to develop adenocarcinoma (2.7-fold increase; P < 0.05) and more likely to develop multiple tumors, as 20% of the beta-pol(+/-) animals died bearing multiple tumors compared with only 5% of the beta-pol(+/-) animals (P < 0.05). In spite of accelerated tumor development, no gross effect of O-pol heterozygosity was seen with respect to life span. However, the survival curves for the beta-pol(+/-) and beta-pol(+/-) mice are not identical. A maximum likelihood estimation analysis showed a modest but significant (P < 0.05) acceleration of the age-dependent mortality rate in beta-pol(+/-) mice. Thus, the beta-pol(+/-) mouse represents a model in which mortality rate and tumor development are accelerated and provides evidence supporting the role of genomic maintenance in both aging and carcinogenesis. C1 Wayne State Univ, Karmanos Canc Inst, Sch Med, Dev Therapeut Program, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pharmacol, Detroit, MI 48201 USA. Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48201 USA. Wayne State Univ, Dept Biol Sci, Detroit, MI 48201 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. RP Cabelof, DC (reprint author), Wayne State Univ, Karmanos Canc Inst, Sch Med, Dev Therapeut Program, 110 E Warren, Detroit, MI 48201 USA. EM d.cabelof@wayne.edu FU NIA NIH HHS [1P01 AG 14674, P01 AG 19316, 1P30 AG 13319, R01 AG 20438, P01 AG 17242]; NIDDK NIH HHS [1R21 DK 62256]; NIEHS NIH HHS [ES 06639, ES 11044, 1F32 ES 013643] NR 35 TC 42 Z9 48 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2006 VL 66 IS 15 BP 7460 EP 7465 DI 10.1158/0008-5472.CAN-06-1177 PG 6 WC Oncology SC Oncology GA 069XU UT WOS:000239483500013 PM 16885342 ER PT J AU Gerdes, MJ Myakishev, M Frost, NA Rishi, V Moitra, J Acharya, A Levy, MR Park, SW Glick, A Yuspa, SH Vinson, C AF Gerdes, Michael J. Myakishev, Maxim Frost, Nicholas A. Rishi, Vikas Moitra, Jaideep Acharya, Asha Levy, Michelle R. Park, Sang-won Glick, Adam Yuspa, Stuart H. Vinson, Charles TI Activator protein-1 activity regulates epithelial tumor cell identity SO CANCER RESEARCH LA English DT Article ID MOUSE SKIN CARCINOGENESIS; EPSILON TRANSGENIC MICE; C-JUN; STEM-CELLS; GENE-EXPRESSION; INDIAN HEDGEHOG; DNA-BINDING; DIFFERENTIATION; AP-1; CARCINOMA AB To examine the consequences of inhibiting activator protein-1 (AP-1) transcription factors in skin, transgenic mice were generated, which use the tetracycline system to conditionally express A-FOS, a dominant negative that inhibits AP-1 DNA binding. Older mice develop mild alopecia and hyperplasia of sebaceous glands, particularly around the eyes. When A-FOS was expressed during chemical-induced skin carcinogenesis, mice do not develop characteristic benign and malignant squamous lesions but instead develop benign sebaceous adenomas containing a signature mutation in the H-ras proto-oncogene. Inhibiting AP-1 activity after tumor formation caused squamous tumors to transdifferentiate into sebaceous tumors. Furthermore, reactivating AP-1 in sebaceous tumors results in a reciprocal transdifferentiation into squamous tumors. In both cases of transdifferentiation, individual cells express molecular markers for both cell types, indicating individual tumor cells have the capacity to express multiple lineages. Molecular characterization of cultured keratinocytes and tumor material indicates that AP-1 regulates the balance between the wnt/beta-catenin and hedgehog signaling pathways that determine squamous and sebaceous lineages, respectively. Chromatin immunoprecipitation analysis indicates that c-Jun binds several wnt promoters, which are misregulated by A-FOS expression, suggesting that members of the wnt pathway can be a primary targets of AP-1 transcriptional regulation. Thus, AP-1 activity regulates tumor cell lineage and is essential to maintain the squamous tumor cell identity. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Lab Metab, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bldg 37,Rm 4068A, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU Intramural NIH HHS NR 54 TC 47 Z9 48 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2006 VL 66 IS 15 BP 7578 EP 7588 DI 10.1158/0008-5472.CAN-06-1247 PG 11 WC Oncology SC Oncology GA 069XU UT WOS:000239483500028 PM 16885357 ER PT J AU Inoue, S Leitner, WW Golding, B Scott, D AF Inoue, Satoshi Leitner, Wolfgang W. Golding, Basil Scott, Dorothy TI Inhibitory effects of B cells on antitumor immunity SO CANCER RESEARCH LA English DT Article ID CD8(+) T-CELLS; CD40 LIGAND; TUMOR IMMUNOSURVEILLANCE; CUTTING EDGE; EXPRESSION; CANCER; MELANOMA; LYMPHOCYTES; ANTIGEN; INTERLEUKIN-10 AB B-cell functions in antitumor immunity are not well understood. In this study, we evaluated the role of B cells in the development of antitumor immunity using Friend murine leukemia virus gag-expressing mouse EL-4 (EL-4 gag), D5 mouse melanoma, or MCA304 mouse sarcoma cells. To screen tumors for susceptibility to B-cell-deficient immune environments, spleen cells from naive C57BL/6 [wild-type (WT)] and B-cell knockout (BKO) mice were cultured with irradiated tumor cells in vitro. When cells were stimulated with EL-4 gag or D5 (but not MCA304 tumors), IFN-gamma production from CD8 T cells and natural killer cells was markedly decreased in WT compared with BKO cultures. IFN-gamma production was correlated with CD40 ligand expression on the tumor and inversely with interleukin-10 (IL-10) production by B cells. Sorted WT B cells produced more IL-10 than CD40 knockout (CD40KO) B cells when cocultured with EL-4 gag or D5 (but not MCA304). IFN-gamma production by BKO cells was reduced by the addition of sorted naive WT B cells (partially by CD40KO B cells) or recombinant mouse IL-10. In vivo tumor progression mirrored in vitro studies in that WT mice were unable to control tumor growth whereas EL-4 gag and D5 tumors (but not MCA304) were eliminated in BKO mice. Robust in vivo antitumor CTLs developed only in BKO tumor-challenged mice. Our studies provide the first mechanistic basis for the concept that B-cell depletion could therapeutically enhance antitumor immune responses to certain tumors by decreasing IL-10 production from B cells. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Rockville, MD 20852 USA. NCI, Dermatol Branch, NIH, Bethesda, MD USA. RP Scott, D (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, 1401 Rockville Pike,HFM-345, Rockville, MD 20852 USA. EM dorothy.scott@fda.hhs.gov RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 FU Intramural NIH HHS NR 45 TC 121 Z9 130 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD AUG 1 PY 2006 VL 66 IS 15 BP 7741 EP 7747 DI 10.1158/0008-5472.CAN-05-3766 PG 7 WC Oncology SC Oncology GA 069XU UT WOS:000239483500048 PM 16885377 ER PT J AU Ciolino, HP MacDonald, CJ Memon, OS Bass, SE Yeh, GC AF Ciolino, Henry P. MacDonald, Christopher J. Memon, Omar S. Bass, Sara E. Yeh, Grace Chao TI Sulindac regulates the aryl hydrocarbon receptor-mediated expression of Phase 1 metabolic enzymes in vivo and in vitro SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; CANCER-CELLS; AH RECEPTOR; SIGNAL-TRANSDUCTION; SULFONE METABOLITE; LUNG TUMORIGENESIS; CYP1A1 EXPRESSION; INDUCE APOPTOSIS; BREAST-CANCER AB Sulindac, a widely used non-steroidal anti-inflammatory drug (NSAID), has been shown to inhibit chemically induced carcinogenesis in animal models. In the present study, we have investigated the molecular mechanism by which sulindac affects the activity and expression of the enzymes that mediate the initial detoxification steps of many environmental carcinogens, the cytochromes P450 1A1, 1A2 and 1B1. Sulindac treatment of Sprague-Dawley rats resulted in a dose-dependent increase in hepatic cytochrome P450 (CYP) enzyme activity and in the expression of hepatic CYPs 1A1 and 1B1 mRNA. In the HepG2 human liver cancer cell line, sulindac caused a sustained, dose-dependent increase in CYP enzyme activity. Sulindac treatment resulted in a profound, dose-dependent increase in CYP 1A1 mRNA and a modest increase in 1A2 mRNA. The increase in CYP 1A1 mRNA induced by sulindac was, like enzyme activity, sustained for several days after the initial treatment. Sulindac induced the transcription of the CYP1A1 gene, as measured by the level of heterogeneous nuclear 1A1 RNA and by actinomycin D chase experiment. Since the transcription of CYP1A1 is under the control of the aryl hydrocarbon receptor (AhR), we examined the ability of sulindac to activate the receptor. Sulindac bound to the AhR, as measured by ligand-binding assay, and induced the binding of the AhR with the xenobiotic-responsive element present in the promoter region of the CYP1A1 gene. These results are the first demonstration that NSAIDs modulate carcinogen metabolic enzymes and provide a novel mechanism to explain the established chemopreventive activity of sulindac. C1 NCI, Cellular Def & Carcinogenesis Sect, Lab Metab, Ctr Canc Res,NIH, Frederick, MD 21701 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Ciolino, HP (reprint author), NCI, Cellular Def & Carcinogenesis Sect, Lab Metab, Ctr Canc Res,NIH, Frederick, MD 21701 USA. EM hcp@mail.utexas.edu FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 44 TC 19 Z9 19 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2006 VL 27 IS 8 BP 1586 EP 1592 DI 10.1093/carcin/bgi359 PG 7 WC Oncology SC Oncology GA 074VY UT WOS:000239841100008 PM 16531450 ER PT J AU Beyerbach, A Rothman, N Bhatnagar, VK Kashyap, R Sabbioni, G AF Beyerbach, Armin Rothman, Nathaniel Bhatnagar, Vijai K. Kashyap, Rekha Sabbioni, Gabriele TI Hemoglobin adducts in workers exposed to benzidine and azo dyes SO CARCINOGENESIS LA English DT Article ID CARCINOGENIC POTENCY DATABASE; UROTHELIAL DNA-ADDUCTS; NAT2 SLOW ACETYLATION; GSTM1 NULL GENOTYPE; BLADDER-CANCER; AROMATIC-AMINES; URINARY METABOLITES; N-ACETYLATION; REDUCTION; BINDING AB Benzidine (Bz) is a known human carcinogen. Several azo dyes have been synthesized with Bz. Bz can be metabolically released from azo dyes. In a group of Indian workers producing Bz and azo dyes the presence of hemoglobin (Hb) adducts was investigated. The following Hb adducts were identified and quantified by GC-MS: Bz, N-acetylbenzidine (AcBz), 4-aminobiphenyl (4ABP), aniline. 4ABP and aniline were quantitatively the major adducts. In the exposed workers (n = 33) all correlations between 4ABP, Bz and AcBz were r = 0.89 (P < 0.01) or greater. The group of workers exposed to Bz (Bz workers, n = 15) had 10-17-fold higher adduct levels than the workers exposed to dyes (dye workers, n = 18). 4ABP can be metabolically released from Bz and azo dyes. Aniline can be metabolically released from azo dyes. Therefore, the presence of 4ABP and aniline as Hb adducts is a consequence of exposure to the parent compounds or to the exposure of Bz and azo dyes and a consequent metabolical release of the arylamine moiety. The mean adduct ratios of 4ABP/(AcBz + Bz) varied up to 4-fold across all seven factories. Therefore, it is possible that 4ABP may have derived from general contamination in the work environment or endogenous metabolism, or a combination of the two. Since 4ABP is also a known human carcinogen, tumors observed in workers exposed to Bz or Bz dyes might be caused by both compounds. Further, these results suggest that understanding the role that genetic variants in NAT1 and NAT2 play in modifying the impact of Bz on bladder cancer risk may be complicated, as N-acetylation detoxifies 4ABP and activates Bz. C1 Inst Environm & Occupation Toxicol, CH-6780 Airolo, Switzerland. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Occupat Hlth, Ahmedabad, Gujarat, India. Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-80336 Munich, Germany. RP Sabbioni, G (reprint author), Inst Environm & Occupation Toxicol, Casella Postale 108, CH-6780 Airolo, Switzerland. EM gabriele.sabbioni@bluewin.ch FU Intramural NIH HHS NR 40 TC 13 Z9 14 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2006 VL 27 IS 8 BP 1600 EP 1606 DI 10.1093/carcin/bgi362 PG 7 WC Oncology SC Oncology GA 074VY UT WOS:000239841100010 PM 16497705 ER PT J AU Tryndyak, VP Muskhelishvili, L Kovalchuk, O Rodriguez-Juarez, R Montgomery, B Churchwell, MI Ross, SA Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Muskhelishvili, Levan Kovalchuk, Olga Rodriguez-Juarez, Rocio Montgomery, Beverly Churchwell, Mona I. Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Effect of long-term tamoxifen exposure on genotoxic and epigenetic changes in rat liver: implications for tamoxifen-induced hepatocarcinogenesis SO CARCINOGENESIS LA English DT Article ID DNA ADDUCT FORMATION; CELL-PROLIFERATION; BREAST-CANCER; GENOMIC HYPOMETHYLATION; HEPATIC DNA; GLOBAL DNA; METHYLATION; HEPATOCYTES; EXPRESSION; INDUCTION AB Tamoxifen is a non-steroidal anti-estrogen used for the treatment of breast cancer and, more recently, as a chemopreventive agent in healthy women at high risk of developing breast cancer. On the other hand, tamoxifen is a potent hepatocarcinogen in rats, with both tumor-initiating and tumor-promoting properties. There is substantial evidence that hepatic tumors in rats are initiated as a result of formation of tamoxifen-DNA adducts; however, events subsequent to DNA adduct formation are not clear. Recently, it has been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic effects, often cause epigenetic alterations. In the current study, we investigated whether or not the mechanism of tamoxifen-induced hepatocarcinogenesis includes both genotoxic and epigenetic components. Female Fisher 344 rats were fed a 420 p.p.m. tamoxifen diet for 6, 12, 18 or 24 weeks. Hepatic tamoxifen-DNA adduct levels, as assessed by high-performance liquid chromatography and electrospray tandem mass spectrometry, were 580 adducts/10(8) nt at 6 weeks, and increased to similar to 1700 adducts/10(8) nt by 18 weeks. Global liver DNA hypomethylation, as determined by an HpaII-based cytosine extension assay, was increased at all time points, with the maximum increase (similar to 200%) occurring at 6 weeks. Protein expressions of maintenance (DNMT1) DNA methyltransferase and de novo DNA methyltransferases DNMT3a and DNMT3b were decreased at all time points. Likewise, trimethylation of histone H4 lysine 20 was significantly decreased at all time points. In contrast, non-target tissues (i.e. mammary gland, pancreas and spleen) did not show any changes in global DNA methylation or DNA methyltransferase activity. These data indicate the importance of genotoxic and epigenetic alterations in the etiology of tamoxifen-induced hepatocarcinogenesis. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 52 TC 54 Z9 57 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2006 VL 27 IS 8 BP 1713 EP 1720 DI 10.1093/carcin/bgl050 PG 8 WC Oncology SC Oncology GA 074VY UT WOS:000239841100023 PM 16632870 ER PT J AU Sharma, S Gao, P Steele, VE AF Sharma, Sheela Gao, Pu Steele, Vernon E. TI The chemopreventive efficacy of inhaled oltipraz particulates in the B[a]P-induced A/J mouse lung adenoma model SO CARCINOGENESIS LA English DT Article ID REPUBLIC-OF-CHINA; STRAIN-A MOUSE; MALE F344 RATS; 5-(2-PYRAZINYL)-4-METHYL-1,2-DITHIOL-3-THIONE OLTIPRAZ; COLON CARCINOGENESIS; MICE; CANCER; TUMORIGENESIS; INDUCTION; INHIBITION AB This study explored the efficacy of oltipraz, a dithiolthione to prevent lung cancer by delivering it directly to the lung as inhaled particulates to obtain maximum efficacy with no toxicity. Two exposure regimens were used to compare the efficacies of early (Regimen-A) versus late (Regimen-B) intervention in prevention of lung tumorigenesis in A/J mice. Female A/J mice were exposed to 10, 30 and 100 mg/m(3) exposure concentrations of oltipraz for 1.0 h a day for 5 days per week for 4 weeks in Regimen A. During the second and third week, mice received totally 6 mg of B[a]P via gavage and after 16 weeks, they were killed for tumor counting and pathology. In Regimen B, mice were treated first with B[a]P and, after a gap of 4 weeks, exposed to oltipraz at 100 mg/m(3) for 16 additional weeks. At 22 weeks, animals were killed and necropsied for tumor scoring. The spontaneous tumors were few in untreated A/J mice (0.7 tumors/lung), whereas there was an average of 16.5 tumors per lung in the B[a]P group (20-fold induction). Evaluation of lung tumor multiplicity following exposure to oltipraz showed that oltipraz inhibited the tumor development in a dose-dependent manner (10-100 mg/m(3)) with inhibition ranging from 37 to 53% in Regimen A and 51% in Regimen B, when compared with the B[a]P group. Analysis of the tumor incidence showed that 81.5% of the animals had 10 or more tumors in the B[a]P group, whereas, in oltipraz exposure groups, there was a significant decrease in Regimen A (24-36%) and in Regimen B (42%). The data from this study show that oltipraz is an effective agent for lung cancer prevention, when it is delivered directly to the target tissue as aerosolized particulates. C1 Alion Life & Environm Sci, Cellular & Mol Toxicol Program, Res Triangle Pk, NC 27709 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Sharma, S (reprint author), Alion Sci & Technol, PO Box 12313, Res Triangle Pk, NC 27709 USA. EM ssharma@alionscience.com FU NCI NIH HHS [N01-CN-25112] NR 43 TC 16 Z9 16 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2006 VL 27 IS 8 BP 1721 EP 1727 DI 10.1093/carcin/bgl052 PG 7 WC Oncology SC Oncology GA 074VY UT WOS:000239841100024 PM 16632869 ER PT J AU Moon, C Krawczyk, M Lakatta, EG Talan, MI AF Moon, Chanil Krawczyk, Melissa Lakatta, Edward G. Talan, Mark I. TI Therapeutic effectiveness of a single vs multiple doses of erythropoietin after experimental myocardial infarction in rats SO CARDIOVASCULAR DRUGS AND THERAPY LA English DT Article DE myocardial infarction; terythropoietin; cardiac remodeling ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; HEART-FAILURE; ARTERY; BRAIN; CARDIOPROTECTION; DYSFUNCTION; APOPTOSIS; OCCLUSION; CYTOKINE; PROTECT AB Background Systemic application of recombinant human erythropoietin (rhEPO) greatly limits cardiac tissue damage and attenuates left ventricular (LV) remodeling after experimentally induced myocardial infarction (MI). However, multiple injections of rhEPO stimulate red blood cell production and elevate the hematocrit (Htc), which might negatively affect the outcome of acute MI. We compared the outcome of experimental MI in rats treated with a single or multiple doses of rhEPO. Materials and Methods Sprague-Dawley male rats were subjected to a permanent ligation of the left descending coronary artery (CL) or sham operation. Immediately after CL animals received either a single i.v. injection of 3,000 IU/kg of rhEPO, or a single injection plus additional injections of the same dose of rhEPO repeated daily for six more days. Echocardiography and blood collection for measurement of Htc were performed prior to, and at 2 and 4 weeks after CL; MI size was measured histologically 4 weeks after CL. ResultsA single injection of rhEPO elevated Htc by 11% (p < 0.05) 1 week after CL, but after multiple rhEPO injections Htc increased by 40%. In untreated rats a 140 and 340% expansion in end-diastolic and end-systolic LV volumes, respectively, and 55% decline in ejection fraction (EF) occurred during the 4 week period following CL. A single rhEPO dose attenuated the LV remodeling and EF reduction by 50%. Repeated rhEPO injections did not elicit any additional benefits in respect to LV remodeling. Moreover, at the end of 4 weeks, MI size was significantly reduced (by 40%) by a single injection, while after repeated rhEPO injections the reduction of MI size was not statistically significant. Conclusion The results of this study indicate that multiple dosing of rhEPO after induced myocardial infarction in rats has no added therapeutic benefits over those achieved by a single dose. C1 NIA, Intramural Res Program, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Talan, MI (reprint author), NIA, Intramural Res Program, Cardiovasc Sci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov FU Intramural NIH HHS NR 33 TC 13 Z9 15 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-3206 J9 CARDIOVASC DRUG THER JI Cardiovasc. Drugs Ther. PD AUG PY 2006 VL 20 IS 4 BP 245 EP 251 DI 10.1007/s10557-006-0080-z PG 7 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 102FE UT WOS:000241795600002 PM 17019537 ER PT J AU Martinou, JC Youle, RJ AF Martinou, J-C Youle, R. J. TI Which came first, the cytochrome c release or the mitochondrial fission? SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID DYNAMIN-RELATED PROTEIN; DOMINANT OPTIC ATROPHY; MARIE-TOOTH-DISEASE; CELL-DEATH; OUTER-MEMBRANE; BAX ACTIVATION; APOPTOSIS; FUSION; OPA1; FRAGMENTATION C1 Univ Geneva, Dept Cell Biol, CH-1211 Geneva 4, Switzerland. Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD USA. RP Martinou, JC (reprint author), Univ Geneva, Dept Cell Biol, 30 Quai Ernest Ansermet, CH-1211 Geneva 4, Switzerland. EM Jean-Claude.martinou@cellbio.unige.ch; youler@ninds.nih.gov NR 57 TC 73 Z9 73 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD AUG PY 2006 VL 13 IS 8 BP 1291 EP 1295 DI 10.1038/sj.cdd.4401985 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 064JK UT WOS:000239084900012 PM 16763618 ER PT J AU Luong, N Davies, CR Wessells, RJ Graham, SM King, MT Veech, R Bodmer, R Oldham, SM AF Luong, Nancy Davies, Claire R. Wessells, Robert J. Graham, Suzanne M. King, M. Todd Veech, Richard Bodmer, Rolf Oldham, Sean M. TI Activated FOXO-mediated insulin resistance is blocked by reduction of TOR activity SO CELL METABOLISM LA English DT Article ID TRANSCRIPTION FACTOR FOXO1; PANCREATIC BETA-CELLS; ELEGANS LIFE-SPAN; CAENORHABDITIS-ELEGANS; PROTEIN-KINASE; C-ELEGANS; MAMMALIAN TARGET; RECEPTOR SUBSTRATE-1; DROSOPHILA HOMOLOG; ENERGY HOMEOSTASIS AB Reducing insulin/IGF signaling allows for organismal survival during periods of inhospitable conditions by regulating the diapause state, whereby the organism stockpiles lipids, reduces fertility, increases stress resistance, and has an increased lifespan. The Target of Rapamycin (TOR) responds to changes in growth factors, amino acids, oxygen tension, and energy status; however, it is unclear how TOR contributes to physiological homeostasis and disease conditions. Here, we show that reducing the function of Drosophila TOR results in decreased lipid stores and glucose levels. Importantly, this reduction of dTOR activity blocks the insulin resistance and metabolic syndrome phenotypes associated with increased activity of the insulin responsive transcription factor, dFOXO. Reduction in dTOR function also protects against age-dependent decline in heart function and increases longevity. Thus, the regulation of dTOR activity may be an ancient "systems biological" means of regulating metabolism and senescence, that has important evolutionary, physiological, and clinical implications. C1 Neurosci & Aging Ctr, Burnham Inst Med Res, Canc Res Ctr, La Jolla, CA 92037 USA. NIAAA, NIH, Rockville, MD 20895 USA. RP Oldham, SM (reprint author), Neurosci & Aging Ctr, Burnham Inst Med Res, Canc Res Ctr, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM soldham@burnham.org FU NHLBI NIH HHS [HL84949] NR 93 TC 94 Z9 97 U1 2 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD AUG PY 2006 VL 4 IS 2 BP 133 EP 142 DI 10.1016/j.cmet.2006.05.013 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 071ZY UT WOS:000239643600007 PM 16890541 ER PT J AU Dhume, A Lu, SJ Horowits, R AF Dhume, Ashwini Lu, Shajia Horowits, Robert TI Targeted disruption of N-RAP gene function by RNA interference: A role for N-RAP in myofibril organization SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE N-RAP; myofibrillogenesis; cardiomyocytes; RNA interference ID CULTURED CHICK CARDIOMYOCYTES; NEBULIN-RELATED PROTEIN; TIME QUANTITATIVE PCR; MUSCLE LIM PROTEIN; STRIATED-MUSCLE; CARDIAC MYOFIBRILLOGENESIS; DILATED CARDIOMYOPATHY; PRECARDIAC MESODERM; INTERCALATED DISKS; MAMMALIAN-CELLS AB N-RAP is a muscle-specific protein concentrated in myofibril precursors during sarcomere assembly and at intercalated disks in adult heart. We used RNA interference to achieve a targeted decrease in N-RAP transcript and protein levels in primary cultures of embryonic mouse cardiomyocytes. N-RAP transcript levels were decreased by similar to 70% within 2 days following transfection with N-RAP specific siRNA. N-RAP protein levels steadily decreased over several days, reaching similar to 50% of control levels within 6 days. N-RAP protein knockdown was associated with decreased myofibril assembly, as assessed by alpha-actinin organization into mature striations. Transcripts encoding N-RAP binding proteins associated with assembling or mature myofibrils, such as alpha-actinin, Krpl, and muscle LIM protein, were expressed at normal levels during N-RAP protein knockdown, and alpha-actinin and Krp-1 protein levels were also unchanged. Transcripts encoding muscle myosin heavy chain and nonmuscle myosin heavy chain IIB were also expressed at relatively normal levels. However, decreased N-RAP protein levels were associated with dramatic changes in the encoded myosin proteins, with muscle myosin heavy chain levels increasing and nonmuscle myosin heavy chain IIB decreasing. N-RAP transcript and protein levels recovered to normal by days 6 and 7, respectively, and the changes in myofibril organization and myosin heavy chain isoform levels were reversed. Our data indicate that we can achieve transient N-RAP protein knockdown using the RNA interference technique and that alpha-actinin organization into myofibrils in cardiomyocytes is closely linked to N-RAP protein levels. Finally, N-RAP protein levels regulate the balance between nonmuscle myosin IIB and muscle myosin by post-trancriptional mechanisms. C1 NIAMSD, Muscle Biol Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, US Dept HHS, NIH, Bldg 50,Room 1154,MSC 8024, Bethesda, MD 20892 USA. EM horowits@helix.nih.gov FU Intramural NIH HHS NR 60 TC 21 Z9 23 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD AUG PY 2006 VL 63 IS 8 BP 493 EP 511 DI 10.1002/cm.20141 PG 19 WC Cell Biology SC Cell Biology GA 066JO UT WOS:000239225700005 PM 16767749 ER PT J AU Yin, PD Das, D Mitsuya, H AF Yin, P. D. Das, D. Mitsuya, H. TI Overcoming HIV drug resistance through rational drug design based on molecular, biochemical, and structural profiles of HIV resistance SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE human immunodeficiency virus; drug resistance; reverse transcriptase inhibitor; protease inhibitor ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 REVERSE-TRANSCRIPTASE; RNASE-H ACTIVITY; NUCLEOSIDE ANALOG RESISTANCE; AMINO-ACID SUBSTITUTIONS; FUSION INHIBITOR T-20; POL GENE-MUTATIONS; ANTI-AIDS DRUGS; PROTEASE INHIBITORS; IN-VITRO AB There are 20 available drugs for the treatment of human immunodeficiency virus (HIV) infection. With a single exception, all of these drugs inhibit either HIV reverse transcriptase or protease. Reverse transcriptase inhibitors can be further categorized as nucleoside/nucleotide analogs or non-nucleoside reverse transcriptase inhibitors. Resistance that has emerged against all available antiretroviral drugs represents a major challenge in the therapy of HIV infection. Nevertheless, extensive analysis of the molecular and structural mechanisms by which such mutations confer resistance has accumulated over the years. This understanding has driven the development and refinement of novel compounds capable of maintaining antiviral activity against both wild-type and drug-resistant HIV strains. The molecular, biochemical, and structural profiles of reverse transcriptase inhibitor and protease inhibitor resistance are discussed. In addition, how this knowledge has been utilized to generate a new generation of antiviral drugs with activity against drug-resistant HIV is reviewed. C1 NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. Kumamoto Univ, Dept Hematol, Kumamoto 860, Japan. Kumamoto Univ, Dept Infect Dis, Kumamoto 860, Japan. RP Mitsuya, H (reprint author), NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, 10 Ctr Dr,Bldg 10,Room 5A11, Bethesda, MD 20892 USA. EM hmitsuya@helix.nih.gov FU Intramural NIH HHS NR 140 TC 36 Z9 39 U1 2 U2 5 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD AUG PY 2006 VL 63 IS 15 BP 1706 EP 1724 DI 10.1007/s00018-006-6009-7 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 073PJ UT WOS:000239754800002 PM 16715409 ER PT J AU Cuthbertson, BJ Bullesbach, EE Gross, PS AF Cuthbertson, Brandon J. Bullesbach, Erika E. Gross, Paul S. TI Discovery of synthetic penaeidin activity against antibiotic-resistant fungi SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE antibiotic resistance; antimicrobial peptides; Cryptococcus neoformans; multidrug-resistant Candida; native chemical ligation ID SHRIMP ANTIMICROBIAL PEPTIDE; NATIVE CHEMICAL LIGATION; CANDIDA-LUSITANIAE; CRYPTOCOCCUS-NEOFORMANS; AMPHOTERICIN-B; FLUCONAZOLE; INFECTION; METHODOLOGY; INCONSPICUA; PROTEINS AB Penaeidins are antimicrobial peptides from shrimp that are constituted by divergent classes of peptide isoforms in an individual organism. Penaeidin sequence variation suggests functional diversity in the host and promises differential activities if applied to treat infections in humans. We have synthesized isoform 4 of penaeidin class 3 from the Atlantic shrimp, Litopenaeus setiferus, by native ligation using three peptide segments. Our synthesis approach led to the discovery of an irreversible side reaction that was successfully suppressed, a discovery, which has particular relevance to the synthesis of cysteine-rich peptides. The antimicrobial activity of full-length penaeidin and the N-terminal proline-rich domain of this isoform were compared with the corresponding peptides of penaeidin class 4 isoform 1 using a wide range of bacteria and fungi. New aspects of penaeidin function are reported that include activity against fungi of the phylum Basidiomycota (Cryptococcus strains), activity against fungi that are pathogenic to humans and effectiveness in the context of antibiotic resistance mechanisms (Cryptococcus and Candida spp.). The proline-rich domain of penaeidin class 4 shows the highest relative antimicrobial activity, while exhibiting no cytotoxicity to human monocytes, and therefore stands out as a potential peptide therapeutic. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Cuthbertson, BJ (reprint author), NIEHS, NIH, POB 12233,MD F3-04, Res Triangle Pk, NC 27709 USA. EM cuthbertsonb@niehs.nih.gov NR 33 TC 15 Z9 18 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD AUG PY 2006 VL 68 IS 2 BP 120 EP 127 DI 10.1111/j.1747-0285.2006.00417.x PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 087WL UT WOS:000240773400006 PM 16999777 ER PT J AU Ahmed, A Rich, MW Fleg, JL Zile, MR Young, JB Kitzman, DW Love, TE Aronow, WS Adams, KF Gheorghiade, M AF Ahmed, Ali Rich, Michael W. Fleg, Jerome L. Zile, Michael R. Young, James B. Kitzman, Dalane W. Love, Thomas E. Aronow, Wilbert S. Adams, Kirkwood F., Jr. Gheorghiade, Mihai TI Effects of digoxin on morbidity and mortality in diastolic heart failure: The ancillary Digitalis Investigation Group trial SO CIRCULATION LA English DT Article DE digoxin; heart failure; morbidity; mortality ID VENTRICULAR SYSTOLIC FUNCTION; EJECTION FRACTION; DIG TRIAL; OLDER-ADULTS; DYSFUNCTION; ASSOCIATION; GLYCOSIDES; OUTCOMES AB Background - About half of the 5 million heart failure patients in the United States have diastolic heart failure (clinical heart failure with normal or near-normal ejection fraction). Except for candesartan, no drugs have been tested in randomized clinical trials in these patients. Although digoxin was tested in an appreciable number of diastolic heart failure patients in the Digitalis Investigation Group ancillary trial, detailed findings from this important study have not previously been published. Methods and Results - Ambulatory chronic heart failure patients (n = 988) with normal sinus rhythm and ejection fraction > 45% (median, 53%) from the United States and Canada (1991 to 1993) were randomly assigned to digoxin (n = 492) or placebo (n = 496). During follow-up with a mean length of 37 months, 102 patients (21%) in the digoxin group and 119 patients (24%) in the placebo group (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.63 to 1.07; P = 0.136) experienced the primary combined outcome of heart failure hospitalization or heart failure mortality. Digoxin had no effect on all-cause or cause-specific mortality or on all-cause or cardiovascular hospitalization. Use of digoxin was associated with a trend toward a reduction in hospitalizations resulting from worsening heart failure (HR, 0.79; 95% CI, 0.59 to 1.04; P = 0.094) but also a trend toward an increase in hospitalizations for unstable angina (HR, 1.37; 95% CI, 0.99 to 1.91; P = 0.061). Conclusions - In ambulatory patients with chronic mild to moderate diastolic heart failure and normal sinus rhythm receiving angiotensin-converting enzyme inhibitor and diuretics, digoxin had no effect on natural history end points such as mortality and all-cause or cardiovascular hospitalizations. C1 Univ Alabama, Birmingham, AL 35294 USA. Washington Univ, St Louis, MO USA. VA Med Ctr, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. New York Med Coll, Valhalla, NY 10595 USA. Univ N Carolina, Chapel Hill, NC USA. Northwestern Univ, Chicago, IL 60611 USA. RP Ahmed, A (reprint author), Univ Alabama, 1530 3rd Ave S,CH-19,Suite 219, Birmingham, AL 35294 USA. EM aahmed@uab.edu RI Ahmed, Ali/A-2934-2008 OI Ahmed, Ali/0000-0002-6832-6424 FU NIA NIH HHS [1-K23-AG19211-04, K23 AG019211, K23 AG019211-04, R01 AG018915, R37 AG018915] NR 29 TC 242 Z9 264 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD AUG 1 PY 2006 VL 114 IS 5 BP 397 EP 403 DI 10.1161/CIRCULATIONAHA.106.628347 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 069CK UT WOS:000239422500011 PM 16864724 ER PT J AU Nadif, R Kleeberger, SR Kauffmann, F AF Nadif, R. Kleeberger, S. R. Kauffmann, F. TI Polymorphisms in manganese superoxide dismutase and catalase genes: functional study in Hong Kong Chinese asthma patients SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Letter C1 INSERM, U780, Villejuif, France. Univ Paris Sud, Fac Med, IFR69, Villejuif, France. Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA. RP Nadif, R (reprint author), INSERM, U780, Villejuif, France. RI Nadif, Rachel/R-2876-2016 OI Nadif, Rachel/0000-0003-4938-9339 NR 6 TC 5 Z9 5 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD AUG PY 2006 VL 36 IS 8 BP 1104 EP 1105 DI 10.1111/j.1365-2222.2006.02545.x PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 069ZA UT WOS:000239487300016 PM 16911367 ER PT J AU Teramoto, H Miwa, H Patel, V Letwin, N Castellone, MD Imai, N Shikami, M Imamura, A Gutkind, JS Nitta, M Lee, NH AF Teramoto, H. Miwa, H. Patel, V. Letwin, N. Castellone, M. D. Imai, N. Shikami, M. Imamura, A. Gutkind, J. S. Nitta, M. Lee, N. H. TI Gene expression changes in a patient presenting nonleukaemic nasal granulocytic sarcoma to acute myelogenous leukaemia using 40 K cDNA microarray SO CLINICAL AND LABORATORY HAEMATOLOGY LA English DT Article DE granulocytic sarcoma; nasal lesion; acute myelogenous leukaemia; cDNA microarray ID MYELOID-LEUKEMIA; CELLS AB This is a case report of granulocytic sarcoma occurring as a nasal lesion prior to the onset of acute myelogenous leukaemia (AML). To understand this case in more detail, we used 40 000 human cDNA microarray to identify the gene expression patterns of nonleukaemic stage bone marrow (BM), AML stage BM and AML stage peripheral blood cells and subsequently define the molecular basis of this disease progression. Of significance, we have tracked the expression profile of BM samples during the course of nonleukaemic to leukaemic progression, and identified a number of genes that may account for the growth potential of leukaemia cells and indicate poor prognosis of this case. C1 Aichi Med Univ, Sch Med, Dept Internal Med, Div Haematol, Nagakute, Aichi 4801195, Japan. Kojin Hosp, Dept Internal Med, Nagoya, Aichi, Japan. NIDR, Oral & Pharyngeal Canc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Inst Genom Res, Dept Funct Genom, Rockville, MD USA. RP Miwa, H (reprint author), Aichi Med Univ, Sch Med, Dept Internal Med, Div Haematol, 21 Karimata, Nagakute, Aichi 4801195, Japan. EM hmiwa@aichi-med-u.ac.jp RI Gutkind, J. Silvio/A-1053-2009; OI CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 NR 11 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0141-9854 J9 CLIN LAB HAEMATOL JI Clin. Lab. Haematol. PD AUG PY 2006 VL 28 IS 4 BP 262 EP 266 DI 10.1111/j.1365-2257.2006.00803.x PG 5 WC Hematology SC Hematology GA 065IR UT WOS:000239153900010 PM 16898967 ER PT J AU Li, ST Eldadah, BA Sharabi, Y Pechnik, S Goldstein, DS AF Li, Sheng-Ting Eldadah, Basil A. Sharabi, Yehonatan Pechnik, Sandra Goldstein, David S. TI Coronary vascular resistance in primary chronic autonomic failure SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE coronary arteries; myocardial blood flow; autonomic failure; autonomic nervous system; position emission tomography; N-13-Ammonia; 6-[F-18]Fluorodopamine ID CARDIAC SYMPATHETIC DENERVATION; BLOOD-FLOW; PARKINSON-DISEASE; HUMANS; 6-FLUORODOPAMINE; SUPERSENSITIVITY; EXERCISE; DOG AB Patient groups with chronic autonomic failure and neuroirnaging evidence of intact or absent cardiac sympathetic innervation had similar mean values for myocardial perfusion. Cardiac sympathetic outflow does not seem to contribute to coronary vascular resistance. C1 NINDS, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, NIH, Clin Neurocardiol Sect, Bldg 10 Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM goldsteind@minds.nih.gov NR 13 TC 2 Z9 2 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD AUG PY 2006 VL 16 IS 4 BP 293 EP 295 DI 10.1007/s10286-006-0353-4 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 073RT UT WOS:000239761000009 PM 16721653 ER PT J AU Cox, MC Low, J Lee, J Walshe, J Denduluri, N Berman, A Permenter, MG Petros, WP Price, DK Figg, WD Sparreboom, A Swain, SM AF Cox, Michael C. Low, Jennifer Lee, James Walshe, Janice Denduluri, Neelima Berman, Arlene Permenter, Matthew G. Petros, William P. Price, Douglas K. Figg, William D. Sparreboom, Alex Swain, Sandra M. TI Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN CYTOCHROME-P450 3A4; ST-JOHNS-WORT; HEALTHY-VOLUNTEERS; UNITED-STATES; PHASE-II; IN-VITRO; CANCER; SUPPLEMENTS; INHIBITION; METABOLISM AB Purpose: The herbal supplement garlic (Allium sativum) is commonly used by cancer patients. Preclinical studies have shown that allicin, a major component of garlic, may affect cytochrome P450 3A4 (CYP3A4) activity. This study examines the influence of garlic supplementation on the pharmacokinetics of docetaxel, a CYP3A4 substrate. Experimental Design: Women with metastatic breast cancer were treated with docetaxel (30 mg/m(2)) given weekly for 3 of 4 weeks. Three days after the initial dose of docetaxel, patients received 600 mg of garlic twice daily for 12 consecutive days. Docetaxel pharmacokinetics were assessed during the first three administrations. Results: In 10 evaluable patients, the mean baseline clearance of docetaxel was 30.8 L/h/m(2) [95% confidence intervals (95% CI), 16.7-44.9]. Coadministration of garlic reduced mean clearance of docetaxel to 23.7 L/h/m(2) (95% Cl, 15.5-31.8) and 20.0 L/h/m(2) (95% Cl, 13.3-26.7) on days 8 and 15, respectively (P = 0.17). Additional pharmacokinetic variables of docetaxel, including peak concentration (P = 0.79), area under the curve (P = 0.36), volume of distribution (P = 0.84), and half-life (P = 0.36), were also not statistically significantly different. The mean area under the curve ratio between day 15 and day 1 was 3.74 in three individuals with the CYP3A5*1A/*1A genotype (all African American) compared with 1.02 in six individuals with the CYP3A5*3C/*3C genotype (all Caucasian). Conclusions: This study indicates that garlic does not significantly affect the disposition of docetaxel. However, it cannot be excluded that garlic decreases the clearance of docetaxel in patients carrying a CYP3A5*1A allele. C1 NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20889 USA. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. W Virginia Univ, Hlth Sci Ctr, Morgantown, WV 26506 USA. RP Swain, SM (reprint author), NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM swains@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016; OI Swain, Sandra/0000-0002-1320-3830 FU Intramural NIH HHS NR 28 TC 41 Z9 42 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2006 VL 12 IS 15 BP 4636 EP 4640 DI 10.1158/1078-0432.CCR-06-0388 PG 5 WC Oncology SC Oncology GA 073NR UT WOS:000239750400025 PM 16899612 ER PT J AU Kawakami, K Terabe, M Kioi, M Berzofsky, JA Puri, RK AF Kawakami, Koji Terabe, Masaki Kioi, Mitornu Berzofsky, Jay A. Puri, Raj K. TI Intratumoral therapy with IL13-PE38 results in effective CTL-mediated suppression of IL-13R alpha 2-expressing contralateral tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID TARGETED CANCER-THERAPY; IL-13 RECEPTOR ALPHA-2; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; NECK-CANCER; HUMAN HEAD; CYTOTOXIN; PROTEIN AB Purpose: IL13-PE38, a targeted cytotoxin comprised of interleukin 13 (IL-13) and a mutated form of Pseudomonas exotoxin, induces specific killing of tumor cells expressing abundant levels of the IL-13R alpha 2 chain. We hypothesized that tumor cells killed by the cytotoxin may release antigens and/or apoptotic bodies when cells are dying, which then induce adoptive immunity, and that the PE38 portion of IL13-PE38 may act as a stimulant for the induction of a CTL response. Experimental Design: To test this hypothesis, we established D5 melanoma tumors with or without expression of the IL-13R alpha 2 chain in both flanks of C57BL/6 mice, and then IL13-PE38 was injected in the right flank tumors only. Results and Conclusions: When animals with IL-13R alpha 2-expressing D5 tumor (right) were injected with IL13-PE38, right flank tumors expressing the IL-13R alpha 2 chain not only showed dramatic regression but contralateral tumors (left flank) also showed tumor regression. Cell depletion experiments in tumor-bearing animals indicated that both CD8(+) and CD4(+) T cells contribute to the regression of contralateral tumors through CTL activation in the periphery and cellular infiltration into tumors. In addition, intratumoral treatment into s.c. tumors of mice bearing metastatic lung tumors with IL13-PE38 showed not only the reduction of treated s.c. tumor but also the reduction of lung metastasis. Thus, IL13-PE38 mediates an antitumor effect not only directly but also indirectly by inducing a host CD8(+) T cell immune response. Accordingly, targeted cytotoxins may be used to treat local disease even if they cannot be administered systemically, and yet may still induce a reasonable systemic antitumor response. C1 US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Tokyo, Japan. RP Kawakami, K (reprint author), Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Sakyo Ku, Yoshida Konoecho, Kyoto 6068501, Japan. EM kawakami-k@umin.ac.jp NR 35 TC 14 Z9 16 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2006 VL 12 IS 15 BP 4678 EP 4686 DI 10.1158/1078-0432.CCR-06-0192 PG 9 WC Oncology SC Oncology GA 073NR UT WOS:000239750400031 PM 16899618 ER PT J AU Zhang, YJ Xiang, LM Hassan, R Paik, CH Carrasquillo, JA Jang, BS Le, N Ho, M Pastan, I AF Zhang, YuJian Xiang, Laiman Hassan, Raffit Paik, Chang H. Carrasquillo, Jorge A. Jang, Beom-su Le, Nhat Ho, Mitchell Pastan, Ira TI Synergistic antitumor activity of taxol and immunotoxin SS1P in tumor-bearing mice SO CLINICAL CANCER RESEARCH LA English DT Article ID INTERSTITIAL FLUID PRESSURE; ENDOTHELIAL-CELL APOPTOSIS; RECOMBINANT IMMUNOTOXIN; INHIBITS ANGIOGENESIS; SOLID TUMORS; CANCER; PACLITAXEL; ANTIBODY; PHARMACOKINETICS; EFFICACY AB Purpose: To investigate the combined antitumor activity in mice of immunotoxin SS1P and Taxol. Methods: Immunodeficient mice were implanted with A431/K5 tumors expressing mesothelin. Established tumors were treated i.v. with immunotoxin SS1P alone, i.p. with Taxol alone, or with the two agents together. SS1P was radiolabeled with In-111 and used to study the effect of Taxol on its uptake by A431/K5 tumors. Results: Using doses at which either agent alone caused stabilization of tumor growth, the combination was synergistic causing long-lasting complete remissions in many animals. In contrast, synergy was not observed when the same cells were treated with these agents in vitro. Tumor uptake of In-111-SS1P was not affected by treatment with Taxol. Conclusion: The combination of Taxol and SS1P exerts a synergistic antitumor effect in animals but not in cell culture. This effect is not secondary to increased tumor uptake of the immunotoxin. Synergy could be due to improved immunotoxin distribution within the tumor or could involve factors released by other cell types in the tumors. C1 NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, Room 5106,37 Convent Dr, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; Ho, Mitchell/F-5059-2015; OI Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural NIH HHS NR 30 TC 56 Z9 56 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD AUG 1 PY 2006 VL 12 IS 15 BP 4695 EP 4701 DI 10.1158/1078-0432.CCR-06-0346 PG 7 WC Oncology SC Oncology GA 073NR UT WOS:000239750400033 PM 16899620 ER PT J AU Schwilke, EW Barnes, AJ Kacinko, SL Cone, EJ Moolchan, ET Huestis, MA AF Schwilke, Eugene W. Barnes, Allan J. Kacinko, Sherri L. Cone, Edward J. Moolchan, Eric T. Huestis, Marilyn A. TI Opioid disposition in human sweat after controlled oral codeine administration SO CLINICAL CHEMISTRY LA English DT Article ID ABUSE-TREATMENT PATIENTS; STRATUM-CORNEUM; GC-MS; COCAINE; PATCH; METABOLITES; PLASMA; URINE; HAIR; SPECTROMETRY AB Background: Characterization of opioid excretion in sweat is important for accurate interpretation of sweat tests in drug treatment, criminal justice, and workplace drug testing programs. Methods: Participants (n = 20) received placebo, 3 low (60 mg/70 kg) or 3 high (120 mg/70 kg) codeine sulfate doses (used as a model for opioid excretion) within 1 week. Codeine and metabolites in sweat were collected with PharmChek (R) Sweat Patches; hourly patches were applied for 1 to 15 h (n = 775) and weekly patches for 7 days (n = 118). Patches were analyzed by solid-phase extraction and gas chromatography-mass spectrometry for codeine, norcodeine, morphine, normorphine, and 6-acetylmorphine. Limits of quantification were 2.5 ng/patch (codeine and morphine) and 5 ng/patch (other analytes). Results: Codeine was the only analyte identified in 12.6% of hourly patches and 83.3% of weekly sweat patches worn during dosing. Weekly patch concentrations (SD) were 38.6 (59.9) ng/patch [median (range), 15.9 (0-225.1) ng/patch] for low and 34.1 (32.7) ng/patch [24.0 (0-96.2) ng/patch] for high codeine doses. Codeine detected 1 week after dosing was 4.6 (5.3) ng/patch [median (range), 4.0 (0-17.1) ng/patch; n = 11] after low and 7.7 (7.1) ng/patch [6.9 (0-20.5) ng/patch; n = 10] after high doses. In total, 2.6% of hourly, 38.5% of low-dose, and 45.5% of high-dose weekly patches contained codeine at the proposed Substance Abuse and Mental Health Services Administration cutoff. Conclusions: Codeine was the only analyte detected, at highly variable concentrations, up to 2 weeks after dosing. These results are consistent, considering the complex processes of codeine deposition in sweat. Sweat testing is a useful alternative technique for qualitative monitoring of opioid use. (c) 2006 American Association for Clinical Chemistry. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, 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 FU Intramural NIH HHS NR 25 TC 24 Z9 26 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD AUG PY 2006 VL 52 IS 8 BP 1539 EP 1545 DI 10.1373/clinchem.2006.067983 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 069WQ UT WOS:000239480300012 PM 16740647 ER PT J AU Lutchman, G Promrat, K Kleiner, DE Heller, T Ghany, MG Yanovski, JA Liang, TJ Hoofnagle, JH AF Lutchman, Glen Promrat, Kittichai Kleiner, David E. Heller, Theo Ghany, Marc G. Yanovski, Jack A. Liang, T. Jake Hoofnagle, Jay H. TI Changes in serum adipokine levels during pioglitazone treatment for nonalcoholic steatohepatitis: Relationship to histological improvement SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID FATTY LIVER-DISEASE; INSULIN-RESISTANCE; ADIPONECTIN; LEPTIN; FIBROSIS; MICE; NASH AB Background & Aims: Thiazolidinedione (TZD) therapy improves liver histology in nonalcoholic steatohepatitis (NASH) through a mechanism possibly related to its insulin-sensitizing or anti-inflammatory activity. This study was conducted to assess changes in serum levels of selected adipokines and proinflammatory cytokines and to relate these changes to the improved liver histology resulting from pioglitazone therapy for NASH. Methods: Serum samples from 18 patients with NASH obtained at day 0 and week 48 of therapy during an open-label study of pioglitazone were tested for adiponectin, leptin, interleukin (IL)-1a, IL-6, and tumor necrosis factor (TNF)-alpha levels. Paired liver biopsy specimens were scored (0-4) for steatosis, parenchymal inflammation, cell injury, and fibrosis. Results: Adiponectin levels increased from 3.7 to 10.3 mu g/mL at week 48 (P <.01); the levels of the other cytokines were unchanged: TNF-alpha, 9.1 vs 8.8 pg/mL; IL-1a, 3.9 vs 3.4 pg/mL; IL-6, 19.4 vs 13.4 pg/mL; and leptin, 24.8 vs 29.6 ng/mL (P >.05 for all). Pioglitazone therapy was associated with improvements in steatosis (2.5 vs 1.0), parenchymal inflammation (3.3 vs 2.1), cell injury (2.2 vs 0.9), and fibrosis (2.0 vs 1.4). The change in adiponectin level was associated with the improvement in steatosis (P =.03) as well as in a summary NASH activity index score (P =.01). Changes in IL-1, IL-6, TNF-alpha, and leptin levels did not correlate with improvements in the histological features. Conclusions: Improvements in liver histology during TZD therapy may be modulated by an adiponectin-mediated effect on insulin sensitivity and hepatic fatty acid metabolism rather than by changes in proinflammatory cytokines. C1 NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Hoofnagle, JH (reprint author), NIDDKD, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bldg 31,Room 9A27, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453; Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999] NR 30 TC 62 Z9 67 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD AUG PY 2006 VL 4 IS 8 BP 1048 EP 1052 DI 10.1016/j.cgh.2006.05.005 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 073BX UT WOS:000239718600018 PM 16814613 ER PT J AU Krupica, T Fry, TJ Mackall, CL AF Krupica, Tom, Jr. Fry, Terry J. Mackall, Crystal L. TI Autoimmunity during lymphopenia: A two-hit model SO CLINICAL IMMUNOLOGY LA English DT Review DE IRIS; autoimmunity; immunoregulation; tolerance; lymphopenia; homeostatic peripheral expansion ID RECONSTITUTION INFLAMMATORY SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; REGULATORY T-CELLS; BONE-MARROW-TRANSPLANTATION; IMMUNE RECOVERY UVEITIS; CUTTING EDGE; RISK-FACTORS; HOMEOSTATIC PROLIFERATION; CYTOMEGALOVIRUS RETINITIS; AIDS PATIENTS AB The immune system has evolved elaborate mechanisms to respond to diverse antigens while minimizing the risk for autoimmune reactivity. During lymphopenia, however, some mechanisms that normally serve to maintain host tolerance are temporarily suspended. Peripheral Tcells proliferate in response to self-antigens in lymphopenic hosts, but proliferation toward these same antigens is prevented when T cell numbers are normal. This process, termed homeostatic peripheral expansion, augments peripheral T cell number and limits repertoire skewing during recovery from lymphopenia and also predisposes lymphopenic hosts to autoimmune disease. This paper reviews murine and human settings in which autoimmunity occurs in the context of lymphopenia. We propose a two-hit model, in which lymphopenia plus another insult is sufficient to induce autoimmune disease. Among the secondary insults that appear sufficient to induce autoimmunity during lymphopenia are overproduction of IL-21 as occurs in the NOD.SCID mouse, depletion of Tregs as demonstrated in murine colitis and gastritis models, and tissue inflammation as seen in HIV infected patients who develop immune reconstitution inflammatory syndrome (IRIS). Delineating critical cofactors which result in autoimmune disease during lymphopenia can provide insight into the pathophysiotogy of naturally occurring autoimmune diseases as well as generating testable hypothesis for inducing tumor-specific autoimmunity in lymphopenic hosts with cancer. Published by Elsevier Inc. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. EM mackallc@mail.nih.gov FU Intramural NIH HHS NR 62 TC 113 Z9 117 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD AUG PY 2006 VL 120 IS 2 BP 121 EP 128 DI 10.1016/j.clim.2006.04.569 PG 8 WC Immunology SC Immunology GA 070SU UT WOS:000239545100001 PM 16766227 ER PT J AU Yang, LT Peng, H Zhu, ZL Li, G Huang, ZT Zhao, ZX Koup, RA Bailer, RT Wu, CY AF Yang, Li-Tao Peng, Hui Zhu, Zhao-Ling Li, Gang Huang, Zi-Tong Zhao, Zhi-Xin Koup, Richard A. Bailer, Robert T. Wu, Chang-You TI Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients SO CLINICAL IMMUNOLOGY LA English DT Article DE SARS; SARS-CoV; S protein; IFN-gamma; cellular immune response; memory T cells ID SPIKE PROTEIN; PROTECTIVE IMMUNITY; LYMPHOCYTES; IDENTIFICATION; GENERATION; ANTIBODIES; EPITOPES; SUBSETS; MONKEYS; VACCINE AB The role of cell-mediated immunity in human SARS-CoV infection is still not welt understood. In this study, we found that memory T-cell responses against the spike (S) protein were persistent for more than I year after SARS-CoV infection by detecting the production of IFN-gamma using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4(+) and CD8(+) Tcells were involved in cellular responses against SARS-CoV infection. Interestingly, most of SARS-CoV S-specific memory CD4(+) Tcells were central memory cells expressing CD45RO(+) CCR7(+) CD62L(-). However, the majority of memory CD8(+) Tcells revealed effector memory phenotype expressing CD45RO(-) CCR7(-) CD62L(-). Thus, our study provides the evidence that SARS-CoV infection in humans can induce cellular immune response that is persistent for a tong period of time. These data may have an important implication in the possibility of designing effective vaccine against SARS-CoV infection, specifically in defining T-cell populations that are implicated in protective immunity. (c) 2006 Elsevier Inc. All rights reserved. C1 Sun Yat Sen Univ, Zhongshan Med Sch, Dept Immunol, Guangzhou, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 3, Guangzhou 510630, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 2, Guangzhou 510120, Peoples R China. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Wu, CY (reprint author), Sun Yat Sen Univ, Zhongshan Med Sch, Dept Immunol, 74 Zhongshan 2nd Rd, Guangzhou, Peoples R China. EM Changyou-wu@yahoo.com RI Peng, Hui/I-8579-2015 OI Peng, Hui/0000-0002-2646-129X NR 26 TC 28 Z9 29 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD AUG PY 2006 VL 120 IS 2 BP 171 EP 178 DI 10.1016/j.clim.2006.05.002 PG 8 WC Immunology SC Immunology GA 070SU UT WOS:000239545100007 PM 16781892 ER PT J AU Mazzocchio, R Kitago, T Liuzzi, G Wolpaw, JR Cohen, LG AF Mazzocchio, Riccardo Kitago, Tomoko Liuzzi, Gianpiero Wolpaw, Jonathan R. Cohen, Leonardo G. TI Plastic changes in the human H-reflex pathway at rest following skillful cycling training SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE plasticity; memory; spinal cord; locomotion; H-reflex ID TRANSCRANIAL MAGNETIC STIMULATION; MOTOR EVOKED-POTENTIALS; ADULT SQUIRREL-MONKEYS; SPINAL-CORD PLASTICITY; CENTRAL-NERVOUS-SYSTEM; MOVEMENT REPRESENTATIONS; PRESYNAPTIC INHIBITION; MUSCLE-SPINDLE; HUMAN WALKING; MODULATION AB Objective: The spinal cord is capable of activity-dependent plasticity, but the extent of its participation in human motor learning is not known. Here, we tested the hypothesis that acquisition of a locomotor-related skill modulates the pathway of the H-reflex, a measure of spinal cord excitability that is susceptible to plastic changes. Methods: Subjects were tested on their ability to establish a constant cycling speed on a recumbent bike despite frequent changes in pedal resistance. The coefficient of variation of speed (CVspeed) measured their ability to acquire this skill (decreasing CVspeed with training reflects performance improvements). Soleus H-reflexes were taken at rest before and after cycling. Results: Ability to establish a target speed increased and H-reflex size decreased more after cycling training involving frequent changes in pedal resistance that required calibrated locomotor compensatory action than with training involving constant pedal resistances and lesser compensation. The degree of performance improvement correlated with the reduction in the amplitude of the H-reflex. Conclusions: Skillful establishment of a constant cycling speed despite changing pedal resistances is associated with persistent modulation of activity in spinal pathways. Significance: Recalibration of activity in the H-reflex pathway may be part of the control strategy required for locomotor-related skill acquisition. