FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Jin, MK Kang, SU Kim, SY Ryu, H Kang, DW Seo, SJ Lee, J Pearce, LV Pavlyukovets, VA Morgan, MA Tran, R Toth, A Lundberg, DJ Blumberg, PM AF Jin, Mi-Kyoung Kang, Sang-Uk Kim, Su Yeon Ryu, HyungChul Kang, Dong Wook Seo, Se Jin Lee, Jeewoo Pearce, Larry V. Pavlyukovets, Vladimir A. Morgan, Matthew A. Tran, Richard Toth, Attila Lundberg, Daniel J. Blumberg, Peter M. TI Stereospecific high-affinity TRPV1 antagonists: Chiral N-(2-benzyl-3-pivaloyloxypropyl) 2-[4-(methylsulfonylamino)phenyl]propionamide analogues SO DRUGS OF THE FUTURE LA English DT Meeting Abstract C1 Seoul Natl Univ, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea. NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JUL PY 2007 VL 32 SU A BP 47 EP 48 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 199IC UT WOS:000248688400100 ER PT J AU Tosh, DK Lee, HW Hou, XY Pei, XY Jacobson, KA Jeong, LS AF Tosh, Dilip K. Lee, Hyuk Woo Hou, Xiyan Pei, Xiaoyuan Jacobson, Kenneth A. Jeong, Lak Shin TI Structure-activity relationships of 2-chloro-N-6-substituted-4 '-thioadenosine-5 ''-dialkylamides as potent and selective human A(3) adenosine receptor antagonists SO DRUGS OF THE FUTURE LA English DT Meeting Abstract C1 Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. NIDDK, Mol Recognit Sect, NIH, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JUL PY 2007 VL 32 SU A BP 53 EP 53 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 199IC UT WOS:000248688400113 ER PT J AU Nightingale, SL Prasher, JM Simonson, S AF Nightingale, Stuart L. Prasher, Joanna M. Simonson, Stewart TI Emergency use authorization (EUA) to enable use of needed products in civilian and military emergencies, United States SO EMERGING INFECTIOUS DISEASES LA English DT Review ID DRUGS AB The US Emergency Use Authorization (EUA) is a critical new tool for medical and public health communities and is applicable for both civilian and military use. It fills the need for timely and practical medical treatment under emergency conditions and authorizes use of the best product available for treatment or prevention when the relevant product has not already been approved or approved for this specific use by the US Food and Drug Administration. The need for and genesis of the EUA, its requirements, its broad application to civilian and military populations, and its features of particular importance to physicians and public health officials are detailed. C1 US Dept Hlth & Human Serv, Washington, DC USA. RP Nightingale, SL (reprint author), NIH, Off Biotechnol Act, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA. EM nightins@od.nih.edu NR 9 TC 20 Z9 22 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JUL PY 2007 VL 13 IS 7 BP 1046 EP 1051 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 186DB UT WOS:000247758200012 PM 18214177 ER PT J AU Subburaju, S Aguilera, G AF Subburaju, Sivan Aguilera, Greti TI Vasopressin mediates mitogenic responses to adrenalectomy in the rat anterior pituitary SO ENDOCRINOLOGY LA English DT Article ID CORTICOTROPIN-RELEASING FACTOR; FOLLICULO-STELLATE CELLS; GROWTH-FACTOR; ARGININE-VASOPRESSIN; PARAVENTRICULAR NUCLEUS; REPEATED RESTRAINT; MITOTIC RESPONSE; BRATTLEBORO RATS; ACTH-SECRETION; MESSENGER-RNA AB To determine whether increased vasopressinergic activity during chronic stress or adrenalectomy mediates trophic changes in the corticotroph, we examined the effect of peripheral V1 receptor blockade in rats, using the antagonist, dGly[Phaa1, D-tyr(et), Lys, Arg] vasopressin (VP), on the number of pituitary cells taking up bromodeoxyuridine (BrdU) and cells containing immunoreactive ACTH (irACTH). Adrenalectomy significantly increased the number of BrdU- and ACTH-labeled cells at 3 and 6 d, and a much larger increase was observed at 28 d. Minipump infusion of V1 antagonist for 28 d, at doses blocking the increases in ACTH and corticosterone induced by exogenous VP, prevented the increases in BrdU incorporation, but not irACTH cells observed 28 d after adrenalectomy. Unexpectedly, colocalization of BrdU with ACTH-positive cells was minor (about three cells per pituitary section), and this was unaffected by adrenalectomy or V1 antagonist infusion. In contrast, adrenalectomy for 6 or 14 d failed to increase BrdU incorporation or irACTH cells in V1b receptor knockout mice while inducing the expected increase in wild-type mice. The data show that VP is required for pituitary mitogenesis after adrenalectomy but, at least in rats, not for increasing the number of corticotrophs. The lack of colocalization of ACTH in mitotic cells suggests that recruitment of corticotrophs during adrenalectomy occurs from undifferentiated cells. C1 NIH, NICHHD, Dev Endocrinol Branch, Sect Endocrine Physiol, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NIH, NICHHD, Dev Endocrinol Branch, Sect Endocrine Physiol, Bldg 10, Bethesda, MD 20892 USA. EM Greti_Aguilera@.nih.gov FU Intramural NIH HHS NR 68 TC 15 Z9 16 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2007 VL 148 IS 7 BP 3102 EP 3110 DI 10.1210/en.2007-0103 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179PN UT WOS:000247302300012 PM 17412807 ER PT J AU Grassadonia, A Tinari, N Fiorentino, B Nakazato, M Chung, HK Giuliani, C Napolitano, G Iacobelli, S Howcroft, TK Singer, DS Kohn, LD AF Grassadonia, Antonino Tinari, Nicola Fiorentino, Bruno Nakazato, Minoru Chung, Hyun-Kyung Giuliani, Cesidio Napolitano, Giorgio Iacobelli, Stefano Howcroft, T. Kevin Singer, Dinah S. Kohn, Leonard D. CA Consorz Interuniversitar Nazl Bion TI Upstream stimulatory factor regulates constitutive expression and hormonal suppression of the 90K (mac-2BP) protein SO ENDOCRINOLOGY LA English DT Article ID CLASS-I EXPRESSION; GROWTH-FACTOR-I; TRANSCRIPTION FACTOR USF; CYSTEINE-RICH DOMAIN; C-ASSOCIATED PROTEIN; GENE-EXPRESSION; BREAST-CANCER; THYROID-CELLS; MONOCLONAL-ANTIBODY; RECEPTOR GENE AB We previously reported that hormones important for the normal growth and function of FRTL-5 rat thyroid cells, TSH, or its cAMP signal plus insulin or IGF-I, could transcriptionally suppress constitutive and gamma-interferon (IFN)-increased synthesis of the 90 K protein ( also known as Mac-2BP). Here we cloned the 5'-flanking region of the rat 90K gene and identified a minimal promoter containing an interferon response element and a consensus E-box or upstream stimulator factor (USF) binding site, which are highly conserved in both the human and murine genes. We show that suppression of constitutive and gamma-IFN-increased 90 K gene expression by TSH/cAMP plus insulin/IGF-I depends on the ability of the hormones to decrease the binding of USF to the E-box, located upstream of the interferon response element. This site is required for the constitutive expression of the 90 K gene. Transfection with USF1 and USF2 cDNAs increases constitutive promoter activity, attenuates the ability of TSH/cAMP plus insulin/IGF-I to decrease constitutive or gamma-IFN-increased 90 K gene expression but does not abrogate the ability of gamma-IFN itself to increase 90 K gene expression. C1 NIDDKD, Cell Regulat Sect, Metab Dis Branch, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ G DAnnunzio Fdn, I-66100 Chieti, Italy. Ohio Univ, Coll Osteopath Med, Dept Biomed Sci, Edison Biotechnol Inst, Athens, OH 45701 USA. RP Grassadonia, A (reprint author), Ctr Serv Biomed, Dipartimento Oncol & Neurosci, Sez Oncol Med, Via Vestini, I-66100 Chieti, Italy. NR 54 TC 3 Z9 3 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2007 VL 148 IS 7 BP 3507 EP 3517 DI 10.1210/en.2007-0024 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 179PN UT WOS:000247302300054 PM 17446190 ER PT J AU Zhang, LP Rothman, N Li, GL Guo, WH Yang, W Hubbard, AE Hayes, RB Yin, SN Lu, W Smith, MT AF Zhang, Luoping Rothman, Nathaniel Li, Guilan Guo, Weihong Yang, Wei Hubbard, Alan E. Hayes, Richard B. Yin, Songnian Lu, Wei Smith, Martyn T. TI Aberrations in chromosomes associated with lymphoma and therapy-related leukemia in benzene-exposed workers SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE benzene; biomarkers; chromosomal rearrangements; leukemia; lymphoma ID DNA TOPOISOMERASE-II; NON-HODGKIN-LYMPHOMA; ACUTE PROMYELOCYTIC LEUKEMIA; IN-SITU HYBRIDIZATION; OCCUPATIONAL-EXPOSURE; ORGANIC-SOLVENTS; POTENTIAL MECHANISM; CHINESE WORKERS; HYDROQUINONE; LEUKEMOGENESIS AB Epidemiological studies show that benzene exposure is associated with an increased incidence of leukemia and perhaps lymphoma. Chromosomal rearrangements are common in these hematopoietic diseases. Translocation 1(14; 18), the long-arm deletion of chromosome 6 [del(6q)], and trisomy 12 are frequently observed in lymphoma patients. Rearrangements of the MLL gene located on chromosome 11 q23, such as t(4;11) and t(6;11), are common in therapy-related leukemias resulting from treatment with topoisomerase 11 inhibiting drugs. To examine numerical and structural changes in these chromosomes (2, 4, 6, 11, 12, 14, and 18), fluorescence in situ hybridization I (FISH) was employed on metaphase spreads from workers exposed to benzene (n = 43) and 1 matched controls (n = 44) from Shanghai, China. Aneuploicly (both monosomy and trisomy) of all seven chromosomes was increased by benzene exposure. Benzene also induced del(6q) in a dose-dependent manner (P-trend = 0.0002). Interestingly, translocations between chromosomes 14 and 18, t(14;18), known to be associated with follicular non-Hodgkin lymphoma, were increased in the highly exposed workers (P < 0.001). On the other hand, translocations between chromosome 11 and other partner chromosomes that are found in therapy-induced leukemias were not increased. These data add weight to the notion that benzene can induce t(14;18) and del(6q) found in lymphoma, but do not support the idea that benzene induces t(4;11 or t(6;11). However, they do not rule out the possibility that other rearrangements of the VILL gene at chromosome 11q23 may be induced by benzene. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. CDC, Natl Inst Occupat Hlth & Dis Control, Beijing, Peoples R China. Shanghai Ctr Dis Control, Shanghai, Peoples R China. RP Zhang, LP (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall, Berkeley, CA 94720 USA. EM luoping@berkeley.edu OI Hayes, Richard/0000-0002-0918-661X FU NIEHS NIH HHS [P42 ES04705, P30 ES01896, R01 ES06721] NR 52 TC 34 Z9 34 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2007 VL 48 IS 6 BP 467 EP 474 DI 10.1002/em.20306 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 196SX UT WOS:000248503400006 PM 17584886 ER PT J AU Fan, JH Wilson, PF Wong, HK Urbin, SS Thompson, LH Wilson, DM AF Fan, Jinshui Wilson, Paul F. Wong, Heng-Kuan Urbin, Salustra S. Thompson, Larry H. Wilson, David M., III TI XRCC1 down-regulation in human cells leads to DNA-damaging agent hypersensitivity, elevated sister chromatid exchange, and reduced survival of BRCA2 mutant cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE X-ray repair cross-complementing gene 1; DNA base excision repair; NHF1-hTERT; CAPAN-1 ID STRAND-BREAK REPAIR; BASE EXCISION-REPAIR; LIGASE-III; POLY(ADP-RIBOSE) POLYMERASE; CHROMOSOME INSTABILITY; CANCER; STABILITY; ROLES; POLYMORPHISMS; SENSITIVITY AB Previous studies using rodent cells indicate that a deficiency in XRCC1 results in reduced single-strand break repair, increased sensitivity to DNA-damaging agents, and elevated levels of sister chromatid exchange (SCE). Epidemiological studies have suggested an association of certain human XRCC1 polymorphisms with genetic instability and cancer susceptibility. However, investigations on the molecular functions of XRCC1 in human cells are limited. To determine the contributions of this nonenzymatic scaffold protein, we suppressed XRCC1 levels in several human cell lines using small interfering RNA (siRNA) technology. We report that XRCC1 down-regulation in HeLa cells leads to a concomitant decrease in the DNA ligase 3 protein level and an impaired nick ligation capacity. In addition, depletion of XRCC1 resulted in a significantly increased sensitivity to the alkylating agent methyl methanesulfonate and the thymidine base analog 5-hydroxymethyl-2'-deoxyuridine, a slightly increased sensitivity to ethyl methanesulfonate, and 1,3-bis(2-chloroethyl)1-nitrosourea, and no change in the response to camptothecin. We also discovered that a 70-80% reduction in XRCC1 protein leads to an elevated level of SCE in both HeLa cells and normal human fibroblasts, but does not affect chromosome aberrations in the diploid fibroblasts. Last, XRCC1 siRNA transfection led to an similar to 40% decrease in the survival of BRCA2-deficient cells, supporting a model whereby the accumulation of unrepaired SSBs leads to the accumulation of cytotoxic DNA double strand breaks following replication fork collapse in cells defective in homologous recombination. C1 NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. Lawrence Livermore Natl Lab, Chem Mat & Life Sci Direct, Livermore, CA USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA11256] NR 58 TC 19 Z9 20 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2007 VL 48 IS 6 BP 491 EP 500 DI 10.1002/em.20312 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 196SX UT WOS:000248503400009 PM 17603793 ER PT J AU Patterson, RM Noga, E Germolec, D AF Patterson, Rachel M. Noga, Edward Germolec, Dori TI Lack of evidence for contact sensitization by Pfiesteria extract SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergic contact dermatitis; contact irritant dermatitis; cytokines; delayed-type hypersensitivity; keratinocytes; Pfiesteria sensitization ID LYMPH-NODE ASSAY; ENVIRONMENTAL EXPOSURE; ESTUARINE WATERS; FISH; PISCICIDA; DINOFLAGELLATE; RATS; HEALTH; TOXIN; IMPAIRMENT AB BACKGROUND: Members of the estuarine dinoflagellate genus Pfiesteria are reported to have been responsible for massive fish kills in the southeastern United States. Some reports suggest that exposure to waters having Pfiesteria blooms or occupation-related exposure might result in Pfiesteria-induced dermal irritation and inflammation. Although the toxin has not been isolated and purified, the original data suggested both hydrophilic and hydrophobic toxic components. Some investigators propose that dermonecrotic properties are associated with a hydrophobic fraction. OBJECTIVES: A bioactive C18-bound putative toxin (CPE) extracted from Pfiesteria-laden aquarium water during active fish-killing conditions was examined in the present study to evaluate its potential to produce inflammation and dermal sensitization and to determine whether the inflammation and dermatitis reported in early human exposure studies were allergic or irritant in nature. RESULTS: This fraction was cytotoxic to mouse Neuro-2A cells and primary human epidermal keratinocytes (NHEK) at a concentration of 1 mg/mL. Balb/C mice exposed to 50-200% CPE by skin painting exhibited a 6-10% increase in ear swelling relative to vehicle-treated mice in a primary irritancy assay. There was no increase in lymph node cell proliferation as measured using the local lymph node assay. Exposure to CPE in culture up-regulated interleukin-8 in NHEK, whereas granulocyte macrophage-colony-stimulating factor and tumor necrosis factor a were only minimally altered. CONCLUSIONS: This study suggests that CPE is cytotoxic to keratinocytes in culture at high concentrations and that it induces mild, localized irritation but not dermal sensitization. C1 NIEHS, Toxicol Operat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Clin Sci, Coll Vet Med, Raleigh, NC 27695 USA. RP Germolec, D (reprint author), NIEHS, Toxicol Operat Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD EC-03, Res Triangle Pk, NC 27709 USA. EM germolec@niehs.nih.gov FU Intramural NIH HHS; PHS HHS [273-99-C-0154] NR 41 TC 0 Z9 0 U1 0 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 JUL PY 2007 VL 115 IS 7 BP 1023 EP 1028 DI 10.1289/ehp.9559 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 185MW UT WOS:000247716100027 PM 17637917 ER PT J AU Qu, W Ke, HN Pi, JB Broderick, D French, JE Webber, MM Waalkes, MP AF Qu, Wei Ke, Hengning Pi, Jingbo Broderick, Daniel French, John E. Webber, Mukta M. Waalkes, Michael P. TI Acquisition of apoptotic resistance in cadmium-transformed human prostate epithelial cells: Bcl-2 overexpression blocks the activation of JNK signal transduction pathway SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE apoptosis; Bcl-2; cadmium; JNK; malignant transformation ID N-TERMINAL KINASE; INDUCED MALIGNANT-TRANSFORMATION; DEATH PATHWAY; CYCLE ENTRY; DNA-DAMAGE; PROTEIN; CANCER; JUN; EXPRESSION; INHIBITOR AB BACKGROUND: We have recently shown that cadmium can induce malignant transformation of the human prostate epithelial cell line (RWPE-1) and that these cadmium-transformed prostate epithelial (CTPE) cells acquire apoptotic resistance concurrently with malignant phenotype. OBJECTIVE: The present study was designed to define the mechanism of acquired apoptotic resistance in CTPE cells. METHODS: Various molecular events associated with apoptosis were assessed in control and CTPE cells that were obtained after 8 weeks of continuous cadmium exposure. RESULTS: Compared with control, CTPE cells showed a generalized resistance to apoptosis induced by cadmium, cisplatin, or etoposide. Signal-regulated mitogen-activated protein kinases, extracellular signal-regulated kinases 1 and 2, c-Jun N-terminal kinases (JNK1 and JNK2), and p38 were phosphorylated in a cadmium concentration-dependent fashion in CTPE and control cells. However, phosphorylated JNK1/2 levels and JNK. kinase activity were much lower in CTPE cells. The pro-apoptotic gene Bax showed lower transcript and protein levels, whereas the anti-apoptotic gene Bcl-2 showed higher levels in CTPE cells. The ratio of Bcl-2/Bax, a key determinant in apoptotic commitment, increased more than 4-fold in CTPE cells. In Bcl-2-transfected PT-67 cells, phosphorylated JNK1/2 levels were much lower after apoptogenic stimulus, and apoptosis induced by cadmium or etoposide was reduced compared with control. Mutation of tyrosine to serine at the 21st amino acid of the Bcl-2 protein BH4 domain resulted in a loss both of suppression of JNK1/2 phosphorylation and its anti-apoptotic function. CONCLUSIONS: CTPE cells become resistant to apoptosis during malignant transformation, and disruption of the JNK pathway and Bcl-2 overexpression play important roles in this resistance. Bcl-2 BH4 domain is required for modulating JNK phosphorylation and anti-apoptotic function. C1 NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, NCI, Comparat Carcinogenesis Lab, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS NR 41 TC 19 Z9 21 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 JUL PY 2007 VL 115 IS 7 BP 1094 EP 1100 DI 10.1289/ehp.10075 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 185MW UT WOS:000247716100038 PM 17637928 ER PT J AU Liu, J Cheng, ML Yang, Q Shan, KR Shen, J Zhou, YS Zhang, XJ Dill, AL Waalkes, MP AF Liu, Jie Cheng, Min-Liang Yang, Qin Shan, Ke-Ren Shen, Jun Zhou, Yushu Zhang, Xinjiang Dill, Anna L. Waalkes, Michael P. TI Blood metallothionein transcript as a biomarker for metal sensitivity: Low blood metallothionein transcripts in arsenicosis patients from Guizhou, China SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE arsenicosis patients; biomarker; blood; buccal cells; metallothionein ID ISOFORM GENE-EXPRESSION; DOUBLE KNOCKOUT MICE; HEPATOCELLULAR-CARCINOMA; DRINKING-WATER; MESSENGER-RNA; HUMAN-LIVER; NULL MICE; CADMIUM; ZINC; CELLS AB BACKGROUND: Because metallothionein (MT) is a metal-binding protein that protects against metal intoxication, it could be a biomarker for individual sensitivity to metal toxicity. OBJECTIVE: We assessed the use of bloodborne MT transcript as a reflection of tissue MT levels and examined the potential role of MT in arsenic toxicity in an environmentally exposed human population. METHOD: Rodents were treated with zinc or nonmetallic MT inducers for 4 days, and the blood and tissues were collected for MT transcript analysis by real-time reverse transcriptase-polymerase chain reaction and MT protein determination by the cadmium-hemoglobin assay. Blood and buccal cell samples were collected from arsenicosis patients and healthy subjects residing in Guizhou, China, and total RNA was isolated for MT transcript analysis. RESULTS: There was a positive correlation between blood MT-1 and MT-2 transcripts and corresponding hepatic or renal MT transcript levels in rats and mice. Furthermore, there was a positive correlation between blood MT-1 and MT-2 transcript and tissue MT protein levels in these animals. A positive correlation also occurred between human blood MTand buccal cell MT transcript levels. MT-1A and MT-2A were the major isoform transcripts in human blood and buccal cells, and significantly lower MT levels were seen in arsenicosis patients compared with healthy subjects. CONCLUSIONS: Blood MT transcript appears to be a useful biomarker of tissue MT levels. Arsenicosis patients in Guizhou show significantly lower MT transcript levels in blood, which may have predisposed this population to arsenic intoxication. C1 NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect,Natl Inst Hlth,Dept H, Res Triangle Pk, NC 27709 USA. Guiyang Med Coll, Guiyang, Peoples R China. SW Prefecture Ctr Dis Control, Xingyi, Guizhou, Peoples R China. Zunyi Med Coll, Zunyi, Peoples R China. RP Waalkes, MP (reprint author), NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect,Natl Inst Hlth,Dept H, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU Intramural NIH HHS NR 45 TC 43 Z9 48 U1 0 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2007 VL 115 IS 7 BP 1101 EP 1106 DI 10.1289/ehp.10035 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 185MW UT WOS:000247716100039 PM 17637929 ER PT J AU Zhou, HB Chen, JW Rissanen, TH Korrick, SA Hu, H Salonen, JT Longnecker, MP AF Zhou, Haibo Chen, Jianwei Rissanen, Tiina H. Korrick, Susan A. Hu, Howard Salonen, Jukka T. Longnecker, Matthew P. TI Outcome-dependent sampling - An efficient sampling and inference procedure for studies with a continuous outcome SO EPIDEMIOLOGY LA English DT Article ID EMPIRICAL LIKELIHOOD METHOD; 2-STAGE CASE-CONTROL; LOGISTIC-REGRESSION; DISEASE; ATHEROSCLEROSIS; EXPOSURE; DESIGNS; MODELS AB To characterize the relation between an exposure and a continuous outcome, the sampling of subjects can be done much as it is in a case-control study, such that the sample is enriched with subjects who are especially informative. In an outcome-dependent sampling design, observations made on a judiciously chosen subset of the base population can provide nearly the same statistical efficiency as observing the entire base population. Reaping the benefits of such sampling, however, requires use of an analysis that accounts for the outcome-dependent sampling. In this report, we examine the statistical efficiency of a plain random sample analyzed with standard methods, compared with that of data collected with outcome-dependent sampling and analyzed by either of 2 appropriate methods. In addition, 3 real datasets were analyzed using an outcome-dependent sampling approach. The results demonstrate the improved statistical efficiency obtained by using an outcome-dependent sampling, and its applicability in a wide range of settings. This design, coupled with an appropriate analysis, offers a cost-efficient approach to studying the determinants of a continuous outcome. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. Univ Rochester, Med Ctr, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. Univ Kuopio, Res Inst Publ Hlth & Clin Nutr, FIN-70211 Kuopio, Finland. Harvard Univ, Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Zhou, HB (reprint author), Univ N Carolina, Dept Biostat, CB 7420, Chapel Hill, NC 27599 USA. EM zhou@bios.unc.edu OI Longnecker, Matthew/0000-0001-6073-5322 FU Intramural NIH HHS [Z01 ES049016-12]; NCI NIH HHS [R01 CA079949, R01 CA79949] NR 26 TC 26 Z9 26 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2007 VL 18 IS 4 BP 461 EP 468 DI 10.1097/EDE.0b013e31806462d3 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 179ZN UT WOS:000247329500011 PM 17568219 ER PT J AU Saldana, TM Basso, O Darden, R Sandler, DP AF Saldana, Tina M. Basso, Olga Darden, Rebecca Sandler, Dale P. TI Carbonated beverages and chronic kidney disease SO EPIDEMIOLOGY LA English DT Article ID RENAL-FAILURE; COLA CONSUMPTION; RISK-FACTORS; NEPHROCALCINOSIS; PHOSPHORUS; DIET; STONES; WOMEN; RATS AB Background: Carbonated beverage consumption has been linked with diabetes, hypertension, and kidney stones, all risk factors for chronic kidney disease. Cola beverages, in particular, contain phosphoric acid and have been associated with urinary changes that promote kidney stones. Methods: We examined the relationship between carbonated beverages (including cola) and chronic kidney disease, using data from 465 patients with newly diagnosed chronic kidney disease and 467 community controls recruited in North Carolina between 1980 and 1982. Results: Drinking 2 or more colas per day was associated with increased risk of chronic kidney disease (adjusted odds ratio = 2.3; 95% confidence interval = 1.4-3.7). Results were the same for regular colas (2.1; 1.3-3.4) and artificially sweetened colas (2.1; 0.7-2.5). Noncola carbonated beverages were not associated with chronic kidney disease (0.94; 0.4-2.2). Conclusions: These preliminary results suggest that cola consumption may increase the risk of chronic kidney disease. C1 NIEHS, Epidemiol Branch, DHHS, NIH, Res Triangle Pk, NC 27709 USA. Westat Corp, Durham, NC USA. RP Sandler, DP (reprint author), NIEHS, Epidemiol Branch, DHHS, NIH, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM sandler@niehs.nih.gov RI Basso, Olga/E-5384-2010; OI Basso, Olga/0000-0001-9298-4921; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS [Z01 ES049028-11] NR 30 TC 28 Z9 30 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2007 VL 18 IS 4 BP 501 EP 506 DI 10.1097/EDE.0b013e3180646338 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 179ZN UT WOS:000247329500017 PM 17525693 ER PT J AU Cui, L Miao, J Furuya, T Li, XY Su, XZ Cui, LW AF Cui, Long Miao, Jun Furuya, Tetsuya Li, Xinyi Su, Xin-Zhuan Cui, Liwang TI MCN5-Mediated histone H3 acetylation plays a key role in gene expression in Plasmodium falciparum SO EUKARYOTIC CELL LA English DT Article ID MUTUALLY EXCLUSIVE EXPRESSION; DNA-POLYMERASE-DELTA; VIRULENCE GENES; ANTIGENIC VARIATION; MALARIA PARASITES; LYSINE METHYLATION; LIFE-CYCLE; GENOME; TRANSCRIPTION; CHROMATIN AB Histone acetylation, regulated by the opposing actions of histone acetyltransferases (RATs) and deacetylases, is an important epigenetic mechanism in eukaryotic transcription. Although an acetyltransferase (PfGCN5) has been shown to preferentially acetylate histone H3 at K9 and K14 in Plasmodium falciparum, the scale of histone acetylation in the parasite genome and its role in transcriptional activation are essentially unknown. Using chromatin immunoprecipitation (ChIP) and DNA microarray, we mapped the global distribution of PfGCN5, histone H3K9 acetylation (H3K9ac) and trimethylation (H3K9m3) in the P. fakiparum genome. While the chromosomal distributions of H3K9ac and PfGCN5 were similar, they are radically different from that of H3K9m3. In addition, there was a positive, though weak correlation between relative occupancy of H3K9ac on individual genes and the levels of gene expression, which was inversely proportional to the distance of array elements from the putative translational start codons. In contrast, H3K9m3 was negatively correlated with gene expression. Furthermore, detailed mapping of H3K9ac for selected genes using ChIP and real-time PCR in three erythrocytic stages detected stage-specific peak H3K9ac enrichment at the putative transcriptional initiation sites, corresponding to stage-specific expression of these genes. These data are consistent with H3K9ac and H3K9m3 as epigenetic markers of active and silent genes, respectively. We also showed that treatment with a PfGCN5 inhibitor led to reduced promoter H3K9ac and gene expression. Collectively, these results suggest that PfGCN5 is recruited to the promoter regions of genes to mediate histone acetylation and activate gene expression in P. falciparum. C1 Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. EM luc2@psu.edu RI Miao, Jun/F-5340-2010; li, xinyi/D-5403-2009; Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013; OI li, xinyi/0000-0001-8791-2931; Furuya, Tetsuya/0000-0003-3979-7072; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS; NIAID NIH HHS [AI064553, R01 AI064553] NR 58 TC 57 Z9 59 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD JUL PY 2007 VL 6 IS 7 BP 1219 EP 1227 DI 10.1128/EC.00062-07 PG 9 WC Microbiology; Mycology SC Microbiology; Mycology GA 191LQ UT WOS:000248133100015 PM 17449656 ER PT J AU Healey, JS Hallstrom, AP Kuck, KH Nair, G Schron, EP Roberts, RS Morillo, CA Connolly, SJ AF Healey, Jeffrey S. Hallstrom, Al. P. Kuck, Karl-Heinz Nair, Girish Schron, Eleanor P. Roberts, Robin S. Morillo, Carlos A. Connolly, Stuart J. TI Role of the implantable defibrillator among elderly patients with a history of life-threatening ventricular arrhythmias SO EUROPEAN HEART JOURNAL LA English DT Article DE implantable defibrillator; ventricular tachycardia; cardiac arrest; mortality; elderly ID ANTIARRHYTHMIC-DRUG THERAPY; CARDIOVERTER-DEFIBRILLATOR; HEART-FAILURE; CARDIAC-RESYNCHRONIZATION; SECONDARY PREVENTION; AMIODARONE; EFFICACY; CIDS AB Aims The implantable defibrillator (ICD) reduces arrhythmic and all-cause mortality in patients with a history of life-threatening ventricular arrhythmias. However, its effectiveness in elderly patients is uncertain, given their competing risk of non-arrhythmic death. Methods and results Individual patient data from all three secondary prevention trials comparing the ICD to amiodarone were pooled. Patients were divided into two groups based on age <75 and >= 75 years. Patient characteristics were reported and the effect of the ICD on ali-cause mortality and arrhythmic death was determined for each group. The effect of age on these outcomes was determined by evaluating the interaction term (age-treatment). A total of 1866 patients were included in this analysis. Their mean age was 63.7 +/- 10.4 years (intra-quartile range 58-71 years). There were 252 patients >= 75 years old (13.5% of total). Patients >= 75 years old had a similar left ventricular (W) ejection fraction (EF)(32.6 +/- 13.7 vs. 33.8 +/- 14.9%, P = 0.20) and baseline prevalence of NYHA class 3 or 4 heart (12.3 vs. 11.8%, P = 0.38) failure as younger patients, but were less likely to have ventricular fibrillation as their presenting arrhythmia (39 vs. 53%. P = 0.0001). Over a mean follow-up of 2.3 years, older patients were more likely to die of non-arrhythmic death (8.74% per year vs. 3.96% per year, P = 0.001) and arrhythmic death (6.73% per year vs. 3.84% per year, P = 0.03). The ICD significantly reduced all-cause and arrhythmic death in patients <75 years old (ail-cause death HR = 0.69, 95% Cl: 0.56-0.85, P < 0.0001; arrhythmic death HR = 0.44, 95% Cl: 0.32-0.62, P < 0.0001), but not in patients >= 75 years old(all-cause death HR = 1.06, 95% Cl: 0.69-1.64, P = 0.79; arrhythmic death HR = 0.90, 95% Cl: 0.42-1.95, P = 0.79). The interaction between age >= 75 and ICD use was of borderline significance in each case (P = 0. 09 and P = 0. 11, respectively). Conclusion Elderly patients with a history of life-threatening ventricular arrhythmias have a high incidence of non-arrhythmic death. In these patients, the ICD may not afford the same survival advantage over arniodarone that is seen in younger patients. ICD therapy should not be withheld based on age alone; however, physicians should carefully consider the risk of non-arrhythmic death among elderly patients when selecting the appropriate therapy for an individual. C1 McMaster Univ, Hamilton Hlth Sci Gen Site, Hamilton, ON L8L 2X2, Canada. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Allgemeines Krankenhaus St Georg, Hamburg, Germany. NHLBI, Bethesda, MD 20892 USA. McMaster Univ, Henderson Res Grp, Hamilton, ON, Canada. RP Healey, JS (reprint author), McMaster Univ, Hamilton Hlth Sci Gen Site, 237 Barton St,E Amilton, Hamilton, ON L8L 2X2, Canada. EM healey@hhsc.ca NR 20 TC 78 Z9 79 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD JUL PY 2007 VL 28 IS 14 BP 1746 EP 1749 DI 10.1093/eurheartj/ehl438 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 199YL UT WOS:000248731000018 PM 17283003 ER PT J AU Garcia-Closas, R Gaycia-Closas, M Kogevinas, M Malats, N Silverman, D Serra, C Taydon, A Carrato, A Castano-Vinyals, G Dosemeci, M Moore, L Rothman, N Sinha, R AF Garcia-Closas, Reina Gaycia-Closas, Montserrat Kogevinas, Manolis Malats, Nuria Silverman, Debra Serra, Consol Taydon, Adonina Carrato, Alfredo Castano-Vinyals, Gemma Dosemeci, Mustafa Moore, Lee Rothman, Nathaniel Sinha, Rashmi TI Food, nutrient and heterocyclic amine intake and the risk of bladder cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE diet; heterocyclic amines; bladder cancer; case-control study; Spain polymorphisms ID VITAMIN-C; UROTHELIAL CANCER; FRUIT CONSUMPTION; US MEN; CAROTENOIDS; VEGETABLES; SMOKING; COHORT; DIET; CARCINOGENESIS AB Fruit and vegetable intake has been linked to bladder cancer risk; however, evidence for other foods or specific dietary factors is inconclusive. The association between diet and bladder cancer risk was evaluated among 912 incident bladder cancer cases and 873 controls in Spain. Data were consistent with a reduced bladder cancer risk associated with high fruit intake; however, the association was significant only among current smokers (OR (95% Cl) for 5th versus 1st quintile: 0.5 (0.3-0.9), p trend = 0.009). Evaluation of food subgroups showed significant inverse associations with high intakes of berries, Liliaceae vegetables and yellow-orange vegetables. The latter association was stronger among individuals with the GSTM1 present than the null genotype (0.4 (0.2, 0.7) and 0.9 (0.6, 1.3), respectively; p for interaction = 0.04). Meat or fish intake, their cooking methods or level of doneness, or heterocyclic amine intakes were not significantly associated with risk. Intake of folate, other B-vitamins (B12, B6, B2) and retinol was also associated with a reduced risk, the strongest associations being for vitamin B6 (0.6 (0.4, 0.8) p trend = 0.0006) and retinol (0.6 (0.4-0.9) p trend = 0.004). Our findings indicate that fruit and vegetable intake, as well as B-vitamin and retinol intake might be associated with a reduced bladder cancer risk. (c) 2007 Elsevier Ltd. All rights reserved. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. Univ Hosp Canary Isl, Res Unit, Tenerife, Spain. IMIM, Resp & Environm Hlth Res Unit, Barcelona, Spain. Univ Pompeu Fabra, Barcelona, Spain. Univ Oviedo, Oviedo, Spain. Hosp Gen Elche, Elche, Spain. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Gaycia-Closas, M (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,6120 Execut Blvd, Rockville, MD 20892 USA. EM montse@nih.gov RI Serra, C/E-6879-2014; Garcia-Closas, Montserrat /F-3871-2015; Sinha, Rashmi/G-7446-2015; Kogevinas, Manolis/C-3918-2017; OI Serra, C/0000-0001-8337-8356; Garcia-Closas, Montserrat /0000-0003-1033-2650; Sinha, Rashmi/0000-0002-2466-7462; Castano-Vinyals, Gemma/0000-0003-4468-1816; Malats, Nuria/0000-0003-2538-3784 FU Intramural NIH HHS NR 45 TC 55 Z9 56 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2007 VL 43 IS 11 BP 1731 EP 1740 DI 10.1016/j.ejca.2007.05.007 PG 10 WC Oncology SC Oncology GA 206QN UT WOS:000249198100022 PM 17596928 ER PT J AU Sabado, RL Babcock, E Kavanagh, DG Tjomsland, V Walker, BD Lifson, JD Bhardwaj, N Larsson, M AF Sabado, Rachel L. Babcock, Ethan Kavanagh, Daniel G. Tjomsland, Veronica Walker, Bruce D. Lifson, Jeffrey D. Bhardwaj, Nina Larsson, Marie TI Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen pathway; antigen presentation; antigen processing; dendritic cells; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR-MEDIATED UPTAKE; IMMUNOGLOBULIN G1 B12; CD8 T-CELLS; DC-SIGN; MANNOSE RECEPTOR; INTRAVAGINAL INOCULATION; CROSS-PRESENTATION; RHESUS MACAQUES; TYPE-1 GP120 AB The outcome following HIV infection depends on the nature and durability of the HIV-specific T cell response induced initially. The activation of protective T cell responses depends upon dendritic cells (DC), antigen-presenting cells which have the capacity to process and present viral antigens. DC pulsed with aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune responses and promote virologic control in chronically HIV-1-infected subjects. To gain an understanding of this phenomenon, we characterized the steps involved in the presentation of antigens derived from aldrithiol-2-treated vs. infectious HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C-type lectins expressed by the DC. Inhibitor studies showed that presentation on MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner, both at the cell surface and within endosomes, and access to the classical endosomal processing pathway. MHC class II presentation of HIV-associated antigens was dependent on active endocytosis, probably receptor-mediated, and subsequent degradation of virions in acidified endosomes in the DC. Our study brings forth new facts regarding the binding, uptake, and processing of chemically inactivated virions leading to efficient antigen presentation and should aid in the design of more effective HIV vaccines. C1 Linkoping Univ, S-58185 Linkoping, Sweden. NYU, Sch Med, Dept Pathol & Med, New York, NY USA. Massachusetts Gen Hosp, Partner AIDS Res Ctr, Charlestown, MA USA. Howard Hughes Med Inst, Chevy Chase, MD USA. NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21701 USA. RP Larsson, M (reprint author), Linkoping Univ, S-58185 Linkoping, Sweden. EM maria@imk.liu.se FU NCI NIH HHS [N01 CO12400]; NIAID NIH HHS [AI55274, AI61684, F32 AI058457-03, F32 AI058457, AI57127, AI52731, AI44628] NR 67 TC 28 Z9 28 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2007 VL 37 IS 7 BP 1752 EP 1763 DI 10.1002/eji.200636981 PG 12 WC Immunology SC Immunology GA 187DS UT WOS:000247828200008 PM 17534864 ER PT J AU Min, B Thornton, A Caucheteux, SM Younes, SA Oh, K Hu-Li, J Paul, WE AF Min, Booki Thornton, Angela Caucheteux, Stephan M. Younes, Souheil-Antoine Oh, Keunhee Hu-Li, Jane Paul, William E. TI Gut flora antigens are not important in the maintenance of regulatory T cell heterogeneity and homeostasis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE BrdU; dynamics; germ-free; homeostasis; regulatory T cells ID GERM-FREE MICE; TRANSCRIPTION FACTOR FOXP3; ORAL TOLERANCE INDUCTION; CUTTING EDGE; CD25(+); EXPANSION; PROLIFERATION; ACTIVATION; EXPRESSION; BACTERIA AB CD25(+) regulatory T cells (Treg) are a heterogeneous population that exists as CD44(low) and CD44(high) cells. Here we report that while both CD44(low) and CD44(high) Treg are anergic and express similar levels of Foxp3, CD44(high) Treg are highly proliferative in vivo and are more potent suppressors in vitro than CD44(low) Treg. From analysis of the properties of Treg derived from germ-free mice, it was concluded that peptide antigens derived from intestinal microorganisms are not essential for the generation, in vivo proliferation or suppressive activity of Treg. Our results suggest that gut flora antigens play little or no role in the heterogeneity and homeostatic regulation of Treg. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol NB30, Cleveland, OH 44195 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Min, B (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol NB30, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM minb@ccf.org RI younes, souheil-antoine/G-4503-2014 OI younes, souheil-antoine/0000-0003-2186-7140 FU Intramural NIH HHS NR 30 TC 50 Z9 50 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2007 VL 37 IS 7 BP 1916 EP 1923 DI 10.1002/eji.200737236 PG 8 WC Immunology SC Immunology GA 187DS UT WOS:000247828200023 PM 17549737 ER PT J AU Blum, A Kryuger, K Eizenberg, MM Tatour, S Vigder, F Laster, Z Front, E AF Blum, Arnon Kryuger, Konstantin Eizenberg, Michal Mashiach Tatour, Sameh Vigder, Fina Laster, Zvi Front, Eran TI Periodontal care may improve endothelial function SO EUROPEAN JOURNAL OF INTERNAL MEDICINE LA English DT Article DE endothelial function; periodontitis; atherosclerosis ID ATHEROSCLEROSIS; DISEASE; RISK AB Background: Periodontitis is a chronic, infectious, insidious disease of the tooth-supporting structures that causes a general inflammatory response. The aims of this study were to determine whether periodontitis is associated with endothelial dysfunction leading to cardiovascular events and whether proper management of periodontal disease would improve endothelial function and prevent cardiovascular events in the future. Methods: Twenty-two patients (12 women, 10 men; 40 +/- 5 years old) took part in the study. All had severe periodontitis (without systemic disorders) and were all treated conservatively. Thirteen patients returned for a second visit after 3 months of treatment. Endothelial function and periodontal status were evaluated on entry into the study and 3 months following treatment. Ten age-matched, healthy volunteers without periodontal disease served as the control group. Results: There was a significant difference between the patient group and the healthy controls: FMD% 4.12 +/- 3.96 vs. 16.60 +/- 7.86% (p=0.0000). Periodontitis improved significantly in all 13 patients who completed 3 months of treatment, and their endothelial function improved as well: FMD% 4.12 +/- 3.96% vs. 11.12 +/- 7.22% (p=0.007). No difference was found in FID% before and after 3 months of treatment: 20.97 +/- 10.66% vs.17.94 +/- 6.23% (p=NS). Conclusions: Periodontitis may be an insidious cause of endothelial dysfunction and cardiovascular events. Treating periodontitis can improve endothelial function and be an important preventive tool for cardiovascular disease. (c) 2007 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. C1 NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. Baruch Padeh Poriya Med Ctr, Dept Internal Med A, IL-15208 Lower Galilee, Israel. Baruch Padeh Poriya Med Ctr, Dept Imaging, IL-15208 Lower Galilee, Israel. Baruch Padeh Poriya Med Ctr, Dept Dent Surg, IL-15208 Lower Galilee, Israel. Emek Yesrael Coll, Dept Hlth Syst Management, Emek Yesrael, Israel. RP Blum, A (reprint author), NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. EM bluma@mail.nih.gov OI Laster, Zvi/0000-0003-3485-842X NR 10 TC 41 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0953-6205 J9 EUR J INTERN MED JI Eur. J. Intern. Med. PD JUL PY 2007 VL 18 IS 4 BP 295 EP 298 DI 10.1016/j.ejim.2006.12.003 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 194TR UT WOS:000248367200006 PM 17574103 ER PT J AU Fidani, L Clarimon, J Goulas, A Hatzitolios, AI Evans, W Tsirogianni, E Hardy, J Kotsis, A AF Fidani, L. Clarimon, J. Goulas, A. Hatzitolios, A. I. Evans, W. Tsirogianni, E. Hardy, J. Kotsis, A. TI Association of phosphodiesterase 4D gene G0 haplotype and ischaemic stroke in a Greek population SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE genetics; gene polymorphism; ischaemic stroke; phosphodiesterase 4D ID PDE4D GENE; POLYMORPHISMS; RISK; CLASSIFICATION; REGION AB We have examined the association of phosphodiesterase 4D (PDE4D) single nucleotide polymorphism (SNP45) and microsatellite marker AC008818-1 with ischaemic stroke, in an independent cohort of Greek patients and control individuals with no clinical manifestations of vascular disease. Significantly different distributions were observed with respect to the AC008818-1 alleles, with allele 148 associating with an increased risk of stroke incidence, and allele 144 with a protective effect. In addition, the haplotype defined by allele 148 and G allele of SNP45 was found to be significantly increased in patients even though no statistically significant differences emerged with respect to SNP45 alone. The previously established association of a PDE4D gene haplotype with ischaemic stroke in a population from Iceland was independently confirmed in our Greek population, suggesting that PDE4D may be involved in the aetiology and pathogenesis of stroke. C1 Aristotle Univ Thessaloniki, Sch Med, Dept Gen Biol, Thessaloniki, Greece. NIH, NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Sch Med, Dept Expt Pharmacol, Thessaloniki, Greece. Aristotle Univ Thessaloniki, AHEPA Hosp, Sch Med, First Propedeut Dept Int Med, Thessaloniki, Greece. Reta Lila Weston Inst Neurol, London, England. RP Fidani, L (reprint author), 6 Dimitriou Gounari Str, GR-54621 Thessaloniki, Greece. EM lfidani@med.auth.gr RI Hardy, John/C-2451-2009; OI Clarimon, Jordi/0000-0002-6824-6942; Hatzitolios, Apostolos/0000-0002-2323-8594 FU Intramural NIH HHS; Medical Research Council [G0701075]; Parkinson's UK [G-0907] NR 22 TC 10 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2007 VL 14 IS 7 BP 745 EP 749 DI 10.1111/j.1468-1331.2007.01767.x PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 183GR UT WOS:000247561200017 PM 17594329 ER PT J AU Lauretani, F Bandinelli, S Benedetta, B Cherubini, A Iorio, AD Ble, A Giacomini, V Corsi, AM Guralnik, JM Ferrucci, L AF Lauretani, F. Bandinelli, S. Benedetta, B. Cherubini, A. Iorio, A. D. Ble, A. Giacomini, V. Corsi, A. M. Guralnik, J. M. Ferrucci, L. TI Omega-6 and omega-3 fatty acids predict accelerated decline of peripheral nerve function in older persons SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE aging; docosahexaenoic acid; InCHIANTI study; omega-6 fatty acids; peripheral nerves ID POLYUNSATURATED FATTY-ACIDS; GAMMA-LINOLENIC ACID; DIABETIC-RATS; CONDUCTION; CURRENTS; BRAIN; PREVENTION; NEUROPATHY; INCHIANTI; MARKERS AB Pre-clinical studies suggest that both omega-6 and omega-3 fatty acids have beneficial effects on peripheral nerve function. Rats feed a diet rich in polyunsaturated fatty acids (PUFAs) showed modification of phospholipid fatty acid composition in nerve membranes and improvement of sciatic nerve conduction velocity (NCV). We tested the hypothesis that baseline plasma omega-6 and omega-3 fatty acids levels predict accelerated decline of peripheral nerve function. Changes between baseline and the 3-year follow-up in peripheral nerve function was assessed by standard surface ENG of the right peroneal nerve in 384 male and 443 female participants of the InCHIANTI study (age range: 24-97 years). Plasma concentrations of selected fatty acids assessed at baseline by gas chromatography. Independent of confounders, plasma omega-6 fatty acids and linoleic acid were significantly correlated with peroneal NCV at enrollment. Lower plasma PUFA, omega-6 fatty acids, linoleic acid, ratio omega-6/omega-3, arachidonic acid and docosahexanoic acid levels were significantly predicted a steeper decline in nerve function parameters over the 3-year follow-up. Low plasma omega-6 and omega-3 fatty acids levels were associated with accelerated decline of peripheral nerve function with aging. C1 Tuscany Reg Hlth Agcy, Florence, Italy. Azienda Sanitary Firenze, Florence, Italy. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Univ Perugia, Sch Med, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. Univ G DAnnunzio, Dept Med & Ssi Aging, Lab Clin Epidemiol, Chieti, Italy. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demograph & Biometry, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, ASTRA Unit, Longitudinal Studies Sect, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Cherubini, Antonio/0000-0003-0261-9897; Lauretani, Fulvio/0000-0002-5287-9972 FU Intramural NIH HHS [Z99 AG999999] NR 34 TC 13 Z9 13 U1 3 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD JUL PY 2007 VL 14 IS 7 BP 801 EP 808 DI 10.1111/j.1468-1331.2007.01860.x PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 183GR UT WOS:000247561200027 PM 17594339 ER PT J AU Mansour, AM Uwaydat, SH Chan, CC AF Mansour, A. M. Uwaydat, S. H. Chan, C.-C. TI Long-term follow-up Bietti crystalline dystrophy SO EUROPEAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE Bietti crystalline dystrophy; crystalline retinopathy; retinal crystals; retinal dystrophy ID MARGINAL CORNEAL-DYSTROPHY; TAPETORETINAL DEGENERATION; RETINAL DYSTROPHY AB PURPOSE. To present a long-term follow-up of Bietti crystalline dystrophy. METHODS. Two brothers are presented including the clinical findings, fluorescein angiography, electrophysiology (electroretinography [ERG]; electrooculography [EOG], adaptometry), optical coherence tomography (OCT), and transmission electron microscopy of bulbar conjunctiva and peripheral blood lymphocytes. The clinical findings were documented over a period of 25 years in one brother and 5 years in the other. RESULTS. The most striking features were deposits in the retina that were formed de novo with old ones replaced by choroidal atrophy in advanced stage of the disease. The light rise (EOG), rod- and cone-driven responses (ERG), and visual fields were affected progressively during the course. These changes of the retinal pigment epithelium and choriocapillaris were observed in the second decade and worsened gradually. OCT demonstrated preferential crystal accumulation in the inner retina. Cytoplasmic lipid crystalline inclusions were found in lymphocytes and conjunctival fibroblasts by transmission electron microscopy. CONCLUSIONS. Bietti crystalline retinopathy is a progressive retinal disease characterized by retinal crystals gradually replaced by atrophy of the retinal pigment epithelium and gradual constriction of visual fields. C1 Amer Univ Beirut, Dept Ophthalmol, Beirut, Lebanon. Univ Texas, Med Branch, Dept Ophthalmol, Galveston, TX 77550 USA. NEI, Dept Ophthalmol, NIH, Bethesda, MD 20892 USA. RP Mansour, AM (reprint author), Amer Univ Beirut, Dept Ophthalmol, Beirut, Lebanon. EM dr.ahmad@cyberia.net.lb NR 5 TC 14 Z9 17 U1 0 U2 0 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-6721 J9 EUR J OPHTHALMOL JI Eur. J. Ophthalmol. PD JUL-AUG PY 2007 VL 17 IS 4 BP 680 EP 682 PG 3 WC Ophthalmology SC Ophthalmology GA 220FX UT WOS:000250143700034 PM 17671952 ER PT J AU Veble, G Podgornik, R AF Veble, G. Podgornik, R. TI The boundary element approach to Van der Waals interactions SO EUROPEAN PHYSICAL JOURNAL E LA English DT Article ID FORCES; VESICLES AB We develop a boundary element method to calculate Van der Waals interactions for systems composed of domains of spatially constant dielectric response of a general boundary shape. We achieve this by rewriting the interaction energy expression presented in Phys. Rev. B, 62 (2000) 6997 exclusively in terms of surface integrals of surface operators. We validate this approach in the Lifshitz case and give numerical results for the interaction of two spheres as well as the van der Waals self-interaction of a uniaxial ellipsoid. Our method is simple to implement and is particularly suitable for a full, non-perturbative numerical evaluation of non-retarded van der Waals interactions between objects of a completely general shape. C1 Univ Ljubljana, Fac Math & Phys, Dept Phys, Ljubljana, Slovenia. Univ Maribor, Ctr Appl Math & Theoret Phys, SLO-2000 Maribor, Slovenia. Univ Ljubljana, Jozef Stefan Inst, Dept Theoret Phys, Ljubljana, Slovenia. NICHHD, LPSB, NIH, Bethesda, MD 20892 USA. RP Veble, G (reprint author), Univ Ljubljana, Fac Math & Phys, Dept Phys, Ljubljana, Slovenia. EM gregor.veble@fmf.uni-lj.si; rudolf.podgornik@fmf.uni-lj.si RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 FU Intramural NIH HHS NR 15 TC 9 Z9 9 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1292-8941 J9 EUR PHYS J E JI Eur. Phys. J. E PD JUL PY 2007 VL 23 IS 3 BP 275 EP 279 DI 10.1140/epje/i2007-10211-7 PG 5 WC Chemistry, Physical; Materials Science, Multidisciplinary; Physics, Applied; Polymer Science SC Chemistry; Materials Science; Physics; Polymer Science GA 201GX UT WOS:000248820600005 PM 17646903 ER PT J AU Saczynski, JS Rebok, GW Whitfield, KE Plude, DL AF Saczynski, Jane S. Rebok, George W. Whitfield, Keith E. Plude, Dana L. TI Spontaneous production and use of mnemonic strategies in older adults SO EXPERIMENTAL AGING RESEARCH LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Gerontological-Society-of-America CY NOV 21-25, 2003 CL San Diego, CA SP Gerontol Soc Amer ID AGE-DIFFERENCES; FREE-RECALL; MEMORY; PERFORMANCE; PERSPECTIVE; BEHAVIOR; ABILITY; HEALTH; YOUNG AB Mnemonic strategy use in older adults has been measured a number of ways, and although strategy measurement has received considerable attention, little work has been done to compare various types of subjective strategy reporting. The authors compared self-generated and endorsed strategies for memory tasks in a sample of 85 African-American and Caucasian older adults and investigated demographic characteristics related to each strategy measurement and the relationship between strategy use and memory performance. Across memory measures, significantly more strategies were endorsed than self-generated. Race, favoring Caucasians, was the most salient demographic predictor of mnemonic strategy usage. Although strategic behavior was associated with ability performance on most memory measures, specific strategies for optimal performance were identified for number and story recall only. Findings highlight the importance of measuring both self-generated and endorsed strategies and confirm previous work on the relationship between strategy use and memory performance. C1 NIA, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. RP Saczynski, JS (reprint author), NIA, 7201 Wisconsin Ave,Room 3C309, Bethesda, MD 20892 USA. EM saczynsj@mail.nih.gov FU NIA NIH HHS [1 R03 AG19879-01] NR 42 TC 10 Z9 10 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-073X J9 EXP AGING RES JI Exp. Aging Res. PD JUL-SEP PY 2007 VL 33 IS 3 BP 273 EP 294 DI 10.1080/03610730701318899 PG 22 WC Geriatrics & Gerontology; Psychology SC Geriatrics & Gerontology; Psychology GA 178RH UT WOS:000247237300002 PM 17497371 ER PT J AU Rath, MF Morin, F Shi, Q Klein, DC Moller, M AF Rath, Martin F. Morin, Fabrice Shi, Qiong Klein, David C. Moller, Morten TI Ontogenetic expression of the Otx2 and Crx homeobox genes in the retina of the rat SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE Otx2; Crx; homeobox; retina; development; rat ID CELL-FATE DETERMINATION; PINEAL-GLAND; PHOTORECEPTOR DIFFERENTIATION; PIGMENT-EPITHELIUM; TRANSCRIPTION FACTORS; N-ACETYLTRANSFERASE; HOMEODOMAIN; NETWORK; SPECIFICATION; ZEBRAFISH AB Otx2 and Crx are vertebrate orthologs of the orthodenticle family of homeobox genes, which are involved in retinal development. In this study, the temporal expression patterns of Otx2 and Crx in the rat retina during embryonic and postnatal stages of development were analyzed in detail. This confirmed the presence of Otx2 mRNA in both the embryonic retinal pigment epithelium and the developing neural retina. During development, the expression of Otx2 persists in the pigment epithelium, whereas Otx2 expression of the neural retina becomes progressively restricted to the outer nuclear layer and the outer part of the inner nuclear layer. Immunohistochemistry revealed that Otx2 protein is also present in cell bodies of the ganglion cell layer, which does not contain the Otx2 transcript, suggesting that Otx2 protein is synthesized in cell bodies of the bipolar neurons and then transported to and taken up by cells in the ganglion cell layer. Crx is also highly expressed in the outer nuclear layer starting at E17 and postnatally in the inner nuclear layer. The onset of expression of Crx lags behind that of Otx2 consistent with evidence that Otx2 activates Crx transcription. These expression patterns are consistent with evidence that Otx2 and Crx function during retinal development and extend the period of probable functionality to the adult. In this regard, these results provide an enhanced and expanded temporal and spatial framework for understanding the multiple roles of Otx2 and Crx in the developing and mature mammalian retina. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Copenhagen, Panum Inst, Dept Neurosci & Pharmacol, DK-2200 Copenhagen, Denmark. Univ Copenhagen, Dept Neurosci & Pharmacol, Panum Inst, DK-2200 Copenhagen, Denmark. NICHHD, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Rath, MF (reprint author), Univ Copenhagen, Dept Neurosci & Pharmacol, Panum Inst, Room 18-2-10,Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM m.rath@mai.ku.dk OI Rath, Martin/0000-0002-4047-6324 NR 39 TC 36 Z9 36 U1 0 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 2007 VL 85 IS 1 BP 65 EP 73 DI 10.1016/j.exer.2007.02.016 PG 9 WC Ophthalmology SC Ophthalmology GA 196UK UT WOS:000248507500009 PM 17467693 ER PT J AU Wang, Z Do, CW Avila, MY Stone, RA Jacobson, KA Civan, MM AF Wang, Zhao Do, Chi Wai Avila, Marcel Y. Stone, Richard A. Jacobson, Kenneth A. Civan, Mortimer M. TI Barrier qualities of the mouse eye to topically applied drugs SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE intraocular pressure; purinergic drugs; miosis; servo-null micropipette system (SNMS); pneumotonometer ID CILIARY EPITHELIAL-CELLS; ADENOSINE RECEPTOR AGONISTS; NORMAL-TENSION GLAUCOMA; INTRAOCULAR-PRESSURE; CL-CHANNELS; MAMMALIAN-CELLS; NUCLEOSIDE; MICE; LATANOPROST; REDUCTION AB The mouse eye displays unusually rapid intraocular pressure (IOP) responses to topically applied drugs as measured by the invasive servo-null micropipette system (SNMS). To learn if the time course reflected rapid drug transfer across the thin mouse cornea and sclera, we monitored a different parameter, pupillary size, following topical application of droplets containing 40 mu M (0.073 mu g) carbachol. No miosis developed from this low carbachol concentration unless the cornea was impaled with an exploring micropipette as used in the SNMS. We also compared the mouse IOP response to several purinergic drugs, measured by the invasive SNMS and non-invasive pneumotonometry. Responses to the previously studied non-selective adenosine-receptor (AR) agonist adenosine, the A(3)-selective agonist Cl-IB-MECA and the A(3)-selective antagonist MRS 1191 were all enhanced to varying degrees, in time and magnitude, by corneal impalement. We conclude that the thin ocular coats of the mouse eye actually present a Substantial barrier to drug penetration. Corneal impalement with even fine-tipped micropipettes can significantly enhance entry of topically-applied drugs into the mouse aqueous humor, reflecting either direct diffusion around the tip or a more complex impalement-triggered change in ocular barrier properties. Comparison of invasive and non-invasive measurement methods can document drug efficacy at intraocular target sites even if topical drug penetration is too slow to manifest convincing physiologic effects in intact eyes. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Penn, Dept Physiol, Sch Med, Philadelphia, PA 19104 USA. Hong Kong Polytech Univ, Sch Optometry, Kowloon, Hong Kong, Peoples R China. Univ Nacl Colombia, Fac Med, Dept Physiol Sci, Bogota, Colombia. Univ Penn, Sch Med, Dept Ophthalmol, Philadelphia, PA 19104 USA. NIDDK, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Civan, MM (reprint author), Univ Penn, Dept Physiol, Sch Med, Richards Bldg, Philadelphia, PA 19104 USA. EM civan@mail.med.upenn.edu RI Jacobson, Kenneth/A-1530-2009; Wang, Zhao/C-2168-2014; OI Jacobson, Kenneth/0000-0001-8104-1493; WANG, ZHAO/0000-0002-4233-9884 FU Intramural NIH HHS [Z01 DK031117-20]; NEI NIH HHS [EY01583, EY13624, P30 EY001583, R01 EY013624, R01 EY013624-07] NR 29 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 EI 1096-0007 J9 EXP EYE RES JI Exp. Eye Res. PD JUL PY 2007 VL 85 IS 1 BP 105 EP 112 DI 10.1016/j.exer.2007.03.006 PG 8 WC Ophthalmology SC Ophthalmology GA 196UK UT WOS:000248507500012 PM 17490649 ER PT J AU Chen, L Gao, ZG Zhu, JQ Rodgers, GP AF Chen, Ling Gao, Zhigang Zhu, Jianqiong Rodgers, Griffin P. TI Identification of CD13(+)CD36(+) cells as a common progenitor for erythroid and myeloid lineages in human bone marrow SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; TRANSIENT MYELOPROLIFERATIVE DISORDER; DOWN-SYNDROME; IN-VITRO; TRANSCRIPTION FACTORS; DIFFERENTIATION; COMMITMENT; LEUKEMIA; BLOOD; EXPRESSION AB Objective. To identify biopotential precursor cells of erythroid and myeloid development in human bone marrow. Materials and Methods. Cells coexpressing CD13 and CD36 (CD13(+)CD36(+)) were investigated by analyzing cell-surface marker expression during erythroid development (induced with a combination of cytokines plus erythropoietin), or myeloid development (induced with the same cocktail of cytokines plus granulocyte colony-stimulating factor of bone marrow-derived CD133 cells in liquid cultures. CD13(+)CD36(+) subsets were also isolated on the 14(th) day of cultures and further evaluated for their hematopoietic clonogenic capacity in methylcellulose. Results. Colony-forming analysis of sorted CD13(+)CD36(+) cells of committed erythroid and myeloid lineages demonstrated that these cells were able to generate erythroid, granulocyte, and mixed erythroid-granulocyte colonies. In contrast, CD13(+)CD36(-) or CD13(-)CD36(+) cells exclusively committed to granulocyte/monocyte or erythroid colonies, respectively, but failed to form mixed erythroid-granulocyte colonies; no colonies were detected in CD13(-)CD36(-) cells with lineage-supporting cytokines. In addition, our data confirmed that erythropoietin induced both erythroid and myeloid commitment, while granulocyte colony-stimulating factor only supported the differentiation of the myeloid lineage. Conclusions. The present data identify some CD13(+)CD36(+) cells as bipotential precursors of erythroid and myeloid commitment in normal hematopoiesis. They provide a physiological explanation for the cell identification of myeloid and erythroid lineages observed in hematopoietic diseases. This unique fraction of CD13(+)CD36(+) cells may be useful for further studies on regulating erythroid and myeloid differentiation during normal and malignant hematopoiesis. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. First Affiliated Hosp, Zunyi Med Coll, Dept Med, Zunyi, Guizhou, Peoples R China. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119,900 Rockville Pike, Bethesda, MD 20892 USA. EM gprod@helix.nih.gov FU Intramural NIH HHS [Z01 DK027008-10] NR 45 TC 15 Z9 17 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 JUL PY 2007 VL 35 IS 7 BP 1047 EP 1055 DI 10.1016/j.exphem.2007.04.003 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 186TL UT WOS:000247801000005 PM 17588473 ER PT J AU Hill, JM Cuasay, K Abebe, DT AF Hill, Joanna M. Cuasay, Katrina Abebe, Daniel T. TI Vasoactive intestinal peptide antagonist treatment during mouse embryogenesis impairs social behavior and cognitive function of adult male offspring SO EXPERIMENTAL NEUROLOGY LA English DT Review DE autism; neurodevelopmental disorder; sociability; social approach; cued and contextual fear conditioning; sex differences; neuropeptide ID DEPENDENT NEUROTROPHIC FACTOR; FETAL VALPROATE SYNDROME; EYE-MOVEMENT SLEEP; EMBRYONIC GROWTH; IGF-I; NEUROPROTECTIVE PEPTIDE; ENVELOPE PROTEIN; ALCOHOL SYNDROME; INBRED STRAINS; DEFICIENT MICE AB Vasoactive intestinal peptide (VIP) is a regulator of rodent ernbryogenesis during the period of neural tube closure. VIP enhanced growth in whole cultured mouse embryos; treatment with a VIP antagonist during embryogenesis inhibited growth and development. VIP antagonist treatment during embryogenesis also had permanent effects on adult brain chemistry and impaired social recognition behavior in adult male mice. The neurological deficits of autism appear to be initiated during neural tube closure and social behavior deficits are among the key characteristics of this disorder that is more common in males and is frequently accompanied by mental retardation. The current study examined the blockage of VIP during embryogenesis as a model for the behavioral deficits of autism. Treatment of pregnant mice with a VIP antagonist during embryonic days 8 through 10 had no apparent effect on the general health or sensory or motor capabilities of adult offspring. However, male offspring exhibited reduced sociability in the social approach task and deficits in cognitive function, as assessed through cued and contextual fear conditioning. Female offspring did not show these deficiencies. These results Suggest that this paradigm has usefulness as a mouse model for aspects of autism as it selectively impairs male offspring who exhibit the reduced social behavior and cognitive dysfunction seen in autism. Furthermore, the study indicates that the foundations of some aspects of social behavior are laid down early in mouse embryogenesis, are regulated in a sex specific manner and that interference with embryonic regulators such as VIP can have permanent effects on adult social behavior. Published by Elsevier Inc. C1 NIMH, Lab Behav Neurosci, NIH, Bethesda, MD 20892 USA. NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 21029 USA. RP Hill, JM (reprint author), NIMH, Lab Behav Neurosci, NIH, 35-1C903, Bethesda, MD 20892 USA. EM hilljoa@mail.nih.gov FU Intramural NIH HHS NR 102 TC 20 Z9 21 U1 3 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JUL PY 2007 VL 206 IS 1 BP 101 EP 113 DI 10.1016/j.expneurol.2007.04.004 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 187CN UT WOS:000247825000014 PM 17521630 ER PT J AU Bagnato, F Evangelou, IE Gallo, A Gaindh, D Yao, K AF Bagnato, Francesca Evangelou, Iordanis E. Gallo, Antonio Gaindh, Deeya Yao, Karen TI The effect of IFN-beta on black holes in patients with multiple sclerosis SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE black holes; IFN-beta; magnetic resonance imaging; multiple sclerosis; T1-hypointensities ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; T1-WEIGHTED SPIN-ECHO; NERVE GROWTH-FACTOR; REGULATORY T-CELLS; MAGNETIC-RESONANCE IMAGES; INTERFERON-BETA; HYPOINTENSE LESIONS; ENHANCING LESIONS; FOLLOW-UP; TRANSFER MR AB Multiple sclerosis (MS) is an immunological disorder of the CNS. Linked to an initial transient inflammation as the result of blood-brain barrier leakage, the disease progresses into a neurodegenerative phase. MRI is the most powerful paraclinical tool for diagnosing and monitoring MS. Although contrast enhancing lesions are the visible events of blood-brain barrier breakdown, accumulation of hypointense lesions, namely black holes, are recognised as irreversible axonal loss. IFN-beta is administered as a first-line drug in MS patients. However, whether the effect of IFN-beta extends beyond just prevention of blood-brain barrier leakage and further prevents the formation of black holes or promotes their recovery once formed, is not yet understood. C1 NIH, NINDS, Neuroimmunol Branch, Bethesda, MD 20892 USA. RP Bagnato, F (reprint author), NIH, NINDS, Neuroimmunol Branch, Bldg 10,Room 5B16,10 Ctr Dr MSC 1400, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov NR 60 TC 6 Z9 7 U1 0 U2 0 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 JUL PY 2007 VL 7 IS 7 BP 1079 EP 1091 DI 10.1517/14712598.7.7.1079 PG 13 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 195CW UT WOS:000248391100013 PM 17665995 ER PT J AU Gunn, AJ Brechbiel, MW Choyke, PL AF Gunn, Andrew J. Brechbiel, Martin W. Choyke, Peter L. TI The emerging role of molecular imaging and targeted therapeutics in peritoneal carcinomatosis SO EXPERT OPINION ON DRUG DELIVERY LA English DT Review DE immunoconjugates; malignant peritoneal mesothelioma; metastatic colorectal cancer; metastatic gastric cancer; metastatic ovarian cancer; metastatic pancreatic cancer; molecular imaging; multi-modality imaging; peritoneal carcinomatosis; photodynamic therapy; radioimmunotherapy ID OVARIAN-CANCER PATIENTS; IN-VIVO EVALUATION; CYTOREDUCTIVE SURGERY; INTRAPERITONEAL RADIOIMMUNOTHERAPY; MONOCLONAL-ANTIBODY; PANCREATIC-CANCER; EMISSION-TOMOGRAPHY; COLON-CANCER; SURGICAL DEBULKING; COLORECTAL-CANCER AB Peritoneal carcinomatosis is a common and often fatal late-stage complication of many gastrointestinal and gynecologic malignancies. This review discusses the ongoing evolution of diagnostic and treatment strategies for peritoneal carcinomatosis and the role that molecular imaging and radioimmunotherapy may play in improving patient survival. An overview of recent developments in targeted imaging and therapeutics for peritoneal carcinomatosis, as well as the authors' opinions as to future developments in this field is also provided. C1 [Gunn, Andrew J.; Brechbiel, Martin W.; Choyke, Peter L.] NCI, NIH, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. RP Gunn, AJ (reprint author), NCI, NIH, Ctr Canc Res, Mol Imaging Program, Bethesda, MD 20892 USA. NR 78 TC 10 Z9 10 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5247 J9 EXPERT OPIN DRUG DEL JI Expert Opin. Drug Deliv. PD JUL PY 2007 VL 4 IS 4 BP 389 EP 402 DI 10.1517/17425247.4.4.389 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 258GS UT WOS:000252857000007 PM 17683252 ER PT J AU Aspord, C Yu, CI Banchereau, J Palucka, AK AF Aspord, Caroline Yu, Chun I. Banchereau, Jacques Palucka, A. Karolina TI Humanized mice for the development and testing of human vaccines SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE CD34 HPC; humanized mice; immune system; immunotherapy; vaccine ID COMBINED IMMUNODEFICIENT MICE; PBL-SCID MICE; HUMAN IMMUNE-SYSTEM; HLA-TRANSGENIC MICE; PERIPHERAL-BLOOD LEUKOCYTES; HEMATOPOIETIC STEM-CELLS; HUMAN CD34(+) CELLS; EPSTEIN-BARR-VIRUS; HUMAN BONE-MARROW; HUMAN T-CELLS AB Mouse models of human disease form a link between genetics and biology. However, mice and humans differ in many aspects of immune system biology. These differences might explain, in part, why many successful preclinical immunotherapy studies in mice turn out to be unsuccessful when used in clinical trials in humans. Pioneering studies in the late 1980s demonstrated the reconstitution of human lympho-hematopoietic cells in immunodeficient mice. Since this time, imnnunodeficient mice are being tested as hosts for human hematopoietic organs or cells in an effort to create an in vivo model of the complete human immune system. Such Humouse models could permit us to generate and test novel human vaccines. C1 [Aspord, Caroline] Baylor Inst Immunol Res, Dallas, TX 75204 USA. Baylor NIAID Cooperat Ctr Translat Res Human Immu, Dallas, TX 75204 USA. EFS Rhone Alpes, Dept Res & Dev, F-38701 La Tronche, France. INSERM, U823, F-38701 La Tronche, France. RP Aspord, C (reprint author), Baylor Inst Immunol Res, Dallas, TX 75204 USA. EM carolineaspord@yahoo.com; karolinp@baylorhealth.edu RI Aspord, Caroline/N-3179-2013 FU Baylor Healthcare Systems Foundation; DANA Foundation; DARPA; National Institutes of Health [CA89440, AI056001, AIO57234, CA78846, CA85540] FX The authors thank their colleagues and collaborators for their contribution to their progresses. The authors are grateful to all former and present members of BIIR. The authors thank M Ramsay and W Duncan for their support. Due to limited space the authors could only cite a fraction of the published work. Supported by Baylor Healthcare Systems Foundation, the DANA Foundation (JB), DARPA (JB), the National Institutes of Health (CA89440 and AI056001 to AKP, AIO57234, CA78846 and CA85540 to J Banchereau). J Banchereau holds the Caruth Chair for Transplantation Immunology Research. AK Palucka holds the Ramsay Chair for Cancer Immunology Research. NR 83 TC 3 Z9 3 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD JUL PY 2007 VL 2 IS 7 BP 949 EP 960 DI 10.1517/17460441.2.7.949 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V12RT UT WOS:000207617000005 PM 23484815 ER PT J AU Horrigan, BJ Smith, W AF Horrigan, Bonnie J. Smith, Wendy TI Cancer research and the OCCAM SO EXPLORE-THE JOURNAL OF SCIENCE AND HEALING LA English DT Editorial Material C1 Natl Canc Inst, Bethesda, MD USA. RP Horrigan, BJ (reprint author), Natl Canc Inst, NIH Campus, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-8307 J9 EXPLORE-NY JI Explore-J Sci. Heal. PD JUL-AUG PY 2007 VL 3 IS 4 BP 397 EP 403 DI 10.1016/j.explore.2007.05.004 PG 7 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 201WK UT WOS:000248863100024 ER PT J AU Crigler, L Kazhanie, A Yoon, TJ Zakhari, J Anders, J Taylor, B Virador, VM AF Crigler, Lauren Kazhanie, Amita Yoon, Tae-Jin Zakhari, Julia Anders, Joanna Taylor, Barbara Virador, Victoria M. TI Isolation of a mesenchymal cell population from murine dermis that contains progenitors of multiple cell lineages SO FASEB JOURNAL LA English DT Article DE epidermal precursors; murine organotypic culture; keratinocytes ID KERATINOCYTE STEM-CELLS; HAIR FOLLICLE DEVELOPMENT; BONE-MARROW; IN-VITRO; SURFACE PHENOTYPE; COLLAGEN MATRIX; PROTEIN-KINASE; SKIN; EXPRESSION; DIFFERENTIATION AB The skin contains two known subpopulations of stem cells/epidermal progenitors: a basal keratinocyte population found in the interfollicular epithelium and cells residing in the bulge region of the hair follicle. The major role of the interfollicular basal keratinocyte population may be epidermal renewal, whereas the bulge population may only be activated and recruited to form a cutaneous epithelium in case of trauma. Using 3-dimensional cultures of murine skin under stress conditions in which only reserve epithelial cells would be expected to survive and expand, we demonstrate that a mesenchymal population resident in neonatal murine dermis has the unique potential to develop an epidermis in vitro. In monolayer culture, this dermal subpopulation has long-term survival capabilities in restricted serum and an inducible capacity to evolve into multiple cell lineages, both epithelial and mesenchymal, depending on culture conditions. When grafted subcutaneously, this dermal subpopulation gave rise to fusiform structures, reminiscent of disorganized muscle, that stained positive for smooth muscle actin and desmin; on typical epidermal grafts, abundant melanocytes appeared throughout the dermis that were not associated with hair follicles. The multipotential cells can be repeatedly isolated from neonatal murine dermis by a sequence of differential centrifugation and selective culture conditions. These results suggest that progenitors capable of epidermal differentiation exist in the mesenchymal compartment of an abundant tissue source and may have a function in mesenchymal-epithelial transition upon insult. Moreover, these cells could be available in sufficient quantities for lineage determination or tissue engineering applications. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Gyeongsang Natl Univ, Coll Med, Dept Dermatol, Jinju, South Korea. RP Virador, VM (reprint author), 9000 Rockville Pike,Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. EM vvirador@helix.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 65 TC 55 Z9 59 U1 0 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2007 VL 21 IS 9 BP 2050 EP 2063 DI 10.1096/fj.06-5880com PG 14 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 182JG UT WOS:000247500300015 PM 17384147 ER PT J AU Marzec, JM Christie, JD Reddy, SP Jedlicka, AE Vuong, H Lanken, PN Aplenc, R Yamamoto, T Yamamoto, M Cho, HY Kleeberger, SR AF Marzec, Jacqui M. Christie, Jason D. Reddy, Sekhar P. Jedlicka, Anne E. Vuong, Hue Lanken, Paul N. Aplenc, Richard Yamamoto, Tae Yamamoto, Masayuki Cho, Hye-Youn Kleeberger, Steven R. TI Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury SO FASEB JOURNAL LA English DT Article DE antioxidant; reactive oxygen species; ALI; acute respiratory distress syndrome; trauma; oxidative stress; translational ID RESPIRATORY-DISTRESS-SYNDROME; GENE; MICE; SUSCEPTIBILITY; ASSOCIATION; EXPRESSION; PROTECTION; DISEASE; ARDS; DIFFERENTIATION AB We recently used positional cloning to identify the transcription factor Nrf2 (NF-E2 related factor 2) as a susceptibility gene in a murine model of oxidant-induced acute lung injury (ALI). NRF2 binds to antioxidant response elements (ARE) and up-regulates protective detoxifying enzymes in response to oxidative stress. This led us to investigate NRF2 as a candidate susceptibility gene for risk of development of ALI in humans. We identified multiple single nucleotide polymorphisms ( SNPs) by resequencing NRF2 in ethnically diverse subjects, and one (-617 C/A) significantly (P < 0.001) diminished luciferase activity of promoter constructs containing the SNP and significantly decreased the binding affinity (P < 0.001) relative to the wild type at this locus (-617 CC). In a nested case-control study, patients with the -617 A SNP had a significantly higher risk for developing ALI after major trauma ( OR 6.44; 95% CI 1.34, 30.8; P=0.021) relative to patients with the wild type (-617 CC). This translational investigation provides novel insight into the molecular mechanisms of susceptibility to ALI and may help to identify patients who are predisposed to develop ALI under at risk conditions, such as trauma and sepsis. Furthermore, these findings may have important implications in other oxidative stress related illnesses. C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol Biostat, Philadelphia, PA USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Penn, Sch Med, Dept Med, Pulm Allergy & Crit Care Div, Philadelphia, PA USA. Childrens Hosp Philadelphia, Philadelphia, PA USA. Univ Tsukuba, Ctr TARA, Tsukuba, Ibaraki, Japan. RP Kleeberger, SR (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, Dept Hlth & Human Serv, NIH, 111 TW Alexander Dr Bldg 101,Rm D240, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov RI Yamamoto, Masayuki/A-4873-2010 FU Intramural NIH HHS; NHLBI NIH HHS [P50 HL-60290-01, R01 HL-66109, K23 HL-04243] NR 45 TC 179 Z9 189 U1 0 U2 11 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUL PY 2007 VL 21 IS 9 BP 2237 EP 2246 DI 10.1096/fj.06-7759com PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 182JG UT WOS:000247500300032 PM 17384144 ER PT J AU Lippincott-Schwartz, J AF Lippincott-Schwartz, J. TI Emerging fluorescence technologies for the analysis of protein localization and organelle dynamics SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 9 EP 9 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800012 ER PT J AU Balatsos, NAA Fragkos-Livanios, L Xiao, Z Samiotaki, M Veenstra, TD Panayotou, G Rogakou, EP AF Balatsos, N. A. A. Fragkos-Livanios, L. Xiao, Z. Samiotaki, M. Veenstra, T. D. Panayotou, G. Rogakou, E. P. TI H2AX dynamically interacts with lamin A/C indicating the existence of H2AX-organized machinery centers in response to DSB SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Balatsos, N. A. A.] Univ Thessaly, Dept Biochem & Biotechnol, Larisa, Greece. [Fragkos-Livanios, L.; Samiotaki, M.; Panayotou, G.; Rogakou, E. P.] BSRC Al Fleming, Vari, Greece. [Xiao, Z.] NCI, NIH, SAIC, Lab Prote & Analyt Technol, 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 80 EP 80 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800147 ER PT J AU Naetar, N Korbei, B Kral, R Stewart, C Foisner, R AF Naetar, N. Korbei, B. Kral, R. Stewart, C. Foisner, R. TI Loss of LAP2 alpha affects nucleoplasmic lamin A/C levels and impairs cell cycle SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Naetar, N.; Korbei, B.; Kral, R.; Foisner, R.] Med Univ Vienna, Vienna, Austria. [Stewart, C.] NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 82 EP 82 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800155 ER PT J AU Bauge, C Leclercq, S Ellissalde, J Kim, S Pujol, J Galera, P Boumediene, K AF Bauge, C. Leclercq, S. Ellissalde, J. Kim, S. Pujol, J. Galera, P. Boumediene, K. TI NF kappa B mediatesIL-1 beta-induced down-regulation of T beta RII through the modulation of Sp3 expression SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Bauge, C.; Pujol, J.; Galera, P.; Boumediene, K.] LBTC EA3214, Caen, France. [Leclercq, S.] St Martin Private Clin, Dept Orthopaed Surg, Caen, France. [Ellissalde, J.] Fac Med, Dept Anat, Caen, France. [Kim, S.] NCI, Lab Chemoprevent 4, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 89 EP 89 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800186 ER PT J AU Cribbs, JT Dagda, RK Merrill, RA Nifoussi, SK Cleland, M Youle, RJ Strack, S AF Cribbs, J. T. Dagda, R. K. Merrill, R. A. Nifoussi, S. K. Cleland, M. Youle, R. J. Strack, S. TI Reversible phosphorylation of the mitochondrial fission/fusion machinery as a determinant for neuronal survival SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Cribbs, J. T.; Dagda, R. K.; Merrill, R. A.; Nifoussi, S. K.; Strack, S.] Univ Iowa, Carver Coll Med, Iowa City, IA USA. [Cleland, M.; Youle, R. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 114 EP 114 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800283 ER PT J AU Hossain, M Akita, N Kobayashi, F Remaley, AT Yokoyama, S Tsujita, M AF Hossain, M. Akita, N. Kobayashi, F. Remaley, A. T. Yokoyama, S. Tsujita, M. TI Contribution of non-apoAI: ABCA1 pathways for cholesterol homeostasis SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Hossain, M.; Akita, N.; Kobayashi, F.; Yokoyama, S.; Tsujita, M.] Nagoya City Univ, Grad Sch Med Sci, Nagoya, Aichi, Japan. [Remaley, A. T.] NIH, NHLBI, Lipoprot Metab Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 120 EP 120 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800305 ER PT J AU Kobrinsky, E Thomas, S Soldatov, N AF Kobrinsky, E. Thomas, S. Soldatov, N. TI Voltage-gated calcium channel dependent intracellular signaling SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Kobrinsky, E.; Thomas, S.; Soldatov, N.] NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 146 EP 146 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283800409 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, NA AF Shabalina, S. A. Ogurtsov, A. Y. Spiridonov, N. A. TI Periodic pattern of secondary structures in prokaryotic and eukaryotic mRNAs SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Shabalina, S. A.; Ogurtsov, A. Y.] NIH, Natl Lib Med, NCBI, Bethesda, MD 20892 USA. [Spiridonov, N. A.] FDA, Bethesda, MD USA. RP Shabalina, SA (reprint author), NIH, Natl Lib Med, NCBI, Bldg 10, Bethesda, MD 20892 USA. RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; NR 0 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 366 EP 366 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283801136 ER PT J AU Parker, JD Malik, M Catherino, WH AF Parker, Jason D. Malik, Minnie Catherino, William H. TI Human myometrium and leiomyomas express gonadotropin-releasing hormone 2 and gonadotropin-releasing hormone 2 receptor SO FERTILITY AND STERILITY LA English DT Article DE GnRH2 and GnRHR2; microarray analysis; RT-PCR; real-time RT-PCR; western blot; immunohistochemistry ID GONADOTROPIN-RELEASING-HORMONE; SMOOTH-MUSCLE-CELLS; RECEPTOR GENE-EXPRESSION; AUTOCRINE GROWTH-FACTOR; GNRH-II; UTERINE LEIOMYOMAS; GYNECOLOGICAL CANCERS; ENDOMETRIAL CANCER; MENSTRUAL-CYCLE; ANALOG THERAPY AB Objective: To determine the presence or absence of a second form of GnRH (GnRH2) and corresponding receptor (GnRHR2) in human uterine myometrium and leiomyomata. Design: Evaluation of human leiomyoma and patient-matched myometrium of differential mRNA and protein expression of GnRH2 and GnRHR2. Setting: University hospital. Patient(S): Eight women undergoing medically indicated hysterectomy for symptomatic fibroids. Intervention(s): Microarray analysis, reverse-transcriptase polymerase chain reaction (RT-PCR), real-time RTPCR, and immunohistochemistry. Main Outcome Measure(s): Expression of mRNA and protein in leiomyoma and patient-matched myometrium. Result(s): Microarray analysis demonstrated expression, and we confirmed the findings by RT-PCR. Real-time RT-PCR demonstrated equivalent expression of the genes in leiomyoma compared with patient-matched myometrium (0.99-fold for GnRH2 and 1.28-fold for GnRHR2). lmmunohistochemistry confirmed the expression of GnRH2 protein in both leiomyoma and myometrium. Conclusion(S): A second form of GnRH and corresponding receptor exists in the fibroid and myometrium. We speculate that an autocrine loop exists. Our findings provide further evidence that GnRH agonists may interact directly with GnRH receptors present in uterine fibroids. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM catheriw@mail.nih.gov OI Malik, Minnie/0000-0003-1129-6575 FU Intramural NIH HHS NR 51 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUL PY 2007 VL 88 IS 1 BP 39 EP 46 DI 10.1016/j.fertnstert.2006.11.098 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 190JC UT WOS:000248054100006 PM 17296196 ER PT J AU Chou, LB Malawer, MM AF Chou, Loretta B. Malawer, Martin M. TI Osteosarcoma of the calcaneus treated with prosthetic replacement with twelve years of followup: A case report SO FOOT & ANKLE INTERNATIONAL LA English DT Article ID TALAR BODY PROSTHESIS; OSTEO-SARCOMA; PHANTOM PAIN; LIMB PAIN; TALUS; FOOT C1 Stanford Univ, Med Ctr, Dept Orthopaed Surg, Stanford, CA 94305 USA. Georgetown Univ, Sch Med, Washington, DC USA. George Washington Univ, Sch Med, Washington, DC USA. NCI, Pediat & Surg Branch, Bethesda, MD 20892 USA. RP Chou, LB (reprint author), Stanford Univ, Med Ctr, Dept Orthopaed Surg, 300 Pasteur Dr,Room R111,MC 534I, Stanford, CA 94305 USA. EM lchou@stanford.edu NR 19 TC 7 Z9 8 U1 0 U2 0 PU AMER ORTHOPAEDIC FOOT & ANKLE SOC, INC PI SEATTLE PA 2517 EASTLAKE AVE EAST, STE 200, SEATTLE, WA 98102 USA SN 1071-1007 J9 FOOT ANKLE INT JI Foot Ankle Int. PD JUL PY 2007 VL 28 IS 7 BP 841 EP 844 DI 10.3113/FAI.2006.0841 PG 4 WC Orthopedics SC Orthopedics GA 187LM UT WOS:000247849200012 PM 17666179 ER PT J AU Li, CJ Li, RW Wang, YH Elsasser, TH AF Li, Cong-jun Li, Robert W. Wang, Yong-hong Elsasser, Ted H. TI Pathway analysis identifies perturbation of genetic networks induced by butyrate in a bovine kidney epithelial cell line SO FUNCTIONAL & INTEGRATIVE GENOMICS LA English DT Article DE apoptosis; butyrate; cell cycle; genetic network ID CHAIN FATTY-ACIDS; HISTONE DEACETYLASE INHIBITOR; PROBE LEVEL DATA; SODIUM-BUTYRATE; COLORECTAL-CANCER; APOPTOSIS; EXPRESSION; GROWTH; ARRAY; NORMALIZATION AB Ruminant species have evolved to metabolize the short-chain volatile fatty acids (VIA), acetate, propionate, and butyrate, to fulfill up to 70% of their nutrient energy requirements. The inherent VIA dependence of ruminant cells was exploited to add a level of increased sensitivity to the study of the role of butyrate gene-response elements in regulatory biochemical pathways. Global gene expression profiles of the bovine kidney epithelial cells regulated by sodium butyrate were investigated with high-density oligonucleotide microarrays. The detailed mechanisms by which butyrate induces cell growth arrest and apoptosis were analyzed using the Ingenuity Pathways Knowledge Base. The functional category and pathway analyses of the microarray data revealed that four canonical pathways (Cell cycles: G2/M DNA damage checkpoint, and pyrimidine metabolism; G1/S checkpoint regulation and purine metabolism) were significantly perturbed. The biologically relevant networks and pathways of these genes were also identified. -IGF2, TGFB1, TP53, E2F4, and CDC2 were established as being centered in these genomic networks. The present findings provide a basis for understanding the full range of the biological roles and the molecular mechanisms that butyrate may play in animal cell growth, proliferation, and energy metabolisms. C1 USDA ARS, Growth Biol Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. USDA ARS, Bovine Funct Genom Lab, Anim & Nat Resources Inst, Beltsville, MD 20705 USA. NCI, SAIC, Frederick, MD 21701 USA. RP Li, CJ (reprint author), USDA ARS, Growth Biol Lab, Anim & Nat Resources Inst, 10300 Baltimore Ave,Bldg 200,Room 209,BARC East, Beltsville, MD 20705 USA. EM cli@anri.barc.usda.gov NR 43 TC 36 Z9 38 U1 2 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1438-793X J9 FUNCT INTEGR GENOMIC JI Funct. Integr. Genomics PD JUL PY 2007 VL 7 IS 3 BP 193 EP 205 DI 10.1007/s10142-006-0043-2 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 177YP UT WOS:000247188700002 PM 17186197 ER PT J AU Belfer, I Hipp, H Bollettino, A McKnight, C Evans, C Virkkunen, M Albaugh, B Max, MB Goldman, D Enoch, MA AF Belfer, I. Hipp, H. Bollettino, A. McKnight, C. Evans, C. Virkkunen, M. Albaugh, B. Max, M. B. Goldman, D. Enoch, M. A. TI Alcoholism is associated with GALR3 but not two other galanin receptor genes SO GENES BRAIN AND BEHAVIOR LA English DT Article DE alcoholism; association study; galanin; galanin receptor; haplotype; linkage disequilibrium; single-nucleotide polymorphism ID STRUCTURED CLINICAL INTERVIEW; ETHANOL INTAKE; MESSENGER-RNA; MOLECULAR CHARACTERIZATION; CHROMOSOMAL LOCALIZATION; HYPOTHALAMIC GALANIN; CLONED HUMAN; RAT; SUBTYPES; EXPRESSION AB The neuropeptide galanin is widely expressed in the periphery and the central nervous system and mediates diverse physiological processes and behaviors including alcohol abuse, depression and anxiety. Four genes encoding galanin and its receptors have been identified (GAL, GALR1, GALR2 and GALR3). Recently we found that GAL haplotypes were associated with alcoholism, raising the possibility that genetic variation in GALR1, GALR2 and GALR3 might also alter alcoholism risk. Tag single nucleotide polymorphisms (SNPs) were identified by genotyping SNP panels in controls from five populations. For the association study with alcoholism, six GALR1, four GALR2 and four GALR3 SNPs were genotyped in a large cohort of Finnish alcoholics and non-alcoholics. GALR3 showed a significant association with alcoholism that was driven by one SNP (rs3091367). Moreover, the combination of the GALR3 rs3091367 risk allele and GAL risk haplotypes led to a modestly increased odds ratio (OR) for alcoholism (2.4) as compared with the effect of either GAL (1.9) or GALR3 alone (1.4). Likewise, the combination of the GALR3 and GAL risk diplotypes led to an increased OR for alcoholism (4.6) as compared with the effect of either GAL (2.0) or GALR3 alone (1.6). There was no effect of GALR1 or GALR2 on alcoholism risk. This evidence suggests that GALR3 mediates the alcoholism-related actions of galanin. C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, Bethesda, MD USA. NIH, NIAAA, DHHS, Bethesda, MD 20892 USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. Ctr Human Behav Studies Inc, Weatherford, OK USA. RP Belfer, I (reprint author), NIH, 5625 Fishers Lane,Suite 3S32,MSC 9412, Bethesda, MD 20892 USA. EM ibelfer@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Hipp, Heather/0000-0002-1089-3928 FU Intramural NIH HHS NR 61 TC 39 Z9 40 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD JUL PY 2007 VL 6 IS 5 BP 473 EP 481 DI 10.1111/j.1601-183X.2006.00275.x PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 184UB UT WOS:000247667000008 PM 17083333 ER PT J AU Rodriguez, V Chen, YD Elkahloun, A Dutra, A Pak, E Chandrasekharappa, S AF Rodriguez, Virginia Chen, Yidong Elkahloun, Abdel Dutra, Amalia Pak, Evgenia Chandrasekharappa, Settara TI Chromosome 8 BAC array comparative genomic hybridization and expression analysis identify amplification and overexpression of TRMT12 in breast cancer SO GENES CHROMOSOMES & CANCER LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; PHENYLALANINE TRANSFER-RNA; CELL-LINES; TUMOR PROGRESSION; PROSTATE-CANCER; DNA; PCR; METHYLATION; MICROARRAYS; NUCLEOSIDE AB Genomic changes in chromosome 8 are commonly observed in breast cancer cell lines and tumors. To fine map such genomic changes by comparative genomic hybridization (CGH), a high resolution (100 kb) chromosome 8 array that can detect single copy changes was developed using Phi29 DNA polymerase amplified BAC (bacterial artificial chromosome) DNA. The BAC array CGH resolved the two known amplified regions (8q21 and 8q24) of a breast cancer cell line (SKBR3) into nine separate regions including six amplicons and three deleted regions, all of which were verified by Fluorescence in situ hybridization. The extent of the gain/loss for each region was validated by qPCR. CGH was performed with a total of 8 breast cancer cell lines, and common regions of genomic amplification/deletion were identified by segmentation analysis. A 1.2-Mb region (125.3-126.5 Mb) and a 1.0-Mb region (128.1-129.1 Mb) in 8q24 were amplified in 7/8 cell lines. A global expression analysis was performed to evaluate expression changes associated with genomic amplification/deletion: a novel gene, TRMT12 (at 125.5 Mb), amplified in 7/8 cell lines, showed highest expression in these cell lines. Further analysis by RT-qPCR using RNA from 30 breast tumors showed that TRMT12 was overexpressed >2 fold in 87% (26/30) of the tumors. TRMT12 is a homologue of a yeast gene encoding a tRNA methyltransferase involved in the posttranscriptional modification of tRNA(Phe), and exploring the biological consequence of its altered expression, may reveal novel pathways in tumorigenesis. This article contains Supplementary Material available at http://www.interscience.wiley.com/jpages/1045-2257/suppmat. Published 2007 Wiley-Liss, Inc. C1 NHGRI, NIH, GTB, Bethesda, MD 20892 USA. NCI, NIH, Canc Genet Branch, Bethesda, MD 20892 USA. NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Chandrasekharappa, S (reprint author), NHGRI, NIH, GTB, Bldg 50,Rm 5232,50 South Dr, Bethesda, MD 20892 USA. EM chandra@mail.nih.gov NR 35 TC 21 Z9 24 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 2007 VL 46 IS 7 BP 694 EP 707 DI 10.1002/gcc.20454 PG 14 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 166XI UT WOS:000246413700009 PM 17440925 ER PT J AU Tirado, Y Williams, MD Hanna, EY Kaye, FJ Batsakis, JG El-Naggar, AK AF Tirado, Yamilet Williams, Michelle D. Hanna, Ehab Y. Kaye, Frederic J. Batsakis, John G. El-Naggar, Adel K. TI CRTCI/MAML2 fusion transcript in high grade mucoepidermoid carcinomas of salivary and thyroid glands and Warthin's tumors: Implications for histogenesis and biologic behavior SO GENES CHROMOSOMES & CANCER LA English DT Article ID OF-THE-LITERATURE; DIFFERENT GENETIC PATHWAYS; CLEAR-CELL HIDRADENOMA; PAROTID-GLAND; MECT1-MAML2; TRANSLOCATION; CANCER; EXPRESSION; EVOLUTION; CLASSIFICATION AB We analyzed 55 primary salivary gland tumors including 22 mucoepidermoid carcinomas (MECs) to determine the association of MECT1/TORC1/CRTC1-MAML2 fusion transcript to tumor types, level of MEC differentiation and clinicopathologic parameters. Our primary salivary gland tumors were composed of 22 MECs, I I Warthin's tumors, 10 adenoid cystic carcinomas, two basaloid carcinomas, five salivary duct carcinomas, and five adenocarcinomas, not otherwise specified. We also included, for the first time, three primary MECs of the thyroid gland. We used nested RT-PCR and subsequent sequencing techniques for detection and verification of the fusion transcript in fresh and archival specimens. Eighteen (81%) of the 22 primary salivary and one of the three thyroid glands with MEC were positive for the fusion transcript. The transcript was detected equally in low, intermediate and high grade as well as low and high stage MECs. Significant correlation between fusion negative tumors and distant metastasis was noted (P = 0.005). Four (36%) of the I I Warthin's tumors were also positive for the transcript. None of the 22 primary non-MEC gland salivary carcinomas were positive for the transcript. We conclude that the CRTC11 MAML2 transcript may be detected in both low and high grade MEC, that fusion negative tumors may define a subset of biologically aggressive MEC's tumors, that the fusion is present in primary MECs of the thyroid gland and is also detectable in Warthin's tumor, and that a subset of MECs can be targeted for therapeutic intervention. Published 2007 Wiley-Liss, lnc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI Naval Hosp, Mech Oncogene Act Sect, Bethesda, MD USA. RP El-Naggar, AK (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, 1515 Holcombe Blvd,Unit 085, Houston, TX 77030 USA. EM anaggar@mdanderson.org RI kaye, frederic/E-2437-2011 NR 56 TC 75 Z9 75 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUL PY 2007 VL 46 IS 7 BP 708 EP 715 DI 10.1002/gcc.20458 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 166XI UT WOS:000246413700010 PM 17437281 ER PT J AU Escalante-Alcalde, D Sanchez-Sanchez, R Stewart, CL AF Escalante-Alcalde, Diana Sanchez-Sanchez, Roberto Stewart, Colin L. TI Generation of a conditional Ppap2b/Lpp3 null allele SO GENESIS LA English DT Article DE Ppap2b; Lpp3; conditional null allele; Cre/loxP system ID LIPID PHOSPHATE PHOSPHATASE-1; CELL; GENE; EXPRESSION; MEMBRANE; CANCER AB Lpp3, formerly known as Pap2b, is a lipid phosphohydrolase enzyme. Some of its substrates and products are lipids with potent biological and signaling activities such as phosphatidic acid, lysophosphatidic acid, sphingosine-1-phosphate, diacylglycerol, sphingosine, and ceramide. Lpp3 is dynamically expressed during development and is widely distributed in adult tissues. Targeted inactivation of Lpp3 gene (Ppap2b) in the mouse results in embryonic lethality because of defects in extraembryonic vascular development and gastrulation. To study the participation of Lpp3 later in development and in specific cell lineages we generated a conditional allele of Ppap2b. This was accomplished by flanking critical exons, responsible for its catalytic activity with loxP sites. A generalized Cre-mediated recombination of this allele yielded a phenotype fundamentally identical to our previously reported Ppap2b null allele. C1 Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico. NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Escalante-Alcalde, D (reprint author), Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Univ, Mexico City 04510, DF, Mexico. EM descalan@ifc.unam.mx NR 19 TC 14 Z9 14 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD JUL PY 2007 VL 45 IS 7 BP 465 EP 469 DI 10.1002/dvg.20314 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 197EF UT WOS:000248536700008 PM 17610274 ER PT J AU Schaid, DJ McDonnell, SK Carlson, EE Thibodeau, SN Ostrander, EA Stanford, JL AF Schaid, Daniel J. McDonnell, Shannon K. Carlson, Erin E. Thibodeau, Stephen N. Ostrander, Elaine A. Stanford, Janet L. TI Affected relative pairs and simultaneous search for two-locus linkage in the presence of epistasis SO GENETIC EPIDEMIOLOGY LA English DT Article DE epistasis; gene-gene interaction; one-sided multivariate test; prostate cancer; quasi-likelihood; score statistic ID CANCER-SUSCEPTIBILITY LOCI; FAMILIAL PROSTATE-CANCER; HIGH-RESOLUTION MAPS; COMPLEX TRAITS; STATISTICAL-METHODS; GENETIC-TRAITS; GENOMIC SCAN; MODELS; TESTS; POLYMORPHISMS AB It is commonly believed that multiple interacting genes increase the susceptibility of genetically complex diseases, yet few linkage analyses of human diseases scan for more than one locus at a time. To overcome some of the statistical and computational limitations of a simultaneous search for two disease susceptibility loci in the presence of epistasis, we developed new score statistics to simultaneously scan for two disease susceptibility loci in pedigree data. These model-free score statistics are based on developments for model-free maximum lod scores, which in turn are based on variance components for indicators of disease status. To overcome reduced power caused by many parameters in the general two-locus model, we impose constraints on ratios of variance components, much like those used for robust single-locus linkage statistics (e.g., minimax constraints). The resulting three-degree of freedom score statistic, constrained as a one-sided multivariate test, can be computed rapidly, making simultaneous search feasible for human genetic linkage studies. Furthermore, using recent developments to rapidly compute simulation P-values for score statistics, it is feasible to empirically evaluate the statistical significance of the proposed score statistics. Application of these methods to two large studies of the genetic linkage of prostate cancer illuminates their strengths and limitations. The results provide weak suggestions for linkage of several pairs of chromosomal regions (chromosome pairs 1-21, 3-13, 5-9, and 14-19), all of which showed stronger linkage signals when the score statistics accounted for epistasis. These novel score statistics should prove useful for linkage studies of other complex human diseases. C1 Mayo Clin & Mayo Fdn, Biostat Sect, Div Biostat, Coll Med, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. RP Schaid, DJ (reprint author), Mayo Clin & Mayo Fdn, Biostat Sect, Div Biostat, Coll Med, 200 1st St SW,Harwick 775, Rochester, MN 55905 USA. EM schaid@mayo.edu OI Ostrander, Elaine/0000-0001-6075-9738 FU NCI NIH HHS [CA72818, CA78836, CA080122, CA90754, CA15083]; NIGMS NIH HHS [GM67768] NR 57 TC 2 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 431 EP 449 DI 10.1002/gepi.20223 PG 19 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700007 PM 17410530 ER PT J AU Hyland, FCL Li, K Barbacioru, C Haque, K De La Vega, FM Welch, RA Lazaruk, K AF Hyland, F. C. L. Li, K. Barbacioru, C. Haque, K. De La Vega, F. M. Welch, R. A. Lazaruk, K. TI Copy number variants of drug metabolizing enzyme genes typed in the HapMap samples SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Appl Biosyst Inc, Foster City, CA 94404 USA. SAIC Frederick, Natl Canc Inst, Core Genotyping Facil, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. RI De La Vega, Francisco/H-3832-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 451 EP 452 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700014 ER PT J AU Pfeiffer, RP AF Pfeiffer, R. P. TI Inference for candidate gene and environmental effects from combined family and case control data SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 NCI, Biostat Branch, DCEG, Bethesda, MD 20894 USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 453 EP 454 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700021 ER PT J AU Andrieu, N Goldstein, AM Schill, W Wild, P AF Andrieu, N. Goldstein, A. M. Schill, W. Wild, P. TI Comparison of nontraditional designs for gene-environment interaction (GEI) detection SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Inst Curie, INSERM, U794, F-75231 Paris, France. NCI, DHHS, NIH, Bethesda, MD 20892 USA. Univ Bremen, Bremen, Germany. RI ANDRIEU, Nadine/H-4255-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 460 EP 460 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700043 ER PT J AU Franceschini, N Cole, SA Laston, S Rose, KM Rutherford, S Goring, HHH Diego, V MacCluer, JW Lee, ET Best, LG Howard, BV Fabsitz, RR Roman, MJ North, KE AF Franceschini, N. Cole, S. A. Laston, S. Rose, K. M. Rutherford, S. Goring, H. H. H. Diego, V. MacCluer, J. W. Lee, E. T. Best, L. G. Howard, B. V. Fabsitz, R. R. Roman, M. J. North, K. E. TI Genetic determinants of pulse pressure in American Indians: the strong heart study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Univ N Carolina, Chapel Hill, NC 27599 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. Univ Oklahoma, Oklahoma City, OK USA. MedStar, Washington, DC USA. NHLBI, Bethesda, MD 20892 USA. Weill Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 472 EP 472 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700085 ER PT J AU Goldin, LR McMaster, ML Bai, Y Ter-Minassian, M Boehringer, S Tucker, MA AF Goldin, L. R. McMaster, M. L. Bai, Y. Ter-Minassian, M. Boehringer, S. Tucker, M. A. TI Genome-wide linkage screen for Waldenstrom macroglobulinemia susceptibility loci in high-risk families SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 NCI, DCEG, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, DCEG, Biostat Branch, Bethesda, MD 20892 USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 473 EP 473 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700089 ER PT J AU Kerstann, KF Goldstein, A Falk, RT Parry, DM AF Kerstann, K. F. Goldstein, A. M. Falk, R. T. Parry, D. M. TI Assessment of cancer risk in first-degree relatives of glioma cases SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 NCI, Div Canc Epidemiol & Genet, DHHS, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 479 EP 479 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700109 ER PT J AU Kim, Y Seo, Y Bailey-Wilson, JE Kim, H AF Kim, Y. Seo, Y. Bailey-Wilson, J. E. Kim, H. TI Investigating association of mitochondrial SNP with type 2 diabetes using machine learning methods SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Seoul Natl Univ, Dept Biostat & Epidemiol, Seoul, South Korea. Univ Texas San Antonio, San Antonio, TX 78285 USA. NHGRI, IDRB, NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0741-0395 EI 1098-2272 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 479 EP 480 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700112 ER PT J AU Klein, AP Duggal, P Lee, K Bailey-Wilson, JE Klein, B Klein, BEK AF Klein, A. P. Duggal, P. Lee, K. Bailey-Wilson, J. E. Klein, B. Klein, B. E. K. TI Correlation analysis of ocular biometric measurements in the Beaver Dam Eye Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Johns Hopkins Med Inst, Dept Oncol & Epidemiol, Baltimore, MD 21205 USA. NHGRI, IDRB, NIH, Baltimore, MD USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 480 EP 480 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700114 ER PT J AU Mandal, DM Halton, SL Bailey-Wilson, JE Rayford, W AF Mandal, D. M. Halton, S. L. Bailey-Wilson, J. E. Rayford, W. TI Clinical factors in prostate cancer affected men with early age at onset: a comparison between African-American and Caucasian cases in Louisiana SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. Baylor Clin, Houston, TX USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 488 EP 488 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700140 ER PT J AU Nicodemus, KK Weinberger, DR Yao, Y AF Nicodemus, K. K. Weinberger, D. R. Yao, Y. TI Development and evaluation of a novel method to control for population stratification: Comparison of genome matching versus structured association strategies SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 NIMH, GCAP, 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 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 491 EP 492 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700153 ER PT J AU Turley-Stoulig, TN Sorant, AJM Bailey-Wilson, JE Mandal, DM AF Turley-Stoulig, T. N. Sorant, A. J. M. Bailey-Wilson, J. E. Mandal, D. M. TI Power and type I error in comparison of linkage analysis methods for complex qualitative traits with rare disease alleles and environmental covariates SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 SE Louisiana Univ, Hammond, LA 70402 USA. NHGRI, NIH, Baltimore, MD USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 501 EP 502 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700188 ER PT J AU Yang, X Sherman, ME Rimm, DL Lissowska, J Brinton, LA Peplonska, B Hewitt, SM Anderson, W Szeszenia-Dabrowska, N Bardin-Mikolajczak, A Zatonski, W Cartun, R Mandich, D Garcia-Closas, M AF Yang, X. Sherman, M. E. Rimm, D. L. Lissowska, J. Brinton, L. A. Peplonska, B. Hewitt, S. M. Anderson, W. F. Szeszenia-Dabrowska, N. Bardin-Mikolajczak, A. Zatonski, W. Cartun, R. Mandich, D. Garcia-Closas, M. TI Differences in risk factors for breast cancer molecular subtypes in a population-based study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 15th Annual Meeting of the International-Genetic-Epidemiology-Society CY NOV 16-17, 2006 CL St Petersburg, FL SP Int Genet Epidemiol Soc C1 NCI, DCEG, NIH, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT 06520 USA. Marie Curie Sklodowska Univ, Ctr Canc, Inst Oncol, PL-20031 Lublin, Poland. Hartford Hosp, Hartford, CT 06115 USA. RI Peplonska, Beata/F-6004-2010; Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD JUL PY 2007 VL 31 IS 5 BP 505 EP 505 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 183WS UT WOS:000247603700201 ER PT J AU Shewmaker, F Mull, L Nakayashiki, T Masison, DC Wickner, RB AF Shewmaker, Frank Mull, Lori Nakayashiki, Toru Masison, Daniel C. Wickner, Reed B. TI Ure2p function is enhanced by its prion domain in Saccharomyces cerevisiae SO GENETICS LA English DT Article ID TRANSLATION TERMINATION; REGULATED TRANSCRIPTION; NUCLEAR-LOCALIZATION; CRYSTAL-STRUCTURE; RELEASE FACTOR; BUDDING YEAST; TOR PROTEINS; FACTOR ERF3; IN-VITRO; NITROGEN AB The Ure2 protein of Saccharomyces cerevisiae can become a prion (infectious protein). At very low frequencies Ure2p forms an insoluble, infectious amyloid known as [URE3], which is efficiently transmitted to progeny cells or mating partners that consequently lose the normal Ure2p nitrogen regulatory function. The [URE3] prion causes yeast cells to grow slowly, has never been identified in the wild, and confers no obvious phenotypic advantage. An N-terminal asparagine-rich domain determines Ure2p prion-forming ability. Since ure2 Delta strains are complemented by plasmids that overexpress truncated forms of Ure2p lacking the prion domain, the existence of the [URE3] prion and the evolutionary conservation of an N-terminal extension have remained mysteries. We find that Ure2p function is actually compromise([ in vivo by truncation of the prion domain. Moreover, Ure2p stability is diminished without the full-length prion domain. Mca1p, like Ure2p, has an N-terminal Q/N-rich domain whose deletion reduces its steady-state levels. Finally, we demonstrate that the prion domain may affect the interaction of Ure2p with other components of the nitrogen regulation system, specifically the negative regulator of nitrogen catabolic genes, Gzf3p. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov FU Intramural NIH HHS NR 49 TC 47 Z9 47 U1 0 U2 6 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2007 VL 176 IS 3 BP 1557 EP 1565 DI 10.1534/genetics.107.074153 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 195MM UT WOS:000248416300016 PM 17507672 ER PT J AU Carmel, L Wolf, YI Rogozin, IB Koonin, EV AF Carmel, Liran Wolf, Yuri I. Rogozin, Igor B. Koonin, Eugene V. TI Three distinct modes of intron dynamics in the evolution of eukaryotes SO GENOME RESEARCH LA English DT Article ID SPLICEOSOMAL INTRONS; MAXIMUM-LIKELIHOOD; PHYLOGENETIC ESTIMATION; EXON STRUCTURES; GENE FAMILIES; EM ALGORITHM; GAIN; RATES; ORIGINS; SITES AB Several contrasting scenarios have been proposed for the origin and evolution of spliceosomal introns, a hallmark of eukaryotic genes. A comprehensive probabilistic model to obtain a definitive reconstruction of intron evolution was developed and applied to 391 sets of conserved genes from 19 eukaryotic species. It is inferred that a relatively high intron density was reached early, i.e., the last common ancestor of eukaryotes contained > 2.15 introns/kilobase, and the last common ancestor of multicellular life forms harbored similar to 3.4 introns/kilobase, a greater intron density than in most of the extant fungi and in some animals. The rates of intron gain and intron loss appear to have been dropping during the last similar to 1.3 billion years, with the decline in the gain rate being much steeper. Eukaryotic lineages exhibit three distinct modes of evolution of the intron-exon structure. The primary, balanced mode, apparently, operates in all lineages. In this mode, intron gain and loss are strongly and positively correlated, in contrast to previous reports on inverse correlation between these processes. The second mode involves an elevated rate of intron loss and is prevalent in several lineages, such as fungi and insects. The third mode, characterized by elevated rate of intron gain, is seen only in deep branches of the tree, indicating that bursts of intron invasion occurred at key points in eukaryotic evolution, such as the origin of animals. Intron dynamics could depend on multiple mechanisms, and in the balanced mode, gain and loss of introns might share common mechanistic features. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 NR 64 TC 98 Z9 101 U1 4 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2007 VL 17 IS 7 BP 1034 EP 1044 DI 10.1101/gr.6438607 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 185HI UT WOS:000247701600008 PM 17495008 ER PT J AU Carmel, L Rogozin, IB Wolf, YI Koonin, EV AF Carmel, Liran Rogozin, Igor B. Wolf, Yuri I. Koonin, Eugene V. TI Evolutionarily conserved genes preferentially accumulate introns SO GENOME RESEARCH LA English DT Article ID SPLICEOSOMAL INTRONS; PROTEIN EVOLUTION; EUKARYOTIC EVOLUTION; MESSENGER-RNA; MEDIATED ENHANCEMENT; EXPRESSION; GAIN; RATES; POSITIONS; ORIGINS AB Introns that interrupt eukaryotic protein-coding sequences are generally thought to be nonfunctional. However, for reasons still poorly understood, positions of many introns are highly conserved in evolution. Previous reconstructions of intron gain and loss events during eukaryotic evolution used a variety of simplified evolutionary models that yielded contradicting conclusions and are not suited to reveal some of the key underlying processes. We combine a comprehensive probabilistic model and an extended data set, including 391 conserved genes from 19 eukaryotes, to uncover previously unnoticed aspects of intron evolution-in particular, to assign intron gain and loss rates to individual genes. The rates of intron gain and loss in a gene show moderate positive correlation. A gene's intron gain rate shows a highly significant negative correlation with the coding-sequence evolution rate; intron loss rate also significantly, but positively, correlates with the sequence evolution rate. Correlations of the opposite signs, albeit less significant ones, are observed between intron gain and loss rates and gene expression level. It is proposed that intron evolution includes a neutral component, which is manifest in the positive correlation between the gain and loss rates and a selection-driven component as reflected in the links between intron gain and loss and sequence evolution. The increased intron gain and decreased intron loss in evolutionarily conserved genes indicate that intron insertion often might be adaptive, whereas some of the intron losses might be deleterious. This apparent functional importance of introns is likely to be due, at least in part, to their multiple effects on gene expression. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Carmel, Liran/A-9681-2008 FU Intramural NIH HHS NR 47 TC 42 Z9 44 U1 0 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2007 VL 17 IS 7 BP 1045 EP 1050 DI 10.1101/gr.5978207 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 185HI UT WOS:000247701600009 PM 17495009 ER PT J AU Jeong, S Hahn, Y Rong, Q Pfeifer, K AF Jeong, Sangkyun Hahn, Yoonsoo Rong, Qi Pfeifer, Karl TI Accurate quantitation of allele-specific expression patterns by analysis of DNA melting SO GENOME RESEARCH LA English DT Article ID GENE-EXPRESSION; MONOALLELIC EXPRESSION; HUMAN GENOME; CELLS; H19; RECEPTORS; DETECT; LOCUS; MOUSE; IGF2 AB Epigenetic and genetic mechanisms can result in large differences in expression levels of the two alleles in a diploid organism. Furthermore, these differences may be critical to phenotypic variations among individuals. In this study, we present a novel procedure and algorithm to precisely and accurately quantitate the relative expression of each allele. This method uses the differential melting properties of DNAs differing at even a single base pair. By referring to the melting characteristics of the two pure alleles, the fractional contribution of the two alleles to any unknown mixture can be mathematically resolved. These methods are highly accurate and precise because each single melting reaction yields multiple data points for analysis. Finally, we discuss how this approach can be used more generally to accurately quantitate gene expression relative to known standards. C1 NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Pfeifer, K (reprint author), NICHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM kpfeifer@mail.nih.gov OI Pfeifer, Karl/0000-0002-0254-682X FU Intramural NIH HHS NR 18 TC 17 Z9 17 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2007 VL 17 IS 7 BP 1093 EP 1100 DI 10.1101/gr.6028507 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 185HI UT WOS:000247701600014 PM 17545578 ER PT J AU Zhang, J Finney, RP Rowe, W Edmonson, M Yang, SH Dracheva, T Jen, J Struewing, JP Buetow, KH AF Zhang, Jinghui Finney, Richard P. Rowe, William Edmonson, Michael Yang, Sei Hoon Dracheva, Tatiana Jen, Jin Struewing, Jeffery P. Buetow, Kenneth H. TI Systematic analysis of genetic alterations in tumors using cancer genome workbench (CGWB) SO GENOME RESEARCH LA English DT Article ID INSERTION-DELETION POLYMORPHISMS; GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; BREAST-CANCER; MUTATIONS; ASSOCIATION; GEFITINIB; SNPS; TOOL AB Systematic investigations of genetic changes in tumors are expected to lead to greatly improved understanding of cancer etiology. To meet the analytical challenges presented by such studies, we developed the Cancer Genome WorkBench (http://cgwb.nci.nih.gov), the first computational platform to integrate clinical tumor mutation profiles with the reference human genome. A novel heuristic algorithm, IndelDetector, was developed to automatically identify insertion/deletion (indel) polymorphisms as well as indel somatic mutations with high sensitivity and accuracy. It was incorporated into an automated pipeline that detects genetic alterations and annotates their effects on protein coding and 3D structure. The ability of the system to facilitate identifying genetic alterations is illustrated in three projects with publicly accessible data. Mutagenesis in tumor DNA replication leading to complex genetic changes in the EGFR kinase domain is suggested by a novel deletion-insertion combination observed in paired tumor-normal lung cancer resequencing data. Automated analysis of 152 genes resequenced by the SeattleSNPs group was able to identify 91% of the 1251 indel polymorphisms discovered by SeattleSNPs. In addition, our system discovered 518 novel indels in this data set, 451 of which were found to be valid by manual inspection of sequence traces. Our experience demonstrates that CGWB not only greatly improves the productivity and the accuracy of mutation identification, but also, through its data integration and visualization capabilities, facilitates identification of underlying genetic etiology. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Wonkwang Univ Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Cheonbuk 570749, South Korea. RP Zhang, J (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. EM jinghuiz@mail.nih.gov RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 25 TC 14 Z9 16 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2007 VL 17 IS 7 BP 1111 EP 1117 DI 10.1101/gr.5963407 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 185HI UT WOS:000247701600016 PM 17525135 ER PT J AU Gershenson, DM Birrer, M AF Gershenson, David M. Birrer, Michael TI Time for action: A "sea change" in treatment strategies for rare types of epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID CLEAR-CELL CARCINOMA; GYNECOLOGIC-ONCOLOGY-GROUP; DISTINCT-HISTOLOGIC-TYPE; SEROUS CARCINOMA; FALLOPIAN-TUBE; LOW-GRADE; GENE-EXPRESSION; POOR-PROGNOSIS; PRIMARY PERITONEAL; CHEMOTHERAPY C1 Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. NCI, Mol Mech Sect, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gershenson, DM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dgershen@mdanderson.org NR 25 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2007 VL 106 IS 1 BP 1 EP 3 DI 10.1016/j.ygyno.2007.05.003 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 183LW UT WOS:000247575300001 PM 17574071 ER PT J AU O'Cleirigh, C Ironson, G Weiss, A Costa, PT AF O'Cleirigh, Conall Ironson, Gail Weiss, Alexander Costa, Paul T., Jr. TI Conscientiousness predicts disease progression (CD4 number and viral load) in people living with HIV SO HEALTH PSYCHOLOGY LA English DT Article DE conscientiousness; personality; HIV/AIDS; HIV disease progression; mediation ID HUMAN-IMMUNODEFICIENCY-VIRUS; 5-FACTOR MODEL; HEALTH BELIEFS; PERSONALITY; ADHERENCE; DEPRESSION; INVENTORY; MORTALITY; MEN; STRESS AB Objective: Psychosocial factors (e.g., depression, avoidant coping, life stress) have been related to disease progression in HIV. This study examined the relationship between the Big Five Conscientiousness factor and HIV disease progression (CD4 cell and viral load) over I year in 119 seropositive participants. The study also examined whether Conscientiousness effects were mediated by adherence, perceived stress, depression, or coping measures. Design: In a 1 -year longitudinal design, participants completed the NEO Five-Factor Inventory Conscientiousness scale (P. T. Costa & R. R. McCrae, 1992). Participants also completed psychosocial assessments and underwent blood draws at initial assessments and 1-year follow-up. Main Outcome Measures: Multiple hierarchical regression models were used to predict change in CD4 cell numbers and viral load log 10, controlling for demographic variables, initial disease status, and antiretroviral medications. Results: Conscientiousness predicted significant increases in CD4 number and significant decreases in viral load at I year. Conscientiousness was related positively to medication adherence and active coping and negatively to depression and perceived stress. Only perceived stress emerged as a possible mediator. Conclusion: The significant relationship between Conscientiousness and medication adherence, distress, and coping suggests that an assessment of Conscientiousness in patients with HIV may help specify or target behavioral interventions to promote optimal disease management. C1 Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. Univ Miami, Dept Psychiat, Coral Gables, FL 33124 USA. NIA, Lab Personal & Cognit, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. RP Ironson, G (reprint author), Univ Miami, Dept Psychol, POB 248185, Coral Gables, FL 33124 USA. EM gironson@aol.com OI Costa, Paul/0000-0003-4375-1712 FU Intramural NIH HHS; NIMH NIH HHS [R01MH066697, R01MH53791, T32MH18917] NR 43 TC 62 Z9 63 U1 3 U2 9 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2007 VL 26 IS 4 BP 473 EP 480 DI 10.1037/0278-6133.26.4.473 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 187EB UT WOS:000247829100011 PM 17605567 ER PT J AU Poremba, A Mishkin, M AF Poremba, Amy Mishkin, Mortimer TI Exploring the extent and function of higher-order auditory cortex in rhesus monkeys SO HEARING RESEARCH LA English DT Article; Proceedings Paper CT Conference on Auditory Cortex - Listening Brain CY SEP, 2006 CL Nottingham, ENGLAND SP MIC Inst Hearing Res DE monkey; vocalization; lateralization; multisensory; temporal pole; superior temporal gyrus ID SUPERIOR TEMPORAL SULCUS; PRIMATE PREFRONTAL CORTEX; CORTICAL CONNECTIONS; MACAQUE MONKEYS; WORKING-MEMORY; COMPLEX SOUNDS; VISUAL AREAS; NEURONS; REPRESENTATION; SUBDIVISIONS AB Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques. cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision Supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere "dominance" during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole "dominance'" appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Iowa, Dept Psychol, Iowa City, IA 52240 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Poremba, A (reprint author), Univ Iowa, Dept Psychol, E124 SSH, Iowa City, IA 52240 USA. EM amy-poremba@uiowa.edu; mm@ln.nimh.