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Siena, Dipartimento Sci Neurol & Comportamento, Sez Neurofisiol Clin, Siena, Italy. New York State Dept Hlth, Wadsworth Ctr, Lab Nervous Syst Disorders, Albany, NY 12237 USA. SUNY Albany, Albany, NY 12246 USA. RP Mazzocchio, R (reprint author), NINDS, Human Cort Physiol Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM mazzocchio@unisi.it; cohenl@ninds.nih.gov RI Mazzocchio, Riccardo/H-4223-2012 OI Mazzocchio, Riccardo/0000-0002-0628-2868 NR 57 TC 25 Z9 25 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 EI 1872-8952 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD AUG PY 2006 VL 117 IS 8 BP 1682 EP 1691 DI 10.1016/j.clinph.2006.04.019 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 075HY UT WOS:000239876700007 PM 16793333 ER PT J AU Gardner, ER Burger, H van Schaik, RH van Oosterom, AT de Bruijn, EA Guetens, G Prenen, H de Jong, FA Baker, SD Bates, SE Figg, WD Verweij, J Sparreboom, A Nooter, K AF Gardner, Erin R. Burger, Herman van Schaik, Ron H. van Oosterom, Allan T. de Bruijn, Ernst A. Guetens, Gunther Prenen, Hans de Jong, Floris A. Baker, Sharyn D. Bates, Susan E. Figg, William D. Verweij, Jaap Sparreboom, Alex Nooter, Kees TI Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CANCER RESISTANCE PROTEIN; SINGLE NUCLEOTIDE POLYMORPHISMS; CHRONIC MYELOID-LEUKEMIA; DRUG-RESISTANCE; ABCG2 BCRP; ORAL BIOAVAILABILITY; MESYLATE GLEEVEC; HEALTHY-SUBJECTS; P-GLYCOPROTEIN; ABCB1 MDR1 AB Objective: Our objective was to explore the relationships between imatinib pharmacokinetics and 9 allelic variants in 7 genes coding for adenosine triphosphate-binding cassette transporters (ABCB1 and ABCG2) and enzymes (cytochrome P450 [CYP] 2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5) of putative relevance for imatinib. Methods. Imatinib transport in vitro was studied by use of human embryonic kidney 293 cells transfected with wild-type ABCG2 and an ABCG2 Q141K clone. Steady-state pharmacokinetics of imatinib was obtained in 82 patients with gastrointestinal stromal tumors treated with oral imatinib at doses ranging from 100 to 1000 mg/d. Genotyping was carried out via direct sequencing or restriction fragment length polymorphism-based techniques. Results. Human embryonic kidney 293 cells transfected with ABCG2 Q141K exhibited greater drug accumulation in vitro in comparison with cells expressing wild-type ABCG2 (P = .028). However, pharmacokinetic parameters of imatinib in vivo were not statistically significantly different in 16 patients who were heterozygous for ABCG2 421C > A compared with 66 patients carrying the wild-type sequence (P = .479). The apparent oral clearance of imatinib was potentially reduced in individuals with at least 1 CYP2D6*4 allele (median, 7.78 versus 10.6 L/h; P = .0695). Pharmacokinetic parameters were not related to any of the other multiple-variant genotypes (P >= .230), possibly because of the low allele frequencies. Conclusions. This study indicates that common genetic variants in the evaluated genes have only a limited impact on the pharmacokinetics of imatinib. Further investigation is required to quantitatively. assess the clinical significance of homozygous variant ABCG2 and CYP2D6 genotypes in patients treated with imatinib. C1 SAIC Frederick, Clin Pharmacol Res Core, Frederick, MD USA. Erasmus Univ, Med Ctr, Dept Med Oncol,Josephine Nefkens Inst, Erasmus MC,Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. Erasmus Univ, Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. Univ Louvain, Dept Oncol, Louvain, Belgium. Univ Antwerp, Dept Chem, B-2020 Antwerp, Belgium. Univ Antwerp, Dept Med Oncol, B-2020 Antwerp, Belgium. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. RP Sparreboom, A (reprint author), St Jude Childrens Hosp, 332 N Lauderdale St, Memphis, TN 38105 USA. EM Alex.Sparreboom@stjude.org RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011; Figg Sr, William/M-2411-2016 FU Intramural NIH HHS [, NIH0011335962]; NCI NIH HHS [N01-CO-12400]; PHS HHS [NIH0011335962] NR 37 TC 86 Z9 89 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2006 VL 80 IS 2 BP 192 EP 201 DI 10.1016/j.clpt.2006.05.003 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 074EF UT WOS:000239794800009 PM 16890580 ER PT J AU Danis, M Linde-Zwirble, WT Astor, A Lidicker, JR Angus, DC AF Danis, Marion Linde-Zwirble, Walter T. Astor, Avraham Lidicker, Jeffrey R. Angus, Derek C. TI How does lack of insurance affect use of intensive care? A population-based study SO CRITICAL CARE MEDICINE LA English DT Article DE health insurance; insurance coverage; intensive care; patient admission; mortality ID HEALTH-INSURANCE; MORTALITY; COVERAGE; CHILDREN AB Objective: One in six Americans aged <65 yrs are without health insurance. Although lack of insurance is associated with reduced access to many health services, the relationship between lack of insurance and use of intensive care services is unclear. We sought to compare the use of intensive care by insured and uninsured populations. Design: Retrospective population-based cross-sectional study of five U.S. states (Florida, Massachusetts, New Jersey, New York, and Virginia), analyzing use of hospital and intensive care unit (ICU) services by all residents of these states <65 yrs of age. Data sources included the five 1999 state hospital discharge databases and the 2000 U.S. Census Bureau Current Population Survey. Setting. Nonfederal hospitals in the five states (all hospitalizations in these during 1999). Interventions: None. Measurements and Main Results. There were 39.3 million and 7.8 million individuals aged 0-64 yrs with and without insurance, respectively, in the five-state sample. The uninsured population was far less likely to be hospitalized (odds ratio [OR], 0.458; 95% confidence interval [CI], 0.456-0.460; p <.001) and to be admitted to the ICU (OR, 0.581, 95% Cl: 0.576-0.587, p <.001). Differences persisted irrespective of age, gender, ethnicity, or reason for admission. Among those hospitalized, the uninsured were more likely to receive intensive care (OR, 1.24; 95% Cl, 1.22-1.25; p <.01). Hospital mortality rates for patients admitted to the ICU ranged by age from 4.0% to 6.9% for the uninsured and from 2.7% to 5.5% for the insured (OR, 1.12-1.54; p <.01). Conclusions: Americans without insurance use ICU services less often than those with insurance, primarily because of decreased likelihood of hospital admission in the first place. Outcome is worse for those who are admitted to the ICU, possibly because they are sicker when they seek care. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. ZD Associates, Perkasie, PA USA. Univ Michigan, Dept Sociol, Ann Arbor, MI 48109 USA. Temple Univ, Dept Stat, Philadelphia, PA 19122 USA. Univ Pittsburgh, Sch Med, Dept Crit Care Med, CRISMA Lab, Pittsburgh, PA USA. RP Danis, M (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RI Angus, Derek/E-9671-2012; Astor, Avi/I-1318-2015 OI Astor, Avi/0000-0002-4720-1841 NR 29 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD AUG PY 2006 VL 34 IS 8 BP 2043 EP 2048 DI 10.1097/01.CCM.0000227657.75270.C4 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 067WU UT WOS:000239334100002 PM 16763518 ER PT J AU Huey, ED Krueger, F Grafman, J AF Huey, Edward D. Krueger, Frank Grafman, Jordan TI Representations in the human prefrontal cortex SO CURRENT DIRECTIONS IN PSYCHOLOGICAL SCIENCE LA English DT Article DE human prefrontal cortex; frontal lobes ID COGNITION; MEMORY AB The prefrontal cortex (PFC) in humans has been studied for more than a century, but many crucial questions about its functions remain unanswered. This paper will highlight a few key differences between human and animal PFCs, and between the human PFC (HPFC) and other parts of the human brain. We then make a case that the HPFC is critically important for executing behaviors over time and integrating disparate information from throughout the brain. Finally, we will focus on our position in the current debate regarding how the HPFC performs its functions and discuss future directions for research. C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 14 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0963-7214 J9 CURR DIR PSYCHOL SCI JI Curr. Dir. Psychol. PD AUG PY 2006 VL 15 IS 4 BP 167 EP 171 DI 10.1111/j.1467-8721.2006.00429.x PG 5 WC Psychology, Multidisciplinary SC Psychology GA 084TP UT WOS:000240557600004 ER PT J AU Leppert, ER Smith, NF Cox, MC Scripture, CD Figg, WD AF Leppert, Erin R. Smith, Nicola F. Cox, Michael C. Scripture, Charity D. Figg, William D. TI Thalidomide metabolism and hydrolysis: Mechanisms and implications SO CURRENT DRUG METABOLISM LA English DT Review DE hydrolysis; hydroxylation; CYP2C19; pharmacokinetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO BIOTRANSFORMATION; NECROSIS-FACTOR-ALPHA; NF-KAPPA-B; MULTIPLE-MYELOMA; TNF-ALPHA; CAPILLARY-ELECTROPHORESIS; HYDROXYLATED METABOLITES; INHIBITS ANGIOGENESIS; PHARMACOKINETICS AB Despite its controversial past, thalidomide is currently under investigation for the treatment of several disease types, ranging from inflammatory conditions to cancer. The mechanism of action of thalidomide is complex and not yet fully understood, but there is some evidence to suggest that metabolism may play a role. Consequently, there has been a considerable effort to characterize the metabolism of thalidomide in recent years. Thalidomide undergoes biotransformation by non-enzymatic hydrolysis and enzyme-mediated hydroxylation to form a multitude of metabolites. Metabolite identification and reaction phenotyping studies have been performed and will be discussed in this review in addition to interspecies differences in thalidomide metabolism. C1 NCI, SAIC Frederick Inc, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, SAIC Frederick Inc, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 63 TC 37 Z9 38 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD AUG PY 2006 VL 7 IS 6 BP 677 EP 685 DI 10.2174/138920006778017777 PG 9 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 062GG UT WOS:000238932000008 PM 16918319 ER PT J AU Liang, XJ Aszalos, A AF Liang, X. -J. Aszalos, A. TI Multidrug transporters as drug targets SO CURRENT DRUG TARGETS LA English DT Review DE drug-drug interactions; P '-glycoprotein; multidrug transporters; cancer chemotherapy; intentional and/or unintentional targets; drug resistance; polypharmacy ID RESISTANCE-ASSOCIATED PROTEIN; ORGANIC ANION TRANSPORTER; CONJUGATE EXPORT PUMP; P-GLYCOPROTEIN MODULATION; DUBIN-JOHNSON-SYNDROME; RENAL PROXIMAL TUBULE; BLOOD-BRAIN-BARRIER; CANCER-CELL LINES; HUMAN TUMOR-CELLS; PHASE-I AB Transport molecules can significantly affect the pharmacodynamics and pharmacokinetics of drugs. An important transport molecule, the 170kDa P-glycoprotein (Pgp), is constitutively expressed at several organ sites in the human body. Pep is expressed at the blood-brain barrier, in the kidneys, liver, intestines and in certain T cells. Other transporters such as the multidrug resistance protein 1 (MRP1) and MRP2 also contribute to drug distribution in the human body, although to a lesser extent than Pap. These three transporters, and especially Pgp, are often targets of drugs. Pgp can be an intentional or unintentional target. It is directly targeted when one wants to block its function by a modifier drug so that another drug, also a substrate of Pgp, call penetrate the cell membrane, which would otherwise be impermeable. Unintentional targeting occurs when several drugs are administered to a patient and as a consequence, the physiological function of Pgp is blocked at different organ sites. Like Pgp, MRP1 also has the capacity to mediate transport of many drugs the other compounds. MRP1 has a protective role in preventing accumulation of toxic compounds and drugs in epithelial tissue covering the choroid plexus/cerebrospinal fluid compartment, oral epithelium. sertoli cells, intesticular tubules and urinary collecting duct cells. MRP2 primarily transports weakly basic drugs and bilirubin from the liver to bile. Most compounds that efficiently block Pap have only low affinity for MRP1 and MRP2. There are only a few effective and specific MRP inhibitors available. Drug targeting of these transporters may play a role in cancer chemotherapy and in the pharmacokinetics of substrate drugs. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Aszalos, A (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 2112, Bethesda, MD 20892 USA. EM aszaolsa@mail.nih.gov NR 114 TC 32 Z9 42 U1 3 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD AUG PY 2006 VL 7 IS 8 BP 911 EP 921 DI 10.2174/138945006778019264 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 064IM UT WOS:000239082400001 PM 16918320 ER PT J AU Chatterjee, DK LaBaer, J AF Chatterjee, Deb K. LaBaer, Joshua TI Protein technologies - Editorial overview SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Editorial Material C1 NCI, Prot Express Lab, Res Technol Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Chatterjee, DK (reprint author), NCI, Prot Express Lab, Res Technol Program, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. EM chatterjee@ncifcrf.gov; josh@hms.harvard.edu NR 0 TC 3 Z9 3 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 2006 VL 17 IS 4 BP 334 EP 336 DI 10.1016/j.copbio.2006.06.016 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 077IU UT WOS:000240023300001 ER PT J AU Grisshammer, R AF Grisshammer, Reinhard TI Understanding recombinant expression of membrane proteins SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID ENDOPLASMIC-RETICULUM; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; TRANSMEMBRANE HELICES; COUPLED RECEPTORS; QUALITY-CONTROL; CALCIUM-PUMP; OVEREXPRESSION; RHODOPSIN; CHANNEL AB Over the past 15 years, numerous reports have been published on the recombinant expression of integral membrane proteins. Some proteins accumulate in the membrane to high levels, whereas other often closely related proteins are barely detected. Understanding the underlying reasons for this variation has proven difficult. Recent studies in this area have provided new insight into the response of host cells to membrane protein expression and into the mechanism of membrane insertion. The successful overproduction of some membrane proteins was shown to be linked to the avoidance of stress responses in the host cell. Furthermore, the cell response to membrane protein production has been quantified and several genes that are either upregulated or downregulated when yields of a membrane-inserted protein are poor were identified. Progress has also been made in understanding how the translocon, which is the site of protein translocation and membrane insertion, decides whether a protein segment is integrated into the membrane or not. Building upon such experiments will lead to targeted approaches for recombinant membrane protein expression. C1 NIDDK, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Grisshammer, R (reprint author), NIDDK, Mol Biol Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM rkgriss@helix.nih.gov RI Grisshammer, Reinhard/C-3089-2015 FU Intramural NIH HHS NR 32 TC 66 Z9 71 U1 1 U2 16 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 2006 VL 17 IS 4 BP 337 EP 340 DI 10.1016/j.copbio.2006.06.001 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 077IU UT WOS:000240023300002 PM 16777403 ER PT J AU Esposito, D Chatterjee, DK AF Esposito, Dominic Chatterjee, Deb K. TI Enhancement of soluble protein expression through the use of fusion tags SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID HIGHLY EFFICIENT EXPRESSION; MALTOSE-BINDING PROTEIN; ETCH VIRUS PROTEASE; ESCHERICHIA-COLI; RECOMBINANT PROTEINS; MAMMALIAN-CELLS; AFFINITY TAGS; PURIFICATION; SOLUBILITY; SYSTEM AB The soluble expression of heterologous proteins in Escherichia coli remains a serious bottleneck in protein production. Although alteration of expression conditions can sometimes solve the problem, the best available tools to date have been fusion tags that enhance the solubility of expressed proteins. However, a systematic analysis of the utility of these solubility fusions has been difficult, and it appears that many proteins react differently to the presence of different solubility tags. The advent of high-throughput structural genomics programs and advances in cloning and expression technology afford us a new way to compare the effectiveness of solubility tags. This data should allow us to better predict the effectiveness of tags currently in use, and might also provide the information needed to identify new fusion tags. C1 NCI, Res Technol Program, Prot Express Lab, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. RP Chatterjee, DK (reprint author), NCI, Res Technol Program, Prot Express Lab, SAIC Frederick Inc, Ft Detrick, MD 21702 USA. EM chatterjee@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 51 TC 240 Z9 266 U1 6 U2 83 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 2006 VL 17 IS 4 BP 353 EP 358 DI 10.1016/j.copbio.2006.06.003 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 077IU UT WOS:000240023300005 PM 16781139 ER PT J AU Hartley, JL AF Hartley, James L. TI Cloning technologies for protein expression and purification SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID SITE-SPECIFIC RECOMBINATION; HIGH-THROUGHPUT EXPRESSION; ESCHERICHIA-COLI; SINORHIZOBIUM-MELILOTI; RAPID CONSTRUCTION; MOLECULAR-CLONING; DNA; TRANSLATION; CLONES; SYSTEM AB Detailed knowledge of the biochemistry and structure of individual proteins is fundamental to biomedical research. To further our understanding, however, proteins need to be purified in sufficient quantities, usually from recombinant sources. Although the sequences of genomes are now produced in automated factories purified proteins are not, because their behavior is much more variable. The construction of plasmids and viruses to overexpress proteins for their purification is often tedious. Alternatives to traditional methods that are faster, easier and more flexible are needed and are becoming available. C1 NCI, SAIC Frederick Inc, Prot Express Lab, Res Technol Program, Ft Detrick, MD 21702 USA. RP Hartley, JL (reprint author), NCI, SAIC Frederick Inc, Prot Express Lab, Res Technol Program, Ft Detrick, MD 21702 USA. EM hartley@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 47 TC 34 Z9 36 U1 1 U2 19 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD AUG PY 2006 VL 17 IS 4 BP 359 EP 366 DI 10.1016/j.copbio.2006.06.011 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 077IU UT WOS:000240023300006 PM 16839756 ER PT J AU Barry, CE Matter, A AF Barry, Clifton E. Matter, Alex TI Next-generation therapeutics - Turning the current 'innovation gap' into an 'innovation leap' SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Editorial Material C1 NIAID, Tuberculosis Res Sect, NIH, Rockville, MD 20852 USA. Novartis Inst Trop Dis, Singapore 138670, Singapore. RP Barry, CE (reprint author), NIAID, Tuberculosis Res Sect, NIH, Rockville, MD 20852 USA. EM clifton_barry@nih.gov RI Barry, III, Clifton/H-3839-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD AUG PY 2006 VL 10 IS 4 BP 291 EP 293 DI 10.1016/j.cbpa.2006.06.029 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 077UQ UT WOS:000240056600001 ER PT J AU Kalil, AC Danner, RL AF Kalil, Andre C. Danner, Robert L. TI L-arginine supplementation in sepsis: beneficial or harmful? SO CURRENT OPINION IN CRITICAL CARE LA English DT Review DE L-arginine; enteral; parenteral; sepsis; septic shock; severe sepsis ID CRITICALLY-ILL PATIENTS; TOTAL PARENTERAL-NUTRITION; RABBIT ENDOTOXIN-SHOCK; NITRIC-OXIDE SYNTHESIS; GUT-DERIVED SEPSIS; CARE-UNIT PATIENTS; CLINICAL-TRIAL; ENTERAL IMMUNONUTRITION; DIETARY ARGININE; PLASMA ARGININE AB Purpose of review Recent results are reviewed on the effects Of L-arginine supplements in excess of standard nutritional practices during severe sepsis and septic shock. Recent findings Septic shock has been alternatively viewed as an L-arginine-deficient state or as a syndrome caused by excess nitric oxide, a vasoactive product Of L-arginine metabolism. L-Arginine has many physiologic and pharmacologic effects that indicate its potential to affect survival in septic patients. Animal studies have documented immunologic effects of L-arginine and of commercial 'immune-enhancing' diets. However, survival studies in small animals have not consistently favored L-arginine. L-Arginine monotherapy in a canine model of septic shock found significant harm at infusion rates of less than twice that administered in standard formulations of total parenteral nutrition. Meanwhile, clinical studies have suffered from lack of statistical power, patient heterogeneity, randomization failures, and use of complex nutritional formulas. Meta-analyses have noted heterogeneity between the effects of immune-enhancing diets in surgical versus medical patients and mixed critically ill populations that include subjects with sepsis, indicating that these results may not be reliably pooled. Summary To date, published evidence has not established the safety and efficacy Of L-arginine at doses above standard dietary practices in severe sepsis or septic shock. C1 Univ Nebraska, Dept Internal Med, Div Infect Dis, Omaha, NE 68182 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kalil, AC (reprint author), 985400 Nebraska Med Ctr, Omaha, NE 68198 USA. EM akalil@unmc.edu NR 54 TC 33 Z9 33 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1070-5295 J9 CURR OPIN CRIT CARE JI Curr. Opin. Crit. Care PD AUG PY 2006 VL 12 IS 4 BP 303 EP 308 DI 10.1097/01.ccx.0000235206.92697.bf PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 073YN UT WOS:000239778800004 PM 16810039 ER PT J AU Belkaid, Y Sun, CM Bouladoux, N AF Belkaid, Yasmine Sun, Cheng Ming Bouladoux, Nicolas TI Parasites and immunoregulatory T cells SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID LEISHMANIA-MAJOR INFECTION; TOLL-LIKE RECEPTOR-2; TGF-BETA; DENDRITIC CELLS; IMMUNE-RESPONSES; IFN-GAMMA; INTERLEUKIN-10 PRODUCTION; INTRACELLULAR PATHOGEN; LYMPHATIC FILARIASIS; PLASMODIUM-CHABAUDI AB Surviving a parasitic infection requires the generation of a controlled immune response. Failure to establish or to maintain homeostatic conditions usually causes disease. Investigation of the immunoregulatory network as the response to the parasitic process or induced by the parasite promises enormous therapeutic benefits for the control of parasitic diseases. Recent findings implicate various populations of regulatory T cells in this homeostatic regulation. C1 NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Intramural NIH HHS NR 75 TC 28 Z9 34 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD AUG PY 2006 VL 18 IS 4 BP 406 EP 412 DI 10.1016/j.coi.2006.05.014 PG 7 WC Immunology SC Immunology GA 067ZP UT WOS:000239341600006 PM 16766171 ER PT J AU Rodriguez, LG Lockett, SJ Holtom, GR AF Rodriguez, Luis G. Lockett, Stephen J. Holtom, Gary R. TI Coherent anti-stokes Raman scattering microscopy: A biological review SO CYTOMETRY PART A LA English DT Review DE CARS microscopy; Raman scattering; vibrational spectroscopy; nonlinear optical effects; live cell imaging ID PROTEIN DISTRIBUTION; HIGH-SENSITIVITY; THIN-FILMS; CELLS; SPECTROSCOPY; VISUALIZATION; GENERATION; RESOLUTION; VESICLES; BILAYERS AB Microscopic imaging of cells and tissues are generated by the interaction of light with either the sample itself or contrast agents that label the sample. Most contrast agents, however, alter the cell in order to introduce molecular labels, complicating live cell imaging. The interaction of light from multiple laser sources has given rise to microscopy, based on Raman scattering or vibrational resonance, which demonstrates selectivity to specific chemical bonds while imaging unmodified live cells. Here, we discuss the nonlinear optical technique of coherent anti-Stokes Raman scattering (CARS) microscopy, its instrumentation, and its status in live cell imaging. (c) 2006 International Society for Analytical Cytology. C1 Pacific NW Natl Lab, Richland, WA 99352 USA. NCI, SAIC Frederick, Image Anal Lab, Frederick, MD 21701 USA. RP Holtom, GR (reprint author), Pacific NW Natl Lab, POB 999-K8-88, Richland, WA 99352 USA. EM gary.holtom@pnl.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 46 TC 57 Z9 60 U1 1 U2 19 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD AUG PY 2006 VL 69A IS 8 BP 779 EP 791 DI 10.1002/cyto.a.20299 PG 13 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 089WE UT WOS:000240911400007 PM 16752420 ER PT J AU Thaler, C Vogel, SS AF Thaler, Christopher Vogel, Steven S. TI Quantitative linear unmixing of CFP and YFP from spectral images acquired with two-photon excitation SO CYTOMETRY PART A LA English DT Article DE CFP; YFP; two-photon; linear-unmixing; FLIM; FRET ID RESONANCE ENERGY-TRANSFER; FLUORESCENCE MICROSCOPY; CELLS AB Background: Spectrally distinct fluorescent proteins (FPs) have been developed permitting the visualization of several proteins simultaneously in living cells. The emission spectra of FPs, in most cases, overlap, making signal separation based on filter technology inefficient and in cases of bleed-through, inaccurate. Spectral imaging can overcome these obstacles through a process called linear unmixing. Given a complex spectra composed of multiple fluorophores, linear unmixing can reduce the complex signal to its individual, weighted, component spectra. Spectral imaging with two-photon excitation allows the collection of nontruncated emission spectra. The accuracy of linear unmixing under these conditions needs to be evaluated. Methods: Capillaries containing defined mixtures of CFP and YFP were used to test the accuracy of linear unmixing using spectral images obtained with two-photon excitation. Results: Linear unmixing can be accurate when wavelength and power-matched reference spectra are provided to the algorithm. Linear unmixing errors can occur due to (1) excitation laser contamination of emission signals, (2) the presence of FRET, (3) poor selection of excitation wavelength, and (4) failure to background subtract reference spectra. Conclusions: Linear unmixing, when judiciously performed, can accurately measure the abundance of CFP and YFP in mixed samples, even when their relative intensities range from 90:1. (c) 2006 International Society for Analytical Cytology. C1 NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Vogel, SS (reprint author), NIAAA, Lab Mol Physiol, NIH, 5625 Fishers Labe, Bethesda, MD 20892 USA. EM stevevog@mail.nih.gov RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 FU NIAAA NIH HHS [Z01AA000452-01] NR 22 TC 18 Z9 18 U1 0 U2 11 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD AUG PY 2006 VL 69A IS 8 BP 904 EP 911 DI 10.1002/cyto.a.20267 PG 8 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 089WE UT WOS:000240911400020 PM 16888770 ER PT J AU Tanaka, TS de Silanes, IL Sharova, LV Akutsu, H Yoshikawa, T Amano, H Yamanaka, S Gorospe, M Ko, MSH AF Tanaka, Tetsuya S. de Silanes, Isabel Lopez Sharova, Lioudmila V. Akutsu, Hidenori Yoshikawa, Toshiyuki Amano, Hisayuki Yamanaka, Shinya Gorospe, Myriam Ko, Minoru S. H. TI Esg1, expressed exclusively in preimplantation embryos, germline, and embryonic stem cells, is a putative RNA-binding protein with broad RNA targets SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE cellular pluripotency; Esg1; immunoprecipitation-microarray; RNA-binding protein ID GENE-EXPRESSION; MESSENGER-RNA; MOUSE EMBRYOS; PLURIPOTENT CELLS; OCT4; NANOG; DIFFERENTIATION; IDENTIFICATION; CONSEQUENCES; BLASTOCYST AB In our earlier attempt to identify genes involved in the maintenance of cellular pluripotency, we found that KH-domain protein Embryonal stem cell-specific gene 1 (Esg1) showed similar expression patterns to those of Oct3/4 (Pou5f1), whereas the forced repression of Oct3/4 in mouse embryonic stem cells immediately downregulated the expression of Esg1. Here we further confirm this overlap by in situ hybridization and immunohistochemical analyses. Both Esg1 transcript and protein exist in the egg and preimplantation embryos. At embryonic day 3.5, blastocyst stage, however, ESG1 protein was more abundant in the inner cell mass (ICM) than in trophectoderm (TE), whereas Esg1 transcript was detected in both the ICM and the TE, particularly in the polar trophectoderm. The presence of an RNA-binding KH-domain in ESG1 led us to search for and identify 902 target transcripts by microarray analysis of immunoprecipitated ESG1 complex. Interaction of 20 target mRNA with ESG1, including Cdc25a, Cdc42, Ezh2, Nfyc and Nr5a2, was further validated by reverse transcriptase-polymerase chain reaction of the immunoprecipitation material, supporting the notion that ESG1 is an RNA-binding protein which associates with specific target transcripts. C1 NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. Kyoto Univ, Inst Frontier Med Sci, Dept Stem Cell Biol, Kyoto 6068507, Japan. RP Ko, MSH (reprint author), NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. EM kom@mail.nih.gov RI Ko, Minoru/B-7969-2009; Lopez de Silanes, Isabel/K-4962-2015 OI Ko, Minoru/0000-0002-3530-3015; Lopez de Silanes, Isabel/0000-0001-6762-9792 FU Intramural NIH HHS NR 44 TC 26 Z9 27 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD AUG PY 2006 VL 48 IS 6 BP 381 EP 390 DI 10.1111/j.1440-169x.2006.00875.x PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 061PM UT WOS:000238884700004 PM 16872451 ER PT J AU Wessels, E Duijsings, D Niu, TK Neumann, S Oorschot, VM de Lange, F Lanke, KHW Klumperman, J Henke, A Jackson, CL Melchers, WJG van Kuppeveld, FJM AF Wessels, Els Duijsings, Daniel Niu, Ting-Kuang Neumann, Steffi Oorschot, Viola M. de lange, Frank Lanke, Kjerstin H. W. Klumperman, Judith Henke, Andreas Jackson, Catherine L. Melchers, Willem J. G. van Kuppeveld, Frank J. M. TI A viral protein that blocks Arf1-mediated COP-I assembly by inhibiting the guanine nucleotide exchange factor GBF1 SO DEVELOPMENTAL CELL LA English DT Article ID ADP-RIBOSYLATION FACTOR; TO-GOLGI TRANSPORT; ENDOPLASMIC-RETICULUM; BREFELDIN-A; 3A PROTEIN; VESICLES; LOCALIZATION; COMPLEX; RNA; MAINTENANCE AB Many viruses modify cellular processes for their own benefit. The enterovirus 3A protein inhibits endoplasmic reticulum (ER)-to-Golgi transport, a function previously suggested to be important for viral suppression of immune responses. Here, we show that a virus carrying a 3A protein defective in inhibiting ER-to-Golgi transport is indeed less virulent in mice, and we unravel the mechanism by which 3A inhibits this trafficking step. Evidence is provided that 3A inhibits the activation of the GTPase ADP-ribosylation factor 1 (Arf1), which regulates the recruitment of the COP4 coat complex to membranes. 3A specifically inhibits the function of GBF1, a guanine nucleotide exchange factor for Arf1, by interacting with its N terminus. By specifically interfering with GBF1-mediated Arf1 activation, 3A may prove a valuable tool in dissecting the early steps of the secretory pathway. C1 Radboud Univ Nijmegen, MedCtr, Nijmegen Ctr Mol Life Sci, Dept Med Microbiol, NL-6500 HB Nijmegen, Netherlands. Radboud Univ Nijmegen, MedCtr, Nijmegen Ctr Mol Life Sci, Microscopial Imaging Ctr, NL-6500 HB Nijmegen, Netherlands. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Jena, Inst Virol & Antiviral Therapy, Med Ctr, D-07745 Jena, Germany. Univ Utrecht, Med Ctr, Dept Cell Biol, NL-3584 CX Utrecht, Netherlands. RP van Kuppeveld, FJM (reprint author), Radboud Univ Nijmegen, MedCtr, Nijmegen Ctr Mol Life Sci, Dept Med Microbiol, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM f.vankuppeveld@ncmls.ru.nl RI Jackson, Catherine/A-3421-2013; Lange, F./L-4471-2015; Melchers, Willem/C-8819-2015 OI Jackson, Catherine/0000-0002-0843-145X; Melchers, Willem/0000-0002-5446-2230 NR 46 TC 87 Z9 90 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD AUG PY 2006 VL 11 IS 2 BP 191 EP 201 DI 10.1016/j.devcel.2006.06.005 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 074ZY UT WOS:000239852700010 PM 16890159 ER PT J AU Schulz, LO Bennett, PH Ravussin, E Kidd, JR Kidd, KK Esparza, J Valencia, ME AF Schulz, Leslie O. Bennett, Peter H. Ravussin, Eric Kidd, Judith R. Kidd, Kenneth K. Esparza, Julian Valencia, Mauro E. TI Effects of traditional and Western environments on prevalence of type 2 diabetes in Pima Indians in Mexico and the U.S SO DIABETES CARE LA English DT Article ID PHYSICAL-ACTIVITY; LIFE-STYLE; INSULIN-RESISTANCE; MELLITUS; OBESITY; DATABASE AB OBJECTIVE - Type 2 diabetes and obesity have genetic and environmental determinants. We studied the effects of different environments on these diseases in Pima Indians in Mexico and the U.S. RESEARCH DESIGN AND METHODS - Adult Pima-Indian and non-Pima populations in the Sierra Madre mountains of Mexico were examined using oral glucose tolerance tests and assessments for obesity, physical activity, and other risk factors. Results were compared with those from Pima Indians in Arizona. Both Pima populations were typed for DNA polymorphisms to establish their genetic similarity. RESULTS - The age- and sex-adjusted prevalence of type 2 diabetes in the Mexican Pima Indians (6.9%) was less than one-fifth that in the U.S. Pima Indians (38%) and similar to that of non-Pima Mexicans (2.6%). The prevalence of obesity was similar in the Mexican Pima Indians (7% in men and 20% in women) and non-Pima Mexicans (9% in men and 27% in women) but was much lower than in the U.S. Pima Indians. Levels of physical activity were much higher in both Mexican groups than in the U.S. Pima Indians. The two Pima groups share considerable genetic similarity relative to other Native Americans. CONCLUSIONS - The much lower prevalence of type 2 diabetes and obesity in the Pima Indians in Mexico than in the U.S. indicates that even in populations genetically prone to these conditions, their development is determined mostly by environmental circumstances, thereby suggesting that type 2 diabetes is largely preventable. This study provides compelling evidence that changes in lifestyle associated with Westernization play a major role in the global epidemic of type 2 diabetes. C1 Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Wisconsin, Dept Hlth Sci, Milwaukee, WI 53201 USA. NIDDK, Phoen Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT USA. Ctr Invest Alimentac & Desarrollo AC, Hermosillo, Sonora, Mexico. RP Ravussin, E (reprint author), Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM ravusse@pbrc.edu FU NIDDK NIH HHS [DK-49957, 76-DK-0256]; NIGMS NIH HHS [GM57672] NR 32 TC 138 Z9 145 U1 1 U2 17 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2006 VL 29 IS 8 BP 1866 EP 1871 DI 10.2337/dc06-0138 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071HA UT WOS:000239589000024 PM 16873794 ER PT J AU Rodriguez, BL Palla, SL Fujimoto, WY Liu, LL Mayer-Davis, EJ Kershnar, A Imperatore, G Daniels, SR Williams, DE Linder, B Bell, RA Wadwa, RP AF Rodriguez, Beatriz L. Palla, Shana L. Fujimoto, Wilfred Y. Liu, Lenna L. Mayer-Davis, Elizabeth J. Kershnar, Ann Imperatore, Giuseppina Daniels, Stephen R. Williams, Desmond E. Linder, Barbara Bell, Ronny A. Wadwa, R. Paul CA SEARCH Diabet Youth Study Grp TI Prevalence of cardiovascular disease risk factors in US children and adolescents with diabetes - The SEARCH for Diabetes in Youth study SO DIABETES CARE LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Diabetes-Association CY JUN 10-14, 2005 CL San Diego, CA SP Amer Diabet Assoc ID CHOLESTEROL EDUCATION-PROGRAM; METABOLIC SYNDROME PHENOTYPE; NUTRITION EXAMINATION SURVEY; NATIONAL-HEALTH; ALL-CAUSE; MORTALITY; AMERICAN; STATEMENT; ASSOCIATION; OBESITY AB OBJECTIVE - The purpose of this study was to determine the prevalence and correlates of selected cardiovascular disease (CVD) risk factors among youth aged < 20 years with diabetes. RESEARCH DESIGN AND METHODS - The analysis included 1,083 girls and 1,013 boys examined as part of the SEARCH for Diabetes in Youth study, a multicenter, population-based stud), of youth 0-19 years of age with diabetes. Diabetes type was determined by a biochemical algorithm based on diabetes antibodies and fasting C-peptide level. CVD risk factors were defined as follows: HDL cholesterol < 40 mg/dl; age- and sex-specific waist circumference > 90th percentile; systolic or diastolic blood pressure > 90th percentile for age, sex, and height or taking medication for high blood pressure; and triglycerides > 110 mg/dl. RESULTS - The prevalence of having at least two CVD risk factors was 21%. The prevalence was 7% among children aged 3-9 years and 25% in youth aged 10-19 years (P < 0.0001), 23% among girls and 19% in boys (P = 0.04), 68% in American Indians, 37% in Asian/Pacific Islanders, 32% in African Americans, 35% in Hispanics, and 16% in non-Hispanic whites (P < 0.0001). At least two CVD risk factors were present in 92% of youth with type 2 and 14% of those with type 1A diabetes (P < 0.0001). In multivariate analyses, age, race/ethnicity, and diabetes type were independently associated With the odds of having at least two CVD risk factors (P < 0.0001). CONCLUSIONS - Many youth with diabetes have multiple CVD risk factors. Recommendations for weight, lipid, and blood pressure control in youth with diabetes need to be followed to prevent or delay the development of CVD as these youngsters mature. C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27157 USA. Univ Hawaii, Pacific Hlth Res Inst, Dept Geriatr Med, Honolulu, HI USA. Pacific Hlth Res Inst, Kona, HI USA. Univ S Carolina, Ctr Res Nutr & Hlth Disparities, Columbia, SC USA. Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC USA. Nalt Ctr Chron Dis Prevent & Hlth Promot, Div Diabet Translat, Ctr Dis Control & Prevent, Atlanta, GA USA. Wake Forest Univ, Sch Med Publ Hlth Sci, Winston Salem, NC USA. Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr Childhood Diabet, Denver, CO USA. Univ Washington, Child Hlth Inst, Seattle, WA USA. Kaiser Permanente, Downey, CA USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Bell, RA (reprint author), Wake Forest Univ, Sch Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM rbell@wfubmc.edu NR 20 TC 101 Z9 101 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 AUG PY 2006 VL 29 IS 8 BP 1891 EP 1896 DI 10.2337/dc06-0310 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071HA UT WOS:000239589000028 PM 16873798 ER PT J AU de Rekeneire, N Kritchevsky, SB Peila, R Kuller, LH Ding, JZ Strotmeyer, ES Colbert, LH Schwartz, AV Visser, M Vellas, B Shorr, RI Harris, TB AF De Rekeneire, Nathalie Kritchevsky, Stephen B. Peila, Rita Kuller, Lewis H. Ding, Jingzhong Strotmeyer, Elsa S. Colbert, Lisa H. Schwartz, Ann V. Visser, Marjolein Vellas, Bruno Shorr, Ronald I. Harris, Tamara B. TI Diabetes, hyperglycemia, and inflammation in older individuals - The health, aging and body composition study SO DIABETES CARE LA English DT Article ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE ATHEROSCLEROSIS; CORONARY-HEART-DISEASE; CHRONIC-RENAL-FAILURE; FACTOR-ALPHA; ADIPOSE-TISSUE; TNF-ALPHA; CARDIOVASCULAR-DISEASE; ACUTE-PHASE AB OBJECTIVE - The objective of this study was to assess the association of inflammation with hyperglycemia (impaired fasting glucose [IFG]/impaired glucose tolerance [IGT] and diabetes in older individuals. RESEARCH DESIGN AND METHODS - Baseline data from the Health, Aging and Body Composition study included 3,075 well-functioning black and white participants, aged 70-79 years. RESULTS - Of the participants, 24% had diabetes and 29% had IFG/IGT at baseline. C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) levels (P < 0.001) were significantly higher among diabetic participants and those with IFG/IGT. Odds of elevated IL-6 and TNF-alpha (> 75th percentile) were, respectively, 1-95 (95% CI 1.56-2.44) and 1.88 (1.51-2.35) for diabetic participants and 1.51 (1.21-1.87) and 1.14 (0.92-1.42) for those with IFG/IGT after adjustment for age, sex, race, smoking, alcohol intake, education, and study site. Odds ratios for elevated CRP were 2.90 (2.13-3.95) and 1.45 (1.03-2.04) women and men and 1.33 (1.07-1.69) for those with IFG/IGT regardless of sex. After adjustment for obesity, fat distribution, and inflammation-related conditions, IL-6 remained significantly related to both diabetes and IFG/IGT. CRP in women and TNF-alpha. in both sexes were significantly related to diabetes, respectively, whereas risk estimates for IFG/IGT were decreased by adjustment for adiposity. Among diabetic participants, higher levels of HbA(1c) were associated with higher levels of all three markers of inflammation, but only CRP remained significant after full adjustment. CONCLUSIONS - Our findings show that dysglycemia is associated with inflammation, and this relationship, although consistent in diabetic individuals, also extends to those with IFG/IGT. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Sticht Ctr Aging, Winston Salem, NC USA. Univ Wisconsin, Dept Kinesiol, Madison, WI USA. Vrije Univ Amsterdam, Ctr Med, Dept Nutr & Hlth, Amsterdam, Netherlands. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP de Rekeneire, N (reprint author), NIA, Lab Epidemiol Demog & Biometry, Suite 3C-309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. EM rekenein@nia.nih.gov RI Strotmeyer, Elsa/F-3015-2014; OI Strotmeyer, Elsa/0000-0002-4093-6036; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2101, N01-AG-6-2106] NR 44 TC 70 Z9 74 U1 1 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 AUG PY 2006 VL 29 IS 8 BP 1902 EP 1908 DI 10.2337/dc05-2327 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071HA UT WOS:000239589000030 PM 16873800 ER PT J AU Looker, HC Knowler, WC Hanson, RL AF Looker, Helen C. Knowler, William C. Hanson, Robert L. TI Stability of body weight in type 2 diabetes - Response to Chaudhry et al. SO DIABETES CARE LA English DT Letter C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. RP Looker, HC (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM hlooker@mail.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD AUG PY 2006 VL 29 IS 8 BP 1991 EP 1991 DI 10.2337/dc06-0876 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071HA UT WOS:000239589000060 PM 16873831 ER PT J AU Fetsch, PA Simsir, A Abati, A AF Fetsch, Patricia A. Simsir, Aylin Abati, Andrea TI There may be "madness in the methods," but the devil is in the details SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter ID OVARIAN-CANCER; DIFFERENTIAL-DIAGNOSIS; EFFUSION CYTOLOGY; PLEURAL EFFUSIONS; MESOTHELIAL CELLS; E-CADHERIN; CALRETININ; SERUM; IMMUNOHISTOCHEMISTRY; IMMUNOCYTOCHEMISTRY C1 NCI, Sect Natl Inst Hlth, Cytopathol Sect, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Sect Natl Inst Hlth, Cytopathol Sect, Bldg 10 Room 2A19, Bethesda, MD 20892 USA. EM abatia@mail.nih.gov NR 28 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD AUG PY 2006 VL 34 IS 8 BP 590 EP 593 DI 10.1002/dc.20461 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 068EA UT WOS:000239354000014 PM 16850490 ER PT J AU Strachan, RT Ferrara, G Roth, BL AF Strachan, Ryan T. Ferrara, Gina Roth, Bryan L. TI Screening the receptorome: an efficient approach for drug discovery and target validation SO DRUG DISCOVERY TODAY LA English DT Review ID PROTEIN-COUPLED RECEPTORS; DESIGNED MULTIPLE LIGANDS; HEART-DISEASE; WEIGHT-GAIN; SEROTONIN RECEPTORS; KINASE INHIBITORS; 5-HT2B RECEPTORS; DRUGGABLE GENOME; MAGIC BULLETS; IN-VITRO AB The receptorome, comprising at least 5% of the human genome, encodes receptors that mediate the physiological, pathological and therapeutic responses to a vast number of exogenous and endogenous ligands. Not surprisingly, the majority of approved medications target members of the receptorome. Several in silico and physical screening approaches have been devised to mine the receptorome efficiently for the discovery and validation of molecular targets for therapeutic drug discovery. Receptorome screening has also been used to discover, and thereby avoid, the molecular targets responsible for serious and unforeseen drug side effects. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Ctr Comprehens Canc, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Ctr Comprehens Canc, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat & Oncol, Ctr Comprehens Canc, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, Ctr Comprehens Canc, Cleveland, OH 44106 USA. EM bryan.roth@case.edu RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01DA01766]; NIMH NIH HHS [K02MH01366, R01MH61887, R01MH57635] NR 74 TC 41 Z9 44 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD AUG PY 2006 VL 11 IS 15-16 BP 708 EP 716 DI 10.1016/j.drudis.2006.06.012 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 075AB UT WOS:000239853000006 PM 16846798 ER PT J AU Hemachandra, AH Klebanoff, MA AF Hemachandra, A. H. Klebanoff, M. A. TI Critical periods of fetal and early childhood brain growth predict childhood cognitive function SO EARLY HUMAN DEVELOPMENT LA English DT Meeting Abstract C1 NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-3782 J9 EARLY HUM DEV JI Early Hum. Dev. PD AUG PY 2006 VL 82 IS 8 BP 534 EP 534 PG 1 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 082FJ UT WOS:000240371800121 ER PT J AU Kelty, MF Barr, RA AF Kelty, MF Barr, RA TI The National Institutes of Health's AREA program in action SO EDUCATIONAL GERONTOLOGY LA English DT Article AB The National Institutes of Health Academic Research Enhancement Award (AREA) program introduces research funding into regional universities and liberal arts colleges where hurdles to successful pursuit of research programs are substantial. Nevertheless, the authors of papers in this issue competed successfully and have benefited undergraduates in their respective institutions, as evidenced both by heightened retention rates and the numbers of student assistants who advance to graduate school. We discuss the role of a summer institute in helping to advance the work of these investigators, and suggest that the network which evolved may be extended as a model for collaborative and interdisciplinary research. We also describe details of the AREA program and where to obtain additional information about it. C1 NIA, Off Extramural Act, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Barr, RA (reprint author), NIA, Off Extramural Act, US Dept HHS, NIH, Gateway Bldg,Room 2C218,7201 Wisconsin Ave,MSC 92, Bethesda, MD 20892 USA. EM Barrr@mail.nih.gov NR 5 TC 3 Z9 3 U1 0 U2 0 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0360-1277 J9 EDUC GERONTOL JI Educ. Gerontol. PD AUG PY 2006 VL 32 IS 7 BP 589 EP 597 DI 10.1080/03601270600723809 PG 9 WC Education & Educational Research; Gerontology SC Education & Educational Research; Geriatrics & Gerontology GA 055KR UT WOS:000238449800010 ER PT J AU Rai, R Mushegian, A Makarova, K Kashina, A AF Rai, Reena Mushegian, Arcady Makarova, Kira Kashina, Anna TI Molecular dissection of arginyltransferases guided by similarity to bacterial peptidoglycan synthases SO EMBO REPORTS LA English DT Article DE arginyltransferase; Ate1; acetyltransferase ID RNA-PROTEIN TRANSFERASE; N-END RULE; IDENTIFICATION AB Post-translational protein arginylation is essential for cardiovascular development and angiogenesis in mice and is mediated by arginyl-transfer RNA-protein transferases Ate1-a functionally conserved but poorly understood class of enzymes. Here, we used sequence analysis to detect the evolutionary relationship between the Ate1 family and bacterial FemABX family of aminoacyl-tRNA-peptide transferases, and to predict the functionally important residues in arginyltransferases, which were then used to construct a panel of mutants for further molecular dissection of mouse Ate1. Point mutations of the residues in the predicted regions of functional importance resulted in changes in enzymatic activity, including complete inactivation of mouse Ate1; other mutations altered its substrate specificity. Our results provide the first insights into the mechanisms of Ate1-mediated arginyl transfer reaction and substrate recognition, and define a new protein superfamily called Dupli-GNAT to reflect its origin by the duplication of the GNAT acetyltransferase domain. C1 Univ Penn, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Missouri, Bioinformat Ctr, Stowers Inst Med Res, Kansas City, MO 64110 USA. Univ Kansas, Sch Med, Dept Microbiol, Kansas City, KS 66160 USA. NCBI, NIH, Bethesda, MD 20894 USA. RP Kashina, A (reprint author), Univ Penn, Dept Anim Biol, 3800 Spruce St, Philadelphia, PA 19104 USA. EM akashina@vet.upenn.edu OI Mushegian, Arcady/0000-0002-6809-9225 NR 17 TC 12 Z9 13 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD AUG PY 2006 VL 7 IS 8 BP 800 EP 805 DI 10.1038/sj.embor.7400747 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 099KL UT WOS:000241593200013 PM 16826240 ER PT J AU Nielsen, L Kaszniak, AW AF Nielsen, Lisbeth Kaszniak, Alfred W. TI Awareness of subtle emotional feelings: A comparison of long-term meditators and nonmeditators SO EMOTION LA English DT Article DE meditation; emotion; visual masking; subjective experience; somatic marker hypothesis ID SKIN-CONDUCTANCE RESPONSES; FEAR-RELEVANT STIMULI; FACIAL EXPRESSIONS; INDIVIDUAL-DIFFERENCES; VISCERAL PERCEPTION; MASKED STIMULI; EXPERIENCE; MOOD; COGNITION; EXPOSURE AB The authors explored whether meditation training to enhance emotional awareness improves discrimination of subtle emotional feelings hypothesized to guide decision-making. Long-term meditators and nonmeditators were compared on measures of self-reported valence and arousal, skin conductance response (SCR), and facial electromyography (EMG) to masked and nonmasked emotional pictures, and on measures of heartbeat detection and self-reported emotional awareness. Groups responded similarly to nonmasked pictures. In the masked condition, only controls showed discrimination in valence self-reports. However, meditators reported greater emotional clarity than controls, and meditators with higher clarity had reduced arousal and improved valence discrimination in the masked condition. These findings provide qualified support for the somatic marker hypothesis and suggest that meditation may influence how emotionally ambiguous information is processed, regulated, and represented in conscious awareness. C1 NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. RP Nielsen, L (reprint author), NIA, Behav & Social Res Program, NIH, 7201 Wisconsin,Suite 533, Bethesda, MD 20892 USA. EM nielsenli@nia.nih.gov NR 59 TC 49 Z9 50 U1 7 U2 26 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD AUG PY 2006 VL 6 IS 3 BP 392 EP 405 DI 10.1037/1528-3542.6.3.392 PG 14 WC Psychology, Experimental SC Psychology GA 081AY UT WOS:000240290800005 PM 16938081 ER PT J AU Couse, JF Yates, MM Rodriguez, KF Johnson, JA Poirier, D Korach, KS AF Couse, John F. Yates, Mariana M. Rodriguez, Karina F. Johnson, Jo Anne Poirier, Donald Korach, Kenneth S. TI The intraovarian actions of estrogen receptor-alpha are necessary to repress the formation of morphological and functional Leydig-like cells in the female gonad SO ENDOCRINOLOGY LA English DT Article ID 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE-1; ELEVATED LUTEINIZING-HORMONE; HUMAN CHORIONIC-GONADOTROPIN; POLYCYSTIC-OVARY-SYNDROME; ANDROGEN-PRODUCING CELLS; TRANSGENIC MICE; SEX REVERSAL; HYDROXYSTEROID DEHYDROGENASES; TESTICULAR STEROIDOGENESIS; DIFFERENTIAL EXPRESSION AB The predisposition of the testis and ovary to primarily synthesize testosterone (T) and estradiol (E2), respectively, is due to gonadal-specific cell types that differentially express the various hydroxysteroid (17 beta) dehydrogenase (HSD17B) isoforms. In testes, Leydig cells rely on LH stimulation to maintain expression of the type 3 (HSD17B3) isoform, which specifically converts androstenedione to T. In ovaries, thecal interstitial (TI) cells also rely on LH to induce androgen synthesis but lack HSD17B3 and therefore secrete androgens of low biological activity. Therefore, thecal cells may possess a mechanism to repress the Leydig cell phenotype and HSD17B3 expression. E2 is known to inhibit experimentally Leydig cell function and proliferation. In the current study, we provide evidence that E2 prevents the development of functional Leydig-like cells in the murine ovary and that this action is mediated by estrogen receptor (ER) alpha. ER alpha-null (alpha ERKO) female mice exhibit testis- like levels of Hsd17b3 expression in the ovaries and male-like levels of plasma T. Herein, we demonstrate that: 1) Hsd17b3 expression in alpha ERKO ovaries is a primary effect of the loss of intraovarian ER alpha actions; 2) alpha ERKO ovarian cells produce substantial levels of T in vitro, and this is blocked by a HSD17B3-specific inhibitor; 3) Hsd17b3 expression in alpha ERKO ovaries is LH regulated and localized to the secondary interstitial (SI)/TI cells; and 4) alpha ERKO SI/TI cells possess Leydig-like ultrastructural features. These data indicate that intraovarian ER alpha actions are required to repress Hsd17b3 expression in the ovary and may be important to maintaining a female phenotype in SI/TI cells. C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. CHU Quebec, Div Med Chem, Oncol & Mol Endocrinol Res Ctr, Quebec City, PQ G1V 4G2, Canada. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X FU Intramural NIH HHS [001-0047-172, NIH0010047172]; PHS HHS [NIH0010047172, 001-0047-172] NR 72 TC 17 Z9 17 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD AUG PY 2006 VL 147 IS 8 BP 3666 EP 3678 DI 10.1210/en.2006-0276 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 064FH UT WOS:000239074100006 PM 16627580 ER PT J AU Mahajan, R Bonner, MR Hoppin, JA Alavanja, MCR AF Mahajan, Rajeev Bonner, Matthew R. Hoppin, Jane A. Alavanja, Michael C. R. TI Phorate exposure and incidence of cancer in the agricultural health study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agriculture; insecticides; neoplasms; occupational exposure; organophosphorus compounds; organothiophosphorus compounds; pesticides; prostate; phorate ID NON-HODGKINS-LYMPHOMA; PROSTATE-CANCER; RISK-FACTORS; PESTICIDE APPLICATORS; ORGANOPHOSPHORUS PESTICIDES; HUMAN CYTOCHROME-P450; FAMILY HISTORY; COHORT; FARMERS; MEN AB BACKGROUND: We recently reported a link between use of the organophosphate pesticide phorate and risk of prostate cancer among applicators with a family history of prostate cancer in the Agricultural Health Study (AHS). OBJECTIVE: This finding, together with findings of associations between other organophosphate pesticides and cancer more broadly, prompted us to examine phorate exposure and overall cancer incidence in the AHS. Adding 3 years of follow-up and using more detailed exposure information allowed us to see whether the prostate cancer finding held. METHODS: The AHS is a prospective study of licensed, restricted-use pesticide applicators from North Carolina and Iowa. To our knowledge, this is the largest examination of workers occupationally exposed to phorate. Pesticide exposure and other information was collected using two self-administered questionnaires completed from 1993 to 1997. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CI), adjusting for potential confounders. RESULTS: Phorate use was not related to the incidence of all cancers combined or to any individual cancer, although we had insufficient numbers to study non-Hodgkin lymphoma or leukemia, which have been linked to organophosphates in other studies. Although prostate cancer risk was not significantly related to phorate use overall or among those without a family history, the risk tended to increase among applicators with a family history of prostate cancer. The interaction RR was 1.53 (95% CI, 0.99-2.37). CONCLUSION: The observed statistical interaction suggests a gene-environment interaction between family history and phorate exposure in the incidence of prostate cancer, but other explanations are also possible. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 8000, Rockville, MD 20852 USA. EM alavanjm@mail.nih.gov FU Intramural NIH HHS NR 42 TC 30 Z9 35 U1 1 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 AUG PY 2006 VL 114 IS 8 BP 1205 EP 1209 DI 10.1289/ehp.8911 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 069SH UT WOS:000239468000042 PM 16882526 ER PT J AU Elliott, L Longnecker, MP Kissling, GE London, SJ AF Elliott, Leslie Longnecker, Matthew P. Kissling, Grace E. London, Stephanie J. TI Volatile organic compounds and pulmonary function in the Third National Health and Nutrition Examination Survey, 1988-1994 SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air fresheners; air pollution (indoor); deodorants; 1,4-dichlorobenzene; exposure; environmental exposure; FEV1; lung function; respiratory function tests; VOC ID BLOOD-CONCENTRATIONS; MASS-SPECTROMETRY; US POPULATION; LUNG-FUNCTION; EXPOSURE; SYMPTOMS; ASTHMA; CHILDREN; MIXTURE; AIR AB BACKGROUND: Volatile organic compounds (VOCs) are present in much higher concentrations indoors, where people spend most of their time, than outdoors and may have adverse health effects. VOCs have been associated with respiratory symptoms, but few studies address objective respiratory end points such as pulmonary function. Blood levels of VOCs may be more indicative of personal exposures than are air concentrations; no studies have addressed their relationship with respiratory outcomes. OBJECTIVE: We examined whether concentrations of 11 VOCs that were commonly identified in blood from a sample of the U.S. population were associated with pulmonary function. METHODS: We used data from 953 adult participants (20-59 years of age) in the Third National Health and Nutrition Examination Survey (1988-1994) who had VOC blood measures as well as pulmonary function measures. Linear regression models were used to evaluate the relationship between 11 VOCs and measures of pulmonary function. RESULTS: After adjustment for smoking, only 1,4-dichlorobenzene (1,4-DCB) was associated with reduced pulmonary function. Participants in the highest decile of 1,4-DCB concentration had decrements of -153 mL [95% confidence interval (CI), -297 to -8] in forced expiratory volume in I see and -346 mL/sec (95% CI, -667 to -24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile. CONCLUSIONS: Exposure to 1,4-DCB, a VOC related to the use of air fresheners, toilet bowl deodorants, and mothballs, at levels found in the U.S. general population, may result in reduced pulmonary function. This common exposure may have long-term adverse effects on respiratory health. C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,Bldg 101,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; Longnecker, Matthew/0000-0001-6073-5322; London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS NR 35 TC 31 Z9 32 U1 1 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 AUG PY 2006 VL 114 IS 8 BP 1210 EP 1214 DI 10.1289/ehp.9019 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 069SH UT WOS:000239468000043 PM 16882527 ER PT J AU Zhang, YH Huang, W London, SJ Song, GX Chen, GH Jiang, LL Zhao, NQ Chen, BH Kan, HD AF Zhang, Yunhui Huang, Wei London, Stephanie J. Song, Guixiang Chen, Guohai Jiang, Lili Zhao, Naiqing Chen, Bingheng Kan, Haidong TI Ozone and daily mortality in Shanghai, China SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; mortality; ozone; time-series studies ID PARTICULATE AIR-POLLUTION; TIME-SERIES; HOSPITAL ADMISSIONS; MEXICO-CITY; LOS-ANGELES; US CITIES; EXPOSURE; ASSOCIATIONS; HEALTH; POLLUTANTS AB BACKGROUND: Controversy remains regarding the relationship between ambient ozone and mortality worldwide. In mainland China, the largest developing country, there has been no prior study investigating the acute effect of O-3 on death risk. Given the changes in types of air pollution from conventional coal combustion to the mixed coal combustion/motor vehicle emissions in China's large cities, it is worthwhile to investigate the acute effect of O-3 on mortality outcomes in the country. OBJECTIVES: We conducted a time-series study to investigate the relation between O-3 and daily mortality in Shanghai using 4 years of daily data (2001-2004). METHODS: We used the generalized additive model with penalized splines to analyze mortality, O-3 pollution, and covariate data in warm and cold seasons. We considered daily counts of all-cause mortality and several causc-specific subcategories (respiratory and cardiovascular). We also examined these associations among several subpopulations based on age and sex. RESULTS: O-3 was significantly associated with total and cardiovascular mortality in the cold season but not in the warm season. In the whole-year analysis, an increase of 10 pg/m(3) of 2-day average (lag01) O-3 corresponds to 0.45% [95% confidence interval (CI), 0.16-0.73%], 0.53% (95% CI, 0.10-0.96%), and 0.35% (95% CI, -0.40 to 1.09%) increase of total nonaccidental, cardiovascular, and respiratory mortality, respectively. In the cold season, the estimates increased to 1.38% (95% CI , 0.68-2.07%), 1.53% (95% CI ,0.54-2.52%), and 0.95% (95% CI, -0.71 to 2.60%), respectively. In the warm season, we did not observe significant associations for both total and causespecific mortality. The results were generally insensitive to model specifications such as lag structure of O-3 concentrations and degree of freedom for time trend. Multipoflutant models indicate that the effect of O-3 was not confounded by particulate matter <= 10 mu m in diameter (PM10) or by sulfur dioxide; however, after adding nitrogen dioxide into the model, the association of O-3 with total and cardiovascular mortality became statistically insignificant. CONCLUSIONS: O-3 pollution has stronger health effects in the cold than in the warm season in Shanghai. Our analyses also.strengthen the rationale for further limiting levels of O-3 pollution in outdoor air in the city. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Shanghai 200433, Peoples R China. Hlth Effects Inst, Boston, MA USA. Shanghai Ctr Dis Control & Prevent, Shanghai, Peoples R China. Shanghai Environm Monitoring Ctr, Shanghai, Peoples R China. Fudan Univ, Sch Publ Hlth, Dept Hlth Stat, Shanghai 200433, Peoples R China. RP Kan, HD (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM kanh@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS NR 51 TC 68 Z9 81 U1 4 U2 27 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2006 VL 114 IS 8 BP 1227 EP 1232 DI 10.1289/ehp.9014 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 069SH UT WOS:000239468000046 PM 16882530 ER PT J AU Lynch, SM Rusiecki, JA Blair, A Dosemeci, M Lubin, J Sandler, D Hoppin, JA Lynch, CF Alavanja, MCR AF Lynch, Shannon M. Rusiecki, Jennifer A. Blair, Aaron Dosemeci, Mustafa Lubin, Jay Sandler, Dale Hoppin, Jane A. Lynch, Charles F. Alavanja, Michael C. R. TI Cancer incidence among pesticide applicators exposed to cyanazine in the agricultural health study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE Agricultural Health Study; cancer; cyanazine; farming; herbicide; pesticides; triazine herbicide ID HERBICIDE MANUFACTURING WORKERS; TRIAZINE HERBICIDES; BREAST-CANCER; GROUND-WATER; RISK-FACTORS; FARMERS; IOWA; LYMPHOMA; ATRAZINE; COHORT AB BACKGROUND: Cyanazine is a common pesticide used frequently in the United States during the 1980s and 1990s. Animal and human studies have suggested that triazines may be carcinogenic, but results have been mixed. We evaluated cancer incidence in cyanazine-exposed pesticide applicators among the 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS). METHODS: We obtained detailed pesticide exposure information from a self-administered questionnaire completed at enrollment (1993-1997). Cancer incidence was followed through January 2002. Over half of cyanazine-exposed applicators had >= 6 years of exposure at enrollment, and approximately 85% had begun using cyanazine before the 1990s. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple cancer sites among cyanazine-exposed applicators. We calculated P-trend values, and all statistical tests were two-sided. Two exposure metrics were used: tertiles of lifetime days of exposure (LD) and intensity-weighted LD. RESULTS: A total of 20,824 cancer-free AHS applicators reported ever using cyanazine at enrollment. Cancer incidence comparisons between applicators with the lowest cyanazine exposure and those with the highest exposure yielded the following for the LD metric: all cancers, RR = 0.99 (95% CI, 0.80-1.24); prostate cancer, RR = 1.23 (95% CI, 0.87-1.70); all lymphohematopoietic cancers, RR = 0.92 (95% CI, 0.50-1.72); non-Hodgkin lymphoma, RR = 1.25 (95% Cl, 0.47-3.35); lung cancer, RR = 0.52 (95% CI, 0.22-1.25). CONCLUSIONS: We did not find any clear, consistent associations between cyanazine exposure and any cancer analyzed. The number of sites was small for certain cancers, limiting any conclusion with regard to ovarian, breast, and some other cancers. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, Epidemiol & Genet Res Program, Div Canc Control & Populat Sci,NIH,Dept Hlth & Hu, Rockville, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP Alavanja, MCR (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Execut Plaza S,Room 8000, Rockville, MD 20892 USA. EM alavanjm@mail.nih.gov FU Intramural NIH HHS NR 36 TC 19 Z9 23 U1 2 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 AUG PY 2006 VL 114 IS 8 BP 1248 EP 1252 DI 10.1289/ehp.8997 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 069SH UT WOS:000239468000050 PM 16882534 ER PT J AU Glass, RL Bridbord, K Rosenthal, J Claudio, L AF Glass, Roger L. Bridbord, Kenneth Rosenthal, Joshua Claudio, Luz TI Global perspective on environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 Fogarty Int Ctr, NIH, Bethesda, MD USA. Mt Sinai Sch Med, New York, NY USA. RP Glass, RL (reprint author), Fogarty Int Ctr, NIH, Bethesda, MD USA. EM glassr@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD AUG PY 2006 VL 114 IS 8 BP A454 EP A455 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 069SH UT WOS:000239468000001 PM 16882505 ER PT J AU Ward, MH de Kok, TM AF Ward, Mary H. de Kok, Theo M. TI Dietary nitrate: Ward et al. respond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID ENDOGENOUS NITROSATION; DRINKING-WATER; NITROSOPROLINE EXCRETION; ASCORBIC-ACID; EXPOSURE; PROLINE C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth Human Serv, NIH, Bethesda, MD 20892 USA. Univ Maastricht, Dept Hlth Risk Anal & Toxicol, Maastricht, Netherlands. Ctr Hosp Univ Quebec, Inst Natl Sante Publ, Unite Rech Sante Publ, Quebec City, PQ, Canada. Texas A&M Univ, Sch Rural Publ Hlth, College Stn, TX USA. So Denmark Univ, Odense, Denmark. Washington State Dept Hlth, Olympia, WA USA. US Geol Survey, Reston, VA 22092 USA. RP Ward, MH (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth Human Serv, NIH, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov RI de Kok, Theo/G-6213-2014 NR 16 TC 2 Z9 2 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 AUG PY 2006 VL 114 IS 8 BP A459 EP A461 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 069SH UT WOS:000239468000006 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Sampling of microbial diversity by complete genomes SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID BACTERIUM CHROMOHALOBACTER-SALEXIGENS; DEINOCOCCUS-GEOTHERMALIS; SEQUENCE; DINOFLAGELLATE; TEMPERATURE; METABOLISM; RESISTANCE; EVOLUTION; DSM-3043; STRAIN C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 30 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD AUG PY 2006 VL 8 IS 8 BP 1313 EP 1317 DI 10.1111/j.1462-2920.2006.01089.x PG 5 WC Microbiology SC Microbiology GA 061PS UT WOS:000238885300001 PM 16872395 ER PT J AU Motamedia, GK Salazar, P Smith, EL Lesser, RP Webber, WRS Ortinski, PI Vicini, S Rogawski, MA AF Motamedia, Gholam K. Salazar, Patricia Smith, Eric L. Lesser, Ronald P. Webber, William R. S. Ortinski, Pavel I. Vicini, Stefano Rogawski, Michael A. TI Termination of epileptiform activity by cooling in rat hippocampal slice epilepsy models SO EPILEPSY RESEARCH LA English DT Article DE cooling; epileptiform discharge; 4-aminopyridine; bicuculline; magnesium free; hippocampus ID SEIZURE-LIKE EVENTS; TEMPERATURE MODULATION; ENTORHINAL CORTEX; LOW MAGNESIUM; GH(3) CELLS; 4-AMINOPYRIDINE; ANTICONVULSANTS; DISCHARGES; GENERATION; RESISTANT AB Cooling has been shown to terminate experimentally induced epileptiform activity in models of epilepsy without causing injury to the cooled brain, suggesting that cooling could represent an approach to seizure control in intractable focal epilepsies. Here we sought to determine the most effective way to apply cooling to abort spontaneous epileptiform discharges in in vitro brain slice models. We induced spontaneous epileptiform activity in rat brain slices by exposure to 4-aminopyridine (4-AP), 4-AP plus bicuculline, and Mg2+-free artificial CSF (aCSF) at 28-34 degrees C. Extracellular field recordings were made at hippocampal or neocortical sites. Slice temperature was reduced by perfusion with cold aCSF. Rapid cooling at rates of 2-5 degrees C/s was compared to cooling at slower rates of 0.1-1 degrees C/s. Cooling at both rates reversibly aborted epileptiform discharges in all three models and at all recording sites. With rapid cooling, small temperature drops were highly effective in terminating discharges, an effect that was sustained for as long as the reduced temperature level was maintained. In contrast, slow cooling required much larger temperature drops to inhibit discharges. With slow cooling, absolute temperature drops to 21-22 degrees C caused a 90% reduction in event frequency, but cooling to 14-15 degrees C was required to terminate discharges. We conclude that rapid cooling as effectively aborts discharges in in vitro epilepsy models as does slow cooling, but the magnitude of the temperature change required is less. Practical devices to inhibit seizure activity may only need to induce small temperature drops, if the cooling can be applied sufficiently rapidly. (c) 2006 Elsevier B.V All rights reserved. C1 NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. Georgetown Univ, Dept Neurol, Washington, DC 20057 USA. Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Mexico City 04510, DF, Mexico. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD 21218 USA. Johns Hopkins Univ, Zanvyl Krieger Mind Brain Inst, Baltimore, MD 21218 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC 20057 USA. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, 35 Convent Dr Room 1C-1002, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU Intramural NIH HHS NR 25 TC 26 Z9 28 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD AUG PY 2006 VL 70 IS 2-3 BP 200 EP 210 DI 10.1016/j.eplepsyres.2006.05.001 PG 11 WC Clinical Neurology SC Neurosciences & Neurology GA 082FH UT WOS:000240371600014 PM 16815680 ER PT J AU Lian, ZX Liu, F Liu, S Xin, H Chen, ZY Tian, JH An, Y Cai, SL AF Lian, Z. X. Liu, F. Liu, S. Xin, H. Chen, Z. Y. Tian, J. H. An, Y. Cai, S. L. TI Cardioprotection of ischemic postconditioning and ATP-postconditioning in rabbits is associated with the activation of adenosine receptors SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Univ Lund Hosp, Dept Cardiol, S-22185 Lund, Sweden. NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. Sahlgrens Univ Hosp, Hjart Karlinst, Klin Expt Forsklab, Gothenburg, Sweden. NR 0 TC 1 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 72 EP 72 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668400280 ER PT J AU Koh, K Quon, M Han, S Shin, M Chung, W Kang, W Shin, E AF Koh, K. Quon, M. Han, S. Shin, M. Chung, W. Kang, W. Shin, E. TI Additive beneficial effects of fenofibrate combined with candesartan in the treatment of hypertriglyceridemic, hypertensive patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 NIH, Diabet Unit, Bethesda, MD 20892 USA. Gil Heart Ctr, Gachon Med Sch, Div Cardiol, Inchon, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 120 EP 120 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668400475 ER PT J AU Ulmer, H Brant, LJ Concin, H Diem, G Rapp, K Weiland, SK Ruttmann, E AF Ulmer, H. Brant, L. J. Concin, H. Diem, G. Rapp, K. Weiland, S. K. Ruttmann, E. CA VHMPP stud grp TI Longitudinal repeated measurements of gamma-glutamyl transferase and the risk for fatal cardio- and cerebrovascular disease SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Univ Ulm, Dept Epidemiol, Ulm, Germany. Agcy Prevent & Social Med, Bregenz, Austria. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Innsbruck Med Unit, Dept Med Stat, Innsbruck, Austria. RI Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Ulmer, Hanno/C-3488-2011 OI Ulmer, Hanno/0000-0001-5911-1002 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 303 EP 303 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668402042 ER PT J AU Koh, K Quon, M Han, S Shin, M Chung, W Kang, W Shin, E AF Koh, K. Quon, M. Han, S. Shin, M. Chung, W. Kang, W. Shin, E. TI Additive beneficial effects of ramipril combined with candesartan in the treatment of hypertensive patients SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract CT 28th Congress of the European-Society-of-Cardiology/World Congress of Cardiology CY SEP 02-06, 2006 CL Barcelona, SPAIN SP European Soc Cardiol, World Heart Federat C1 Gil Heart Ctr, Div Cardiol, Gachon Med Sch, Inchon, South Korea. NIH, Diabet Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X EI 1522-9645 J9 EUR HEART J JI Eur. Heart J. PD AUG PY 2006 VL 27 SU 1 BP 497 EP 497 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 086JA UT WOS:000240668403317 ER PT J AU Baum, M Cassileth, BR Daniel, R Ernst, E Filshie, J Nagel, GA Horneber, M Kohn, M Lejeune, S Maher, J Terje, R Smith, WB AF Baum, Michael Cassileth, Barrie R. Daniel, Rosy Ernst, Edzard Filshie, Jacqueline Nagel, Gerd Arno Horneber, Markus Kohn, Michelle Lejeune, Stephane Maher, Jane Terje, Risberg Smith, Wendy B. TI The role of complementary and alternative medicine in the management of early breast cancer: Recommendations of the European Society of Mastology (EUSOMA) SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE breast cancer; CAM; EUSOMA AB Patients diagnosed with breast cancer have many needs that for a start include the expectation of cure. Where cure is unlikely there is always a place for hope and spiritual support. Furthermore whether dealing with the early stages or with the advanced disease patients require symptomatic control that encompasses pain relief, control of nausea and vomiting and psychological distress. To achieve all of these goals there is a need that goes beyond the role of scientific medicine. This position papers describes the guidelines for the use of complimentary and alternative medicine (CAM) developed by a workshop on behalf of the European Society of Mastology (EUSOMA). (c) 2006 Elsevier Ltd. All rights reserved. C1 UCL, Portland Hosp, Dept Surg, London W1N 6AH, England. Mem Sloan Kettering Canc Ctr, Integrat Med Serv, New York, NY 10021 USA. Hlth Creat, Bristol, Avon, England. Peninsula Med Sch, Dept Complementary Med, Exeter, Devon, England. Royal Marsden Hosp, Dept Anaesthet & Pain Management, Sutton, Surrey, England. Compatence AAssn, Basel, Switzerland. Klinikum Nord, Inst Med Onkol Haematol & Einheit Knochenmarktran, Nurnberg, Germany. Macmillan Canc Relief, London, England. European Org Res Treatment Canc, Ctr Data, Brussels, Belgium. Macmillan Canc Relief, Serv Dev, London, England. Univ Tromso, Dept Oncol, N-9001 Tromso, Norway. NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Baum, M (reprint author), UCL, Portland Hosp, Dept Surg, Consulting Rooms,212-214 Great Portland St, London W1N 6AH, England. EM michael@mbaum.freeserve.co.uk NR 2 TC 13 Z9 13 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD AUG PY 2006 VL 42 IS 12 BP 1711 EP 1714 DI 10.1016/j.ejca.2006.02.019 PG 4 WC Oncology SC Oncology GA 082AV UT WOS:000240359600014 PM 16806902 ER PT J AU Malekshah, AF Kimiagar, M Saadatian-Elahi, M Pourshams, A Nouraie, M Goglani, G Hoshiarrad, A Sadatsafavi, M Golestan, B Yoonesi, A Rakhshani, N Fahimi, S Nasrollahzadeh, D Salahi, R Ghafarpour, A Semnani, S Steghens, JP Abnet, CC Kamangar, F Dawsey, SM Brennan, P Boffetta, P Malekzadeh, R AF Malekshah, A. F. Kimiagar, M. Saadatian-Elahi, M. Pourshams, A. Nouraie, M. Goglani, G. Hoshiarrad, A. Sadatsafavi, M. Golestan, B. Yoonesi, A. Rakhshani, N. Fahimi, S. Nasrollahzadeh, D. Salahi, R. Ghafarpour, A. Semnani, S. Steghens, J. P. Abnet, C. C. Kamangar, F. Dawsey, S. M. Brennan, P. Boffetta, P. Malekzadeh, R. TI Validity and reliability of a new food frequency questionnaire compared to 24 h recalls and biochemical measurements: pilot phase of Golestan cohort study of esophageal cancer SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE validity; reliability; esophageal cancer; cohort study; Iran ID RELATIVE VALIDITY; URINARY NITROGEN; EPIC PROJECT; VITAMIN-C; DIETARY; REPRODUCIBILITY; IRAN; VALIDATION; CAROTENOIDS; BIOMARKERS AB Background: A pilot study was carried out to evaluate validity and reproducibility of a food frequency questionnaire (FFQ), which was designed to be used in a prospective cohort study in a population at high risk for esophageal cancer in northern Iran. Methods: The FFQ was administered four times to 131 subjects, aged 35-65 years, of both sexes. Twelve 24-h dietary recalls for two consecutive days were administered monthly during 1 year and used as a reference method. The excretion of nitrogen was measured on four 24-h urine samples, and plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol was measured from two time points. Relative validity of FFQ and 24-h diet recall was assessed by comparing nutrient intake derived from both methods with the urinary nitrogen and plasma levels of beta-carotene, retinol, vitamin C and alpha-tocopherol. Results: Correlation coefficients comparing energy and nutrients intake based on the mean of the four FFQ and the mean of twelve 24-h diet recalls were 0.75 for total energy, 0.75 for carbohydrates, 0.76 for proteins and 0.65 for fat. Correlation coefficients between the FFQ-based intake and serum levels of beta-carotene, retinol, vitamin C and vitamin E/alpha-tocopherol were 0.37, 0.32, 0.35 and 0.06, respectively. Correlation coefficients between urinary nitrogen and FFQ-based protein intake ranged from 0.23 to 0.35. Intraclass correlation coefficients used to measure reproducibility of FFQ ranged from 0.66 to 0.89. Conclusion: We found that the FFQ provides valid and reliable measurements of habitual intake for energy and most of the nutrients studied. C1 Univ Tehran Med Sci, Digest Dis Res Ctr, Shariati Hosp, Tehran, Iran. Int Agcy Res Canc, F-69372 Lyon, France. Hop Edouard Herriot, Lyon, France. EA 3090, Lyon, France. Shaheed Beheshti Univ Med Sci, Natl Nutr & Food Sci Res Inst, Tehran, Iran. Golestan Univ Med Sci, Gorgan, Iran. Natl Canc Inst, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Malekzadeh, R (reprint author), Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. EM malek@ams.ac.ir RI Abnet, Christian/C-4111-2015; Houshyarrad, Anahita/H-4607-2016; Semnani, Shahryar/N-2270-2016; OI Abnet, Christian/0000-0002-3008-7843; Houshyarrad, Anahita/0000-0001-5698-8239; Semnani, Shahryar/0000-0002-8768-6142; Malekzadeh, Reza/0000-0003-1043-3814 NR 32 TC 67 Z9 70 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD AUG PY 2006 VL 60 IS 8 BP 971 EP 977 DI 10.1038/sj.ejcn.1602407 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 069SY UT WOS:000239469700007 PM 16465196 ER PT J AU Ronningen, KS Paltiel, L Meltzer, HM Nordhagen, R Lie, KK Hovengen, R Haugen, M Nystad, W Magnus, P Hoppin, JA AF Ronningen, Kjersti S. Paltiel, Liv Meltzer, Helle M. Nordhagen, Rannveig Lie, Kari K. Hovengen, Ragnhild Haugen, Margaretha Nystad, Wenche Magnus, Per Hoppin, Jane A. TI The biobank of the Norwegian mother and child cohort Study: A resource for the next 100 years SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE automation; biobank; Birth Cohort Study; DNA; plasma; quality control ID PREVENTION; CENTERS AB Introduction: Long-term storage of biological materials is a critical component of any epidemiological study. In designing specimen repositories, efforts need to balance future needs for samples with logistical constraints necessary to process and store samples in a timely fashion. Objectives: In the Norwegian Mother and Child Cohort Study (MoBa), the Biobank was charged with long-term storage of more than 380,000 biological samples from pregnant women, their partners and their children for up to 100 years. Methods: Biological specimens include whole blood, plasma, DNA and urine; samples are collected at 50 hospitals in Norway. All samples are sent via ordinary mail to the Biobank in Oslo where the samples are registered, aliquoted and DNA extracted. DNA is stored at -20 degrees C while whole blood, urine and plasma are stored at -80 degrees C. Results: As of July 2006, over 227,000 sample sets have been collected, processed and stored at the Biobank. Currently 250-300 sets are received daily. An important part of the Biobank is the quality control program. Conclusion: With the unique combination of biological specimens and questionnaire data, the MoBa Study will constitute a resource for many future investigations of the separate and combined effects of genetic, environmental factors on pregnancy outcome and on human morbidity, mortality and health in general. C1 Norwegian Inst Publ Hlth, Div Epidemiol, N-0403 Oslo, Norway. Norwegian Inst Publ Hlth, Div Environm Med, N-0403 Oslo, Norway. NIEHS, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Ronningen, KS (reprint author), Norwegian Inst Publ Hlth, Div Epidemiol, 4404,Nydalen, N-0403 Oslo, Norway. EM kjersti.skjold.ronningen@fhi.no OI Meltzer, Helle Margrete/0000-0002-3591-7017 FU NIEHS NIH HHS [N01 ES 85433, N01ES85433, Z01 ES044008-05]; NINDS NIH HHS [U01 NS047537, U01 NS 047537] NR 10 TC 90 Z9 91 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PD AUG PY 2006 VL 21 IS 8 BP 619 EP 625 DI 10.1007/s10654-006-9041-x PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 093KX UT WOS:000241168300006 PM 17031521 ER PT J AU Mahesh, SP Li, ZQ Liu, BY Fariss, RN Nussenblatt, RB AF Mahesh, Sankaranarayana P. Li, Zhuqing Liu, Baoying Fariss, Robert N. Nussenblatt, Robert B. TI Expression of GITR ligand abrogates immunosuppressive function of ocular tissue and differentially modulates inflammatory cytokines and chemokines SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE costimulation; GITRL; immune privilege; ocular autoimmunity; retinal pigment epithelial cells ID REGULATORY T-CELLS; TUMOR-NECROSIS-FACTOR; INDUCED TNF RECEPTOR; RETINAL-PIGMENT EPITHELIUM; IMMUNE PRIVILEGE; INDUCED APOPTOSIS; INDUCE APOPTOSIS; FAS LIGAND; SUPPRESSION; ACTIVATION AB The glucocorticoid-induced TNF-related receptor ligand (GITRL) was previously shown to be constitutively expressed at low levels in human eye, including retinal pigment epithelial (RPE) cells. By expressing enhanced yellow fluorescent protein-tagged human GITRL in human RPE cells, we investigated the significance of expression of GITRL on human ocular tissue. Confocal immunofluorescence microscopy and flow cytometry confirmed the surface expression of GITRL on RPE cells. However, a soluble form of GITRL was also detected. Remarkably, expression of GITRL on the RPE cells abrogated RPE-mediated immunosuppression of CD3(+) T cells, implicated as a possible mechanism for ocular immune privilege. This abrogation of immunosuppression by GITRL-RPE was dependent on GITR-GITRL interaction and could not be mimicked by anti-CD28 antibody. Analysis of cytokine profiles revealed high level of TGF-beta during the immunosuppression by RPE cells while expression of GITRL abrogated the RPE cell-induced TGF-beta secretion. Expression of GITRL also stimulates secretion of an array of proinflammatory cytokines/chemokines from T cells. GITR-GITRL interaction provides a unique proinflammatory costimulation that may signal through a different pathway than that of CD28-B7 costimulation. This study implicated that GITRL could be a potential candidate for regulation of the ocular immune privilege and the balance between immune privilege and inflammation. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112,10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov NR 44 TC 23 Z9 24 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 AUG PY 2006 VL 36 IS 8 BP 2128 EP 2138 DI 10.1002/eji.200635893 PG 11 WC Immunology SC Immunology GA 075BB UT WOS:000239855900013 PM 16874737 ER PT J AU Chen, X Oppenheim, JJ Winkler-Pickett, RT Ortaldo, JR Howard, OMZ AF Chen, Xin Oppenheim, Joost J. Winkler-Pickett, Robin T. Ortaldo, John R. Howard, O. M. Zack TI Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+)CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4(+)CD25(+) T regulatory cells; dexamethasone; experimental autoimmune encephalomyelitis; IL-2 ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNOLOGICAL SELF-TOLERANCE; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; CONTROLLED-TRIAL; CUTTING EDGE; CD4(+)CD25(+); INTERLEUKIN-2; IL-2; INDUCTION AB IL-2 is crucial for the production of CD4(+)CD25(+) T regulatory (Treg) cells while important for the generation of effective T cell-mediated immunity. How to exploit the capacity of IL-2 to expand Treg cells, while restraining activation of T effector (Teff) cells, is an important and unanswered therapeutic question. Dexamethasone (Dex), a synthetic glucocorticoid steroid, has been reported to suppress IL-2-mediated activation of Teff cells and increase the proportion of Treg cells. Thus, we hypothesized that glucocorticoids may be useful as costimulants to amplify IL-2-mediated selective expansion of Treg cells. We show in this study that short-term simultaneous administration of Dex and IL-2 markedly expanded functional suppressive Foxp3(+)CD4(+)CD25(+) T cells in murine peripheral lymphoid tissues. In a myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (EAE) mouse model, we observed that splenic CD4(+)CD25(+) T cells failed to suppress the proliferation of CD4(+)CD25(-) T cells. Pretreatment with Dex/IL-2 remarkably increased the proportion of CD4(+)FoxP3(+) cells and partially restored the function of splenic CD4(+) CD25(+) T cells, and inhibited the development of EAE. Therefore, the combination of glucocorticoid and IL-2, two currently used therapeutics, may provide a novel approach for the treatment of autoimmune diseases, transplant rejection and graft-vs.-host disease. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick, Ctr Canc Res,NIH, Frederick, MD 21701 USA. Natl Canc Inst, Expt Immunol Lab, Canc Res Ctr, Lab Expt Immunol,NIH, Frederick, MD USA. RP Chen, X (reprint author), NCI, Mol Immunoregulat Lab, Canc Res Ctr, NIH, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM chenxin@mail.nih.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 44 TC 113 Z9 123 U1 2 U2 6 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 AUG PY 2006 VL 36 IS 8 BP 2139 EP 2149 DI 10.1002/eji.2006.35873 PG 11 WC Immunology SC Immunology GA 075BB UT WOS:000239855900014 PM 16841298 ER PT J AU Hope, BT Simmons, DE Mitchell, TB Kreuter, JD Mattson, BJ AF Hope, Bruce T. Simmons, Danielle E. Mitchell, Tim B. Kreuter, Justin D. Mattson, Brandi J. TI Cocaine-induced locomotor activity and Fos expression in nucleus accumbens are sensitized for 6 months after repeated cocaine administration outside the home cage SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE caudate-putamen; neuroadaptation; novel environment; psychostimulant; sensitization; striatum ID MESSENGER-RNA EXPRESSION; EARLY GENE-EXPRESSION; VENTRAL TEGMENTAL AREA; C-FOS; STRIATAL NEURONS; ENVIRONMENTAL CONTEXT; CHRONIC AMPHETAMINE; BASAL GANGLIA; BEHAVIORAL SENSITIZATION; IMMUNOREACTIVE NEURONS AB Induction of the immediate early gene protein product Fos has been used extensively to assess neural activation in the striatum after repeated cocaine administration to rats in their home cages but rarely after repeated administration outside the home cage, which produces more robust locomotor sensitization. In the present study, we found cocaine-induced Fos expression in nucleus accumbens, but not caudate-putamen, was enhanced 1 and 6 months after repeated drug administration in locomotor activity chambers. Double-labelling of Fos protein and enkephalin mRNA indicated that Fos expression in nucleus accumbens was enhanced in enkephalin-positive, but not enkephalin-negative, medium spiny neurons. In contrast, cocaine-induced Fos expression was absent altogether in nucleus accumbens and unaltered in caudate-putamen 1 month after repeated cocaine administration in the home cage. As cocaine-induced locomotor activity was also enhanced 1 and 6 months after repeated cocaine administration in locomotor activity chambers, we wanted to confirm that neuronal activity in nucleus accumbens mediates cocaine-induced locomotor activity using our particular treatment regimen. Bilateral infusions of the GABA agonists baclofen and muscimol (1 mu g/side) into nucleus accumbens of sensitized rats blocked cocaine-induced Fos expression and locomotor activity. Thus, while neuronal activity in both D1- and D2-type neurons in nucleus accumbens can mediate acute cocaine-induced locomotor activity, the enhanced activation of enkephalinergic D2-type neurons suggests that these latter neurons mediate the enhancement of cocaine-induced locomotor activity for up to 6 months after repeated drug administration outside the home cage. C1 NIA, Behav Neurosci Branch, Intramural Res Program, Natl Inst Drug Abuse,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Hope, BT (reprint author), NIA, Behav Neurosci Branch, Intramural Res Program, Natl Inst Drug Abuse,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bhope@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 FU Intramural NIH HHS NR 59 TC 48 Z9 49 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2006 VL 24 IS 3 BP 867 EP 875 DI 10.1111/j.1460-9568.2006.04969.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 074AD UT WOS:000239783300021 PM 16930414 ER PT J AU Radley, JJ Johnson, LR Janssen, WGM Martino, J Lamprecht, R Hof, PR LeDoux, JE Morrison, JH AF Radley, Jason J. Johnson, Luke R. Janssen, William G. M. Martino, Jeremiah Lamprecht, Raphael Hof, Patrick R. LeDoux, Joseph E. Morrison, John H. TI Associative Pavlovian conditioning leads to an increase in spinophilin-immunoreactive dendritic spines in the lateral amygdala SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dendritic spine; electron microscopy; fear conditioning; immunohistochemistry; learning; rat; spinophilin ID LONG-TERM POTENTIATION; FEMALE RHESUS-MONKEYS; SYNAPTIC-TRANSMISSION; STRUCTURAL-CHANGES; PREFRONTAL CORTEX; PYRAMIDAL NEURONS; MEMORY FORMATION; AUDITORY-CORTEX; FEAR MEMORY; RAT AB Changes in dendritic spine number and shape are believed to reflect structural plasticity consequent to learning. Previous studies have strongly suggested that the dorsal subnucleus of the lateral amygdala is an important site of physiological plasticity in Pavlovian fear conditioning. In the present study, we examined the effect of auditory fear conditioning on dendritic spine numbers in the dorsal subnucleus of the lateral amygdala using an immunolabelling procedure to visualize the spine-associated protein spinophilin. Associatively conditioned rats that received paired tone and shock presentations had 35% more total spinophilin-immunoreactive spines than animals that had unpaired stimulation, consistent with the idea that changes in the number of dendritic spines occur during learning and account in part for memory. C1 Salk Inst Biol Studies, Neuronal Struct & Funct Lab, La Jolla, CA 92037 USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. NYU, Ctr Neural Sci, New York, NY 10003 USA. NIMH, Conte Ctr Neurosci Fear & Anxiety, New York, NY USA. RP Radley, JJ (reprint author), Salk Inst Biol Studies, Neuronal Struct & Funct Lab, La Jolla, CA 92037 USA. EM radley@salk.edu RI Morrison, John/F-9229-2012 FU NIMH NIH HHS [P50 MH58911] NR 63 TC 29 Z9 31 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2006 VL 24 IS 3 BP 876 EP 884 DI 10.1111/j.1460-9568.2006.04962.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 074AD UT WOS:000239783300022 PM 16930415 ER PT J AU Brown, PL Kiyatkin, EA AF Brown, P. Leon Kiyatkin, Eugene A. TI The role of peripheral Na plus channels in triggering the central excitatory effects of intravenous cocaine SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE behavior; brain temperature; cocaine methiodide; dopamine uptake inhibition; metabolic brain activation; procaine; rats ID CENTRAL-NERVOUS-SYSTEM; POSITRON-EMISSION-TOMOGRAPHY; LOCAL-ANESTHETICS; DOPAMINE UPTAKE; UPTAKE INHIBITION; RHESUS-MONKEYS; INTRAADMINISTRATION ASSOCIATIONS; REINFORCING PROPERTIES; BRAIN TEMPERATURE; SODIUM-CHANNELS AB While alterations in dopamine (DA) uptake appear to be a critical mechanism underlying locomotor and reinforcing effects of cocaine (COC), many centrally mediated physiological and affective effects of this drug are resistant to DA receptor blockade and are expressed more quickly following an intravenous (i.v.) injection than expected based on the dynamics of drug concentration in the brain. Because COC is also a potent local anesthetic, its rapid action on Na+ channels may be responsible for triggering these effects. We monitored temperatures in the nucleus accumbens, temporal muscle and skin together with conventional locomotion during a single i.v. injection of COC (1 mg/kg), procaine (PRO, 5 mg/kg; equipotential anesthetic dose), a short-acting local anesthetic drug that, like COC, interacts with Na+ channels, and cocaine methiodide (COC-MET, 1.31 mg/kg, equimolar dose), a quaternary COC derivative that is unable to cross the blood-brain barrier. In this way, we explored not only the importance of Na+ channels in general, but also the importance of central vs. peripheral Na+ channels specifically. COC induced locomotor activation, temperature increase in the brain and muscle, and a biphasic temperature fluctuation in skin. Though PRO did not induce locomotor activation, it mimicked, to a greater degree, the temperature effects of COC. Therefore, Na+ channels appear to be a key substrate for COC-induced temperature fluctuations in the brain and periphery. Similar to PRO, COC-MET had minimal effects on locomotion, but mimicked COC in its ability to increase brain and muscle temperature, and induce transient skin hypothermia. It appears therefore that COC's interaction with peripherally located Na+ channels triggers its central excitatory effects manifested by brain temperature increase, thereby playing a major role in drug sensing and possibly contributing to COC reinforcement. C1 Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, DHHS,NIH, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Branch, Intramural Res Program, DHHS,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 67 TC 10 Z9 10 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD AUG PY 2006 VL 24 IS 4 BP 1182 EP 1192 DI 10.1111/j.1460-9568.2006.05001.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 076TE UT WOS:000239979800023 PM 16930444 ER PT J AU Tomiyama, K Makihara, Y Yamamoto, H O'Sullivan, G Nally, RE Tighe, O Kinsella, A Fienberg, AA Grandy, DK Sibley, DR Croke, DT Koshikawa, N Waddington, JL AF Tomiyama, Katsunori Makihara, Yasuyuki Yamamoto, Hiroshi O'Sullivan, Gerard Nally, Rachel E. Tighe, Orna Kinsella, Anthony Fienberg, Allen A. Grandy, David K. Sibley, David R. Croke, David T. Koshikawa, Noriaki Waddington, John L. TI Disruption of orofacial movement topographies in congenic mutants with dopamine D(5) but not D(4) receptor or DARPP-32 transduction 'knockout' SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE orofacial movements; dopamine receptors; D(4) 'knockout'; D(5) 'knockout'; DARPP-32 'knockout'; topographical assessment ID ETHOLOGICALLY BASED RESOLUTION; INDUCED BEHAVIORAL TOPOGRAPHY; TARGETED GENE DELETION; D1-LIKE RECEPTORS; PHARMACOLOGICAL CHARACTERIZATION; PHENOTYPIC RESOLUTION; ADENYLYL-CYCLASE; JAW MOVEMENTS; MICE; D-1-LIKE AB The rote of D(1)-like [D(1), D(5)] and D(2)-like [D(2), D(3), D(4)] dopamine receptors and dopamine transduction via DARPP-32 in topographies of orofacial movement was assessed in restrained mice with congenic D(4) vs. D(5) receptor vs. DARPP-32 'knockout'. D(4) and DARPP-32 mutants evidenced no material phenotype; also, there were no alterations in topographical responsivity to either the selective D(2)-like agonist RU 24213 or the selective D(1)-like agonist SK and F 83959. In contrast, D(5) mutants evidenced an increase in spontaneous vertical jaw movements, which habituated more slowly than in wildtypes, and a decrease in horizontal jaw movements; topographical responsivity to SK and F 83959 and RU 24213 was unaltered. D(5) receptors regulate distinct topographies of vertical and horizontal jaw movement in an opposite manner. In assuming that the well-recognised rote of the D(1)-like family in regulating orofacial movements involves primarily D(1) receptors, a role for their D(5) counterparts may have been overlooked. (c) 2005 Elsevier B.V. and ECNP. All rights reserved. C1 Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Nihon Univ, Adv Res Inst Sci & Humanities, Tokyo 102, Japan. Nihon Univ, Sch Dent, Dept Pharmacol, Tokyo 101, Japan. Nihon Univ, Sch Dent, Dept Oral & Maxillofacial Surg, Tokyo 101, Japan. Royal Coll Surgeons Ireland, Dept Biochem, Dublin 2, Ireland. Dublin Inst Technol, Sch Math, Dublin 8, Ireland. Rockefeller Univ, Mol & Cellular Neurosci Lab, New York, NY 10021 USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97239 USA. NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. Nihon Univ, Sch Dent, Dent Res Ctr, Tokyo 101, Japan. RP Waddington, JL (reprint author), Royal Coll Surgeons Ireland, Dept Clin Pharmacol, St Stephens Green, Dublin 2, Ireland. EM jwadding@rcsi.ie FU NIDA NIH HHS [DA 12062, DA 10044]; NIMH NIH HHS [MH 40899, MH 39327] NR 47 TC 11 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD AUG PY 2006 VL 16 IS 6 BP 437 EP 445 DI 10.1016/j.euroneuro.2005.11.012 PG 9 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 068HI UT WOS:000239363600006 PM 16413758 ER PT J AU Mark, HFL Sokolic, RA Mark, Y AF Mark, Hon Fong L. Sokolic, Robert A. Mark, Yvonne TI Conventional cytogenetics and FISH in the detection of BCR/ABL fusion in chronic myeloid leukemia (CML) SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Review DE ABL; BCR; BCR/ABL; CML; chronic myeloid leukemia; FISH; fluorescent in situ hybridization ID CHRONIC MYELOGENOUS LEUKEMIA; IN-SITU HYBRIDIZATION; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOCYTIC-LEUKEMIA; CHRONIC GRANULOCYTIC-LEUKEMIA; IMATINIB MESYLATE THERAPY; WORLD-HEALTH-ORGANIZATION; STEM-CELL TRANSPLANTATION; MINIMAL RESIDUAL DISEASE; ABL TYROSINE KINASE C1 Boston Univ, Sch Med, Cytogenet Labs, Boston, MA 02118 USA. Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Mark, HFL (reprint author), Boston Univ, Sch Med, Cytogenet Labs, 700 Albany St, Boston, MA 02118 USA. EM hflmark@bu.edu; sokolicr@mail.nih.gov; ymark1@jhu.edu RI Sokolic, Robert/I-6072-2012 FU Intramural NIH HHS NR 82 TC 13 Z9 16 U1 2 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD AUG PY 2006 VL 81 IS 1 BP 1 EP 7 DI 10.1016/j.yexmp.2006.03.004 PG 7 WC Pathology SC Pathology GA 065IX UT WOS:000239154500001 PM 16729999 ER PT J AU Lee, JW Fuda, H Javitt, NB Strott, CA Rodriguez, IR AF Lee, Jung Wha Fuda, Hirotoshi Javitt, Norman B. Strott, Charles A. Rodriguez, Ignacio R. TI Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE cholesterol efflux; macula; 7-ketocholesterol; ARPE19; photoreceptors ID LOW-DENSITY-LIPOPROTEIN; CEREBROTENDINOUS XANTHOMATOSIS; RPE CELLS; IN-VITRO; CHOLESTEROL; 7-KETOCHOLESTEROL; METABOLISM; OXIDATION; OXYSTEROL; BIOSYNTHESIS AB Sterol 27-hydroxylase (CYP27A1) is a mitochondrial P-450 enzyme with broad substrate specificity for C27 sterols including 7-ketocholesterol (7kCh). CYP27A1 is widely expressed in human tissues but has not been previously demonstrated in the retina. In this study, we examined the expression and localization of CYP27A1 in the monkey retina where it localized mainly to the photoreceptor inner segments. CYP27A1 was also observed in Muller cells with faint immuno staining detected in the RPE and choriocapillaris. We also determined that the 27-hydroxylation of 7-ketocholesterol (27OH7kCh) rendered it non-toxic to cultured RPE cells. Moreover, the 27OH7kCh when mixed with 7-ketocholesterol significantly reduced the toxicity of 7-ketocholesterol. These data, when taken in context of the known functions of CYP27A1 imply that expression in the retina serves to modify the biological activity of oxidized sterols that are either transported or generated locally by photo-oxidation. Published by Elsevier Ltd. C1 NEI, Mechanisms Retinal Dis Sect, LRCMB, NIH, Bethesda, MD 20892 USA. NICHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. NYU, Med Ctr, Div Gastroenterol, New York, NY 10016 USA. RP Rodriguez, IR (reprint author), NEI, Mechanisms Retinal Dis Sect, LRCMB, NIH, 7 Mem Dr,MSC0706,Bldg 7,Room 302, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov FU Intramural NIH HHS [ZIA EY000307-15] NR 31 TC 36 Z9 36 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD AUG PY 2006 VL 83 IS 2 BP 465 EP 469 DI 10.1016/j.exer.2005.11.018 PG 5 WC Ophthalmology SC Ophthalmology GA 061ND UT WOS:000238878400028 PM 16549062 ER PT J AU Wang, ZY Yang, D Chen, Q Leifer, CA Segal, DM Su, SB Caspi, RR Howard, ZOM Oppenheim, JJ AF Wang, Zhao Yuan Yang, De Chen, Qian Leifer, Cindy A. Segal, David M. Su, Shao Bo Caspi, Rachel R. Howard, Zack O. M. Oppenheim, Joost J. TI Induction of dendritic cell maturation by pertussis toxin and its B subunit differentially initiate Toll-like receptor 4-dependent signal transduction pathways SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID NF-KAPPA-B; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IFN-REGULATORY FACTOR-3; BORDETELLA-PERTUSSIS; CYTOKINE PRODUCTION; BONE-MARROW; RESPONSES; ACTIVATION; EXPRESSION; LIPOPOLYSACCHARIDE AB Objective. Pertussis toxin (PT) has the capacity to activate dendritic cells (DCs) for the augmentation of cell-mediated immune responses. To investigate the mechanism(s) by which PT activates DCs, we investigated the effects of PT and its B-oligomer (PTB) on the maturation of human and mouse DCs and determined whether PT could act as a pathogen-associated molecular pattern to activate one of the Toll-like receptors (TLRs). Methods. The effects of PT and PTB on the maturation of human and mouse DCs were analyzed in terms of surface marker expression, cytokine production, antigen-presenting capacity, and intracellular signaling. The participation of TLR4 in PT-induced signaling was determined by comparing the effect of PT on DCs derived from TLR4-deficient and wildtype mice, as well as by measuring PT-induced NF-kappa B activation in HEK293 cells transiently transfected to express various TLRs. Results. Although both promoted phenotypic and functional maturation DCs, however, unlike PT that induced DC production of interleukin (IL)-6, tumor necrosis factor-alpha, IL-12, and interferon-inducible protein, PTB was capable of stimulating the production of interferon-inducible protein. Bone marrow-derived DCs from C3H/HeJ mice with defective TLR-4 alleles were unresponsive to PT and PTB, whereas DCs from C3WHeN mice responded. In addition, PT induced NF-kappa B activation and IL-8 production in HEK293 cells transfected with a combination of TLR4 and MD2 but not in nontransfected or TLR2-transfected HEK293 cells. Comparison of the patterns of cytokine induction and intracellular signaling events in DCs treated by PT and PTB revealed that although PT, like lipopolysaccharide, triggered both MyD88-dependent and -independent pathways, PTB preferentially triggered MyD88-independent pathways. Interestingly, mouse splenocyte proliferation in response to PT and PTB was only partially dependent on TLR4. Conclusion. The data identify PT as another pathogen-associated molecular pattern that induces DC maturation in a TLR4-dependent manner. Unlike PT, which triggers both MyD88-dependent and -independent pathways, PTB only triggers the MyD88-independent pathway in DCs. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NCI Frederick, CCR, LMI, Frederick, MD 21702 USA. SAIC Frederick, Intramural Basic Res Program, Frederick, MD 21702 USA. Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD USA. NEI, Immunol Lab, NIH, Bethesda, MD USA. RP Oppenheim, JJ (reprint author), NCI Frederick, CCR, LMI, Bldg 560,Room 21-89, Frederick, MD 21702 USA. EM oppenhei@mail.ncifcrf.gov OI Caspi, Rachel/0000-0002-7140-7671 FU NCI NIH HHS [N01-CO-12400, K22 CA113705] NR 43 TC 34 Z9 36 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD AUG PY 2006 VL 34 IS 8 BP 1115 EP 1124 DI 10.1016/j.exphem.2006.04.025 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 073OG UT WOS:000239751900018 PM 16863919 ER PT J AU Ghribi, O Larsen, B Schrag, M Herman, MM AF Ghribi, Othman Larsen, Brian Schrag, Matthew Herman, Mary M. TI High cholesterol content in neurons increases BACE, beta-amyloid, and phosphorylated tau levels in rabbit hippocampus SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; A beta; BACE1; cholesterol; hippocampus; rabbit; tau; ERK ID ACTIVATED PROTEIN-KINASE; TRIPLE-TRANSGENIC MODEL; ALZHEIMERS-DISEASE; PRECURSOR PROTEIN; A-BETA; ENDOPLASMIC-RETICULUM; SECRETORY PATHWAY; LIPID RAFTS; MOUSE MODEL; IN-VIVO AB Epidemiological, cellular, and animal studies suggest that abnormalities in cholesterol metabolism may contribute to the etiology of Alzheimer's disease by increasing the generation of beta-amyloid (A beta). However, the mechanism by which cholesterol increases A beta levels is not fully understood. In the present study, we demonstrate that feeding rabbits with 1% cholesterol for 7 months causes an increase in cholesterol content in neurons. High cholesterol content in neurons is accompanied by an increase in the level of BACE 1, the enzyme that initially cleaves beta-amyloid precursor protein to generate A, causing the accumulation of A beta 1 -42 peptide. These effects correlate with the phosphorylation of tau and the activation of extracellular signal-regulated protein kinase (ERK). Our data suggest that excessive cholesterol content in neurons, following long-term dietary cholesterol, may underlie the increase in BACE1 and A beta levels. Increased A beta levels may in turn trigger the phosphorylation of tau by activating ERK. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58202 USA. NIMH, IRP, NIH, Bethesda, MD 20892 USA. RP Ghribi, O (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, 501 N Columbia Rd, Grand Forks, ND 58202 USA. EM oghribi@medicine.nodak.edu FU NCRR NIH HHS [5P20RR017699] NR 42 TC 99 Z9 101 U1 3 U2 7 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 AUG PY 2006 VL 200 IS 2 BP 460 EP 467 DI 10.1016/j.expneurol.2006.03.019 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 072BH UT WOS:000239647100019 PM 16696972 ER PT J AU Bagnato, F Riva, M Antonelli, G AF Bagnato, Francesca Riva, Marco Antonelli, Guido TI Neutralising antibodies to IFN-beta in patients with multiple sclerosis SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE interferon-beta; multiple sclerosis; neutralising antibodies ID SECONDARY PROGRESSIVE MS; RANDOMIZED CONTROLLED TRIAL; RECOMBINANT HUMAN INTERFERON-BETA-1A; RELAPSING-REMITTING MS; BINDING-ANTIBODIES; FOLLOW-UP; IFN-BETA-1B TREATMENT; MYASTHENIA-GRAVIS; CEREBRAL ATROPHY; DOUBLE-BLIND AB The development of neutralising antibodies (NABs), or neutralising activity in the absence of NABs, is a potential complication of therapy with interferon (IFN)-beta for patients with multiple sclerosis, limiting therapeutic efficacy. Discontinuation of IFN-beta therapy in patients found to have sustained titres of NABs > 1:100 over an interval of 3 - 6 months has been recently proposed as a Level A recommendation. The extent to which NABs are causative, rather than an epiphenomenon, in determining drug failure has been a matter of numerous investigations and is still controversial. Thus, further studies are warranted for determining the role that NABs may play in reducing the response to the drug. In particular, the effects of NABs in reducing the efficacy of IFN-beta therapy beyond clinical relapse rate and lesion load on conventional imaging are not as yet fully understood. C1 Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dept Expt Med & Pathol, Sect Virol, I-00185 Rome, Italy. RP Bagnato, F (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5B16, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov NR 98 TC 1 Z9 1 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD AUG PY 2006 VL 6 IS 8 BP 773 EP 785 DI 10.1517/14712598.6.8.773 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 068MP UT WOS:000239378700005 PM 16856799 ER PT J AU Robinette, D Neamati, N Tomer, KB Borchers, CH AF Robinette, David Neamati, Nouri Tomer, Kenneth B. Borchers, Christoph H. TI Photoaffinity labeling combined with mass spectrometric approaches as a tool for structural proteomics SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE mass spectrometry; molecular modeling; photoaffinity labeling; photolabeling; protein-drug interactions; protein-peptide interactions; stoichiometry; structural proteomics; structure-based drug design ID LIGAND-BINDING SITE; CORTICOTROPIN-RELEASING FACTOR; P-GLYCOPROTEIN; CROSS-LINKING; PROTEIN INTERACTIONS; IDENTIFICATION; RECEPTOR; DOMAIN; EXPRESSION; PEPTIDES AB Protein chemistry, such as crosslinking and photoaffinity labeling, in combination with modern mass spectrometric techniques, can provide information regarding protein-protein interactions beyond that normally obtained from protein identification and characterization studies. While protein crosslinking can make tertiary and quaternary protein structure information available, photoaffinity labeling can be used to obtain structural data about ligand-protein interaction sites, such as oligonucleotide-protein, drug-protein and protein-protein interaction. In this article, we describe mass spectrometry-based photoaffinity labeling methodologies currently used and discuss their current limitations. We also discuss their potential as a common approach to structural proteomics for providing 3D information regarding the binding region, which ultimately will be used for molecular modeling and structure-based drug design. C1 Univ N Carolina, UNC Duke Proteom Core Facil, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. NIEHS, NIH, DHHS, Mass Spectrometry Grp,Lab Struct Biol, Res Triangle Pk, NC 27709 USA. RP Borchers, CH (reprint author), Univ N Carolina, UNC Duke Proteom Core Facil, Dept Biochem & Biophys, CB7260, Chapel Hill, NC 27599 USA. EM robinett@med.unc.edu; neamati@usc.edu; tomer@niehs.nih.gov; Christoph_Borchers@med.unc.edu RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS [Z01 ES050150-12]; NIAID NIH HHS [9P30 AI050410, P30 AI050410] NR 46 TC 43 Z9 43 U1 1 U2 23 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD AUG PY 2006 VL 3 IS 4 BP 399 EP 408 DI 10.1586/14789450.3.4.399 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 089ZF UT WOS:000240919700021 PM 16901199 ER PT J AU Gustofson, RL Kim, N Liu, S Stratton, P AF Gustofson, Robert L. Kim, Nancy Liu, Shannon Stratton, Pamela TI Endometriosis and the appendix: a case series and comprehensive review of the literature SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest DE endometriosis; appendix; appendectomy; pelvic pain; right lower quadrant; laparoscopy ID LOWER QUADRANT PAIN; PELVIC PAIN; LAPAROSCOPIC APPENDECTOMY; VERMIFORM APPENDIX; ABDOMINAL-PAIN; INTUSSUSCEPTION; PREGNANCY; WOMEN; PERFORATION; INTESTINES AB Objective: To report the prevalence of appendical disease in women with chronic pelvic pain undergoing laparascopy for possible endometriosis, summarize the literature and more accurately estimate the prevalence of endometriosis of the appendix. Design: Prospective case series and literature review. Setting: Academic research institute. Patient(s): One hundred thirty-three patients with chronic pelvic pain and possible endometriosis undergoing laparascopy. Intervention(s): History, physical exam, and abdominopelvic laparascopy. Endometriosis and adhesions were excised using selective Nd:YAG contact laser trabeculoplasty and pathologically evaluated. Only patients with visible abnormalities involving the appendix were treated via concurrent laparascopic appendectomy. Main Outcome Measure(s): Appendiceal abnormalities at laparascopy. Result(s): Of 133 patients, 13 had a previous appendectomy with unknown pathology. Of the remaining 120 patients, 109 reported right lower quadrant pain. Of this subgroup, six patients had appendiceal pathology, four with pathology-confirmed endometriosis, one with Crohn's disease suspected at laparascopy, and one with chronic appendicitis. The prevalence of appendiceal endometriosis in patients with biopsy-proven endometriosis (n = 97) or with right lower quadrant pain (n = 109) was 4.1% and 3.7% respectively. This rate was similar to the 2.8% prevalence confirmed by literature review in patients with endometriosis but was much higher than that reported in all patients (0.4%). Conclusion(s): Appendiceal endometriosis, while relatively uncommon in patients with endometriosis, is rare in the general population. In patients with right lower quadrant or pelvic pain, the appendix should be inspected for endometriosis and evidence of nongynecologic disease. C1 NICHD, RBMB, NIH, Bethesda, MD 20892 USA. RP Stratton, P (reprint author), NICHD, RBMB, NIH, 10 Ctr Dr MSC 1109,Bldg 10,CRC,1-3140, Bethesda, MD 20892 USA. EM strattop@cc1.nichd.nih.gov FU Intramural NIH HHS NR 52 TC 40 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2006 VL 86 IS 2 BP 298 EP 303 DI 10.1016/j.fertnstert.2005.12.076 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 072TU UT WOS:000239696700005 PM 16828481 ER PT J AU Copperman, AB DeCherney, A AF Copperman, Alan B. DeCherney, Alan TI The ever-rising spiral of technology and cost - Reply SO FERTILITY AND STERILITY LA English DT Letter C1 Mt Sinai Med Ctr, New York, NY 10029 USA. NICHD, RBMB, NIH, Bethesda, MD USA. RP Copperman, AB (reprint author), Mt Sinai Med Ctr, New York, NY 10029 USA. NR 1 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD AUG PY 2006 VL 86 IS 2 BP 497 EP 498 DI 10.1016/j.fertnstert.2006.04.009 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 072TU UT WOS:000239696700046 ER PT J AU Ehrenshaft, M Mason, RP AF Ehrenshaft, Marilyn Mason, Ronald P. TI Protein radical formation on thyroid peroxidase during turnover as detected by immuno-spin trapping SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE thyroid peroxidase; radical; DMPO; immuno-spin trapping ID MITOCHONDRIAL CYTOCHROME-C; HYDROGEN-PEROXIDE; HORSERADISH-PEROXIDASE; CATALYZED IODINATION; SODIUM-AZIDE; IMMUNOCHEMICAL DETECTION; IMMUNODOMINANT REGION; 3-DIMENSIONAL MODEL; MEDIATED OXIDATION; IODINE DEFICIENCY AB Thyroid peroxidase (TPO) is a 933 amino acid residue, heme-containing, integral membrane glycoprotein that catalyzes two steps in the maturation of the thyroid hormone precursor. As with other peroxidases, these reactions require hydrogen peroxide and initial enzyme oxidation. Previous researchers studied the oxidative state of the TPO heme moiety using spectrophotometric and catalytic analyses. We use a novel antiserum to 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to detect radical-derived DMPO spin-trapped TPO. Our work reveals that TPO generates radical adducts in the presence of H2O2, but that the generation of these adducts can be suppressed by the addition of substrates and inhibitors. Chemical alteration of the tyrosine residues of TPO greatly reduces the generation of TPO-DMPO adducts. Iodide strongly suppresses the H2O2-generated production of TPO radical adducts and protects the enzyme from loss of enzyme activity. Because the normal catalytic mechanism of TPO involves the production of radical species, TPO is potentially more susceptible to oxidative damage than most enzymes which do not require H2O2 as a substrate. We hypothesize that oxidatively damaged TPO may trigger the production of anti-TPO autoantibodies, resulting in the development of autoimmune thyroid disorders. Evidence that correlates iodine deficiencies with development of thyroid autoimmune disorders supports this conjecture. Published by Elsevier Inc. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Ehrenshaft, M (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F0-01,111 TW Alexander Dr,RTP, Res Triangle Pk, NC 27709 USA. EM ehrensh1@niehs.nih.gov FU Intramural NIH HHS NR 52 TC 37 Z9 37 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD AUG 1 PY 2006 VL 41 IS 3 BP 422 EP 430 DI 10.1016/j.freeradbiomed.2006.02.023 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 068CO UT WOS:000239349700006 PM 16843823 ER PT J AU Di Gregorio, C Frattini, M Maffei, S Ponti, G Losi, L Pedroni, M Venesio, T Bertario, L Varesco, L Risio, M de Leon, MP AF Di Gregorio, Carmela Frattini, Milo Maffei, Stefania Ponti, Giovanni Losi, Lorena Pedroni, Monica Venesio, Tiziana Bertario, Lucio Varesco, Liliana Risio, Mauro de Leon, Maurizio Ponz TI Immunohistochemical expression of MYH protein can be used to identify patients with MYH-associated polyposis SO GASTROENTEROLOGY LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; FAMILIAL ADENOMATOUS POLYPOSIS; BASE EXCISION-REPAIR; GENE-MUTATIONS; GERMLINE MUTATIONS; LYNCH-SYNDROME; HUMAN MUTY; LOCALIZATION; HOMOLOG; MTH1 AB Background&Aims: MYH-associated polyposis is a recently described, autosomal-recessive disease characterized by multiple colorectal adenomas and cancer. There are only few immunohistochemical studies of the MYH protein. We investigated the expression pattern of the MYH protein to evaluate whether a immunohistochemical approach could be used in clinical practice to screen patients for germline mutations in the MYH gene. Methods: The expression of MYH, MSH2, MLH1, and MSH6 proteins was studied by immunohistochemistry in 20 samples (colorectal adenomas or cancer) from 18 patients with biallelic MYH mutation, in 11 samples from patients with germline adenomatous polyposis coli (APC) mutations, in 20 samples from patients with sporadic colorectal cancers, and in 10 samples from patients with normal colonic mucosa without malignancies. Results: In all cases the mismatch repair proteins were expressed normally. Nuclear and cytoplasmic immunoreactivity for the MYH protein were observed in normal colorectal mucosa, in sporadic colorectal carcinomas, and in adenomas and carcinomas from patients carrying APC germline mutations. Adenomas and carcinomas from patients with MYH biallelic mutation showed a different pattern of expression: a strong granular cytoplasmic staining was observed without any nuclear expression. The same immunophenotype was observed in the surrounding normal mucosa. Conclusions: Patients with biallelic MYH mutations showed disappearance of staining from the nucleus, and segregation of immunoreactivity in the cytoplasm, both in neoplastic and surrounding healthy mucosa. Because this pattern of expression seems to be specific for biallelic mutations, it follows that immunohistochemistry might be used in clinical practice to screen patients at risk for MYH-associated polyposis. C1 Hosp Carpi, Div Pathol, Modena, Italy. Natl Canc Inst, Lab Expt Mol Pathol, I-20133 Milan, Italy. Univ Modena & Reggio Emilia, Dept Internal Med, I-41100 Modena, Italy. Univ Modena & Reggio Emilia, Dept Pathol, I-41100 Modena, Italy. Inst Canc Res & Treatment, Unit Pathol, Turin, Italy. Natl Canc Inst, Italian Registry Hereditary Colorectal Tumors, I-20133 Milan, Italy. Natl Canc Inst, Genoa, Italy. RP de Leon, MP (reprint author), Univ Modena & Reggio Emilia, Policlin, Dipartimento Med & Special Med, Via Pozzo 71, I-41100 Modena, Italy. EM deleon@unimo.it RI Ponti, Giovanni/A-5565-2012; Losi, Lorena/B-2583-2012; Ponz de Leon, Maurizio/A-9356-2015; Pedroni, Monica/C-9384-2015 OI Ponti, Giovanni/0000-0002-1971-7306; Losi, Lorena/0000-0002-8483-3936; Ponz de Leon, Maurizio/0000-0003-4465-1043; Pedroni, Monica/0000-0001-5374-5362 NR 23 TC 17 Z9 17 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2006 VL 131 IS 2 BP 439 EP 444 DI 10.1053/j.gastro.2006.05.049 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 072WX UT WOS:000239704800016 PM 16890597 ER PT J AU Conjeevaram, HS Fried, MW Jeffers, LJ Terrault, NA Wiley-Lucas, TE Afdhal, N Brown, RS Belle, SH Hoofnagle, JH Kleiner, DE Howell, CD AF Conjeevaram, Hari S. Fried, Michael W. Jeffers, Lennox J. Terrault, Norah A. Wiley-Lucas, Thelma E. Afdhal, Nezam Brown, Robert S. Belle, Steven H. Hoofnagle, Jay H. Kleiner, David E. Howell, Charles D. CA Virahep-C Study Grp TI Peginterferon and ribavirin treatment in African American and Caucasian American patients with hepatitis C genotype 1 SO GASTROENTEROLOGY LA English DT Article ID COMBINATION THERAPY; VIRUS-INFECTION; PLUS RIBAVIRIN; UNITED-STATES; COMPLICATIONS; INTERFERON; ALPHA-2B AB Background&Aims: Compared with Caucasian Americans (CA), African Americans (AA) with chronic hepatitis C are less likely to respond to interferon-based antiviral therapy. Methods: In a multicenter treatment trial, 196 AA and 205 CA treatment-naive patients with hepatitis C virus (HCV) genotype 1 infection were treated with peginterferon alfa-2a (180 mu g/wk) and ribavirin (1000-1200 mg/day) for up to 48 weeks. The primary end point was sustained virologic response (SVR). Results: Baseline features were similar among AA and CA, including HCV-RNA levels and histologic severity, but AA had higher body weights, a higher prevalence of diabetes and hypertension, and lower alanine transaminase levels (P <.001 for all). The SVR rate was 28% in AA and 52% in CA (P <.0001). Racial differences in viral responses were evident as early as treatment week 4. Breakthrough viremia was more frequent among AA than CA (13% vs 6%, P =.05); relapse rates were comparable (32% vs 25%, P =.30). Proportions of patients with serious adverse events and dose modifications and discontinuations were similar among AA and CA. In multiple regression analyses, CA had a higher SVR rate than AA (relative risk, 1.96; 95% confidence interval, 1.48-2.60; P <.0001). Other factors independently associated with higher SVR included female sex, lower baseline HCV-RNA level, less hepatic fibrosis, and more peginterferon taken. Conclusions: AA with chronic hepatitis C genotype 1 have lower rates of virologic response to peginterferon and ribavirin than CA. These differences are not explained by disease characteristics, baseline viral levels, or amount of medication taken. C1 Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Miami, Miami, FL 33152 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rush Univ, Chicago, IL 60612 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. New York Presbyterian Med Ctr, New York, NY USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. NIDDK, Bethesda, MD USA. Natl Canc Inst, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. RP Conjeevaram, HS (reprint author), Univ Michigan, Div Gastroenterol, 3912 Taubman Ctr,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM omsairam@umich.edu OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR000042, M01 RR000046, M01 RR00645, M01 RR16500, M02 RR000079]; NIDDK NIH HHS [U01 DK60327, U01 DK60309, U01 DK60324, U01 DK60329, U01 DK60335, U01 DK60340, U01 DK60341, U01 DK60342, U01 DK60344, U01 DK60345, U01 DK60346, U01 DK60349, U01 DK60352] NR 19 TC 347 Z9 356 U1 0 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD AUG PY 2006 VL 131 IS 2 BP 470 EP 477 DI 10.1053/j.gastro.2006.06.008 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 072WX UT WOS:000239704800020 PM 16890601 ER PT J AU Zhang, YH Luo, T Sargent, TD AF Zhang, YH Luo, T Sargent, TD TI Expression of TFAP2 beta and TFAP2 gamma genes in Xenopus laevis SO GENE EXPRESSION PATTERNS LA English DT Article DE neural crest; epidermis; transcription factor; induction; Wnt; BMP; TFAP2 ID TRANSCRIPTION FACTOR AP-2; NEURAL CREST SPECIFICATION; DNA-BINDING; INDUCTION; DEFECTS AB The embryonic expression patterns of two additional members of the transcription factor TFAP2 family in Xenopus laevis, TFAP2 beta and TFAP2 gamma, are described. Both genes share overlapping expression domains with the previously characterized TFAP2 alpha in this species, although differences exist. All three genes are expressed in the neural crest (NC) region at late gastrula to early neurula stages. TFAP2 alpha and TFAP2 gamma are also expressed in outer, epidermal cells, while TFAP2 beta is essentially NC-specific. All three are induced by Wnt/beta-catenin - BMP signals and all bind to a consensus TFAP2 recognition site from an epidermal keratin gene. Published by Elsevier B.V. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Sargent, TD (reprint author), NICHHD, Mol Genet Lab, NIH, Bldg 6B,Room 412, Bethesda, MD 20892 USA. EM tsargent@nih.gov FU Intramural NIH HHS NR 36 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-133X J9 GENE EXPR PATTERNS JI Gene Expr. Patterns PD AUG PY 2006 VL 6 IS 6 BP 589 EP 595 DI 10.1016/j.modgep.2005.11.011 PG 7 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 054RF UT WOS:000238395600002 PM 16414310 ER PT J AU Backman, CM Malik, N Zhang, YJ Shan, L Grinberg, A Hoffer, BJ Westphal, H Tomac, AC AF Baeckman, Cristina M. Malik, Nasir Zhang, YaJun Shan, Lufei Grinberg, Alex Hoffer, Barry J. Westphal, Heiner Tomac, Andreas C. TI Characterization of a mouse strain expressing Cre recombinase from the 3 ' untranslated region of the dopamine transporter locus SO GENESIS LA English DT Article DE cre-IoxP; dopamine; transporter; monoamine; knockin; IRES ID MESSENGER-RNA; GENE-EXPRESSION; KNOCKOUT MICE; RAT-BRAIN; NEURONS; REPORTER; AMPHETAMINE; CONSUMPTION; COCAINE; LACKING AB Dopamine (DA) neurotransmission has been implicated in several neurological and psychiatric disorders. The dopamine transporter (DAT) is highly expressed in dopaminergic neurons of the ventral mesencephalon and regulates neurotransmission by transporting DA back into the presynaptic terminals. To mediate restricted DNA recombination events into DA neurons using the Cre/loxP technology, we have generated a knockin mouse expressing Cre recombinase under the transcriptional control of the endogenous DAT promoter. To minimize interference with DAT function by preservation of both DAT alleles, Cre recombinase expression was driven from the 3' untranslated region (TUTR) of the endogenous DAT gene by means of an internal ribosomal entry sequence. Crossing this murine line with a LacZ reporter showed colocalization of DAT immunocytochemistry and P-galactosidase staining in all regions analyzed. This knockin mouse can be used for generating tissue specific knockouts in mice carrying genes flanked by loxP sites, and will facilitate the analysis of gene function in dopaminergic neurons. C1 Natl Inst Drug Abuse, Cellular Neurobiol Sect, NIH, Baltimore, MD 21224 USA. NICHHD, Lab Mammalian Genes & Dev, Bethesda, MD 20892 USA. RP Backman, CM (reprint author), Natl Inst Drug Abuse, Cellular Neurobiol Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM cbackman@mail.nih.gov RI backman, cristina/C-1276-2013; Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU Intramural NIH HHS NR 31 TC 92 Z9 92 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD AUG PY 2006 VL 44 IS 8 BP 383 EP 390 DI 10.1002/dvg.20228 PG 8 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 075DY UT WOS:000239864800005 PM 16865686 ER PT J AU Noguchi, Y Kurima, K Makishima, T de Angelis, MH Fuchs, H Frolenkov, G Kitamura, K Griffith, AJ AF Noguchi, Yoshihiro Kurima, Kiyoto Makishima, Tomoko de Angelis, Martin Hrabe Fuchs, Helmut Frolenkov, Gregory Kitamura, Ken Griffith, Andrew J. TI Multiple quantitative trait loci modify cochlear hair cell degeneration in the Beethoven (Tmc1(Bth)) mouse model of progressive hearing loss DFNA36 SO GENETICS LA English DT Article ID AUDITORY NEUROPATHY; MUTANT MICE; GENE; DOMINANT; DEAFNESS; MUTATIONS; LOCALIZATION; OTOF AB Dominant mutations of transmembrane channel-like gene 1 (TMC1) cause progressive sensorineural hearing loss in humans and Beethoven (Tmc1(Bth/+)) mice. Here we show that Tmc1(Bth/+) mice on a C3HeB/FeJ strain background have selective degeneration of inner hair cells while outer hair cells remain structurally and functionally intact. Inner hair cells primarily function as afferent sensory cells, whereas outer hair cells are electromotile amplifiers of auditory stimuli that can be functionally assessed by distortion product otoacoustic emission (DPOAE) analysis. When C3H-Tmc1(Bth/Bth) is crossed with either C57BL/6J or DBA/2J wild-type mice, F-1 hybrid Tmc1(Bth/+) progeny have increased hearing loss associated with increased degeneration of outer hair cells and diminution of DPOA-E amplitudes but no difference in degeneration of inner hair cells. We mapped at least one quantitative trait locus (QTL), Tmc1m1, for DPOAE amplitude on chromosome 2 in [(C/B) F-1 X C]N-2-Tmc1(Bth/+) backcross progeny, and three other QTL on chromosomes 11 (Tmc1m2), 12 (Tmc1m3), and 5 (Tmc1m4) in [(C/D)F-1 X C]N-2-Tmc1(Bth/+) progeny. The polygenic basis of outer hair cell degeneration in Beethoven mice provides a model system for the dissection of common, complex hearing loss phenotypes, such as presbycusis, that involve outer hair cell degeneration in humans. C1 Natl Inst Deafness & Other Commun Disorders, Sect Gene Struct & Funct, NIH, Rockville, MD 20850 USA. Tokyo Med & Dent Univ, Dept Otolaryngol, Grad Sch, Tokyo 1138519, Japan. GSF, Res Ctr Environm & Hlth, Inst Expt Genet, D-85764 Neuherberg, Germany. RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Gene Struct & Funct, NIH, 5 Res Court, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov RI Fuchs, Helmut/M-7347-2014; Hrabe de Angelis, Martin/F-5531-2012; OI Fuchs, Helmut/0000-0002-5143-2677; Hrabe de Angelis, Martin/0000-0002-7898-2353; Frolenkov, Gregory/0000-0002-9810-5024 FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000060] NR 32 TC 27 Z9 28 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD AUG PY 2006 VL 173 IS 4 BP 2111 EP 2119 DI 10.1534/genetics.106.057372 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 085RA UT WOS:000240620100024 PM 16648588 ER PT J AU Adachi, M Kurotani, R Morimura, K Shah, Y Sanford, M Madison, BB Gumucio, DL Marin, HE Peters, JM Young, HA Gonzalez, FJ AF Adachi, M. Kurotani, R. Morimura, K. Shah, Y. Sanford, M. Madison, B. B. Gumucio, D. L. Marin, H. E. Peters, J. M. Young, H. A. Gonzalez, F. J. TI Peroxisome proliferator activated receptor gamma in colonic epithelial cells protects against experimental inflammatory bowel disease SO GUT LA English DT Article ID PPAR-GAMMA; LIGAND ROSIGLITAZONE; ISCHEMIA-REPERFUSION; EXPERIMENTAL COLITIS; ULCERATIVE-COLITIS; MICE; CARCINOGENESIS; EXPRESSION; GENE; DIFFERENTIATION AB Introduction: Peroxisome proliferator activated receptor gamma (PPAR gamma) is expressed in epithelial cells, macrophage, and T and B lymphocytes. Ligand induced activation of PPAR gamma was reported to attenuate colitis activity but it is not clear whether this protection is mediated by epithelial or leucocyte PPAR gamma. Methods: Mice with targeted disruption of the PPAR gamma gene in intestinal epithelial cells, generated using a villin-Cre transgene and floxed PPAR gamma allele and designated PPAR gamma(Delta IEpC), were compared with littermate mice having only the PPAR gamma floxed allele with no Cre transgene that expressed PPAR gamma in the gut, designated PPAR gamma(F/F). Colitis was induced by administering dextran sodium sulphate (DSS) and the two mouse lines compared for typical symptoms of disease and expression of inflammatory cytokines. \ Results: PPAR gamma(Delta IEpC) mice displayed reduced expression of the PPAR gamma target genes ADRP and FABP in the gut but were otherwise normal. Increased susceptibility to DSS induced colitis, as defined by body weight loss, colon length, diarrhoea, bleeding score, and altered histology, was found in PPAR gamma(Delta DIEpC) mice in comparison with PPAR gamma(F/F) mice. Interleukin (IL)-6, IL-1 beta, and tumour necrosis factor a mRNA levels in colons of PPAR gamma Delta(DIEpC) mice treated with DSS were higher than in similarly treated PPAR gamma(F/F) mice. The PPAR gamma ligand rosiglitazone decreased the severity of DSS induced colitis and suppressed cytokine production in both PPAR gamma(F/F) and PPAR gamma Delta(DIEpC) mice. Conclusions: These studies reveal that PPAR gamma expressed in the colonic epithelium has an endogenous role in protection against DSS induced colitis and that rosiglitazone may act through a PPARc independent pathway to suppress inflammation. C1 NCI, NIH, Lab Metab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Lab Expt Immunol, Frederick, MD 21701 USA. Univ Michigan, Dept Cell & Dev Biol, Sch Med, Ann Arbor, MI 48109 USA. Penn State Univ, Dept Vet Sci, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. RP Gonzalez, FJ (reprint author), NCI, NIH, Lab Metab, Canc Res Ctr, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Peters, Jeffrey/D-8847-2011 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005708-14] NR 55 TC 109 Z9 111 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD AUG PY 2006 VL 55 IS 8 BP 1104 EP 1113 DI 10.1136/gut.2005.081745 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 064EW UT WOS:000239073000014 PM 16547072 ER PT J AU Little, JA McGowan, VR Kato, GJ Partovi, KS Feld, JJ Maric, I Martyr, S Taylor, JG Machado, RF Heller, T Castro, O Gladwin, MT AF Little, Jane A. McGowan, Vicki R. Kato, Gregory J. Partovi, Kristine S. Feld, Jordan J. Maric, Irina Martyr, Sabrina Taylor, James G. Machado, Roberto F. Heller, Theo Castro, Oswaldo Gladwin, Mark T. TI Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience from the National Institutes of Health and a literature review SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE sickle cell disease; erythropoietin; hydroxyurea; pulmonary hypertension ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; FETAL-HEMOGLOBIN; RENAL-FAILURE; RISK-FACTORS; ANEMIA; POLYMERIZATION; CREATININE; PARADOX; APLASIA; PATIENT AB Erythropoietin is being used more widely in the management of sickle cell disease (SCID, inclusive of homozygous sickle beta, SS, and compound heterozygous sickle beta thalassemia, S beta degrees thal), often in conjunction with hydroxyurea (HU). Herein, we summarize the published experience with erythropoietin use in SCID, in 39 patients (SS, n=30; S beta degrees thal, n=9) who were treated between 1990 and 1996; and in 13 patients with sickle syndromes (SS, n=12, compound heterozygous SC disease, n=1) who were treated with erythropoietin or darbepoietin at the National Institutes of Health (NIH) since 2002. The dose range of erythropoietin for SCID in the published series, at a median of > 200 U/Kg/dose, is higher than that used in end-stage renal disease. The median duration of erythropoietin therapy was >= 3 months, with minimal reported side-effects. At the NIH, the median age of sickle syndrome patients who received erythropoietin or darbepoietin (both referred to as EPO in the NIH series) was 51 (24 to 70) years; 12/13 patients had sickle-associated pulmonary hypertension. Eleven out of the 13 patients were treated with both HU and EPO for > 4 months (median of 11 months on EPO) without complication. Of the 13 patients, five (all SS) with pulmonary hypertension were given EPO for reticulocytopenia (< 100,000/PL) on HU; 5/13 patients (all SS), with pulmonary hypertension, were given EPO and HU concurrently, in the light of an estimated glomerular filtration rate of < 80 mL/minute. Three of the 13 patients (2 SS, 1 SC) were treated with EPO for miscellaneous reasons. Hematologic responses, detailed herein, suggest that EPO therapy may allow more aggressive HU dosing in high-risk SCID patients and in the setting of mild renal insufficiency, common to the aging sickle cell population. Furthermore EPO appears to be safe in SCID, particularly when used in conjunction with HU. We outline our current therapeutic strategy for EPO use in SCID. C1 NHLBI, Vasc Med Branch, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIDDK, Liver Dis Branch, Bethesda, MD USA. Ctr Clin, Dept Lab Med, NIH, Bethesda, MD USA. Ctr Clin, Crit Care Med Dept, NIH, Bethesda, MD USA. Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. RP Little, JA (reprint author), NHLBI, Vasc Med Branch, Ctr Clin, NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr,MSC 1476, Bethesda, MD 20892 USA. EM janelittle@mail.nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Taylor, James/0000-0002-4421-1809 FU Intramural NIH HHS [ZIA HL005802-05, ZIA HL005802-04, ZIA HL006014-01, ZIA HL006014-02] NR 57 TC 28 Z9 28 U1 0 U2 7 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD AUG PY 2006 VL 91 IS 8 BP 1076 EP 1083 PG 8 WC Hematology SC Hematology GA 070LI UT WOS:000239523500010 PM 16885048 ER PT J AU Abrams, DB AF Abrams, DB TI Applying transdisciplinary research strategies to understanding and eliminating health disparities SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE transdisciplinary; disparities; health ID SOCIOECONOMIC-STATUS; TOBACCO DEPENDENCE; PROMOTION RESEARCH; ALLOSTATIC LOAD; RE-AIM; INTERVENTIONS; SMOKING; FUTURE; EPIDEMIOLOGY; TRANSLATION AB This overview for the special issue of Health Education & Behavior on "Health Disparities and Social Inequities" briefly outlines the transdisciplinary (TD) approach to research and examines the scope of TD science. The need to embrace basic science as well as several domains of applied research is discussed along the TD "pipeline" from discovery to development to delivery to policy. The overview concludes with selected examples of the emerging TD science of disparities. One central challenge for a TD approach is the need to strengthen what is being called "the science of dissemination" along with improving the "dissemination of evidence-based science." C1 NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Abrams, DB (reprint author), NIH, Off Behav & Social Sci Res, 31 Ctr Dr,Bldg 31,Room B2B37, Bethesda, MD 20892 USA. EM Abramsd@od.nih.gov NR 73 TC 46 Z9 48 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD AUG PY 2006 VL 33 IS 4 BP 515 EP 531 DI 10.1177/1090198106287732 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 056QR UT WOS:000238540700008 PM 16769758 ER PT J AU Jin, DJ Yang, Y Zhou, Y AF Jin, D. J. Yang, Y. Zhou, Y. TI Study of the transcription machinery and gene regulation in Helicobacter pylori SO HELICOBACTER LA English DT Meeting Abstract CT 19th International Workshop on Helicobacter and Related Bacteric in Chronic Digestive Inflammation CY SEP 07-09, 2006 CL Wroclaw, POLAND C1 NCI, NIH, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD AUG PY 2006 VL 11 IS 4 BP 329 EP 329 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 063GC UT WOS:000239005100039 ER PT J AU Arlen, PM Dahut, WL Gulley, JL AF Arlen, Philip M. Dahut, William L. Gulley, James L. TI Immunotherapy for prostate cancer: What's the future? SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; PHASE-II TRIAL; MEMBRANE ANTIGEN; RADICAL PROSTATECTOMY; DENDRITIC CELLS; TUMOR-CELLS; MONOCLONAL-ANTIBODY; ANTITUMOR IMMUNITY; CARCINOMA-CELLS; COSTIMULATORY MOLECULES AB Prostate cancer is the most common noncutaneous cancer and second leading cause of cancer death among US men. A greater understanding of basic immunologic principles has led to a variety of new techniques, which has led to advancements in prostate cancer vaccines. This article discusses the rationale for the development of antibody-based therapy and vaccines therapy, including whole tumor cells, dendritic cells, and pox viral vectors. A summary of selected clinical studies incorporating these strategies and new approaches incorporating a combination of immunotherapy with traditional treatments for prostate cancer is presented. C1 NCI, Clin Res Grp, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Med Oncol Branch, Genitourinary & Gynecol Clin Res Sect, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Arlen, PM (reprint author), NCI, Clin Res Grp, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM pa52s@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 75 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD AUG PY 2006 VL 20 IS 4 BP 965 EP + DI 10.1016/j.hoc.2006.03.003 PG 20 WC Oncology; Hematology SC Oncology; Hematology GA 072TQ UT WOS:000239696300014 PM 16861126 ER PT J AU Morishima, C Morgan, TR Everhart, JE Wright, EC Shiffman, ML Everson, GT Lindsay, KL Lok, ASF Bonkovsky, HL Di Bisceglie, AM Lee, WM Dienstag, JL Ghany, MG Gretch, DR AF Morishima, Chihiro Morgan, Timothy R. Everhart, James E. Wright, Elizabeth C. Shiffman, Mitchell L. Everson, Gregory T. Lindsay, Karen L. Lok, Anna S. F. Bonkovsky, Herbert L. Di Bisceglie, Adrian M. Lee, William M. Dienstag, Jules L. Ghany, Marc G. Gretch, David R. CA HALT-C Trial Grp TI HCV RNA detection by TMA during the hepatitis C antiviral long-term treatment against cirrhosis (Halt-C) trial SO HEPATOLOGY LA English DT Article ID TRANSCRIPTION-MEDIATED AMPLIFICATION; INTERFERON-ALPHA THERAPY; ANALYTE-SPECIFIC REAGENT; VIRUS-RNA; VIROLOGICAL RESPONSE; PERFORMANCE-CHARACTERISTICS; PEGINTERFERON ALPHA-2A; QUALITATIVE ASSAY; FOLLOW-UP; QUANTIFICATION AB For making treatment decisions related to chronic hepatitis C, the utility of HCV RNA tests with increased sensitivity has not been defined. Prior interferon nonresponders with advanced fibrosis (n = 1,145) were retreated with peginterferon alpha-2a and ribavirin. Patients who were HCV RNA-negative by a polymerase chain reaction (PCR)-based assay (Roche COBAS Amplicor (TM) HCV Test, v. 2.0; lower limit of detection [LOD] 100 IU/mL) at week 20 (W20) received treatment for 48 weeks. Stored specimens were tested using the Bayer VERSANT (R) HCV RNA Qualitative (TMA) Assay (LOD 9.6 IU/mL) and compared to PCR results for the ability to predict sustained virological response (SVR, defined as undetectable HCV RNA by PCR at W72). Nearly all PCR-positive samples (1006/1007, 99.9%) were positive as assessed by TMA. Among 1,294 PCR-negative samples, 22% were TMA-positive. Negative TMA results were more predictive of SVR than were negative PCR results at W12 (82% vs. 64%, P <.001) and at W20 (66% vs. 52%, P = 0.001). SVR was more likely the earlier TMA had become negative during treatment (82% at W12, 44% at W20, 20% at W24). Among 45 patients who were TMA-positive but were PCR-negative at W20 and W24, none achieved SVR (95% CI: 0%-8%). Approximately 10% of patients with a single positive TMA result at the end of treatment still achieved SVR. In conclusion, negative TMA results at or after W12 were superior to negative PCR results for predicting SVR. In patients with negative PCR results during treatment, a single positive TMA test did not exclude SVR, although persistently positive tests did. C1 Univ Washington, Dept Lab Med, Seattle, WA 98104 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. New England Res Inst, Watertown, MA 02172 USA. Virginia Commonwealth Univ, Med Ctr, Hepatol Sect, Richmond, VA USA. Univ Colorado, Sch Med, Sect Hepatol, Div Gastroenterol & Hepatol, Denver, CO 80202 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. Univ Texas, SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Gastroenterol Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Morishima, C (reprint author), Univ Washington, Dept Lab Med, Box 359690, Seattle, WA 98104 USA. EM chihiro@u.washington.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01RR-00051, M01RR-00042, M01RR-00043, M01RR-00065, M01RR-00633, M01RR-00827, M01RR-01066, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2318, N01-DK-9-2319, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2322, N01-DK-9-2323, N01-DK-9-2324, N01-DK-9-2325, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2328] NR 22 TC 37 Z9 39 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD AUG PY 2006 VL 44 IS 2 BP 360 EP 367 DI 10.1002/hep.21265 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 070LF UT WOS:000239523200010 PM 16871570 ER PT J AU Brillon, DJ Sison, CP Salbe, AD Poretsky, L AF Brillon, D. J. Sison, C. P. Salbe, A. D. Poretsky, L. TI Reproducibility of a glycemic response to mixed meals in type 2 diabetes mellitus SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE diabetes; mixed meal; glycemic response; glycemic index; glucose levels ID BLOOD-GLUCOSE; INSULIN RESPONSES; PLASMA-GLUCOSE; CARBOHYDRATE EXCHANGE; DIETARY CARBOHYDRATE; FIBER CONTENT; INDEX; FOODS; COMPLICATIONS; PROGRESSION AB Objective: To evaluate the inter-patient and intra-patient reproducibility of the glycemic response to a mixed meal in individuals with type 2 diabetes mellitus (DM). Subjects/Setting: Six individuals with DM were admitted to the General Clinical Research Center for 6 days. Intervention: Subjects consumed 3 different meal plans consisting of 4 meals daily (breakfast, lunch, dinner and snack) on 2 separate occasions. Serum insulin and glucose levels were sampled at 19 time points every day. The glycemic response (GR) to a meal was calculated as the area under the glucose response curve after consumption of a given meal. In addition, the incremental area under the curve (IGR) was calculated assuming a pre-prandial (baseline) glucose value before each meal as zero. Results: Intra-patient correlation coefficients (R) of GR for meals in subjects with DM were quite good, ranging 0.69-0.94. The range of the inter-patient coefficients of variation (CV) for the same meals was 21.5-30.4%. For IGR, the R values ranged from 0.64 to 0.91 for 8 out of 12 meals, confirming good intra-patient reproducibility for these meals. CV for IGR ranged from 31% to 113%. Conclusions: For patients with DM, the GR of individual meals exhibits excellent intrapatient reproducibility, allowing prediction of the glycemic response to a given meal in an individual subject. However, significant inter-patient variability of the GR precludes its use for the prediction of post-prandial glucose concentrations in groups of patients with diabetes. C1 New York Presbyterian Hosp, Dept Med, Div Endocrinol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. N Shore Long Isl Jewish Inst Med Res, Biostat Unit, Manhasset, NY 11030 USA. NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Beth Israel Med Ctr, Dept Med, Div Endocrinol & Metab, New York, NY 10003 USA. Albert Einstein Coll Med, New York, NY 10003 USA. RP Poretsky, L (reprint author), Beth Israel Med Ctr, 317 E 17th St,Fierman Hall,7th Floor, New York, NY 10003 USA. EM lporetsk@bethisraelny.org FU NCRR NIH HHS [M01RR0004741] NR 42 TC 0 Z9 0 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD AUG PY 2006 VL 38 IS 8 BP 536 EP 542 DI 10.1055/s-2006-949526 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 083QR UT WOS:000240473800011 PM 16941281 ER PT J AU Pichler, I Mueller, JC Stefanov, SA de Grandi, A Volpato, CB Pinggera, GK Mayr, A Ogriseg, M Ploner, F Meitinger, T Pramstaller, PP AF Pichler, Irene Mueller, Jakob C. Stefanov, Stefan A. de Grandi, Alessandro Volpato, Claudia Beu Pinggera, Gerd K. Mayr, Agnes Ogriseg, Martin Ploner, Franz Meitinger, Thomas Pramstaller, Peter P. TI Genetic structure in contemporary South Tyrolean isolated populations revealed by analysis of Y-chromosome, mtDNA, and Alu polymorphisms SO HUMAN BIOLOGY LA English DT Article DE alpine populations; South Tyrol; Y chromosome; mtDNA; Alu; Ladins; demographic history ID INSERTION POLYMORPHISMS; SEQUENCE DIVERSITY; PCR ASSAY; HAPLOTYPES; SAMPLE; ALPS; MICROSATELLITE; EVOLUTION; LINEAGES; MUTATION AB Most of the inhabitants of South Tyrol in the eastern Italian Alps can be considered isolated populations because of their physical separation by mountain barriers and their sociocultural heritage. We analyzed the genetic structure of South Tyrolean populations using three types of genetic markers: Y-chromosome, mitochondrial DNA (mtDNA), and autosomal Ala markers. Using random samples taken from the populations of Val Venosta, Val Pusteria, Val Isarco, Val Badia, and Val Gardena, we calculated genetic diversity within and among the populations. Microsatellite diversity and unique event polymorphism diversity (on the Y chromosome) were substantially lower in the Ladin-speaking population of Val Badia compared to the neighboring German-speaking populations. In contrast, the genetic diversity of mtDNA haplotypes was lowest for the upper Val Venosta and Val Pusteria. These data suggest a low effective population size, or little admixture, for the gene pool of the Ladin-speaking population from Val Badia. Interestingly, this is more pronounced for Ladin males than for Ladin females. For the pattern of genetic Ala variation, both Ladin samples (Val Gardena and Val Badia) are among the samples with the lowest diversity. An admixture analysis of one German-speaking valley (Val Venosta) indicates a relatively high genetic contribution of Ladin origin. The reduced genetic diversity and a high genetic differentiation in the Rhaetoroman- and German-speaking South Tyrolean populations may constitute an important basis for future medical genetic research and gene mapping studies in South Tyrol. C1 European Acad Bolzano, Inst Med Genet, I-39100 Bolzano, Italy. Tech Univ Munich, Inst Med Stat & Epidemiol, D-8000 Munich, Germany. Tech Univ Munich, Inst Psychiat & Psychotherapy, D-8000 Munich, Germany. Hertie Inst Clin Brain Res, Tubingen, Germany. GSF Natl Res Inst Environm & Hlth, Inst Human Genet, Neuherberg, Germany. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. Hosp Brunico, Dept Lab Med, Brunico Bruneck, Italy. Hosp Bressanone, Dept Lab Med, Bressanone Brixen, Italy. Hosp Vipiteno, Dept Lab Med, Vipiteno Sterzing, Italy. Tech Univ Munich, Inst Human Genet, D-8000 Munich, Germany. Cent Hosp Bolzano, Dept Neurol, Bolzano, Italy. Univ Lubeck, Dept Neurol, Lubeck, Germany. RP Pichler, I (reprint author), European Acad Bolzano, Inst Med Genet, Viale Druso 1, I-39100 Bolzano, Italy. RI Pramstaller, Peter/C-2357-2008; Meitinger, Thomas/O-1318-2015 NR 47 TC 18 Z9 18 U1 0 U2 0 PU WAYNE STATE UNIV PRESS PI DETROIT PA 4809 WOODWARD AVE, DETROIT, MI 48201-1309 USA SN 0018-7143 J9 HUM BIOL JI Hum. Biol. PD AUG PY 2006 VL 78 IS 4 BP 441 EP 464 DI 10.1353/hub.2006.0057 PG 24 WC Biology; Genetics & Heredity SC Life Sciences & Biomedicine - Other Topics; Genetics & Heredity GA 134HL UT WOS:000244074000004 PM 17278620 ER PT J AU Husain, FT Fromm, SJ Pursley, RH Hosey, LA Braun, AR Horwitz, B AF Husain, Fatima T. Fromm, Stephen J. Pursley, Randall H. Hosey, Lara A. Braun, Allen R. Horwitz, Barry TI Neural bases of categorization of simple speech and nonspeech sounds SO HUMAN BRAIN MAPPING LA English DT Article DE brain; human; functional magnetic resonance imaging; phonemes; auditory; hemispheric asymmetry ID TREATED RHESUS-MONKEYS; WORKING-MEMORY; CATEGORICAL PERCEPTION; AUDITORY-CORTEX; ENHANCED DISCRIMINABILITY; COGNITIVE CONJUNCTION; PHONETIC BOUNDARIES; FUNCTIONAL MRI; ONSET-TIME; FMRI AB Categorization is fundamental to our perception and understanding of the environment. However, little is known about the neural bases underlying the categorization of sounds. Using human functional magnetic resonance imaging (fMRI) we compared the brain responses to a category discrimination task with an auditory discrimination task using identical sets of sounds. Our stimuli differed along two dimensions: a speech-nonspeech dimension and a fast-slow temporal dynamics dimension. All stimuli activated regions in the primary and nonprimary auditory cortices in the temporal cortex and in the parietal and frontal cortices for the two tasks. When comparing the activation patterns for the category discrimination task to those for the auditory discrimination task, the results show that a core group of regions beyond the auditory cortices, including inferior and middle frontal gyri, dorsomedial frontal gyrus, and intraparietal sulcus, were preferentially activated for familiar speech categories and for novel nonspeech categories. These regions have been shown to play a role in working memory tasks by a number of studies. Additionally, the categorization of nonspeech sounds activated left middle frontal gyrus and right parietal cortex to a greater extent than did the categorization of speech sounds. Processing the temporal aspects of the stimuli had a greater impact on the left lateralization of the categorization network than did other factors, particularly in the inferior frontal gyrus, suggesting that there is no inherent left hemisphere advantage in the categorical processing of speech stimuli, or for the categorization task itself. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Brain Imaging & Modeling Sect, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Language Sect, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Husain, FT (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Brain Imaging & Modeling Sect, Bldg 10,Rm 8S2335E,9000 Rockville Pike, Bethesda, MD 20892 USA. EM husainf@nidcd.nih.gov FU Intramural NIH HHS [Z99 CT999999] NR 80 TC 36 Z9 36 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1065-9471 J9 HUM BRAIN MAPP JI Hum. Brain Mapp. PD AUG PY 2006 VL 27 IS 8 BP 636 EP 651 DI 10.1002/hbm.20207 PG 16 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 067QC UT WOS:000239316700002 PM 16281285 ER PT J AU Panhuysen, CI Karban, A Manning, AK Bayless, TM Duerr, RH Bailey-Wilson, JE Epstein, EH Brant, SR AF Panhuysen, Carolien I. Karban, Amir Manning, Alisa Knodle Bayless, Theodore M. Duerr, Richard H. Bailey-Wilson, Joan E. Epstein, Ervin H., Jr. Brant, Steven R. TI Identification of genetic loci for basal cell nevus syndrome and inflammatory bowel disease in a single large pedigree SO HUMAN GENETICS LA English DT Article ID AFFECTED RELATIVE PAIRS; LINKAGE ANALYSIS; CROHNS-DISEASE; CARCINOMA SYNDROME; SUSCEPTIBILITY LOCI; ULCERATIVE-COLITIS; PROVIDES EVIDENCE; GORLIN-SYNDROME; COMPLEX TRAITS; MUTATIONS AB Basal Cell Nevus Syndrome (BCNS) is an autosomal dominant disease. PTCH1 gene mutations have been found responsible in many but not all pedigrees. Inflammatory Bowel Disease (IBD) is a complex genetic disorder, disproportionate in Ashkenazim, and characterized by chronic intestinal inflammation. We revisited a large Ashkenazim pedigree, first reported in 1968, with multiple diagnoses of BCNS and IBD, and with a common genetic cause for both disorders proposed. We expanded the pedigree to four generations and performed a genome-wide linkage study for BCNS and IBD traits. Twelve members with BCNS, seven with IBD, five with both diagnoses and eight unaffected were genotyped. Both non-parametric (GENEHUNTER 2.1) and parametric (FASTLINK) linkage analyses were performed and a validation through simulation was performed. BCNS linked to chromosome 9q22 (D9S1120) just proximal to the PTCH1 gene (NPL=3.26, P=0.003; parametric two-point LOD=2.4, parametric multipoint LOD=3.7). Novel IBD linkage evidence was observed at chromosome 1p13 (D1S420, NPL 3.92, P=0.0047; parametric two-point LOD=1.9). Linkage evidence was also observed to previously reported IBD loci on 4q, (D4S2623, NPL 3.02, P=0.012; parametric two-point LOD=2.15), 10q23 (D10S1225 near DLG5, NPL 3.33, P=0.0085; parametric two-point LOD=1.3), 12 overlapping the IBD2 locus (D12S313, NPL 2.6, P=0.018; parametric two-point LOD=1.52), and 7q (D7S510 and D7S3046, NPL 4.06, P=0.0035; parametric two-point LOD=2.18). In this pedigree affected by both BCNS and IBD, the two traits and their respective candidate genetic loci segregate independently; BCNS maps to the PTCH1 gene and IBD maps to several candidate regions, mostly overlapping previously observed IBD loci. C1 JHUSOM, Baltimore, MD 21231 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. NHGRI, NIH, Baltimore, MD USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Boston Univ, Sch Med, Genet Program, Dept Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Johns Hopkins Univ, Sch Med, Dept Med, Harvey M & Lyn P Meyerhoff Inflammatory Bowel Dis, Baltimore, MD 21205 USA. Rambam Med Ctr, Dept Gastroenterol, Haifa, Israel. RP Brant, SR (reprint author), JHUSOM, 1503 E Jefferson St, Baltimore, MD 21231 USA. EM sbrant@jhmi.edu OI Duerr, Richard/0000-0001-6586-3905; Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCRR NIH HHS [RR00052]; NIDDK NIH HHS [R01DK58189] NR 49 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD AUG PY 2006 VL 120 IS 1 BP 31 EP 41 DI 10.1007/s00439-006-0163-8 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 061HD UT WOS:000238861300003 PM 16733713 ER PT J AU Cutler, JA AF Cutler, Jeffrey A. TI Thiazide-associated glucose abnormalities: Prognosis, etiology, and prevention - Is potassium balance the key? SO HYPERTENSION LA English DT Editorial Material ID LIPID-LOWERING TREATMENT; ATTACK TRIAL ALLHAT; HYPERTENSIVE PATIENTS; ANTIHYPERTENSIVE TREATMENT; INTOLERANCE; OUTCOMES; DIURETICS; THERAPY; HYPOKALEMIA C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Cutler, JA (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM CutlerJ@nhlbi.nih.gov NR 19 TC 26 Z9 26 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 2006 VL 48 IS 2 BP 198 EP 200 DI 10.1161/01.HYP.0000231339.51310.b3 PG 3 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 069DZ UT WOS:000239427900005 PM 16801479 ER PT J AU Franceschini, N MacCluer, JW Goring, HHH Cole, SA Rose, KM Almasy, L Diego, V Laston, S Lee, ET Howard, BV Best, LG Fabsitz, RR Roman, MJ North, KE AF Franceschini, Nora MacCluer, Jean W. Goring, Harald H. H. Cole, Shelley A. Rose, Kathryn M. Almasy, Laura Diego, Vincent Laston, Sandra Lee, Elisa T. Howard, Barbara V. Best, Lyle G. Fabsitz, Richard R. Roman, Mary J. North, Karl E. TI A quantitative trait loci-specific gene-by-sex interaction on systolic blood pressure among American Indians - The Strong Heart Family Study SO HYPERTENSION LA English DT Article DE epidemiology; blood pressure; gender ID ANGIOTENSIN-CONVERTING ENZYME; WIDE LINKAGE ANALYSIS; ESSENTIAL-HYPERTENSION; CARDIOVASCULAR-DISEASE; PEDIGREE ANALYSIS; GENOME SCANS; HYPERGEN; SUSCEPTIBILITY; EXTENSIONS; PHENOTYPES AB Age-adjusted systolic blood pressure is higher in males than females. Genetic factors may account for this sex-specific variation. To localize sex-specific quantitative trait loci (QTL) influencing blood pressure, we conducted a genome scan of systolic blood pressure, in males and females, separately and combined, and tested for aggregate and QTL-specific genotype-by-sex interaction in American Indian participants of the Strong Heart Family Study. Blood pressure was measured 3 times and the average of the last 2 measures was used for analyses. Systolic blood pressure was adjusted for age and antihypertensive treatment within study center. We performed variance component linkage analysis in the full sample and stratified by sex among 1168 females and 726 males. Marker allele frequencies were derived using maximum likelihood estimates based on all individuals, and multipoint identity-by-descent sharing was estimated using Loki. We detected suggestive evidence of a QTL influencing systolic blood pressure on chromosome 17 at 129 cM between markers D17S784 and D17S928 (logarithm of odds [LOD]=2.4). This signal substantially improved when accounting for QTL-specific genotype-by-sex interaction (P=0.04), because we observed an LOD score of 3.3 for systolic blood pressure in women on chromosome 17 at 136 cM. The magnitude of the linkage signal on chromosome 17q25.3 was slightly attenuated when participants taking anti hypertensive medications were excluded, although suggestive evidence for linkage was still identified (LOD=2.8 in women). Accounting for interaction with sex improved our ability to detect QTLs and demonstrated the importance of considering genotype-by-sex interaction in our search for blood pressure genes. C1 Univ N Carolina, Sch Publ Hlth, Bank Amer Ctr, Dept Epidemiol, Chapel Hill, NC 27514 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. Univ Oklahoma, Coll Publ Hlth, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Univ Oklahoma, Coll Publ Hlth, Hlth Sci Ctr, Oklahoma City, OK USA. MedStar Res Inst, Washington, DC USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. RP Franceschini, N (reprint author), Univ N Carolina, Sch Publ Hlth, Bank Amer Ctr, Dept Epidemiol, 137 E Franklin St,Suite 306,CB 8050, Chapel Hill, NC 27514 USA. EM noraf@unc.edu OI Diego, Vincent/0000-0002-0007-2085 FU NHLBI NIH HHS [U01 HL065520, U01 HL41652, U01 HL65520, U01 HL41642, U01 HL65521, U01 HL41654]; NIMH NIH HHS [MH059490] NR 42 TC 16 Z9 17 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD AUG PY 2006 VL 48 IS 2 BP 266 EP 270 DI 10.1161/01.HYP.0000231651.91523.7e PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 069DZ UT WOS:000239427900020 PM 16818806 ER PT J AU Moreau-Villeger, V Delingette, H Sermesant, M Ashikaga, H McVeigh, E Ayache, N AF Moreau-Villeger, Valerie Delingette, Herve Sermesant, Maxime Ashikaga, Hiroshi McVeigh, Elliot Ayache, Nicholas TI Building maps of local apparent conductivity of the epicardium with a 2-D electrophysiological model of the heart SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE data assimilation; electrophysiology; heart modeling; inverse problem; parameter estimation; reaction-diffusion system AB In this paper, we address the problem of estimating the parameters of an electrophysiological model of the heart from a set of electrical recordings. The chosen model is the reaction-diffusion model on the transmembrane potential proposed by Aliev and Panfilov. For this model of the transmembrane, we estimate a local apparent two-dimensional conductivity from a measured depolarization time distribution. First, we perform an initial adjustment including the choice of initial conditions and of a set of global parameters. We then propose a local estimation by minimizing the quadratic error between the depolarization time computed by the model and the measures. As a first step we address the problem on the epicardial surface in the case of an isotropic version of the Aliev and Panfilov model. The minimization is performed using Brent method without computing the derivative of the error. The feasibility of the approach is demonstrated on synthetic electrophysiological measurements. A proof of concept is obtained on real electrophysiological measures of normal and infarcted canine hearts. C1 INRIA, ASCLEPIOS Res Project, F-06902 Sophia Antipolis, France. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Delingette, H (reprint author), INRIA, ASCLEPIOS Res Project, 2004 Route Lucioles, F-06902 Sophia Antipolis, France. EM Herve.Delingette@inria.fr OI Sermesant, Maxime/0000-0002-6256-8350; Ashikaga, Hiroshi/0000-0003-3689-6892 NR 31 TC 22 Z9 22 U1 0 U2 0 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD AUG PY 2006 VL 53 IS 8 BP 1457 EP 1466 DI 10.1109/TBME.2006.877794 PG 10 WC Engineering, Biomedical SC Engineering GA 066XH UT WOS:000239263400001 PM 16916080 ER PT J AU Zheng, LX Lenardo, M AF Zheng, Lixin Lenardo, Michael TI T helper 2 cells' preferred way to die SO IMMUNITY LA English DT Editorial Material ID DEATH C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zheng, LX (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 7 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2006 VL 25 IS 2 BP 187 EP 188 DI 10.1016/j.immuni.2006.08.006 PG 2 WC Immunology SC Immunology GA 077RM UT WOS:000240047500003 PM 16920635 ER PT J AU Shevach, EM AF Shevach, Ethan M. TI From vanilla to 28 flavors: Multiple varieties of T regulatory cells SO IMMUNITY LA English DT Editorial Material ID PLASMACYTOID DENDRITIC CELLS; TRANSCRIPTION FACTOR FOXP3; HUMAN PERIPHERAL-BLOOD; CUTTING EDGE; TGF-BETA; ACTIVATION; PHENOTYPE; ANTIGEN; LYMPHOCYTES; GENERATION AB Numerous T cell subpopulations have now been claimed to exhibit regulatory activity. Shevach discusses the current understanding of the different subsets of T regulatory cells and provides a perspective on the current areas of uncertainly and controversy in the field. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov NR 41 TC 367 Z9 382 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2006 VL 25 IS 2 BP 195 EP 201 DI 10.1016/j.immuni.2006.08.003 PG 7 WC Immunology SC Immunology GA 077RM UT WOS:000240047500006 PM 16920638 ER PT J AU Sciammas, R Shaffer, AL Schatz, JH Zhao, H Staudt, LM Singh, H AF Sciammas, Roger Shaffer, A. L. Schatz, Jonathan H. Zhao, Hong Staudt, Louis M. Singh, Harinder TI Graded expression of interferon regulatory factor-4 coordinates isotype switching with plasma cell differentiation SO IMMUNITY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; B-CELLS; TRANSCRIPTION FACTOR; LYMPHOCYTE DIFFERENTIATION; GENE-EXPRESSION; MATURE B; SECRETING CELLS; IRF FAMILY; BLIMP-1; ACTIVATOR AB Molecular mechanisms underlying the coordination of isotype switching with plasma cell differentiation are poorly understood. We show that interferon regulatory factor-4 (IRF-4) regulates both processes by controlling the expression of the Aicda and Prdm1 genes, which encode AID and Blimp-1, respectively. Genome-wide analysis demonstrated that Irf4(-/-) B cells failed to induce the entire Blimp-1 -dependent plasma cell program. Restoration of AID or Blimp-1 expression in Irf4(-/-) B cells promoted isotype switching or secretion, respectively. IRF-4 was expressed in a graded manner in differentiating B cells and targeted Prdm1. Higher concentration of IRF-4 induced Prdm1 and consequently the transition from a germinal center gene expression program to that of a plasma cell. We propose a gene-regulatory network in which graded expression of IRF-4 developmentally coordinates isotype switching with plasma cell differentiation. C1 Univ Chicago, Howard Hughes Med Inst, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), Univ Chicago, Howard Hughes Med Inst, Dept Mol Genet & Cell Biol, Chicago, IL 60637 USA. EM lstaudt@mail.nih.gov; hsingh@uchicago.edu OI Schatz, Jonathan/0000-0003-1842-228X FU Intramural NIH HHS NR 39 TC 241 Z9 243 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD AUG PY 2006 VL 25 IS 2 BP 225 EP 236 DI 10.1016/j.immuni.2006.07.009 PG 12 WC Immunology SC Immunology GA 077RM UT WOS:000240047500009 PM 16919487 ER PT J AU Wang, E Panelli, M Marincola, FM AF Wang, Ena Panelli, Monica Marincola, Francesco M. TI Autologous tumor rejection in humans: Trimming the myths SO IMMUNOLOGICAL INVESTIGATIONS LA English DT Review DE immunization immunotherapy/interleukin-2/melanoma; Epstein-Barr virus; basal cell carcinoma; renal cell carcinoma ID CD8(+) T-CELLS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISEASE; MELANOMA PATIENTS; METASTATIC MELANOMA; PEPTIDE VACCINE; CANCER-PATIENTS; IN-VIVO; HUMAN-PAPILLOMAVIRUS; GENE POLYMORPHISMS; ANTIGEN EXPRESSION AB There is overwhelming evidence that the human immune system can keep in check the growth of autologous tumors. Yet, this phenomenon is rare and most often tumors survive striking a balance with the host's immune system. The well-documented coexistence of immune cells that can recognize cancer and their targets within the same host is reminiscent of chronic allograft rejection well-controlled by immune suppression or of a lingering tissue-specific autoimmune reaction. In this review, we argue that autologous tumor rejection represents a distinct form of tissue-specific rejection similar to acute allograft rejection or to flares of autoimmunity. Here we discuss similarities within the biology of these phenomena that may converge into a common immunological constant of rejection. The purpose is to simplify the basis of immune rejection to its bare bones critically dissecting the significance of those components proposed by experimental models as harbingers of this final outcome. C1 NIH, Immunogenet Sect, Transfus Med Dept, Ctr Clin, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Transfus Med Dept, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM FMarincola@cc.nih.gov NR 116 TC 8 Z9 8 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0882-0139 J9 IMMUNOL INVEST JI Immunol. Invest. PD AUG-DEC PY 2006 VL 35 IS 3-4 BP 437 EP 458 DI 10.1080/08820130600762385 PG 22 WC Immunology SC Immunology GA 074OI UT WOS:000239821300010 PM 16916761 ER PT J AU Shevach, EM DiPaolo, RA Andersson, J Zhao, DM Stephens, GL Thornton, AM AF Shevach, Ethan M. DiPaolo, Richard A. Andersson, John Zhao, Dong-Mei Stephens, Geoffrey L. Thornton, Angela M. TI The lifestyle of naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells SO IMMUNOLOGICAL REVIEWS LA English DT Review DE autoimmune gastritis; regulatory T cells ID TRANSCRIPTION FACTOR FOXP3; CUTTING EDGE; IN-VITRO; INTESTINAL INFLAMMATION; FOREIGN ANTIGEN; DENDRITIC CELLS; TRANSGENIC MICE; CD25(+); ACTIVATION; EXPRESSION AB Numerous studies over the past 10 years have demonstrated the importance of naturally occurring CD4(+)CD25(+)Foxp3(+) regulatory T cells (nTregs) in immune regulation. We analyzed the mechanism of action of nTregs in a well-characterized model of autoimmune gastritis and demonstrated that nTregs act at an early stage of disease progression to inhibit the differentiation of naive T cells to pathogenic T-helper 1 effectors. The effects of nTregs in this model are not antigen-specific but are mediated by activation of the nTregs by ubiquitous self-peptide major histocompatibility complex class II complexes together with cytokines released by activated effector cells. Studies in vitro confirmed that some nTregs exist in an activated state in vivo and can be activated to exert non-specific suppressor effector function by stimulation with interleukin-2 in the absence of engagement of their T-cell receptor. Natural Tregs can differentiate in vitro to exhibit potent granzyme B-dependent, partially perforin-independent cytotoxic cells that are capable of specifically killing antigen-presenting B cells. Natural Treg-mediated killing of antigen-presenting cells may represent one pathway by which they can induce long-lasting suppression of autoimmune disease. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315, Bethesda, MD 20892 USA. EM eshevach@niaid.nih.gov RI Andersson, John/A-4436-2009; OI Andersson, John/0000-0003-2799-6349 NR 36 TC 307 Z9 324 U1 4 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2006 VL 212 BP 60 EP 73 DI 10.1111/j.0105-2896.2006.00415.x PG 14 WC Immunology SC Immunology GA 065WB UT WOS:000239189600005 PM 16903906 ER PT J AU Belkaid, Y Blank, RB Suffia, I AF Belkaid, Yasmine Blank, Rebecca B. Suffia, Isabelle TI Natural regulatory T cells and parasites: a common quest for host homeostasis SO IMMUNOLOGICAL REVIEWS LA English DT Review DE immunity; parasite; regulatory T cells ID LEISHMANIA-MAJOR INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; TGF-BETA; DENDRITIC CELLS; IN-VIVO; BALB/C MICE; CUTANEOUS LEISHMANIASIS; LATENT LEISHMANIASIS; AIRWAY INFLAMMATION AB This review discusses the roles played by natural CD4(+)CD25(+) regulatory T cells (natural Tregs) during parasitic infections. Natural Tregs may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural Tregs also help to limit collateral tissue damage caused by vigorous antimicrobial immune responses. We discuss the hypothesis that parasites have evolved means to manipulate the host's natural Treg population, thereby generating conditions that secure survival in their vertebrate host for an extended period of time. C1 NIAID, Mucosal Immunol Unit, NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), NIAID, Mucosal Immunol Unit, NIH, Parasit Dis Lab, 4 Ctr DDr,B1-28, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov FU Intramural NIH HHS NR 102 TC 90 Z9 99 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD AUG PY 2006 VL 212 BP 287 EP 300 DI 10.1111/j.0105-2896.2006.00409.x PG 14 WC Immunology SC Immunology GA 065WB UT WOS:000239189600020 PM 16903921 ER PT J AU Tkaczyk, C Jensen, BM Iwaki, S Gilfillan, AM AF Tkaczyk, Christine Jensen, Bettina M. Iwaki, Shoko Gilfillan, Alasdair M. TI Adaptive and innate immune reactions regulating mast cell activation: from receptor-mediated signaling to responses SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID FC-EPSILON-RI; PROTEIN-KINASE-C; TOLL-LIKE RECEPTORS; HIGH-AFFINITY RECEPTOR; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; N-TERMINAL KINASE; DEPENDENT CYTOKINE PRODUCTION; ALPHA GENE-EXPRESSION; FACTOR-KAPPA-B; TNF-ALPHA AB Mast cells play a role in the body's defense mechanisms associated with innate and adaptive immune reactions. When activated by such reactions, mast cells secrete a diverse group of inflammatory mediators whose role is to help the body destroy or clear parasites, bacteria, and viruses. It is the same mediators produced by these defense mechanisms, however, that are responsible for the adverse inflammatory cellular reactions that are manifested in allergic disease states such as asthma. A better understanding of the mechanisms by which these immunologic processes affect mast cell activation may provide insight into how these detrimental aspects of mast cell activation may be isolated from the beneficial aspects. Thus, in this article, we discuss the current understanding about how innate and adaptive immune responses lead to the release of inflammatory mediators from mast cells and discuss the intracellular signaling mechanisms that regulate these responses. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Gilfillan, AM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM agilfillan@niaid.nih.gov FU Intramural NIH HHS NR 140 TC 14 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 2006 VL 26 IS 3 BP 427 EP + DI 10.1016/j.iac.2006.05.011 PG 25 WC Allergy; Immunology SC Allergy; Immunology GA 090QY UT WOS:000240967200005 PM 16931287 ER PT J AU Wilson, TM Metcalfe, DD Robyn, J AF Wilson, Todd M. Metcalfe, Dean D. Robyn, Jamie TI Treatment of systemic mastocytosis SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID MAST-CELL DISEASE; TYROSINE KINASE INHIBITOR; CHRONIC MYELOGENOUS LEUKEMIA; BONE-MARROW-TRANSPLANTATION; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOMONOCYTIC LEUKEMIA; BULLOUS URTICARIA PIGMENTOSA; ORAL DISODIUM-CROMOGLYCATE; COMPARING INTERFERON-ALPHA; CHRONIC MYELOID-LEUKEMIA AB Systemic mastocytosis is a heterogeneous disorder characterized by diverse signs and symptoms. No curative therapy presently exists. Conventional management has relied on agents that antagonize mediators released by mast cells, inhibit mediator secretion, or modulate mast cell proliferation. Recent advances in our molecular understanding of the pathophysiology of systemic mastocytosis have provided new therapeutic considerations. Conventional management and promising novel agents are summarized in this review. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Robyn, J (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM jrobyn@niaid.nih.gov FU Intramural NIH HHS NR 166 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD AUG PY 2006 VL 26 IS 3 BP 549 EP + DI 10.1016/j.iac.2006.05.009 PG 26 WC Allergy; Immunology SC Allergy; Immunology GA 090QY UT WOS:000240967200011 PM 16931293 ER PT J AU Semnani, RT Keiser, PB Coulibaly, YI Keita, F Diallo, AA Traore, D Diallo, DA Doumbo, OK Traore, SF Kubofcik, J Klion, AD Nutman, TB AF Semnani, Roshanak Tolouei Keiser, Paul B. Coulibaly, Yaya I. Keita, Falaye Diallo, Abdallah A. Traore, Diakaridia Diallo, Dapa A. Doumbo, Ogobara K. Traore, Sekou F. Kubofcik, Joseph Klion, Amy D. Nutman, Thomas B. TI Filaria-induced monocyte dysfunction and its reversal following treatment SO INFECTION AND IMMUNITY LA English DT Article ID HEAT-SHOCK PROTEINS; HUMAN LYMPHATIC FILARIASIS; HUMAN DENDRITIC CELLS; MANSONELLA-PERSTANS; WUCHERERIA-BANCROFTI; IMMUNE-RESPONSE; BRUGIA-MALAYI; T-CELLS; LOA-LOA; MACROPHAGES AB Monocyte dysfunction in filarial infection has been proposed as one mechanism underlying the diminished antigen-specific T-cell response seen in patent lymphatic filariasis. Cytokine/chemokine production and gene expression in monocytes from fillaria-infected patients and uninfected healthy donors were assessed unstimulated and in response to stimulation with Staphylococcus aureus Cowan I bacteria plus gamma interferon both before and 8 months following treatment. Monocytes from filaria-infected individuals were studded with intracellular microfilarial antigens. Furthermore, monocytes from these individuals were less capable of producing interleukin-8 (IL-8), Exodus II, MIP-1 alpha, MIP-1 beta, and IL-1 alpha and preferentially expressed genes involved in apoptosis and adhesion compared with monocytes from uninfected donors. Eight months following treatment with a single dose of ivermectin-albendazole, some of these defects were reversed, with monocyte production of IL-8, IL-1 alpha, MIP-1 alpha, and IL-10 being comparable to that seen in the uninfected controls. In addition, a marked increase in mRNA expression of genes associated with protein metabolism, particularly heat shock proteins, was seen compared with pretreatment expression. These data suggest that the function and gene expression of monocytes in filaria-infected patients are altered but that this dysfunction is partially reversible following antifilarial treatment. C1 NIAID, LPD, NIH, Helminth Immunol Sect, Bethesda, MD 20892 USA. Univ Mali, Sch Med, Dept Epidemiol, Bamako, Mali. Univ Mali, Sch Med, Dept Parasit Dis, Bamako, Mali. RP Semnani, RT (reprint author), NIAID, LPD, NIH, Helminth Immunol Sect, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. EM rsemnani@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 FU Intramural NIH HHS NR 31 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2006 VL 74 IS 8 BP 4409 EP 4417 DI 10.1128/IAI.01106-05 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 068NO UT WOS:000239381400003 PM 16861626 ER PT J AU Pechous, R Celli, J Penoske, R Hayes, SF Frank, DW Zahrt, TC AF Pechous, Roger Celli, Jean Penoske, Renee Hayes, Stanley F. Frank, Dara W. Zahrt, Thomas C. TI Construction and characterization of an attenuated purine auxotroph in a Francisella tularensis live vaccine strain SO INFECTION AND IMMUNITY LA English DT Article ID TULAREMIA VACCINE; SALMONELLA-TYPHIMURIUM; MURINE MACROPHAGES; INDUCED APOPTOSIS; EFFICACY; MOUSE; MICE; IMMUNIZATION; PERSISTENCE; POLYMERASE AB Francisella tularensis is a facultative intracellular pathogen and is the etiological agent of tularemia. It is capable of escaping from the phagosome, replicating to high numbers in the cytosol, and inducing apoptosis in macrophages of a variety of hosts. F. tularensis has received significant attention recently due to its potential use as a bioweapon. Currently, there is no licensed vaccine against F. tularensis, although a partially protective live vaccine strain (LVS) that is attenuated in humans but remains fully virulent for mice was previously developed. An F. tularensis LVS mutant deleted in the purMCD purine biosynthetic locus was constructed and partially characterized by using an allelic exchange strategy. The F. tularensis LVS Delta purMCD mutant was auxotrophic for purines when grown in defined medium and exhibited significant attenuation in virulence when assayed in murine macrophages in vitro or in BALB/c mice. Growth and virulence defects were complemented by the addition of the purine precursor hypoxanthine or by introduction of purMCDN in trans. The F. tularensis LVS Delta purMCD mutant escaped from the phagosome but failed to replicate in the cytosol or induce apoptotic and cytopathic responses in infected cells. Importantly, mice vaccinated with a low dose of the F. tularensis LVS Delta purMCD mutant were fully protected against subsequent lethal challenge with the LVS parental strain. Collectively, these results suggest that F. tularensis mutants deleted in the purMCD biosynthetic locus exhibit characteristics that may warrant further investigation of their use as potential live vaccine candidates. C1 Med Coll Wisconsin, Dept Microbiol & Mol Genet, Milwaukee, WI 53226 USA. NIAID, Rocky Mt Labs, Lab Intracellular Parasites, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Labs, Microscopy Core Unit, NIH, Hamilton, MT 59840 USA. RP Zahrt, TC (reprint author), Med Coll Wisconsin, Dept Microbiol & Mol Genet, 8701 Watertow Plank Rd, Milwaukee, WI 53226 USA. EM tzahrt@mcw.edu FU Intramural NIH HHS; NIAID NIH HHS [U54 AI057153, U54-AI-057153] NR 35 TC 61 Z9 61 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2006 VL 74 IS 8 BP 4452 EP 4461 DI 10.1128/IAI.00666-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 068NO UT WOS:000239381400008 PM 16861631 ER PT J AU Singh, S Miura, K Zhou, H Muratova, O Keegan, B Miles, A Martin, LB Saul, AJ Miller, LH Long, CA AF Singh, Sanjay Miura, Kazutoyo Zhou, Hong Muratova, Olga Keegan, Brian Miles, Aaron Martin, Laura B. Saul, Allan J. Miller, Louis H. Long, Carole A. TI Immunity to recombinant Plasmodium falciparum merozoite surface protein 1 (MSP1): Protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity SO INFECTION AND IMMUNITY LA English DT Article ID CARBOXYL-TERMINAL FRAGMENT; APICAL MEMBRANE ANTIGEN-1; BLOOD-STAGE VACCINE; SACCHAROMYCES-CEREVISIAE; SEQUENCE DIVERSITY; MALARIA; CHALLENGE; INVASION; IMMUNIZATION; INFECTION AB A number of malarial blood-stage candidate vaccines are currently being tested in human clinical trials, but our understanding of the relationship between clinical immunity and data obtained from in vitro assays remains inadequate. An in vitro assay which could reliably predict protective immunity in vivo would facilitate vaccine development. Merozoite surface protein1 (MSP1) is a leading blood-stage malaria vaccine candidate, and anti-MSP1 antibodies from individuals that are clinically immune to malaria inhibit the invasion of Plasmodium merozoites into erythrocytes in vitro. Using expression in Escherichia coli and subsequent refolding, we have produced two allelic forms of MSP1(42) (FVO and 3D7). Aotus nancymai monkeys were immunized with MSP1(42)-FVO, MSP1(42)-3D7, or a combination of FVO and 3D7 allelic forms, (MSP1(42)-C1) and were subsequently challenged with Plasmodium falciparum FVO parasites. Sera obtained prior to challenge were tested by standardized enzyme-linked immunosorbent assay (ELISA) to determine antibody titer, and immunoglobulin G (IgG) fractions were also obtained from the same sera; the IgG fractions were tested in an in vitro growth inhibition (GI) assay to evaluate biological activity of the antibodies. Regardless of the immunogen used, all monkeys that had > 200,000 ELISA units against MSP1(42)-FVO antigen before challenge controlled their infections. By contrast, all monkeys whose purified IgGs gave < 60% inhibition activity in an in vitro GI assay with P. falciparum FVO required treatment for high parasitemia after challenge. There is a strong correlation between ELISA units (Spearman rank correlation of greater than 0.75) or GI activity (Spearman rank correlation of greater than 0.70) and protective immunity judged by various parameters (e.g., cumulative parasitemia or day of patency). These data indicate that, in this monkey model, the ELISA and GI assay values can significantly predict protective immunity induced by a blood-stage vaccine, and they support the use of these assays as part of evaluation of human clinical trials of MSPI-based vaccines. C1 NIAID, Malaria Vaccine Dev Branch, Antigen Res Sect, NIH, Rockville, MD 20852 USA. RP Singh, S (reprint author), NIAID, Malaria Vaccine Dev Branch, Antigen Res Sect, NIH, TW1,5640 Fishers Lane, Rockville, MD 20852 USA. EM ssingh@niaid.nih.gov RI Saul, Allan/I-6968-2013; Martin, Laura/N-1789-2013 OI Saul, Allan/0000-0003-0665-4091; Martin, Laura/0000-0002-4431-4381 FU Intramural NIH HHS NR 34 TC 98 Z9 99 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 AUG PY 2006 VL 74 IS 8 BP 4573 EP 4580 DI 10.1128/IAI.01679-05 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 068NO UT WOS:000239381400021 PM 16861644 ER PT J AU Shelburne, SA Sumby, P Sitkiewicz, I Okorafor, N Granville, C Patel, P Voyich, J Hull, R Deleo, FR Musser, JM AF Shelburne, Samuel A., III Sumby, Paul Sitkiewicz, Izabela Okorafor, Nnaja Granville, Chanel Patel, Payal Voyich, Jovanka Hull, Richard DeLeo, Frank R. Musser, James M. TI Maltodextrin utilization plays a key role in the ability of group A Streptococcus to colonize the oropharynx SO INFECTION AND IMMUNITY LA English DT Article ID COMPLETE GENOME SEQUENCE; GRAM-POSITIVE BACTERIA; ESCHERICHIA-COLI; HUMAN SALIVA; MYCOBACTERIUM-TUBERCULOSIS; CATABOLITE REPRESSION; PATHOGENIC BACTERIA; MICROARRAY ANALYSIS; SUGAR METABOLISM; COMPLEMENT GENE AB Analysis of multiple group A Streptococcus (GAS) genomes shows that genes encoding proteins involved in carbohydrate utilization comprise some 15% of the core GAS genome. Yet there is a limited understanding of how carbohydrate utilization contributes to GAS pathogenesis. Previous genome-wide GAS studies led us to a focused investigation of MalE, a putative maltodextrin-binding protein. Analysis of 28 strains of 22 distinct M protein serotypes showed that MalE is highly conserved among diverse GAS strains. malE transcript levels were significantly increased during growth in human saliva compared to growth in a chemically defined glucose-containing medium or a nutrient-rich medium. MalE was accessible to antibody binding, indicating that it is expressed on the GAS cell surface. Moreover, growth in human saliva appeared to increase MalE surface expression compared to growth in a nutrient-rich medium. Analysis of a Delta malE isogenic mutant strain revealed decreased growth in human saliva compared to wild-type GAS. Radiollabeled carbohydrate binding assays showed that MalE was required for the binding of maltose but not glucose. The Delta malE isogenic mutant strain colonized a lower percentage of GAS-challenged mice compared to wild-type and genetically complemented strains. Furthermore, decreased numbers of CFU were recovered from mice infected with the Delta malE strain compared to those infected with wild-type GAS. These data demonstrate that maltodextrin acquisition is likely to be a key factor in the ability of GAS to successfully infect the oropharynx. Further investigation into carbohydrate transport and metabolism pathways may yield novel insights into GAS pathogenesis. C1 Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77025 USA. Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77025 USA. EM jmmusser@tmh.tmc.edu RI Sitkiewicz, Izabela/G-5058-2011; OI Sitkiewicz, Izabela/0000-0001-8228-9917; DeLeo, Frank/0000-0003-3150-2516 FU NCRR NIH HHS [K12 RR 17655-04] NR 62 TC 42 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2006 VL 74 IS 8 BP 4605 EP 4614 DI 10.1128/IAI.00477-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 068NO UT WOS:000239381400025 PM 16861648 ER PT J AU Kubler-Kielb, J Liu, TY Mocca, C Majadly, F Robbins, JB Schneerson, R AF Kubler-Kielb, Joanna Liu, Teh-Yung Mocca, Christopher Majadly, Fathy Robbins, John B. Schneerson, Rachel TI Additional conjugation methods and immunogenicity of Bacillus anthracis poly-gamma-D-glutarnic acid-protein conjugates SO INFECTION AND IMMUNITY LA English DT Article ID PROTECTIVE ANTIGEN; CAPSULE; VACCINE; POLYSACCHARIDE; ANTIBODIES; RECOVERY; CRM197; MUTANT; TOXIN; MICE AB The capsule of Bacillus anthracis, composed of poly-gamma-D-glutamic acid (gamma DPGA), is an essential virulence factor of B. anthracis. The capsule inhibits innate host defense through its antiphagocytic action. gamma DPGA is a poor immunogen, but when covalently bound to a carrier protein, it elicits serum antibodies. To identify the optimal construct for clinical use, synthetic gamma DPGAs of different lengths were bound to carrier proteins at different densities. The advantages of the synthetic over the natural polypeptide are the homogeneous chain length and end groups, allowing conjugates to be accurately characterized and standardized and their chemical compositions to be related to their immunogenicities. In the present study, we evaluated, in addition to methods reported by us, hydrazone, oxime, and thioether linkages between gamma DPGA and several proteins, including bovine serum albumin, recombinant Pseudomonas aeruginosa exotoxin A, recombinant B. anthracis protective antigen (rPA), and tetanus toxoid (TT). The effects of the dosage and formulation on the immunogenicities of the conjugates were evaluated in mice. All conjugates were immunogenic. The optimal gamma DPGA chain length of 10 to 15 amino acids and the density, an average of 15 mol gamma DPGA per mol of protein, were confirmed. The thioether bond was the optimal linkage type, and TT and rPA were the best carriers. The optimal dosage was 1.2 to 2.5 mu g of gamma DPGA per mouse, and adsorption of the conjugates onto aluminum hydroxide significantly increased the antibody response to the protein with a lesser effect on anti-gamma DPGA levels. C1 NICHD, NIH, LDMI, Bethesda, MD 20892 USA. RP Kubler-Kielb, J (reprint author), NICHD, NIH, LDMI, 9000 Rockville Pike,Bldg 6,Rm 1A05, Bethesda, MD 20892 USA. EM kielbj@mail.nih.gov FU Intramural NIH HHS NR 29 TC 21 Z9 22 U1 0 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2006 VL 74 IS 8 BP 4744 EP 4749 DI 10.1128/IAI.00315-06 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 068NO UT WOS:000239381400039 PM 16861662 ER PT J AU Li, Y Li, XM Haley, M Fitz, Y Gerstenberger, E Banks, SM Eichacker, PQ Cui, XZ AF Li, Yan Li, Xuemei Haley, Michael Fitz, Yvonne Gerstenberger, Eric Banks, Steven M. Eichacker, Peter Q. Cui, Xizhong TI DTPA Fe(III) decreases cytokines and hypotension but worsens survival with Escherichia coli sepsis in rats SO INTENSIVE CARE MEDICINE LA English DT Article DE DTPA Fe(III); sepsis; septic shock; nitric oxide inhibition; treatment ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; SEPTIC SHOCK; REACTIVE OXYGEN; INHIBITION; MODEL; SUPEROXIDE; PERITONITIS; ENDOTOXIN; EFFICACY AB Objective: Nonselective inhibition of nitric oxide (NO) with NO synthase antagonists decreases hypotension but worsens outcome clinically. We investigated whether iron (III) complex of diethylenetriaminepentaacetic acid [DTPA Fe(III)], a scavenger of NO as well as other oxidant mediators, has similar divergent effects in E. coli challenged rats. Methods: Animals with venous and arterial catheters and challenged with intrabronchial or intravenous E. coli were randomized to treatment with DTPA Fe(III) in doses from 3 to 800 mg/kg or placebo. Mean blood pressure (MBP) was measured in all animals and plasma NO, cytokines, and blood and lung leukocyte and bacteria counts in animals administered intrabronchial E. coli and DTPA Fe( III) 50 mg/kg or placebo. Animals received antibiotics and were observed 168 h. Results: Independent of drug regimen or infection site, compared to placebo, DTPA Fe( III) increased MBP although this was greater with high vs. lower doses. Despite increased MBP, DTPA Fe(III) worsened the hazards ratio of survival. At 6 and 24 h DTPA Fe(III) decreased NO but not significantly and decreased four cytokines (tumor necrosis factor-alpha, interleukins 1 and 10, and macrophage inflammatory protein 3 alpha) and lung lavage neutrophils. From 6 to 24 h DTPA Fe(III) increased blood bacteria. Conclusions: DTPA Fe(III) while increasing blood pressure has the potential to worsen outcome in sepsis. Further preclinical testing is required before this agent is applied clinically. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Cui, XZ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. EM cxizhong@mail.cc.nih.gov NR 37 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD AUG PY 2006 VL 32 IS 8 BP 1263 EP 1270 DI 10.1007/s00134-006-0234-2 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 074LI UT WOS:000239813300025 PM 16775718 ER PT J AU Kamangar, F Qiao, YL Schiller, JT Dawsey, SM Fears, T Sun, XD Abnet, CC Zhao, P Taylor, PR Mark, SD AF Kamangar, F Qiao, YL Schiller, JT Dawsey, SM Fears, T Sun, XD Abnet, CC Zhao, P Taylor, PR Mark, SD TI Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high-risk region in China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE esophageal cancer; human papillomavirus; serology ID VIRUS-LIKE PARTICLES; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; SQUAMOUS-CELL CARCINOMA; GENERAL-POPULATION; TYPE-16 INFECTION; SERUM ANTIBODIES; CERVICAL-CANCER; SEXUAL-BEHAVIOR; HPV AB Each year, esophageal and gastric cancers cause more than 900,006 deaths worldwide. Human papilloma virus (HPV), especially type 16, has been suggested to have a role in the etiology of esophageal cancer, however, the results of previous seroepidemiological studies have not been consistent. We conducted a large prospective study to examine the association between serum antibodies to HPV 16, HPV 18 and HPV 73 and subsequent development of esophageal squamous cell carcinoma (ESCC), gastric cardia adenocarcinoma (GCA), and gastric noncardia adenocarcinoma (GNCA) in a high-risk population for these cancers in Linxian, China. Case and control subjects for this study were selected from the 29,584 participants of the Linxian General Population Trial. Prediagnostic serum samples from 99 cases of ESCC, 100 cases of GCA, 70 cases of GNCA, and 381 age- and sex- matched controls were selected for this study. The presence of antibodies to HPV virus-like particles was determined by type-specific enzyme-linked immunosorbent assays. Fewer than 15% of ESCC, GCA, or GNCA cases were positive for each HPV type, and no significant associations were found. The adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for HPV 16 seropositivity and ESCC, GCA, and GNCA risk were 1.6 (0.8-3.3), 1.3 (0.6-2.8) and 0.4 (0.1-1.6), respectively. The comparable ORs (95% CIs) for HPV 18 were 1.0 (0.4-2.2), 0.9 (0.4-2.1) and 1.5 (0.6-3.4). For HPV 73, these figures were 1.3 (0.6-2.5), 1.2 (0.6-2.3) and 0.9 (0.4-2.1). The results of this study do not support a major role for HPV 16, HPV 18 and HPV 73 in the etiology of esophageal and gastric cancers in Linxian, China. (c) 2006 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100037, Peoples R China. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kamangar, F (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS,Rm 3034, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov; qiaoy@public.bta.net.cn RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS NR 29 TC 52 Z9 59 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD AUG 1 PY 2006 VL 119 IS 3 BP 579 EP 584 DI 10.1002/ijc.21871 PG 6 WC Oncology SC Oncology GA 055UU UT WOS:000238476800014 PM 16496409 ER PT J AU Ribas-Fito, N Gladen, BC Brock, JW Klebanoff, MA Longnecker, MP AF Ribas-Fito, Nuria Gladen, Beth C. Brock, John W. Klebanoff, Mark A. Longnecker, Matthew P. TI Prenatal exposure to 1,1-dichloro-2,2-bis (p-chlorophenyl)ethylene (p,p '-DDE) in relation to child growth SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE p,p '-DDE; growth; children; cohort ID POLYCHLORINATED-BIPHENYLS; DICHLORODIPHENYL DICHLOROETHENE; DDT; MALARIA; HEIGHT; PESTICIDES; SUCCESS; PCBS; RISK AB Objective To examine the relation between prenatal 1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (p,p'-DDE) exposure (a metabolite of the insecticide DDT) and child growth during the first 7 years of life. Design Prospective cohort study. Participants 1712 children born between 1959 and 1966 with measured p,p'-DDE concentrations in their mother's serum samples from pregnancy. Setting Multicenter US Collaborative Perinatal Project (CPP). Results The highest prenatal concentrations of p,p'-DDE ( >= 60 mu g/l), as compared with the lowest (< 15 mu g/l), were associated with decreased height at age 1 year [adjusted coefficient (SE) = -0.72 cm (0.37), n = 1540], 4 years [-1.14 cm (0.56), n = 1289], and 7 years [-2.19 (0.46), n = 1371]. Among subjects in lower categories of exposure no association was observed. Conclusions The findings suggest that high prenatal exposure to p,p'-DDE decreases height in children. Impaired growth may be a general indicator of toxicity and suggests that specific organ systems (e.g. endocrine) could be affected. C1 Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, Barcelona 08003, Spain. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Dept Hlth & Human Serv, Atlanta, GA USA. RP Ribas-Fito, N (reprint author), Inst Municipal Invest Med, Resp & Environm Hlth Res Unit, C Dr Aiguader,80, Barcelona 08003, Spain. EM nribas@imim.es OI Longnecker, Matthew/0000-0001-6073-5322 NR 23 TC 27 Z9 27 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2006 VL 35 IS 4 BP 853 EP 858 DI 10.1093/ije/dyl067 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090GR UT WOS:000240939300008 PM 16606643 ER PT J AU Titus-Ernstoff, L Troisi, R Hatch, EE Wisei, LA Palmer, J Hyer, M Kaufman, R Adam, E Strohsnitter, W Noller, K Herbst, AL Gibson-Chambers, J Hartge, P Hoover, RN AF Titus-Ernstoff, Linda Troisi, Rebecca Hatch, Elizabeth E. Wisei, Lauren A. Palmer, Julie Hyer, Marianne Kaufman, Raymond Adam, Ervin Strohsnitter, William Noller, Kenneth Herbst, Arthur L. Gibson-Chambers, Jennifer Hartge, Patricia Hoover, Robert N. TI Menstrual and reproductive characteristics of women whose mothers were exposed in utero to diethylstilbestrol (DES) SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diethylstilbestrol; prenatal exposure; maternal exposure; menstruation; reproductive histories; infertility; epigenetic alternations ID PRENATAL EXPOSURE; CANCER-RISK; FEMALE MICE; FOLLOW-UP; C-FOS; EXPRESSION; PROTOONCOGENE; ESTROGEN; TRACT; MEN AB Background In women, prenatal exposure to diethylstilbestrol (DES) is associated with adult reproductive dysfunction. The mouse model, which replicates many DES outcomes, suggests DES causes epigenetic alterations, which are transmissable to daughters of prenatally exposed animals. We report menstrual and reproductive characteristics in a unique cohort comprising daughters of women exposed prenatally to DES. Methods Menstrual and reproductive outcomes and baseline characteristics were assessed by mailed questionnaire in 793 women whose mothers had documented information regarding in utero DES exposure. Results Mean age at menarche was 12.6 years in both groups, but daughters of the exposed women attained menstrual regularization later (mean age of 16.2 years vs. 15.8 years; P = 0.05), and were more likely to report irregular menstrual periods, odds ratio (OR) = 1.54 [95% confidence interval (95% CI 1.02-2.32)]. A possible association between mothers' DES exposure and daughters' infertility was compatible with chance, age, and cohort adjusted OR = 2.19 (95% CI 0.95-5.07). We found limited evidence that daughters of the exposed had more adverse reproductive outcomes, but daughters of exposed women had fewer live births (1.6) than the unexposed (1.9) (P = 0.005). Conclusions The high risk of reproductive dysfunction seen in women exposed to DES in utero was not observed in their daughters, but most women in our cohort have not yet attempted to start their families, and further follow-up is needed to assess their reproductive health. Our findings of menstrual irregularity and possible infertility in third-generation women are preliminary but compatible with speculation regarding transgenerational transmission of DES-related epigenetic alterations in humans. C1 Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH 03756 USA. Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Slone Epidemiol Ctr, Boston, MA 02215 USA. Informat Management Serv Inc, Rockville, MD 20852 USA. Methodist Hosp, Dept Obstet & Gynecol, Houston, TX 77030 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Titus-Ernstoff, L (reprint author), Dartmouth Coll Sch Med, Dept Community & Family Med, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM Linda.Titus-Ernstoff@Dartmouth.edu OI Hatch, Elizabeth/0000-0001-7901-3928; Wise, Lauren/0000-0003-2138-3752 FU NCI NIH HHS [CP 51010, CP 01012] NR 39 TC 38 Z9 38 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2006 VL 35 IS 4 BP 862 EP 868 DI 10.1093/ije/dyl106 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090GR UT WOS:000240939300010 PM 16723367 ER PT J AU Hemachandra, AH Klebanoff, MA Duggan, AK Hardy, JB Furth, SL AF Hemachandra, Anusha H. Klebanoff, Mark A. Duggan, Anne K. Hardy, Janet B. Furth, Susan L. TI The association between intrauterine growth restriction in the full-term infant and high blood pressure at age 7 years: results from the Collaborative Perinatal Project SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE hypertension; fetal programming; placenta; anthropometry; neonatal ID FOR-GESTATIONAL-AGE; BIRTH-WEIGHT; FETAL ORIGINS; CHEST CIRCUMFERENCE; HEAD CIRCUMFERENCE; PLACENTAL WEIGHT; ADULT LIFE; CHILDHOOD; HYPERTENSION; CHILDREN AB Objective To use neonatal and placental anthropometry as proxy measures of intrauterine growth restriction (IUGR) and to relate these to blood pressure later in childhood. Study design A post hoc analysis of full-term white and black children from the Collaborative Perinatal Project, followed from birth until age 7 years (n = 29 710). Blood pressure above the 90th percentile by gender and race was considered high blood pressure. Anthropometric measures at birth included birth weight, ponderal index (PI, birth weight/birth length(3)), head to chest circumference (HCC) ratio, and placental ratio percentage (PRP, placental weight*100/birth weight). Results Among anthropometric measures, PI, HCC, and birth weight were not associated with high systolic blood pressure at age 7 years, but PRP was. In multiple logistic regression, high systolic blood pressure and widened pulse pressure were both predicted by increased PRP [odds ratio (OR) 1.03 and 1.04, P < 0.001] but not by birth weight, when adjusted for gender, race, and maternal education. High diastolic blood pressure was weakly predicted by birth weight (OR 1.10, P = 0.05) but not by PRP. Conclusions PRP is associated with an increased risk for high systolic blood pressure and pulse pressure later in childhood, whereas birth weight, PI, and HCC are not. The proportion of placental weight to birth weight is a useful marker of IUGR for studying the developmental origins of adult disease hypothesis. C1 Johns Hopkins Univ, Sch Med, Div Neonatol, Dept Pediat, Baltimore, MD USA. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Gen Pediat, Dept Pediat, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Pediat Nephrol, Dept Pediat, Baltimore, MD USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. RP Hemachandra, AH (reprint author), NICHD, DESPR, NIH, 6100 Bldg,Room 7B05, Bethesda, MD 20892 USA. EM hemachaa@mail.nih.gov FU NIDDK NIH HHS [U01DK66174]; NIMH NIH HHS [1R03MH07033-01A1] NR 47 TC 41 Z9 41 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2006 VL 35 IS 4 BP 871 EP 877 DI 10.1093/ije/dyl080 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090GR UT WOS:000240939300012 PM 16766538 ER PT J AU Freedman, LS Potischman, N Kipnis, V Midthune, D Schatzkin, A Thompson, FE Troiano, RP Prentice, R Patterson, R Carroll, R Subar, AF AF Freedman, Laurence S. Potischman, Nancy Kipnis, Victor Midthune, Douglas Schatzkin, Arthur Thompson, Frances E. Troiano, Richard P. Prentice, Ross Patterson, Ruth Carroll, Raymond Subar, Amy F. TI A comparison of two dietary instruments for evaluating the fat-breast cancer relationship SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE breast cancer; dietary fat; food frequency questionnaire; multiple-day food record ID FOOD FREQUENCY QUESTIONNAIRE; WOMENS HEALTH TRIAL; ENERGY-ADJUSTMENT MODELS; NUTRITIONAL EPIDEMIOLOGY; MEASUREMENT ERROR; COHORT; RISK; PARTICIPANTS; FEASIBILITY; RELIABILITY AB Background Previous research suggests food diaries may be more efficient than food frequency questionnaires (FFQ) in detecting a dietary fat-breast cancer relationship. We assessed this further using 4 day food records (FRs) and FFQs in a large sample. Methods Participants were from the non-intervention group of the dietary modification component of the Women's Health Initiative Clinical Trial: 603 breast cancer cases and 1206 controls matched on age, clinic, and length of follow-up. Relative risks (RRs) were estimated using unconditional logistic regression, adjusted for confounders and for the selection into the trial of women with an FFQ report exceeding 32% calories from fat. Direct comparison of the statistical power of the two instruments used the standardized log RR. An alternative analysis after removing subjects with missing covariate data was also conducted. Results The RR estimate for breast cancer in the top quintile of total fat intake, adjusted for confounders and total energy, was 1.82 (P for trend 0.02) for the FR but 0.67 for the FFQ (P for trend 0.24). Following adjustment for selection, estimates were 2.09 (P for trend 0.008) for the FR (alternative: 2.54, P for trend 0.006) and 1.71 (P for trend 0.18) for the FFQ (alternative: 1.24, P for trend 0.41). Similar results were seen for fat subtypes, particularly unsaturated fats. Comparisons showed higher statistical power for the FR than the FFQ (e.g. total fat, P = 0.08: alternative P = 0.01). Conclusions Alternative instruments, such as FRs, may be preferable to FFQs for evaluating diet-disease relationships in cohort studies. The results support a positive association between dietary fat and breast cancer. C1 Gertner Inst Epidemiol, Tel Hashomer, Israel. NCI, Div Canc Control & Populat Studies, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Kipnis, V (reprint author), Natl Canc Inst, 6130 Execut Blvd,Suite 3124, Rockville, MD 20852 USA. EM victor_kipnis@nih.gov OI Troiano, Richard/0000-0002-6807-989X FU NCI NIH HHS [CA-57030, CA53996]; NIEHS NIH HHS [P30-ES09106] NR 35 TC 93 Z9 95 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2006 VL 35 IS 4 BP 1011 EP 1021 DI 10.1093/ije/dyl085 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090GR UT WOS:000240939300033 PM 16672309 ER PT J AU Goldstein, AM Dondon, MG Andrieu, N AF Goldstein, Alisa M. Dondon, Marie-Gabrielle Andrieu, Nadine TI Unconditional analyses can increase efficiency in assessing gene-environment interaction of the case-combined-control design SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE gxE interaction; unconditional logistic regression analysis; conditional analysis; sibling controls; population-based controls ID POPULATION STRATIFICATION; ASCERTAINMENT BIAS; CANCER; QUANTIFICATION; VARIANTS AB Background A design combining both related and unrelated controls, named the case-combined-control design, was recently proposed to increase the power for detecting gene-environment (GxE) interaction. Under a conditional analytic approach, the case-combined-control design appeared to be more efficient and feasible than a classical case-control study for detecting interaction involving rare events. Methods We now propose an unconditional analytic strategy to further increase the power for detecting gene-environment (GxE) interactions. This strategy allows the estimation of GxE interaction and exposure (E) main effects under certain assumptions (e.g. no correlation in E between siblings and the same exposure frequency in both control groups). Only the genetic (G) main effect cannot be estimated because it is biased. Results Using simulations, we show that unconditional logistic regression analysis is often more efficient than conditional analysis for detecting GxE interaction, particularly for a rare gene and strong effects. The unconditional analysis is also at least as efficient as the conditional analysis when the gene is common and the main and joint effects of E and G are small. Conclusions Under the required assumptions, the unconditional analysis retains more information than does the conditional analysis for which only discordant case-control pairs are informative leading to more precise estimates of the odds ratios. C1 NCI, Genet Epidemiol Branch, NIH, DHHS, Bethesda, MD 20892 USA. Inst Curie, Serv Biostat, INSERM, F-75248 Paris 5, France. RP Goldstein, AM (reprint author), NCI, Genet Epidemiol Branch, NIH, DHHS, Execut Plaza S,Room 7004,6120 Execut Blvd,MSC 723, Bethesda, MD 20892 USA. EM goldstea@exchange.nih.gov RI ANDRIEU, Nadine/H-4255-2014 FU Intramural NIH HHS NR 13 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD AUG PY 2006 VL 35 IS 4 BP 1067 EP 1073 DI 10.1093/ije/dy1048 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 090GR UT WOS:000240939300040 PM 16556643 ER PT J AU Martin-Soelch, C Stocklin, M Dammann, G Opwis, K Seifritz, E AF Martin-Soelch, Chantal Stoecklin, Markus Dammann, Gerhard Opwis, Klaus Seifritz, Erich TI Anxiety trait modulates psychophysiological reactions, but not habituation processes related to affective auditory stimuli SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article DE emotion; sounds; psychophysiology; habituation; anxiety; orienting reaction; autonomic system ID PHYSIOLOGICAL-RESPONSES; EMOTION; AMYGDALA; HUMANS; ACTIVATION; MECHANISMS; PICTURES; LOOKING; AROUSAL; REFLEX AB Background: It is well known that there are specific peripheral activation patterns associated with the emotional valence of sounds. However, it is unclear how these effects adapt over time. The personality traits influencing these processes are also not clear. Anxiety disorders influence the autonomic activation related to emotional processing. However. personality anxiety trans have never been studied in the context of affective auditory stimuli. Methods: Heart rate, skin Conductance. zygomatic muscle activity and subjective rating, of emotional valence and arousal were recorded in healthy subjects during the presentation of pleasant. unpleasant. and neutral sounds. Recordines were repeated I week later to examine possible time-dependent changes related to habituation and sensitization processes. Results and conclusion: There was not a generalized habituation or sensitization process related to the repeated presentation of affective sounds, but rather, specific adaptation processes for each physiological measure. These observations; are consistent with previous studies performed with affective pictures and simple tones. Thus. the measures of skin conductance activity showed the strongest changes over little. including habituation during the first presentation session and sensitization at the end of the second presentation session. whereas the facial electromyographic activity habituated only for the neutral stimuli and the heart rate did not habituate at all. Finally. we showed that the measure of personality trait anxiety influenced the orienting reaction to affective sounds. but not the adaptation processes related to the repeated presentation of these Sounds. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Basel, Dept Psychol, CH-4055 Basel, Switzerland. NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Univ Basel, Psychiat Clin, CH-4025 Basel, Switzerland. Univ Bern, Hosp Clin Psychiat, CH-3000 Bern, Switzerland. RP Martin-Soelch, C (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, 15K North Dr,Room 201,MSC 2670, Bethesda, MD 20892 USA. EM martinsoelchc@mail.nih.gov NR 37 TC 19 Z9 19 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD AUG PY 2006 VL 61 IS 2 BP 87 EP 97 DI 10.1016/j.ijpsycho.2005.07.009 PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 065UQ UT WOS:000239185700001 PM 16135389 ER PT J AU Chaaya, M Mehio-Sibai, A El-Chemaly, S AF Chaaya, M. Mehio-Sibai, A. El-Chemaly, S. TI Smoking patterns and predictors of smoking cessation in elderly populations in Lebanon SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE smoking cessation; elderly; health ID OLDER PATIENTS; QUIT SMOKING; DEPRESSION; PREVALENCE; ATTITUDES; TOBACCO; SMOKERS; PLAN; CARE; AGE AB OBJECTIVE: To investigate smoking patterns in an elderly, low-income population and to identify predictors of smoking cessation, in addition to analyzing the importance of smoking in relation to other risk factors for hospitalization. DESIGN: The data were part of an urban health study conducted among 740 individuals aged >= 60 years in three suburban communities of low socio-economic status in Beirut, one of them a refugee camp. A detailed interview schedule was administered that included comprehensive social and health information. RESULTS: The overall prevalence of current smokers was 28.1%. Almost half of the group were ever smokers, of whom 44% had quit smoking when they experienced negative health effects. Having at least one chronic illness and having a functional disability significantly increased the odds of smoking cessation. In addition, being a former smoker increased the likelihood of hospital admission. CONCLUSIONS: This study is of particular importance, as it has implications for similar low-income and refugee communities in the region and elsewhere. There is a need for more concerted efforts by public health officials to target elderly individuals as a group for smoking cessation interventions, particularly now that mortality and health benefits have been well documented. C1 Amer Univ Beirut, Fac Hlth Sci, Dept Epidemiol & Populat Hlth, Beirut, Lebanon. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Chaaya, M (reprint author), Amer Univ Beirut, Fac Hlth Sci, Dept Epidemiol & Populat Hlth, POB 11-0236, Beirut, Lebanon. EM mchaaya@aub.edu.lb OI Sibai, Abla/0000-0002-1851-5606 FU Wellcome Trust [, 074986] NR 29 TC 11 Z9 13 U1 0 U2 2 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD AUG PY 2006 VL 10 IS 8 BP 917 EP 923 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 065XY UT WOS:000239194700016 PM 16898378 ER PT J AU Hundley, AF Brown, MB Brubaker, L Cundiff, GW Kreder, K Lotze, P Richter, HE Zyczynski, H Weber, AM Visco, AG AF Hundley, AF Brown, MB Brubaker, L Cundiff, GW Kreder, K Lotze, P Richter, HE Zyczynski, H Weber, AM Visco, AG TI A multicentered comparison of measurements obtained with microtip and external water pressure transducers SO INTERNATIONAL UROGYNECOLOGY JOURNAL LA English DT Article; Proceedings Paper CT Joint Meeting of the International-Continence-Society/International-Urogynecological-Associat ion CY AUG 25-27, 2004 CL Paris, FRANCE SP Int Continence Soc, Int UroGynecol Assoc DE microtip; pressure transducer; cough pressure; valsalva; correlation ID GENUINE STRESS-INCONTINENCE; LEAK-POINT PRESSURES; WOMEN AB This study compared simultaneous intravesical pressure readings obtained with catheter-mounted microtip transducers and external water pressure transducer catheters during filling cystometry. Women undergoing multichannel urodynamic testing were randomly assigned to one of three groups: two microtip catheters, two external water pressure transducer catheters, or one of each type. Intravesical pressure was measured simultaneously for each transducer combination in each subject for minimal and maximal Valsalva effort and minimal, moderate, and maximal cough effort at two sequential bladder volumes (150 and 300 ml). Paired t tests were used to compare the means of the intravesical pressure obtained by the two types of catheters. The largest mean differences were observed when comparing microtip and water pressure transducers. Correlations of maximum pressure were consistently high between two microtip transducers and two water pressure transducers but lower for the microtip-water combination. Excellent reproducibility was demonstrated with transducers of similar types for intravesical pressures recorded during Valsalva and cough in women without prolapse. However, considerable variability was seen in pressures recorded by different transducers, particularly dependent on the water catheter manufacturer, indicating that intravesical pressure recordings from microtip and water-based systems are not interchangeable. C1 Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27515 USA. Baylor Coll Med, Div Female Pelv Med & Reconstruct Surg, Houston, TX 77030 USA. Univ Alabama, Continence Ctr, Birmingham, AL USA. Magee Womens Hosp, Div Female Pelv Med & Reconstruct Pelv Surg, Pittsburgh, PA USA. NICHHD, Bethesda, MD 20892 USA. Univ N Carolina, Div Female Pelv Med & Reconstruct Pelv Surg, Chapel Hill, NC USA. Univ Michigan, Data Coordinating Ctr, Pelv Floor Disorders Network, Ann Arbor, MI 48109 USA. Loyola Univ, Div Female Pelv Med & Reconstuct Pelv Surg, Maywood, IL 60153 USA. Johns Hopkins Bayview Med Ctr, Div Female Pelv Med & Reconstuct Pelv Surg, Baltimore, MD USA. Univ Iowa, Div Female Pelv Med & Reconstuct Pelv Surg, Iowa City, IA USA. RP Visco, AG (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27515 USA. RI Hundley, Andrew/E-3279-2011 FU NICHD NIH HHS [U10 HD41268, U10 HD41248, U01 HD41249, U10 HD041261, U10 HD041263, U10 HD41250, U10 HD41261, U10 HD41263, U10 HD41267, U10 HD41269] NR 8 TC 8 Z9 8 U1 0 U2 2 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-3462 J9 INT UROGYNECOL J JI Int. Urogynecol. J. PD AUG PY 2006 VL 17 IS 4 BP 400 EP 406 DI 10.1007/s00192-005-0027-0 PG 7 WC Obstetrics & Gynecology; Urology & Nephrology SC Obstetrics & Gynecology; Urology & Nephrology GA 049ND UT WOS:000238022400019 PM 16284710 ER PT J AU Smaoui, N Chaabouni, M Sergeev, YV Kallel, H Li, SL Mahfoudh, N Maazoul, F Kammoun, H Gandoura, N Bouaziz, A Nouiri, E M'Rad, R Chaabouni, H Hejtmancik, JF AF Smaoui, Nizar Chaabouni, Myriam Sergeev, Yuri V. Kallel, Habib Li, Shouling Mahfoudh, Neila Maazoul, Faouzi Kammoun, Hassen Gandoura, Najoua Bouaziz, Asma Nouiri, Ezzedine M'Rad, Ridha Chaabouni, Habiba Hejtmancik, J. Fielding TI Screening of the eight BBS genes in Tunisian families: No evidence of triallelism SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BARDET-BIEDL-SYNDROME; HUMAN OBESITY SYNDROME; RETINAL DYSTROPHY; SYNDROME LOCUS; IDENTIFICATION; MUTATIONS; PROTEIN; INHERITANCE; MICE; POPULATION AB PURPOSE. To study Bardet-Biedl syndrome ( BBS) in the Tunisian population and determine the presence of triallelism in the eight identified BBS genes. METHODS. DNA samples were collected from 19 consanguineous Tunisian families with BBS. Genome-wide scans were performed with microsatellite markers in 12 families, and two-point linkage analyses were performed. Direct sequencing was used to screen patients with BBS for mutations in all eight identified BBS genes. RESULTS. Mutations in the BBS genes were identified in nine families. In addition, a large consanguineous family ( 57004) showed linkage to the BBS7 locus, although no mutation was identified. Five novel mutations were present in the nine families: one in BBS2 ( c. 565C > T, p. ArgR189Stop), one in BBS5 ( c. 123delA, p. Gly42GlufsX11), one in BBS7 ( g. 47247455_47267458del20004insATA, p. Met284LysfsX7), and two in BBS8 ( c. 459 + 1G > A, p. Pro101LeufsX12 and c. 355_356insGGTGGAAGGCCAGGCA, p. Thr124ArgfsX43). CONCLUSIONS. All families in which mutations were identified show changes in both copies of the mutant gene, and inheritance patterns in all families are consistent with autosomal recessive inheritance excluding any evidence of triallelism in the BBS genes in Tunisia. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. EPS Charles Nicolle, Dept Congenital & Hereditary Dis, Tunis, Tunisia. Hosp Ras Djebel, Bizerte, Tunisia. Med Fac Sfax, Sfax, Tunisia. Univ Hosp Bizerte, Dept Pediat, Bizerte, Tunisia. Univ Hosp Nabeul, Dept Pediat, Nabeul, Tunisia. Med Fac Tunis, Dept Genet, Tunis, Tunisia. RP Smaoui, N (reprint author), NEI, OGVFB, NIH, Bldg 10,Room 10N200,10 Ctr Dr MSC 1860, Bethesda, MD 20892 USA. EM smaouin@nei.nih.gov OI kamoun, hassen/0000-0002-1798-3862 FU Intramural NIH HHS NR 42 TC 25 Z9 26 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD AUG PY 2006 VL 47 IS 8 BP 3487 EP 3495 DI 10.1167/iovs.05-1334 PG 9 WC Ophthalmology SC Ophthalmology GA 069JC UT WOS:000239441200037 PM 16877420 ER PT J AU Raz-Prag, D Ayyagari, R Fariss, RN Mandal, MNA Vasireddy, V Majchrzak, S Webber, AL Bush, RA Salem, N Petrukhin, K Sieving, PA AF Raz-Prag, Dorit Ayyagari, Radha Fariss, Robert N. Mandal, Md Nawajes A. Vasireddy, Vidyullatha Majchrzak, Sharon Webber, Andrea L. Bush, Ronald A. Salem, Norman, Jr. Petrukhin, Konstantin Sieving, Paul A. TI Haploinsufficiency is not the key mechanism of pathogenesis in a heterozygous Elovl4 knockout mouse model of STGD3 disease SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; RDS MUTANT MICE; MACULAR DYSTROPHY; DOCOSAHEXAENOIC ACID; RETINITIS-PIGMENTOSA; LONG-CHAIN; WILD-TYPE; ENDOPLASMIC-RETICULUM; GENE-EXPRESSION; DEGENERATION AB PURPOSE. Autosomal dominant Stargardt-like (STGD3) disease results from mutations in the ELOVL4 gene (elongation of very-long-chain fatty acids). This study was undertaken to characterize a mouse model with a targeted deletion of Elovl4 and to explore the role of this gene in retinal/macular degeneration. METHODS. A construct targeted to exon 2 of the Elovl4 gene was used to suppress expression of the gene. Elovl4 homozygous pups were nonviable and were not available for study. Hence, the analysis was performed on heterozygous Elovl4(+/-) mice 16 to 22 month of age and littermate wild-type (WT) control mice of the same age. Characterization included examining gene message and protein levels, electroretinogram (ERG), retinal morphology and ultrastructure, and plasma and retinal fatty acid composition. RESULTS. Although the level of Elovl4 mRNA was reduced in Elovl4(+/-) retinas, only minimal morphologic abnormalities were found, and the retinal (ERG) function was essentially normal in Elovl4(+/-) retinas compared with the WT control retinas. Systemic fatty acid profiles of Elovl4(+/-) mice were unremarkable, although the concentration of several fatty acids was significantly lower in Elovl4(+/-) retinas, particularly the monounsaturated fatty acids. CONCLUSIONS. The detailed characterization of this animal model provides the first in vivo evidence that Elovl4 haploinsufficiency is not the underlying key disease mechanism in STGD3. The results are consistent with a dominant negative mechanism for the deletion mutation. The Elovl4 knockout mouse is one of three complementary animal models that will help elucidate the disease mechanism. C1 NEI, NIH, NIDCD, Bethesda, MD 20892 USA. Univ Michigan, WK Kellogg Eye Ctr, Ann Arbor, MI 48105 USA. NEI, Biol Imaging Core, Bethesda, MD 20892 USA. RP Sieving, PA (reprint author), NEI, NIH, NIDCD, 31 Ctr Dr,Bldg 31,Room 6A03,MSC 2510, Bethesda, MD 20892 USA. EM paulsieving@nei.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01 DC000065-04] NR 49 TC 31 Z9 31 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 AUG PY 2006 VL 47 IS 8 BP 3603 EP 3611 DI 10.1167/iovs05-1527 PG 9 WC Ophthalmology SC Ophthalmology GA 069JC UT WOS:000239441200052 PM 16877435 ER PT J AU Maminishkis, A Chen, S Jalickee, S Banzon, T Shi, G Wang, FE Ehalt, T Hammer, JA Miller, SS AF Maminishkis, Arvydas Chen, Shan Jalickee, Stephen Banzon, Tina Shi, Guangpu Wang, Fei E. Ehalt, Todd Hammer, Jeffrey A. Miller, Sheldon S. TI Confluent monolayers of cultured human fetal retinal pigment epithelium exhibit morphology and physiology of native tissue SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; HUMAN TRACHEAL EPITHELIUM; ION-TRANSPORT MECHANISMS; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; TIGHT JUNCTIONS; CELL-CULTURE; FLUID TRANSPORT; CHOROIDAL NEOVASCULARIZATION; MEDIATED EXPRESSION AB PURPOSE. Provide a reproducible method for culturing confluent monolayers of hfRPE cells that exhibit morphology, physiology, polarity, and protein expression patterns similar to native tissue. METHODS. Human fetal eyes were dissected on arrival, and RPE cell sheets were mechanically separated from the choroid and cultured in a specifically designed medium comprised entirely of commercially available components. Physiology experiments were performed with previously described techniques. Standard techniques were used for immunohistochemistry, electron microscopy, and cytokine measurement by ELISA. RESULTS. Confluent monolayers of RPE cell cultures exhibited epithelial morphology and heavy pigmentation, and electron microscopy showed extensive apical membrane microvilli. The junctional complexes were identified with immunofluorescence labeling of various tight junction proteins. The mean transepithelial potential (TEP) was 2.6 +/- 0.8 mV, apical positive, and the mean transepithelial resistance ( R T) was 501 +/- 138 Omega (.) cm(2) (mean +/- SD; n = 35). Addition of 100 mu M adenosine triphosphate (ATP) to the apical bath increased net fluid absorption from 13.6 +/- 2.6 to 18.8 +/- 4.6 mu L (.) cm(-2) per hour (mean +/- SD; n = 4). In other experiments, VEGF was mainly secreted into the basal bath (n = 10), whereas PEDF was mainly secreted into the apical bath (n = 10). CONCLUSIONS. A new cell culture procedure has been developed that produces confluent primary hfRPE cultures with morphological and physiological characteristics of the native tissue. Epithelial polarity and function of these easily reproducible primary cultures closely resemble previously studied native human fetal and bovine RPE-choroid explants. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Miller, SS (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM millers@nei.nih.gov FU Intramural NIH HHS; NEI NIH HHS [Z01 EY000419-02] NR 98 TC 184 Z9 188 U1 1 U2 9 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 AUG PY 2006 VL 47 IS 8 BP 3612 EP 3624 DI 10.1167/iovs.05-1622 PG 13 WC Ophthalmology SC Ophthalmology GA 069JC UT WOS:000239441200053 PM 16877436 ER PT J AU Read, SW Rupert, A Stevens, R O'Shea, A Sereti, I AF Read, Sarah W. Rupert, Adam Stevens, Randy O'Shea, Angeline Sereti, Irini TI Delayed sample processing leads to marked decreases in measured plasma IL-7 levels SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID T-CELL HOMEOSTASIS; INTERLEUKIN-7; SURVIVAL C1 NIAID, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, AIDS Monitoring Lab, Clin Serv Program, Frederick, MD 21701 USA. RP Read, SW (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD AUG 1 PY 2006 VL 42 IS 4 BP 511 EP 512 DI 10.1097/01.qai.0000225741.16840.ac PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 064ZL UT WOS:000239129100020 PM 16810117 ER PT J AU Schmidt, P Baumritter, A Ciner, E Cyert, L Dobson, V Haas, B Kulp, MT Maguire, M Moore, B Orel-Bixler, D Quinn, G Redford, M Schultz, J Ying, GS AF Schmidt, Paulette Baumritter, Agnieshka Ciner, Elise Cyert, Lynn Dobson, Velma Haas, Beth Kulp, Marjean Taylor Maguire, Maureen Moore, Bruce Orel-Bixler, Deborah Quinn, Graham Redford, Maryann Schultz, Janet Ying, Gui-Shuang CA Vision Preschoolers Study Res TI Predictive value of photoscreening and traditional screening of preschool children SO JOURNAL OF AAPOS LA English DT Letter ID VISION; TESTS C1 Ohio State Univ, Coll Optometry, Columbus, OH 43210 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. Penn Coll Optometry, Elkins Pk, PA USA. Northeastern State Univ, Coll Optometry, Tahlequah, OK USA. Univ Arizona, Dept Ophthalmol, Tucson, AZ USA. New England Coll Optometry, Boston, MA USA. Univ Calif Berkeley, Sch Optometry, Berkeley, CA 94720 USA. Childrens Hosp Philadelphia, Div Pediat Ophthalmol, Philadelphia, PA 19104 USA. NEI, Lourie Ctr Early Head Start, Beltsville, MD USA. RP Schmidt, P (reprint author), Ohio State Univ, Coll Optometry, 338 W 10Th Ave, Columbus, OH 43210 USA. NR 3 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD AUG PY 2006 VL 10 IS 4 BP 377 EP 378 DI 10.1016/j.jaapos.2006.06.003 PG 2 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 083MF UT WOS:000240459300020 PM 16935243 ER PT J AU Tuma, F Loeber, R Lochman, JE AF Tuma, Farris Loeber, Rolf Lochman, John E. TI Introduction to special section on the National Institute of Health state of the science report on violence prevention SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. RP Tuma, F (reprint author), NIMH, 6001 Execut Blvd,Room 7111,MSC 9632, Bethesda, MD 20892 USA. EM ftuma@nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD AUG PY 2006 VL 34 IS 4 BP 451 EP 456 DI 10.1007/s10802-006-9039-6 PG 6 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 077GW UT WOS:000240018100001 PM 16832608 ER PT J AU Price, LN Reider, EE Robertson, EB AF Price, LeShawndra N. Reider, Eve E. Robertson, Elizabeth B. TI Health-risking social behaviors: Moving forward SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE youth violence; drug abuse; antisocial behavior; child conduct problems; conduct disorder; externalizing behaviors ID ANTISOCIAL-BEHAVIOR; SENSATION SEEKING; MARIJUANA USE; LIFE-COURSE; FOLLOW-UP; ADOLESCENCE; CHILDHOOD; GENOTYPE; DISORDER; CARE AB The National Institute of Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA) have a long history of supporting investigator-initiated research and research training to enhance the scientific understanding of and effective interventions for a range of problems associated with youth violence. New technologies are emerging and basic research has promise for increasing our understanding of how biological factors operate in conjunction with other factors to contribute to violent behavior, psychopathology, and drug abuse. This article describes emerging areas and directions for research in this important area of public health. C1 NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Price, LN (reprint author), NIMH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM lprice@mail.nih.gov NR 24 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD AUG PY 2006 VL 34 IS 4 BP 489 EP 494 DI 10.1007/s10802-006-9041-z PG 6 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 077GW UT WOS:000240018100005 ER PT J AU Budhani, S Richell, RA Blair, RJR AF Budhani, Salima Richell, Rebecca A. Blair, R. James R. TI Impaired reversal but intact acquisition: Probabilistic response reversal deficits in adult individuals with psychopathy SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE psychopathy; response reversal; integrated emotion systems model; fear dysfunction position ID ORBITOFRONTAL CORTEX DYSFUNCTION; PREFRONTAL CORTEX; REWARD; MODULATION; AMYGDALA; EMOTION; TENDENCIES; PREDICTION; OFFENDERS; BEHAVIOR AB The performance of adult psychopathic individuals on a novel response reversal task involving 2 reward-punishment contingencies (100-0 and 80-20) was investigated. In line with predictions, adults with psychopathy presented with impairment on the response reversal component but not on the acquisition component of this task. This selective impairment for response reversal was seen for both reward-punishment contingencies and was related to the tendency of individuals with psychopathy to be less likely to stay with a rewarded correct response to a stimulus on the subsequent presentation of that stimulus. Results are discussed with reference to current models of the development of psychopathy. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxeity Disorders Program, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxeity Disorders Program, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 44 TC 59 Z9 59 U1 1 U2 15 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2006 VL 115 IS 3 BP 552 EP 558 DI 10.1037/0021-843X.115.3.552 PG 7 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 068JH UT WOS:000239369300016 PM 16866595 ER PT J AU Mitchell, DGV Richell, RA Leonard, A Blair, RJR AF Mitchell, Derek G. V. Richell, Rebecca A. Leonard, Alan Blair, R. James R. TI Emotion at the expense of cognition: Psychopathic individuals outperform controls on an operant response task SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article DE psychopathy; antisocial behavior; amygdala; attention ID CONDITIONED SUPPRESSION; ANTISOCIAL-BEHAVIOR; FACIAL EXPRESSIONS; PASSIVE-AVOIDANCE; VISUAL-ATTENTION; AMYGDALA; MODULATION; OFFENDERS; RECOGNITION; STIMULI AB The impact of emotional stimuli on a simple motor response task in individuals with psychopathy and comparison individuals was investigated. Psychopathy was assessed using the Psychopathy Checklist Revised (Hare, 1991). Participants were presented with the Emotional Interrupt Task, in which they responded with left and right button presses to shapes that were temporally bracketed by positive, negative, and neutral visual images taken from the International Affective Picture System. The comparison group showed increased response latencies if the shape was temporally bracketed by either a positive or negative emotional stimulus relative to a neutral stimulus. Individuals with psychopathy did not show this modulation of reaction time for either positive or negative emotional stimuli. Results are discussed with reference to current models regarding the modulation of attention by emotion and the emotional impairment seen in individuals with psychopathy. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. UCL, Dept Psychol, London WC1E 6BT, England. Her Majestys Prison Wormwood Scrubs, Dept Psychol, London, England. RP Mitchell, DGV (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr, Bethesda, MD 20892 USA. EM mitchelld@mail.nih.gov NR 56 TC 61 Z9 62 U1 8 U2 19 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD AUG PY 2006 VL 115 IS 3 BP 559 EP 566 DI 10.1037/0021-0021-843X.115.3.559 PG 8 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 068JH UT WOS:000239369300017 PM 16866596 ER PT J AU Rogers, AS AF Rogers, Audrey Smith TI The final word on HIV infection in American youth: Test! SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material ID ADOLESCENTS; PATTERNS; REACH; AIDS; CARE C1 NIH, Bethesda, MD 20892 USA. RP Rogers, AS (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD AUG PY 2006 VL 39 IS 2 BP 147 EP 149 DI 10.1016/j.jadohealth.2006.05.018 PG 3 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 069KS UT WOS:000239445700001 ER PT J AU Shearer, WT DeVille, JG Samson, PM Moye, JH Fletcher, CV Church, JA Spiegel, HML Palumbo, P Fenton, T Smith, ME Graham, B Kraimer, JM Olson, WC AF Shearer, William T. DeVille, Jaime G. Samson, Pearl M. Moye, John H., Jr. Fletcher, Courtney V. Church, Joseph A. Spiegel, Hans M. L. Palumbo, Paul Fenton, Terence Smith, M. Elizabeth Graham, Bobbie Kraimer, Joyce M. Olson, William C. CA Pediat AIDS Clin Trials Grp Protocol 351 Study Grp TI Susceptibility of pediatric HIV-1 isolates to recombinant CD4-IgG(2) (PRO 542) and humanized mAb to the chemokine receptor CCR5 (PRO 140) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENTRY INHIBITORS; INFECTION C1 Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Immunol, Houston, TX 77030 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Clin Pharmacol, Denver, CO USA. Childrens Hosp Los Angeles, Keck Sch Med, Los Angeles, CA 90027 USA. Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NIAID, Pediat Med Branch, Div AIDS, Bethesda, MD 20892 USA. Frontier Sci Fdn, Amherst, NY USA. Progen Pharmaceut Inc, Tarrytown, NY USA. Social & Sci Syst Inc, Silver Spring, MD USA. RP Shearer, WT (reprint author), Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. FU NCRR NIH HHS [RR 00043, RR 00188, RR 00240, RR 00865, RR 02172, RR 00071, RR 00645, RR 00533]; NIAID NIH HHS [AI 41110, AI 27550, AI 66239, AI 41089, AI 32921, AI 48278, AI 43084, AI 27551] NR 11 TC 14 Z9 14 U1 0 U2 3 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 AUG PY 2006 VL 118 IS 2 BP 518 EP 521 DI 10.1016/j.jaci.2006.03.028 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 075IH UT WOS:000239877700031 PM 16890780 ER PT J AU Boger-Megiddo, I Shaw, DWW Friedman, SD Sparks, BF Artru, AA Giedd, JN Dawson, G Dager, SR AF Boger-Megiddo, Inbal Shaw, Dennis W. W. Friedman, Seth D. Sparks, Bobbi F. Artru, Alan A. Giedd, Jay N. Dawson, Geraldine Dager, Stephen R. TI Corpus callosum morphometrics in young children with autism spectrum disorder SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article DE MRI; autism; brain structure; corpus callosum ID DIAGNOSTIC OBSERVATION SCHEDULE; SEX-DIFFERENCES; BRAIN SIZE; MRI; VOLUME; INDIVIDUALS; LIFE AB This study assessed midsagittal corpus callosum cross sectional areas in 3-4 year olds with autism spectrum disorder (ASD) compared to typically developing (TD) and developmentally delayed (DD) children. Though not different in absolute size compared to TD, ASD callosums were disproportionately small adjusted for increased ASD cerebral volume. ASD clinical subgroup analysis revealed greater proportional callosum reduction in the more severely affected autistic disorder (AD) than in pervasive developmental disorder-not otherwise specified (PDD-NOS) children. DD children had smaller absolute callosums than ASD and TD. Subregion analysis revealed widely distributed callosum differences between ASD and TD children. Results could reflect decreased inter-hemispheric connectivity or cerebral enlargement due to increase in tissues less represented in the corpus callosum in ASD. C1 Childrens Hosp & Reg Med Ctr, Dept Radiol, Seattle, WA 98105 USA. Canc Epidemiol Res Coop, Publ Hlth Sci, Seattle, WA USA. Univ Washington, Sch Med, Dept Radiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Ctr Human Dev & Disabil, Dept Psychol, Seattle, WA 98195 USA. NIMH, Bethesda, MD 20892 USA. RP Shaw, DWW (reprint author), Childrens Hosp & Reg Med Ctr, Dept Radiol, 5C-1,4800 Sand Point Way NE, Seattle, WA 98105 USA. EM dennis.shaw@seattlechildrens.org RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU NICHD NIH HHS [2P01 HD34565] NR 31 TC 55 Z9 57 U1 1 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD AUG PY 2006 VL 36 IS 6 BP 733 EP 739 DI 10.1007/s10803-006-0121-2 PG 7 WC Psychology, Developmental SC Psychology GA 077GY UT WOS:000240018300004 PM 16625438 ER PT J AU Chin, MS Caruso, RC Detrick, B Hooks, JJ AF Chin, Marian S. Caruso, Rafael C. Detrick, Barbara Hooks, John J. TI Autoantibodies to p75/LEDGF, a cell survival factor, found in patients with atypical retinal degeneration SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE autoantibody; p75/LEDGF/DFS70; ATR-X; retinal degeneration ID CANCER-ASSOCIATED RETINOPATHY; MELANOMA-ASSOCIATED RETINOPATHY; RECOVERIN-ASSOCIATED RETINOPATHY; GROWTH-FACTOR LEDGF/P75; STRESS-RELATED GENES; AUTOIMMUNE RETINOPATHY; ANTIRETINAL ANTIBODIES; ONCHOCERCA-VOLVULUS; ATOPIC-DERMATITIS; OXIDATIVE STRESS AB We have identified a group of patients with an atypical retinal degeneration having anti-retinal autoantibodies in their sera. This select population is characterized by a progressively severe loss of vision associated with a decrease in photoreceptor function, abnormal pigmentation of the retinal pigment epithelium and a negative family history of retinal dystrophy. Immunohistochemical analysis on mouse retinal tissues with sera from this group of patients demonstrated high titers of anti-retinal antibodies (320 to 1280). Anti-retinal reactivity at these levels was not detected in sera from normal individuals, or from patients with uveitis or known genetic retinal degenerations. One antigen that was identified from a retina cDNA library with sera from a patient with atypical retinal degeneration was lens epithelium-derived growth factor (LEDGF). Western blot analysis revealed that sera from all three patients demonstrated reactivity to p75/LEDGF, a survival factor that protects cells from oxidative, thermal and UV damage. In conclusion, we have found a novel group of patients with a retinal degeneration of non-paraneoplastic, non-familial origin demonstrating immunoreactivity to an autoantigen, p75/LEDGF, heretofore not associated with this disease. Finally, identification of specific anti-retinal antibodies may have applications in the diagnosis and management of retinal degeneration. Published by Elsevier Ltd. C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Visual Funct Sect, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. RP Hooks, JJ (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N248, Bethesda, MD 20892 USA. EM hooksj@nei.nih.gov FU Intramural NIH HHS NR 52 TC 25 Z9 25 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD AUG PY 2006 VL 27 IS 1 BP 17 EP 27 DI 10.1016/j.jaut.2006.04.002 PG 11 WC Immunology SC Immunology GA 084QH UT WOS:000240549000003 PM 16757148 ER PT J AU Chikova, AK Schaaper, RM AF Chikova, Anna K. Schaaper, Roel M. TI Mutator and antimutator effects of the bacteriophage P1 hot gene product SO JOURNAL OF BACTERIOLOGY LA English DT Article ID DNA-POLYMERASE-III; ESCHERICHIA-COLI; THETA-SUBUNIT; EPSILON-SUBUNIT; PROOFREADING EXONUCLEASE; MUTATIONAL ANALYSIS; HOLOENZYME; REPLICATION; PROTEINS; GENOME AB The Hot (homolog of theta) protein of bacteriophage P1 can substitute for the Escherichia coli DNA polymerase III theta subunit, as evidenced by its stabilizing effect on certain dnaQ mutants that carry an unstable polymerase III epsilon proofreading subunit (antimutator effect). Here, we show that Hot can also cause an increase in the mutability of various E. coli strains (mutator effect). The hot mutator effect differs from the one caused by the lack of theta. Experiments using chimeric theta/Hot proteins containing various domains of Hot and theta along with a series of point mutants show that both N- and C-terminal parts of each protein are important for stabilizing the F subunit. In contrast, the N-terminal part of Hot appears uniquely responsible for its mutator activity. C1 Natl Inst Environm Hlth Sci, Genet Mol Lab, Res Triangle Pk, NC 27709 USA. Russian Acad Med Sci, DI Ivanovskii Virol Inst, Moscow 123098, Russia. RP Schaaper, RM (reprint author), Natl Inst Environm Hlth Sci, Genet Mol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov FU Intramural NIH HHS NR 34 TC 8 Z9 8 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 AUG PY 2006 VL 188 IS 16 BP 5831 EP 5838 DI 10.1128/JB.00630-06 PG 8 WC Microbiology SC Microbiology GA 073AS UT WOS:000239715200018 PM 16885451 ER PT J AU Palmieri, D Horak, CE Lee, JH Halverson, DO Steeg, PS AF Palmieri, Diane Horak, Christine E. Lee, Jong-Heun Halverson, Douglas O. Steeg, Patricia S. TI Translational approaches using metastasis suppressor genes SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE Nm23; RhoGDI2; metastasis; metastasis suppressor; breast; cancer; histidine protein kinase ID NUCLEOSIDE-DIPHOSPHATE KINASE; BREAST-CARCINOMA CELLS; PROTEIN-COUPLED RECEPTOR; AUTONOMOUS LETHAL MUTATION; HETEROTRIMERIC G-PROTEINS; ENERGY PHOSPHATE TRANSFER; C-MYC OVEREXPRESSION; DNA-REPAIR NUCLEASE; CANCER METASTASIS; ESCHERICHIA-COLI AB Cancer metastasis is a significant contributor to breast cancer patient morbidity and mortality. In order to develop new anti-metastatic therapies, we need to understand the biological and biochemical mechanisms of metastasis. Toward these efforts, we and others have studied metastasis suppressor genes, which halt metastasis in vivo without affecting primary tumor growth. The first metastasis suppressor gene identified was nm23, also known as NDP kinase. Nm23 represents the most widely validated metastasis suppressor gene, based on transfection and knock-out mouse strategies. The biochemical mechanism of metastasis suppression via Nm23 is unknown and likely complex. Two potential mechanisms include binding proteins and a histidine kinase activity. Elevation of Nm23 expression in micrometastatic tumor cells may constitute a translational strategy for the limitation of metastatic colonization in high risk cancer patients. To date, medroxyprogesterone acetate (MPA) has been identified as a candidate compound for clinical testing. C1 NCI, Womens Canc Sect, Lab Mol Pharmacol, Canc Res Ctr,NIH, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Lab Mol Pharmacol, Canc Res Ctr,NIH, Bldg 37,Room 1122, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov RI Palmieri, Diane/B-4258-2015 FU Intramural NIH HHS NR 116 TC 33 Z9 34 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD AUG PY 2006 VL 38 IS 3-4 BP 151 EP 161 DI 10.1007/s10863-006-9039-9 PG 11 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 116RN UT WOS:000242820100002 PM 16944301 ER PT J AU Burton, RA Tjandra, N AF Burton, Robert A. Tjandra, Nico TI Determination of the residue-specific N-15 CSA tensor principal components using multiple alignment media SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alignment; chemical shift anisotropy; chemical shift tensor; NMR; residual dipolar couplings ID CHEMICAL-SHIFT ANISOTROPY; SOLID-STATE NMR; CROSS-CORRELATED RELAXATION; PROTEIN SECONDARY STRUCTURE; NUCLEAR-MAGNETIC-RESONANCE; DENSITY-FUNCTIONAL THEORY; LIQUID-CRYSTALLINE PHASE; HIGH-RESOLUTION NMR; DIPOLAR COUPLINGS; BIOLOGICAL MACROMOLECULES AB The individual components of the backbone N-15 CSA tensor, sigma(11), sigma(22), sigma(33), and the orientation of sigma(11) relative to the NH bond described by the angle beta have been determined for uniformly labeled N-15, C-13 ubiquitin from partial alignment in phospholipid bicelles, Pf1 phage, and poly(ethylene glycol) by measuring the residue-specific residual dipolar couplings and chemical shift deviations. No strong correlation between any of the CSA tensor components is observed with any single structural feature. However, the experimentally determined tensor components agree with the previously determined average CSA principal components [Cornilescu and Bax (2000) J. Am. Chem. Soc. 122, 10143-10154]. Significant deviations from the averages coincide with residues in beta-strand or extended regions, while alpha-helical residue tensor components cluster close to the average values. C1 NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Mol Biol Lab, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM tjandran@nhlbi.nih.gov FU Intramural NIH HHS NR 56 TC 12 Z9 12 U1 0 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD AUG PY 2006 VL 35 IS 4 BP 249 EP 259 DI 10.1007/s10858-006-9037-6 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 077ZK UT WOS:000240070300003 PM 16823597 ER PT J AU Brandish, PE Chiu, CS Schneeweis, J Brandon, NJ Leech, CL Kornienko, O Scolnick, EM Strulovici, B Zheng, W AF Brandish, Philip E. Chiu, Chi-Sung Schneeweis, Jonathan Brandon, Nicholas J. Leech, Clare L. Kornienko, Oleg Scolnick, Edward M. Strulovici, Berta Zheng, Wei TI A cell-based ultra-high-throughput screening assay for identifying inhibitors of D-amino acid oxidase SO JOURNAL OF BIOMOLECULAR SCREENING LA English DT Article DE D-amino acid oxidase; DAO; cell-based enzyme assay; high-throughput screening; uHTS; schizophrenia ID SCINTILLATION PROXIMITY ASSAY; D-SERINE; SCHIZOPHRENIA; CLOZAPINE; PROTEIN; GLYCINE; GENE AB Enzymes are often considered less "druggable" targets than ligand-regulated proteins such as G-protein-coupled receptors, ion channels, or other hormone receptors. Reasons for this include cellular location (intracellular vs. cell surface), typically lower affinities for the binding, of small molecules compared to ligand-specific receptors, and binding (catalytic) sites that are often charged or highly polar. A practical drawback to the discovery of compounds targeting enzymes is that screening of compound libraries is typically carried out in cell-free activity assays using purified protein in an inherently artificial environment. Cell-based assays, although often arduous to design for enzyme targets, are the preferred discovery toot for the screening of large compound libraries. The authors have recently described a novel cell-based approach to screening for inhibitors of a phosphatase enzyme and now report on the development and implementation of a homogeneous 3456-well plate assay for D-amino acid oxidase (DAO). Human DAO was stably expressed in Chinese hamster ovary (CHO) cells, and its activity was measured as the amount of hydrogen peroxide detected in the growth medium following feeding the cells with D-serine. In less than 12 weeks, the authors proved the concept in 96- and then 384-well formats, miniaturized the assay to the 3456-well (nanoplate) scale, and screened a library containing more than I million compounds. They have identified several cell-permeable inhibitors of DAO from this cell-based high-throughput screening, which provided the discovery program with a few novel and attractive lead structures. C1 Dept Neurobiol, West Point, PA USA. Dept Automated Biotechnol, N Wales, PA USA. Merck & Co Inc, Dept Mol & Cellular Neurosci, Terlings Pk, England. RP Zheng, W (reprint author), NHGRI, NIH, Chem Genom Ctr, 9800 Med Ctr Dr,MSC-3370, Bethesda, MD 20892 USA. EM wzheng@mail.nih.gov OI Zheng, Wei/0000-0003-1034-0757 NR 19 TC 21 Z9 22 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1087-0571 J9 J BIOMOL SCREEN JI J. Biomol. Screen PD AUG PY 2006 VL 11 IS 5 BP 481 EP 487 DI 10.1177/1087057106288181 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry GA 077AD UT WOS:000239999200003 PM 16760370 ER PT J AU Ahmet, I Lakatta, EG Talan, MI AF Ahmet, Ismayil Lakatta, Edward G. Talan, Mark I. TI The effect of long-term pharmacological manipulation of beta-adrenergic receptors on mortality in the model of chronic heart failure in rats SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 270 BP S84 EP S84 DI 10.1016/j.cardfail.2006.06.285 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000270 ER PT J AU O'Connor, CM Hasselblad, V Tasissa, G Pauly, DF Russell, SD Nohria, A Koelling, TM Binanay, C Shah, MR Sopko, G Califf, RM Stevenson, LW AF O'Connor, C. M. Hasselblad, V. Tasissa, G. Pauly, D. F. Russell, S. D. Nohria, A. Koelling, T. M. Binanay, C. Shah, M. R. Sopko, G. Califf, R. M. Stevenson, L. W. TI The ESCAPE discharge risk score: Don't go home without it SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 DUMC, Duke Clin Res Inst, Durham, NC USA. Univ Florida, Gainesville, FL USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Alabama, Birmingham, AL USA. Georgetown Univ, Sch Med, Washington, DC USA. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 385 BP S117 EP S117 DI 10.1016/j.cardfail.2006.06.404 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000385 ER PT J AU Rogers, JG Tasissa, G Francis, GS DiSalvo, TG Leier, CV Wagoner, LE Pina, IL Stevenson, LW Sopko, G O'Connor, CM AF Rogers, J. G. Tasissa, G. Francis, G. S. DiSalvo, T. G. Leier, C. V. Wagoner, L. E. Pina, I. L. Stevenson, L. W. Sopko, G. O'Connor, C. M. TI Sustained reduction in symptoms related to reduction of filling pressures during hospitalization for heart failure SO JOURNAL OF CARDIAC FAILURE LA English DT Meeting Abstract CT 10th Annual Scientific Meeting of the Heart-Failure-Society-of-America CY SEP 10-13, 2006 CL Seattle, WA SP Heart Failure Soc Amer C1 DUMC, Duke Clin Res Inst, Durham, NC USA. Cleveland Clin, Cleveland, OH 44106 USA. UNC, Chapel Hill, NC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Hosp, Cincinnati, OH USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD AUG PY 2006 VL 12 IS 6 SU 1 MA 364 BP S111 EP S111 DI 10.1016/j.cardfail.2006.06.469 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 079VC UT WOS:000240205000364 ER PT J AU Fatemi, M Wade, PA AF Fatemi, Mehrnaz Wade, Paul A. TI MBD family proteins: reading the epigenetic code SO JOURNAL OF CELL SCIENCE LA English DT Article DE DNA methylation; transcriptional repression; epigenetics; methyl CpG binding protein ID CPG-BINDING-PROTEINS; DEPENDENT TRANSCRIPTIONAL REPRESSOR; CHROMATIN-REMODELING COMPLEX; HISTONE DEACETYLASE COMPLEX; METHYL-CPG; DNA METHYLATION; RETT-SYNDROME; CHROMOSOMAL PROTEIN; GENE-EXPRESSION; MECP2 AB Methylation of DNA in mammalian cells serves to demarcate functionally specialized regions of the genome and is strongly associated with transcriptional repression. A highly conserved family of DNA-binding proteins characterized by a common sequence motif is widely believed to convert the information represented by methylation patterns into the appropriate functional state. This family, the MBD family, has been characterized at both the biochemical and genetic levels. A key issue, given their highly similar DNA-binding surfaces, is whether the individual MBD proteins bind differentially to distinct regions within the genome and, if so, by what mechanism. Somewhat surprisingly, some MBD family members, such as MeCP2, have considerable selectivity for specific sequences. Other family members, such as MBD2, appear to bind with somewhat relaxed specificity to methylated DNA. Recent genetic and molecular experiments have shed considerable light on these and other issues relevant to the chromosomal biology of this interesting protein family. C1 Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. RP Wade, PA (reprint author), Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, 111 TW Alexander Dr,Mail Drop D4-04, Res Triangle Pk, NC 27709 USA. EM wadep2@niehs.nih.gov FU Intramural NIH HHS NR 54 TC 57 Z9 61 U1 1 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD AUG 1 PY 2006 VL 119 IS 15 BP 3033 EP 3037 DI 10.1242/jcs.03099 PG 5 WC Cell Biology SC Cell Biology GA 080FS UT WOS:000240233900003 PM 16868031 ER PT J AU Loukinov, D Ghochikyan, A Mkrtichyan, M Ichim, TE Lobanenkov, VV Cribbs, DH Agadjanyan, MG AF Loukinov, Dmitri Ghochikyan, Anahit Mkrtichyan, Mikayel Ichim, Thomas E. Lobanenkov, Victor V. Cribbs, David H. Agadjanyan, Michael G. TI Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE BORIS; CT antigens; breast cancer; mammary tumor; vaccine ID COSTIMULATORY MOLECULES; CANCER/TESTIS ANTIGENS; CANCER-IMMUNOTHERAPY; MAMMARY-CARCINOMA; T-LYMPHOCYTES; VACCINES; GENE; EXPRESSION; RESPONSES; CTCF AB Cancer testis (CT) antigens are promising candidates for tumor vaccines due to their immunogenicity and tissue-restricted expression. Recently, we identified a novel cancer testis gene, BORIS, whose expression is restricted to male testis after puberty and is strictly absent in non-malignant female tissue. BOR/Sencodes a DNA-binding protein that shares 11 zing finger (ZF) with transcription factor CTCF and differs at the N- and C-termini. CTCF has been implicated in epigenetic regulation of imprinting, X chromosome inactivation, repression, and activation of cancer testis antigens. BORIS expression has been documented in cancers of diverse histological origin, including, but not limited to breast, prostate, ovary, gastric, liver, endometrial, glia, colon, and esophagus. Interestingly, BORIS induces demethylation and subsequent expression of many cancer-testis genes, including MAGE-A1 and NY-ESO-1, indicating that it is expressed very early in malignancy and might be an attractive candidate for immunotherapy. In this study we tested BORIS as a vaccine in a very aggressive, highly metastatic, and poorly immunogenic murine model of mammary carcinoma. Immunizations with a DNA encoding the mutant form of murine BORIS antigen (pmBORIS lacking DNA-binding function) significantly prolonged survival, and inhibited tumor growth in BALB/c mice inoculated with 4T1 cells. Priming with pmBORIS mixed with molecular adjuvant and boosting with adenoviral vector expressing mBORIS was generally more effective, suggesting that the vaccination protocol could be further optimized. This is the first report demonstrating the feasibility of vaccination with a cancer associated epigenetic regulator for the induction of tumor inhibition. C1 Inst Mol Med, Dept Mol Immunol, Huntington Beach, CA 92647 USA. NIAID, Bethesda, MD USA. Oncomune LLC, Miami, FL USA. Univ Calif Irvine, Inst Brain Aging & Dementia, Dept Neurol, Irvine, CA 92717 USA. RP Agadjanyan, MG (reprint author), Inst Mol Med, Dept Mol Immunol, 16371 Gothard St, Huntington Beach, CA 92647 USA. EM magadjanyan@immed.org OI Lobanenkov, Victor/0000-0001-6665-3635; Ghochikyan, Anahit/0000-0001-5436-0616 NR 31 TC 28 Z9 29 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG 1 PY 2006 VL 98 IS 5 BP 1037 EP 1043 DI 10.1002/jcb.20953 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 067XV UT WOS:000239336800001 PM 16741971 ER PT J AU Rao, MS AF Rao, Mahendra S. TI Are there morally acceptable alternatives to blastocyst derived ESC? SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE hESC; karyotype; characterization; mitochondrial sequencing; methylation ID EMBRYONIC STEM-CELLS; PROGENITOR CELLS; BONE-MARROW; MOUSE; MUSCLE; BRAIN AB ESC derivation, use and SCNT have raised many moral and ethical issues. In this opinion piece I have focused on the argument that morally less ambiguous alternatives to ESC derived from the ICM of blastocysts exist. These possibilities range from using multiple adult stem cell populations each of which is uniquely suited for a particular disease target or identifying adult ESC-like populations, using transdifferentiated ESC-like cells or alternate methods of deriving ESC. I suggest that while it is important to support such efforts current results do not provide sufficient compelling data to allow one to stop the use of ESC and perhaps adult cells will never be a reliable alternative. All options need to be fully explored and decisions need to be made with scientific rigor and respect for each individuals moral compass. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Rao, MS (reprint author), NIA, Gerontol Res Ctr, Stem Cell Biol Unit, Natl Inst Hlth, Baltimore, MD 21224 USA. EM raomah@grc.nia.nih.gov NR 15 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD AUG 1 PY 2006 VL 98 IS 5 BP 1054 EP 1061 DI 10.1002/jcb.20723 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 067XV UT WOS:000239336800003 PM 16598787 ER PT J AU Leibenluft, E Cohen, P Gorrindo, T Brook, JS Pine, DS AF Leibenluft, Ellen Cohen, Patricia Gorrindo, Tristan Brook, Judith S. Pine, Daniel S. TI Chronic versus episodic irritability in youth: A community-based, longitudinal study of clinical and diagnostic associations SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID BIPOLAR DISORDER; INTERVIEW SCHEDULE; EARLY-ADULTHOOD; CHILDREN; ADOLESCENCE; ADHD; RELIABILITY; MANIA; PSYCHOPATHOLOGY; COMORBIDITY AB Objective: Irritability is both a normal developmental phenomenon and a common psychiatric symptom in children. In psychiatric nosology, a distinction is made between chronic and episodic irritability. This study examines the validity of this distinction. Methods: A sample of 776 youths received Diagnostic and Statistical Manual of Mental Disoders (DSM)-based structured interviews at three time points. Questions regarding episodic and chronic irritability were used to create scales measuring these constructs; associations with age, gender, and diagnosis were examined. Results: Episodic and chronic irritability differed in their associations with age. The longitudinal stability within irritability type was stronger than between types. In longitudinal analyses, chronic irritability at time 1 (mean age 13.8 +/- 2.6 years) predicted attention-deficit/hyperactivity disorder at time 2 (mean age 16.2 +/- 2.8 years) and major depression at time 3 (mean age 22.1 +/- 2.7 years). Episodic irritability at time 1 predicted simple phobia and mania at time 2. Conclusions: Episodic and chronic irritability in adolescents appear to be stable, distinct constructs. Further research is needed to elucidate the longitudinal associations of each with specific psychiatric diagnoses. C1 NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, Dept Psychiat, Div Epidemiol & Mental Disorders, New York, NY 10032 USA. Columbia Univ, New York, NY USA. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. RP Leibenluft, E (reprint author), NIMH, Mood & Anxiety Program, NIH, Dept Hlth & Human Serv, Bldg 10,Room 4N-208,10 Ctr Dr MSC 1255, Bethesda, MD 20892 USA. EM LEIBS@MAIL.NIH.GOV FU NIDA NIH HHS [DA 00244, DA 03188]; NIMH NIH HHS [MH 36071, MH 38916, MH 49191] NR 33 TC 102 Z9 102 U1 2 U2 9 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD AUG PY 2006 VL 16 IS 4 BP 456 EP 466 DI 10.1089/cap.2006.16.456 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 091DR UT WOS:000241007000008 PM 16958570 ER PT J AU Cabiya, JJ Canino, G Chavez, L Ramirez, R Alegria, M Shrout, P Hohman, A Bravo, M Bauermeister, JJ Maritinez-Taboas, A AF Cabiya, Jose J. Canino, Glorisa Chavez, Ligra Ramirez, Rafael Alegria, Margenta Shrout, Patrick Hohman, Ann Bravo, Milagros Bauermeister, Jose J. Maritinez-Taboas, Alfonso TI Gender disparities in mental health service use of Puerto Rican children and adolescents SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE service development; public health; disruptive behavior; internalizing disorder ID DIAGNOSTIC INTERVIEW SCHEDULE; GREAT SMOKY MOUNTAINS; FUNCTIONAL IMPAIRMENT; PSYCHIATRIC-DISORDERS; TEST-RETEST; RELIABILITY; CARE; IV; PREVALENCE; VERSION AB Background: Differences in service utilization indicating that boys use more mental health services than girls were analyzed to see if they could be explained by known correlates of service use. These correlates were arranged into individual ( severe emotional disturbance, level of impairment and externalizing disorders), family ( parental education, psychopathology and parental concern) and school factors ( difficulties with school work). The objectives were to understand and identify the factors accounting for gender differences in mental health service utilization in order to develop alternatives to promote equity in service delivery. Methods: A representative sample of 1,896 children 4 to 17 years of age and their primary caretakers were interviewed for this study. Reports of service use were obtained using the Service Assessment for Children and Adolescents. Logistic regression was used to assess the relationship between gender and service use, adjusting for known correlates. Results: Our results showed that, except for impairment, other individual, family and school factors did not explain gender differences in service utilization. Males with impairment were 2.87 times more likely to receive services than impaired females (p <= .01), and this result continued to hold true for impaired undiagnosed boys compared to impaired diagnoses-free girls (p <= .001). Conclusions: Our findings showed a service disparity between impaired boys and girls who did not meet criteria for a DSM IV diagnosis, but no observed differences in service use between boys and girls who met criteria for severe emotional disturbance ( SED). Continued investigations are necessary to analyze, assess and understand the different circumstances that bring boys and girls into treatment, followed by the development of appropriate intervention programs at the school and community levels. C1 Carlos Albizu Univ, San Juan, PR 00902 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Harvard Univ, Boston, MA 02115 USA. NYU, New York, NY USA. NIMH, Bethesda, MD 20892 USA. RP Cabiya, JJ (reprint author), Carlos Albizu Univ, POB 9023711,Old San Juan Stn, San Juan, PR 00902 USA. EM jcabiya@albizu.edu OI ramirez, rafael/0000-0002-9504-7260 FU NIMH NIH HHS [MH54827, P01 MH 59876-02]; NIMHD NIH HHS [P20 MD000537-01, R24 MD00152-01] NR 48 TC 19 Z9 19 U1 4 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD AUG PY 2006 VL 47 IS 8 BP 840 EP 848 DI 10.1111/j.1469-7610.2006.01623.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 065ID UT WOS:000239152500011 PM 16898998 ER PT J AU Marx, SJ Simonds, WF AF Marx, Stephen J. Simonds, William F. TI Editorial: Imaging to detect early endocrine cancers SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID JAW TUMOR SYNDROME; FAMILIAL ISOLATED HYPERPARATHYROIDISM; SPORADIC PARATHYROID TUMORS; HRPT2 GENE; PARAFIBROMIN; MUTATIONS; TRANSCRIPTION; CARCINOMA; GERMLINE; COMPLEX C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Marx, SJ (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Room 9C-103,MSC 1804, Bethesda, MD 20892 USA. EM stephenM@intra.niddk.nik.gov FU Intramural NIH HHS NR 20 TC 0 Z9 0 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2861 EP 2863 DI 10.1210/jc.2006-1226 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700009 PM 16894022 ER PT J AU Van, PL Bakalov, VK Bondy, CA AF Van, Phillip L. Bakalov, Vladimir K. Bondy, Carolyn A. TI Rapid communication - Monosomy for the X-chromosome is associated with an atherogenic lipid profile SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; DENSITY-LIPOPROTEIN CHOLESTEROL; HORMONE REPLACEMENT THERAPY; METABOLIC SYNDROME; MENOPAUSAL STATUS; GENDER; AGE; DISEASE; WOMEN AB Context and Objective: Men typically have a more atherogenic lipid profile than women characterized by higher low-density lipoprotein (LDL) cholesterol and triglyceride levels and reduced lipid particle size, contributing to a greater risk for coronary disease. To determine whether X-chromosomal gene dosage affects lipid metabolism independent of sex steroid effects, we compared lipid profiles in age- and body mass-matched young women with ovarian failure, differing only in X-chromosome dosage. Design, Setting, and Patients: Women with premature ovarian failure associated with monosomy X or Turner syndrome (TS, n = 118) were compared with women with 46, XX premature ovarian failure (n = 51) in an in-patient clinical research center unit at the National Institutes of Health. These women were normally on estrogen replacement treatment but discontinued the estrogen 2 wk before study. Major Outcomes: Fasting lipid levels and nuclear magnetic resonance lipid particle profiles in the two study groups were the major outcomes. Results: Average age and body mass were similar in the two groups of women, but LDL cholesterol (P = 0.001) and triglyceride levels (P = 0.0005) were higher in the TS group. Also among women with TS, average LDL particle size was reduced (P < 0.0001) and LDL particle concentration increased, with a 2-fold increase in the smallest particle categories (P < 0.0001). Whereas total high-density lipoprotein cholesterol levels were similar, high-density lipoprotein particle size was significantly smaller in women with TS, compared with women with premature ovarian failure (P < 0.0001). Conclusions: Women with 45, X with ovarian failure exhibit a distinctly more atherogenic lipid profile than 46, XX women with ovarian failure, suggesting that the second X-chromosome contributes to a more salutary lipid profile in normal women, independent of sex steroid effects. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bondy, CA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov FU Intramural NIH HHS NR 23 TC 33 Z9 34 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2867 EP 2870 DI 10.1210/jc.2006-0503 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700011 PM 16705071 ER PT J AU Meigs, JB Wilson, PWF Fox, CS Vasan, RS Nathan, DM Sullivan, LM D'Agostino, RB AF Meigs, James B. Wilson, Peter W. F. Fox, Caroline S. Vasan, Ramachandran S. Nathan, David M. Sullivan, Lisa M. D'Agostino, Ralph B. TI Body mass index, metabolic syndrome, and risk of type 2 diabetes or cardiovascular disease SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORONARY-HEART-DISEASE; INSULIN-RESISTANCE; FAT DISTRIBUTION; NORMAL-WEIGHT; POSTMENOPAUSAL WOMEN; ABDOMINAL ADIPOSITY; OBESE INDIVIDUALS; MEN; MELLITUS; HEALTHY AB Context: Metabolic risk conferred by adiposity may be due to associated risk factor clustering. Objective: The objective of this study was to assess risk for diabetes or cardiovascular disease (CVD) stratified by body mass index (BMI) and the presence or absence of metabolic syndrome (MetS) or insulin resistance (IR). Design, Setting, and Participants: This was a community-based, longitudinal study of 2902 people (55% women, mean age 53 yr) without diabetes or CVD in 1989-1992 followed for up to 11 yr. We categorized subjects by normal weight (BMI < 25 kg/m(2)), overweight (25-29.9 kg/m(2)), or obese (> 30 kg/m(2)) and by the National Cholesterol Education Program's Adult Treatment Panel MetS or the top quartile of homeostasis model IR. We used proportional hazard models to estimate risk relative to normal weight and no MetS or IR. Main Outcome Measure: Incident type 2 diabetes (treatment or fasting glucose >= 7 mmol/liter, 141 events) or CVD (myocardial infarction, stroke, or claudication, 252 events) were measured. Results: Among 1056 normal-weight subjects, 7% had MetS and a risk factor-adjusted relative risk for diabetes of 3.97 (95% confidence interval, 1.35-11.6) and for CVD of 3.01 (1.68-5.41). Among 638 obese subjects, 37% did not have MetS or significantly increased risk. Obese subjects with MetS had an adjusted relative risk for diabetes of 10.3 (5.44-19.5) and for CVD of 2.13 (1.43-3.18). Results were similar in analyses of BMI-IR categories. Conclusions: People with normal weight and MetS or IR or with obesity but no MetS or IR were not uncommon in our sample. Risk factor clustering or IR appear to confer much of the risk for diabetes or CVD commonly associated with elevated BMI. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, NHLBI,Framingham Heart Study, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Endocrinol & Hypertens, Boston, MA 02115 USA. Boston Univ, Sch Med, NHLBI, Framingham Heart Study, Boston, MA 02215 USA. Boston Univ, Sch Med, NHLBI, Evans Dept Med,Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Med, NHLBI, Prevent Med Sect, Boston, MA 02215 USA. Boston Univ, Dept Math Stat & Consulting, Boston, MA 02118 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Stanford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01 HC 25195, 2K24 HL 04334] NR 49 TC 392 Z9 406 U1 4 U2 25 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2906 EP 2912 DI 10.1210/jc.2006-0594 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700018 PM 16735483 ER PT J AU Akintoye, SO Kelly, MH Brillante, B Cherman, N Turner, S Butman, JA Robey, PG Collins, MT AF Akintoye, Sunday O. Kelly, Marilyn H. Brillante, Beth Cherman, Natasha Turner, Sarah Butman, John A. Robey, Pamela G. Collins, Michael T. TI Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID STIMULATORY G-PROTEIN; RECEPTOR ANTAGONIST; FIBROUS DYSPLASIA; BINDING PROTEIN-3; MOLECULAR-BASIS; BONE; MARKERS; DEFECTS AB Context: GH excess affects approximately 20% of the patients with McCune-Albright syndrome (MAS). MAS is caused by sporadic, postzygotic, activating mutations in the GNAS gene, which codes for the cAMP-regulating protein, G(s)alpha (gsp oncogene). These same mutations are found in approximately one third of the sporadic cases of acromegaly. Objective: We examined efficacy of the GH receptor antagonist, pegvisomant, in controlling gsp oncogene-mediated GH excess and skeletal disease (fibrous dysplasia of bone) associated with MAS. Setting and Patients: Five MAS patients with GH excess were treated with 20 mg/d sc injection of pegvisomant for 12 wk in a randomized, double-blind, placebo-controlled crossover study at the National Institutes of Health. Main Outcome Measures: The primary measure of efficacy was normalization of IGF-I. Secondary outcome measures were reduction in serum IGF binding protein-3 (IGFBP-3), improvement of fatigue and sweating, and reduction in markers of bone metabolism and bone pain. Results: Combined mean changes in serum IGF-I at 6 and 12 wk were -236.4 ng/ml (53%, P < 0.005) and -329.8 ng/ml (62%, P < 0.001), respectively. IGFBP-3 decreased by 0.8 mg/liter (24%, P < 0.01) and 2.9 mg/liter (37%, P < 0.005), respectively. There were no significant changes in signs and symptoms of acromegaly or markers of bone metabolism and bone pain, nor was there a significant change in pituitary size. Retrospective comparison of the degree of control achieved with pegvisomant vs. other medications (long-acting octreotide +/- dopamine agonist) in the same group showed that the two regimens were similarly effective. Conclusions: Pegvisomant effectively reduced IGF-I and IGFBP-3 levels in gsp-mediated GH excess but had no effect on fibrous dysplasia. C1 Dept Hlth & Human Serv, Craniofacial & Skeletal Dis Branch, Clin Ctr, NIH, Bethesda, MD 20892 USA. Dept Hlth & Human Serv, Diagnost Radiol Dept, Clin Ctr, NIH, Bethesda, MD 20892 USA. RP Akintoye, SO (reprint author), Univ Penn, Sch Dent Med, Dept Oral Med, Robert Schattner Ctr, Ctr Room,209,240 S 40th St, Philadelphia, PA 19104 USA. EM akintoye@dental.upenn.edu RI Butman, John/A-2694-2008; Robey, Pamela/H-1429-2011; OI Robey, Pamela/0000-0002-5316-5576; Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS NR 24 TC 21 Z9 22 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 2960 EP 2966 DI 10.1210/jc.2005-2661 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700026 PM 16720661 ER PT J AU Semple, RK Soos, MA Luan, J Mitchell, CS Wilson, JC Gurnell, M Cochran, EK Gorden, P Chatterjee, VKK Wareham, NJ O'Rahilly, S AF Semple, R. K. Soos, M. A. Luan, J. Mitchell, C. S. Wilson, J. C. Gurnell, M. Cochran, E. K. Gorden, P. Chatterjee, V. K. K. Wareham, N. J. O'Rahilly, S. TI Elevated plasma adiponectin in humans with genetically defective insulin receptors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GLUCOSE-INTOLERANCE; RESISTANCE; LEPTIN; LIPOATROPHY; THERAPY; SERUM; MICE AB Context: Adiponectin has been suggested to play a role in the etiopathogenesis of at least some forms of insulin resistance, in part based on a strong correlation between plasma levels of adiponectin and measures of insulin sensitivity. Objective: The objective of the study was to establish whether this relationship is maintained at extreme levels of insulin resistance. Design/Setting: This was a cross-sectional study in a university teaching hospital of subjects recruited from the United Kingdom and the United States. Participants: Participants included 75 subjects with a range of syndromes of severe insulin resistance and 872 nondiabetic controls. Outcome Measures: Fasting plasma insulin, adiponectin, and leptin were measured. Results: Unexpectedly, subjects with mutations in the insulin receptor, despite having the most severe degree of insulin resistance, had elevated plasma adiponectin [median 24.4 mg/liter; range 6.6-36.6 (normal adult range for body mass index 20 kg/m(2) = 3-19 mg/liter)], whereas all other subjects had low adiponectin levels (median 2.0 mg/liter; range 0.12-11.2). Plasma leptin in all but one subject with an insulin receptoropathy was low or undetectable [median 0.5 ng/ml; range 0-16: normal adult range for body mass index of < 25 kg/m(2) = 2.4-24.4 (female) and 0.4-8.3 ng/ml (male)]. Conclusions: We conclude that the relationship between plasma adiponectin and insulin sensitivity is complex and dependent on the precise etiology of defective insulin action and that the combination of high plasma adiponectin with low leptin may have clinical utility in patients with severe insulin resistance as a marker of the presence of a genetic defect in the insulin receptor. C1 Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England. Univ Cambridge, Addenbrookes Hosp, Dept Med, Cambridge, England. Natl Inst Diabet & Digest & Kidney Dis, Clin Epidemiol Branch, Bethesda, MD 20892 USA. Univ Cambridge, Elsie Widdowson Lab, Inst Publ Hlth, Cambridge CB1 9NL, England. Univ Cambridge, Med Res Council Epidemiol Unit, Cambridge CB1 9NL, England. RP Semple, RK (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Clin Biochem, Cambridge, England. EM rks16@cam.ac.uk OI Semple, Robert/0000-0001-6539-3069 FU Medical Research Council [MC_U106179471]; Wellcome Trust NR 19 TC 83 Z9 85 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD AUG PY 2006 VL 91 IS 8 BP 3219 EP 3223 DI 10.1210/jc.2006-0166 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 071LM UT WOS:000239603700064 PM 16705075 ER PT J AU Crowley, W Courtney, J Jameson, L Pardes, H Moskowitz, J Orringer, E Rubenstein, A Wood, A Rettig, R Ausiello, D Brenner, D Collins, F Elias, J Greene, W Horowitz, R Jameson, L Kieff, E Thompson, C Swain, JL AF Crowley, William, Jr. Courtney, John Jameson, Larry Pardes, Herbert Moskowitz, Jay Orringer, Eugene Rubenstein, Arthur Wood, Alastair Rettig, Richard Ausiello, Dennis Brenner, David Collins, Francis Elias, Jack Greene, Warner Horowitz, Ralph Jameson, Larry Kieff, Elliott Thompson, Craig Swain, Judith L. TI The Clinical Research Forum and Association of American Physicians disagree with criticism of the NIH Roadmap SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Letter ID RESEARCH ENTERPRISE C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. New York Presbyterian Hosp, New York, NY USA. Columbia Univ, Sch Med, New York, NY 10027 USA. Penn State Univ, University Pk, PA 16802 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Penn, Philadelphia, PA 19104 USA. Vanderbilt Univ, Nashville, TN 37240 USA. Cornell Univ, Sch Med, Ithaca, NY 14853 USA. NIH, Ctr Human Genet, Bethesda, MD USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Crowley, W (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM crowley.william@mgh.harvard.edu NR 6 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2006 VL 116 IS 8 BP 2058 EP 2059 DI 10.1172/JCI29557 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 070DA UT WOS:000239499300001 PM 16886049 ER PT J AU Conville, PS Zelazny, AM Witebsky, FG AF Conville, Patricia S. Zelazny, Adrian M. Witebsky, Frank G. TI Analysis of secA1 gene sequences for identification of Nocardia species SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION-ENDONUCLEASE ANALYSIS; RIBOSOMAL-RNA GENE; FARCINICA; PATHOGEN AB Molecular methodologies, especially 16S rRNA gene sequence analysis, have allowed the recognition of many new species of Nocardia and to date have been the most precise methods for identifying isolates reliably to the species level. We describe here a novel method for identifying Nocardia isolates by using sequence analysis of a portion of the secA1 gene. A region of the secA1 gene of 30 type or reference strains of Nocardia species was amplified using secA1-specific primers. Sequence analysis of 468 bp allowed clear differentiation of all species, with a range of interspecies similarity of 85.0% to 98.7%. Corresponding 16S rRNA gene sequences of a 1,285-bp region for the same isolates showed a range of interspecies similarity of 94.4 to 99.8%. In addition to the type and reference strains, a 468-bp fragment of the secA1 gene was sequenced from 40 clinical isolates of 12 Nocardia species previously identified by 16S rRNA gene sequence analysis. The secA1 gene sequences of most isolates showed >99.0% similarity to the secA1 sequences of the type or reference strain to which their identification corresponded, with a range of 95.3 to 100%. Comparison of the deduced 156 amino acid sequences of the SecA1 proteins of the clinical isolates showed between zero and two amino acid residue differences compared to that of the corresponding type or reference strain. Sequencing of the secA1 gene, and using deduced amino acid sequences of the SecA1 protein, may provide a more discriminative and precise method for the identification of Nocardia isolates than 16S rRNA gene sequencing. C1 NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,US Dept Hlth & Human S, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,US Dept Hlth & Human S, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM pconville@nih.gov FU Intramural NIH HHS NR 13 TC 37 Z9 41 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD AUG PY 2006 VL 44 IS 8 BP 2760 EP 2766 DI 10.1128/JCM.00155-06 PG 7 WC Microbiology SC Microbiology GA 076UG UT WOS:000239982800013 PM 16891489 ER PT J AU Fears, TR Guerry, D Pfeiffer, RM Sagebiel, RW Elder, DE Halpern, A Holly, EA Hartge, P Tucker, MA AF Fears, Thomas R. Guerry, DuPont Pfeiffer, Ruth M. Sagebiel, Richard W. Elder, David E. Halpern, Allan Holly, Elizabeth A. Hartge, Patricia Tucker, Margaret A. TI Identifying individuals at high risk of melanoma: A practical predictor of absolute risk SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; AMERICAN JOINT COMMITTEE; ATTRIBUTABLE RISK; CANCER; PROBABILITIES; SURVEILLANCE; NEVI AB Purpose We developed a model to estimate the 5-year absolute risk of melanoma to efficiently identify individuals at increased risk of melanoma for potential interventions. Patients and Methods We used data from a case-control study with 718 non-Hispanic white patients with invasive cutaneous melanoma from melanoma clinics in Philadelphia, PA and San Francisco, CA; matched controls were 945 patients from outpatient clinics with similar catchment areas. All participants underwent extensive interviews and skin examinations. We selected easily obtained clinical characteristics and responses to simple questions for study in order to develop sex-specific relative risk models. These models were combined with incidence and mortality rates by United States geographic areas to develop estimates of the absolute risk of developing melanoma within 5 years. Results Relative risk models yielded an attributable risk of 86% for men and 89% for women, using at most seven variables. Attributable risks did not vary by age, ultraviolet B flux or hours outdoors. The absolute individual risks varied widely, depending on age, other host characteristics, and geographic area. Individual absolute risk can be estimated using a program available online. Conclusion Our procedures allow for estimating the absolute risk of developing melanoma to assist in the identification of patients at high risk. Such high-risk individuals could undergo interventions including a complete skin examination, counseling to avoid sun exposures, regular self and professional surveillance, or participation in prevention trials. It is important to emphasize that these projections are not intended to identify current melanoma cases. C1 NCI, Div Canc Epidemioil & Genet, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Melanoma Program, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Calif San Francisco, Melanoma Clin, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Mem Sloan Kettering Canc Ctr, Serv Dermatol, New York, NY 10021 USA. RP Fears, TR (reprint author), NCI, Div Canc Epidemioil & Genet, NIH, Execut Plaza S,Room 8040, Bethesda, MD 20892 USA. EM fearst@epndce.nci.nih.gov RI Pfeiffer, Ruth /F-4748-2011; Tucker, Margaret/B-4297-2015 NR 24 TC 60 Z9 60 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 AUG 1 PY 2006 VL 24 IS 22 BP 3590 EP 3596 DI 10.1200/JCO.2005.04.1277 PG 7 WC Oncology SC Oncology GA 069JY UT WOS:000239443400014 PM 16728488 ER PT J AU Cloughesy, TF Wen, PY Robins, HI Chang, SM Groves, MD Fink, KL Junck, L Schiff, D Abrey, L Gilbert, MR Lieberman, F Kuhn, J DeAngelis, LM Mehta, M Raizer, JJ Yung, WKA Aldape, K Wright, J Lamborn, KR Prados, MD AF Cloughesy, Timothy F. Wen, Patrick Y. Robins, H. Ian Chang, Susan M. Groves, Morris D. Fink, Karen L. Junck, Larry Schiff, David Abrey, Lauren Gilbert, Mark R. Lieberman, Frank Kuhn, John DeAngelis, Lisa M. Mehta, Minesh Raizer, Jeff J. Yung, W. K. Alfred Aldape, Ken Wright, John Lamborn, Kathleen R. Prados, Michael D. TI Phase II trial of tipifarnib in patients with recurrent malignant glioma either receiving or not receiving enzyme-inducing antiepileptic drugs: A North American Brain Tumor Consortium study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FARNESYL TRANSFERASE INHIBITOR; GLIOBLASTOMA-MULTIFORME; ADVANCED CANCER; R115777; PACLITAXEL; RAS; ANTICONVULSANTS; THERAPY; KINASE AB Purpose A phase 11 study was undertaken in patients with recurrent malignant glioma to determine the efficacy and safety of tipifarnib, a farnesyltransferase inhibitor, dosed at the respective maximum-tolerated dose (MTD) for patients receiving and not receiving enzyme-inducing antiepileptic drugs (EIAEDs). Because tipifarnib undergoes extensive hepatic metabolism, MTD is doubled in patients on EIAEDs. The population included 67 patients with glioblastoma multiforme (GBM) and an exploratory group of 22 patients with anaplastic glioma (AG). Patients and Methods Patients received tipifarnib (300 and 600 mg bid for 21 days every 4 weeks in non-EIAED and EIAED patients, respectively). All patients were assessable for efficacy and safety. Results Two AG patients (9.1%) and eight GBM patients (11.9%) had progression-free survival (PFS) more than 6 months. Among the latter eight GBM patients, six of 36 patients (16.7%; 95% Cl, 7% to 32%) were not receiving EIAEDs and two of 31 patients (6.5%; 95% Cl, 1% to 20%) were receiving EIAEDs. Four patients had partial responses in group A GBM and one patient had a partial response group B GBM. An exploratory comparison of PFS between GBM groups A and B was statistically significant (P = .01). Patients not receiving EIAEDs had a higher incidence and increased severity of hematologic events. However, the incidence and severity of rash (the previously determined dose-limiting toxicity in patients receiving EIAEDs) seemed similar in EIAED and non-EIAED subgroups. Conclusion Tipifarnib (300 mg bid for 21 days every 4 weeks) shows modest evidence of activity in patients with recurrent GBM who are not receiving EIAEDs and is generally well tolerated in this population. C1 Univ Calif Los Angeles, Neurooncol Program, David Geffen Sch Med, Los Angeles, CA 90095 USA. Univ Calif San Francisco, Neurooncol Serv, San Francisco, CA 94143 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA. Univ Wisconsin Hosp, Madison, WI USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dept Neurol, Dallas, TX 75235 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Univ Michigan Hosp, Dept Neurol, Ann Arbor, MI 48109 USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Cloughesy, TF (reprint author), Univ Calif Los Angeles, Neurooncol Program, David Geffen Sch Med, 710 Westwood Plaza,Reed Bldg,Room 1-230, Los Angeles, CA 90095 USA. EM tcloughe@ucla.edu RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA62455-08, 5-U01CA62399-09, CA16672, CA62412, CA6242, CA62426, U01CA62399, U01CA62405, U01CA62407-08, U01CA62421-08, U01CA62422]; NCRR NIH HHS [M01 RR03186, M01-RR00042, M01-RR00056, M01-RR00079, M01-RR00633, M01-RR0865] NR 24 TC 104 Z9 105 U1 0 U2 5 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2006 VL 24 IS 22 BP 3651 EP 3656 DI 10.1200/JCO.2006.06.2323 PG 6 WC Oncology SC Oncology GA 069JY UT WOS:000239443400023 PM 16877733 ER PT J AU Fouladi, M Furman, WL Chin, T Freeman, BB Dudkin, L Stewart, CF Krailo, MD Speights, R Ingle, AM Houghton, PJ Wright, J Adamson, PC Blaney, SM AF Fouladi, Maryam Furman, Wayne L. Chin, Thomas Freeman, Burgess B., III Dudkin, Lorina Stewart, Clinton F. Krailo, Mark D. Speights, Roseanne Ingle, Ashish M. Houghton, Peter J. Wright, John Adamson, Peter C. Blaney, Susan M. TI Phase I study of depsipeptide in pediatric patients with refractory solid tumors: A children's oncology group report SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; CHROMOBACTERIUM-VIOLACEUM NO-968; ACUTE MYELOID-LEUKEMIA; CANCER CELLS; CARCINOMA-CELLS; DOWN-REGULATION; RETINOIC ACID; CYCLIN D1; FR901228; APOPTOSIS AB Purpose To determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLT), pharmacokinetic profile, and pharmacodynamics of the histone deacetylase inhibitor, depsipeptide, in children with refractory or recurrent solid tumors. Patients and Methods Depsipeptide was administered as a 4-hour infusion weekly for 3 consecutive weeks every 28 days at dose levels of 10 mg/m(2), 13 mg/m(2), 17 mg/m(2), and 22 mg/m(2). Pharmacokinetics and histone acetylation studies were performed in the first course. The levels of H3 histone and acetyl-H3 histone were evaluated in peripheral blood mononuclear cells (PBMC) using immunofluorescence techniques. Results There were 24 patients, and 18 who were assessable were enrolled. DLTs included reversible, asymptomatic T-wave inversions, without any associated changes in troponin levels or evidence of ventricular dysfunction, in the inferior leads in two patients at 22 mg/m(2) and in the lateral leads in one patient at 13 mg/m(2) (n = 1), and transient asymptomatic sick sinus syndrome and hypocalcemia in one patient at 17 mg/m(2). At the MTD (17 mg/m(2)), the median depsipeptide clearance was 6.8 L/h/m(2) with an area under the plasma depsipeptide concentration-time curve from 0 to infinity of 2,414 ng/mL/h, similar to adults. Accumulation of acetylated H3 histones was seen in all patients in a dose independent manner, with maximal accumulation at a median of 4 hours, (range, 0 hours to 20 hours) after the end of the infusion. No objective tumor responses were observed. Conclusion Depsipeptide is well tolerated in children with recurrent or refractory solid tumors when administered weekly for 3 consecutive weeks every 28 days and inhibits histone deacetylase activity in PBMC in a dose-independent manner. The recommended phase 11 dose in children with solid tumors is 17 mg/m(2). C1 St Jude Childrens Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. St Jude Childrens Hosp, Dept Mol Pharmacol, Memphis, TN 38105 USA. St Jude Childrens Hosp, Dept Pharmaceut Sci, Memphis, TN 38105 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Oncol Grp Operat Ctr, Arcadia, CA USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. RP Fouladi, M (reprint author), St Jude Childrens Hosp, Dept Hematol Oncol, 332 N Lauderdale St, Memphis, TN 38105 USA. EM maryam.fouladi@stjude.org RI Houghton, Peter/E-3265-2011 NR 42 TC 55 Z9 60 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 1 PY 2006 VL 24 IS 22 BP 3678 EP 3685 DI 10.1200/JCO.2006.06.4964 PG 8 WC Oncology SC Oncology GA 069JY UT WOS:000239443400027 ER PT J AU Blohm, G Optican, LM Lefevre, P AF Blohm, Gunnar Optican, Lance M. Lefevre, Philippe TI A model that integrates eye velocity commands to keep track of smooth eye displacements SO JOURNAL OF COMPUTATIONAL NEUROSCIENCE LA English DT Review DE Saccades; smooth pursuit; updating; double step remapping ID POSTERIOR PARIETAL CORTEX; TEMPORAL VISUAL AREA; LATERAL INTRAPARIETAL AREA; MEMORY-GUIDED SACCADES; RAPID BEHAVIORAL MODIFICATION; DORSOLATERAL PONTINE NUCLEUS; RETICULARIS TEGMENTI PONTIS; MOVEMENT-RELATED ACTIVITY; PURKINJE-CELL ACTIVITY; DOUBLE-STEP SACCADES AB Past results have reported conflicting findings on the oculomotor system's ability to keep track of smooth eye movements in darkness. Whereas some results indicate that saccades cannot compensate for smooth eye displacements, others report that memory-guided saccades during smooth pursuit are spatially correct. Recently, it was shown that the amount of time before the saccade made a difference: short-latency saccades were retinotopically coded, whereas long-latency saccades were spatially coded. Here, we propose a model of the saccadic system that can explain the available experimental data. The novel part of this model consists of a delayed integration of efferent smooth eye velocity commands. Two alternative physiologically realistic neural mechanisms for this integration stage are proposed. Model simulations accurately reproduced prior findings. Thus, this model reconciles the earlier contradictory reports from the literature about compensation for smooth eye movements before saccades because it involves a slow integration process. C1 York Univ, Ctr Vis Res, Toronto, ON M3J 1P3, Canada. Univ Catholique Louvain, Lab Neurophysiol, B-1200 Brussels, Belgium. Univ Catholique Louvain, CESAME, B-1348 Louvain, Belgium. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Blohm, G (reprint author), York Univ, Ctr Vis Res, Toronto, ON M3J 1P3, Canada. EM blohm@yorku.ca FU Intramural NIH HHS NR 142 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0929-5313 J9 J COMPUT NEUROSCI JI J. Comput. Neurosci. PD AUG PY 2006 VL 21 IS 1 BP 51 EP 70 DI 10.1007/s10827-006-7199-6 PG 20 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA 071KM UT WOS:000239601100004 PM 16633937 ER PT J AU Ivanov, AA Costanzi, S Jacobson, KA AF Ivanov, Andrei A. Costanzi, Stefano Jacobson, Kenneth A. TI Defining the nucleotide binding sites of P2Y receptors using rhodopsin-based homology modeling SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE GPCRs; P2Y receptors; homology modeling; binding mode; ligand recognition; nucleotides ID MOLECULAR RECOGNITION; PURINERGIC RECEPTORS; EXTRACELLULAR LOOPS; LIGAND RECOGNITION; ANALOGS; H-P2Y(1)-RECEPTOR; MUTAGENESIS; ANTAGONISTS; AGONIST AB Ongoing efforts to model P2Y receptors for extracellular nucleotides, i.e., endogenous ADP, ATP, UDP, UTP, and UDP-glucose, were summarized and correlated for the eight known subtypes. The rhodopsin-based homology modeling of the P2Y receptors is supported by a growing body of site-directed mutagenesis data, mainly for P2Y(1) receptors. By comparing molecular models of the P2Y receptors, it was concluded that nucleotide binding could occur in the upper part of the helical bundle, with the ribose moiety accommodated between transmembrane domain (TM) 3 and TM7. The nucleobase was oriented towards TM1, TM2, and TM7, in the direction of the extracellular side of the receptor. The phosphate chain was oriented towards TM6, in the direction of the extracellular loops (ELs), and was coordinated by three critical cationic residues. In particular, in the P2Y(1), P2Y(2), P2Y(4), and P2Y(6) receptors the nucleotide ligands had very similar positions. ADP in the P2Y(12) receptor was located deeper inside the receptor in comparison to other subtypes, and the uridine moiety of UDP-glucose in the P2Y(14) receptor was located even deeper and shifted toward TM7. In general, these findings are in agreement with the proposed binding site of small molecules to other class A GPCRs. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Computat Chem Core Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS NR 24 TC 27 Z9 27 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD AUG PY 2006 VL 20 IS 7-8 BP 417 EP 426 DI 10.1007/s10822-006-9054-2 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 109RL UT WOS:000242326100002 PM 17016747 ER PT J AU Kansa, NS Crane, NJ Dhanani, NN Alemozaffarl, M Elster, EA Pinto, PA AF Kansa, N. S. Crane, N. J. Dhanani, N. N. Alemozaffarl, M. Elster, E. A. Pinto, P. A. TI Visual enhancement of laparoscopic nephrectomy with the 3 charge coupled device (CCD) camera SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD AUG PY 2006 VL 20 SU 1 BP A8 EP A8 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 075ST UT WOS:000239906200033 ER PT J AU Kansal, NS Alemozaffar, M Dhanani, NN Gorbach, A Gage, F Kirk, A Elster, EA Pinto, PA AF Kansal, N. S. Alemozaffar, M. Dhanani, N. N. Gorbach, A. Gage, F. Kirk, A. Elster, E. A. Pinto, P. A. TI Intra-operative ureteral identification with infrared imaging SO JOURNAL OF ENDOUROLOGY LA English DT Meeting Abstract C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD AUG PY 2006 VL 20 SU 1 BP A250 EP A250 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 075ST UT WOS:000239906201264 ER PT J AU Kirk, KL AF Kirk, Kenneth L. TI Fluorine in medicinal chemistry: Recent therapeutic applications of fluorinated small molecules SO JOURNAL OF FLUORINE CHEMISTRY LA English DT Review DE fluorinated drugs; central nervous system; metabolic disorders; cardiovascular disease; antibacterial agents; antifungal therapy ID MELANIN-CONCENTRATING-HORMONE; ESTER TRANSFER PROTEIN; HMG-COA REDUCTASE; ACTIVATED RECEPTOR-DELTA; DIPEPTIDYL-PEPTIDASE-IV; LIVER-GLYCOGEN PHOSPHORYLASE; RESOLUTION CRYSTAL-STRUCTURE; HEALTHY MALE-VOLUNTEERS; ANTIFUNGAL AGENTS; ANTIBACTERIAL ACTIVITIES AB Advances in the development of newly developed fluorinated drugs, approved or in clinical trials, as organized by biological targets/disease states, are reviewed. In a few cases, compounds in early stages of development will be discussed, particularly where new promising targets are involved. Important topics such as anticancer and antiviral drugs were covered in the two previous reviews in this series. Included herein will be fluorinated drugs for treatment of diseases of the central nervous system, various cardiovascular diseases and obesity, antibacterial agents, and antifungal therapy. Published by Elsevier B.V. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov NR 95 TC 561 Z9 565 U1 12 U2 91 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-1139 J9 J FLUORINE CHEM JI J. Fluor. Chem. PD AUG PY 2006 VL 127 IS 8 BP 1013 EP 1029 DI 10.1016/j.jfluchem.2006.06.007 PG 17 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 075HE UT WOS:000239874500002 ER PT J AU Dwyer, JT Picciano, MF Betz, JM Fisher, KD Saldanha, LG Yetley, EA Coates, PM Radimer, K Bindewald, B Sharpless, KE Holden, J Andrews, K Zhao, CW Harnly, J Wolff, WR Perry, CR AF Dwyer, JT Picciano, MF Betz, JM Fisher, KD Saldanha, LG Yetley, EA Coates, PM Radimer, K Bindewald, B Sharpless, KE Holden, J Andrews, K Zhao, CW Harnly, J Wolff, WR Perry, CR TI Progress in development of an integrated dietary supplement ingredient database at the NIH Office of Dietary Supplements SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT United States National Nutrient Databank Conference CY JUN 23-26, 2004 CL Univ, Iowa, Iowa Memorial Union, Iowa City, IA HO Univ, Iowa, Iowa Memorial Union DE dietary supplements; analytical substantiation; dietary supplement composition; dietary supplement ingredient database; NHANES; DSID; dietary supplement labels; certified reference materials; standard reference materials ID AMERICA-NHANES; EAT; HEALTH; FOOD AB Several activities of the Office of Dietary Supplements (ODS) at the National Institutes of Health involve enhancement of dietary supplement databases. These include an initiative with US Department of Agriculture to develop an analytically substantiated dietary supplement ingredient database (DSID) and collaboration with the National Center for Health Statistics to enhance the dietary supplement label database in the National Health and Nutrition Examination Survey (NHANES). The many challenges that must be dealt with in developing an analytically supported DSID include categorizing product types in the database, identifying nutrients, and other components of public health interest in these products and prioritizing which will be entered in the database first. Additional tasks include developing methods and reference materials for quantifying the constituents, finding qualified laboratories to measure the constituents, developing appropriate sample handling procedures, and finally developing representative sampling plans. Developing the NHANES dietary supplement label database has other challenges such as collecting information on dietary supplement use from NHANES respondents, constant updating and refining of information obtained, developing default values that can be used if the respondent cannot supply the exact supplement or strength that was consumed, and developing a publicly available label database. Federal partners and the research community are assisting in making an analytically supported dietary supplement database a reality. (c) 2005 Elsevier Inc. All rights reserved. C1 NIH, Off Dietary Supplements, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Dietary Supplement Methods & Reference Mat Progra, Off Dietary Supplements, Bethesda, MD 20892 USA. Ctr Dis Control, US Dept Hlth & Human Serv, Natl Hlth & Nutr Examinat Survey, Natl Ctr Hlth Stat, Atlanta, GA 30333 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. USDA ARS, Nutr Data Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. USDA ARS, Food Composit Lab, Beltsville Human Nutr Res Ctr, Beltsville, MD USA. USDA ARS, Div Res & Dev, Fairfax, VA USA. RP Dwyer, JT (reprint author), NIH, Off Dietary Supplements, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM dwyerj1@od.nih.gov OI Dwyer, Johanna/0000-0002-0783-1769; Sharpless, Katherine/0000-0001-6569-198X FU NIH HHS [Y01 OD001298-01] NR 21 TC 17 Z9 17 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 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD AUG PY 2006 VL 19 SU S BP S108 EP S114 DI 10.1016/j.jfca.2005.09.001 PG 7 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 053IV UT WOS:000238299700018 PM 25309034 ER PT J AU Pennington, J Stumbo, P AF Pennington, J Stumbo, P TI The 28th United States National Nutrient Databank Conference - From farm to fork: Practical applications of food composition data SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. RP Pennington, J (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM Phyllis-stumbo@uiowa.edu NR 1 TC 0 Z9 0 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD AUG PY 2006 VL 19 SU S BP S1 EP S3 DI 10.1016/j.jfca.2006.02.003 PG 3 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 053IV UT WOS:000238299700001 ER PT J AU Sudore, RL Yaffe, K Satterfield, S Harris, TB Mehta, KM Simonsick, EM Newman, AB Rosano, C Rooks, R Rubin, SM Ayonayon, HN Schillinger, D AF Sudore, Rebecca L. Yaffe, Kristine Satterfield, Suzanne Harris, Tamara B. Mehta, Kala M. Simonsick, Eleanor M. Newman, Anne B. Rosano, Caterina Rooks, Ronica Rubin, Susan M. Ayonayon, Hilsa N. Schillinger, Dean TI Limited literacy and mortality in the elderly: The health, aging, and body composition study SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 28th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 11-14, 2005 CL New Orleans, LA SP Soc Gen Internal Med DE educational status; mortality; aged; literacy; health status ID MANAGED CARE ORGANIZATION; MENTAL-STATE-EXAMINATION; COGNITIVE DECLINE; OLDER-ADULTS; EUROPEAN POPULATIONS; HOSPITAL ADMISSION; MEDICARE ENROLLEES; INEQUALITIES; KNOWLEDGE; SERVICES AB Background: While limited literacy is common and its prevalence increases with age, no prospective study has assessed whether limited literacy is associated with mortality in older adults. Objective: To assess the association of limited literacy with mortality. Design and Setting: Five-year prospective study from 1999 to 2004 of community-dwelling elders from Memphis, TN, and Pittsburgh, PA, who were from the Health, Aging, and Body Composition study. Subjects' literacy was assessed with the Rapid Estimate of Adult Literacy in Medicine. Scores were categorized into limited (0 to 8th grade reading level) or adequate literacy (>= 9th grade reading level). Participants: Two thousand five hundred and twelve black and white elders without baseline functional difficulties or dementia. Measurements: Time to death. Results: Participants' mean age was 75.6 years, 48% were male, 38% were black, and 24% had limited literacy; the median follow-up time was 4.2 years. Compared with those with adequate literacy, those with limited literacy had a higher risk of death (19.7% vs 10.6%) with a hazard ratio (HR) of 2.03 (95% confidence intervals [CI], 1.62 to 2.55). After adjusting for demographics and socioeconomic status, co-morbid conditions, self-rated health status, health-related behaviors, health care access measures, and psychosocial status, limited literacy remained independently associated with mortality (HR 1.75; 95% CI, 1.27 to 2.41). Conclusions: Limited literacy is independently associated with a nearly 2-fold increase in mortality in the elderly. Given the growth of the aging population and the prevalence of chronic diseases, the mechanisms by which limited literacy is associated with mortality in the elderly warrant further investigation. C1 Univ Calif San Francisco, VAMC, San Francisco, CA 94121 USA. Univ Tennessee, Memphis, TN 38163 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Clin Res Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Kent State Univ, Kent, OH 44242 USA. RP Sudore, RL (reprint author), Univ Calif San Francisco, VAMC, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM rsucsf@yahoo.com RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506; Rosano, Caterina/0000-0002-4271-6010 FU NCRR NIH HHS [K23 RR016539, K-23 RR16539-03]; NIA NIH HHS [AG000212, N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, T32 AG000212] NR 53 TC 178 Z9 183 U1 4 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD AUG PY 2006 VL 21 IS 8 BP 806 EP 812 DI 10.1111/j.1525-1497.2006.00539.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 061QZ UT WOS:000238888800003 PM 16881938 ER PT J AU Ala-Laurila, P Kolesnikov, AV Crouch, RK Tsina, E Shukolyukov, SA Govardovskii, VI Koutalos, Y Wiggert, B Estevez, ME Cornwall, MC AF Ala-Laurila, Petri Kolesnikov, Alexander V. Crouch, Rosalie K. Tsina, Efthymia Shukolyukov, Sergey A. Govardovskii, Victor I. Koutalos, Yiannis Wiggert, Barbara Estevez, Maureen E. Cornwall, M. Carter TI Visual cycle: Dependence of retinol production and removal on photoproduct decay and cell morphology SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Article ID ALL-TRANS-RETINOL; ROD OUTER SEGMENT; TIGER SALAMANDER RETINA; GATED ION CHANNELS; DARK-ADAPTATION; BINDING PROTEIN; PIGMENT REGENERATION; INDICATOR YELLOW; LIGHT ADAPTATION; PHOTORECEPTORS AB The visual cycle is a chain of biochemical reactions that regenerate visual pigment following exposure to light. Initial steps, the liberation of all-trans retinal and its reduction to all- trans retinol by retinol dehydrogenase (RDH), take place in photoreceptors. We performed comparative microspectrophotometric and microfluorometric measurements on a variety of rod and cone photoreceptors isolated from salamander retinae to correlate the rates of photoproduct decay and retinol production. Metapigment decay rate was spatially uniform within outer segments and 50 - 70 times faster in the cells that contained cone-type pigment (SWS2 and M/LWS) compared to cells with rod-type pigment (RH1). Retinol production rate was strongly position dependent, fastest at the base of outer segments. Retinol production rate was 10 - 40 times faster in cones with cone pigments (SWS2 and M/LWS) than in the basal OS of rods containing rod pigment (RH1). Production rate was approximately five times faster in rods containing cone pigment ( SWS2) than the rate in basal OS of rods containing the rod pigment ( RH1). We show that retinol production is defined either by metapigment decay rate or RDH reaction rate, depending on cell type or outer segment region, whereas retinol removal is defined by the surface-to-volume ratio of the outer segment and the availability of retinoid binding protein (IRBP). The more rapid rates of retinol production in cones compared to rods are consistent with the more rapid operation of the visual cycle in these cells. C1 Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. Russian Acad Sci, Inst Evolutionary Physiol & Biochem, St Petersburg 194223, Russia. Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Univ Athens, Dept Ophthalmol, Agia Sophia Childrens Hosp, Athens 11527, Greece. NEI, NIH, Bethesda, MD 20892 USA. RP Ala-Laurila, P (reprint author), Boston Univ, Sch Med, Dept Physiol & Biophys, Boston, MA 02118 USA. EM pal@bu.edu OI Cornwall, M./0000-0002-0847-939X; Ala-Laurila, Petri/0000-0002-6139-6825 FU NEI NIH HHS [EY01157, EY04939, EY14850, R01 EY001157, R01 EY004939, R01 EY014850] NR 59 TC 52 Z9 55 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD AUG PY 2006 VL 128 IS 2 BP 153 EP 169 DI 10.1085/jgp.200609557 PG 17 WC Physiology SC Physiology GA 069CL UT WOS:000239422600003 PM 16847097 ER PT J AU Hayashi, K Hooper, LC Chin, MS Nagineni, CN Detrick, B Hooks, JJ AF Hayashi, Kozaburo Hooper, Laura C. Chin, Marian S. Nagineni, Chandrasekharam N. Detrick, Barbara Hooks, John J. TI Herpes simplex virus 1 (HSV-1) DNA and immune complex (HSV-1-human IgG) elicit vigorous interleukin 6 release from infected corneal cells via Toll-like receptors SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; DOUBLE-STRANDED-RNA; NF-KAPPA-B; STROMAL KERATITIS; TYPE-1 DNA; OCULAR DISEASE; BACTERIAL-DNA; CPG MOTIFS; ACTIVATION; INFLAMMATION AB Toll-like receptor 3 (TLR-3) and TLR-9 gene expression and interleukin 6 (IL-6) secretion were studied in corneal cells with components of herpes simplex virus (HSV). Human corneal epithelial cells (HCEs) and primary human corneal fibroblasts (HCRFs) were infected with live HSV or UV-inactivated HSV (UV-HSV), transfected with HSV DNA or treated with HSV-anti-HSV IgG immune complexes. Gene expression of TLR-3 and -9 was analysed by real-time PCR. Supernatants were assayed for IL-6 by ELISA. Incubation of HCEs and HCRFs with live HSV-1, UV-HSV and HSV DNA resulted in augmented TLR-3 and -9 gene expression and IL-6 release. Moreover, infected or transfected HCRFs released greater amounts of IL-6 than did HCEs. As virus is frequently in the form of neutralized virus immune complexes, the ability of these immune complexes to interact with TLRs and trigger IL-6 production was evaluated. Here, it is shown that HSV-anti-HSV IgG complexes were as potent as HSV DNA in their ability to induce IL-6. Treatment of HCRFs transfected with HSV DNA with the TLR-9-inhibitory oligomer iODN, anti-TLR-3 antibody or phosphatidylinositol 3-kinase inhibitor indicated that IL-6 release from HCRFs was mediated by TLR-3 and -9 gene expression. These results demonstrated that neutralized HSV immune complexes were as potent as HSV DNA in enhancing IL-6 release from corneal fibroblasts. These phenomena were mediated via augmented TLR-3 and -9 gene expression. C1 NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Sch Med, Baltimore, MD USA. RP Hayashi, K (reprint author), NEI, Immunol & Virol Sect, Immunol Lab, NIH, Bldg 10,Room 10N248,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hayashik@nei.nih.gov FU Intramural NIH HHS NR 49 TC 35 Z9 38 U1 0 U2 1 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 AUG PY 2006 VL 87 BP 2161 EP 2169 DI 10.1099/vir.0.81772-0 PN 8 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 071OW UT WOS:000239612500007 PM 16847112 ER PT J AU Danis, M Ginsburg, M Goold, SD AF Danis, Marion Ginsburg, Marjorie Goold, Susan Dorr TI The coverage priorities of disabled adult Medi-Cal beneficiaries SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE Medicaid; insurance benefits; cost and benefits; social policy; health policy; consumer preference ID HEALTH-INSURANCE; MANAGED CARE AB Medi-Cal, like other Medicaid programs around the U.S., has been pressed to cut its budget. We report the results of a project using the CHAT (Choosing Healthplans All Together) exercise, designed to ascertain the priorities of disabled adult Medi-Cal beneficiaries to inform any decisions regarding Medi-Cal benefits. Participants voiced greatest interest in maintaining a wide spectrum of benefits and access to a large pool of providers and were most willing to restrict pharmacy benefits. The resulting findings may be of value to legislators drafting Medicaid proposals that revise benefits for this vulnerable population. C1 NIH, Dept Clin Bioeth, Sect Eth & Hlth Policy, Bethesda, MD 20892 USA. Sacramento Healthcare Decis, Rancho Cordova, CA USA. Univ Michigan, Sch Med, Bioeth Program, Ann Arbor, MI 48109 USA. RP Danis, M (reprint author), NIH, Dept Clin Bioeth, Sect Eth & Hlth Policy, Bldg 10, Bethesda, MD 20892 USA. EM mdanis@nih.gov OI Goold, Susan Dorr/0000-0002-0258-9774 NR 15 TC 3 Z9 3 U1 1 U2 1 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD AUG PY 2006 VL 17 IS 3 BP 592 EP 609 DI 10.1353/hpu.2006.0103 PG 18 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 077SJ UT WOS:000240050100012 PM 16960324 ER PT J AU Guo, XM Shen, HX Xiao, XS Dai, QL Li, SQ Jia, XY Hejtmancik, JF Zhang, QJ AF Guo, Xiangming Shen, Huangxuan Xiao, Xueshan Dai, Qilin Li, Shiqiang Jia, Xiaoyun Hejtmancik, J. Fielding Zhang, Qingjiong TI Cataracts, ataxia, short stature, and mental retardation in a Chinese family mapped to Xpter-q13.1 SO JOURNAL OF HUMAN GENETICS LA English DT Article DE cataract; cerebellar ataxia; short stature; mental retardation; X-linked recessive ID MARINESCO-SJOGREN-SYNDROME; MUTATIONS; LINKAGE; SIL1; GENE AB Six males in a Chinese family affected by congenital cataracts, cerebellar ataxia, short stature, and mental retardation, which were tentatively named CASM syndrome. Eight female carriers in the family had cataracts alone. Linkage analysis demonstrated that the disease is transmitted through X-linked inheritance, either by setting the syndrome in males as an X-linked recessive trait, or by setting cataracts in the family as an X-linked dominant trait. The gene responsible for the syndrome is mapped to Xpter-Xq13.1, with the highest lod score of 3.91 for DXS1226, DXS991, and DXS1213 at theta = 0. Haplotype analysis identified that the allele harboring the disease gene co-segregated with all female carriers as well as affected males in the family. Clinically and genetically, the disease in this family is different from any known disease. Major features of CASM syndrome that distinguish it from other diseases are X-linked inheritance and cataracts in carrier females. C1 Sun Yat Sen Univ, Dept Ophthalm Genet & Mol Biol, Zhongshan Ophthal Ctr, Guangzhou 510060, Peoples R China. Sun Yat Sen Univ, Key Lab Ophthalmol & Minist Educ, Guangzhou 510060, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, Guangzhou 510080, Peoples R China. NEI, Ophthal Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, QJ (reprint author), Sun Yat Sen Univ, Dept Ophthalm Genet & Mol Biol, Zhongshan Ophthal Ctr, 54 Xianlie Rd, Guangzhou 510060, Peoples R China. EM qingjiongzhang@yahoo.com NR 19 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1434-5161 J9 J HUM GENET JI J. Hum. Genet. PD AUG PY 2006 VL 51 IS 8 BP 695 EP 700 DI 10.1007/s10038-006-0009-1 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 078TY UT WOS:000240128100002 PM 16832577 ER PT J AU Pardigon, N Takeda, K Saunier, B Hornung, F Gibbs, J Weisberg, A Contractor, N KelsalW, B Bennink, JR Yewdell, JW AF Pardigon, Nathalie Takeda, Kazuyo Saunier, Bertrand Hornung, Felicita Gibbs, James Weisberg, Andrea Contractor, Nikhat KelsalW, Brian Bennink, Jack R. Yewdell, Jonathan W. TI CD8 alpha alpha-mediated intraepithelial lymphocyte snatching of thymic leukemia MHC class Ib molecules in vitro and in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTESTINAL EPITHELIAL-CELLS; INTERLEUKIN-10-DEFICIENT MICE; LAMINA PROPRIA; ACTIVATION; ANTIGEN; BINDING; MEMORY; CD8; DIFFERENTIATION; ENTEROCOLITIS AB Thymic leukemia (TL) is a MHC class Ib molecule that interacts with CD8 alpha alpha homodimers. CD8 alpha alpha is abundantly expressed by intraepithelial T lymphocytes (IELs) located in close proximity to TL-expressing intestinal epithelial cells. In this study, we show that CD8 alpha alpha(+) IELs "snatch" TL from the plasma membrane of TL-expressing cells and express TL in its proper orientation on their own cell surface. TL snatching is enhanced by cross-linking of IEL TCRs in a phosphatidylinositol kinase-dependent manner, and results in overall alterations to the IEL cell surface detected by enhanced binding of peanut agglutinin lectin. Induction of bowel inflammation results in the presence of TL on IELs, probably via in vivo snatching, providing the initial evidence for the interaction of CD8 alpha alpha IELs with intestinal cells. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Viral Dis Lab, NIH, Room 211,Bldg 4,4 Ctr Dr, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS NR 20 TC 15 Z9 15 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 1 PY 2006 VL 177 IS 3 BP 1590 EP 1598 PG 9 WC Immunology SC Immunology GA 065DT UT WOS:000239140300033 PM 16849467 ER PT J AU Vesikari, T Karvonen, AV Majuri, J Zeng, SQ Pang, XL Kohberger, R Forrest, BD Hoshino, Y Chanock, RM Kapikian, AZ AF Vesikari, Timo Karvonen, Aino V. Majuri, Jukka Zeng, Shang-Qin Pang, Xiao-Li Kohberger, Robert Forrest, Bruce D. Hoshino, Yasutaka Chanock, Robert M. Kapikian, Albert Z. TI Safety, efficacy, and immunogenicity of 2 doses of bovine-human (UK) and rhesus-rhesus-human rotavirus reassortant tetravalent vaccines in Finnish children SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID YOUNG-CHILDREN; INFANTS; TRIAL; INTUSSUSCEPTION; GASTROENTERITIS; SEROTYPES; ADULTS; WC3 AB Background. Live oral rhesus-rhesus-human rotavirus reassortant tetravalent (RRV-TV) vaccine was efficacious against rotavirus gastroenteritis but was withdrawn because of a rare association with intussusception. A corresponding tetravalent (types G1, G2, G3, and G4) reassortant vaccine based on bovine-human (UK) rotavirus reassortant tetravalent (BRV- TV) vaccine was developed concurrently. Methods. Before the withdrawal of RRV-TV vaccine, parallel placebo-controlled trials of BRV- TV vaccine ( observer blinded) versus RRV-TV vaccine (double blinded) with a 2: 1 ratio of vaccine: placebo were conducted in Finland in a total of 510 infants. Two doses of study vaccine or placebo were administered at ages 3 and 5 months. Results. The first dose of RRV-TV vaccine was followed by a significant excess rate of febrile reactions (36%), whereas the rate of fever after the administration of BRV- TV vaccine did not differ significantly from that in the placebo group. Neither vaccine induced diarrhea. A seroresponse was detected in 97% of BRV- TV vaccine recipients and 94% of RRV-TV vaccine recipients. Both vaccines were equally effective, with 68%-69% efficacy against any and 88%-100% efficacy against severe rotavirus gastroenteritis during the first epidemic season. Conclusions. BRV- TV vaccine is a promising new candidate rotavirus vaccine, with low reactogenicity and high efficacy. Two doses of BRV- TV or RRV-TV vaccine are sufficient for the induction of protection against severe rotavirus disease. C1 Univ Tampere, Sch Med, Vaccine Res Ctr, Tampere 33520, Finland. Wyeth Vaccine Res, Pearl River, NY USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Vesikari, T (reprint author), Univ Tampere, Sch Med, Vaccine Res Ctr, Biokatu 10, Tampere 33520, Finland. EM timo.vesikari@uta.fi NR 30 TC 42 Z9 45 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2006 VL 194 IS 3 BP 370 EP 376 DI 10.1086/505151 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 064WN UT WOS:000239120900015 PM 16826486 ER PT J AU Rennert, OM AF Rennert, O. M. TI Medical genomics? A walk in the garden of Eden SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 NICHHD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 2 EP 2 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100005 ER PT J AU Oglesbee, D Gunay-Aygun, M Matern, D Tortorelli, S Hahn, SH Rinaldo, P Ward, C Moran, R AF Oglesbee, D. Gunay-Aygun, M. Matern, D. Tortorelli, S. Hahn, S. H. Rinaldo, P. Ward, C. Moran, R. TI A mild Amish variant of propionic acidemia is detectable by newborn screening with tandem mass spectrometry SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Mayo Clin, Coll Med, Biochem Genet Lab, Rochester, MN USA. NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Akron Childrens Hosp, Dept Genet, Akron, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 20 EP 20 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100054 ER PT J AU Cheng, SH Li, X Jiang, J McVie-Wylie, A Thurberg, BL Raben, N Mattaliano, RJ Zhu, Y AF Cheng, S. H. Li, X. Jiang, J. McVie-Wylie, A. Thurberg, B. L. Raben, N. Mattaliano, R. J. Zhu, Y. TI Carbohydrate-remodeled alpha-glucosidase with higher affinity for the mannose 6-phosphate receptor demonstrates improved delivery to muscles of Pompe mice SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Genzyme Corp, Framingham, MA 01701 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 29 EP 29 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100091 ER PT J AU Ries, M Beck, M Clarke, JTR Whybra, C Timmons, M Robinson, C Pastores, G Kampmann, C Brady, RO Schiffmann, R AF Ries, M. Beck, M. Clarke, J. T. R. Whybra, C. Timmons, M. Robinson, C. Pastores, G. Kampmann, C. Brady, R. O. Schiffmann, R. TI The safety and clinical benefit of agalsidase alfa in children with Fabry disease SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Mainz, Childrens Hosp, Ctr Lysosomal Storage Dis, D-6500 Mainz, Germany. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. NYU, Dept Neurol, New York, NY 10012 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 133 EP 133 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100506 ER PT J AU Shen, JS Meng, XL Ohashi, T Eto, Y AF Shen, J. S. Meng, X. L. Ohashi, T. Eto, Y. TI In vivo evidence of morphological improvement of twitcher oligodendrocytes by GALC transduction SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 Jikei Univ, Sch Med, Dept Gene Therapy, Inst DNA Med, Tokyo, Japan. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Clin Genom, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. Jikei Univ, Sch Med, Dept Pediat, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 136 EP 136 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100518 ER PT J AU Meng, X Chan, W Owen, R AF Meng, X. Chan, W. Owen, R. TI Activation of luteinizing hormone/human choriogodanotropin receptor leads to neuronal differentiation of PC12 cells SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Meeting Abstract C1 NICHHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 SU 1 BP 142 EP 142 PG 1 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 083OC UT WOS:000240467100542 ER PT J AU Buist, NRM Glenn, B Vugrek, O Wagner, C Stabler, S Allen, RH Pogribny, I Schulze, A Zeisel, SH Baric, I Mudd, SH AF Buist, N. R. M. Glenn, B. Vugrek, O. Wagner, C. Stabler, S. Allen, R. H. Pogribny, I. Schulze, A. Zeisel, S. H. Baric, I. Mudd, S. H. TI S-Adenosylhomocysteine hydrolase deficiency in a 26-year-old man SO JOURNAL OF INHERITED METABOLIC DISEASE LA English DT Article ID N-METHYLTRANSFERASE DEFICIENCY; TOTAL HOMOCYSTEINE; MASS-SPECTROMETRY; FOLATE-DEFICIENCY; INBORN ERROR; SERUM; METABOLISM; METHIONINE; DISORDER; QUANTITATION AB This paper reports the third proven human case of deficient S-adenosylhomocysteine (AdoHcy) hydrolase activity. The patient is similar to the only two previously reported cases with this disorder in having severe myopathy, developmental delay, elevated serum creatine kinase (CK) concentrations, and hypermethioninaemia. Although he has been followed from infancy, the basic enzyme deficiency was established only at age 26 years. The diagnosis was based on markedly elevated plasma concentrations of both AdoHcy and S-adenosylmethionine, some 20% of the mean control activity of AdoHcy hydrolase activity in haemolysates of his red-blood cells, and two missense mutations in his gene encoding AdoHcy hydrolase. He had low values of erythrocyte phosphatidylcholine and plasma free choline and marginally elevated excretion of guanidinoacetate, suggesting that the elevated AdoHcy may have been inhibiting methylation of phosphatidylethanolamine and guanidinoacetate. His leukocyte DNA was globally more methylated than the DNA's of his parents or the mean extent of methylation measured in age-matched control subjects. C1 Oregon Hlth Sci Univ, Dept Pediat, Portland, OR 97225 USA. Oregon Hlth Sci Univ, Dept Med Genet, Portland, OR 97225 USA. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37212 USA. Rudjer Boskovic Inst, Dept Mol Med, Zagreb, Croatia. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Childrens Hosp, Heidelberg, Germany. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Hosp Ctr, Dept Pediat, Zagreb, Croatia. Sch Med, Zagreb, Croatia. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Buist, NRM (reprint author), Oregon Hlth Sci Univ, Dept Pediat, 8510 SW White Pine Lane, Portland, OR 97225 USA. EM Buistnrm@aol.com FU NIA NIH HHS [AG-09834, R01 AG009834]; NIDDK NIH HHS [DK15289, DK55865, P30 DK026657, P30 DK056350-08, R01 DK055865-06A1, R37 DK015289, DK56359, 5P30 DK26657, P30 DK056350, R01 DK015289, R01 DK055865] NR 27 TC 39 Z9 42 U1 0 U2 3 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0141-8955 J9 J INHERIT METAB DIS JI J. Inherit. Metab. Dis. PD AUG PY 2006 VL 29 IS 4 BP 538 EP 545 DI 10.1007/s10545-006-0240-0 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 078MH UT WOS:000240107400006 PM 16736098 ER PT J AU Stewart, MJ Kulkarni, SB Meusel, TR Imani, F AF Stewart, Michael J. Kulkarni, Sandhya B. Meusel, Tiffany R. Imani, Farhad TI c-Jun N-terminal kinase negatively regulates dsRNA and RSV induction of tumor necrosis factor-alpha transcription in human epithelial cells SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID DOUBLE-STRANDED-RNA; SYNCYTIAL VIRUS-INFECTION; DEPENDENT PROTEIN-KINASE; HUMAN B-CELLS; GENE-EXPRESSION; KAPPA-B; DENDRITIC CELLS; IN-VITRO; SIGNALING PATHWAYS; INTERFERON-ALPHA AB Secretion of inflammatory cytokines is the initial step of the immune response to viral infections. This innate immune response is mediated by the expression of a variety of cytokines, exemplified by tumor necrosis factor-alpha (TNF-alpha). The presence of dsRNA during viral infections is a key step in activation of several signaling pathways, including protein kinase R (PKR), toll-like receptor 3 (TLR3), mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1), interferon regulatory factors (IRFs), and NF-kappa B pathways, which are all relevant in the expression of inflammatory cytokines. We previously reported that PKR and p38 MAPK were required for dsRNA and viral induction of inflammatory cytokines in epithelial cells. Here, we report that activation of c-Jun N-terminal kinase (JNK) during dsRNA treatment or respiratory syncytial viral (RSV) infection negatively regulates the induction of TNF-alpha in human epithelial cells. Inhibition of JNK by a pharmacologic inhibitor showed that expression of TNF-alpha increased following both dsRNA treatment and infection with RSV. Importantly, transfection of epithelial cells with a dominant-negative mutant of JNK significantly increased dsRNA induction of TNF-alpha. The mechanism by which JNK inhibition increases TNF-alpha induction appears to be through p38 MAPK activation. Our data show that JNK is a negative regulator of dsRNA and RSV induction of TNF-alpha expression and, thus, may act as a counterbalance to proinflammatory signals generated during viral infections. C1 NIEHS, NIH, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. RP Imani, F (reprint author), NIEHS, NIH, Lab Resp Biol, MD 02-1,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM imani@niehs.nih.gov NR 67 TC 15 Z9 16 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2006 VL 26 IS 8 BP 521 EP 533 DI 10.1089/jir.2006.26.521 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 075VW UT WOS:000239914700002 PM 16881863 ER PT J AU Emmert, S Wetzig, T Imoto, K Khan, SG Oh, KS Laspe, P Zachmann, K Simon, JC Kraemer, KH AF Emmert, S. Wetzig, T. Imoto, K. Khan, S. G. Oh, K. S. Laspe, P. Zachmann, K. Simon, J. C. Kraemer, K. H. TI A novel complex insertion/deletion mutation in the XPC DNA repair gene leads to skin cancer in an Iraqi family SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR) CY SEP 06-07, 2006 CL Paris, FRANCE SP European Soc Dermatol Res C1 Univ Gottingen, Dept Dermatol, D-3400 Gottingen, Germany. Univ Leipzig, Dept Dermatol, D-7010 Leipzig, Germany. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2006 VL 126 SU 3 BP 35 EP 35 PG 1 WC Dermatology SC Dermatology GA 117RY UT WOS:000242891900193 ER PT J AU Huegel, R Schwarz, A Tuexen, N Velasco, P Lange-Asschenfeldt, B Schwarz, T AF Huegel, R. Schwarz, A. Tuexen, N. Velasco, P. Lange-Asschenfeldt, B. Schwarz, T. TI Ultraviolet-B irradiation induces vascular hyperpermeability in the skin of SKH1 mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR) CY SEP 06-07, 2006 CL Paris, FRANCE SP European Soc Dermatol Res C1 Univ Kiel, Dept Dermatol, D-2300 Kiel, Germany. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2006 VL 126 SU 3 BP 76 EP 76 PG 1 WC Dermatology SC Dermatology GA 117RY UT WOS:000242891900441 ER PT J AU Tormo, D Ferrer, A Gaffal, E Steitz, J Wenzel, J Heukamp, L Malumbres, M Barbacid, M Merlino, G Tuting, T AF Tormo, D. Ferrer, A. Gaffal, E. Steitz, J. Wenzel, J. Heukamp, L. Malumbres, M. Barbacid, M. Merlino, G. Tuting, T. TI Oncogenic CDK4 mutation promotes rapid growth of invasive metastatic melanoma in carcinogen-treated HGF/SF-transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR) CY SEP 06-07, 2006 CL Paris, FRANCE SP European Soc Dermatol Res C1 Uniklin Bonn, Lab Expt Dermatol, Bonn, Germany. Uniklin Bonn, Inst Pathol, Bonn, Germany. CNIO, Madrid, Spain. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RI Malumbres, Marcos/E-8834-2011; Heukamp, Lukas/A-8338-2013 OI Malumbres, Marcos/0000-0002-0829-6315; NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2006 VL 126 SU 3 BP 82 EP 82 PG 1 WC Dermatology SC Dermatology GA 117RY UT WOS:000242891900481 ER PT J AU Tang, X Kim, A Zhu, Y Han, L Kopelovich, L Bickers, D Athar, M AF Tang, X. Kim, A. Zhu, Y. Han, L. Kopelovich, L. Bickers, D. Athar, M. TI P53 modulation by CP-31398 enhances its mitochondrial translocation leading to induction of apoptosis and blockade of the growth of UVB-induced squamous cell carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the European-Society-of-Dermatology-Research (ESDR) CY SEP 06-07, 2006 CL Paris, FRANCE SP European Soc Dermatol Res C1 Columbia Univ, Dept Dermatol, New York, NY 10027 USA. NCI, Canc Cheoprevent Div, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD AUG PY 2006 VL 126 SU 3 BP 83 EP 83 PG 1 WC Dermatology SC Dermatology GA 117RY UT WOS:000242891900484 ER PT J AU Zudaire, E Portal-Nunez, S Cuttitta, F AF Zudaire, Enrique Portal-Nunez, Sergio Cuttitta, Frank TI The central role of adrenomedullin in host defense SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE PAMP; AMBP-1; septic shock ID MACROPHAGE CELL-LINE; GENE-RELATED PEPTIDE; ACUTE SEPTIC PERITONITIS; NECROSIS-FACTOR-ALPHA; COMPLEMENT FACTOR-H; MAST-CELLS; BINDING PROTEIN-1; PROINFLAMMATORY CYTOKINES; ANTIMICROBIAL PEPTIDES; INNATE IMMUNITY AB Thirteen years after the isolation of adrenomedullin (AM) from a human pheochromocytoma, the literature is awash with reports describing its implication in countless physiological and disease mechanisms ranging from vasodilatation to cancer promotion. A growing body of evidence illustrates AM as a pivotal component in normal physiology and disease with marked beneficial effects in the host defense mechanism. Exogenous administration of AM as well as its ectopic overexpression and the use of drugs, which potentiates its activity, are promising strategies for treatment of septic shock and several other pathogen-related disorders. Although major progress toward this end has been achieved over the past few years, our further understanding of the pleiotropic mechanisms involved with AM as a protective peptide is paramount to maximize its clinical application. J. Leukoc. Biol. 80: 237-244; 2006. C1 NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Zudaire, E (reprint author), NCI, Cell & Canc Biol Branch, NIH, Bldg 10,Room 13N262, Bethesda, MD 20892 USA. EM zudairee@mail.nih.gov RI Portal-Nunez, Sergio/L-7391-2014; Cuttitta, Frank/B-4758-2016 OI Portal-Nunez, Sergio/0000-0003-0659-1545; NR 103 TC 43 Z9 43 U1 0 U2 4 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 AUG PY 2006 VL 80 IS 2 BP 237 EP 244 DI 10.1189/jlb.0206123 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119ME UT WOS:000243015600004 PM 16769769 ER PT J AU Rosenberg, HF AF Rosenberg, Helene F. TI Interview with Dr. Andrew Issekutz regarding Pivotal Advance: Endothelial growth factors VEGF and bFGF differentially modulate monocyte and neutrophil recruitment to inflammation SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Editorial Material ID ADHESION MOLECULE EXPRESSION; FGF-2 C1 NIAID, Allerg Dis Lab, NIH, Bethesda, MD 20892 USA. RP Rosenberg, HF (reprint author), NIAID, Allerg Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hrosenherg@niaid.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD AUG PY 2006 VL 80 IS 2 BP 245 EP 246 DI 10.1189/jlb.1306718 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119ME UT WOS:000243015600005 ER PT J AU Igarashi, M Ma, K Chang, L Bell, JM Rapoport, SI Demar, JC AF Igarashi, Miki Ma, Kaizong Chang, Lisa Bell, Jane M. Rapoport, Stanley I. DeMar, James C., Jr. TI Low liver conversion rate of alpha-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet SO JOURNAL OF LIPID RESEARCH LA English DT Article DE incorporation; turnover; synthesis; pulse labeling; infusion; diet ID LOW-DENSITY LIPOPROTEIN; POLYUNSATURATED FATTY-ACIDS; CHAIN ACYL-COA; ARACHIDONIC-ACID; BRAIN PHOSPHOLIPIDS; NUTRITIONAL DEPRIVATION; KINETIC-ANALYSIS; GENE-EXPRESSION; ADULT-RAT; N-3 AB We quantified the rates of incorporation of alpha-linolenic acid (alpha-LNA; 18:3n-3) into "stable" lipids (triacylglycerol, phospholipid, cholesteryl ester) and the rate of conversion of a-LNA to docosahexaenoic acid (DHA; 22: 6n-3) in the liver of awake male rats on a high-DHA containing diet after a 5-min intravenous infusion of [1-C-14]alpha-LNA. At 5 min, 72.7% of liver radioactivity (excluding unesterified fatty acid radioactivity) was in stable lipids, with the remainder in the aqueous compartment. Using our measured specific activity of liver alpha-LNA-CoA, in the form of the dilution coefficient lambda(alpha-LNA-CoA), we calculated incorporation rates of unesterified a-LNA into liver triacylglycerol, phospholipid, and cholesteryl ester as 2,401, 749, and 9.6 nmol/s/g x 10(-4), respectively, corresponding to turnover rates of 3.2, 8.7, and 2.9%/min and half-lives of 8-24 min. A lower limit for the DHA synthesis rate from alpha-LNA equaled 15.8 nmol/s/g X 10(-4) (0.5% of the net incorporation rate). Thus, in rats on a high-DHA containing diet, rates of beta-oxidation and esterification of alpha-LNA into stable liver lipids are high, whereas its conversion to DHA is comparatively low and insufficient to supply significant DHA to the brain. High incorporation and turnover rates likely reflect a high secretion rate by liver of stable lipids within very low density lipoproteins. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Igarashi, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM mikii@mail.nih.gov RI Igarashi, Miki/B-1085-2017 FU Intramural NIH HHS NR 73 TC 35 Z9 36 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2006 VL 47 IS 8 BP 1812 EP 1822 DI 10.1194/jlr.M600030-JLR200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077IS UT WOS:000240023100021 PM 16687661 ER PT J AU Viswanadha, S Londos, C AF Viswanadha, Srikant Londos, Constantine TI Optimized conditions for measuring lipolysis in murine primary adipocytes SO JOURNAL OF LIPID RESEARCH LA English DT Article DE glycerol; adenosine; cell concentrations ID HORMONE-SENSITIVE LIPASE; DEPENDENT PROTEIN-KINASE; ACID-BINDING PROTEIN; FAT-CELL LIPOLYSIS; ADIPOSE-TISSUE; GLUCOSE-METABOLISM; RAT ADIPOCYTES; DIABETIC MICE; PERILIPIN-A; TRANSLOCATION AB The current literature on lipolysis in murine primary adipocytes is rife with experiments performed under conditions not optimized for reproducible and reliable results. Here, we present conditions for optimizing the measurement of lipolysis in murine adipocytes. We demonstrate that adenosine management is of paramount importance in evaluating the lipolytic response under basal and stimulated conditions. Also, adipocyte concentrations in the 10,000-15,000 cells per milliliter range produce a greater increase in stimulated lipolysis than higher concentrations, and the response is further enhanced by agitating the cells. C1 NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Londos, C (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM deanl@intra.niddk.nih.gov FU Intramural NIH HHS NR 32 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD AUG PY 2006 VL 47 IS 8 BP 1859 EP 1864 DI 10.1194/jlr.D600005-JLR200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 077IS UT WOS:000240023100026 PM 16675855 ER PT J AU Richani, K Romero, R Kim, YM Cushenberry, E Soto, E Han, YM Espinoza, J Kim, CJ AF Richani, Karina Romero, Roberto Kim, Yeon Mee Cushenberry, Enola Soto, Eleazar Han, Yu Mi Espinoza, Jimmy Kim, Chong Jai TI Tissue microarray: An effective high-throughput method to study the placenta for clinical and research purposes SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE placenta; tissue microarray; immunohistochemistry; in situ hybridization ID IN-SITU HYBRIDIZATION; GENE AMPLIFICATION; BREAST-CARCINOMA; CANCER SPECIMENS; EXPRESSION; TECHNOLOGY; VALIDATION; IDENTIFICATION; MALIGNANCIES; RECEPTOR AB Objective. Tissue microarray (TMA) technology allows simultaneous examination of the expression of many molecular markers (protein, mRNA, DNA, etc.) with high-throughput. The application of this technology, to date, has been largely confined to the study of cancer. Placental pathology poses unique challenges because of the size of the organ, its complex anatomy, as well as its histological heterogeneity. The objective of this study was to assess the feasibility and efficiency of TMAs for immunohistochemistry and in situ hybridization of placental tissues. Study design. TMAs were constructed using an automated tissue arrayer. Standard 0.6-mm or 1-mm microarray needles were used. Villous parenchyma, basal plate, and chorioamniotic membranes were targeted in each block. Five mu m-thick TMA sections underwent immunohistochemical analysis of both cytoplasmic and nuclear antigens using a panel of antibodies against a variety of cytoplasmic [cytokeratin-7, vascular endothelial growth factor (VEGF), and protein Z], membranous (endoglin), and nuclear (c-fos and c-jun) antigens. mRNA in situ hybridization for surfactant protein A (SP-A) and chromogenic in situ hybridization for the Y chromosome (DYZ1) were also performed. Results. Validation of TMA immunoreactivity demonstrated comparable results with corresponding whole sections. When a two-tiered scoring system (positive/negative) was employed, there was agreement between two and three cores and whole tissue sections (kappa > 0.7). When a three-tiered scoring system (negative, weak-positive, or strong-positive) was used, the data from three cores showed the highest agreement with whole tissue sections (kappa > 0.7). In situ hybridization experiments for mRNA and DNA were also successful in that the signals were readily detectable. Successful transfer from the donor block to the recipient block differed according to the anatomical compartment. The transfer efficiency of villous parenchyma, basal plate, and chorioamniotic membranes were 96.9% (875/903), 76.7% (115/150), and 75.4% (224/297), respectively. Conclusion. TMA is a practical and effective tool for high-throughput molecular analysis of the human placenta. Duplicate and triplicate cores offer agreement with whole tissue sections for two-category distinction immunostaining. TMA also affords relevant results from in situ hybridization experiments for mRNA and DNA. The major advantages are the conservation of tissues and reagents, simultaneous comparison of molecular markers in different anatomical compartments of the placenta, and reduction of experimental error. C1 NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. RP Romero, R (reprint author), NICHD, Perinatal Res Branch, NIH, DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 25 TC 12 Z9 12 U1 0 U2 1 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 AUG PY 2006 VL 19 IS 8 BP 509 EP 515 DI 10.1080/14767050600852718 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 089IV UT WOS:000240874900010 PM 16966117 ER PT J AU Cabral, WA Milgrom, S Letocha, AD Moriarty, E Marini, JC AF Cabral, W. A. Milgrom, S. Letocha, A. D. Moriarty, E. Marini, J. C. TI Biochemical screening of type I collagen in osteogenesis imperfecta: detection of glycine substitutions in the amino end of the alpha chains requires supplementation by molecular analysis SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SENSITIVE GEL-ELECTROPHORESIS; CHEMICAL CLEAVAGE; MUTATIONS; HETEROGENEITY; AMPLIFICATION; PROCOLLAGEN; COL1A1; DNA AB Background: The biochemical test for osteogenesis imperfecta (OI) detects structural abnormalities in the helical region of type I collagen as delayed electrophoretic migration of alpha chains on SDS-urea-PAGE. Sensitivity of this test is based on overmodification of alpha chains in helices with a glycine substitution or other structural defect. The limits of detectability have not been reported. Methods: We compared the collagen electrophoretic migration of 30 probands ( types III or IV OI) with known mutations in the amino half of the alpha 1(I) and alpha a2(I) chains. Differences in sensitivity were examined by 5% and 6% SDS-urea-PAGE, and with respect to alpha chain, location along the chain, and substituting amino acid. Results: Sensitivity was enhanced on 5% gels, and by examination of intracellular and secreted collagen. In a1( I), substitutions in the first 100 residues were not detectable; 7% of cases in the current Mutation Consortium database are in this region. alpha 1(I) substitutions between residues 100 and 230 were variably detectable, while those after residue 232 were all detected. In alpha 2(I), variability of electrophoretic detection extended through residue 436. About a third of cases in the Consortium database are located in the combined variable detection region. Biochemical sensitivity did not correlate with substituting residue. Conclusions: Complete testing of probands with normal type I collagen biochemical results requires supplementation by molecular analysis of cDNA or gDNA in the amino third of alpha 1(I) and amino half of alpha 2(I). Mutation detection in OI is important for counselling, reproductive decisions, exclusion of child abuse, and genotype-phenotype correlations. C1 NICHD, Bone & Extracellular Matrix Branch, Sect Connect Tissue Disorders, NIH, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHD, Bone & Extracellular Matrix Branch, Sect Connect Tissue Disorders, NIH, 9000 Rockville Pike 10-9S241, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov NR 25 TC 11 Z9 11 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2006 VL 43 IS 8 AR 685 DI 10.1136/jmg.2005.040493 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 069FZ UT WOS:000239433100009 PM 16882741 ER PT J AU Kim, H Mittal, DP Iadarola, MJ Dionne, RA AF Kim, H. Mittal, D. P. Iadarola, M. J. Dionne, R. A. TI Genetic predictors for acute experimental cold and heat pain sensitivity in humans SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID ACID AMIDE HYDROLASE; NERVE-FIBERS; ION-CHANNEL; TRP CHANNEL; ASSOCIATION; RECEPTOR; POLYMORPHISM; PERCEPTION; EXPRESSION; CAPSAICIN AB Background: The genetic contribution to pain sensitivity underlies a complex composite of parallel pain pathways, multiple mechanisms, and diverse inter-individual pain experiences and expectations. Methods: Variations for genes encoding receptors related to cold and heat sensation, such as transient receptor potential A subtype 1 (TRPA1), M subtype 8 (TRPM8), V subtype 1 (TRPV1), delta opioid receptor subtype 1 (OPRD1), catechol O-methyltransferase ( COMT), and fatty acid amide hydrolyase ( FAAH), were investigated in four major ethnic populations. Results: We defined 13 haplotype blocks in European Americans, seven blocks in African Americans, seven blocks in Hispanic subjects, and 11 blocks in Asian Americans. Further study in European American subjects found significant associations between short duration cold pain sensitivity and variations in TRPA1, COMT, and FAAH in a gender dependent manner. Our observations demonstrate that genetic variations in TRPA1, COMT, and FAAH contribute gender specifically to individual variations in short duration cold pain sensitivity in a European American cohort. Conclusions: The effects of TRPA1 variations on experimental short duration heat pain sensitivity may contribute to interindividual variation in pain sensitivity in humans. C1 NINR, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Dionne, RA (reprint author), Bldg 10 CRC East Wing,Rm 2 1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov FU Intramural NIH HHS NR 34 TC 98 Z9 102 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2006 VL 43 IS 8 AR e40 DI 10.1136/jmg.2005.036079 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 069FZ UT WOS:000239433100013 PM 16882734 ER PT J AU Shabbir, MI Ahmed, ZM Khan, SY Riazuddin, S Waryah, AM Khan, SN D Camps, R Ghosh, M Kabra, M Belyantseva, IA Friedman, TB Riazuddin, S AF Shabbir, M. I. Ahmed, Z. M. Khan, S. Y. Riazuddin, Saima Waryah, A. M. Khan, S. N. D Camps, R. Ghosh, M. Kabra, M. Belyantseva, I. A. Friedman, T. B. Riazuddin, Sheikh TI Mutations of human TMHS cause recessively inherited non-syndromic hearing loss SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID SYNDROME-TYPE-I; UNCONVENTIONAL MYOSIN; DEAFNESS DFNB3; MAPS; LOCUS; GENE; PCDH15; MICE; EAR; STEREOCILIA AB Background: Approximately half the cases of prelingual hearing loss are caused by genetic factors. Identification of genes causing deafness is a crucial first step in understanding the normal function of these genes in the auditory system. Recently, a mutant allele of Tmhs was reported to be associated with deafness and circling behaviour in the hurry-scurry mouse. Tmhs encodes a predicted tetraspan protein of unknown function, which is expressed in inner ear hair cells. The human homologue of Tmhs is located on chromosome 6p. Objective: To determine the cause of deafness in four consanguineous families segregating recessive deafness linked to markers on chromosome 6p21.1-p22.3 defining a novel DFNB locus. Results: A novel locus for non-syndromic deafness DFNB67 was mapped in an interval of approximately 28.51 cM on human chromosome 6p21.1-p22.3. DNA sequence analysis of TMHS revealed a homozygous frameshift mutation (246delC) and a missense mutation (Y127C) in affected individuals of two families segregating non-syndromic deafness, one of which showed significant evidence of linkage to markers in the DFNB67 interval. The localisation of mTMHS in developing mouse inner ear hair cells was refined and found to be expressed briefly from E16.5 to P3. Conclusions: These findings establish the importance of TMHS for normal sound transduction in humans. C1 Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. Natl Inst Deafness & Other Commun Disorders, Lab Mol Genet, Sect Human Genet, NIH, Rockville, MD USA. All India Inst Med Sci, Dept Paediat, Genet Unit, New Delhi, India. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Nasim Khan, Shaheen/F-2135-2015; OI Waryah, Ali/0000-0002-2596-9032 FU Intramural NIH HHS; NIDCD NIH HHS [T32 DC000035, Z01 DC000039] NR 30 TC 40 Z9 42 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD AUG PY 2006 VL 43 IS 8 AR 634 DI 10.1136/jmg.2005.039834 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 069FZ UT WOS:000239433100002 PM 16459341 ER PT J AU Pandrea, I Silvestri, G Onanga, R Veazey, RS Marx, PA Hirsch, V Apetrei, C AF Pandrea, Ivona Silvestri, Guido Onanga, Richard Veazey, Ronald S. Marx, Preston A. Hirsch, Vanessa Apetrei, Cristian TI Simian immunodeficiency viruses replication dynamics in African non-human primate hosts: common patterns and species-specific differences SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Symposium on Nonhuman Primate Models for AIDS CY SEP 21-24, 2005 CL Portland, OR SP Organ Natl Primate Res Ctr DE African green monkeys; Mandrills; non-human primates; plasma viral loads; SIVagm; SIVmnd; SIVsmm; sooty mangabeys ID MANDRILLS MANDRILLUS-SPHINX; T-CELL TURNOVER; GREEN MONKEYS; SOOTY MANGABEYS; VIRAL-LOAD; NATURAL INFECTION; SIVAGM INFECTION; RHESUS MACAQUES; AIDS; HIV AB Methods To define potential common features of simian immunodeficiency virus (SIV) infections in different naturally infected host species, we compared the dynamics of viral replication in 31 African green monkeys (10 sabeus, 15 vervets and seven Caribbean AGMs), 14 mandrills and three sooty mangabeys (SMs) that were experimentally infected with their species-specific viruses. Results After infection, these SIVs replicated rapidly reaching viral loads (VLs) of 10(5)-10(9) copies/ml of plasma between days 9-14 post-infection (p.i). Set point viremia was established between days 42 and 60 p.i., with levels of approximately 10(5)-10(6) copies/ml in SM and mandrills, and lower levels (10(3)-10(5) copies/ml) in AGMs. VL during the chronic phase did not correlate with viral genome structure: SIVmnd-2 (a vpx-containing virus) and SIVmnd-1 (which does not contain vpu or vpx) replicated to similar levels in mandrills. VL was dependent on virus strain: vervets infected with three different viral strains showed different patterns of viral replication. The pattern of viral replication of SIVagm.sab, which uses both CCR5 and CXCR4 co-receptors was similar to those of the other viruses. Conclusions Our results show a common pattern of SIV replication in naturally and experimentally infected hosts. This is similar overall to that observed in pathogenic SIV infection of macaques. This result indicates that differences in clinical outcome between pathogenic and non-pathogenic infections rely on host responses rather than the characteristics of the virus itself. C1 Tulane Univ, Div Comparat Pathol, Primate Res Ctr, Covington, LA 70433 USA. Tulane Univ, Sch Publ Hlth, Sch Med, Dept Pathol, New Orleans, LA 70118 USA. Univ Penn, Clin Virol Lab, Philadelphia, PA 19104 USA. Ctr Int Rech Med, Franceville, Gabon. Tulane Univ, Sch Publ Hlth, Dept Trop Med, Covington, LA 70433 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Pandrea, I (reprint author), Tulane Univ, Div Comparat Pathol, Primate Res Ctr, 18703 Three Rivers Rd, Covington, LA 70433 USA. EM ipandrea@tulane.edu FU NCRR NIH HHS [P20 RR-020159, P51 RR-000164, P51-RR00165]; NIAID NIH HHS [R01 AI-052775, R01 AI-064066, R01 AI065325, R01 AI49080, R21 AI-054234] NR 58 TC 42 Z9 42 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 BP 194 EP 201 DI 10.1111/j.1600-0684.2006.00168.x PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300003 PM 16872282 ER PT J AU Mattapallil, JJ Hill, B Douek, DC Roederer, M AF Mattapallil, Joseph J. Hill, Brenna Douek, Daniel C. Roederer, Mario TI Systemic vaccination prevents the total destruction of mucosal CD4 T cells during acute SIV challenge SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article; Proceedings Paper CT 23rd Annual Symposium on Nonhuman Primate Models for AIDS CY SEP 21-24, 2005 CL Portland, OR SP Organ Natl Primate Res Ctr DE acute infection; blood; CCR5; CD4 T cells; gut; human immunodeficiency virus; immunodeficiency; intestine; mucosa; rhesus; simian immunodeficiency virus; T cell ID SIMIAN IMMUNODEFICIENCY VIRUS; CELLULAR IMMUNE-RESPONSES; RHESUS-MONKEYS; GASTROINTESTINAL-TRACT; HIV-1 INFECTION; NEUTRALIZING ANTIBODIES; VAGINAL TRANSMISSION; CD8(+) LYMPHOCYTES; TYPE-1 INFECTION; FLOW-CYTOMETRY AB Background Acute human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infections are accompanied by a systemic loss of memory CD4 T cells, with mucosal sites serving as a major site for viral replication, dissemination and CD4 T cell depletion. Protecting the mucosal CD4 T cell compartment thus is critical to contain HIV, and preserve the integrity of the mucosal immune system. The primary objective of this study was to determine if systemic vaccination with DNA/rAd-5 encoding SIV-mac239-env, gag and pol could prevent the destruction of CD4 T cells in mucosal tissues. Methods Rhesus macaques were immunized with DNA/r-Ad-5 encoding SIV genes and compared with those immunized with sham vectors following high dose intravenous challenge with SIVmac251. SIV specific CD4 and CD8 T cell responses, cell associated viral loads and mucosal CD4 T cell dynamics were evaluated. Results Strong SIV specific immune responses were induced in mucosal tissues of vaccinated animals as compared with sham controls. These responses expanded rapidly following challenge suggesting a strong anamnestic response. Immune responses were associated with a decrease in cell associated viral loads, and a loss of fewer mucosal CD4 T cells. Approximately 25% of mucosal CD4 T cells were preserved in vaccinated animals as compared with < 5% in sham controls. These results demonstrate that systemic immunization strategies can induce immune responses in mucosal tissues that can protect mucosal CD4 T cells from complete destruction following challenge. Conclusions Preservation of mucosal CD4 T cells can contribute to maintaining immune competence in mucosal tissues and provide a substantial immune benefit to the vaccinees. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. RP Mattapallil, JJ (reprint author), 40 Convent Dr,Room 5610, Bethesda, MD 20895 USA. EM jmattapallil@mail.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS NR 42 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 BP 217 EP 224 DI 10.1111/j.1600-0684.2006.00170.x PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300006 PM 16872285 ER PT J AU Dang, Q Goeken, R Dehghani, H Brown, CR Buckler-White, A Plishka, R Hirsch, VM AF Dang, Que Goeken, Robert Dehghani, Houman Brown, Charles R. Buckler-White, Alicia Plishka, Ronald Hirsch, Vanessa M. TI Evolution of unique genotypes of SIV in the blood and CSF of two macaques with SIV-encephalitis SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 3 BP 272 EP 272 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300014 ER PT J AU Mahalanabis, M Blay, W Hirsch, VM Haigwood, NL AF Mahalanabis, M. Blay, W. Hirsch, V. M. Haigwood, N. L. TI Similarities in SIV and SHIV envelope variation and the development on neutralizing antibodies in macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. NIAID, LMM, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 4 BP 272 EP 272 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300015 ER PT J AU Schmitz, J Acierno, P Kuroda, M Newberg, M Mattapallil, J Roederer, M Kim, EY Powers, J Wolinsky, S Piatak, M Lifson, J Montefiori, D Letvin, N Veazey, R AF Schmitz, Joern Acierno, Paula Kuroda, Marcelo Newberg, Michael Mattapallil, Joseph Roederer, Mario Kim, Eun-Young Powers, Jennifer Wolinsky, Steven Piatak, Michael, Jr. Lifson, Jeffrey Montefiori, David Letvin, Norman Veazey, Ronald TI Depletion of gastrointestinal CD4+ T cells during primary SIV infection is not caused by SIV-specific CD8+ T cell responses SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02115 USA. Tulane Univ, Natl Primate Res Ctr, Covington, LA 70433 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. SAIC Frederick Inc, AIDS Vaccine Program, Natl Canc Inst, Frederick, MD 21702 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 9 BP 274 EP 275 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300020 ER PT J AU Pandrea, I Apetrei, C Dufour, J Dillon, N Katz, N Barbercheck, J Diop, OM Bohm, R Marx, PA Barre-Sinoussi, F Hirsch, V Muller-Trutwin, MC Lackner, AA Veazey, RS AF Pandrea, Ivona Apetrei, Cristian Dufour, Jason Dillon, Nora Katz, Nathalia Barbercheck, Joseph Diop, Ousmane M. Bohm, Rudolf Marx, Preston A. Barre-Sinoussi, Francoise Hirsch, Vanessa Muller-Trutwin, Michaela C. Lackner, Andrew A. Veazey, Ronald S. TI Dramatic CD4+ T cell depletion in the intestine is a hallmark of SIV infection in natural hosts. results from Caribbean AGMs SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. Inst Pasteur, F-75015 Paris, France. Inst Pasteur, Dackar, Senegal. NIAID, NIH, Boston, MA 02115 USA. RI Barre-Sinoussi, Francoise/G-8355-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 15 BP 277 EP 277 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300026 ER PT J AU Hryniewicz, A Edghill-Smith, Y Blanset, D Lowy, I Tsai, WP Vaccari, M Franchini, GA AF Hryniewicz, Anna Edghill-Smith, Yvette Blanset, Diann Lowy, Israel Tsai, Wen-Po Vaccari, Monica Franchini, Genoveffa A. TI Treatment with anti-CTLA4 antibody of SIVmac251-infected macaques is well tolerated and may augment anti-SIV cellular immune responses SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. Medarex, Bloomsbury, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 19 BP 279 EP 279 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300030 ER PT J AU Kumar, S Boyer, JD Calarota, SA Sidhu, MK Lewis, M Pavlakis, G Felber, B Weiner, D AF Kumar, Sanjeev Boyer, Jean D. Calarota, Sandra A. Sidhu, Maninder K. Lewis, Mark Pavlakis, George Felber, Barbara Weiner, David TI DNA immunotherapy and IL-12 suppresses viral replication following the cessation of anti-retroviral drugs SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Emory Univ, Atlanta, GA 30322 USA. Wyeth, Vaccine Discovery, Pearl River, NY 10965 USA. Bioqual, Frederick, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 23 BP 280 EP 280 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300034 ER PT J AU Vaccari, M Tsai, WP Hryniewicz, A Nacsa, J Heraud, JM Doster, MN Panicali, D Schmitz, JE Reimann, KA Franchini, G AF Vaccari, Monica Tsai, Wen-Po Hryniewicz, Anna Nacsa, Janos Heraud, Jean-Michel Doster, Melvin N. Panicali, Dennis Schmitz, Joern E. Reimann, Keith A. Franchini, Genoveffa TI Contribution of antigen-specific CD4+ T cells to the generation of SIV-specific CD8+ memory cells SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Therion Biol, Cambridge, MA 02142 USA. RI HERAUD, Jean-Michel/O-1464-2013 OI HERAUD, Jean-Michel/0000-0003-1107-0859 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 29 BP 283 EP 283 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300040 ER PT J AU Gauduin, MC Yu, Y Pierce, J Barabasz, AF Piatak, M Lifson, JD Desrosiers, RC Johnson, RP AF Gauduin, Marie-Claire Yu, Yi Pierce, Jeannie Barabasz, Amy F. Piatak, Mike Lifson, Jeffrey D. Desrosiers, Ronald C. Johnson, R. Paul TI Functional and phenotypic heterogeneity of SIV-specific CD4+ T cell responses in attenuated and wild-type SIV infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, NEPRc, Div Immunol, Southborough, MA 01772 USA. SAIC Frederick Inc, NCI Frederick, Frederick, MD 21702 USA. Harvard Univ, NEPRC, Sch Med, Div Microbiol, Southborough, MA 01772 USA. MGH, Infect Dis Unit, Boston, MA 02114 USA. MGH, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 31 BP 284 EP 285 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300043 ER PT J AU Evans, DT Sanford, HB Bricker, JE DeGottardi, MQ Piatak, M Lifson, JD Mansfield, KG Johnson, RP Desrosiers, RC AF Evans, David T. Sanford, Hannah B. Bricker, Jennifer E. DeGottardi, M. Quinn Piatak, Michael Lifson, Jeffrey D. Mansfield, Keith G. Johnson, R. Paul Desrosiers, Ronald C. TI The site of inoculation with VSV G trans-complemented single-cycle SIV influences the properties of virus-specific T cell responses SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. SAIC Frederick Inc, Natl Canc Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 34 BP 285 EP 285 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300045 ER PT J AU Kaur, A Sanford, HB Garry, D Lang, S Klumpp, S Bronson, RT Lifson, JD Rosati, M Pavlakis, GN Felber, BK Knipe, DM Desrosiers, RC AF Kaur, Amitinder Sanford, Hannah B. Garry, Deirdre Lang, Sabine Klumpp, Sherry Bronson, Roderick T. Lifson, Jefferey D. Rosati, Margherita Pavlakis, George N. Felber, Barbara K. Knipe, David M. Desrosiers, Ronald C. TI The ability of DNA priming to boost immune responses to recombinant herpes simplex virus vector and to protect against challenge by simian immunodeficiency virus SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SAIC Frederick Inc, Natl Canc Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 37 BP 286 EP 287 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300048 ER PT J AU Mattapallil, J Douek, D Martin, M Montefiori, D Letvin, N Nabel, G Roederer, M AF Mattapallil, Joseph Douek, Daniel Martin, Malcolm Montefiori, David Letvin, Norm Nabel, Gary Roederer, Mario TI Vaccination protects against the massive destruction of memory CD4 T-cells during acute SIV infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NIAID, Vaccine Res Ctr, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Duke Med Sch, Durham, NC USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 36 BP 286 EP 286 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300047 ER PT J AU Van Rompay, KKA Earl, P Abel, K Schmidt, K Colon, R Blackwood, E Easlick, J Buonocore-Buzzelli, L Moss, B Rose, J Marthas, ML AF Van Rompay, Koen K. A. Earl, Pat Abel, Kristina Schmidt, Kim Colon, Roxanna Blackwood, Emily Easlick, Juliet Buonocore-Buzzelli, Linda Moss, Bernard Rose, John Marthas, Marta L. TI Topical oral delivery of replicating, recombinant vesicular stomatitis virus (VSV)-based SIV vaccines in newborn rhesus macaques: Safety and immunogenicity SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Calif Natl Primate Res Ctr, Davis, CA USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT 06520 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 35 BP 286 EP 286 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300046 ER PT J AU Pal, R Venzon, D Kalyanaraman, VS Montefiori, D Hocker, L Hudacik, L Rose, N Nacsa, J Edghill-Smith, Y Belyakov, I Berzofsky, J Parks, RW Markham, P Franchini, G AF Pal, Ranajit Venzon, David Kalyanaraman, Vaniambadi S. Montefiori, David Hocker, Lindsey Hudacik, Lauren Rose, Nicolas Nacsa, Janos Edghill-Smith, Yvette Belyakov, Igor Berzofsky, Jay Parks, Robyn Washington Markham, Phillip Franchini, Genoveffa TI Priming of rhesus macaques with ALVAC-HIV-1 vaccines via systemic route followed by boosting with human immunodeficiency virus type 1 (HIV-1) envelope protein controls viremia in systemic and mucosal compartments and protects from loss of CD4+T-cells following challenge with pathogenic SHIV isolates SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Adv BioSci Labs, Kensington, MD 20895 USA. NCI, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 39 BP 287 EP 287 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300050 ER PT J AU Laird, ME Igarashi, T Martin, MA Desrosiers, RC AF Laird, Melissa E. Igarashi, Tatsuhiko Martin, Malcom A. Desrosiers, Ronald C. TI What determines the strain specificity of the neutralizing antibody response? SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 46 BP 290 EP 290 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300057 ER PT J AU Chung, HK Pise-Masison, CA Radonovich, MF Brady, J Pal, R Cristillo, A Markham, PD AF Chung, Hye-kyung Pise-Masison, Cynthia A. Radonovich, Michael F. Brady, John Pal, Ranajit Cristillo, Anthony Markham, Phillip D. TI Comparison of cellular gene expression profiles in PBMC from rhesus macaques that control or do not control SHIV infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Adv BioSci Labs Inc, Kensington, MD 20895 USA. NCI, Cellular Oncol Lab, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 65 BP 297 EP 298 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300076 ER PT J AU Jiang, YH Emau, P Tian, BP Bekele, G Cairns, JS Gupta, K Tsai, CC AF Jiang, Y. H. Emau, P. Tian, B. P. Bekele, G. Cairns, J. S. Gupta, K. Tsai, C. -C. TI Enhanced infectivity of a CCR5-using shiv derived from intestinal lymphocytes of an infected pigtailed macaque at late stage of infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. Henry M Jackson Fdn, Mercer Isl, WA 98040 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 81 BP 303 EP 304 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300092 ER PT J AU Yuan, F Oswald, K Cline, AN Coalter, VJ Poore, B Bischofberger, N Lifson, RD Piatak, M AF Yuan, Fang Oswald, Kelli Cline, A. Nicole Coalter, Vicky J. Poore, Barbara Bischofberger, Norbert Lifson, Rey D. Piatak, Michael, Jr. TI Dynamics of antiviral responses and selection of M184V drug resistant mutations with FTC monotherapy of chronic infection with SIVmac239 SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 SAIC Frederick, AIDS Vaccine Program, NCI, Frederick, MD 21702 USA. Gilead Sci Inc, Foster City, CA 94404 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 83 BP 304 EP 305 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300094 ER PT J AU Ambrose, Z Wiegand, A Kimata, J Maldarelli, F Hughes, SH Palmer, S Mellors, JW Coffin, JM Lifson, RD Ramani, VNK AF Ambrose, Zandrea Wiegand, Ann Kimata, Jason Maldarelli, Frank Hughes, Stephen H. Palmer, Sarah Mellors, John W. Coffin, John M. Lifson, Rey D. Ramani, Vineet N. Kewal TI Drug resistance mutations detected in RT-SHIV-infected macaques treated with a single dose of non-nucleoside RT inhibitor (NNRTI) SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NCI, AIDS Vaccine Program, Frederick, MD 21701 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 85 BP 305 EP 305 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300096 ER PT J AU Lafont, BAP McGraw, CM Willey, RL Nishimura, Y Igarashi, T Buckler-White, A Plishka, RJ Buckler, CE Martin, MA AF Lafont, Bernard A. P. McGraw, Christopher M. Willey, Ronald L. Nishimura, Yoshiaki Igarashi, Tatsuhiko Buckler-White, Alicia Plishka, Ronald J. Buckler, Charles E. Martin, Malcolm A. TI The pig-tailed macaque MHC class I allele Mane-A*03 presents dominant SIV gag responses to multiple epitopes in SHIV infected animals SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RI Lafont, Bernard/B-7236-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 95 BP 308 EP 308 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300106 ER PT J AU Andersen, H Barsov, EV Trivett, MT Princiotta, MF Lifson, JD Ott, DE Ohlen, C AF Andersen, Hanne Barsov, Eugene V. Trivett, Matthew T. Princiotta, Michael F. Lifson, Jeffrey D. Ott, David E. Ohlen, Claes TI Immortalization of SIV-specific CTL clones using a retroviral vector encoding the human telomerase gene SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 102 BP 310 EP 311 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300113 ER PT J AU Hryniewicz, A Betts, MR Edghill-Smith, Y Vaccari, M Franchini, G AF Hryniewicz, Anna Betts, Michael R. Edghill-Smith, Yvette Vaccari, Monica Franchini, Genoveffa TI CD107 as a marker of antigen-specific CD8+ effector T cells in macaques SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 100 BP 310 EP 310 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300111 ER PT J AU Gomez-Roman, VR Florese, RH Jean-Patterson, L Peng, B Venzon, D Aldrich, K Robert-Guroff, M AF Gomez-Roman, V. Raul Florese, Ruth H. Jean-Patterson, L. Peng, Bo Venzon, David Aldrich, Kris Robert-Guroff, Marjorie TI Evaluation of antibody-dependent cell-mediated cytotoxicity using a sensitive, rapid fluorometric assay SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 104 BP 311 EP 311 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300115 ER PT J AU Patterson, LJ Kalman, J Malkevitch, N Demberg, T Richardson, E Aldrich, K Kalyanaraman, VS Robert-Guroff, M AF Patterson, L. Jean Kalman, Jennifer Malkevitch, Nina Demberg, Thorsten Richardson, Ersell Aldrich, Kris Kalyanaraman, V. S. Robert-Guroff, Marjorie TI Induction of strong HIV/SIV-specific CD8+ memory cells and proliferative responses in peripheral blood and bronchial alveolar lavage samples of rhesus macaques following mucosal immunization with replicating AD5HR-HIV/SIV recombinants SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Vaccine Branch, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, NSW 20895, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 110 BP 313 EP 314 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300121 ER PT J AU Zheng, YF Wu, YT Qurmanov, I Goeken, R Hirsch, VM AF Zheng, Yanfang Wu, Yuntao Qurmanov, Ilnour Goeken, Robert Hirsch, Vanessa M. TI A nonintegrated mutant simian immunodeficiency virus transcribes persistently in rhesus macrophages in vitro SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NIAID, NIH, Mol Microbiol Lab, Bethesda, MD 20892 USA. George Mason Univ, Dept Mol & Microbiol, Manassas, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 114 BP 315 EP 315 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300125 ER PT J AU Hel, Z Tsai, WP Tryniszewska, E Nacsa, J Markham, PD Lewis, MG Pavlakis, GN Felber, BK Tartaglia, J Franchini, G AF Hel, Zdenek Tsai, Wen-Po Tryniszewska, Elzbieta Nacsa, Janos Markham, Phillip D. Lewis, Mark G. Pavlakis, George N. Felber, Barbara K. Tartaglia, Jim Franchini, Genoveffa TI Improved protection from simian AIDs by the addition of nonstructural SIV genes despite antigen competition SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Adv Biosci Labs, Kensington, MD 20895 USA. Bioqual, Rockville, MD 20850 USA. Sanofi Pasteur, Toronto, ON M2R 3T4, Canada. RP Hel, Z (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 119 BP 317 EP 317 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300130 ER PT J AU Heraud, JM Golding, H Edghill-Smith, Y Manischewitz, J King, LR Tsai, WP Hryniewicz, A Ayala, V Kalyanaraman, V Silvera, P Bray, M Seder, R Hooper, JW Franchini, G AF Heraud, Jean-Michel Golding, Hana Edghill-Smith, Yvette Manischewitz, Jody King, Lisa R. Tsai, Wen-Po Hryniewicz, Anna Ayala, Victor Kalyanaraman, V. S. Silvera, Peter Bray, Mike Seder, Robert Hooper, Jay W. Franchini, Genoveffa TI Protection from lethal monkeypox challenge afforded by a four-gene-combination DNA vaccine followed by boosting with CpG-adjuvanted monkeypox proteins plus CpG SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. Adv Biosci Labs, Bethesda, MD 20895 USA. So Res Inst, Frederick, MD 21701 USA. NIAID, Bethesda, MD 20892 USA. Vaccine Res Ctr, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RI HERAUD, Jean-Michel/O-1464-2013 OI HERAUD, Jean-Michel/0000-0003-1107-0859 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 120 BP 317 EP 317 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300131 ER PT J AU von Gegerfelt, A Valentin, A Patel, V Morrow, M Alicea, C Rosati, M Marthas, M Ruprecht, R Felber, BK Pavlakis, GN AF von Gegerfelt, Agneta Valentin, Antonio Patel, Vainav Morrow, Matthew Alicea, Candido Rosati, Margherita Marthas, Marta Ruprecht, Ruth Felber, Barbara K. Pavlakis, George N. TI Preservation of SIV-specific subset of cells with central memory phenotype SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 NCI, Frederick, MD 21702 USA. Calif Natl Primate Res Ctr, Davis, CA 95616 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 122 BP 318 EP 318 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300133 ER PT J AU Kutzler, MA Boyer, JD Kumar, S Sidhu, M Roopchand, V Pavlakis, GN Felber, BK Montefiori, D Silvera, P Letvin, N Waldmann, TA Weiner, DB AF Kutzler, Michele A. Boyer, Jean D. Kumar, Sanjeev Sidhu, Maninder Roopchand, Vidia Pavlakis, George N. Felber, Barbara K. Montefiori, David Silvera, Peter Letvin, Norman Waldmann, Thomas A. Weiner, David B. TI Protection against simian/human immunodeficiency virus 89.6P replication in macaques following co-immunization with SIV antigen and an optimized rhesus IL-15 plasmid is not associated with IFN-gamma secretion by T lymphocytes SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Wyeth Lederle, Vaccine Discovery, Pearl River, NY USA. NCI, Basic Res Lab, NIH, Frederick, MD 21701 USA. So Res Inst, Frederick, MD USA. Harvard Univ, Boston, MA 02115 USA. NCI, NIH, Metab Branch, Bethesda, MD 20892 USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 126 BP 319 EP 320 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300137 ER PT J AU Polacino, P Zhu, Y Klots, I Sheikh, N Larsen, K Anderson, D Richardson, B Bess, J Schneider, D Arthur, LO Lifson, JD Benveniste, RE Hu, SL AF Polacino, Patricia Zhu, Yongde Klots, Igor Sheikh, Nadeem Larsen, Kay Anderson, David Richardson, Barbra Bess, Julian, Jr. Schneider, Douglas Arthur, Larry O. Lifson, Jeffrey D. Benveniste, Raoul E. Hu, Shiu-Lok TI Sequence analysis of breakthrough viruses in macaques immunized with different - Primeboost regimens and challenged with a pathogenic uncloned SIVmne SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Washington, Washington Natl Primate Res Ctr, Seattle, WA 98195 USA. SAIC, Frederick, MD 21702 USA. NCI, Frederick, MD 21702 USA. RI Hu, Shiu-Lok/A-3196-2008; Bess, Jr., Julian/B-5343-2012 OI Hu, Shiu-Lok/0000-0003-4336-7964; NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2006 VL 35 IS 4-5 MA 127 BP 320 EP 320 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 063GU UT WOS:000239007300138 ER PT J AU Cohen, TV Randall, WR AF Cohen, Tatiana V. Randall, William R. TI The regulation of acetylcholinesterase by cis-elements within intron I in cultured contracting myotubes SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE acetylcholinesterase; contraction; GABP; gene regulation; muscle culture; transcription factor ID EMBRYONIC RAT MYOTUBES; GA-BINDING-PROTEIN; RECEPTOR GENE-EXPRESSION; MESSENGER-RNA STABILITY; SKELETAL-MUSCLE FIBERS; TRANSCRIPTION FACTOR; ELECTRICAL-ACTIVITY; MYOGENIC DIFFERENTIATION; ALPHA-SUBUNIT; KINASE-C AB The onset of spontaneous contraction in rat primary muscle cultures coincides with an increase in acetylcholinesterase (AChE) activity. In order to establish whether contractile activity modulates the rate of AChE transcript synthesis, and what elements of the gene are determinant, we examined the promoter and intron I in contracting muscle cultures. Ache genomic fragments attached to a luciferase reporter were transfected into muscle cultures that were either electrically stimulated or paralyzed with tetrodotoxin to enhance or inhibit contractions, respectively. Cultures transfected with intron I-containing constructs showed a 2-fold increase in luciferase activity following electrical stimulation, compared to tetrodotoxin treatment, suggesting that this region contains elements responding to contractile activity. Deleting a 780 bp distal region within intron I, containing an N-box element at +890 bp, or introducing a 2-bp mutation within its core sequence, eliminated the contraction-induced response. In contrast, mutating an N-box element at +822 bp had no effect on the response. Furthermore, co-transfecting a dominant negative GA-binding protein (GABP), a transcription factor known to selectively bind N-box elements, reduced the stimulation-mediated increase. Our results suggest that the N-box within intron I at +890 bp is a regulatory element important in the transcriptional response of Ache to contractile activity in muscle. C1 Univ Maryland, Sch Med, Dept Pharmacol & Expt Therapeut, Baltimore, MD 21201 USA. RP Randall, WR (reprint author), NCI, POB B, Frederick, MD 21702 USA. EM wrandall@umaryland.edu NR 40 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2006 VL 98 IS 3 BP 723 EP 734 DI 10.1111/j.1471-4159.2006.03897.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 063GV UT WOS:000239007400009 PM 16787423 ER PT J AU Choi, SH Langenbach, R Bosetti, F AF Choi, Sang-Ho Langenbach, Robert Bosetti, Francesca TI Cyclooxygenase-1 and-2 enzymes differentially regulate the brain upstream NF-kappa B pathway and downstream enzymes involved in prostaglandin biosynthesis SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cyclooxygenase; prostaglandin E synthase; phospholipase A(2); PGE(2); NF-kappa B ID CYTOSOLIC PHOSPHOLIPASE A(2); CENTRAL-NERVOUS-SYSTEM; ARACHIDONIC-ACID CASCADE; E-2 BIOSYNTHESIS; E SYNTHASE; TRANSCRIPTIONAL REGULATION; 3'-UNTRANSLATED REGION; GENE-EXPRESSION; MESSENGER-RNA; NITRIC-OXIDE AB We have recently reported that cyclooxygenase (COX)-2-deficiency affects brain upstream and downstream enzymes in the arachidonic acid (AA) metabolic pathway to prostaglandin E-2 (PGE(2)), as well as enzyme activity, protein and mRNA levels of the reciprocal isozyme, COX-1. To gain a better insight into the specific roles of COX isoforms and characterize the interactions between upstream and downstream enzymes in brain AA cascade, we examined the expression and activity of COX-2 and phospholipase A(2) enzymes (cPLA(2) and sPLA(2)), as well as the expression of terminal prostaglandin E synthases (cPGES, mPGES-1, and - 2) in wild type and COX-1(-/-) mice. We found that brain PGE(2) concentration was significantly increased, whereas thromboxane B2 (TXB2) concentration was decreased in COX-1(-/-) mice. There was a compensatory up-regulation of COX-2, accompanied by the activation of the NF-kappa B pathway, and also an increase in the upstream cPLA(2) and sPLA(2) enzymes. The mechanism of NF-kappa B activation in the COX-1(-/-) mice involved the up-regulation of protein expression of the p50 and p65 subunits of NF-kappa B, as well as the increased protein levels of phosphorylated I kappa B alpha and of phosphorylated IKK alpha/beta. Overall, our data suggest that COX-1 and COX-2 play a distinct role in brain PG biosynthesis, with basal PGE(2) production being metabolically coupled with COX-2 and TXB2 production being preferentially linked to COX-1. Additionally, COX-1 deficiency can affect the expression of reciprocal and coupled enzymes, COX-2, Ca2+-dependent PLA(2), and terminal mPGES-2, to overcome defects in brain AA cascade. C1 Natl Inst Aging, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC USA. RP Bosetti, F (reprint author), Natl Inst Aging, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000423-02] NR 55 TC 42 Z9 45 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2006 VL 98 IS 3 BP 801 EP 811 DI 10.1111/j.1471-4159.2006.03926.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 063GV UT WOS:000239007400016 PM 16787416 ER PT J AU Zhang, DH Stumpo, DJ Graves, JP DeGraff, LM Grissom, SF Collins, JB Li, LP Zeldin, DC Blackshear, PJ AF Zhang, Donghui Stumpo, Deborah J. Graves, Joan P. DeGraff, Laura M. Grissom, Sherry F. Collins, Jennifer B. Li, Leping Zeldin, Darryl C. Blackshear, Perry J. TI Identification of potential target genes for RFX4_v3, a transcription factor critical for brain development SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain; CX3C ligand 1; microarray; mouse; regulatory factor X4 variant transcript 3 ID CENTRAL-NERVOUS-SYSTEM; DNA-BINDING PROTEIN; REGULATORY FACTOR-X; RETINOIC ACID; CHEMOKINE FRACTALKINE; REPRESSION DOMAINS; HOMEOBOX GENE; EXPRESSION; DIFFERENTIATION; DROSOPHILA AB Regulatory factor X4 variant transcript 3 (Rfx4_v3) gene disruption in mice demonstrated that interruption of a single allele (heterozygous, +/-) prevented formation of the subcommissural organ, resulting in congenital hydrocephalus, while interruption of two alleles (homozygous, -/-) caused fatal failure of dorsal midline brain structure formation. To identify potential target genes for RFX4_v3, we used microarray analysis to identify differentially expressed genes in Rfx4_v3-deficient mouse brains at embryonic day 10.5, before gross structural changes were apparent. Of 109 differentially expressed transcripts, 24 were chosen for validation and 22 were confirmed by real-time PCR. Many validated genes encoded critical proteins involved in brain morphogenesis, such as the signaling components in the Wnt, bone morphogenetic protein (BMP) and retinoic acid (RA) pathways. Cx3cl1, a CX3C-type chemokine gene that is highly expressed in brain, was down-regulated in the Rfx4_v3-null mice. Both human and mouse Cx3cl1 proximal promoters contained highly conserved X-boxes, known cis-acting elements for RFX protein binding. Using the Cx3cl1 promoter as an example of a target gene, we demonstrated direct binding of RFX4_v3 to the Cx3cl1 promoter, and trans-acting activity of RFX4_v3 protein to stimulate gene expression. These data suggest that RFX4_v3 may act upstream of critical signaling pathways in the process of brain development. C1 NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Grp, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clerical Res, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Neurobiol Lab, NIH, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Black009@niehs.nih.gov FU Intramural NIH HHS NR 54 TC 15 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2006 VL 98 IS 3 BP 860 EP 875 DI 10.1111/j.1471-4159.2006.03930.x PG 16 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 063GV UT WOS:000239007400021 PM 16893423 ER PT J AU Furay, AR Murphy, EK Mattson, MP Guo, Z Herman, JP AF Furay, A. R. Murphy, E. K. Mattson, M. P. Guo, Z. Herman, J. P. TI Region-specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adrenocorticotropic releasing hormone; chaperone protein; corticosterone; hypothalamo-pituitary-adrenal axis ID MESSENGER-RNA EXPRESSION; CIRCADIAN-RHYTHM; RAT HIPPOCAMPUS; SPATIAL MEMORY; HYPOTHALAMIC-LESIONS; CHAPERONE MACHINERY; STRESS; CORTICOSTERONE; ADRENALECTOMY; BINDING AB The hippocampal glucocorticoid receptor (GR) is involved in negative feedback regulation of the hypothalamo-pituitary-adrenal axis and is believed to transduce the deleterious effects of glucocorticoids in depression and age-related memory loss. Regulation and intracellular trafficking of the GR are critical determinants of GR action in both health and disease. Here, we show dynamic regulation of GR and its interaction with its principal intracellular chaperone, heat-shock protein (HSP) 90, across the circadian cycle. Our initial experiments indicate that cytosolic hippocampal GR protein is elevated in the evening (PM), whereas nuclear GR and cytosolic HSP90, HSP70 and heat-shock cognate 70 (HSC70), are unchanged. In contrast, there are no changes in examined proteins in the hypothalamus. Immunoprecipitation experiments reveal increased GR-HSP90 associations in the hippocampus in the PM, whereas binding in the hypothalamus is decreased in the PM. Given that GR requires HSP90 for ligand binding, the data suggest that circadian GR signaling capacity is regulated in a region-specific pattern. C1 Univ Cincinnati, Dept Psychiat, Coll Med, Cincinnati, OH 45237 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RP Furay, AR (reprint author), Univ Cincinnati, Dept Psychiat, Coll Med, 2170 E Galbraith Rd,Bldg E,Room 205, Cincinnati, OH 45237 USA. EM furayar@uc.edu RI Mattson, Mark/F-6038-2012; Herman, James/D-4960-2015 OI Herman, James/0000-0003-3571-2406 FU NIA NIH HHS [AG12962]; NIDDK NIH HHS [DK59803] NR 48 TC 19 Z9 19 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2006 VL 98 IS 4 BP 1176 EP 1184 DI 10.1111/j.1471-4159.2006.03953.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 067MM UT WOS:000239307200017 PM 16895583 ER PT J AU Ravni, A Eiden, LE Vaudry, H Gonzalez, BJ Vaudry, D AF Ravni, Aurelia Eiden, Lee E. Vaudry, Hubert Gonzalez, Bruno J. Vaudry, David TI Cycloheximide treatment to identify components of the transitional transcriptome in PACAP-induced PC12 cell differentiation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cycloheximide; early response genes; microarray; PACAP; transitional transcriptome ID CYCLASE-ACTIVATING POLYPEPTIDE; NF-KAPPA-B; PROTEIN-SYNTHESIS; C-FOS; PHEOCHROMOCYTOMA CELLS; GENE-EXPRESSION; BINDING-SITES; MESSENGER-RNA; UP-REGULATION; KINASE GENE AB Pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neurite outgrowth, reduces proliferation and inhibits apoptosis of PC12 cells. We have partially characterized the transcriptome changes induced by PACAP after 6 h of treatment, when commitment to differentiation has occurred. Here, we have investigated the effects of a 6-h treatment with PACAP (10(-7) M) in the presence of cycloheximide (5 mu M) to identify, via superinduction, components of the transitional transcriptome initially induced by PACAP and potentially participating in the regulation of late-response genes required for differentiation. Approximately 100 new transcripts were identified in this screen, i.e. as many individual genes as make up the 6-h PACAP differentiation transcriptome itself. Six known transcripts in this cohort were then measured at several time points between 0 and 6 h by real-time PCR to determine whether these transcripts are induced early following PACAP treatment in the absence of cycloheximide, and therefore may be of functional importance in differentiation. Five out of the six transcripts were indeed induced by PACAP alone soon (between 30 min and 3 h) after cell treatment. beta-Cell translocation gene 2, antiproliferative (Btg2), serum/glucocorticoid-regulated kinase (Sgk), nuclear factor for the kappa chain of B-cells (NF kappa B), seven in absentia homologue 2 (Siah2) and FBJ osteosarcoma related oncogene (Fos) showed a 2.5-200-fold induction by PACAP between 15 min and 3 h, and mRNA levels returned either to baseline or near baseline after 6 h. This work provides new information concerning genes whose transient regulation early after PACAP exposure may contribute to the expression of the differentiated transcriptome in PC12 cells, and should help to elucidate the molecular mechanisms involved in the control of nerve cell survival and differentiation. C1 Univ Rouen, INSERM, European Inst Peptide Res,U413, Lab Cellular & Mol Neuroendocrinol,IFRMP 23, F-76821 Mont St Aignan, France. NIMH, NIH, Sect Mol Neurosci, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Vaudry, H (reprint author), Univ Rouen, INSERM, European Inst Peptide Res,U413, Lab Cellular & Mol Neuroendocrinol,IFRMP 23, F-76821 Mont St Aignan, France. EM eidenl@mail.nih.gov; hubert.vaudry@univ-rouen.fr RI Gonzalez, Bruno/E-6103-2016; OI Eiden, Lee/0000-0001-7524-944X; Vaudry, David/0000-0003-3567-7452 FU Intramural NIH HHS [Z01 MH002386-21, Z01 MH002386-22, Z99 MH999999, ZIA MH002386-23] NR 42 TC 19 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2006 VL 98 IS 4 BP 1229 EP 1241 DI 10.1111/j.1471-4159.2006.03962.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 067MM UT WOS:000239307200021 PM 16787409 ER PT J AU Li, J Yin, CY Okamoto, H Jaffe, H Oldfield, EH Zhuang, ZP Vortmeyer, AO Rushing, EJ AF Li, Jie Yin, Chunyue Okamoto, Hiroaki Jaffe, Howard Oldfield, Edward H. Zhuang, Zhengping Vortmeyer, Alexander O. Rushing, Elisabeth J. TI Proteomic analysis of inclusion body myositis SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE inclusion body myositis; inflammatory myopathy; mass spectrometry; proteomics; 2-d PAGE ID MITOCHONDRIAL CREATINE-KINASE; OXIDATIVE STRESS; MUSCLE-FIBERS; AMYLOID-BETA; TRANSTHYRETIN VAL122ILE; INFLAMMATORY MYOPATHIES; SUPEROXIDE-DISMUTASE; ENERGY-METABOLISM; EXPRESSION; DISEASES AB Sporadic inclusion body myositis (IBM) is the most frequently acquired inflammatory myopathy of late adult life, yet its diagnostic criteria and pathogenesis remain poorly defined. Because effective treatment is lacking, research efforts have intensified to identify specific markers for this debilitating disorder. In this study, proteomic analysis of 4 cases of sporadic IBM was compared with 5 cases of inflammatory myopathy without clinicopathologic features of IBM to distinguish the IBM-specific proteome. Proteins were separated by 2-dimensional polyacrylamide gel electrophoresis and profiled by mass spectrometric sequencing. Expression of most proteins remained unchanged; however, 16 proteins were upregulated and 6 proteins were downregulated in IBM compared with cases of non-IBM inflammatory myopathy. These IBM-specific proteins included apolipoprotein A-I, amyloid beta precursor protein, and transthyretin, which have been associated with amyloidosis; superoxide dismutase, enolase, and various molecular chaperones indicate perturbations in detoxification, energy metabolism, and protein folding, respectively. The IBM-downregulated proteins mainly serve as carriers for muscle contraction and other normal muscle functions. We further applied Western blot and immunohistochemistry to verify the proteomic findings. This study validates proteomics as a powerful tool in the study of muscle disease and indicates a unique pattern of protein expression in IBM. C1 Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Prot Peptide Sequencing Facil, NIH, Bethesda, MD 20892 USA. RP Rushing, EJ (reprint author), Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. EM rushinge@afip.osd.mil NR 46 TC 25 Z9 26 U1 0 U2 4 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 AUG PY 2006 VL 65 IS 8 BP 826 EP 833 DI 10.1097/01.jnen.0000228204.19915.69 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 100TR UT WOS:000241692300010 PM 16896316 ER PT J AU Nakahara, H Morita, K Wurtz, RH Optican, LM AF Nakahara, Hiroyuki Morita, Kenji Wurtz, Robert H. Optican, Lance M. TI Saccade-related spread of activity across superior colliculus may arise from asymmetry of internal connections SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID NEURAL-NETWORK MODEL; INTERMEDIATE GRAY LAYER; NIGRA PARS RETICULATA; EYE-MOVEMENTS; GAZE SHIFTS; REVERSIBLE INACTIVATION; INTRINSIC CIRCUITRY; SUBSTANTIA NIGRA; MIGRAINE AURA; MOVING HILL AB The superior colliculus (SC) receives a retinotopic projection of the contralateral visual field in which the representation of the central field is expanded with respect to the peripheral field. The visual projection forms a nonlinear, approximately logarithmic, map on the SC. Models of the SC commonly assume that the function defining the strength of neuronal connections within this map (the kernel) depends only on the distance between two neurons, and is thus isotropic and homogeneous. However, if the connection strength is based on the distance between two stimuli in sensory space, the kernel will be asymmetric because of the nonlinear projection onto the brain map. We show, using a model of the SC, that one consequence of these asymmetric intrinsic connections is that activity initiated at one point spreads across the map. We compare this simulated spread with the spread observed experimentally around the time of saccadic eye movements with respect to direction of spread, differing effects of local and global inhibition, and the consequences of localized inactivation on the SC map. Early studies suggested that the SC spread was caused by feedback of eye displacement during a saccade, but subsequent studies were inconsistent with this feedback hypothesis. In our new model, the spread is autonomous, resulting from intrinsic connections within the SC, and thus does not depend on eye movement feedback. Other sensory maps in the brain ( e. g., visual cortex) are also nonlinear and our analysis suggests that the consequences of asymmetric connections in those areas should be considered. C1 RIKEN, Brain Sci Inst, Lab Math Neurosci & Integrated Theoret Neurosci, Wako, Saitama, Japan. Univ Tokyo, Inst Ind Sci, Tokyo, Japan. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Nakahara, H (reprint author), RIKEN, Brain Sci Inst, Lab Integrated Theoret Neurosci, Hirosawa 2-1, Wako, Saitama, Japan. EM hn@brain.riken.jp RI Nakahara, Hiroyuki/N-5411-2015 OI Nakahara, Hiroyuki/0000-0001-6891-1175 FU Intramural NIH HHS NR 61 TC 8 Z9 8 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD AUG PY 2006 VL 96 IS 2 BP 765 EP 774 DI 10.1152/jn.01372.2005 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 062VW UT WOS:000238974700027 PM 16672297 ER PT J AU Kupersmith, MJ Heller, G Cox, TA AF Kupersmith, Mark J. Heller, Gordon Cox, Terry A. TI Magnetic resonance angiography and clinical evaluation of third nerve palsies and posterior communicating artery aneurysms SO JOURNAL OF NEUROSURGERY LA English DT Article DE posterior communicating aneurysm; third nerve palsy; magnetic resonance angiography ID UNRUPTURED INTRACRANIAL ANEURYSMS; OCULOMOTOR PALSY; MR-ANGIOGRAPHY; SUBARACHNOID HEMORRHAGE; CEREBRAL-ANGIOGRAPHY; PUPIL; PARESIS; RISK; PARALYSIS; TROCHLEAR AB Object. The authors conducted a study to determine the utility of the clinical profile and magnetic resonance (MR) angiography in evaluating patients with isolated third cranial nerve palsies or posterior communicating artery (PCoA) aneurysms. Methods. Three-dimensional time-of-flight MR angiography was per-formed in a consecutive series of patients with isolated acute third cranial nerve palsy not due to a ruptured aneurysm and in patients with unruptured PCoA aneurysms. A neuroradiologist, masked to the identities of the patients, interpreted reformatted maximum intensity projection (MIP) and source images of the PCoAs and aneurysms. The investigators assessed clinical features of oculomotor nerve dysfunction and focal head pain. Cases involving cranial third nerve palsy without aneurysms were classified as Group 1 (no case entailed catheter-based angiography), and cases involving PCoA aneurysms seen on MR angiography (42 cases confirmed by catheter-based angiography) were classified as Group 2. The mean age of the 73 patients in Group 1 was 60.1 years and that of the 45 patients in Group 2 was 59.1 years (p = 0.37). The pattern and severity of oculomotor (p = 0.61) and lid (p = 0.83) dysfunction and pain frequency (p = 0.2) were similar for the 73 patients with vasculopathy in Group 1 and the 15 symptomatic patients in Group 2. Abnormal pupils were observed in 38% of the patients in Group 1 and 80% of those in Group 2 (p = 0.016). In cases of complete external third nerve palsy, nine of 22 in Group 1 and none of four in Group 2 had normal pupil function. For all patients, source imaging showed 206 PCoAs (85%) and MIP imaging demonstrated 120 PCoAs (49%). Of 48 aneurysms (three bilateral), MIP imaging showed 44 (92%) and source imaging showed 47 (98%). Only a 2-mm aneurysm seen on catheter-based angiography was missed by MR angiography. Symptomatic aneurysms were equal or greater than 4 min in size. Conclusions. Only the presence of complete external third nerve palsy and normal pupil function allowed ischemia to be clinically distinguished from a PCoA aneurysm in a patient with isolated third nerve palsy and no subarachnoid hemorrhage. When source image MR angiography demonstrates normal findings, catheter-based angiography need not be performed in these patients, even if pupil function is abnormal. C1 Albert Einstein Coll Med, New York Eye & Ear Infirm, Roosevelt Hosp, Inst Neurol & Neurosurg,Neuroophthalmol Serv, New York, NY 10019 USA. NEI, Bethesda, MD 20892 USA. RP Kupersmith, MJ (reprint author), Albert Einstein Coll Med, New York Eye & Ear Infirm, Roosevelt Hosp, Inst Neurol & Neurosurg,Neuroophthalmol Serv, 1000 10th Ave, New York, NY 10019 USA. EM mkuper@bethisraelny.org NR 33 TC 17 Z9 18 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2006 VL 105 IS 2 BP 228 EP 234 DI 10.3171/jns.2006.105.2.228 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 070PF UT WOS:000239534400014 PM 17219827 ER PT J AU Ammerman, JM Lonser, RR Dambrosia, J Butman, JA Oldfield, EH AF Ammerman, Joshua M. Lonser, Russell R. Dambrosia, James Butman, John A. Oldfield, Edward H. TI Long-term natural history of hemangioblastomas in patients with von Hippel-Lindau disease: implications for treatment SO JOURNAL OF NEUROSURGERY LA English DT Article DE hemangioblastoma; natural history; treatment planning; von Hippel-Lindau disease ID RECEPTOR INHIBITOR SU5416; GAMMA-KNIFE RADIOSURGERY; CENTRAL-NERVOUS-SYSTEM; THERAPY; BRAIN AB Object. In the course of their lives most patients with von Hippel-Lindau (VHL) disease require treatment for several symptom-producing hemangioblastomas of the cerebellum, brainstem, or spinal cord. However, many tumors never produce symptoms and do not require treatment. Detection at an early stage of lesions that will later produce symptoms and ultimately require treatment would allow for earlier excision of hemangioblastomas of the spinal cord, brainstem, or cerebellum, and may identify cerebellar hemangioblastomas that can be treated with radiosurgery at a stage before treatment is contraindicated because of tumor size or the presence of an associated cyst. Methods. To identify features predictive of symptom development that might allow for earlier treatment of smaller, presymptomatic hemangioblastomas in patients with VHL disease, the authors reviewed and analyzed the serial clinical and imaging findings in all patients with VHL disease who were followed up at the National Institutes of Health for more than 10 years. Features predictive of symptom formation were determined by recursive partition and regression analyses. Nineteen patients (10 men and nine women; mean age 32.6 +/- 11.6 years) harboring a total of 143 hemangioblastomas were identified (mean follow-up duration 12.4 +/- 1.4 years). Hemangioblastomas were located in the cerebellum (68 hemangioblastomas, 48% of patients), brainstem (17 hemangioblastomas, 12% of patients), and spinal cord (58 hemangioblastomas, 40% of patients). Despite measurable growth in almost all hemangioblastomas (138 lesions, 97% of patients), only 58 (41% of patients) became symptomatic. Hemangioblastomas grew in a stuttering pattern. (mean growth period 13 +/- 15 months, mean quiescent period 25 +/- 19 months). Twenty-six (45%) of the hemangioblastomas that eventually produced symptoms were not among the tumors that were apparent on the initial MR imaging study. Depending on location, the hemangioblastoma size and/or tumor and cyst growth rates predicted symptom development and the need for treatment (p < 0.05). Cerebellar hemangioblastomas growing faster than 112 mm(3)/month or larger than 69 mm(3) with associated tumor and cyst growth rates greater than 14 mm(3)/month became symptomatic (100% sensitivity, 72% specificity). Brainstem hemangioblastomas larger than 245 mm(3) with growth rates greater than 0.1 mm(3)/month became symptomatic (75% sensitivity, 89% specificity). Spinal hemangioblastomas larger than 22 mm(3) became symptomatic (79% sensitivity, 94% specificity). Conclusions. Because hemangioblastomas exhibit a stuttering growth pattern, frequently remain asymptomatic, and do not require treatment for long intervals, unqualified radiographic progression is not an indication for treatment. Basing the decision to intervene in individual tumors solely on radiographic progression would have resulted in approximately four additional procedures per patient during the 10-year study period. Threshold values are presented for tumor size and/or tumor and cyst growth rates that can be used to predict symptom formation and future need for treatment. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Neurol Surg, Washington, DC 20037 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM eo10d@nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 19 TC 76 Z9 81 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2006 VL 105 IS 2 BP 248 EP 255 DI 10.3171/jns.2006.105.2.248 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 070PF UT WOS:000239534400017 PM 17219830 ER PT J AU Jarrell, ST Vortmeyer, AO Linehan, WM Oldfield, EH Lonser, RR AF Jarrell, S. Taylor Vortmeyer, Alexander O. Linehan, W. Marston Oldfield, Edward H. Lonser, Russell R. TI Metastases to hemangioblastomas in von Hippel-Lindau disease SO JOURNAL OF NEUROSURGERY LA English DT Article DE hemangioblastoma; metastasis; tumor-to-tumor metastasis; von Hippel-Lindau disease ID RENAL-CELL CARCINOMA; CENTRAL-NERVOUS-SYSTEM; OF-THE-LITERATURE; DIFFERENTIAL-DIAGNOSIS; CEREBELLAR HEMANGIOBLASTOMA; BRAIN METASTASIS; SPINAL-CORD; TUMOR; FIBRONECTIN; MANAGEMENT AB Object. Patients with hereditary cancer syndromes may be at increased risk for the development of tumor-to-tumor metastases. To gain insight into the biological nature of these lesions in the central nervous system (CNS), to determine their prevalence in a familial neoplasia syndrome, and to better define their management, the authors retrospectively examined a series of cases in which metastatic lesions developed within hemangioblastomas in patients with von Hippel-Lindau (VHL) disease. Methods. The study included all cases of VHL disease in which patients underwent resection of a CNS hemangioblastoma that contained a metastasis or were found at autopsy to have a metastasis to a hemangioblastoma between January 2002 and December 2005 at the National Institute of Neurological Disorders and Stroke (NINDS). Clinical, histopathological, imaging, and surgical and/or autopsy findings were analyzed. Metastasis to a CNS hemangioblastoma was found in six resected tumors (8% of all hemangioblastomas resected from patients with VHL disease at the NINDS during the study period) from six patients (five women, one man; mean age at surgery 42.5 years). The primary site of metastatic disease was the kidney in five patients (renal cell carcinoma) and the pancreas in one (a pancreatic neuroendocrine tumor). Only one patient had systemic metastases at the time of resection of the hemangioblastoma containing the metastasis. Neurologically, all patients had remained at baseline or were improved at last clinical follow-up examination (mean follow-up duration 16.5 months, range 3-40 months). In all cases, postoperative imaging revealed that the hemangioblastoma resection was complete, and there was no evidence of recurrence in any of the patients at the last follow up. Two patients (including one who was also in the surgical group) were found at autopsy to have CNS metastases exclusively to spinal hemangioblastomas. Conclusions. Hemangioblastomas are an early and preferred site for metastasis in VHL disease. Emerging histopathological techniques may lead to recognition of an increasing number of cases of tumor-to-hemangioblastoma metastasis. Management of cases involving tumor-to-hemangioblastoma metastases in VHL disease should be based on the histological characteristics of the primary tumor, extent of the primary disease, and completeness of the resection. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20894 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20894 USA. George Washington Univ, Med Ctr, Dept Neurosurg, Washington, DC 20037 USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20894 USA. EM lonserr@ninds.nih.gov FU Intramural NIH HHS NR 41 TC 32 Z9 33 U1 2 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD AUG PY 2006 VL 105 IS 2 BP 256 EP 263 DI 10.3171/jns.2006.105.2.256 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 070PF UT WOS:000239534400018 PM 17219831 ER PT J AU Parry, DM AF Parry, Dilys M. TI NF2 and spinal tumors SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Letter ID GENOTYPE AB Object. The authors conducted a study to examine the incidence, classification, and progression of spinal tumors in patients with neurofibromatosis Type 2 (NF2) treated at a single center, and to examine relationships with the known mutational subtypes of NF2. Methods. They performed a retrospective review of clinical records, neuroimaging studies, and genetic data obtained in 61 patients with NF2. Forty-one (67%) of 61 patients harbored one or more spinal tumors. Thirty-four patients had undergone serial spinal magnetic resonance imaging during a mean follow-up period of 52 months (range 10-103 months; median 53 months). In 16 patients there were multiple extramedullary tumors smaller than 5 mm, which raid not progress. Fourteen patients harbored at least one extramedullary tumor that was greater than 5 mm; of these, radiological progression was demonstrated or spinal tumor excision was performed during the follow-up period in eight cases (57%). Eleven patients harbored intramedullary cord tumors in addition to small and large extramedullary tumors, three (27%) of which exhibited radiological progression. In cases in which genotypes were known, protein-truncating mutations were significantly more likely to be associated with the presence of spinal tumors than in other types (p = 0.03, Fisher exact test). No associations between clinical behavior of spinal tumors and genotype, however, could be demonstrated. Conclusions. Spinal tumors in cases involving NF2 are heterogeneous in type, distribution, and behavior but larger-size tumors are more likely to progress significantly. Intramedullary tumors usually accompany multiple extramedullary tumors. In the authors' experience subtyping of the NF2 mutation has not yet influenced management. Protein-truncating mutations are associated with an increased prevalence of spinal tumors. C1 NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Parry, DM (reprint author), NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD AUG PY 2006 VL 5 IS 2 BP 179 EP 179 DI 10.3171/spi.2006.5.2.179 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 070PH UT WOS:000239534800014 PM 16925089 ER PT J AU Akhyani, N Fotheringham, J Yao, K Rashti, F Jacobson, S AF Akhyani, Nahid Fotheringham, Julie Yao, Karen Rashti, Farzin Jacobson, Steven TI Efficacy of antiviral compounds in human herpesvirus-6-infected glial cells SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE anti-viral; CNS; glial cells; HHV-6; quantitative PCR ID BONE-MARROW-TRANSPLANTATION; MULTIPLE-SCLEROSIS; HUMAN-HERPESVIRUS-6 INFECTION; HUMAN ASTROCYTES; GENE-EXPRESSION; BRAIN-TISSUE; 6 VARIANTS; T-CELLS; ENCEPHALITIS; VIRUS AB The beta-herpesvirus human herpesvirus-6 (HHV-6) is becoming increasingly recognized as an important pathogen in immunocompromised patients, particularly in post bone marrow transplant (BMT). Reactivation of latent HHV-6 resulting in encephalitis has been reported in BMT and stem cell transplant (SCT) patients. The development of HHV-6 encephalitis can be a fatal complication, the frequency of which is increasing likely due to improved diagnosis with quantitative polymerase chain reaction (PCR) of cerebrospinal fluid. There are currently no antiviral compounds approved for HHV-6, nor have any controlled clinical trials been conducted. The frequency and severity of HHV-6 encephalitis in both immunocompetent and immunocompromised patients necessitates studies on the usefulness of currently available anti-viral compounds. The authors compared the antiviral efficacy of four drugs currently used for cytomegalovirus (CMV) infection, a beta-herpesvirus sharing homology with HHV-6. In HHV-6A- and HHV-6B-infected T cells, acyclovir, ganciclovir, foscarnet, and cidofovir exhibited antiviral activity consistent with that published in other studies. In HHV-6-infected human astrocytes (U251), however, only foscarnet and cidofovir exhibited antiviral activity and this effect was restricted to infection with HHV-6 variant A. In pathological brain sections from patients with neurological disorders such as multiple sclerosis and epilepsy, HHV-6 has been localized to glial cells. Determination of antiviral activity in human glial fibrillary acidic protein (GFAP)-positive astrocytes of currently used antiviral compounds is essential for potential treatment of HHV-6 and neurological disorders. Our data highlight the necessity for further study of antiviral compound in HHV-6-infected glial cells as well as the development of more selective compounds for HHV-6. C1 NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Howard Univ, Coll Med, Washington, DC 20059 USA. RP Akhyani, N (reprint author), NINDS, Viral Immunol Sect, NIH, 10 Ctr Dr,Bldg 10 Room 5B16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 48 TC 17 Z9 18 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD AUG PY 2006 VL 12 IS 4 BP 284 EP 293 DI 10.1080/13550280600880772 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 083DE UT WOS:000240435300005 PM 16966219 ER PT J AU Wang, INE Mitroo, S Chen, FH Lu, HH Doty, SB AF Wang, I-Ning E. Mitroo, Siddarth Chen, Faye H. Lu, Helen H. Doty, Stephen B. TI Age-dependent changes in matrix composition and organization at the ligament-to-bone insertion SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE aging; insertion; fibrocartilage; mineralization ID ANTERIOR CRUCIATE LIGAMENT; MEDIAL COLLATERAL LIGAMENT; POSTNATAL-DEVELOPMENT; ATTACHMENT ZONES; PROTEIN COMP; KNEE-JOINT; X COLLAGEN; RAT KNEE; TENDON; RECONSTRUCTION AB Injuries to the anterior cruciate ligament (ACL) often occur at the ligament-to-bone insertion site; thus, an in-depth understanding of the native insertion is critical in identifying the etiology of failure and devising optimal treatment protocols for ACL injuries. The objective of this study is to conduct a systematic characterization of the ACL-to-bone interface, focusing on structural and compositional changes as a function of age. Using a bovine model, three age groups were studied: Neonatal (1-7 days old), Immature (2-6 months old), and Mature (2-5 years old). The distribution of types I, II, X collagen, decorin, cartilage oligomeric matrix protein (COMP), glycosaminoglycan (GAG), alkaline phosphatase (ALP) activity, and minerals at the ACL-to-bone insertion were examined. Additionally, cell aspect ratio, size, and distribution across the insertion were quantified. The ACL-to-bone insertion is divided into four regions: ligament, nonmineralized interface, mineralized interface, and bone. Both region-dependent and age-dependent structural and compositional changes at the insertion site were observed in this study. The interface in the skeletally immature group resembled articular cartilage, while the adult interface was similar to fibrocartilaginous tissue. Age-dependent changes in extracellular matrix composition (type X collagen, sulfated glycosaminoglycan), cellularity, ALP activity, and mineral distribution were also found. Marked differences in collagen fiber orientation between the femoral and tibial insertions were observed, and these differences became more pronounced with age. (c) 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 Columbia Univ, Dept Biomed Engn, Biomat & Interface Tissue Engn Lab, New York, NY 10027 USA. Columbia Univ, Coll Dent Med, New York, NY 10032 USA. Hosp Special Surg, Analyt Microscopy, New York, NY 10021 USA. NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Lu, HH (reprint author), Columbia Univ, Dept Biomed Engn, Biomat & Interface Tissue Engn Lab, 1210 Amsterdam Ave,351 Engn Terrace Bldg,MC 8904, New York, NY 10027 USA. EM h12052@columbia.edu FU NIAMS NIH HHS [1R21 AR052402-01A1] NR 41 TC 48 Z9 48 U1 1 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD AUG PY 2006 VL 24 IS 8 BP 1745 EP 1755 DI 10.1002/jor.20149 PG 11 WC Orthopedics SC Orthopedics GA 068HO UT WOS:000239364300018 PM 16779829 ER EF