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [R01 DC007156]; NIMH NIH HHS [R03 MH066922-01, R03 MH066922] NR 54 TC 22 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD JUL PY 2007 VL 229 IS 1-2 BP 14 EP 23 DI 10.1016/j.heares.2007.01.003 PG 10 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 191PI UT WOS:000248143100003 PM 17321703 ER PT J AU Yee, LJ Tang, YM Kleiner, DE Wang, D Im, K Wahed, A Tong, XM Rhodes, S Su, XW Whelan, RM Fontana, RJ Ghany, MG Borg, B Liang, TJ Yang, HY AF Yee, Leland J. Tang, Yong-Ming Kleiner, David E. Wang, Dai Im, KyungAh Wahed, Abdus Tong, Xiaomei Rhodes, Shannon Su, Xiaowen Whelan, R. Margaret Fontana, Robert J. Ghany, Marc G. Borg, Brian Liang, T. Jake Yang, Huiying CA Virahep-C Study Grp TI Myxovirus-1 and protein kinase haplotypes and fibrosis in chronic hepatitis C virus SO HEPATOLOGY LA English DT Article ID INTERLEUKIN-10 GENE PROMOTER; MULTILOCUS GENOTYPE DATA; GROWTH-FACTOR-BETA; LIVER FIBROSIS; CYTOKINE PRODUCTION; INTERFERON-GAMMA; NATURAL-HISTORY; FACTOR-ALPHA; INFECTION; POLYMORPHISM AB Candidate genes, including myxovirus resistance-1 (Mx1), protein kinase (PKR), transforming growth factor-beta 1 (TGF-beta), interleukin-10 (IL-10), and interferon-gamma (IFN-gamma), were evaluated for associations with liver fibrosis in 374 treatment-naive patients with genotype-1 chronic HCV infection [194 Caucasian Americans (CAs) and 180 African Americans (AAs)], using a genetic haplotype approach. Among the 18 haplotypes that occurred with a frequency >= 5% in the cohort overall, the Mx1-(-123C)-(+6886A)-(+19820G(379V))-(+38645T) (abbreviated Mx1-CAGT), and PKR-(+110T)-(+ 7949G)-(+ 13846A)-(+22937T)-(+403427) (abbreviated PKR-TGATT) haplotypes were independently associated with less severe hepatic fibrosis (Ishak >= 3 versus < 3). These associations persisted after adjustment for potential confounders such as alcohol use, sex, age (which is strongly correlated with the estimated duration of HCV infection [Spearman's correlation coefficient (r(s)) = 0.6)], and race (for Mx1-CAGT:OR = 0.33; 95% CI: 0.16-0.68; P = 0.0027; and for PKR-TGATT: OR = 0.56; 95% CI: 0.32-0.98; P = 0.0405). Population structure was evaluated using the structured association method using data from 161 ancestry-informative markers and did not affect our findings. We used an independent cohort of 34 AA and 160 CA in an attempt to validate our findings, although notable differences were found in the characteristics of the two patient groups. Although we observed a similar protective trend for the Mx1-CAGT haplotype in die validation set, the association was not statistically significant. Conclusion: In addition to either factors, polymorphisins in cytokine genes may play a role in the progression of HCV-related fibrosis; however, further studies are needed. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Dept Med, Div Infect Dis, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Div Med Genet, Dept Pediat, Los Angeles, CA 90048 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NIDDKD, Liver Dis Sect, Bethesda, MD 20892 USA. RP Yee, LJ (reprint author), A511 Crabtree Hall,130 DeSoto St, Pittsburgh, PA 15232 USA. EM YeeL@edc.pitt.edu RI Wahed, Abdus/A-6441-2008; OI Wahed, Abdus/0000-0001-6911-7221; Kleiner, David/0000-0003-3442-4453 FU NCRR NIH HHS [1KL2 RR024154-01, M01 RR000042, M01 RR00046, M01 RR00645, M01 RR16500, M02 RR000079]; NIDDK NIH HHS [U01 DK60329, U01 DK60309, U01 DK60324, U01 DK60327, U01 DK60335, U01 DK60340, U01 DK60341, U01 DK60342, U01 DK60344, U01 DK60345, U01 DK60346, U01 DK60349, U01 DK60352] NR 43 TC 9 Z9 9 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 JUL PY 2007 VL 46 IS 1 BP 74 EP 83 DI 10.1002/hep.21636 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 184JJ UT WOS:000247637000012 PM 17526009 ER PT J AU Lok, AS Zoulim, F Locarnini, S Bartholomeusz, A Ghany, MG Pawlotsky, JM Liaw, YF Mizokami, M Kuiken, C AF Lok, Anna S. Zoulim, Fabien Locarnini, Stephen Bartholomeusz, Angeline Ghany, Marc G. Pawlotsky, Jean-Michel Liaw, Yun-Fan Mizokami, Masashi Kuiken, Carla CA Hepatitis B Drug Resistance Work TI Antiviral drug-resistant HBV: Standardization of nomenclature and assays and recommendations for management SO HEPATOLOGY LA English DT Review ID HEPATITIS-B-VIRUS; PROLONGED LAMIVUDINE THERAPY; LINE PROBE ASSAY; IN-VITRO; ADEFOVIR DIPIVOXIL; CROSS-RESISTANCE; ENTECAVIR RESISTANCE; POLYMERASE MUTATIONS; YMDD-MOTIF; WILD-TYPE AB Substantial advances have been made in the treatment of chronic hepatitis B in the past decade. Approved treatments for chronic hepatitis B include 2 formulations of interferon and 4 nucleos(t)ide analogues (NAs). Sustained viral suppression is rarely achieved after withdrawal of a 48-week course of NA therapy, necessitating long, and in many cases, indefinite treatment with increasing risk of development of drug resistance. Antiviral resistance and poor adherence are the most important factors in treatment failure of hepatitis B. Thus, there is a need to standardize nomenclature relating to hepatitis B antiviral resistance, and to define genotypic, phenotypic, and clinical resistance to NA therapy. C1 Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. INSERM, U271, F-69008 Lyon, France. Univ Lyon 1, F-69365 Lyon, France. Hospices Civils Lyon, Lyon, France. Victorian Infect Dis Reference Lab, Melbourne, Vic, Australia. NIH, NIDDK, Liver Dis Branch, Bethesda, MD 20892 USA. Univ Paris 12, Hop Henri Mondor, French Natl Reference Ctr Viral Hepatitis B,C & D, Dept Virol, F-94010 Creteil, France. Univ Paris 12, Hop Henri Mondor, INSERM, U841, F-94010 Creteil, France. Chang Gung Univ, Mem Hosp, Liver Res Unit, Taipei, Taiwan. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi, Japan. Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM USA. RP Lok, AS (reprint author), Univ Michigan, Div Gastroenterol, 3912 Taubman Ctr, Ann Arbor, MI 48109 USA. EM aslok@umich.edu RI Liaw, Yun-Fan /B-4305-2009; Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NIAID NIH HHS [AI060449]; NIDDK NIH HHS [U01 DK57577] NR 81 TC 274 Z9 340 U1 3 U2 26 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD JUL PY 2007 VL 46 IS 1 BP 254 EP 265 DI 10.1002/hep.21698 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 184JJ UT WOS:000247637000031 PM 17596850 ER PT J AU Aweeka, FT Kang, M Yu, JY Lizak, P Alston, B Chung, RT AF Aweeka, F. T. Kang, M. Yu, J-Y Lizak, P. Alston, B. Chung, R. T. CA AIDS Clin Trials Grp 5092s Study T TI Pharmacokinetic evaluation of the effects of ribavirin on zidovudine triphosphate formation: ACTG 5092s Study Team SO HIV MEDICINE LA English DT Article DE hepatitis C virus treatment; intracellular zidovudine; pharmacokinetics; ribavirin ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHRONIC HEPATITIS-C; REVERSE-TRANSCRIPTASE; IN-VITRO; PHOSPHORYLATION; REPLICATION; ANTAGONIZES; ANEMIA AB Objectives Ribavirin (RBV) is used for the treatment of hepatitis C virus (HCV) infection in subjects with HIV-1 infection who may require antiretroviral treatment (ART) with nucleoside reverse transcriptase inhibitors including zidovudine (ZDV). We sought to investigate the potential antagonism between RBV and ZDV by evaluating the impact of RBV on the formation of intracellular ZDV triphosphate (TP) in HIV-infected patients receiving ZDV who were treated for HCV infection. Methods Serial plasma and intracellular ZDV TP pharmacokinetics (PK) were determined in 14 subjects at entry (within 2 weeks prior to RBV administration) and at 8 weeks following initiation of RBV. Intracellular ZDV TP in peripheral blood mononuclear cells (PBMC) was quantified by a validated cartridge/liquid chromatography/tandem mass spectrometry method. PK exposure was estimated from the steady-state area under the concentration vs time curve (AUC(0-12 h)) in plasma and PBMC. Results Ribavirin did not have a statistically significant impact on ZDV TP AUC(0-12 h), plasma ZDV AUC(0-12 h) or the ratio of ZDV TP AUC(0-12 h) to plasma ZDV AUC(0-12 h), although there was a trend towards an increase post-RBV ratio compared with pre-RBV. There was extensive variability in the ZDV TP AUC(0-12 h). Conclusions Ribavirin did not inhibit formation of ZDV TP in PBMC in 14 patients receiving ZDV as part of ART and RBV-based HCV therapy for 8 weeks. These results are consistent with those of a previously published limited study in seven subjects. These PK findings should be weighed carefully against emerging clinical reports of significant anaemia associated with combination ZDV and high-dose RBV therapy. C1 Univ Calif San Francisco, Drug Res Unit, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Aweeka, FT (reprint author), Univ Calif San Francisco, Drug Res Unit, 521 Parnassus Ave, San Francisco, CA 94143 USA. EM faweeka@sfghsom.ucsf.edu FU NIAID NIH HHS [AI38858] NR 13 TC 11 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD JUL PY 2007 VL 8 IS 5 BP 288 EP 294 DI 10.1111/j.1468-1293.2007.00472.x PG 7 WC Infectious Diseases SC Infectious Diseases GA 177CB UT WOS:000247130100004 PM 17561874 ER PT J AU Josephs, JS Fleishman, JA Gaist, P Gebo, KA AF Josephs, J. S. Fleishman, J. A. Gaist, P. Gebo, K. A. CA HIV Res Network TI Use of complementary and alternative medicines among a multistate, multisite cohort of people living with HIV/AIDS SO HIV MEDICINE LA English DT Article DE alternative therapy; complementary therapy; highly active antiretroviral therapy; HIV Research Network; illicit drug use ID HIV-INFECTED PATIENTS; ACTIVE ANTIRETROVIRAL THERAPY; HEALTH-SERVICES UTILIZATION; UNITED-STATES; CLINICAL-TRIALS; PATTERNS; DISEASE; AIDS; CARE; DETERMINANTS AB Objective The aim of the study was to assess the prevalence of and factors associated with use of complementary or alternative medicine (CAM) in a multistate, multisite cohort of HIV-infected patients. Methods During 2003, 951 adult patients from 14 sites participated in face-to-face interviews. Patients were asked if they received treatment from any alternative therapist or practitioner in the previous 6 months. Logistic regression was performed to examine associations between demographic and clinical variables and CAM use. Results The majority of the participants were male (68%) and African American (52%) with a median age of 45 years (range 20-85 years). Sixteen per cent used any CAM in the 6 months prior to the interview. Factors associated with use of CAM were the HIV risk factor injecting drug use [adjusted odds ratio (AOR) 0.51] compared with men who have sex with men (MSM), former drug use (AOR=2.12) compared with never having used drugs, having a college education (AOR=2.43), and visiting a mental health provider (AOR=2.76). Conclusions This study demonstrated similar rates of CAM use in the current highly active antiretroviral therapy (HAART) era compared with the pre-HAART era. Factors associated with CAM - such as education, use of mental health services, and MSM risk factor - suggest that CAM use may be associated with heightened awareness regarding the availability of such therapies. Given the potential detrimental interactions of certain types of CAM and HAART, all HIV-infected patients should be screened for use of CAM. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. NIH, Bethesda, MD 20892 USA. RP Gebo, KA (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, 1830 E Monument St,Room 435, Baltimore, MD 21287 USA. EM kgebo@jhmi.edu RI Gebo, Kelly/B-9223-2009 FU NIDA NIH HHS [K23-DA00523] NR 28 TC 23 Z9 24 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD JUL PY 2007 VL 8 IS 5 BP 300 EP 305 DI 10.1111/j.1468-1293.2007.00474.x PG 6 WC Infectious Diseases SC Infectious Diseases GA 177CB UT WOS:000247130100006 PM 17561876 ER PT J AU Schaid, DJ Stanford, JL McDonnell, SK Suuriniemi, M McIntosh, L Karyadi, DM Carlson, EE Deutsch, K Janer, M Hood, L Ostrander, EA AF Schaid, Daniel J. Stanford, Janet L. McDonnell, Shannon K. Suuriniemi, Miia McIntosh, Laura Karyadi, Danielle M. Carlson, Erin E. Deutsch, Kerry Janer, Marta Hood, Lee Ostrander, Elaine A. TI Genome-wide linkage scan of prostate cancer Gleason score and confirmation of chromosome 19q SO HUMAN GENETICS LA English DT Article ID RADICAL RETROPUBIC PROSTATECTOMY; AGGRESSIVENESS LOCI; ALLELIC IMBALANCE; SUSCEPTIBILITY; FAMILIES; GENETICS; GENES; ROGERS,WILL; PROGRESSION; DISEASE AB Despite evidence that prostate cancer has a genetic etiology, it has been extremely difficult to confirm genetic linkage results across studies, emphasizing the large extent of genetic heterogeneity associated with this disease. Because prostate cancer is common-approximately one in six men will be diagnosed with prostate cancer in their life-genetic linkage studies are likely plagued by phenocopies (i.e., men with prostate cancer due to environmental or lifestyle factors), weakly penetrant alleles, or a combination of both, making it difficult to replicate linkage findings. One way to account for heterogeneous causes is to use clinical information that is related to the aggressiveness of disease as an endpoint for linkage analyses. Gleason grade is a measure of prostate tumor differentiation, with higher grades associated with more aggressive disease. This semi-quantitative score has been used as a quantitative trait for linkage analysis in several prior studies. Our aim was to determine if prior linkage reports of Gleason grade to specific loci could be replicated, and to ascertain if new regions of linkage could be found. Gleason scores were available for 391 affected sib pairs from 183 hereditary prostate cancer pedigrees as part of the PROGRESS study. Analyzing Gleason score as a quantitative trait, and using microsatellite markers, suggestive evidence for linkage (P-value <= 0.001) was found on chromosomes 19q and 5q, with P-values <= 0.01 observed on chromosomes 3q, 7q, and 16q. Our results confirm reports of Gleason score linkage to chromosome 19q and suggest new loci for further investigation. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin, Div Biostat, Rochester, MN USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Inst Syst Biol, Seattle, WA USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, Bldg 50,Room 5351,50 S Dr,MSC 8000, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [K05 CA90754, R01 CA080122, R01 CA78836] NR 27 TC 16 Z9 17 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD JUL PY 2007 VL 121 IS 6 BP 729 EP 735 DI 10.1007/s00439-007-0368-5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 178SC UT WOS:000247239400009 PM 17486369 ER PT J AU Palazzolo, I Burnett, BG Young, JE Brenne, PL La Spada, AR Fischbeck, KH Howell, BW Pennuto, M AF Palazzolo, Isabella Burnett, Barrington G. Young, Jessica E. Brenne, Phebe L. La Spada, Albert R. Fischbeck, Kenneth H. Howell, Brian W. Pennuto, Maria TI Akt blocks ligand binding and protects against expanded polyglutamine androgen receptor toxicity SO HUMAN MOLECULAR GENETICS LA English DT Article ID BULBAR MUSCULAR-ATROPHY; TRANSGENIC MOUSE MODEL; HUNTINGTONS-DISEASE; KENNEDY-DISEASE; MOTOR-NEURONS; SURVIVAL; NEURODEGENERATION; PHOSPHORYLATION; TRANSCRIPTION; EXPRESSION AB Spinal and bulbar muscular atrophy (SBMA) is a progressive neurodegenerative disease caused by an expansion of the polyglutamine tract in the androgen receptor (AR). Here, we investigated the regulation of AR phosphorylation in order to understand factors that may modify SBMA disease progression. We show that expanded polyglutamine AR is phosphorylated by Akt. Substitution of the AR at two Akt consensus sites, S215 and S792, with aspartate, which mimics phosphorylation, reduces ligand binding, ligand-dependent nuclear translocation, transcriptional activation and toxicity of expanded polyglutamine AR. Co-expression of constitutively active Akt and the AR has similar consequences, which are blocked by alanine substitutions at residues 215 and 792. Furthermore, in motor neuron-derived MN-1 cells toxicity associated with polyglutamine-expanded AR is rescued by co-expression with Akt. Insulin-like growth factor-1 (IGF-1) stimulation, which activates several cell survival promoting pathways, also reduces toxicity of the expanded polyglutamine AR in MN-1 cells, in a manner dependent upon phospho-inositol-3-kinase. IGF-1 rescue of AR toxicity is diminished by alanine substitutions at the Akt consensus sites. These results highlight potential targets for therapeutic intervention in SBMA. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med & Neurol, Seattle, WA 98195 USA. Univ Washington, Ctr Neurogenet & Neurotherapeut, Seattle, WA 98195 USA. RP Pennuto, M (reprint author), NINDS, Neurogenet Branch, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM pennutom@ninds.nih.gov OI Howell, Brian/0000-0002-0204-0773; Pennuto, Maria/0000-0001-8634-0767 FU Intramural NIH HHS; NINDS NIH HHS [R01-NS41648]; Telethon [GFP04005] NR 35 TC 74 Z9 75 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 1 PY 2007 VL 16 IS 13 BP 1593 EP 1603 DI 10.1093/hmg/ddm109 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 195YA UT WOS:000248447200008 PM 17470458 ER PT J AU Leoyklang, P Suphapeetiporn, K Siriwan, P Desudchit, T Chaowanapanja, P Gahl, WA Shotelersuk, V AF Leoyklang, Petcharat Suphapeetiporn, Kanya Siriwan, Pichit Desudchit, Tayard Chaowanapanja, Pattraporn Gahl, William A. Shotelersuk, Vorasuk TI Heterozygous nonsense mutation SATB2 associated with cleft palate, osteoporosis, and cognitive defects SO HUMAN MUTATION LA English DT Article DE SATB2; cleft palate; osteoporosis; cognitive deficit; epilepsy ID CANDIDATE GENES; BINDING PROTEIN; EXPRESSION; 2Q32-Q33; MANNER AB Studies of human chromosomal aberrations and knockout (KO) mice have suggested SATB2 as a candidate gene for a human malformation syndrome of craniofacial patterning and brain development. Of 59 unrelated patients with craniofacial dysmorphism, with or without mental retardation, one 36-year-old man had a nonsynonymous mutation in SATB2. The affected individual exhibited craniofacial dysmorphisms including cleft palate, generalized osteoporosis, profound mental retardation, epilepsy and a jovial personality. He carries a de novo germline nonsense mutation (c.715C > T, p.R239X) in the exon 6 of SATB2. Expression studies showed that the mutant RNA was stable, expected to produce a truncated protein predicted to retain its dimerization domain and exert a dominant negative effect. This new syndrome is the first determined to result from mutation of a gene within the family that encodes nuclear matrix-attachment region (MAR) proteins. C1 King Chulalongkorn Mem Hosp, Dept Pediat, Div Med Genet & Metab, Bangkok 10330, Thailand. Chulalongkorn Univ, Dept Surg, Bangkok 10330, Thailand. Chulalongkorn Univ, Fac Med, Dept Radiol, Bangkok 10330, Thailand. NHGRI, Sect Human Biochem Genet, Med Res Branch, NIH, Bethesda, MD 20892 USA. RP Shotelersuk, V (reprint author), King Chulalongkorn Mem Hosp, Dept Pediat, Div Med Genet & Metab, Sor Kor Bldg,11th Floor, Bangkok 10330, Thailand. EM vorasuk.s@chula.ac.th NR 15 TC 60 Z9 62 U1 4 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD JUL PY 2007 VL 28 IS 7 BP 732 EP 738 DI 10.1002/humu.20515 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 184FT UT WOS:000247627200014 PM 17377962 ER PT J AU Lindheimer, MD Romero, R AF Lindheimer, Marshall D. Romero, Roberto TI Emerging roles of antiangiogenic and angiogenic proteins in pathogenesis and prediction of preeclampsia SO HYPERTENSION LA English DT Editorial Material ID SFLT-1 C1 Univ Chicago, Div Biol Sci, Dept Obstet & Gynecol, Chicago, IL 60637 USA. NICHHD, NIH, Dept Hlth & Human Serv, Div Intramural Res,Perinatol Res Branch, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI USA. RP Lindheimer, MD (reprint author), Univ Chicago, Div Biol Sci, Dept Obstet & Gynecol, Chicago, IL 60637 USA. EM mlindhei@medicine.bsd.uchicago.edu FU Intramural NIH HHS NR 12 TC 24 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2007 VL 50 IS 1 BP 35 EP 36 DI 10.1161/HYPERTENSIONAHA.107.089045 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600007 PM 17515451 ER PT J AU Kim, SM Chen, LM Faulhaber-Walter, R Oppermann, M Huang, YN Mizel, D Briggs, JP Schnermann, J AF Kim, Soo Mi Chen, Limeng Faulhaber-Walter, Robert Oppermann, Mona Huang, Yuning Mizel, Diane Briggs, Josephine P. Schnermann, Jurgen TI Regulation of renin secretion and expression in mice deficient in ss 1-and ss 2-adrenergic receptors SO HYPERTENSION LA English DT Article DE plasma renin; salt intake; aldosterone; furosemide; angiotensin-converting enzyme inhibition; candesartan; sympathetic nervous system ID BETA-ADRENERGIC STIMULATION; RENAL NERVES; ORNITHINE DECARBOXYLASE; GENE-EXPRESSION; NACL INTAKE; RAT-KIDNEY; RELEASE; ISOPROTERENOL; RECEPTORS; ADENOSINE AB The present experiments were performed in beta 1/beta 2-adrenergic receptor - deficient mice (beta 1/beta 2ADR(-/-)) to assess the role of beta-adrenergic receptors in basal and regulated renin expression and release. On a control diet, plasma renin concentration (in ng angiotensin I per mL per hour), determined in tail vein blood, was significantly lower in beta 1/beta 2ADR(-/-) than in wild- type (WT) mice (222 +/- 65 versus 1456 +/- 335; P < 0.01). Renin content and mRNA were 77% and 65 +/- 5% of WT. Plasma aldosterone (in picograms per mL) was also significantly reduced (420 +/- 36 in beta 1/beta 2ADR(-/-) versus 692 +/- 59 in WT). A low-salt diet (0.03%) for 1 week increased plasma renin concentration significantly in both beta 1/beta 2ADR(-/-) and WT mice (to 733 +/- 54 and 2789 +/- 555), whereas a high-salt diet (8%) suppressed it in both genotypes (to 85 +/- 24 in beta 1/beta 2ADR(-/-) and to 676 +/- 213 in WT). The absolute magnitude of salt-induced changes of plasma renin concentration was markedly greater in WT mice. Acute stimulation of renin release by furosemide, quinaprilat, captopril, or candesartan caused significant increases of plasma renin concentration in both beta 1/beta 2ADR(-/-) and WT mice, but again the absolute changes were greater in WT mice. We conclude that maintenance of normal levels of renin synthesis and release requires tonic beta-adrenergic receptor activation. In the chronic absence of beta-adrenergic receptor input, the size of the releasable renin pool decreases with a concomitant reduction in the magnitude of the plasma renin concentration changes caused by variations of salt intake or acute stimulation with furosemide, angiotensin-converting enzyme, or angiotensin type 1 receptor inhibition, but regulatory responsiveness is nonetheless maintained. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Schnermann, J (reprint author), NIDDKD, NIH, 10 Ctr Dr,MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU Intramural NIH HHS NR 24 TC 39 Z9 43 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 JUL PY 2007 VL 50 IS 1 BP 103 EP 109 DI 10.1161/HYPERTENSIONAHA.107.087577 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600019 PM 17515456 ER PT J AU Gu, DF Rice, T Wang, SP Yang, WJ Gu, C Chen, CS Hixson, JE Jaquish, CE Yao, ZJ Liu, DP Rao, DC He, J AF Gu, Dongfeng Rice, Treva Wang, Shiping Yang, Wenjie Gu, Chi Chen, Chung-Shiuan Hixson, James E. Jaquish, Cashell E. Yao, Zhi-Jian Liu, De-Pei Rao, Dabeeru C. He, Jiang TI Heritability of blood pressure responses to dietary sodium and potassium intake in a Chinese population SO HYPERTENSION LA English DT Article DE blood pressure; dietary sodium; heritability; potassium supplementation; salt sensitivity ID SALT-SENSITIVITY; DETERMINANTS; METAANALYSIS; HYPERTENSION; FAMILIES; TRIALS; GENES; HEART AB The heritability of blood pressure responses to dietary intervention has not been well studied. We examined the heritability of blood pressure responses to dietary sodium and potassium intake in a family feeding study among 1906 study participants living in rural North China. The dietary intervention included a 7-day low-sodium feeding (51.3 mmol per day), a 7-day high-sodium feeding (307.8 mmol per day), and a 7-day high-sodium plus potassium supplementation (60 mmol per day). Blood pressure was measured 9 times during the 3-day baseline period preceding the intervention and also during the last 3 days of each intervention phase using a random-zero sphygmomanometer. Heritability was computed using maximum likelihood methods under a variance components model as implemented in the computer program SOLAR. The heritabilities of baseline blood pressure were 0.31 for systolic, 0.32 for diastolic, and 0.34 for mean arterial pressure. The heritabilities increased significantly under dietary intervention and were 0.49, 0.49, and 0.51 during low sodium; 0.47, 0.49, and 0.51 during high sodium; and 0.51, 0.52, and 0.53 during potassium supplementation for systolic, diastolic, and mean arterial pressure, respectively. The heritabilities for percentage of blood pressure responses to low sodium were 0.20, 0.21, and 0.23; to high-sodium were 0.22, 0.33, and 0.33; and to potassium supplementation were 0.24, 0.21, and 0.25 for systolic, diastolic, and mean arterial pressure, respectively. Our study indicated that the heritabilities of blood pressure under controlled dietary sodium and potassium intake were significantly higher than those under a usual diet. In addition, the heritabilities of blood pressure responses to dietary sodium and potassium intake were moderate in this study population. C1 Chinese Acad Med Sci, Fu Wai Hosp, Cardiovasc Inst, Beijing 100037, Peoples R China. Washington Univ, Sch Med, St Louis, MO USA. Tulane Univ, Sch Publ Hlth & Trop Med, New Orleans, LA 70118 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. NHLBI, NIH, Bethesda, MD 20892 USA. Chinese Natl Human Genome Ctr Beijing, Beijing, Peoples R China. Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100730, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. RP Gu, DF (reprint author), Fu Wai Hosp, Cardiovasc Inst, Div Populat Genet & Prevent, 167 Beilishi Rd, Beijing 100037, Peoples R China. EM gudongfeng@vip.sina.com; jhe@tulane.edu RI Rice, Treva/D-1385-2009; Gu, Charles/A-7934-2010 OI Gu, Charles/0000-0002-8527-8145 FU NHLBI NIH HHS [U01 HL072507-01, U01 HL072507-02, U01 HL072507, U01 HL072507-03, U01 HL072507-03S1, U01 HL072507-04, U01 HL072507-04S1, U01HL072507] NR 22 TC 42 Z9 46 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2007 VL 50 IS 1 BP 116 EP 122 DI 10.1161/HYPERTENSIONAHA.107.088310 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600021 PM 17485599 ER PT J AU Rana, S Karumanchi, SA Levine, RJ Venkatesha, S Rauh-Hain, JA Tamez, H Thadhani, R AF Rana, Sarosh Karumanchi, S. Ananth Levine, Richard J. Venkatesha, Shivalingappa Rauh-Hain, Jose Alejandro Tamez, Hector Thadhani, Ravi TI Sequential changes in antiangiogenic factors in early pregnancy and risk of developing preeclampsia SO HYPERTENSION LA English DT Article DE antiangiogenic factors; sFlt1; soluble endoglin; preeclampsia; predictive test ID GROWTH-FACTOR RECEPTOR-1; ANGIOGENIC FACTORS; SOLUBLE ENDOGLIN; HYPOXIA AB Concentrations of soluble fms-like tyrosine kinase 1 (sFlt1) and soluble endoglin (sEng) increase in maternal blood with the approach of clinical preeclampsia. Although alterations in these circulating antiangiogenic factors herald the signs and symptoms of preeclampsia, in vitro studies suggest they may also play a role in regulating early placental cytotrophoblast functions. Early pregnancy changes in sFlt1 and sEng may thus identify women destined to develop preeclampsia. We performed a nested case-control study of 39 women who developed preeclampsia and 147 contemporaneous normotensive controls each with serum collected in the first (11 to 13 weeks of gestation) and second (17 to 20 weeks) trimesters. Whereas levels of sFlt1 and sEng at 11 to 13 weeks were similar between cases and controls (sFlt1: 3.5 +/- 0.3 ng/mL versus 3.0 +/- 0.1, P = 0.14; sEng 6.9 +/- 0.3 ng/mL versus 6.6 +/- 0.2, P = 0.37, respectively), at 17 to 20 weeks both were elevated in the women destined to develop preeclampsia (sFlt1: 4.1 +/- 0.5 ng/mL versus 3.1 +/- 0.1, P < 0.05; sEng, 6.4 +/- 0.4 ng/mL versus 5.2 +/- 0.1, P < 0.01). Women who developed preterm (< 37 weeks) preeclampsia demonstrated even greater sequential changes: difference [ delta{d}] between second and first trimester levels: dsFlt1, 0.63 +/- 0.91 ng/mL in preterm PE versus 0.05 +/- 0.15 in controls; dsEng, 0.73 +/- 0.77 ng/mL versus -1.32 +/- 0.18, P < 0.01. Similar findings were noted in a cross-sectional analysis of specimens collected from the Calcium for Preeclampsia Prevention Study. In conclusion, sequential changes in antiangiogenic factors during early pregnancy may be useful for predicting preterm preeclampsia. C1 Brown Univ, Women & Infants Hosp, Div Maternal Fetal Med, Providence, RI 02912 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA 02115 USA. NICHHD, NIH, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. RP Thadhani, R (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM rthadhani@partners.org FU Intramural NIH HHS; NHLBI NIH HHS [HL079594]; NICHD NIH HHS [HD 39223]; NIDDK NIH HHS [DK 065997, DK 67397] NR 21 TC 152 Z9 161 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2007 VL 50 IS 1 BP 137 EP 142 DI 10.1161/HYPERTENSIONAHA.107.087700 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600024 PM 17515455 ER PT J AU Wang, M Zhang, J Jiang, LQ Spinetti, G Pintus, G Monticone, R Kolodgie, FD Virmani, R Lakatta, EG AF Wang, Mingyi Zhang, Jing Jiang, Li-Qun Spinetti, Gaia Pintus, Gianfranco Monticone, Robert Kolodgie, Frank D. Virmani, Renu Lakatta, Edward G. TI Proinflammatory profile within the grossly normal aged human aortic wall SO HYPERTENSION LA English DT Article; Proceedings Paper CT 6th International Workshop on Structure and Function of the Vascular System CY FEB 01-03, 2007 CL Paris, FRANCE DE human; aging; arterial remodeling; Ang II; matrix metalloproteinase (MMP); MCP-1 ID SMOOTH-MUSCLE-CELLS; CARDIOVASCULAR-DISEASE ENTERPRISES; MYOSIN HEAVY-CHAIN; ANGIOTENSIN-II; MATRIX METALLOPROTEINASE-2; MYOCARDIAL-INFARCTION; MAJOR SHAREHOLDERS; CORONARY-ARTERIES; EXPRESSION; RENIN AB Studies in animal models demonstrate that angiotensin II and its downstream signaling molecules, that is, matrix metalloproteinases and monocyte chemoattractant protein-1, increase within the diffusely thickened intima of central arteries with aging. Whether such age-related changes occur within the human arterial wall is unknown. We harvested "grossly normal thoracic aortas" from 5 young (20 +/- 3 years) and 5 old white males (65 +/- 6 years) at necropsy, after death from traumatic causes. The intimae of older samples were markedly and diffusely thickened compared with younger intimae and contained increased levels of angiotensin-converting enzyme, angiotensin II, angiotensin II receptor type 1, matrix metalloproteinases 2/9, monocyte chemoattractant protein-1, and collagen I and III proteins. In situ activities of metalloproteinases 2/9 were also significantly enhanced within old, normal aortas. The thickened intima of older aortas also contained a 5-fold increase in the embryonic form of smooth muscle myosin heavy chain - labeled cells than that of younger aortas, and these fetal-type cells were colocalized with angiotensin II protein staining. The ability of isolated smooth muscle cells to invade an artificial basement membrane in response to a monocyte chemoattractant protein-1 gradient increased with age. Furthermore, angiotensin II increased the invasive capacity of young smooth muscle cells, and this effect was reduced by a metalloproteinase inhibitor or an angiotensin II receptor blocker. Thus, in the absence of lipid infiltration, the aged human aortic wall exhibits a proinflammatory profile that renders it a fertile substrate for the development of arterial disease, for example, atherosclerosis and hypertension. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH,Intramural Res Program, Baltimore, MD 21224 USA. Armed Forces Inst Pathol, Dept Cardiovasc Pathol, Washington, DC 20306 USA. Univ Sassari, Sch Med, Div Biochem, Dept Biomed Sci, I-07100 Sassari, Italy. CVPath Inst Inc, Gaithersburg, MD USA. RP Wang, M (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH,Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mingyiw@grc.nia.nih.gov OI Spinetti, Gaia/0000-0001-7996-6809 FU Intramural NIH HHS NR 39 TC 94 Z9 99 U1 0 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 JUL PY 2007 VL 50 IS 1 BP 219 EP 227 DI 10.1161/HYPERTENSIONAHA.107.089409 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180XP UT WOS:000247401600036 PM 17452499 ER PT J AU Seisler, AR Sheehan, FT AF Seisler, Andrea R. Sheehan, Frances T. TI Normative three-dimensional patellofemoral and tibiofemoral kinematics: A dynamic, in vivo study SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE femur; gender; healthy; kinematics; knee; patella; patellofemoral; tibia; tibiofemoral ID ANTERIOR CRUCIATE LIGAMENT; SINGLE-PLANE FLUOROSCOPY; PASSIVE KNEE-JOINT; GENDER-DIFFERENCES; PATELLAR TRACKING; COORDINATE SYSTEM; WEIGHT-BEARING; PAIN SYNDROME; MOTION; EXTENSION AB In order to advance biomechanical modeling, knee joint implant design and clinical treatment of knee joint pathology, accurate in vivo kinematic data of the combined patellofemoral and tibiofemoral joint during volitional activity are critical. For example, one cause of the increased prevalence of anterior knee pain in the female population is hypothesized to be altered tibiofemoral kinematics, resulting in pathological patellofemoral kinematics. Thus, the objectives of this paper were to test the hypothesis that knee joint kinematics vary based on gender and to explore the correlation between the 3-D kinematics of the patellofemoral and tibiofemoral joints. In order to accomplish these goals, a large (n = 34) normative database of combined six degree of freedom patellofemoral and tibiofemoral kinematics, acquired noninvasively during volitional knee extension-flexion using fast-PC (dynamic) magnetic resonance imaging, was established. In this normative database, few correlations between tibiofemoral and patellofemoral kinematics were found. Specifically, tibial external rotation did not predict lateral patellar tilt, as has been stated in previous studies. In general, significant differences could not be found based on gender. Further investigation into these relationships in the presence of pathology is warranted. C1 NIH, Phys Disabil Branch, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Sheehan, FT (reprint author), NIH, Phys Disabil Branch, CRC Rm 1-1469,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. EM fsheehan@cc.nih.gov RI sheehan, frances/B-6962-2009 NR 42 TC 43 Z9 43 U1 1 U2 7 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 JUL PY 2007 VL 54 IS 7 BP 1333 EP 1341 DI 10.1109/TBME.2007.890735 PG 9 WC Engineering, Biomedical SC Engineering GA 180UD UT WOS:000247390700018 PM 17605365 ER PT J AU Amsen, D Antov, A Jankovic, D Sher, A Radtke, F Souabni, A Busslinger, M McCright, B Gridley, T Flavell, RA AF Amsen, Derk Antov, Andrey Jankovic, Dragana Sher, Alan Radtke, Freddy Souabni, Abdallah Busslinger, Meinrad McCright, Brent Gridley, Thomas Flavell, Richard A. TI Direct regulation of Gata3 expression determines the T helper differentiation potential of notch SO IMMUNITY LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; NF-KAPPA-B; GENE-EXPRESSION; LINEAGE COMMITMENT; IN-VIVO; RBP-J; SCHISTOSOMA-MANSONI; HEMATOPOIETIC-CELLS; TH2 DEVELOPMENT; OX40 LIGAND AB CD4(+) T helper cells differentiate into T helper 1 (Th1) or Th2 effector lineages, which orchestrate immunity to different types of microbes. Both Th1 and Th2 differentiation can be induced by Notch, but what dictates which of these programs is activated in response to Notch is not known. By using T cell-specific gene ablation of the Notch effector RBP-J or the Notch1 and 2 receptors, we showed here that Notch was required on CD4+ T cells for physiological Th2 responses to parasite antigens. GATA-3 was necessary for Notch-induced Th2 differentiation, and we identified an upstream Gata3 promoter as a direct target for Notch signaling. Moreover, absence of GATA-3 turned Notch from a Th2 inducer into a powerful inducer of Th1 differentiation. Therefore, GaW is a critical element determining inductive Th2 differentiation and limiting Th1 differentiation by Notch. C1 Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Swiss Inst Expt Canc Res, CH-1066 Epalinges, Switzerland. Res Inst Mol Pathol, A-1030 Vienna, Austria. Jackson Lab, Bar Harbor, ME 04609 USA. Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT 06520 USA. RP Amsen, D (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Cell Biol & Histol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM d.amsen@amc.uva.nl RI Busslinger, Meinrad/J-1249-2016 OI Busslinger, Meinrad/0000-0002-9111-9351 FU NINDS NIH HHS [R01 NS036437, R01 NS036437-12, NS036437] NR 69 TC 236 Z9 251 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2007 VL 27 IS 1 BP 89 EP 99 DI 10.1016/j.immuni.2007.05.021 PG 11 WC Immunology SC Immunology GA 195FO UT WOS:000248398100011 PM 17658279 ER PT J AU Verbeek, R van der Mark, K Wawrousek, EF Plomp, AC van Noort, JM AF Verbeek, Richard van der Mark, Koen Wawrousek, Eric F. Plomp, Arianne C. van Noort, Johannes M. TI Tolerization of an established alpha B-crystallin-reactive T-cell response by intravenous antigen SO IMMUNOLOGY LA English DT Article DE alpha B-crystallin; T cells; tolerance; multiple sclerosis; autoimmunity ID MULTIPLE-SCLEROSIS; IMMUNOLOGICAL-TOLERANCE; CANDIDATE AUTOANTIGEN; DENDRITIC CELLS; ORAL TOLERANCE; IN-VITRO; MEMORY; EXPOSURE; AUTOIMMUNE; EXPRESSION AB Tolerance induction to prevent activation of a naive T-cell repertoire has been well documented in rodents and can be readily achieved by intravenous, oral or intranasal administration of antigen in the absence of adjuvants. In autoimmune diseases such as multiple sclerosis (MS) the presence of an established memory/effector T-cell repertoire against self-antigens is likely to be more relevant than the potential reactivity of naive T cells. Methods to eliminate such an established T-cell response are less well understood. In this study, we explored the effectiveness of intravenous soluble antigen to eliminate a pre-existing T-cell response against alpha B-crystallin, a candidate autoantigen in MS. We used mice that are deficient for the target antigen. This condition allowed for a vigourous T-cell and antibody response to develop upon immunization, and eliminated all possible endogenous mechanisms of tolerance for alpha B-crystallin that are found in normal rodents. When applied 3 weeks after priming with alpha B-crystallin, intravenous administration of soluble antigen almost completely abrogated the established T-cell response in a dose-dependent manner as evidenced by T-cell non-responsiveness in tolerized animals to a re-challenge with antigen in complete Freund's adjuvant. Evaluating delayed-type hypersensitivity responses after tolerance induction revealed that the tolerizing effect was achieved within 24 hr. Furthermore, the tolerizing effect was found to be antigen-specific and long lasting. In contrast, serum antibody levels were markedly increased. Our data clarify that in the absence of any natural form of immune regulation, antigen-specific memory/effector T cells can be effectively silenced by intravenous antigen. C1 TNO Qual Life, Dept Biosci, NL-2301 CE Leiden, Netherlands. NEI, Lab Mol & Dev Biol, NIH, Bethesda, MD 20892 USA. RP van Noort, JM (reprint author), TNO Qual Life, Dept Biosci, POB 2215, NL-2301 CE Leiden, Netherlands. EM Hans.vannoort@tno.nl RI Wawrousek, Eric/A-4547-2008; OI van Noort, Johannes/0000-0002-9060-5921 NR 38 TC 8 Z9 8 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JUL PY 2007 VL 121 IS 3 BP 416 EP 426 DI 10.1111/j.1365-2567.2007.02592.x PG 11 WC Immunology SC Immunology GA 172HC UT WOS:000246793800013 PM 17386078 ER PT J AU Liu, YY Wang, ZR Thomas, J Goodwin, KJ Stavrou, S Neville, DM AF Liu, Yuan Yi Wang, Zhirui Thomas, Judith Goodwin, K. Jeanine Stavrou, Scott Neville, David M., Jr. TI Polymorphisms of CD3 epsilon in cynomolgus and rhesus monkeys and their relevance to anti-CD3 antibodies and immunotoxins SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE T cell; CD3 epsilon; polymorphism; monkey; anti-CD3 antibody; immunotoxin ID T-CELL DEPLETION; DIFFERENTIATION ANTIGENS; MACACA-FASCICULARIS; CRYSTAL-STRUCTURE; CD3 POLYMORPHISM; SURFACE DISPLAY; LYMPHOCYTES; COMPLEX; PROTEIN; IDENTIFICATION AB The monoclonal antibody FN18 has been used as a marker for monkey T cells and as a T-cell-depleting reagent when conjugated to diphtheria toxin that was mutated to prevent binding to non-targeted cells. The antibody recognizes a conformational epitope on the ectodomain of monkey CD3e and displays a range of binding activity to the T cells from different rhesus and cynomolgus monkeys. Our quantitative fluorescence-activated cell sorting analysis of the FN18 reactivity to T cells from different rhesus and cynomolgus monkeys showed that there are at least three levels of FN18 reactivity in the monkeys tested: high, moderate and low. On the basis of available DNA sequence information, we determined the gene structure of rhesus CD3e chain and designed primers that can be used to amplify and quickly sequence the ectodomain of monkey CD3e. Our sequence analysis revealed that the extent of nucleotide sequence variation in this area is greater than that previously reported. In addition to the amino acids at positions 45 and 50, we demonstrated that position 35 of CD3e was also important and substitution of amino acid A for V at this position greatly reduced T-cell reactivity to FN18. We found that T cells from monkeys with high FN18 reactivity all had V, E and R at positions 35, 45 and 50 in CD3e, respectively; those having low FN18 reactivity were homozygous in CD3e with at least one of the changes: V35 to A, E45 to G and R to 50Q, whereas members in the moderate group are heterozygous, having both V and A, E and G, R and Q at these locations. A cytotoxicity assay revealed that T cells from a heterozygous rhesus monkey with moderate FN18 reactivity were much (about 40 times) less sensitive to a FN18-derived immunotoxin than those from a homozygous rhesus monkey having high FN18 reactivity. C1 NIMH, Mol Biol Lab, Sect Biophys Chem, Bethesda, MD 20892 USA. Univ Alabama, Med Ctr, Dept Surg, Sect Transplantat Immunol, Birmingham, AL USA. RP Liu, YY (reprint author), NIMH, Mol Biol Lab, Sect Biophys Chem, Bldg 10 Rm 3D46,10 Ctr Dr, Bethesda, MD 20892 USA. EM yyliu@mail.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [5 U19 DK57958-07] NR 32 TC 7 Z9 7 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUL PY 2007 VL 85 IS 5 BP 357 EP 362 DI 10.1038/sj.icb.7100042 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 191BB UT WOS:000248103700004 PM 17325695 ER PT J AU Greene, JM Collins, F Lefkowitz, EJ Roos, D Scheuermann, RH Sobral, B Stevens, R White, O Di Francesco, V AF Greene, John M. Collins, Frank Lefkowitz, Elliot J. Roos, David Scheuermann, Richard H. Sobral, Bruno Stevens, Rick White, Owen Di Francesco, Valentina TI National institute of allergy and infectious diseases bioinformatics resource centers: New assets for pathogen informaticsv SO INFECTION AND IMMUNITY LA English DT Review ID COLLECTION C1 SRA Int Inc, Hlth Res Syst, Rockville, MD 20852 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Penn, Penn Genom Inst, Philadelphia, PA 19104 USA. Univ Texas SW, Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Virginia Informat Inst, Blacksburg, VA 24061 USA. Univ Chicago, Dept Comp Sci, Chicago, IL 60637 USA. Inst Genom Res, Rockville, MD 20850 USA. NIH, NIAID, Div Microbiol & Infect Dis, Bethesda, MD 20892 USA. RP Di Francesco, V (reprint author), NIH, NIAID, DMID, 6610 Rockledge Dr,Room 6004,MSC 6603, Bethesda, MD 20850 USA. EM vdifrancesco@niaid.nih.gov NR 10 TC 40 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2007 VL 75 IS 7 BP 3212 EP 3219 DI 10.1128/IAI.00105-07 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185JP UT WOS:000247707600001 PM 17420237 ER PT J AU DeFilippis, I de Andrade, CF Silva, L Prevots, DR Vicente, ACP AF DeFilippis, Ivano de Andrade, Claudia Ferreira Silva, Luciete Prevots, D. Rebecca Vicente, Ana Carolina P. TI PorA variable antigenic regions VR1, VR2, and VR3 of Neisseria meningitidis serogroups B and C isolated in brazil from 1999 to 2004 SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; VESICLE VACCINE; IMMUNOGENICITY; MENINGOCOCCI; PEPTIDE; EFFICACY; DISEASE; DESIGN; STRAIN; CHILE AB The high genetic diversity found among the PorA regions VR1 and VR2 of 101 Neisseria meningitidis isolates from patients with meningococcal disease and healthy carriers in Brazil contrasts with the stability found in the PorA VR3 of these isolates. The presence of VR3 epitope variant 35 or 36 on the surfaces of 87% of the strains analyzed suggests that these antigens should be considered for inclusion in new formulations of vaccines against serogroup B meningococci in Brazil. C1 Fundacao Oswaldo Cruz, Natl Inst Qual Control Hlth, BR-21045900 Rio De Janeiro, Brazil. NIAID, NIH, Bethesda, MD 20892 USA. Fundacao Oswaldo Cruz, Leonidas & Maria Deane Res Ctr, BR-69057070 Manaus, Amazonas, Brazil. Fundacao Oswaldo Cruz, Inst Oswaldo Cruz, Dept Genet, BR-21045900 Rio De Janeiro, Brazil. RP DeFilippis, I (reprint author), Fundacao Oswaldo Cruz, INCQS, Av Brasil,4365,Manguinhos, BR-21045900 Rio De Janeiro, Brazil. EM ivano.defilippis@incqs.fiocruz.br FU Wellcome Trust NR 24 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2007 VL 75 IS 7 BP 3683 EP 3685 DI 10.1128/IAI.01721-06 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185JP UT WOS:000247707600052 PM 17502397 ER PT J AU Schreiber, MJ Ong, SH Holland, RCG Hibberd, ML Vasudevan, SG Mitchell, WP Holmes, EC AF Schreiber, Mark J. Ong, Swee Hoe Holland, Richard C. G. Hibberd, Martin L. Vasudevan, Subhash G. Mitchell, Wayne P. Holmes, Edward C. TI DengueInfo: A web portal to dengue information resources SO INFECTION GENETICS AND EVOLUTION LA English DT Article DE denguelnfo; dengue virus; genomics; epidemiology; nomenclature AB DengueInfo, (http://www.dengueinfo.org) is a web portal and database that brings clarity to dengue research by integrating the growing number of complete genome sequences of dengue virus with relevant literature and curated epidemiological information. Additionally, it represents a repository of on-going prospective and retrospective studies of dengue disease severity. We intend the database to be a flagship resource for the dengue community, providing standardized and high quality information and facilitating research into key aspects of dengue biology and assisting in its control. To aid this process we also introduce a standard nomenclature for dengue isolates inspired by globally accepted system used for influenza virus. (c) 2007 Elsevier B.V. All rights reserved. C1 Novartis Inst Trop Dis, Singapore 138670, Singapore. Genome Inst Singapore, Singapore 138672, Singapore. Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Schreiber, MJ (reprint author), Novartis Inst Trop Dis, Chromos 05-01,10 Biopolis Rd, Singapore 138670, Singapore. EM mark.schreiher@novartis.com RI Mitchell, Wayne/C-5219-2008; Hibberd, Martin/D-5050-2009; OI Holmes, Edward/0000-0001-9596-3552 NR 3 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1348 J9 INFECT GENET EVOL JI Infect. Genet. Evol. PD JUL PY 2007 VL 7 IS 4 BP 540 EP 541 DI 10.1016/j.meegid.2006.02.002 PG 2 WC Infectious Diseases SC Infectious Diseases GA 185TL UT WOS:000247733200018 PM 17350350 ER PT J AU Santos, A Ribeiro, JMC Lehane, MJ Gontijo, NF Veloso, AB Sant'anna, MRV Araujo, RN Grisard, EC Pereira, MH AF Santos, Adriana Ribeiro, Jose Marcos C. Lehane, Michael J. Gontijo, Nelder Figueiredo Veloso, Artur Botelho Sant'anna, Mauricio R. V. Araujo, Ricardo Nascimento Grisard, Edmundo C. Pereira, Marcos Horacio TI The sialotranscriptome of the blood-sucking bug Triatoma brasiliensis (Hemiptera, Triatominae) SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE saliva; transcriptome; hematophagy; salivary proteins; Triatoma brasiliensis ID RHODNIUS-PROLIXUS; SALIVARY-GLAND; NITRIC-OXIDE; CHAGAS-DISEASE; HEME PROTEIN; ANTICOAGULANT ACTIVITY; HEMATOPHAGOUS INSECTS; PLATELET-AGGREGATION; MOLECULAR-CLONING; ARTHROPOD SALIVA AB Triatoma brasiliensis is the most important autochthon vector of Trypanosoma cruzi in Brazil, where it is widely distributed in the semiarid areas of the Northeast. In order to advance the knowledge of the salivary biomolecules of Triatominae, a salivary gland cDNA library of T brasiliensis was mass sequenced and analyzed. Polypeptides were sequenced by HPLC/Edman degradation experiments. Then 1712 cDNA sequences were obtained and grouped in 786 clusters. The housekeeping category had 24.4% and 17.8% of the clusters and sequences, respectively. The putatively secreted category contained 47.1% of the clusters and 68.2% of the sequences. Finally, 28.5% of the clusters, containing 14% of all sequences, were classified as unknown. The sialoma of T brasiliensis showed a high amount and great variety of different lipocalins (93.8% of secreted proteins). Remarkably, a great number of serine proteases that were not observed in previous blood-sucking sialotranscriptomes were found. Nine Kazal peptides were identified, among them one with high homology to the tabanid vasodilator vasotab, suggesting that the Triatoma vasodilator could be a Kazal protein. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Fed Minas Gerais, Dept Parasitol, Lab Fis Insetos Hematofagos, ICB, BR-31270 Belo Horizonte, MG, Brazil. NIAID, NIH, Sect Vector Biol, Lab Malaria & Vector Res, Rockville, MD 20852 USA. Univ Liverpool Liverpool Sch Trop Med, Liverpool L3 5QA, Merseyside, England. Univ Fed Santa Catarina, CCB, MIP, Lab Protozool, BR-88040900 Florianopolis, SC, Brazil. RP Pereira, MH (reprint author), Univ Fed Minas Gerais, Dept Parasitol, Lab Fis Insetos Hematofagos, ICB, Caixa Postal 486, BR-31270 Belo Horizonte, MG, Brazil. EM marcoshp@icb.ufmg.br RI Pereira, Marcos/A-3774-2012; Marion-Poll, Frederic/D-8882-2011; Grisard, Edmundo/A-7338-2015; OI Marion-Poll, Frederic/0000-0001-6824-0180; Grisard, Edmundo/0000-0001-8916-8296; Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS; Wellcome Trust [, 069518] NR 77 TC 51 Z9 53 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 EI 1879-0240 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD JUL PY 2007 VL 37 IS 7 BP 702 EP 712 DI 10.1016/j.ibmb.2007.04.004 PG 11 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 185JN UT WOS:000247707400006 PM 17550826 ER PT J AU Terawaki, S Tanaka, Y Nagakura, T Hayashi, T Shibayama, S Muroi, K Okazaki, T Mikami, B Garboczi, DN Honjo, T Minato, N AF Terawaki, Selgo Tanaka, Yoshimasa Nagakura, Tornokazu Hayashi, Tarnon Shibayama, Shiro Muroi, Kaori Okazaki, Taku Mikami, Bunzo Garboczi, David N. Honjo, Tasuku Minato, Nagahiro TI Specific and high-affinity binding of tetramerized PD-L1 extracellular domain to PD-1-expressing cells: possible application to enhance T cell function SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE affinity; cancer; immunoreceptor; infection; tetramer ID PROGRAMMED DEATH-1; B7 FAMILY; DILATED CARDIOMYOPATHY; TUMOR-CELLS; YVKM MOTIF; RECEPTOR; EXPRESSION; B7-H1; MICE; BLOCKADE AB The negative co-stimulatory receptor, programmed cell death 1 (PD-1), is induced on activated T cells and delivers inhibitory signals upon engagement with its ligands PD-L1 and PD-L2, which are expressed on various somatic cells and certain cancers. Accumulating evidence suggests that interfering with the PD-1-PD-L1 interaction may result in the restoration of defective T cell functions in cancer and chronic viral infection. Herein, we established procedures to produce large amounts of renatured recombinant extracellular domain proteins of mouse PDA (mPD-1) and PD-L1. While monomeric mPD-1 and mouse PD-L1 (mPD-L1) only marginally interacted with the cells expressing their counterpart proteins, their tetramerization markedly enhanced the affinity with the K(d) of mPD-L1 tetramer being nearly 1 00-fold lower than that of the corresponding monomer. The affinity of mPD-L1 tetramer was even higher than a high-affinity anti-PD-1 mAb, and it efficiently inhibited the binding of mPD-L1/Fc-chimeric protein to mPD-1(+) cells. Functionally, mPD-L1 tetramer significantly enhanced the proliferative responses as well as the cytotoxic activity of T cells against specific target cells in vitro. The results suggest that oligomeric PD-L1 extracellular domains may provide a potential means to restore T cell functions in cancer and viral infection in humans. C1 Kyoto Univ, Grad Sch Biostudies, Lab Immunol & Cell Biol, Sakyo Ku, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Med, Dept Immuol & Genom Med, Sakyo Ku, Kyoto 6068501, Japan. Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan. Ono Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3004247, Japan. Kyoto Univ, Grad Sch Med, Century Ctr Excellence Program, Sakyo Ku, Kyoto 6068501, Japan. Kyoto Univ, Grad Sch Agr, Lab Food Qual Design & Dev, Kyoto 6000011, Japan. NIAID, Immunogenet Lab, Sturct Biol Sect, Rockville, MD 20852 USA. RP Minato, N (reprint author), Kyoto Univ, Grad Sch Biostudies, Lab Immunol & Cell Biol, Sakyo Ku, Yoshida Konoe, Kyoto 6068501, Japan. EM minato@imm.med.kyoto-u.ac.jp RI Honjo, Tasuku/N-4470-2016 FU Intramural NIH HHS NR 45 TC 4 Z9 4 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUL PY 2007 VL 19 IS 7 BP 881 EP 890 DI 10.1093/intimm/dxm059 PG 10 WC Immunology SC Immunology GA 205PU UT WOS:000249127900007 PM 17606978 ER PT J AU De Los Rios, P Petermann, T AF De Los Rios, P. Petermann, T. TI Existence, cost and robustness of spatial small-world networks SO INTERNATIONAL JOURNAL OF BIFURCATION AND CHAOS LA English DT Article DE networks; small-world; robustness ID COMPLEX NETWORKS; OPTIMIZATION; PERCOLATION; MODEL AB Small-world networks embedded in Euclidean space represent useful cartoon models for a number of real systems such as electronic circuits, communication systems, the large-scale brain architecture and others. Since the small-world behavior relies on the presence of long-range connections that are likely to have a cost which is a growing function of the length, we explore whether it is possible to choose suitable probability distributions for the shortcut lengths so as to preserve the small-world feature and, at the same time, to minimize the network cost. The flow distribution for such networks, and their robustness, are also investigated. C1 [De Los Rios, P.] Ecole Polytech Fed Lausanne, Inst Theoret Phys, CH-1015 Lausanne, Switzerland. [Petermann, T.] NIMH, Unit Neural Network Physiol, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP De Los Rios, P (reprint author), Ecole Polytech Fed Lausanne, Inst Theoret Phys, BSP 720, CH-1015 Lausanne, Switzerland. RI De Los Rios, Paolo/B-2456-2010; EPFL, LBS/B-3567-2010 OI De Los Rios, Paolo/0000-0002-5394-5062; NR 29 TC 4 Z9 4 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-1274 J9 INT J BIFURCAT CHAOS JI Int. J. Bifurcation Chaos PD JUL PY 2007 VL 17 IS 7 BP 2331 EP 2342 DI 10.1142/S0218127407018427 PG 12 WC Mathematics, Interdisciplinary Applications; Multidisciplinary Sciences SC Mathematics; Science & Technology - Other Topics GA 246QL UT WOS:000252021900009 ER PT J AU Shin, A Shrubsole, MJ Ness, RM Wu, HY Sinha, R Smalley, WE Shyr, Y Zheng, W AF Shin, Aesun Shrubsole, Martha J. Ness, Reid M. Wu, Huiyun Sinha, Rashmi Smalley, Walter E. Shyr, Yu Zheng, Wei TI Meat and meat-mutagen intake, doneness preference and the risk of colorectal polyps: The Tennessee Colorectal Polyp Study SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE colorectal neoplasms; meat; carcinogenesis; nutrition ID FOOD FREQUENCY QUESTIONNAIRE; HETEROCYCLIC AMINE CONTENT; GRILLED RED MEAT; HYPERPLASTIC POLYPS; MICROSATELLITE INSTABILITY; CANCER-RISK; WELL-DONE; CIGARETTE-SMOKING; GENETIC SUSCEPTIBILITY; SERRATED ADENOMAS AB Although meat intake has been fairly consistently linked to the risk of colorectal cancer, only a few studies have evaluated meat intake by doneness level and the heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) produced by high temperature cooking of meat in relation to colorectal adenomatous and hyperplastic polyps. We evaluated these associations in a large colonoscopy-based case-control study. Included in this study were participants with adenomatous polyp only (n = 573), hyperplastic polyp only (n = 256), or both adenomatous and hyperplastic polyps (n = 199), and 1,544 polyp-free controls. In addition to information related to demographic and other lifestyle factors, meat intake by cooking method and doneness preference were obtained through telephone interviews. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals for the association between exposures and colorectal polyp risks. Presence of hyperplastic polyp was found to be positively associated with high consumption of total meat (P-trend = 0.076) or red meat (Pt,,nd = 0.060), with an approximate 50-60% elevated risk observed in the highest vs. the lowest intake group. High intake of 2-amino-I-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo [4,5]quinoxaline (DiMeIQx) were associated with increased risk for hyperplastic polyp (Pt,,nd = 0.036 and 0.038, respectively). With a possible exception of the intake of total well-done meats (Pt,,nd = 0.055) or well-done red Meats (Ptr,nd = 0.074) with the risk of large adenomas, no other positive association was found specifically for the risk of adenomas with any of the exposure variables aforementioned. This study provides additional support for a positive association of high intake of red meat with colorectal adenomas, and suggests that high intake of meats and meat carcinogens may also be associated with hyperplastic polyps. (C) 2007 Wiley-Liss, Inc. C1 Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Med Ctr N S 1211, Nashville, TN 37232 USA. VA Tennessee Valley Geriatr Res Educ & Clin Ctr, Nashville, TN USA. Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Vanderbilt Univ, Sch Med, Div Gastroenterol, Nashville, TN USA. Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Zheng, W (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Med Ctr N S 1211, 1161 21st Ave S, Nashville, TN 37232 USA. EM wei.zheng@vanderbilt.edu RI Shin, Aesun/E-9145-2014; Sinha, Rashmi/G-7446-2015; Shrubsole, Martha/K-5052-2015 OI Shin, Aesun/0000-0002-6426-1969; Sinha, Rashmi/0000-0002-2466-7462; Shrubsole, Martha/0000-0002-5591-7575 FU NCI NIH HHS [P50 CA095103, P50 CA950103, R01 CA097386, R01 CA97386] NR 47 TC 41 Z9 42 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2007 VL 121 IS 1 BP 136 EP 142 DI 10.1002/ijc.22664 PG 7 WC Oncology SC Oncology GA 166ZP UT WOS:000246420500018 PM 17354224 ER PT J AU Chen, ZG Fu, LP Herrero, R Schiffman, M Burk, RD AF Chen, Zigui Fu, Leiping Herrero, Rolando Schiffman, Mark Burk, Robert D. TI Identification of a novel human papillomavirus (HPV97) related to HPV18 and HPV45 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; novel type; phylogeny; evolution ID CERVICAL-CARCINOMA CELLS; BINDING-SITES; MESSENGER-RNA; TYPE-16; DNA; E7; E6; TRANSCRIPTION; PROTEINS; P53 AB Human papillomavirus (HPV) type 97 was identified and the genome was cloned from cervicovaginal cells of a Costa Rican woman with a normal Pap smear. The HPV97 L1 open reading frame (ORF) was most closely related to HPV45 (84% identity) and HPV18 (79% identity), placing it into the high-risk alpha 7 species. Ectopic expression of the HPV97 E6 and E7 proteins significantly decreased steady state p53 and pRb levels using an in vitro cotransfection assay, respectively. These data suggest that HPV97 shares a most recent common ancestor with HPV18 and HPV45 and should be evaluated in cancer specimens from different geographic populations. (C) 2007 Wiley-Liss, Inc. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Costa Rican Fdn Hlth Sci, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. US Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NCI, NIH, Bethesda, MD USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Obstet Gynecol & Womans Hlth, Bronx, NY 10467 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. RP Chen, ZG (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Ullmann Bldg Room 515,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM zchen@aecom.yu.edu; burk@aecom.yu.edu RI Chen, Zigui/E-8490-2017 FU NCI NIH HHS [CA78527] NR 39 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2007 VL 121 IS 1 BP 193 EP 198 DI 10.1002/ijc.22632 PG 6 WC Oncology SC Oncology GA 166ZP UT WOS:000246420500025 PM 17351898 ER PT J AU Pinheiro, AP Thornton, LM Plotonicov, KH Tozzi, F Klump, KL Berrettini, WH Brandt, H Crawford, S Crow, S Fichter, MM Goldman, D Halmi, KA Johnson, C Kaplan, AS Keel, P LaVia, M Mitchell, J Rotondo, A Strober, M Treasure, J Woodside, DB Von Holle, A Hamer, R Kaye, WH Bulik, CM AF Pinheiro, Andrea Poyastro Thornton, Laura M. Plotonicov, Katherine H. Tozzi, Federica Klump, Kelly L. Berrettini, Wade H. Brandt, Harry Crawford, Steven Crow, Scott Fichter, Manfred M. Goldman, David Halmi, Katherine A. Johnson, Craig Kaplan, Allan S. Keel, Pamela LaVia, Maria Mitchell, James Rotondo, Alessandro Strober, Michael Treasure, Janet Woodside, D. Blake Von Holle, Ann Hamer, Robert Kaye, Walter H. Bulik, Cynthia M. TI Patterns of menstrual disturbance in eating disorders SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article; Proceedings Paper CT International Conference on Eating Disorders of the Academy-for-Eating-Disorders CY JUN 07-10, 2006 CL Barcelona, SPAIN SP Acad Eating Disorders DE eating disorders; menstrual dysfunction; body mass index; purging behaviors; binge eating; personality; comorbidity ID FUNCTIONAL HYPOTHALAMIC AMENORRHEA; CANADIAN COMMUNITY SAMPLE; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; NEUROENDOCRINE CONTROL; REPRODUCTIVE FUNCTION; STRUCTURED INTERVIEW; LONGITUDINAL DATA; BODY-WEIGHT; DSM-IV AB Objective: To describe menstrual disturbance in eating disorders (ED). Method: We describe menstrual history in 1,705 women and compare eating, weight, and psychopathological traits across menstrual groups. Results: Menstrual dysfunction occurred across all eating disorder subtypes. Individuals with normal menstrual history and primary amenorrhea reported the highest and lowest lifetime body mass index (BMI), respectively. Normal menstruation and oligomenorrhea groups reported greater binge eating, vomiting, and appetite suppressant use. Amenorrhea was associated with lower caloric intake and higher exercise. Harm avoidance, novelty seeking, perfectionism, and obsessionality discriminated among menstrual status groups. No differences in comorbid Axis I and II disorders were observed. Conclusion: Menstrual dysfunction is not limited to any eating disorder subtype. BMI, caloric intake, and exercise were strongly associated with menstrual function. Menstrual status is not associated with comorbidity. Menstrual irregularity is an associated feature of all ED rather than being restricted to AN only. (c) 2007 by Wiley Periodicals, Inc. C1 Univ N Carolina, Dept Psychiat, Neurosci Hosp, Chapel Hill, NC 27599 USA. Univ Fed Sao Paulo, Escola Paulista Med, Dept Psiquiat, Sao Paulo, Brazil. Univ Pittsburgh, Dept Psychiat, Med Ctr, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Sheppard Pratt Hlth Syst, Ctr Eating Disorders, Towson, MD USA. Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. Univ Munich, Dept Psychiat, Munich, Germany. Roseneck Hosp Behav Med, Prien Am Chiemsee, Germany. NIAAA, NIH, Rockville, MD 20852 USA. New York Presbyterian Hosp, Westchester Div, Weill Cornell Med Coll, White Plains, NY USA. Laureate Psychiat Clin & Hosp, Tulsa, OK USA. Univ Toronto, Toronto Gen Hosp, Dept Psychiat, Univ Hlth Network, Toronto, ON M5G 1L7, Canada. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Neuropsychiat Res Inst, Fargo, ND USA. Univ N Dakota, Sch Med & Hlth Sci, Dept Clin Neurosci, Grand Forks, ND 58201 USA. Univ Pisa, Dept Psychiat Pharmacol & Biotechnol, Pisa, Italy. Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Resnick Neurpsychiat Hosp, Los Angeles, CA USA. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Bulik, CM (reprint author), Univ N Carolina, Dept Psychiat, Neurosci Hosp, 1st Floor,101 Manning Dr,CB 7160, Chapel Hill, NC 27599 USA. EM cbulik@med.unc.edu RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Tozzi, Federica/0000-0002-3536-2920; Treasure, Janet/0000-0003-0871-4596 NR 67 TC 61 Z9 62 U1 6 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD JUL PY 2007 VL 40 IS 5 BP 424 EP 434 DI 10.1002/eat.20388 PG 11 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 180IN UT WOS:000247356400005 ER PT J AU FitzGerald, MP Janz, NK Wren, PA Wei, JT Weber, AM Ghetti, C Cundiff, GW AF FitzGerald, M. P. Janz, N. K. Wren, P. A. Wei, J. T. Weber, A. M. Ghetti, C. Cundiff, G. W. CA Pelvic Floor Disorders Network TI Prolapse severity, symptoms and impact on quality of life among women planning sacrocolpopexy SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Society-of-Gynecologic-Surgeons CY APR 04-06, 2005 CL Rancho Mirage, CA SP Soc Gynecol Surg DE pelvic organ prolapse; quality of life; pelvic floor dysfunction ID PELVIC ORGAN PROLAPSE; LOCATION AB Objectives: To explore the relationship between severity of pelvic organ prolapse (POP), symptoms of pelvic dysfunction and quality of life using validated measures. Method: Baseline data from 314 participants in the Colpopexy And Urinary Reduction Efforts (CARE) trial were analyzed. Pelvic symptoms and impact were assessed using the Pelvic Floor Distress Inventory (PFDI) and the Pelvic Floor Impact Questionnaire (PFIQ). PFDI and PFIQ scores were compared by prolapse stage and history of incontinence or POP surgery. Regression analyses were performed to identify other predictors of symptoms and impact. Results: Women were predominantly (90%) Caucasian and had mean age of 61 years. Women with stage II POP, especially those with prior surgery, reported more symptoms and impact than women with more advanced POP. There were no other significant predictors of symptoms or life impact. Conclusions: Women planning sacrocolpopexy with stage II prolapse and prior pelvic surgery reported more symptoms and quality of life impact than those with more advanced prolapse. (c) 2007 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 Loyola Univ, Med Ctr, Div Female Pelv Med & Reconstruct Surg, Maywood, IL 60153 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Oakland Univ, Rochester, MI 48063 USA. NICHHD, Contracept & Reprod Hlth Branch, Ctr Populat Res, Bethesda, MD 20892 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Johns Hopkins Sch Med, Baltimore, MD USA. RP FitzGerald, MP (reprint author), Loyola Univ, Med Ctr, Div Female Pelv Med & Reconstruct Surg, 2160 S 1st Ave,Bldg 103,Room 1004, Maywood, IL 60153 USA. EM Mfitzg8@lumc.edu RI Wei, John/E-8967-2012 FU NICHD NIH HHS [U10 HD41250, U01 HD41249, U10 HD41260, U10 HD41263, U10 HD41267, U10 HD41268, U10 HD41269] NR 9 TC 13 Z9 15 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD JUL PY 2007 VL 98 IS 1 BP 24 EP 28 DI 10.1016/j.ijgo.2007.03.018 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 191TQ UT WOS:000248155300006 PM 17477927 ER PT J AU Michels, KB Willett, WC Graubard, BI Vaidya, RL Cantwell, MM Sansbury, LB Forman, MR AF Michels, K. B. Willett, W. C. Graubard, B. I. Vaidya, R. L. Cantwell, M. M. Sansbury, L. B. Forman, M. R. TI A longitudinal study of infant feeding and obesity throughout life course SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE overweight; infant feeding; breastfeeding; infant formula ID OVERWEIGHT STATUS; GROWTH VELOCITY; UNITED-STATES; BIRTH-WEIGHT; BODY-SIZE; BREAST; DURATION; WOMEN; RISK; CHILDHOOD AB Background: The Centers for Disease Control and Prevention and the US Department of Health and Human Services promote breastfeeding as a strategy for reducing childhood overweight. We evaluated the relation between infant feeding and the development of overweight and obesity throughout life course. Methods: We investigated the association between infant feeding and obesity among 35526 participants in the Nurses' Health Study II who were followed prospectively from 1989 to 2001. Mothers of participants provided information by mailed questionnaires on the duration of breast- and bottle-feeding, as well as the type of milk or milk substitute in the bottle. Information on body shape at ages 5 and 10, weight at age 18, current weight between 1989 and 2001, and height was reported by the participants. Results: The duration of breastfeeding, including exclusive breastfeeding, was not related to being overweight (25 <= body mass index (BMI) <30 kg/m(2)) or obese (BMI >= 30 kg/m2) during adult life. Women who were exclusively breastfed for more than 6 months had a risk of 0.94 (95% confidence interval (CI) 0.83-1.07) of becoming obese as adults compared with women who were not breastfed. Exclusive breastfeeding for more than 6 months was associated with leaner body shape at age 5 (odds ratio (OR)=0.81; 95% CI 0.65-1.01 for the highest vs the lowest category of body shape) compared to women who were not breastfed or breastfed for less than 1 week, but this association did not persist during adolescence or adulthood. Conclusions: We did not find that having been breastfed was associated with women's likelihood of becoming overweight or obese throughout life course. Although breastfeeding promotes the health of mother and child, it is unlikely to play an important role in controlling the obesity epidemic. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr,Dept Obstet Gyneco, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NCI, NIH, Bethesda, MD 20892 USA. Queens Univ Belfast, Ctr Clin & Populat Sci, Belfast BT7 1NN, Antrim, North Ireland. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Michels, KB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Obstet & Gynecol Epidemiol Ctr,Dept Obstet Gyneco, 221 Longwood Ave, Boston, MA 02115 USA. EM kmichels@rics.bwh.harvard.edu FU CCR NIH HHS [N02-RC-17027]; NCI NIH HHS [CA50385] NR 37 TC 63 Z9 64 U1 2 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 2007 VL 31 IS 7 BP 1078 EP 1085 DI 10.1038/sj.ijo.0803622 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 182EJ UT WOS:000247487600007 PM 17452993 ER PT J AU McKean-Cowdin, R Li, X Bernstein, L McTiernan, A Ballard-Barbash, R Gauderman, WJ Gilliland, F AF McKean-Cowdin, R. Li, X. Bernstein, L. McTiernan, A. Ballard-Barbash, R. Gauderman, W. J. Gilliland, F. TI The ADRB3 Trp64Arg variant and obesity in African-American breast cancer cases SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE African American; visceral fat; cancer; magnetic resonance imaging ID BODY-MASS INDEX; BETA(3)-ADRENERGIC RECEPTOR GENE; INSULIN-RESISTANCE SYNDROME; PHYSICAL-ACTIVITY LEVELS; VISCERAL FAT; ADJUVANT CHEMOTHERAPY; ADRENERGIC-RECEPTOR; BETA-3-ADRENERGIC RECEPTOR; POSTMENOPAUSAL WOMEN; SEX-HORMONES AB Objective: To determine if a missense change at codon 64 of ADRB3 (Trp64Arg), a candidate obesity gene, is associated with obesity and levels of subcutaneous or visceral fat in African-American breast cancer cases. Several observational studies have found that women, who are overweight or obese at the time of diagnosis, as well as those who gain weight after diagnosis, are at greater risk for breast cancer recurrence and death than non-overweight women. Design: Prospective cohort of breast cancer cases. Subjects: 219 African-American breast cancer patients participating in the Los Angeles component of the Health, Eating, Activity and Lifestyle Study. Measures: ADRB3 Trp64Arg genotype, measures of weight including body mass index (BMI), weight gain (weight 5 years before diagnosis compared with weight at 30 months after diagnosis), obesity (BMI >= 30 kg/m(2)), waist/hip circumference and visceral or subcutaneous fat were determined by magnetic resonance imaging. Results: African-American women who were homozygous for the ADRB3 wild-type allele had significantly higher mean visceral fat levels than women who carried the variant (P=0.04), and were significantly more likely to be obese (odd ratios (OR)=2.1, 95% confidence interval (CI)=1.1-4.2). The association with obesity was most pronounced among women who were premenopausal (OR=4.8, 95% CI=1.3-18), who received chemotherapy for their breast cancer (OR=6.1, 95% CI=1.8-20), or who were not physically active (OR=3.9, 95% CI=1.5-9.7). Conclusion: The wild- type allele of the ADRB3 missense change was associated with measures of obesity in our sample of African-American women. The association was modified by menopausal status, history of chemotherapy and modest levels of physical activity. These results will need to be confirmed in an independent sample. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Washington, DC USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP McKean-Cowdin, R (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1441 Eastlake Ave,MS-44 Room 4419A, Los Angeles, CA 90033 USA. EM mckeanco@usc.edu FU NCI NIH HHS [N01 PC035138-22, N01 PC067010, N01-PC-35139, N01PC35139, PC-67010]; NICHD NIH HHS [N01 HD3-3175] NR 57 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD JUL PY 2007 VL 31 IS 7 BP 1110 EP 1118 DI 10.1038/sj.ijo.0803554 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 182EJ UT WOS:000247487600012 PM 17264845 ER PT J AU Huff, J Sass, J AF Huff, James Sass, Jennifer TI Atrazine - A likely human carcinogen? SO INTERNATIONAL JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Letter ID RAMAZZINI-FOUNDATION; INDUSTRY INFLUENCE; IARC MONOGRAPHS; PUBLIC-HEALTH; CHEMICALS; PROGRAM; BIOASSAYS; CANCER C1 Natl Inst Environm Sci, Res Triangle Pk, NC 27709 USA. Natl Resources Def Council, Washington, DC 20005 USA. RP Huff, J (reprint author), Natl Inst Environm Sci, Res Triangle Pk, NC 27709 USA. NR 19 TC 5 Z9 5 U1 0 U2 3 PU ABEL PUBLICATION SERVICES PI BURLINGTON PA 1611 AQUINAS COURT, BURLINGTON, NC 27215 USA SN 1077-3525 J9 INT J OCCUP ENV HEAL JI Int. J. Occup. Environ. Health PD JUL-SEP PY 2007 VL 13 IS 3 BP 356 EP 358 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 209QN UT WOS:000249403200013 ER PT J AU Price, DJ Ravindranath, T Kaler, SG AF Price, David J. Ravindranath, Thyyar Kaler, Stephen G. TI Internal jugular phlebectasia in Menkes disease SO INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY LA English DT Article DE internal jugular phlebectasia; venous aneurysm; neck mass; Menkes disease ID CANDIDATE GENE; VENOUS ANEURYSMS; CHILDREN; DIAGNOSIS; ENCODES; VEIN AB Pediatric neck masses should trigger a high. index of suspicion for certain genetic disorders of connective tissue. To highlight this, we report on three infants with Menkes disease, an inherited disorder of copper transport, who developed large, unilateral neck masses at between 7 and 17 months of age. All were identified in imaging studies as internal jugular phlebectasia. The masses, which enlarged on crying or exertion, have remained clinically benign in these patients for 20, 17, and 2 months, respectively. While arterial tortuosity and aneurysms have been reported often in Menkes disease, venous phlebectasia has rarely been described. We speculate that tow activity of the copper-dependent enzyme, lysyl oxidase, leading to reduced tensile-strength in the deep cervical fascia comprising the carotid sheath may predispose to internal jugular phlebectasia in these individuals. Improved survival and neurological outcomes in infants with Menkes disease due to advances in early diagnosis and treatment may be associated with recognition of novel clinical stigmata of this condition such as internal jugular phlebectasia. Published by Elsevier. Ireland Ltd. C1 NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. New York Med Coll, Valhalla, NY 10595 USA. Columbia Univ, Med Ctr, Dept Pediat, Div Crit Care Med, New York, NY 10027 USA. RP Kaler, SG (reprint author), NICHHD, Unit Pediat Genet, Lab Clin Genom, NIH, Bldg 10,Room 5-2571,10 Ctr Dr MSC 1832, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU Intramural NIH HHS [Z01 HD008768-04] NR 20 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-5876 J9 INT J PEDIATR OTORHI JI Int. J. Pediatr. Otorhinolaryngol. PD JUL PY 2007 VL 71 IS 7 BP 1145 EP 1148 DI 10.1016/j.ijporl.2007.02.021 PG 4 WC Otorhinolaryngology; Pediatrics SC Otorhinolaryngology; Pediatrics GA 182GT UT WOS:000247493800021 PM 17482283 ER PT J AU Siedner, MJ Pandori, M Leon, SR Espinosa, BJ Hall, ER Caceres, C Coates, TJ Klausner, JD AF Siedner, Mark J. Pandori, Mark Leon, Segundo R. Espinosa, Benjamin J. Hall, Eric R. Caceres, Carlos Coates, Thomas J. Klausner, Jeffrey D. CA NIMH Collaborat HIV STD P T G TI Facilitating lymphogranuloma venereum surveillance with the use of real time polymerase chain reaction SO INTERNATIONAL JOURNAL OF STD & AIDS LA English DT Letter ID UNITED-KINGDOM; MEN; SEX; INFECTION; PROCTITIS; HERPES C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Baltimore, MD USA. San Francisco Dept Publ Hlth, Publ Hlth Lab, San Francisco, CA USA. Univ Peruana Cayetano Heredia, Fac Salud Publ, Lima, Peru. USN, Med Res Ctr, Dept Bacteriol, Lima, Peru. Univ Calif Los Angeles, David Geffen Sch Med, Program Global Hlth, Los Angeles, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. NIMH, Multisite Int Grp, Bethesda, MD 20892 USA. RP Siedner, MJ (reprint author), 6633 Hanover Dr, San Jose, CA 95129 USA. EM msiedner@gmail.com OI Caceres, Carlos/0000-0002-8101-0790 NR 15 TC 3 Z9 3 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1G 0AE, ENGLAND SN 0956-4624 J9 INT J STD AIDS JI Int. J. STD AIDS PD JUL PY 2007 VL 18 IS 7 BP 506 EP 507 DI 10.1258/095646207781147256 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 192DB UT WOS:000248179900018 PM 17623514 ER PT J AU Kim, MK Na, JR Lee, TH Im, WT Soung, NK Yang, DC AF Kim, Myung Kyum Na, Ju-Ryun Lee, Tae-Hoo Im, Wan-Taek Soung, Nak-Kyun Yang, Deok-Chun TI Solirubrobacter soli sp nov., isolated from soil of a ginseng field SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DEOXYRIBONUCLEIC-ACID; GEN. NOV.; BACTERIUM AB A Gram-positive, non-spore-forming, rod-shaped and non-motile bacterium, strain Gsoil 355(T) was isolated from soil of a ginseng field in South Korea. In phylogenetic analyses based on 16S rRNA gene sequences, strain Gsoil 355(T) showed the highest levels of sequence similarity with respect to Solirubrobacter pauli B33D1(T) (97.4 %), Conexibacter woesei DSM 14684(T) (94.2%) and Patulibacter minatonensis KV-614(T) (91.8 %). The strain possesses menaquinone MK-7(H-4) and contains C-16:0 and C-18:0 omega 9c as the predominant fatty acids. The DNA G + C content is 71.5 mol%. On the basis of genotypic and phenotypic characteristics, strain Gsoil 355(T) represents a novel species of the genus Solirubrobacter, for which the name Solirubrobacter soli sp. nov. is proposed. The type strain is Gsoil 355(T) (= KCTC 12628(T) = LMG 23485(T)). C1 Kyung Hee Univ, Coll Life Sci, Dept Oriental Med & Mat & Proc, Kyunggido, South Korea. Korea Adv Inst Sci & Technol, Dept Biol Sci, Environm & Mol Microbiol Lab, Taejon 305701, South Korea. Natl Canc Inst, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Yang, DC (reprint author), Kyung Hee Univ, Coll Life Sci, Dept Oriental Med & Mat & Proc, 1 Seocheon Dong, Kyunggido, South Korea. EM deokchunyang@yahoo.co.kr NR 21 TC 14 Z9 15 U1 1 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD JUL PY 2007 VL 57 BP 1453 EP 1455 DI 10.1099/ijs.0.64715-0 PN 7 PG 3 WC Microbiology SC Microbiology GA 195SR UT WOS:000248432500016 PM 17625174 ER PT J AU Merrick, J AF Merrick, Joav TI Convention on the rights of persons with disabilities SO INTERNATIONAL JOURNAL ON DISABILITY AND HUMAN DEVELOPMENT LA English DT Editorial Material C1 [Merrick, Joav] Minist Social Affairs, Jerusalem, Israel. [Merrick, Joav] NICHHD, Bethesda, MD USA. RP Merrick, J (reprint author), Minist Social Affairs, Jerusalem, Israel. EM jmerrick@zahav.net.il NR 2 TC 0 Z9 0 U1 1 U2 2 PU FREUND PUBLISHING HOUSE LTD PI TEL AVIV PA PO BOX 35010, TEL AVIV 61350, ISRAEL SN 1565-012X J9 INT J DISABIL HUM DE JI Int. J. Disabil. Hum. Dev. PD JUL-SEP PY 2007 VL 6 IS 3 BP 225 EP 225 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 279YK UT WOS:000254391600001 ER PT J AU Goldberg, AFX Ritter, LM Khattree, N Peachey, NS Fariss, RN Dang, L Yu, MZ Bottrell, AR AF Goldberg, Andrew F. X. Ritter, Linda M. Khattree, Nidhi Peachey, Neal S. Fariss, Robert N. Dang, Loan Yu, Minzhong Bottrell, Alyssa R. TI An intramembrane glutamic acid governs peripherin/rds function for photoreceptor disk morphogenesis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID DEGENERATION SLOW RDS; DOMINANT RETINITIS-PIGMENTOSA; TIME QUANTITATIVE PCR; TRANSGENIC MICE; RETINAL DEGENERATION; ROD PHOTORECEPTORS; MUTANT MICE; TETRASPANIN SUPERFAMILY; MOLECULAR-CLONING; MEMBRANE-PROTEIN AB PURPOSE. Peripherin/rds (P/rds), the product of the retinal degeneration slow (rds) gene, is a tetraspanin protein that plays a pivotal role for photoreceptor outer segment (OS) structure and is involved in a broad spectrum of inherited retinal degenerations. P/rds interacts with the homologous protein rom-1, previously proposed to regulate P/rds function. The authors examined the significance of an intramembrane glutamic acid conserved in all P/rds proteins (and many other tetraspanins) but absent in all rom-1 orthologs. METHODS. The authors performed isosteric glutamine substitution of the conserved glutamate at position 276, in the fourth transmembrane domain of bovine P/rds, and expressed E276Q P/rds in COS-1 cells and in transgenic mouse photoreceptors of rds +/+, -/+, and -/- backgrounds. Western blot, immunoprecipitation, and sedimentation analyses were used to assess protein structure and interactions. Microscopy and electroretinography were used to characterize transgenic protein localization and retinal photoreceptor structure and function. RESULTS. E276Q P/rds was expressed, assembled, and properly localized in photoreceptor OSs of transgenic mice. In contrast to wild-type (WT) P/rds, however, this mutant did not rescue the OS structural defects observed in rds -/- and -/+ mice. Moreover, E276Q expression did not prevent the retinal degeneration that occurred as a consequence of OS disruption. CONCLUSIONS. E276 plays a critical role in P/rds support of photoreceptor OS structure. This finding provides a molecular rationale for asymmetry in P/rds and rom-1 function and for rom-1 regulation of P/rds activity. These findings also suggest that ionizable intramembrane residues may serve regulatory roles for tetraspanin proteins more generally. C1 Oakland Univ, Eye Res Inst, Rochester, MI 48309 USA. Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Cleveland VA Med Ctr, Cleveland, OH USA. NEI, NIH, Bethesda, MD USA. RP Goldberg, AFX (reprint author), Oakland Univ, Eye Res Inst, 417 Dodge Hall, Rochester, MI 48309 USA. EM goldberg@oakland.edu RI Peachey, Neal/G-5533-2010 FU NCRR NIH HHS [RR017890]; NEI NIH HHS [EY013246, EY014803, EY15638] NR 60 TC 18 Z9 18 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2007 VL 48 IS 7 BP 2975 EP 2986 DI 10.1167/iovs.07-0049 PG 12 WC Ophthalmology SC Ophthalmology GA 187NT UT WOS:000247855600005 PM 17591862 ER PT J AU Cassoux, N Giron, A Bodaghi, B Tran, THC Baudet, S Davy, F Chan, CC Lehoang, P Merle-Beral, H AF Cassoux, Nathalie Giron, Alain Bodaghi, Bahram Tran, Thi H. C. Baudet, Sylvie Davy, Frederic Chan, Chi C. Lehoang, Phuc Merle-Beral, Helene TI IL-10 measurement in aqueous humor for screening patients with suspicion of primary intraocular lymphoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NERVOUS-SYSTEM LYMPHOMA; ANTERIOR-CHAMBER PARACENTESIS; GENE REARRANGEMENT; DIAGNOSIS; UVEITIS; INTERLEUKIN-10; FLUID AB PURPOSE. To determine the value of IL-10 measurement in aqueous humor (AH) for screening in primary intraocular lymphoma (PIOL). METHODS. One hundred consecutive diagnostic or therapeutic vitrectomies were performed in patients with uveitis. During surgery, 100 mu L of both AH and pure vitreous was taken. IL-10 levels were determined with a standard quantitative sandwich enzyme immunoassay technique. Patients were distributed in two groups: 51 patients with proven PIOL, 108 patients with uveitis divided into 74 with uveitis of proven etiology and 34 with idiopathic uveitis. Groups were compared by ANOVA and the Tukey-Kramer test or nonparametric Wilcoxon test. Distributions were compared by using the chi(2) test. Segmentation was derived from the ROC curves by choosing a tradeoff between sensitivity and specificity. RESULTS. In patients with PIOL, IL-10 mean values were 2205.5 pg/mL (median: 1467 pg/mL) in the vitreous and 543.4 pg/mL (median: 424 pg/mL) in AH. In patients with uveitis (idiopathic and diagnostic uveitis), mean values were 26.6 pg/ mL ( median: 8 pg/mL) in the vitreous, and 21.9 pg/mL (median: 8 pg/mL) in AH. IL-10 mean values were significantly different between patients with PIOL and patients with uveitis (P < 10(-3)). The areas under the curves were 0.989 and 0.962 for vitreous and AH, respectively. A cutoff of 50 pg/ mL in the AH was associated with a sensitivity of 0.89 and a specificity of 0.93. In the vitreous, a cutoff value of 400 pg/ mL yielded a specificity of 0.99 and a sensitivity of 0.8. CONCLUSIONS. Diagnosis of PIOL is often made months or years after the initial onset of ocular symptoms. Cytology remains the gold standard for diagnosis. However, measurement of IL-10 in the AH is a good screening test to reduce diagnostic delays. C1 Hop La Pitie Salpetriere, Dept Ophthalmol, F-75013 Paris, France. Hop La Pitie Salpetriere, Dept Hematol, F-75013 Paris, France. INSERM, Unite 678, F-75730 Paris, France. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Cassoux, N (reprint author), Hop La Pitie Salpetriere, Dept Ophthalmol, 83 Blvd Hop, F-75013 Paris, France. EM nathalie.cassoux@psl.aphp.fr FU Intramural NIH HHS [Z01 EY000222-22] NR 30 TC 64 Z9 68 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2007 VL 48 IS 7 BP 3253 EP 3259 DI 10.1167/iovs.06-0031 PG 7 WC Ophthalmology SC Ophthalmology GA 187NT UT WOS:000247855600039 PM 17591896 ER PT J AU Bryant, AS Leighty, RM Shen, XL Brouwers, P AF Bryant, Allison S. Leighty, Robert M. Shen, XianLin Brouwers, Pim TI Response to "Predictors of repeat pregnancy among HIV-1-infected women - New epidemiology, old challenges" SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID UNINTENDED PREGNANCY; UNITED-STATES C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Clin Trials & Survey Corp, Baltimore, MD USA. Baylor Coll Med, Houston, TX 77030 USA. NIMH, Rockville, MD 20857 USA. RP Bryant, AS (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 8 TC 0 Z9 0 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 JUL 1 PY 2007 VL 45 IS 3 BP 369 EP 369 DI 10.1097/QAI.0b013e3180691145 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 183KY UT WOS:000247572900023 ER PT J AU Brunssen, SH Harry, GJ AF Brunssen, Susan H. Harry, G. Jean TI Diffuse white matter injury and neurologic outcomes of infants born very preterm in the 1990s SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE neurologic outcomes; oligodendrocytes; premature infant; white matter injury ID LOW-BIRTH-WEIGHT; NEONATAL RESEARCH NETWORK; MATERNAL INFECTION; MAGNESIUM-SULFATE; PERIVENTRICULAR LEUKOMALACIA; NEURODEVELOPMENTAL OUTCOMES; DEVELOPMENTAL-DISABILITY; CHILDREN BORN; TERM; AGE AB Neurocognitive outcomes of infants born very preterm (less than 32 weeks gestation) remain a major concern in perinatal practice. Very preterm birth rates have increased, with enhanced survival since 1990. As focal brain lesions become less common, diffuse injury to both gray and white matter is now the primary focus for improving neurologic outcomes in survivors. Recent evidence supports preoligodendrocytes as the principal cellular target of diffuse white matter injury due to their susceptibility to hypoxic-ischemic and inflammatory insults. An understanding of their development and vulnerability can inform acute nursing care of very preterm infants. C1 Univ N Carolina, Sch Med, Sch Nursing, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Neurodev Disorders Res Ctr, Chapel Hill, NC 27599 USA. NIEHS, Neurotoxicol Grp, Neurobiol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Brunssen, SH (reprint author), Univ N Carolina, Sch Med, Sch Nursing, Chapel Hill, NC 27599 USA. EM brunssen@email.unc.edu NR 50 TC 6 Z9 10 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD JUL-AUG PY 2007 VL 36 IS 4 BP 386 EP 395 DI 10.1111/J.1552-6909.2007.00156.x PG 10 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 193KG UT WOS:000248272300016 PM 17594417 ER PT J AU Brass, DM Hollingsworth, JW Fessler, MB Savov, JD Maxwell, AB Whitehead, GS Burch, LH Schwartz, DA AF Brass, David M. Hollingsworth, John W. Fessler, Michael B. Savov, Jordan D. Maxwell, Abby B. Whitehead, Gregory S. Burch, Lauranell H. Schwartz, David A. TI The IL-1 type 1 receptor is required for the development of LPS-induced airways disease SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE LPS; endotoxin; airway disease; IL-1; IL-1 receptor; airway remodeling ID TOLL-LIKE RECEPTOR-4; PLASMINOGEN-ACTIVATOR; PULMONARY-FIBROSIS; EXPRESSION; GENE; MICE; FIBROBLASTS; INHALATION; IL-1-BETA; MEDIATORS AB Background: The contribution of IL-1 beta signaling through the IL-1 type 1 receptor (Il-1R1) to the development of persistent LPS-induced airway disease has not been investigated. Objective: To determine the importance of signaling through the IL-1 type I receptor in the development of LPS-induced airway disease. Methods: We exposed IL-1R1-deficient (C57BL/6(IL-1RI-/-)) mice to an aerosol of LPS or filtered air for I day, I week, or 4 weeks. Results: After 4 weeks of LPS inhalation, C57BL/6(IL-1RI-/-) mice failed to develop significant submucosal thickening, whereas C57BL/6 mice had significantly thickened submucosa in small, medium, and large airways compared with those of unexposed control mice. Cell proliferation in the airways of both the 1-week and 4-week LPS-exposed C57BL/6(IL-1RI-/-) mice was significantly reduced compared with LPS-exposed C57BL/6 mice. mRNA for type III alpha-3 procollagen was significantly elevated over baseline in C57BL/6 yet remained unchanged compared with baseline in C57BL/6(IL-1RI-/-) mice after 1 week or 4 weeks of LPS inhalation. mRNA for tissue inhibitor of metalloprotease 1 in C57BL/6 mice in the 1-week and 4-week groups was significantly elevated over both control mice and C57BL/6(IL-1RI-/-) Mice. Conclusion: These data support the hypothesis that signaling through the IL-1 receptor modulates extracellular matrix homeostasis in response to inhaled LPS. Clinical implications: Attenuating IL-1R1-mediated signaling might be an effective therapy against the development of airway remodeling in chronic inflammatory diseases. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC 27706 USA. RP Brass, DM (reprint author), Natl Inst Environm Hlth Sci, Rall Bldg,Room C224,POB 12233,MD C2-15,111 Alexan, Res Triangle Pk, NC 27709 USA. EM brassd@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101947-03, Z01 ES101946-03, Z01 ES101945-03]; NIEHS NIH HHS [Z01 ES101946, ES12717, Z01 ES101947, K08 ES012717, Z01 ES101945] NR 24 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2007 VL 120 IS 1 BP 121 EP 127 DI 10.1016/j.jaci.2007.03.051 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 190NS UT WOS:000248066400017 PM 17512577 ER PT J AU Simons, FER Frew, AJ Ansotegui, IJ Bochner, BS Golden, DBK Finkelman, FD Leung, DYM Lotvall, J Marone, G Metcalfe, DD Muller, U Rosenwasser, LJ Sampson, HA Schwartz, LB van Hage, M Walls, AF AF Simons, F. Estelle R. Frew, Anthony J. Ansotegui, Ignacio J. Bochner, Bruce S. Golden, David B. K. Finkelman, Fred D. Leung, Donald Y. M. Lotvall, Jan Marone, Gianni Metcalfe, Dean D. Mueller, Ulrich Rosenwasser, Lanny J. Sampson, Hugh A. Schwartz, Lawrence B. van Hage, Marianne Walls, Andrew F. TI Risk assessment in anaphylaxis: Current and future approaches SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE anaphylaxis; mast cell; basophil; IgE; Fc epsilon RI; histamine; tryptase; most cell carboxypeptidase; allergens; insect venom allergy; food allergy ID HYMENOPTERA VENOM ALLERGY; INSECT-STING CHALLENGE; HUMAN MAST-CELLS; FC-EPSILON-RI; BASOPHIL ACTIVATION TEST; PEANUT ALLERGY; FOOD ALLERGY; IN-VITRO; SKIN PRICK; FATAL REACTIONS AB Risk assessment of individuals with anaphylaxis is currently hampered by lack of (1) an optimal and readily available laboratory test to confirm the clinical diagnosis of an anaphylaxis episode and (2) an optimal method of distinguishing allergen-sensitized individuals who are clinically tolerant from those at risk for anaphylaxis episodes after exposure to the relevant allergen. Our objectives were to review the effector mechanisms involved in the pathophysiology of anaphylaxis; to explore the possibility of developing an optimal laboratory test to confirm the diagnosis of an anaphylaxis episode, and the possibility of improving methods to distinguish allergen sensitization from clinical reactivity; and to develop a research agenda for risk assessment in anaphylaxis. Researchers from the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergology and Clinical Immunology held a PRACTALL (Practical Allergy) meeting to discuss these objectives. New approaches being investigated to support the clinical diagnosis of anaphylaxis include serial measurements of total tryptase in serum during an anaphylaxis episode, and measurement of baseline total tryptase levels after the episode. Greater availability of the test for mature beta-tryptase, a more specific mast cell activation marker for anaphylaxis than total tryptase, is needed. Measurement of chymase, mast cell carboxypeptidase A3, platelet-activating factor, and other mast cell products may prove to be useful. Consideration should be given to measuring a panel of mediators from mast cells and basophils. New approaches being investigated to help distinguish sensitized individuals at minimum or no risk from those at increased risk of developing anaphylaxis include measurement of the ratio of allergen-specific IgE to total IgE, determination of IgE directed at specific allergenic epitopes, measurement of basophil activation markers by using flow cytometry, and assessment of allergen-specific cytokine responses. Algorithms have been developed for risk assessment of individuals with anaphylaxis, along with a research agenda for studies that could lead to an improved ability to confirm the clinical diagnosis of anaphylaxis and to identify allergen-sensitized individuals who are at increased risk of anaphylaxis. C1 Univ Manitoba, Dept Pediat & Child Hlth, Dept Immunol, Winnipeg, MB R3T 2N2, Canada. Brighton Gen Hosp, Dept Resp Med, Brighton, E Sussex, England. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Royal Hosp, Belfast, Antrim, North Ireland. Univ Cincinnati, Coll Med, Div Immunol, Cincinnati, OH 45221 USA. Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA. Dept Resp Med & Allergol, Gothenburg, Sweden. Univ Naples Federico 2, Div Clin Immunol & Allergy, Naples, Italy. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Bern, Inselspital, Med Klin, CH-3010 Bern, Switzerland. Childrens Mercy Hosp & Clin, Dept Pediat, Kansas City, MO 64108 USA. Mt Sinai Sch Med, Dept Pediat & Biomed Sci, New York, NY 10029 USA. Virginia Commonwealth Univ, Div Rheumatol Allergy & Immunol, Richmond, VA 23284 USA. Karolinska Inst & Univ Hosp, Dept Med Clin Immunol & Allergy, Stockholm, Sweden. Southampton Gen Hosp, Immunopharmacol Grp, Southampton, Hants, England. RP Simons, FER (reprint author), 820 Sherbrook St, Winnipeg, MB R3A 1R9, Canada. EM Imcniven@hsc.mb.ca RI van Hage, Marianne/A-9678-2017 OI van Hage, Marianne/0000-0003-3091-1596 FU Department of Health [H039]; Intramural NIH HHS; Medical Research Council [G0500729] NR 150 TC 140 Z9 143 U1 1 U2 18 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2007 VL 120 IS 1 SU S BP S2 EP S24 DI 10.1016/j.jaci.2007.05.001 PG 23 WC Allergy; Immunology SC Allergy; Immunology GA 193KY UT WOS:000248274100002 PM 17602945 ER PT J AU Trucksess, MW Weaver, CM Oles, CJ Rump, LV White, KD Betz, JM Rader, JI AF Trucksess, Mary W. Weaver, Carol M. Oles, Carolyn J. Rump, Lydia V. White, Kevin D. Betz, Joseph M. Rader, Jeanne I. TI Use of multitoxin immunoaffinity columns for determination of aflatoxins and ochratoxin a in ginseng and ginger SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; MEDICINAL HERBS; TURKEY; CONTAMINATION; PERFORMANCE; MYCOTOXINS; EXTRACTS; CLEANUP; PLANTS; ROOTS AB Conditions were optimized for the simultaneous, alkaline, aqueous methanol extraction of aflatoxins (AFL), i.e., B-1 (AFB(1)), B-2 (AFB(2)), Gi (AFG(1)), and G(2) (AFG(2)), and ochratoxin A (OTA) with subsequent purification, isolation, and determination of the toxins in ginseng and ginger. Powdered roots were extracted with methanol-0.5% NaHCO3 solution (7 + 3). After shaking and centrifugation, the supernatant was diluted with 100 mM phosphate buffer containing 1 % Tween 20 and filtered through glass microfiber filter paper. The filtrate was then passed through an immunoaffinity column, and the toxins were eluted with methanol. The AFL were separated and determined by reversed-phase liquid chromatography (RPLC) with fluorescence detection after postcolumn UV photochemical derivatization. OTA was separated and determined by RPLC with fluorescence detection. Recoveries of AFL added at 2-16 ng/g and OTA added at 1-8 ng/g to ginseng were 72-80 and 86-95%, respectively. Recoveries of AFL and OTA added to ginger were similar to those for ginseng. A total of 39 commercially available ginger products from 6 manufacturers were analyzed. Twenty-six samples were found to be contaminated with AFL at 1-31 ng/g and 29 samples, with OTA at 1-10 ng/g. Ten samples contained no AFL or 07A. Ten ginseng finished products were also analyzed; 3 contained AFL at 0.1 ng/g and 4 contained CITA at levels ranging from 0.4 to 1.8 ng/g. LC/tandem mass spectrometry with multiple-reaction monitoring of 3 collisionally induced product ions from the protonated molecular ions of OTA, AFB(1), and AFG(1) was used to confirm the identities of the toxins in extracts of the finished products. C1 US FDA, College Pk, MD 20740 USA. Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov NR 16 TC 24 Z9 25 U1 1 U2 9 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2007 VL 90 IS 4 BP 1042 EP 1049 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 196YT UT WOS:000248520200025 PM 17760342 ER PT J AU Ershler, WB AF Ershler, William B. TI A gripping reality: oxidative stress, inflammation, and the pathway to frailty SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material ID NF-KAPPA-B; INTERLEUKIN-6 GENE-EXPRESSION; REPRESSION; INHIBITION; SARCOPENIA C1 NIA, Clin Res Branch, Harbor Hosp, Baltimore, MD 21224 USA. RP Ershler, WB (reprint author), NIA, Clin Res Branch, Harbor Hosp, Baltimore, MD 21224 USA. EM ershlerwi@mail.nih.gov NR 12 TC 24 Z9 24 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2007 VL 103 IS 1 BP 3 EP 5 DI 10.1152/japplphysiol.00375.2007 PG 3 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KK UT WOS:000248410900002 PM 17431088 ER PT J AU Howard, C Ferrucci, L Sun, K Fried, LP Walston, J Varadhan, R Guralnik, JM Semba, RD AF Howard, Caitlin Ferrucci, Luigi Sun, Kai Fried, Linda P. Walston, Jeremy Varadhan, Ravi Guralnik, Jack M. Semba, Richard D. TI Oxidative protein damage is associated with poor grip strength among older women living in the community SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE aging; sarcopenia; interleukin-6; oxidative stress; protein carbonyls ID HUMAN SKELETAL-MUSCLE; STRESS; DNA; SARCOPENIA; INCREASES; MARKERS; LIPIDS AB Grip strength, an indicator of muscle strength, has been shown to be a predictor of poor outcomes among older adults. Protein carbonylation, an indicator of oxidative damage to proteins, leads to cellular dysfunction and a decline in tissue function. Oxidative stress has been implicated in the pathogenesis of sarcopenia. The objective was to determine whether serum protein carbonyl concentrations are associated with grip strength in older women living in the community. A cross-sectional study was conducted in 672 women, aged 65 and older, from the Women's Health and Aging Study (WHAS) I, the one-third most disabled women residing in the community in Baltimore, MD. Protein carbonyl;and grip strength were measured in each patient. In a multivariate analysis adjusting for age, race, body mass index, and Mini-Mental;Status Examination score, protein carbonyls (nmol/mg) were associated with grip strength (beta = -6.77, P < 0.01). The statistical;association was unchanged after the analysis adjusted for hypertension, congestive heart failure, and depression. Ordered logistic regression models adjusted for the above factors showed that protein carbonyls are associated with increased odds of being in the lower quartiles of grip strength (odds ratio 8.74, 95% confidence interval (06-71.89, P = 0.043), These results suggest oxidative protein damage is independently associated with low grip strength among older women living in the community. Increased oxidative stress may lie contributing to loss of muscle strength in older adults. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Epidemiol Demog & Biometry Branch, Bethesda, MD 20892 USA. RP Howard, C (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM chowar17@jhmi.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [P30 AG021334, P30-AG-021334, R01 AG027012, R01-AG-027012] NR 22 TC 77 Z9 78 U1 0 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2007 VL 103 IS 1 BP 17 EP 20 DI 10.1152/japplphysiol.00133.2007 PG 4 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KK UT WOS:000248410900005 PM 17379753 ER PT J AU Cohen, O Kanana, H Zoizner, R Gross, C Meiri, U Stern, MD Gerstenblith, G Horowitz, M AF Cohen, Omer Kanana, Hifa Zoizner, Ronen Gross, Chaya Meiri, Uri Stern, Michael D. Gerstenblith, Gary Horowitz, Michal TI Altered Ca2+ handling and myofilament desensitization underlie cardiomyocyte performance in normothermic and hyperthermic heat-acclimated rat hearts SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE cardiomyocyte contractility; calcium transients; ryanodine receptors; L-type calcium channel; phospholamban ID DIHYDROPYRIDINE RECEPTORS; CARDIAC-HYPERTROPHY; PAPILLARY-MUSCLE; SKELETAL-MUSCLE; CALCIUM; PROTEINS; EXPRESSION; RESPONSES; PHOSPHORYLATION; CALSEQUESTRIN AB Heat acclimation (AC) improves cardiac mechanical and metabolic performance. Using cardiomyocytes and isolated hearts from 30-day and 2-day acclimated rats (AC and AC-2d, 34 degrees C), we characterized cellular contractile mechanisms under normothermic (37 degrees C) and hyperthermic (39-42 degrees C) conditions. To determine contractile responses, Ca2+ transients (Ca2+ T), sarcoplasmic reticulum (SR) Ca2+ pool size (fura-2/indo-1 fluorescence), force generation [amplitude systolic motion (ASM)], L-type Ca2+ channels [dihydropyridine receptor (DHPR)], ryanodine receptors (RyRs), and total (PLBt) and phosphorylated phospholamban [serine phosphorylated (PLBs) and theonine phosphorylated (PLBtr)] proteins and transcripts were measured (Western blot, RT-PCR). Cardiac mechanical performance was measured using a Langendorff system. We demonstrated that AC and AC-2d increased Ca2+ T amplitude (148% and 147%, respectively) and twitch force (180% and 130%, respectively) and desensitized myofilaments, as indicated by a rightward shift in the ASM-Ca2+ relationships, despite no change in SR Ca2+ pool size. Hence, generation of higher Ca2+ T underlies greater force development in AC and AC-2d myocytes. In isolated hearts, ryanodine administration eliminated differences between AC and control (C) hearts, implying an important role for RyRs in that acclimation phase. Increased expression of DHPR and RyRs, and decreased PLBs/PLBt in AC hearts only, suggest that different pathways increase force generation in the AC-2d vs. AC myocytes. At basal beating rates, hyperthermia (39-41 degrees C) enhanced pressure generation in AC hearts. C hearts failed to restitute pressure beyond 39 degrees C. Increased beating frequency produced negative inotropic response. In C cardiomyocytes, hyperthermia elevated basal cytosolic Ca2+ and tension, Ca2+ T, and ASM. AC myocytes enhanced Ca2+ T but showed myofilament desensitization, suggesting its involvement in cardiac protection against hyperthermia. Collectively, both Ca2+ turnover and myofilament responsiveness are important adaptive acclimatory targets during normothermic and hyperthermic conditions. C1 Hebrew Univ Jerusalem, Hadassah Med Ctr, Fac Med Dent, Environm Physiol Lab, IL-91120 Jerusalem, Israel. Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA. NIA, Gerontol Res Ctr, Lab Cardiovasc Sci, Baltimore, MD 21224 USA. RP Kanana, H (reprint author), Hebrew Univ Jerusalem, Hadassah Med Ctr, Fac Med Dent, Environm Physiol Lab, POB 12272, IL-91120 Jerusalem, Israel. EM horowitz@cc.huji.ac.il NR 39 TC 21 Z9 22 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD JUL PY 2007 VL 103 IS 1 BP 266 EP 275 DI 10.1152/japplphysiol.01351.2006 PG 10 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 195KK UT WOS:000248410900036 PM 17395755 ER PT J AU Corrigan, PW Watson, AC Otey, E Westbrook, AL Gardner, AL Lamb, TA Fenton, WS AF Corrigan, Patrick W. Watson, Amy C. Otey, Emeline Westbrook, Anne L. Gardner, April L. Lamb, Theodore A. Fenton, Wayne S. TI How do children stigmatize people with mental illness? SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID ATTRIBUTIONAL ANALYSIS; PREJUDICE; MODEL; RESPONSIBILITY; DANGEROUSNESS; PERCEPTIONS; ATTITUDES; VIOLENCE; AIDS AB A way to promote eliminating stigma surrounding mental illnesses is targeting the phenomenon in children. This study's purpose is to validate models of mental illness stigma on children in Grades 6-8. Children completed the revised Attribution Questionnaire in a pretest of a larger study on a mental health education program. Data from this study permitted testing of roles of demographics in these social cognitive models. Subsequent analyses using manifest model structural equations were mixed, but mostly showed adequate fit for multiple versions of the models. These results suggest that models of blame and dangerousness are relevant to the way 10 to 13-year-olds stigmatize mental illness. Demographics were not found to fit these models satisfactorily. Implications of these findings for stigma-change agenda are discussed. C1 IIT, Joint Res Programs Psychiat Rehabil, Chicago, IL 60616 USA. Univ Illinois, Chicago, IL 60680 USA. NIMH, Bethesda, MD 20892 USA. Biol Sci Curriculum Study, Colorado Springs, CO USA. RP Corrigan, PW (reprint author), IIT, Joint Res Programs Psychiat Rehabil, 3424 S State St,1st Floor, Chicago, IL 60616 USA. EM corrigan@iit.edu NR 34 TC 10 Z9 10 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD JUL PY 2007 VL 37 IS 7 BP 1405 EP 1417 DI 10.1111/j.1559-1816.2007.00218.x PG 13 WC Psychology, Social SC Psychology GA 183NY UT WOS:000247580700001 ER PT J AU Ranquet, C Gottesman, S AF Ranquet, Caroline Gottesman, Susan TI Translational regulation of the Escherichia coli stress factor RpoS: a role for SsrA and Lon SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STATIONARY-PHASE REGULATION; SMALL STABLE RNA; MESSENGER-RNA; STOP CODONS; TRANS-TRANSLATION; PROTEIN-SYNTHESIS; TAGGED PROTEINS; QUALITY-CONTROL; TAGGING SYSTEM; 10SA RNA AB Escherichia coli cell viability during starvation is strongly dependent on the expression of the rpoS gene, encoding the RpoS sigma subunit of RNA polymerase. RpoS abundance has been reported to be regulated at many levels, including transcription initiation, translation, and protein stability. The regulatory RNA SsrA (or tmRNA) has both tRNA and mRNA activities, relieving ribosome stalling and cotranslationally tagging proteins. We report here that SsrA is needed for the correct high-level translation of RpoS. The ATP-dependent protease Lon was also found to negatively affect RpoS translation, but only at low temperature. We suggest that SsrA may indirectly improve RpoS translation by limiting ribosome stalling and depletion of some component of the translation machinery. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bldg 37,Room 5132, Bethesda, MD 20892 USA. EM susang@helix.nih.gov FU Intramural NIH HHS NR 47 TC 26 Z9 27 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2007 VL 189 IS 13 BP 4872 EP 4879 DI 10.1128/JB.01838-06 PG 8 WC Microbiology SC Microbiology GA 183ZY UT WOS:000247612100034 PM 17449615 ER PT J AU Wickstrum, JR Skredenske, JM Kolin, A Jin, DJ Fang, J Egan, SM AF Wickstrum, Jason R. Skredenske, Jeff M. Kolin, Ana Jin, Ding J. Fang, Jianwen Egan, Susan M. TI Transcription activation by the DNA-binding domain of the AraC family protein RhaS in the absence of its effector-binding domain SO JOURNAL OF BACTERIOLOGY LA English DT Article ID AMP RECEPTOR PROTEIN; C-TERMINAL DOMAIN; ESCHERICHIA-COLI; FUNCTIONAL DOMAINS; CLONING VECTORS; ALPHA-SUBUNIT; OPERON; PURIFICATION; PROMOTER; GENE AB The Escherichia coli L-rhamnose-responsive transcription activators RhaS and RhaR both consist of two domains, a C-terminal DNA-binding domain and an N-terminal dimerization domain. Both function as dimers and only activate transcription in the presence of L-rhamnose. Here, we examined the ability of the DNA-binding domains of RhaS (RhaS-CTD) and RhaR (RhaR-CTD) to bind to DNA and activate transcription. RhaS-CTD and RhaR-CTD were both shown by DNase I footprinting to be capable of binding specifically to the appropriate DNA sites. In vivo as well as in vitro transcription assays showed that RhaS-CTD could activate transcription to high levels, whereas RhaR-CTD was capable of only very low levels of transcription activation. As expected, RhaS-CTD did not require the presence Of L-rhamnose to activate transcription. The upstream half-site at rhaBAD and the downstream half-site at rhaT were found to be the strongest of the known RhaS half-sites, and a new putative RhaS half-site with comparable strength to known sites was identified. Given that cyclic AMP receptor protein (CRP), the second activator required for full rhaBAD expression, cannot activate rhaBAD expression in a Delta rhaS strain, it was of interest to test whether CRP could activate transcription in combination with RhaS-CTD. We found that RhaS-CTD allowed significant activation by CRP, both in vivo and in vitro, although full-length RhaS allowed somewhat greater CRP activation. We conclude that RhaS-CTD contains all of the determinants necessary for transcription activation by RhaS. C1 Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. NCI, Transcript Control Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Ctr,NIH, Frederick, MD 21702 USA. Univ Kansas, Bioinformat Core Facil, Lawrence, KS 66045 USA. RP Egan, SM (reprint author), Univ Kansas, Dept Mol Biosci, 1200 Sunnyside Ave, Lawrence, KS 66045 USA. EM sme@ku.edu OI Egan, Susan/0000-0002-4078-5899 FU NCRR NIH HHS [P20 RR17708, P20 RR017708, P20 RR016475]; NIGMS NIH HHS [R01 GM055099, R29 GM055099, GM55099] NR 49 TC 19 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2007 VL 189 IS 14 BP 4984 EP 4993 DI 10.1128/JB.00530-07 PG 10 WC Microbiology SC Microbiology GA 189WQ UT WOS:000248019700002 PM 17513476 ER PT J AU Tjandra, N Suzuki, M Chang, SL AF Tjandra, Nico Suzuki, Motoshi Chang, Shou-Lin TI Refinement of protein structure against non-redundant carbonyl C-13 NMR relaxation SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE protein structure refinement; NMR; N-15 relaxation; C-13 ' relaxation; Xplor-NIH; yeast Fis1 protein ID ROTATIONAL DIFFUSION ANISOTROPY; RESIDUAL DIPOLAR COUPLINGS; CHEMICAL-SHIFT ANISOTROPY; LIQUID-CRYSTALLINE PHASE; BACKBONE DYNAMICS; SPECTROSCOPY; ORIENTATIONS; POLYPEPTIDE; INFORMATION; CALMODULIN AB Carbonyl C-13' relaxation is dominated by the contribution from the C-13' chemical shift anisotropy (CSA). The relaxation rates provide useful and non-redundant structural information in addition to dynamic parameters. It is straightforward to acquire, and offers complimentary structural information to the N-15 relaxation data. Furthermore, the non-axial nature of the C-13' CSA tensor results in a T-1/T-2 value that depends on an additional angular variable even when the diffusion tensor of the protein molecule is axially symmetric. This dependence on an extra degree of freedom provides new geometrical information that is not available from the NH dipolar relaxation. A protocol that incorporates such structural restraints into NMR structure calculation was developed within the program Xplor-NIH. Its application was illustrated with the yeast Fis1 NMR structure. Refinement against the C-13' T-1/T-2 improved the overall quality of the structure, as evaluated by cross-validation against the residual dipolar coupling as well as the N-15 relaxation data. In addition, possible variations of the CSA tensor were addressed. C1 NIH, NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. Natl Tsing Hua Univ, Dept Life Sci, Inst Bioinformat & Struct Biol, Hsinchu 30055, Taiwan. RP Tjandra, N (reprint author), NIH, NHLBI, Lab Mol Biophys, Bldg 50,Room 3503, Bethesda, MD 20892 USA. EM nico@helix.nih.gov; slchang@life.nthu.edu.tw FU Intramural NIH HHS NR 42 TC 5 Z9 5 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 2007 VL 38 IS 3 BP 243 EP 253 DI 10.1007/s10858-007-9165-7 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 179RI UT WOS:000247307400005 PM 17554496 ER PT J AU Cauley, JA Danielson, ME Boudreau, RM Forrest, KY Zmuda, JM Pahor, M Tylavsky, FA Cummings, SR Harris, TB Newman, AB AF Cauley, Jane A. Danielson, Michelle E. Boudreau, Robert M. Forrest, Kimberly Yz Zmuda, Joseph M. Pahor, Marco Tylavsky, Frances A. Cummings, Steven R. Harris, Tamara B. Newman, Anne B. CA Health ABC Study TI Inflammatory markers and incident fracture risk in older men and women: The health aging and body composition study SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoporosis; inflammation; fractures; women; cytokines ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; BONE-MINERAL DENSITY; CARDIOVASCULAR-DISEASE; OSTEOCLAST FORMATION; SOLUBLE INTERLEUKIN-6; ESTROGEN DEFICIENCY; IN-VIVO; RECEPTOR; ASSOCIATION AB The inflammation of aging hypothesis purports that aging is the accumulation of damage, which results, in part, from chronic activation of inflammation process. We tested this hypothesis in relationship to fractures in 2985 men and women enrolled in the Health ABC study. Results showed that subjects with the greatest number of inflammatory markers have the highest risk of fracture. Introduction: Cytokines play major roles in regulating bone remodeling in the bone microenvironment, but their relationship to fractures is uncertain. Materials and Methods: The study population includes 2985 well-functioning white and black women and men (42%, black; 51%, women) 70-79 yr of age enrolled in the Health Aging and Body Composition Study. Inflammatory markers were measured in frozen serum using standardized assays. We measured interleukin (IL-6), TNF alpha, C-reactive protein (CRP), and soluble receptors (IL-2 sR, IL-6 sR, TNF sRIand TNF sR2).Cytokine-soluble receptors were measured in a subset (n = 1430). Total hip BMD was measured by DXA. During 5.8 +/- 1.6 yr of 95% complete follow-up, incident fractures were confirmed in 268 subjects. The risk of fracture was compared among subjects with the highest inflammatory markers (quartile 4) versus lower levels (quartiles 1, 2, and 3) using proportional hazard models. Results and Conclusions: Subjects who fractured were more likely to be white and female. Baseline markers of inflammation were higher among subjects who subsequently experienced an incident fracture. In multivariate models, the relative risk of fracture (95% Cls) for subjects with the highest inflammatory markers (quartile 4) compared with those with lower inflammatory markers (quartiles 1, 2, and 3) was 1.34 (0.99, 1.82) for CRP; 1.28 (0.95-1.74) for IL-6; 1.28 (0.97-1.70) for TNF alpha; 1.52 (1.04-2.21) for IL-2 sR; 1.33 (0.90-1.96) for IL-6 sR; 1.73 (1.18-2.55) for TNF sR1 and 1.48 (1.01-2.20) for TNF sR2. In subjects with three or more (out of seven) high inflammatory markers, the relative risk of fracture was 2.65 (1.44-4.89) in comparison with subjects with no elevated markers. (p trend = 0.001). We conclude that elevated inflammatory markers are prognostic for fractures, extending the inflammation hypothesis of aging to osteoporotic fractures. C1 Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Slippery Rock Univ, Dept Hlth & Safety, Slippery Rock, PA 16057 USA. Univ Florida, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. CPMC, San Francisco Coordinating Ctr, San Francisco, CA USA. NIA, Lab Epidemiol Demog Biometry, Bethesda, MD 20892 USA. RP Cauley, JA (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 130 DeSoto St,Crabtree A524, Pittsburgh, PA 15261 USA. EM jcauley@edc.pitt.edu RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Boudreau, Robert/0000-0003-0162-5187 FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 44 TC 108 Z9 109 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUL PY 2007 VL 22 IS 7 BP 1088 EP 1095 DI 10.1359/JBMR.070409 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 181QQ UT WOS:000247451600016 PM 17419681 ER PT J AU Mohla, S AF Mohla, Suresh TI Tumor microenvironment SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article ID INFLAMMATION; CANCER C1 NCI, Tumor Biol & Metastasis Branch, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Mohla, S (reprint author), 6130 Execut Blvd,EPN 5038,Mailstop 7364, Bethesda, MD 20892 USA. EM sm82e@nih.gov NR 12 TC 7 Z9 13 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2007 VL 101 IS 4 BP 801 EP 804 DI 10.1002/jcb.21320 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 185EQ UT WOS:000247694600001 PM 17407156 ER PT J AU Wallqvist, A Huang, RL Covell, DG AF Wallqvist, Anders Huang, Ruili Covell, David G. TI Chemoinformatic analysis of NCI preclinical tumor data: Evaluating compound efficacy from mouse xenograft data, NCI-60 screening data, and compound descriptors SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID IN-VITRO; STRUCTURAL DATABASES; CLONOGENIC-ASSAY; PREDICTIVE-VALUE; DRUG DISCOVERY; MODELS; TRIALS; CHEMOTHERAPY; SIMILARITY AB We provide a chemoinformatic examination of the NCI public human tumor xenograft data to explore relationships between small molecules, treatment modality, efficacy, and toxicity. Efficacy endpoints of tumor weight reduction (TW) and survival time increase (ST) compared to tumor bearing control mice were augmented by a toxicity measure, defined as the survival advantage of treated versus control animals (TX). These endpoints were used to define two independent therapeutic indices (TIs) as the ratio of efficacy (TW or ST) to toxicity (TX). Linear models predictive of xenograft endpoints were successfully constructed (0.67 < r(2) <= 0.74)(observed_versus_predicted) using a model comprised of variables in treatment modality, chemoinformatic descriptors, and in vitro cell growth inhibition in the NCI 60-cell assay. Cross-validation analysis based on randomly chosen training subsets found these predictive correlations to be robust. Model-based sensitivity analysis found chemistry and growth inhibition to provide the best, and treatment modality the worst, indicators of xenograft endpoint. The poor predictive power derived from treatment alone appears to be of less importance to xenograft outcome for compounds having strongly similar chemical and biological features. ROC-based model validation found a 70% positive predictive value for distinguishing FDA approved oncology agents from available xenograft tested compounds. Additional chemoinformatic applications are provided that relate xenograft outcome to biological pathways and putative mechanism of compound action. These results find a strong relationship between xenograft efficacy and pathways comprised of genes having highly correlated mRNA expressions. Our analysis demonstrates that chemoinformatic studies utilizing a combination of xenograft data and in vitro preclinical testing offer an effective means to identify compound classes with superior efficacy and reduced toxicity. C1 NCI, Dev Therapeut Program, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Lab Computat Technol, Frederick, MD 21702 USA. RP Wallqvist, A (reprint author), NCI, Dev Therapeut Program, Frederick, MD 21702 USA. EM wallqvist@ncifcrf.gov OI wallqvist, anders/0000-0002-9775-7469 FU NCI NIH HHS [N01-CO-12400] NR 38 TC 7 Z9 7 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 EI 1549-960X J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD JUL-AUG PY 2007 VL 47 IS 4 BP 1414 EP 1427 DI 10.1021/ci700132u PG 14 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 192HQ UT WOS:000248192200014 PM 17555311 ER PT J AU Borodina, YV Bolton, E Fontaine, F Bryant, SH AF Borodina, Yulia V. Bolton, Evan Fontaine, Fabien Bryant, Stephen H. TI Assessment of conformational ensemble sizes necessary for specific resolutions of coverage of conformational space SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID BOUND LIGAND CONFORMATIONS; FORCE-FIELD; PERFORMANCE; EFFICIENT; PROTEINS; CATALYST; DATABASE; RESPECT; BINDING; OMEGA AB The size of conformational ensembles required for regular coverage of the conformational space of druglike molecules was examined. Using the conformer generation program Omega, the number of regularly distributed conformers (NRC) of flexible compounds was determined as a function of the root-mean-square deviation (RMSD) resolution of coverage. A regression equation was developed predicting the NRC of a molecule as a function of RMSD. The model yielded R-2 of 0.91 for both training and test sets, which consisted of 3414 and 3352 compounds, respectively. Utilizing 14 504 ligands from the Protein Data Bank with experimentally determined 3-D conformations, the regression equation was applied to the estimation of the NRC and the success rate of reproduction of experimental conformations from a theoretical conformation ensemble as a function of RMSD and flexibility was explored. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Bryant, SH (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. EM bryant@ncbi.nlm.nih.gov FU Intramural NIH HHS [Z01 LM100604-04] NR 29 TC 21 Z9 21 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD JUL-AUG PY 2007 VL 47 IS 4 BP 1428 EP 1437 DI 10.1021/ci7000956 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 192HQ UT WOS:000248192200015 PM 17569521 ER PT J AU Pine, DS AF Pine, Daniel S. TI Research Review: A neuroscience framework for pediatric anxiety disorders SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Review DE anxiety; children and axdolescents; amygdala; prefrontal cortex; threat ID MAJOR DEPRESSIVE DISORDER; PREFRONTAL CORTEX; PANIC DISORDER; BEHAVIORAL-INHIBITION; FACIAL EXPRESSIONS; ATTENTIONAL BIAS; PSYCHIATRIC-DISORDERS; AMYGDALA ACTIVATION; SOCIAL COGNITION; FEARFUL FACES AB Across a range of mammalian species, early developmental variations in fear-related behaviors constrain patterns of anxious behavior throughout life. Individual differences in anxiety among rodents and non-human primates have been shown to reflect early-life influences of genes and the environment on brain circuitry. However, in humans, the manner in which genes and the environment developmentally shape individual differences in anxiety and associated brain circuitry remains poorly specified. The current review presents a conceptual framework that facilitates clinical research examining developmental influences on brain circuitry and anxiety. Research using threat-exposure paradigms might most directly integrate basic and clinical perspectives on pediatric anxiety. C1 NIMH, Bethesda, MD 20817 USA. RP Pine, DS (reprint author), NIMH, Bldg 15-K Room 110 MSC-2670, Bethesda, MD 20817 USA. EM daniel.pine@nih.gov NR 85 TC 122 Z9 127 U1 6 U2 26 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 JUL PY 2007 VL 48 IS 7 BP 631 EP 648 DI 10.1111/j.1469-7610.2007.01751.x PG 18 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 182AJ UT WOS:000247477200002 PM 17593144 ER PT J AU Negrete, A Ling, TC Lyddiatt, A AF Negrete, Alejandro Ling, Tau Chuan Lyddiatt, Andrew TI Aqueous two-phase recovery of bio-nanoparticles: A miniaturization study for the recovery of bacteriophage T4 SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE nanoparticulate; aqueous two-phase system; recovery; bacteriophage T4 ID SERUM-ALBUMIN; PLASMID DNA; SYSTEMS; PURIFICATION; CHROMATOGRAPHY; EXTRACTION; PARTITION; TEMPERATURE; PARTICLES; PROTEINS AB Biotechnology industry has recently been demanding nanoparticulate products (20-200 nm) such as viruses, plasmids, virus-like particles and drug delivery assemblies. These products are mainly used as gene delivery systems in gene therapy protocols. During the process development for the manufacture of these products, it is crucial to optimize the recovery and purification steps. Unfortunately, the high value of some bio-nanoparticles complicates the optimization studies. The solvent extraction method with aqueous two-phase systems (ATPS) has been used to successfully recover bioproducts on a large scale. In this study, the potential miniaturization of ATPS is presented. The partition behavior of pure bovine serum albumin (BSA) in PEG-800-phosphate and bacteriophage T4 in PEG 8000-phosphate and PEG 600-sulphate systems were studied at three different scales (10 g, 2 g and 300 mu l). The results obtained showed that the volume ratio (V-R) for BSA (V-R = 1.0) was comparable to the blank systems at the scales studied. Additionally, the partition coefficient (K) was also similar (K= 0.05) with more than 82% of BSA concentrated in the bottom phase. Same system was challenged with bacteriophage T4 showing a V-R = 1.0 and K greater than 5 with the infective particles concentrated in the top phase. The bacteriophage T4 was concentrated in opposite phase in the PEG-600-sulfate system with a consistent VR = 0.8 and K < 0.2 for the scales analyzed. The partition behavior the bacteriophage T4 was comparable to that reported previously for adenoviral vectors in same system at 15 ml scale, The results obtained demonstrated that the miniaturization of ATPS is feasible and reproducible for the two models selected. This provides significant information about the miniaturization process of such ATPS for their potential generic applications in the recovery of different bio-nanoparticle products. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Birmingham, Sch Engn, Dept Chem Engn, Biochem Recovery Grp, Birmingham B15 2TT, W Midlands, England. RP Negrete, A (reprint author), Natl Inst Hlth Natl Heart Lung & Blood Inst, 9000 Rockville Pike Bldg 10,Room 7D04, Bethesda, MD 20892 USA. EM negretea@rhlbi.nih.gov RI Ling, Tau Chuan/F-5137-2011 NR 32 TC 29 Z9 29 U1 2 U2 13 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 JUL 1 PY 2007 VL 854 IS 1-2 BP 13 EP 19 DI 10.1016/j.jchromb.2007.03.041 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 191WE UT WOS:000248161900003 PM 17448735 ER PT J AU Baron, J AF Baron, Jeffrey TI Editorial: Growth hormone therapy in childhood: Titration Versus weight-based dosing? SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID IDIOPATHIC SHORT STATURE; IGF-BINDING PROTEIN-3; FACTOR-I; CONSTITUTIONAL DELAY; CANCER RISK; CHILDREN; GH; REPLACEMENT; MATURATION; PLATE C1 NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NIH, Dev Endocrinol Branch, Bldg 10-CRC,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov NR 25 TC 5 Z9 5 U1 1 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2007 VL 92 IS 7 BP 2436 EP 2438 DI 10.1210/jc.2007-0900 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187ME UT WOS:000247851000008 PM 17616638 ER PT J AU Giri, N Batista, DL Alter, BP Stratakis, CA AF Giri, Neelam Batista, Dalia L. Alter, Blanche P. Stratakis, Constantine A. TI Endocrine abnormalities in patients with fanconi anemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-HORMONE DEFICIENCY; PITUITARY-STALK INTERRUPTION; APLASTIC-ANEMIA; BIALLELIC MUTATIONS; GLUCOSE-INTOLERANCE; INSULIN RESISTANCE; DIABETES-MELLITUS; 2 SIBLINGS; CHILDREN; DISEASE AB Background: Fanconi anemia ( FA) is an inherited disorder with chromosomal instability, bone marrow failure, developmental defects, and a predisposition to cancer. Systematic and comprehensive endocrine function data in FA are limited. Objective: We studied a cohort of FA patients enrolled in the National Cancer Institute's Inherited Bone Marrow Failure Syndrome study. Study Design and Patients: Retrospective review of the medical records of 45 FA patients (ages 2-49 yr), 23 of whom were intensively evaluated at the National Institutes of Health. Anthropometric measurements, GH, IGF-I, IGF binding protein-3, thyroid, gonadal hormone, lipid levels, glucose homeostasis, brain imaging, and bone mineral density were obtained in these latter patients. Results: Endocrine abnormalities were present in 73%, including short stature and/or GH deficiency (51%), hypothyroidism (37%), mid-line brain abnormalities (17%) (these patients had very short stature and 60% were GH-deficient); abnormal glucose/insulin metabolism (39%); obesity (27%); dyslipidemia (55%); and metabolic syndrome (21%). Patients with any endocrine abnormality were shorter than those without; only GH deficiency correlated significantly with short stature (P = 0.01). In addition, 65% of peripubertal or postpubertal patients had gonadal dysfunction. Ninety-two percent of the patients 18 yr or older had osteopenia or osteoporosis. Conclusions: Endocrine dysfunction is widespread in children and adults with FA; we expand the FA phenotype to include early onset osteopenia/osteoporosis and lipid abnormalities. Despite the reputation of FA as a progressive, lethal disease, proper management of the full spectrum of FA-related endocrinopathy offers major opportunities to reduce morbidity and improve quality of life. Our findings emphasize the need for comprehensive endocrine and metabolic evaluation and long-term follow-up in patients with FA. C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Giri, N (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 7024, Rockville, MD 20852 USA. EM girin@mail.nih.gov FU Intramural NIH HHS NR 42 TC 55 Z9 56 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2007 VL 92 IS 7 BP 2624 EP 2631 DI 10.1210/jc.2007-0135 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 187ME UT WOS:000247851000036 PM 17426088 ER PT J AU Ito, SJ Chen, C Satoh, J Yim, SH Gonzalez, FJ AF Ito, Shinji Chen, Chi Satoh, Junko Yim, SunHee Gonzalez, Frank J. TI Dietary phytochemicals regulate wholebody CYP1A1 expression through an arylhydrocarbon receptor nuclear translocator-dependent system in gut SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; HYPOXIA-INDUCIBLE FACTOR-1; CYTOCHROME-P450 ENZYMES; SMALL-INTESTINE; AROMATIC-HYDROCARBON; METABOLIC-ACTIVATION; ADULT TISSUES; MICE LACKING; BISPHENOL-A; MOUSE AB Cytochrome P450 1A1 (CYP1A1) is one of the most important detoxification enzymes due to its broad substrate specificity and wide distribution throughout the body. On the other hand, CYP1A1 can also produce highly carcinogenic intermediate metabolites through oxidation of polycyclic aromatic hydrocarbons. We describe what we believe to be a novel regulatory system for whole-body CYP1A1 expression by a factor originating in the gut. A mutant mouse was generated in which the arylhydrocarbon receptor nuclear translocator (Arnt) gene is disrupted predominantly in the gut epithelium. Surprisingly, CYP1A1 mRNA expression and enzymatic activities were markedly elevated in almost all non-gut tissues in this mouse line. The induction was even observed in early-stage embryos in pregnant mutant females. Interestingly, the upregulation was CYP1A1 selective and lost upon administration of a synthetic purified diet. Moreover, the increase was recovered by addition of the natural phytochemical indole-3-carbinol to the purified diet. These results suggest that an Arnt-dependent pathway in gut has an important role in regulation of the metabolism of dietary CYP1A1 inducers and whole-body CYP1A1 expression. This machinery might be involved in naturally occurring carcinogenic processes and/or other numerous biological responses mediated by CYP1A1 activity. C1 NCI, Lab Metab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Canc Res Ctr, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov RI Chen, Chi/B-4618-2008 FU Intramural NIH HHS NR 51 TC 42 Z9 42 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2007 VL 117 IS 7 BP 1940 EP 1950 DI 10.1172/JCI31647 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 187HG UT WOS:000247837700026 PM 17607366 ER PT J AU Espinel-Ingroff, A Fothergill, A Ghannoum, M Manavathu, E Ostrosky-Zeichner, L Pfaller, MA Rinaldi, MG Schell, W Walsh, TJ AF Espinel-Ingroff, A. Fothergill, A. Ghannoum, M. Manavathu, E. Ostrosky-Zeichner, L. Pfaller, M. A. Rinaldi, M. G. Schell, W. Walsh, T. J. TI Quality control and reference guidelines for CLSI broth microdilution method (M38-A document) for susceptibility testing of anidulafungin against molds SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ASPERGILLUS; CASPOFUNGIN; MK-0991; FUNGI AB The CLSI (formerly NCCLS) M38-A document for antifungal susceptibility testing of filamentous fungi does not describe guidelines for echinocandins. A multicenter study (eight centers) evaluated inter- and intralaboratory reproducibilities of two reading times (24 and 48 h or 48 and 72 h) and two end points (MICs and minimum effective concentrations [MECs]) for evaluating anidulafungin against molds. Anidulafungin MICs (>= 50% inhibition) and MECs (morphological hyphal changes) were determined for seven Aspergillus isolates (four species) and one isolate each of Fusarium moniliforme, Fusarium solani, and Paecilomyces variotii and for two Scedosporium apiospermum isolates. The inter- and intralaboratory reproducibilities of 10 replicate tests performed in each laboratory on 10 different days for each isolate was 100% at 24 h (MECs, <= 0.015 mu g/ml) for six Aspergillus and P. variotii isolates. The reproducibility was 94 to 96.7% at 72 h (MECs, 1 to 8 mu g/ml) for S. apiospermum and 96.7 to 97.5% at 48 h (MICs, >= 32 mu g/ml) for both Fusarium isolates. Introduction of these identified optimum testing conditions for anidulafungin into future versions of the M38 document is warranted. C1 VCU Med Ctr, Richmond, VA 23298 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Wayne State Univ, Detroit, MI USA. Univ Texas, Houston Med Sch, Houston, TX USA. Univ Iowa, Coll Med, Iowa City, IA USA. Duke Univ, Durham, NC USA. NCI, Bethesda, MD 20892 USA. RP Espinel-Ingroff, A (reprint author), VCU Med Ctr, 1101 E Marshall St,Sanger Hall,Room 7-049,POB 980, Richmond, VA 23298 USA. EM avingrof@vcu.edu NR 11 TC 22 Z9 23 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 JUL PY 2007 VL 45 IS 7 BP 2180 EP 2182 DI 10.1128/JCM.00399-07 PG 3 WC Microbiology SC Microbiology GA 190QB UT WOS:000248072900014 PM 17475760 ER PT J AU Conville, PS Witebsky, FG AF Conville, Patricia S. Witebsky, Frank G. TI Organisms designated as Nocardia asteroides drug pattern type VI are members of the species Nocardia cyriacigeorgica SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION-ENDONUCLEASE ANALYSIS; RIBOSOMAL-RNA GENE; AD-HOC-COMMITTEE; BETA-LACTAMS; IDENTIFICATION; SUSCEPTIBILITY; SEQUENCES; DATABASE; STRAINS; PATIENT AB Nocardia cyriacigeorgica has recently been described as an "emerging" pathogen. However, DNA-DNA hybridization results confirm that Nocardia asteroides drug pattern type VI, which has long been recognized as a common and significant pathogen in the United States, belongs to the species N. cyriacigeorgica. C1 US Dept HHS, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), US Dept HHS, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr,NIH, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM pconville@nih.gov FU Intramural NIH HHS NR 24 TC 18 Z9 19 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUL PY 2007 VL 45 IS 7 BP 2257 EP 2259 DI 10.1128/JCM.00133-07 PG 3 WC Microbiology SC Microbiology GA 190QB UT WOS:000248072900025 PM 17475753 ER PT J AU Demark-Wahnefried, W Clipp, EC Lipkus, IM Lobach, D Snyder, DC Sloane, R Peterson, B Macri, JM Rock, CL McBride, CM Kraus, WE AF Demark-Wahnefried, Wendy Clipp, Elizabeth C. Lipkus, Isaac M. Lobach, David Snyder, Denise Clutter Sloane, Richard Peterson, Bercedis Macri, Jennifer M. Rock, Cheryl L. McBride, Colleen M. Kraus, William E. TI Main outcomes of the FRESH START trial: A sequentially tailored, diet and exercise mailed print intervention among breast and prostate cancer survivors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID CURRENT HEALTH BEHAVIORS; QUALITY-OF-LIFE; PHYSICAL-ACTIVITY; FUNCTIONAL ASSESSMENT; TEACHABLE MOMENT; RANDOMIZED-TRIAL; CLINICAL-TRIALS; DIAGNOSIS; PLASMA; TERM AB Purpose Cancer survivors are at increased risk for cardiovascular disease, diabetes, osteoporosis, and second primary tumors. Healthful lifestyle practices may improve the health and well-being of survivors. The FRESH START trial tested the efficacy of sequentially tailored versus standardized mailed materials on improving cancer survivors' diet and exercise behaviors. Methods Five hundred forty-three individuals with newly diagnosed locoregional breast or prostate cancer were recruited from 39 states and two provinces within North America. Participants were randomly assigned either to a 10-month program of tailored mailed print materials promoting fruit and vegetable (F&V) consumption, reducing total/saturated fat intake, and/or increasing exercise or to a 10-month program of nontailored mailed materials on diet and exercise available in the public domain. Telephone surveys conducted at baseline and 1 year assessed body mass index (BMI), dietary consumption, physical activity, and other psychosocial/behavioral indices. Clinical assessments were conducted on a 23% subsample; information was used to validate self-reports. Results Five hundred nineteen participants completed the 1-year follow-up (4.4% attrition; sample characteristics: 57 +/- 10.8 years old, 83% white, 56% female, 64% overweight/obese, and 0% underweight). Although both arms significantly improved their lifestyle behaviors (P < .05), significantly greater gains occurred in the FRESH START intervention versus the control arm (practice of two or more goal behaviors: +34% v +18%, P < .0001; exercise minutes per week: +59.3 v +39.2 minutes, P + .02; F&V per day: +1.1 v +0.6 servings, P = .01; total fat: -4.4% v -2.1%, P < .0001; saturated fat: -1.3% v -0.3%, P < .0001; and BMI: -0.3 v +0.1 kg/m(2), respectively, P = .004). Conclusion Mailed material interventions, especially those that are tailored, are effective in promoting healthful lifestyle changes among cancer survivors. Further study is needed to determine sustainability, cost to benefit, and generalizability to other cancer populations. C1 Duke Univ, Med Ctr, Duke Sch Nursing, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Durham, NC 27710 USA. Duke Univ, Med Ctr, Duke Ctr Aging, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Vet Affairs Med Ctr, Durham, NC USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA. RP Demark-Wahnefried, W (reprint author), Duke Univ, Med Ctr, Duke Sch Nursing, Box 3322, Durham, NC 27710 USA. EM demar001@mc.duke.edu OI Kraus, William E/0000-0003-1930-9684 FU NCI NIH HHS [CA63782, CA74000, CA81191, R01 CA081191]; NCRR NIH HHS [M01-RR-30] NR 68 TC 139 Z9 139 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 JUL 1 PY 2007 VL 25 IS 19 BP 2709 EP 2718 DI 10.1200/JCO.2007.10.7094 PG 10 WC Oncology SC Oncology GA 187QB UT WOS:000247862000015 PM 17602076 ER PT J AU Pickering, RP Grant, BF Chou, SP Compton, WM AF Pickering, Roger P. Grant, Bridget F. Chou, S. Patricia Compton, Wilson M. TI Are overweight, obesity, and extreme obesity associated with psychopathology? Results from the national epidemiologic survey on alcohol and related conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; BODY-MASS INDEX; MAJOR DEPRESSIVE DISORDER; GENERAL-POPULATION SAMPLE; BIPOLAR-I DISORDER; UNITED-STATES; PSYCHIATRIC-DISORDERS; DRUG MODULES; SOCIOECONOMIC-STATUS; HISPANIC IMMIGRANTS AB Objective: This study examined associations of overweight, obesity, and extreme obesity with sociodemographic characteristics and specific DSM-IV Axis I and II disorders among men and women. Method: Face-to-face interviews were conducted in a large national survey of the adult U.S. population conducted from 2001 to 2002. Results: In general, black men; black, Hispanic, and Native American women; women who were not married/cohabiting; and those residing in the South and Midwest and in rural areas were at greatest risk of overweight, obesity, and extreme obesity. Women with obesity and extreme obesity were more likely to have atypical major depressive episodes in their bipolar illness. Panic disorder was associated (odds ratio [OR] = 1.5) with overweight among men, and specific phobia was associated with overweight (OR = 1.2) and obesity (OR = 1.3) among women. Antisocial personality disorder was also associated with overweight (OR = 1.5) and extreme obesity (OR = 1.9) among women, and avoidant personality disorder was associated (OR = 1.7) with extreme obesity among women. Conclusion: Obesity among women appears to be related to episodes of major depression with atypical features occurring in established bipolar I disorder. Due to symptom overlap, panic disorder among overweight men may signal the presence of an undiagnosed illness such as cardiovascular disease or diabetes mellitus, type 2. More frequent exposure/vulnerability to stress may predispose overweight.obese women to specific phobia. Treatment guidelines for psychiatric disorders need to address the management of comorbid overweight and obesity, and treatment guidelines for obesity need to address the management of comorbid psychopathology. C1 NIAAA, NIH, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res,Dept Hlth & Human, Bethesda, MD 20892 USA. NIDA, NIH, Div Epidemiol, Serv & Prevent Res,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, NIH, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res,Dept Hlth & Human, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov NR 65 TC 55 Z9 55 U1 3 U2 16 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2007 VL 68 IS 7 BP 998 EP 1009 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 196PK UT WOS:000248494300004 PM 17685734 ER PT J AU Rosenthal, RN Brady, KT Levounis, P Willenbring, ML AF Rosenthal, Richard N. Brady, Kathleen T. Levounis, Petros Willenbring, Mark L. TI Advances in the treatment of alcohol dependence SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CENTRAL-NERVOUS-SYSTEM; PROJECT MATCH; DRINKING OUTCOMES; CONTINGENCY MANAGEMENT; CLIENT HETEROGENEITY; CLINICAL-TRIAL; AMINO-ACIDS; NALTREXONE; ETHANOL C1 Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. St Lukes Roosevelt Hosp, Dept Psychiat, New York, NY USA. Med Univ S Carolina, Dept Psychiat, Clin Neurosci Div, Charleston, SC 29425 USA. NIAAA, NIH, Div Treatment & Recovery Res, Bethesda, MD USA. RP Rosenthal, RN (reprint author), Columbia Univ Coll Phys & Surg, Dept Psychiat, 722 W 168th St, New York, NY 10032 USA. NR 89 TC 0 Z9 0 U1 2 U2 4 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUL PY 2007 VL 68 IS 7 BP 1117 EP 1128 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 196PK UT WOS:000248494300021 ER PT J AU Yamaguchi, K Sugiyama, T Takizawa, M Yamamoto, N Honda, M Natori, M AF Yamaguchi, Koushi Sugiyama, Takahiro Takizawa, Mari Yamamoto, Naoki Honda, Mitsuo Natori, Michiya TI Viability of infectious viral particles of HIV and BMCs in breast milk SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE HIV; MTCT; breastfeeding ID IMMUNODEFICIENCY-VIRUS TYPE-1; TO-CHILD TRANSMISSION; POSTNATAL TRANSMISSION; WOMEN AB Background: Infectious factors in breast milk such as viral particles and living infected cells are of prime importance in the transmission of HIV by breastfeeding. Objectives: To perform effective approaches for reducing HIV transmission via breastfeeding, we investigated the biological importance of infectious viral particles and infected BMCs in breast milk. Study design: Alteration of viral infectivity was monitored using a modified experimental infection assay that exploited the cytotoxicity of breast milk, and BMC viability was evaluated by flow-cytometric analysis. Results: Infectious viral particles were found to decrease time-dependently after contact with breast milk, whereas BMCs showed prolonged survival in breast milk. Conclusions: The biological importance of infected BMCs in breast milk for the transmission of HIV via breastfeeding was considered. (C) 2007 Elsevier B.V. All rights reserved. C1 Natl Ctr Child Hlth & Dev, Dept Perinatol, Div Maternal Med, Setagaya Ku, Tokyo 1578535, Japan. Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan. Noritake Co, Ctr Res & Dev, Nishi Ku, Nagoya, Aichi 4518501, Japan. NIAID, NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Yamaguchi, K (reprint author), Natl Ctr Child Hlth & Dev, Dept Perinatol, Div Maternal Med, Setagaya Ku, Okura 2-10-1, Tokyo 1578535, Japan. EM yamaguchi-k@ncchd.go.jp NR 10 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD JUL PY 2007 VL 39 IS 3 BP 222 EP 225 DI 10.1016/j.jcv.2007.04.011 PG 4 WC Virology SC Virology GA 191CS UT WOS:000248108100012 PM 17526428 ER PT J AU Parker, EA Hegde, A Buckley, M Barnes, KM Baron, J Nilsson, O AF Parker, E. A. Hegde, A. Buckley, M. Barnes, K. M. Baron, J. Nilsson, O. TI Spatial and temporal regulation of GH-IGF-related gene expression in growth plate cartilage SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID MESSENGER-RIBONUCLEIC-ACID; LONGITUDINAL BONE-GROWTH; CHONDROCYTES IN-VIVO; SOMATOMEDIN HYPOTHESIS; HORMONE RECEPTOR; RNA EXPRESSION; RESTING ZONE; INSULIN; MICE; CHONDROGENESIS AB Previous studies of the GH-IGF system gene expression in growth plate using immunohistochemistry and in situ hybridization have yielded conflicting results. We therefore studied the spatial and temporal patterns of mRNA expression of the GHIGF system in the rat proximal tibial growth plate quantitatively. Growth plates were rnicrodissected into individual zones. RNA was extracted, reverse transcribed and analyzed by real-time PCR. In 1-week-old animals, IGF-I mRNA expression was minimal in growth plate compared with perichondrium, metaphyseal bone, muscle, and liver (70-, 130-, 215-, and 400-fold less). In contrast, IGF-II mRNA was expressed at higher levels than in bone and liver (65- and 2-fold). IGF-II expression was higher in the proliferative and resting zones compared with the hypertrophic zone (P < 0-001). GH receptor and type 1 and 2 IGF receptors were expressed throughout the growth plate. Expression of IGF-binding proteins (IGFBPs)-1 through -6 mPNA was low throughout the growth plate compared with perichondriurn and bone. With increasing age (3-, 6-, 9-, and 12-week castrated rats), IGF-I mRNA levels increased in the proliferative zone (PZ) but remained at least tenfold lower than levels in perichondriurn and bone. IGF-II mRNA decreased dramatically in PZ (780-fold; P<0-001) whereas, type 2 IGF receptor and IGFBP-1, IGFBP-2, IGFBP-3, and IGFBP-4 increased significantly with age in growth plate and/or surrounding perichondrium and bone. These data suggest that IGF-I protein in the growth plate is not produced primarily by the chondrocytes themselves. Instead, it derives from surrounding perichondrium and bone. In addition, the decrease in growth velocity that occurs with age may be caused, in part, by decreasing expression of IGF-II and increasing expression of type 2 IGF receptor and multiple IGFBPs. C1 NICHHD, NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Karolinska Univ Hosp, Karolinska Inst, Pediat Endocrinol Unit, Dept Woman & Child Hlth, SE-17176 Stockholm, Sweden. RP Baron, J (reprint author), NICHHD, NIH, Dev Endocrinol Branch, Bldg 10-CRC,Rm 1-3330,MSC 1103,10 Ctr Dr, Bethesda, MD 20892 USA. EM jeffrey.baron@nih.gov OI Nilsson, Ola/0000-0002-9986-8138 FU Intramural NIH HHS NR 37 TC 28 Z9 31 U1 4 U2 7 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD JUL PY 2007 VL 194 IS 1 BP 31 EP 40 DI 10.1677/JOE-07-0012 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 195JH UT WOS:000248408000004 PM 17592018 ER PT J AU Chernomordik, LV AF Chernomordik, Leonid V. TI Cell fusion: From early intermediates to syncytium formation. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 NICHHD, Sect Membrane Biol, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 5 BP 2a EP 2a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600007 ER PT J AU Shnyrova, A Ayllon, J Villar, E Zimerberg, J Frolov, V AF Shnyrova, Anna Ayllon, Juan Villar, Enrique Zimerberg, Joshua Frolov, Vadim TI Formation of virus-like vesicles through assembling of proteolipid domains. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20847 USA. Univ Salamanca, Dept Bioquim & Biol Mol, E-37008 Salamanca, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 16 BP 8a EP 8a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600018 ER PT J AU He, LM Wu, LG AF He, Liming Wu, Ling-Gang TI Multiple modes of fusion and retrieval at the calyx of held synapse SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 NINDS, Synapt Transmiss Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 22 BP 10a EP 10a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600024 ER PT J AU Lizunov, VA Lisinski, I Cushman, SW Zimmerberg, J AF Lizunov, Vladimir A. Lisinski, Ivonne Cushman, Samuel W. Zimmerberg, Joshua TI Role of the exocyst in insulin-stimulated translocation of GLUT4 in primary isolated adipose cells. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 Inst Child Hlth & Human Dev, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NIH, NIDDK, Expt Diabet Metab & Nutr Sect, Diabet Branch, Bethesda, MD 20892 USA. RI Lizunov, Vladimir/B-5468-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 39 BP 17a EP 17a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600041 ER PT J AU Lizunov, VA Kirchhausen, T Zimmerberg, J AF Lizunov, Vladimir A. Kirchhausen, Tom Zimmerberg, Joshua TI Reversible fluctuations of the endocytotic fission pore induced by dynamin inhibitor dynasore. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 NIH, NICHHD, Lab Mol Cellular & Mol Phys, Bethesda, MD 20892 USA. Harvard Med Sch, Ctr Blood Res Inst Biomed Res, Dept Cell Biol, Boston, MA 02115 USA. RI Lizunov, Vladimir/B-5468-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 40 BP 17a EP 17a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600042 ER PT J AU Akimov, SA Frolov, VAJ Zimmerberg, J Chizmadzhev, YA Cohen, FS AF Akimov, Sergey A. Frolov, Vladimir A. J. Zimmerberg, Joshua Chizmadzhev, Yuri A. Cohen, Fredric S. TI Describing domain formation in membranes as a process of wetting of protein by lipids. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Lab Bioelectrochem, Moscow 119991, Russia. NIH, NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. Rush Univ, Med Ctr, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RI Chizmadzhev, Yuri/L-1984-2013; Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 44 BP 18a EP 19a PG 2 WC Physiology SC Physiology GA 182RB UT WOS:000247520600046 ER PT J AU Akimov, SA Bashkirov, PV Zimmerberg, J Frolov, VA AF Akimov, Sergey A. Bashkirov, Pavel V. Zimmerberg, Joshua Frolov, Vadim A. TI A possible role of curvature scaffolding in dynamin-induced fission of membrane nanotube. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 Russian Acad Sci, Frumkin Inst Phys Chem & Electrochem, Lab Bioelectrochem, Moscow 199991, Russia. NIH, NICHHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. RI Bashkirov, Pavel/J-2385-2012; Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 43 BP 18a EP 18a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600045 ER PT J AU Ferguson, ML Prasad, K Boukari, H Sackett, DL Krueger, S Lafer, EM Nossal, R AF Ferguson, Matthew L. Prasad, Kondury Boukari, Hacene Sackett, Dan L. Krueger, Susan Lafer, Eileen M. Nossal, Ralph TI Small angle neutron scattering studies of clathrin triskelia in solution show evidence of molecular flexibility. SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the Society-of-General-Physiologists CY SEP 05-09, 2007 CL Marine Biol Lab, Woods Hole, MA SP Soc Gene Physiol HO Marine Biol Lab C1 NIH, NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Natl Inst Stand & Technol, Ctr Neutron Res, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD JUL PY 2007 VL 130 IS 1 MA 42 BP 18a EP 18a PG 1 WC Physiology SC Physiology GA 182RB UT WOS:000247520600044 ER PT J AU Ai, AL Peterson, C Tice, TN Huang, B Rodgers, W Bolling, SF AF Ai, Amy L. Peterson, Christopher Tice, Terrence N. Huang, Bu Rodgers, Willard Bolling, Steven F. TI The influence of prayer coping on mental health among cardiac surgery patients - The role of optimism and acute distress SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Review DE acute stress disorder; anxiety; cardiovascular disease; depression; open-heart surgery; optimism; prayer coping; preoperative PTSD symptoms ID BYPASS GRAFT-SURGERY; QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; DIAGNOSTIC INTERVIEW SCHEDULE; PRIVATE RELIGIOUS ACTIVITY; CORONARY-ARTERY-DISEASE; PANIC DISORDER; DEPRESSIVE SYMPTOMATOLOGY; PHYSICAL HEALTH; OLDER PATIENTS AB To address the inconsistent findings and based on Hegel's dialectic contradictive principle, this study tested a parallel mediation model that may underlie the association of using prayer for coping with cardiac surgery outcomes. Three sequential interviews were conducted with 310 patients who underwent open-heart surgery. A structural equation model demonstrated that optimism mediated the favorable effect of prayer coping. Prayer coping was also related to preoperative stress symptoms, which had a counterbalance effect on outcomes. Age was associated with better preoperative mental health, but age-related chronic conditions were associated with poor outcomes; both of these were mediated through the same mediators. C1 Univ Washington, Seattle, WA 98195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Ai, AL (reprint author), NCI, 6130 Execut Blvd,MSC 7326,Room 4052, Bethesda, MD 20892 USA. EM moserr@mail.nih.gov FU NCCIH NIH HHS [P50 AT00011]; PHS HHS [1 R03 AGO 15686-01] NR 101 TC 18 Z9 18 U1 2 U2 8 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD JUL PY 2007 VL 12 IS 4 BP 580 EP 596 DI 10.1177/1359105307078164 PG 17 WC Psychology, Clinical SC Psychology GA 187TQ UT WOS:000247871800003 PM 17584810 ER PT J AU Guo, T Wang, WJ Rudnick, PA Song, T Li, J Zhuang, ZP Weil, RJ DeVoe, DL Lee, CS Balgley, BM AF Guo, Tong Wang, Weijie Rudnick, Paul A. Song, Tao Li, Jie Zhuang, Zhengping Weil, Robert J. DeVoe, Don L. Lee, Cheng S. Balgley, Brian M. TI Proteome analysis of microdissected formalin-fixed and paraffin-embedded tissue specimens SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE proteomics; mass spectrometry; formalin-fixed; tissue; microdissection ID LASER-CAPTURE MICRODISSECTION; TANDEM MASS-SPECTROMETRY; LARGE-SCALE ANALYSIS; LIQUID-CHROMATOGRAPHY; ANTIGEN RETRIEVAL; IDENTIFICATION TECHNOLOGY; SHOTGUN PROTEOMICS; LC-MS/MS; PROTEINS; SECTIONS AB Targeted proteomics research, based on the enrichment of disease-relevant proteins from isolated cell populations selected from high-quality tissue specimens, offers great potential for the identification of diagnostic, prognostic, and predictive biological markers for use in the clinical setting and during preclinical testing and clinical trials, as well as for the discovery and validation of new protein drug targets. Formalin-fixed and paraffin embedded (FFPE) tissue collections, with attached clinical and outcome information, are invaluable resources for conducting retrospective protein biomarker investigations and performing translational studies of cancer and other diseases. Combined capillary isoelectric focusing/nano-reversed-phase liquid chromatography separations equipped with nano-electrospray ionization-tandem mass spectrometry are employed for the studies of proteins extracted from microdissected FFPE glioblastoma tissues using a heat-induced antigen retrieval (AR) technique. A total of 14,478 distinct peptides are identified, leading to the identification of 2733 non-redundant SwissProt protein entries. Eighty-three percent of identified FFPE tissue proteins overlap with those obtained from the pellet fraction of fresh-frozen tissue of the same patient. This large degree of protein overlapping is attributed to the application of detergent-based protein extraction in both the cell pellet preparation protocol and the AR technique. C1 Calibrant Biosyst, Gaithersburg, MD 20878 USA. Univ Maryland, Dept Chem & Biochem, Biomed Engn Program, College Pk, MD USA. Univ Maryland, Dept Mech Engn & Bioengn, Biomed Engn Program, College Pk, MD USA. Natl Neurol Disorders & Stroke, Mol Pathogenesis Unit, Surg Neurol Branch, Bethesda, MD USA. Cleveland Clin Fdn, Brain Tumor Inst, Cleveland, OH 44195 USA. RP Balgley, BM (reprint author), Calibrant Biosyst, 910 Clopper Rd,Suite 220N, Gaithersburg, MD 20878 USA. EM brian.balgley@calibrant.com RI DeVoe, Don/A-2891-2011; OI DeVoe, Don/0000-0002-7740-9993; Balgley, Brian/0000-0002-3509-4567 FU NCI NIH HHS [CA103086, CA107988]; NCRR NIH HHS [RR021239, RR021862] NR 55 TC 85 Z9 86 U1 0 U2 8 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUL PY 2007 VL 55 IS 7 BP 763 EP 772 DI 10.1369/jhc.7A7177.2007 PG 10 WC Cell Biology SC Cell Biology GA 179JA UT WOS:000247284500010 PM 17409379 ER PT J AU Kong, HJ Anderson, DE Lee, CH Jang, MK Tamura, T Tailor, P Cho, HK Cheong, JH Xiong, HB Morse, HC Ozato, K AF Kong, Hee Jeong Anderson, D. Eric Lee, Chang Hoon Jang, Moon Kyoo Tamura, Tomohiko Tailor, Prafullakumar Cho, Hyun Kook Cheong, JaeHun Xiong, Huabao Morse, Herbert C., III Ozato, Keiko TI Cutting edge: Autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; REGULATORY FACTOR-8; INTERLEUKIN-12; TRANSCRIPTION; LIGASE; TRAF6; ICSBP AB IFN regulatory factor (IRF)-8 is a transcription factor important for the development and function of macrophages. It plays a critical role in the induction of cytokine genes, including IL-12p40. Immunopurification and mass spectrometry analysis found that IRF-8 interacted with Ro52 in murine macrophages upon IFN-gamma and TLR stimulation. Ro52 is an IFN-inducible protein of the tripartite motif (TRIM) family and is an autoantigen present in patients with Sjogren's syndrome and systemic lupus erythematosus. Ro52 has a RING motif and is capable of ubiquitinating itself. We show that IRF-8 is ubiquitinated by Ro52 both in vivo and in vitro. Ectopic expression of Ro52 enhanced IL-12p40 expression in IFN-gamma/TLR-stimulated macrophages in an IRF-8-dependent manner. Together, Ro52 is an E3 ligase for IRF-8 that acts in a non-degradation pathway of ubiquitination, and contributes to the elicitation of innate immunity in macrophages. C1 NICHHD, Lab Mol Growth Regulat, GDP, NIH, Bethesda, MD 20892 USA. NIDDKD, Proteom & Mass Spectrometry Facil, NIH, Bethesda, MD USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. Natl Fisheries Res & Dev Inst, Biotechnol Res Inst, Pusan, South Korea. Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. RP Ozato, K (reprint author), NICHHD, Lab Mol Growth Regulat, GDP, NIH, Bldg 6,Room 2A01,6 Ctr Dr, Bethesda, MD 20892 USA. EM ozatok@nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS NR 24 TC 99 Z9 105 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 JUL 1 PY 2007 VL 179 IS 1 BP 26 EP 30 PG 5 WC Immunology SC Immunology GA 182IF UT WOS:000247497600005 PM 17579016 ER PT J AU Wang, JH Roderiquez, G Jones, T McPhie, P Norcross, MA AF Wang, Jinhai Roderiquez, Gregory Jones, Taneishia McPhie, Peter Norcross, Michael A. TI Control of in vitro immune responses by regulatory oligodeoxynucleotides through inhibition of pIII promoter directed expression of MHC class II transactivator in human primary monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; COLONY-STIMULATING FACTOR; COMPLEX CLASS-I; SUPPRESSIVE OLIGODEOXYNUCLEOTIDES; BACTERIAL-DNA; CPG OLIGODEOXYNUCLEOTIDES; SCAVENGER RECEPTORS; BETA-CHEMOKINES; DENDRITIC CELLS; CCR5 EXPRESSION AB Ag presentation is a key step in the initiation of adaptive immune responses that depends on the expression of MHC Ags and costimulatory molecules. Immune-enhancing CpG and non-CPG oligodeoxynucleotides (ODNs) stimulate Ag presentation by stimulating the expression of these molecules and by promoting dendritic cell maturation. In this report, we identify immuno-regulatory orthophosphorothioate non-CpG molecules, referred to as regulatory ODNs (rODNs), by their ability to inhibit allogeneic monocyte-stimulated T cell responses and down-regulate HLA-DR in human primary monocytes. The rODNs promoted the survival of macrophages and were able to activate IL-8 secretion through a chloroquine-resistant pathway. Messenger RNAs for HLA-DR alpha and beta and the MHC CIITA were reduced by rODNs but not by stimulatory CpG ODN2006 and non-CpG ODN2006a. CIITA transcription in monocytes was controlled primarily by promoter III and not by promoter I or IV. rODNs blocked promoter III-directed transcription of CIITA in these cells. Under conditions that induced dendritic cell differentiation, rODNs also reduced HLA-DR expression. The activity of rODNs is phosphorothioate chemistry and G stretch dependent but TLR9 independent. G tetrads were detected by circular dichroism in active rODNs and associated with high m.w. multimers on non-denaturing gels. Heat treatment of rODNs disrupted G tetrads, the high m.w. aggregates, and the HLA-DR inhibitory activity of the ODNs. The inhibition of immune responses by regulatory oligodeoxynucleotides may be useful for the treatment of immune-mediated disorders including autoimmune diseases and graft rejection. C1 US FDA, NIH, Div Therapeut Proteins, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, NIH, Div Therapeut Proteins, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bldg 29B,Room 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM jinhai.wang@fda.hhs.gov NR 47 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 45 EP 52 PG 8 WC Immunology SC Immunology GA 182IF UT WOS:000247497600009 PM 17579020 ER PT J AU Leung, WH Bolland, S AF Leung, Wai-Hang Bolland, Silvia TI The inositol 5 '-phosphatase SHIP-2 negatively regulates IgE-induced mast cell degranulation and cytokine production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FC-EPSILON-RI; TYROSINE PHOSPHORYLATION; 5-PHOSPHATASE SHIP2; GAMMA-RIIB; 5'-INOSITOL PHOSPHATASE; SIGNALING PATHWAY; PLASMA-MEMBRANE; B ACTIVITY; RECEPTOR; PROTEIN AB Aggregation of the high-affinity IgE receptor (Fc epsilon RI) on mast cells initiates signaling pathways leading to degranulation and cytokine release. It has been reported that SHIP-1 negatively regulates Fc epsilon RI-triggered pathways but it is unknown whether its homologous protein SHIP-2 has the same function. We have used a lentiviral-based RNA interference technique to obtain SHIP-2 knockdown bone marrow-derived mast cells (BMMCs) and have found that elimination of SHIP-2 results in both increased mast cell degranulation and cytokine (IL-4 and IL-13) gene expression upon Fc epsilon RI stimulation. Elimination of SHIP-2 from BMMCs has no effect on Fc epsilon RI-triggered calcium flux, tyrosine phosphorylation of MAPKs or in actin depolymerization following activation. Rather, we observe that absence of SHIP-2 results in increased activation of the small GTPase Rac-1 and in enhanced microtubule polymerization upon Fc epsilon RI engagement. Coimmunoprecipitation experiments in rat basophilic leukemia (RBL 2H3) cells show that SHIP-2 interacts with the Fc epsilon RI beta-chain, Gab2 and Lyn and that unlike SHIP-1, it does not associate with SHC in mast cells. Our results report a negative regulatory role of SHIP-2 on mast cell activation that is calcium independent and distinct from the regulation by SHIP-1. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr,Twinbrook 2,Room 217, Rockville, MD 20852 USA. EM sbolland@nih.gov FU Intramural NIH HHS NR 55 TC 37 Z9 39 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 95 EP 102 PG 8 WC Immunology SC Immunology GA 182IF UT WOS:000247497600015 PM 17579026 ER PT J AU Yu, Q Xu, M Sen, JM AF Yu, Qing Xu, Mai Sen, Jyoti Misra TI beta-catenin expression enhances IL-7 receptor signaling in thymocytes during positive selection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; LINEAGE DECISION; DEFICIENT MICE; CYTOKINE; DIFFERENTIATION; LYMPHOPOIESIS; HEMATOPOIESIS; TRANSDUCTION; HOMEOSTASIS; ACTIVATION AB Differentiation of CD4(+)CD8(+) double-positive thymocytes into CD8(+) single-positive (SP) thymocytes is regulated by TCR and cytokine receptor signals. Previously, we have shown that expression of stabilized beta-catenin, the major transcriptional cofactor of T cell factor, results in increase in both CD4SP and CD8SP thymocytes with a preferential effect on CD8SP thymocytes. In this report, using mice expressing stabilized beta-catenin and mice with T cell specific deletion of beta-catenin, we show that beta-catenin expression augments IL-7R alpha-chain expression and down-regulates suppressor of cytokine signaling-1 expression in thymocytes undergoing positive selection. Consequently, beta-catenin expression augments IL-7R signaling in thymocytes during positive selection and promotes the development of CD8SP thymocytes. C1 NIA, Gerontol Res Ctr, Lymphocyte Dev Unit, Immunol Lab,NIH, Baltimore, MD 21224 USA. RP Sen, JM (reprint author), NIA, Gerontol Res Ctr, Lymphocyte Dev Unit, Immunol Lab,NIH, Room 4-B-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Jyoti-Sen@NIH.gov FU Intramural NIH HHS [Z01 AG000768-04] NR 26 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 126 EP 131 PG 6 WC Immunology SC Immunology GA 182IF UT WOS:000247497600019 PM 17579030 ER PT J AU Chen, X Baumel, M Mannel, DN Howard, OMZ Oppenheim, JJ AF Chen, Xin Baeumel, Monika Maennel, Daniela N. Howard, O. M. Zack Oppenheim, Joost J. TI Interaction of TNF with TNF receptor type 2 promotes expansion and function of mouse CD4(+)CD25(+) T regulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; IMMUNOSUPPRESSIVE PROPERTIES; RHEUMATOID-ARTHRITIS; CECAL LIGATION; SEPTIC SHOCK; IN-VIVO; SEPSIS; ALPHA; THERAPY; MICE AB Although TNF is a major proinflammatory cytokine, increasing evidence indicates that TNF also has immunosuppressive feedback effects. We have demonstrated in this study that, in both resting and activated states, mouse peripheral CD4(+)CD25(+) T regulatory, cells (Tregs) expressed remarkably higher surface levels of TNFR2 than CD4(+)CD25(-) T effector cells (Teffs). In cocultures of Tregs and Teffs, inhibition of proliferation of Teffs by Tregs was initially transiently abrogated by exposure to TNF, but longer exposure to TNF restored suppressive effects. Cytokine production by Teffs remained continually suppressed by Tregs. The profound anergy of Tregs in response to TCR stimulation was overcome by TNF, which expanded the Treg population. Furthermore, in synergy with IL-2, TNF expanded Tregs even more markedly up-regulated expression of CD25 and FoxP3 and phosphorylation of STAT5, and enhanced the suppressive activity of Tregs. Unlike TNF, IL-1 beta and IL-6 did not up-regulate FoxP3-expressing Tregs. Furthermore, the number of Tregs increased in wild-type mice, but not in TNFR2(-/-) mice following sublethal cecal ligation and puncture. Depletion of Tregs significantly decreased mortality following cecal ligation and puncture. Thus, the stimulatory effect of TNF on Tregs resembles the reported costimulatory effects of TNF on Teffs, but is even more pronounced because of the higher expression of TNFR2 by Tregs. Moreover, our study suggests that the slower response of Tregs than Teffs to TNF results in delayed immunosuppressive feedback effects. C1 NCI, Basic Res Program, Mol Immunoregulat Lab, Ctr Canc Res,SAIC Frederick, Frederick, MD 21702 USA. Univ Regensburg, Inst Immunol, D-8400 Regensburg, Germany. RP Chen, X (reprint author), NCI, Basic Res Program, Mol Immunoregulat Lab, Ctr Canc Res,SAIC Frederick, PO Box B,Bldg 560,Room 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 34 TC 204 Z9 219 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 154 EP 161 PG 8 WC Immunology SC Immunology GA 182IF UT WOS:000247497600022 PM 17579033 ER PT J AU Shirota, H Petrenko, L Hong, C Klinman, DM AF Shirota, Hidekazu Petrenko, Lev Hong, Choongman Klinman, Dennis M. TI Potential of transfected muscle cells to contribute to DNA vaccine immunogenicity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN-PRESENTING CELLS; CYTOTOXIC T-LYMPHOCYTES; MARROW-DERIVED CELLS; DIRECT GENE-TRANSFER; PLASMID DNA; IN-VIVO; SKELETAL-MUSCLE; ENDOTHELIAL-CELLS; IMMUNE-RESPONSE; DENDRITIC CELLS AB The mechanism(s) by which DNA vaccines trigger the activation of Ag-specific T cells is incompletely understood. A series of in vivo and in vitro experiments indicates plasmid transfection stimulates muscle cells to up-regulate expression of MHC class I and costimulatory molecules and to produce multiple cytokines and chemokines. Transfected muscle cells gain the ability to directly present Ag to CD8 T cells through an IFN-regulatory factor 3-dependent process. These findings suggest that transfected muscle cells at the site of DNA vaccination may contribute to the magnitude and/or duration of the immune response initiated by professional APCs. C1 NCI, NIH, Expt Immunol Lab, Frederick, MD 21702 USA. RP Klinman, DM (reprint author), NCI, NIH, Expt Immunol Lab, Bldg 567,Room 205, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov NR 52 TC 29 Z9 29 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 329 EP 336 PG 8 WC Immunology SC Immunology GA 182IF UT WOS:000247497600042 PM 17579053 ER PT J AU Hwang, IY Park, C Kehrl, JH AF Hwang, Il-Young Park, Chung Kehrl, John H. TI Impaired trafficking of Gnai2(+/-) and Gnai2(-/-) T lymphocytes: Implications for T cell movement within lymph nodes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; HETEROTRIMERIC G-PROTEINS; MOLECULAR-MECHANISMS; B-LYMPHOCYTE; IN-VIVO; RECIRCULATION; CHEMOTAXIS; CHEMOKINES; MIGRATION; EXPRESSION AB Signals generated by the engagement of chemoattractants with their cognate receptors orchestrate lymphocyte movements into and out of lymphoid organs and sites of inflammation. Yet, the role of chemokines in organizing lymphocyte movements in lymphoid organs is controversial. Recent evidence suggests that the extensive network of fibroblastic reticular cells within. the T cell areas helps guide T cells. The expression of adhesion molecules and chemokines by fibroblastic reticular cells most likely facilitates their influence on T cell movements. Consistent with this hypothesis, CD4 T cells with defective chemokine receptor signaling move very differently within lymph nodes than do normal cells. For the imaging studies, we used CD4 T cells prepared from Gnai2(-/-) mice, which lack G(alpha i2), expression. We first demonstrate that CD4 as well as CD8 T cells from these mice are markedly defective in chemokine receptor signaling. Gnai2(-/-) T cells have profound defects in chemokine-induced intracellular calcium mobilization, chemotaxis, and homing, whereas Gnai2(+/-) T cells exhibit modest defects. Intravital imaging revealed that within the inguinal lymph nodes Gnai2(-/-) CD4 T accumulate at the cortical ridge, poorly accessing the lymph node paracortex. They also lack the customary amoeboid-like cell movements and active membrane projections observed with normal CD4 T cells. These results demonstrate the importance of G(alpha i2) for T lymphocyte chemokine receptor signaling and argue that local chemoattractants regulate the movement of CD4 T cells in lymph nodes. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B08,10 Ctr Dr MSC 1876, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X NR 35 TC 27 Z9 27 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 439 EP 448 PG 10 WC Immunology SC Immunology GA 182IF UT WOS:000247497600053 PM 17579064 ER PT J AU Allen, SD Garrett, JT Rawale, SV Jones, AL Phillips, G Forni, G Morris, JC Oshima, RG Kaumaya, PTP AF Allen, Stephanie D. Garrett, Joan T. Rawale, Sharad V. Jones, Audra L. Phillips, Gary Forni, Guido Morris, John C. Oshima, Robert G. Kaumaya, Pravin T. P. TI Peptide vaccines of the HER-2/neu dimerization loop are effective in inhibiting mammary tumor growth in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-BREAST-CANCER; T-CELL IMMUNITY; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; FACTOR RECEPTOR; ADJUVANT CHEMOTHERAPY; CIRCULAR-DICHROISM; CRYSTAL-STRUCTURE; HER2 ACTIVATION; DISULFIDE BONDS AB Human epidermal growth factor receptor-2 (HER-2)/neu (ErbB2), a member of the epidermal growth factor family of receptors, is overexpressed in 20-30% of breast cancers. It is an attractive target for receptor-directed antitumor therapy using mAbs. Unlike other epidermal growth factor receptor family members, HER-2/neu does not bind a high-affinity ligand, but rather functions as the preferred dimerization partner. Pertuzumab (Omnitarg) is a humanized mAb directed against the HER-2/neu dimerization domain that inhibits receptor signaling. The recent definition of the crystal structure of the HER-2/neu-pertuzumab complex demonstrated that the receptor dimerization region encompassed residues 266-333. Based on the three-dimensional structure of the complex, we have designed three conformational peptide constructs (sequences 266-296, 298-333, and 315-333) to mimic regions of the dimerization loop of the receptor and to characterize their in vitro and in vivo antitumor efficacy. All the constructs elicited high-affinity peptide Abs that inhibited multiple signaling pathways including HER-2/neu-specific inhibition of cellular proliferation and cytoplasmic receptor domain phosphorylation. All the peptide Abs showed Ab-dependent cellular cytotoxicity to varying degrees with the 266-296 constructs being equally effective as compared with Herceptin. The 266-296 peptide vaccine had statistically reduced tumor onset in both transplantable tumor models (FVB/n and BALB/c) and significant reduction in tumor development in two transgenic mouse tumor models (BALB-neuT and VEGF(+/-)Neu2-5(+/-)). The 266-296 construct represents the most promising candidate for antitumor vaccination and could also be used to treat a variety of cancers with either normal or elevated expression of HER-2 including breast, lung, ovarian, and prostate. C1 Ohio State Univ, Columbus, OH 43210 USA. Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Ohio State Univ, Chem Biol Interface Program, Columbus, OH 43210 USA. Univ Turin, Dept Clin & Biol Sci, Turin, Italy. Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA. Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA. NCI, Canc Res Ctr, Metab Branch, Bethesda, MD 20892 USA. Burnham Inst Med Res, Oncodev Biol Program, La Jolla, CA 92037 USA. Ohio State Univ, Arthur G James Comprehens Canc Ctr, Columbus, OH 43210 USA. RP Kaumaya, PTP (reprint author), Ohio State Univ, Suite 316 Med Res Facil,420 West 12th Ave, Columbus, OH 43210 USA. EM Kaumaya.1@osu.edu FU NCI NIH HHS [CA 84356] NR 49 TC 31 Z9 35 U1 3 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 472 EP 482 PG 11 WC Immunology SC Immunology GA 182IF UT WOS:000247497600057 PM 17579068 ER PT J AU Kowalski, RJ Zeevi, A Mannon, RB Britz, JA Carruth, LM AF Kowalski, Richard J. Zeevi, Adriana Mannon, Roslyn B. Britz, Judith A. Carruth, Lucy M. TI Immunodiagnostics: Evaluation of functional T-cell immunocompetence in whole blood independent of circulating cell numbers SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Article ID CYTOKINE FLOW-CYTOMETRY; TRANSPLANT RECIPIENTS; ANTIRETROVIRAL THERAPY; VIROLOGICAL RESPONSES; SMALLPOX VACCINATION; IMMUNE FUNCTION; INFECTION; ASSAY; ALEMTUZUMAB; MECHANISMS AB The need for a systematic approach for immune function monitoring has becoming increasingly apparent in the past decade due to the rapid expansion of the development and use of immunomodulatory drug therapies and vaccines. While there has been a great deal of progress in the development of methodologies for evaluating and enumerating T-lymphocyte responses to infection and cancer, the translation of these assays into the clinical setting has remained seemingly elusive. This is likely due to inherent difficulties in the standardization and validation of cell-based assays. Here, we describe a novel assay that measures ATP production in CD4(+) T-lymphocytes in response to stimulation. Results from the test, unlike absolute cell counts, assess the functional response of lymphocytes. Clinical utility of the assay has been demonstrated in managing immunosuppression in solid organ transplant recipients such that adverse events such as infection and rejection can be avoided. The need for a global immune response test in the clinical setting of transplantation and the value of such a test in post-transplant management is discussed. Furthermore, additional applications of this assay for monitoring diseases that impact immune function including autoimmunity and infection are considered. C1 [Kowalski, Richard J.] Cylex Inc, Prod Dev, Columbia, MD 21045 USA. [Zeevi, Adriana] Univ Pittsburgh, Med Ctr, Dept Pathol, Thomas E Starzl Transplant Inst, Pittsburgh, PA USA. [Mannon, Roslyn B.] NIDDK, Transplantat Branch, NIH, Bethesda, MD USA. RP Carruth, LM (reprint author), Cylex Inc, Prod Dev, 8980-I Old Annapolis Rd, Columbia, MD 21045 USA. EM lcarruth@cylex.net NR 48 TC 14 Z9 14 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PD JUL-SEP PY 2007 VL 4 IS 3 BP 225 EP 232 DI 10.1080/15476910701385638 PG 8 WC Toxicology SC Toxicology GA 300KL UT WOS:000255822600006 PM 18958732 ER PT J AU Taha, TE Hoover, DR Kumwenda, NI Fiscus, SA Kafulafula, G Nkhoma, C Chen, S Piwowar, E Broadhead, RL Jackson, JB Miotti, PG AF Taha, Taha E. Hoover, Donald R. Kumwenda, Newton I. Fiscus, Susan A. Kafulafula, George Nkhoma, Chiwawa Chen, Shu Piwowar, Estelle Broadhead, Robin L. Jackson, J. Brooks Miotti, Paolo G. TI Late postnatal transmission of HIV-1 and associated factors SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 16th International AIDS Conference CY AUG 13-18, 2006 CL Toronto, CANADA ID TO-CHILD TRANSMISSION; IMMUNODEFICIENCY-VIRUS TYPE-1; SINGLE-DOSE NEVIRAPINE; POSTEXPOSURE PROPHYLAXIS; BREAST-MILK; WOMEN; QUANTITATION; PREVENTION; ZIDOVUDINE; RESISTANCE AB Background. The present study was undertaken to determine the risk and timing of late postnatal transmission ( LPT) of human immunodeficiency virus type 1 ( HIV-1). Methods. Breast-fed infants previously enrolled in 2 trials of antiretroviral prophylaxis were monitored in Malawi. Kaplan-Meier and proportional hazard models assessed cumulative incidence and association of factors with LPT. Results. Overall, 98 infants were HIV infected, and 1158 were uninfected. The cumulative risk of LPT at age 24 months was 9.68% ( 95% confidence interval, 7.80%-11.56%). The interval hazards at 1.5-6, 6-12, 12-18, and 18-24 months were 1.22%, 4.05%, 3.48%, and 1.27%, respectively. Conclusions. The risk of LPT beyond 6 months is substantial. Weaning at 6 months could prevent 185% of LPT. C1 Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NIH, Off AIDS Res, Bethesda, MD USA. Rutgers State Univ, Dept Stat, Piscataway, NJ USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. Univ Malawi, Coll Med, Dept Obstet & Gynecol, Zomba, Malawi. Univ Malawi, Coll Med, Dept Pediat, Zomba, Malawi. Johns Hopkins Univ, Coll Med, Minist Hlth, Res Project, Blantyre, Malawi. RP Taha, TE (reprint author), Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, 615 N Wolfe St,Rm E7138, Baltimore, MD 21205 USA. EM ttaha@jhsph.edu FU FIC NIH HHS [5 R03 TW01199]; NIAID NIH HHS [U01 AI068613, U01 AI068613-02, U01 AI48005] NR 15 TC 41 Z9 43 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2007 VL 196 IS 1 BP 10 EP 14 DI 10.1086/518511 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175BL UT WOS:000246987100004 PM 17538877 ER PT J AU Phogat, S Wyatt, RT Hedestam, GBK AF Phogat, S. Wyatt, R. T. Hedestam, G. B. Karlsson TI Inhibition of HIV-1 entry by antibodies: potential viral and cellular targets SO JOURNAL OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT Symposium on HIV Neutralizing Antibodies - Relevance to Pathogenesis and Vaccines CY OCT, 2006 CL Karolinska Inst, Stockholm, SWEDEN HO Karolinska Inst DE HIV-1; neutralizing antibodies; vaccine; envelope glycoprotein; receptors; incorporated proteins ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODY; GP120 ENVELOPE GLYCOPROTEIN; CD4 BINDING-SITE; CD4-INDUCED CONFORMATIONAL-CHANGES; CHEMOKINE RECEPTOR GENE; NEUTRALIZING ANTIBODIES; RHESUS MACAQUES; VACCINE DESIGN; SMALL-MOLECULE AB Vaccine-induced antibodies that interfere with viral entry are the protective correlate of most existing prophylactic vaccines. However, for highly variable viruses such as HIV-1, the ability to elicit broadly neutralizing antibody responses through vaccination has proven to be extremely difficult. The major targets for HIV-1 neutralizing antibodies are the viral envelope glycoprotein trimers on the surface of the virus that mediate receptor binding and entry. HIV-1 has evolved many mechanisms on the surface of envelope glycoproteins to evade antibody-mediated neutralization, including the masking of conserved regions by glycan, quaternary protein interactions and the presence of immunodominant variable elements. The primary challenge in the development of an HIV-1 vaccine that elicits broadly neutralizing antibodies therefore lies in the design of suitable envelope glycoprotein immunogens that circumvent these barriers. Here, we describe neutralizing determinants on the viral envelope glycoproteins that are defined by their function in receptor binding or by rare neutralizing antibodies isolated from HIV-infected individuals. We also describe the nonvariable cellular receptors involved in the HIV-1 entry process, or other cellular proteins, and ongoing studies to determine if antibodies against these proteins have efficacy as therapeutic reagents or, in some cases, as vaccine targets to interfere with HIV-1 entry. C1 Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Swedish Inst Infect Dis Control, Solna, Sweden. RP Hedestam, GBK (reprint author), Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Box 280, S-17177 Stockholm, Sweden. EM gunilla.karlsson.hedestam@ki.se FU Intramural NIH HHS [Z99 AI999999] NR 153 TC 33 Z9 35 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-6820 J9 J INTERN MED JI J. Intern. Med. PD JUL PY 2007 VL 262 IS 1 BP 26 EP 43 DI 10.1111/j.1365-2796.2007.01820.x PG 18 WC Medicine, General & Internal SC General & Internal Medicine GA 183OB UT WOS:000247581000003 PM 17598813 ER PT J AU Tanioka, M Masaki, T Ono, R Nagano, T Otoshi-Honda, E Matsumura, Y Takigawa, M Inui, H Miyachi, Y Moriwaki, S Nishigori, C AF Tanioka, Miki Masaki, Taro Ono, Ryusuke Nagano, Tohru Otoshi-Honda, Eriko Matsumura, Yasuhiro Takigawa, Masahiro Inui, Hiroki Miyachi, Yoshiki Moriwaki, Shinichi Nishigori, Chikako TI Molecular analysis of DNA polymerase eta gene in Japanese patients diagnosed as xeroderma pigmentosum variant type SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID ERROR-PRONE; SENSITIVITY; REPAIR; EUKARYOTES; MUTATIONS; CAFFEINE; BYPASS; CELLS; LIGHT; RNA AB POLH mutations were identified in 16 Japanese patients, who were diagnosed, both clinically and at a cellular level, as being of the xeroderma pigmentosum variant type (XPV). While all the patients developed skin cancer with an average onset of the cancer at 45 years, in non-XP Japanese the onset was at over 70 years. All the cell strains from the patients were normal or slightly hypersensitive to UV and most of these showed enhanced UV sensitivity when the post-UV colony formation was performed in the presence of caffeine. Immunoprecipitation analysis with two kinds of anti-POLH protein antibodies revealed that cells from 13 patients did not show the 83 kDa POLH band and that cells from one patient had a faint 83 kDa band. All of these 14 cell strains, without a POLH band or with a weak POLH band, had mutations in the POLH gene. The IP analysis of the POLH protein revealed a very useful method for screening the patients suspected of XPV. Seven mutations in the POLH gene including three novel mutations were identified. Among the mutations detected, 11 alleles out of 28 (39%) were G490T mutations. C1 Kobe Univ, Grad Sch Med, Div Dermatol, Dept Dermatol,Chuo Ku, Kobe, Hyogo 6500017, Japan. Kyoto Univ, Grad Sch Med, Dept Dermatol, Kyoto, Japan. Hamamatsu Univ Sch Med, Dept Dermatol, Hamamatsu, Shizuoka 43131, Japan. Natl Canc Inst, DNA Repair Sect, Basic Res Lab, Ctr Canc Res, Bethesda, MD USA. Hamamatsu Univ Sch Med, Photon Med Res Ctr, Hamamatsu, Shizuoka 43131, Japan. RP Nishigori, C (reprint author), Kobe Univ, Grad Sch Med, Div Dermatol, Dept Dermatol,Chuo Ku, 7-5-1 Kusunoki cho, Kobe, Hyogo 6500017, Japan. EM chikako@med.kobe-u.ac.jp NR 22 TC 26 Z9 29 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2007 VL 127 IS 7 BP 1745 EP 1751 DI 10.1038/sj.jid.5700759 PG 7 WC Dermatology SC Dermatology GA 184YB UT WOS:000247677400032 PM 17344931 ER PT J AU Zocchi, L Terrinoni, A Candi, E Ahvazi, B Bagetta, G Corasaniti, MT Lena, AM Melino, G AF Zocchi, Loredana Terrinoni, Alessandro Candi, Eleonora Ahvazi, Bijan Bagetta, Giacinto Corasaniti, M. Tiziana Lena, Anna M. Melino, Gerry TI Identification of transglutaminase 3 splicing isoforms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter ID BARRIER FUNCTION; STRUCTURAL BASIS; HUMAN EPIDERMIS; MICE LACKING; GENE FAMILY; EXPRESSION; SKIN; KERATINOCYTES; NUCLEOTIDES; ENVELOPE C1 Univ Roma Tor Vergata, Biochem Lab, IDI, IRCCS, Rome, Italy. NIAMSD, NIH, Crystallog Facil, Off Sci & Technol, Bethesda, MD 20892 USA. Univ Calabria, Dept Pharmacobiol, I-87036 Cosenza, Italy. Univ Magna Graecia, Dept Pharmacol Sci, Catanzaro, Italy. Univ Roma Tor Vergata, Ctr Expt Neuropharmacol, Rome, Italy. Univ Leicester, Toxicol Unit, MRC, Leicester, Leics, England. RP Zocchi, L (reprint author), Univ Roma Tor Vergata, Biochem Lab, IDI, IRCCS, Rome, Italy. EM melino@uniroma2.it RI Corasaniti, Maria Tiziana/N-1332-2015; Bagetta, Giacinto/E-8402-2012 OI Corasaniti, Maria Tiziana/0000-0001-6472-0697; Bagetta, Giacinto/0000-0001-8540-6218 FU Intramural NIH HHS; Medical Research Council [MC_U132670600]; Telethon [GGP04110] NR 27 TC 2 Z9 2 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2007 VL 127 IS 7 BP 1791 EP 1794 DI 10.1038/sj.jid.5700768 PG 4 WC Dermatology SC Dermatology GA 184YB UT WOS:000247677400043 PM 17380116 ER PT J AU Nordlind, K Thorslund, K Lonne-Ralim, SB Mohabbati, S Berki, T Morales, M Azmitia, E AF Nordlind, Klis Thorslund, Kristoffer Lonne-Ralim, Sol-Britt Mohabbati, Sheila Berki, Timea Morales, Marisela Azmitia, Efrain TI Serotonin receptors in psoriasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 1st World Psoriasis and Psoriatic Arthritis Conference CY MAY 31-JUN 04, 2006 CL Stockholm, SWEDEN SP Int Federat Psoriasis Assoc C1 Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden. Uppsala Univ, Uppsala, Sweden. Univ Pecs, Pecs, Hungary. Natl Inst Drug Abuse, Baltimore, MD USA. NYU, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2007 VL 127 IS 7 MA 21 BP 1803 EP 1803 PG 1 WC Dermatology SC Dermatology GA 184YB UT WOS:000247677400066 ER PT J AU Ledesma-Carbayo, MJ Kellman, P Arai, AE McVeigh, ER AF Ledesma-Carbayo, Maria J. Kellman, Peter Arai, Andrew E. McVeigh, Elliot R. TI Motion corrected free-breathing Delayed-enhancement imaging of myocardial infarction using nonrigid registration SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE delayed enhancement; myocardial infarction; free-breathing; motion correction; nonrigid registration; SENSE ID AUTOMATED FEATURE ANALYSIS; RESPIRATORY MOTION; SIZING ALGORITHM; DEFORMATION; IMAGES; MRI; VALIDATION; ULTRASOUND; INTENSITY; TRUEFISP AB Purpose: To develop and test an automatic free-breathing, delayed enhancement imaging method with improved image signal-to-noise ratio (SNR). Materials and Methods: The proposed approach uses free-breathing, inversion-recovery single-shot fast imaging with steady precession (FISP) delayed-enhancement with respiratory motion compensation based on nonrigid image registration. Motion-corrected averaging is used to enhance SNR. Results: Fully automatic, nonrigid registration was compared to previously validated rigid body registration that required user interaction. The performance was measured using the variance of edge positions in intensity profiles through the myocardial infarction (MI) enhanced region and through the right ventricular (RV) wall. Measured variation of the MI edge was 1.16 +/- 0.71 mm (N = 6 patients; mean +/- SD) for rigid body and 1.08 +/- 0.76 mm for nonrigid registration (no significant difference). On the other hand, significant improvement (P < 0.005) was found in the measurements at the RV edge where the SD was 2.06 +/- 0.56 mm for rigid body and 0.59 +/- 0.22 mm for nonrigid registration. Conclusion: The proposed approach achieves delayed enhancement images with high resolution and SNR without requiring a breathhold. Motion correction of free-breathing delayed-enhancement imaging using nonrigid image registration may be implemented in a fully automatic fashion and performs uniformly well across the full field of view (FOV). C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. Univ Politecn Madrid, ETSI Telecommun, Madrid, Spain. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, 10 Ctr Dr,MSC 1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov RI Ledesma-Carbayo, Maria /D-5529-2009 OI Ledesma-Carbayo, Maria /0000-0001-6846-3923 FU Intramural NIH HHS NR 25 TC 37 Z9 39 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUL PY 2007 VL 26 IS 1 BP 184 EP 190 DI 10.1002/jmri.20957 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 198RF UT WOS:000248644500027 PM 17659545 ER PT J AU Shmueli, K Thomas, DL Ordidge, RJ AF Shmueli, Karin Thomas, David L. Ordidge, Roger J. TI Design, construction and evaluation of an anthropomorphic head phantom with realistic susceptibility artifacts SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE anthropomorphic head phantom; susceptibility artifacts; high-field MRI; geometric distortion; signal dropout assessment ID MAGNETIC-FIELD; HUMAN BRAIN; MRI; ACCURACY; IMAGES; INHOMOGENEITY; SENSITIVITY; HOMOGENEITY; TISSUE; PET AB Purpose: To design and construct an anthropomorphic head phantom using materials of appropriate magnetic susceptibility and air spaces of realistic dimensions, with the aim of reproducing the susceptibility artifacts found in the human brain. Materials and Methods: The phantom is based on a plastic skull filled with MnCl(2)-doped water. Materials to mimic soft tissue (wax) and bone (plastic skull) were chosen based on mass susceptibility measurements using a superconducting quantum interference device (SQUID) magnetometer. The phantom was designed for and evaluated at 4.7T using field mapping and echo-planar imaging (EPI). Results: The main magnetic field (B(0)) maps of the phantom resemble those of four volunteers' brains and have similar standard deviations (SDs). Maps of the B(0) field gradients in the phantom and real brains are also similar. The phantom has relaxation times close to those of brain tissue at 4.7T. Gradient-echo (GE)-EPI images of the phantom suffer from susceptibility artifacts comparable to those in real heads and at anatomically realistic locations. Conclusion: The phantom is a useful tool for evaluating and comparing different susceptibility artifact reduction techniques. The phantom could also be used to test CT-MRI coregistration in the presence of susceptibility artifacts since the water-filled brain cavity is both CT- and MR-visible. C1 NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. UCL, Wellcome Trust High Field Magnet Resonance Res La, Dept Med Phys & Bioengn, London, England. RP Shmueli, K (reprint author), NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, 10 Ctr Dr,Bldg 10,Rm B1D-728, Bethesda, MD 20892 USA. EM shmuelik@mail.nih.gov RI Ordidge, Roger/F-2755-2010; Shmueli, Karin/B-9432-2017; OI Ordidge, Roger/0000-0002-1005-3654 FU Wellcome Trust [045939, 065690, 075929] NR 21 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD JUL PY 2007 VL 26 IS 1 BP 202 EP 207 DI 10.1002/jmri.20993 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 198RF UT WOS:000248644500030 PM 17659546 ER PT J AU Espinoza, J Chaiworapongsa, T Romero, R Kim, YM Kim, GJ Nien, JK Kusanovic, YP Erez, O Bujold, E Goncalves, LF Gomez, R Edwin, S AF Espinoza, Jimmy Chaiworapongsa, Tinnakorn Romero, Roberto Kim, Yeon Mee Kim, Gi Jin Nien, Jyh Kae Kusanovic, Yuan Pedro Erez, Offer Bujold, Emmanuel Goncalves, Luis F. Gomez, Ricardo Edwin, Samuel TI Unexplained fetal death: Another anti-angiogenic state SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE preterm labor; preterm PROM; fetal death; acute pyelonephritis; great obstetrical syndrome; soluble VEGFR-1 ID ENDOTHELIAL GROWTH-FACTOR; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS; FACTOR RECEPTOR; HUMAN PLACENTA; HISTOLOGIC CHORIOAMNIONITIS; HEMOCHORIAL PLACENTATION; HUMAN TROPHOBLAST; DOWN-REGULATION; EXPRESSION AB Background. Pregnancy creates a unique situation in which both vasculogenesis and extensive angiogenesis are required for successful fetal and placental development. Recently, the soluble form of vascular endothelial growth factor (VEGF) receptor-1 (sVEGFR-1), an antagonist to VEGF and placental growth factor (PIGF) (two important angiogenic factors), has been implicated in the pathophysiology of preeclampsia and small for gestational age (SGA) without preeclampsia. There is, however, a paucity of information concerning plasma sVEGFR-1 concentrations in other obstetrical disorders. The purpose of this study was to determine plasma sVEGFR-1 concentrations in normal pregnancy, term gestation in labor, and in patients with pregnancy complications including spontaneous preterm labor, preterm, premature rupture of the membranes (PROM), fetal death, and acute pyelonephritis. Methods. A cross-sectional study was conducted to determine the concentrations of sVEGFR-1 in plasma obtained from 499 women in the following groups: (1) non-pregnant women (n = 40); (2) pregnant women (n = 135); (3) normal pregnant women at term in labor (n = 60), (4) fetal death (n = 60); (5) spontaneous preterm labor with intact membranes (n = 102); (6) preterm PROM (n = 64); and (7) pregnancy with acute pyelonephritis (n = 38). Since plasma sVEGFR-1 concentration changes with gestational age, the difference between the actual and the expected plasma sVEGFR-1 concentration (derived from regression equation of :normal pregnancy) for each patient (delta value) was calculated and used to examine the differences of plasma sVEGFR-1 concentrations among various groups. Plasma concentrations of sVEGFR-1 were determined by enzyme-linked immunoassay. Regression analysis and non-parametric statistics were used for analysis. Results. (1) Normal pregnant women before term had a median plasma sVEGFR-1 concentration significantly higher than non-pregnant women (p < 0.001); (2) plasma sVEGFR-1 concentration increased with advancing gestational age in normal pregnancy (r = 0.5; p < 0.001); (3) there was no significant difference in the median delta plasma concentration of sVEGFR-1 between normal pregnant A omen at term with and without labor (p = 0.09); (4) patients with fetal death had a median delta plasma concentration of sVEGFR-1 significantly higher than normal pregnant women (p = 0.001). Among patients with fetal death, those with unexplained causes (p = 0.04) and those with preeclampsia (p < 0.001) had a significantly higher delta plasma sVEGFR-1 concentration than normal pregnant women; and (5) there was no significant difference in the median delta plasma sVEGFR-1 concentration between normal pregnancy and preterm labor with intact membranes, preterm. PROM (regardless of the presence or absence of microbial invasion of the amniotic cavity), or acute pyelonephritis (all p > 0.05). Conclusions. Plasma sVEGFR-1 concentration is increased in a subset of patients with fetal death, but does not change in term and preterm parturition, rupture of fetal membranes, or acute pyelonephritis. C1 Wayne State Univ, Perinatol Res Branch, NICHD,Hutzel Womens Hosp, NIH,DHHS, Detroit, MI 48201 USA. Wayne State Univ, Dept Obstet & Gynecol, Hutzel Womens Hosp, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. Wayne State Univ, Hutzel Hosp, Dept Pathol, Detroit, MI 48201 USA. Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP, Puente Alto, Chile. RP Romero, R (reprint author), Wayne State Univ, Perinatol Res Branch, NICHD,Hutzel Womens Hosp, NIH,DHHS, 3990 John R Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 48 TC 35 Z9 37 U1 0 U2 2 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 JUL PY 2007 VL 20 IS 7 BP 495 EP 507 DI 10.1080/14767050701413022 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 196TQ UT WOS:000248505500001 PM 17674262 ER PT J AU Coutinho-Abreu, IV Balbino, VQ Valenzuela, JG Sonoda, IV Ramalho-Ortigao, JM AF Coutinho-Abreu, I. V. Balbino, V. Q. Valenzuela, J. G. Sonoda, I. V. Ramalho-Ortigao, J. M. TI Structural characterization of acetylcholinesterase 1 from the sand fly Lutzomyia longipalpis (Diptera : Psychodidae) SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Lutzomyia longipalpis; acetyleholinesterase; organophosphorus resistance; carbamate resistance ID CDNA-ENCODING ACETYLCHOLINESTERASE; MOSQUITO CULEX-PIPIENS; MEDIATED INSECTICIDE RESISTANCE; AMINO-ACID SUBSTITUTION; COLORADO POTATO BEETLE; INSENSITIVE ACETYLCHOLINESTERASE; POINT MUTATIONS; MOLECULAR-FORMS; APHIS-GOSSYPII; SWISS-MODEL AB Acetylcholinesterase (AChE) plays a key role in cholinergic impulse transmission, and it is the target enzyme for organophosphorus and carbamate insecticides. Two genes, AceI and AceII, have been characterized from different insect species, and point mutations in either gene can lead to significant resistance to these classes of insecticides. In this report, we describe the partial characterization of the AceI gene from Lutzomyia longipalpis (Lutz & Neiva) (Diptera: Psychodidae), and we show that the possibility exists for the development of a resistant phenotype to organophosphates and carbamates in sand flies. Our results point to the presence of a single AceI gene in L. longipalpis (LIAce1) and that AChE activity is inhibited by organophosphorus at a concentration of 5 X 10(-5) M. Regarding insecticide resistance, analysis of the truncated LlAce1 cDNA suggests that a single missense mutation leading to a glycine-to-serine substitution at amino acid position 119 (G119S) may arise in L. longipalpis, similar to what has been detected in Anopheles gambiae s.s. Another missense mutation involved in resistant phenotypes, F331W, detected in Culex tritaeniorhynchus Giles, is less likely to occur in L. longipalpis, because it faces codon constraint in this sand fly species. Comparison of the three-dimensional structures of the deduced amino acid sequence of the truncated LLAChE1 with that of An. gambiae and Cx. tritaeniorhynchus also suggests that similar structural modifications due to the missense amino acid changes in the active site gorge are detected in all three insects. C1 Univ Fed Pernambuco, Lab Genet Mol Humana, Dept Genet, BR-50670901 Recife, PE, Brazil. NIH, Vector Mol Biol Unit, LMVR, Bethesda, MD 20892 USA. RP Ramalho-Ortigao, JM (reprint author), Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. EM mortigao@nd.edu RI Balbino, Valdir/B-1410-2008; Ramalho-Ortigao, Marcelo/E-8225-2011 NR 58 TC 9 Z9 9 U1 0 U2 5 PU ENTOMOLOGICAL SOC AMER PI ANNAPOLIS PA 3 PARK PLACE, STE 307, ANNAPOLIS, MD 21401-3722 USA SN 0022-2585 EI 1938-2928 J9 J MED ENTOMOL JI J. Med. Entomol. PD JUL PY 2007 VL 44 IS 4 BP 639 EP 650 DI 10.1603/0022-2585(2007)44[639:SCOAFT]2.0.CO;2 PG 12 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 185ZH UT WOS:000247748400013 PM 17695019 ER PT J AU Denny, CC Grady, C AF Denny, Colleen C. Grady, Christine TI Clinical research with economically disadvantaged populations SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID INFORMED-CONSENT; TRIALS; PARTICIPATION; BIOETHICS; AFRICA; UNDUE AB Concerns about exploiting the poor or economically disadvantaged in clinical research are widespread in the bioethics community. For some, any research that involves economically disadvantaged individuals is de facto ethically problematic. The economically disadvantaged are thought of as "venerable" to exploitation, impaired decision making, or both, thus requiring either special protections or complete exclusion from research. A closer examination of the worries about vulnerabilities among the economically disadvantaged reveals that some of these worries are empirically or logically untenable, while others can be better resolved by improved study designs than by blanket exclusion of poorer individuals from research participation. The scientific objective to generate generalisable results and the ethical objective to fairly distribute both the risks and benefits of research oblige researchers not to unnecessarily bar economically disadvantaged subjects from clinical research participation. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Denny, CC (reprint author), NIH, Dept Clin Bioeth, 10 Ctr Dr,10-1C118, Bethesda, MD 20892 USA. EM dennycc@cc.nih.gov NR 29 TC 17 Z9 18 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD JUL 1 PY 2007 VL 33 IS 7 BP 382 EP 385 DI 10.1136/jme.2006.017681 PG 4 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 184NU UT WOS:000247649500003 PM 17601862 ER PT J AU Boretsky, YR Pynyaha, YV Boretsky, VY Kutsyaba, VI Protchenko, OV Philpott, CC Sibirny, AA AF Boretsky, Yuriy R. Pynyaha, Yuriy V. Boretsky, Volodymyr Y. Kutsyaba, Vasyl I. Protchenko, Olga V. Philpott, Caroline C. Sibirny, Andriy A. TI Development of a transformation system for gene knock-out in the flavinogenic yeast Pichia guilliermondii SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE riboflavin biosynthesis; codon usage; deletion cassette; transformation; URA3 marker; yeast Pichia guilliermondii ID CANDIDA-ALBICANS; RIBOFLAVIN; MUTANTS; IDENTIFICATION; USAGE; IRON AB Pichia guilliermondii is a representative of a yeast species, all of which over-synthesize riboflavin in response to iron deprivation. Molecular genetic studies in this yeast species have been hampered by a lack of strain-specific tools for gene manipulation. Stable P guilliermondii ura3 mutants were selected on the basis of 5'-fluoroorotic acid resistance. Plasmid carrying Saccharomyces cerevisiae URA3 gene transformed the mutant strains to prototrophy with a low efficiency. Substitution of a single leucine codon CUG by another leucine codon CUC in the URA3 gene increased the efficiency of transformation 100 fold. Deletion cassettes for the RIBI and RIB7 genes, coding for GTP cyclohydrolase and riboflavin synthase, respectively, were constructed using the modified URA3 gene and subsequently introduced into a P. guilliermondii ura3 strain. Site-specific integrants were identified by selection for the Rib(-) Ura(+) phenotype and confirmed by PCR analysis. Transformation of the P guilliermondii ura3 strain was performed using electroporation, spheroplasting or lithium acetate treatment. Only the lithium acetate transformation procedure provided selection of uracil prototrophic, riboflavin deficient recombinant strains. Depending on the type of cassette, efficiency of site-specific integration was 0.1% and 3-12% in the case of the RIBI and RIB7 genes, respectively. We suggest that the presence of the ARS element adjacent to the 3' end of the RIB] gene significantly reduced the frequency of homologous recombination. Efficient gene deletion in P. guilliermondii can be achieved using the modified URA3 gene of S. cerevisiae flanked by 0.8-0.9 kb sequences homologous to the target gene. (C) 2007 Elsevier B.V. All rights reserved. C1 Natl Acad Sci Ukraine, Inst Cell Biol, Dept Mol Genet & Biotechnol, UA-79005 Lvov, Ukraine. NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. Rzeszow Univ, Dept Met Engn, PL-35601 Rzeszow, Poland. RP Sibirny, AA (reprint author), Natl Acad Sci Ukraine, Inst Cell Biol, Dept Mol Genet & Biotechnol, Dragomanov Str 14-16, UA-79005 Lvov, Ukraine. EM sibirny@cellbiol.lviv.ua OI Boretsky, Yuriy/0000-0001-7892-8915 NR 29 TC 18 Z9 19 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 EI 1872-8359 J9 J MICROBIOL METH JI J. Microbiol. Methods PD JUL PY 2007 VL 70 IS 1 BP 13 EP 19 DI 10.1016/j.mimet.2007.03.004 PG 7 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 191DG UT WOS:000248109500002 PM 17467833 ER PT J AU Gannot, G Tangrea, MA Erickson, HS Pinto, PA Hewitt, SM Chuaqui, RF Gillespie, JW Emmert-Buck, MR AF Gannot, Gallya Tangrea, Michael A. Erickson, Heidi S. Pinto, Peter A. Hewitt, Stephen M. Chuaqui, Rodrigo F. Gillespie, John W. Emmert-Buck, Michael R. TI Layered peptide array for multiplex immunohistochemistry SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID TISSUE; ANTIBODIES; SAMPLES AB ]Layered peptide array is a new methodology for multiplex molecular measurements from two-dimensional fife science platforms. The technology can be used in several different configurations depending on the needs of the investigator. Described here is an indirect layered peptide array (ELPA) that is capable of measuring proteins on a solid surface, such as target antigens on a tissue section. A prototype ELPA system was developed and subsequently examined for reproducibility and specificity and then compared with standard immunohistochemistry. Semiquantitative, multiplex proteomic analysis of histological sections was achieved with up to 20 membranes. The experimental variability was 18%. Overall, the data suggest that iLPA technology will be a relatively simple and inexpensive method for molecular measurements from tissue sections. C1 NCI, Ctr Canc Res, Pathol Lab, Ctr Adv Technol,Pathogenet Unit, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Ctr Adv Technol,Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Dept Urol Oncol, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Tissue Array Res Program, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Ctr Canc Res, Pathol Lab, Ctr Adv Technol,Pathogenet Unit, 8717 Grovemont Cir, Bethesda, MD 20892 USA. EM mbuck@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS NR 14 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD JUL PY 2007 VL 9 IS 3 BP 297 EP 304 DI 10.2353/jmoldx.2007.060143 PG 8 WC Pathology SC Pathology GA 185DJ UT WOS:000247691200004 PM 17591928 ER PT J AU Quignodon, L Grijota-Martinez, C Compe, E Guyot, R Allioli, N Laperriere, D Walker, R Meltzer, P Mader, S Samarut, J Flamant, F AF Quignodon, Laure Grijota-Martinez, Carmen Compe, Emmanuel Guyot, Romain Allioli, Nathalie Laperriere, David Walker, Robert Meltzer, Paul Mader, Sylvie Samarut, Jacques Flamant, Frederic TI A combined approach identifies a limited number of new thyroid hormone target genes in post-natal mouse cerebellum SO JOURNAL OF MOLECULAR ENDOCRINOLOGY LA English DT Article ID CENTRAL CONGENITAL HYPOTHYROIDISM; OLIGODENDROCYTE PRECURSOR CELLS; RESPONSE ELEMENTS; RECEPTOR ALPHA-1; KNOCKOUT MICE; MICROARRAY ANALYSIS; BRAIN-DEVELOPMENT; SYNAPTOTAGMIN-IV; RAT-BRAIN; TR-ALPHA AB Thyroid hormones act directly on gene transcription in the post-natal developing cerebellum, controlling neuronal, and glial cell differentiation. We have combined three experimental approaches to identify the target genes that are underlying this phenomenon: 1) a microarray analysis of gene expression to identify hormone responsive genes in the cerebellum of Pax8(-/-) mice, a transgenic mouse model of congenital hypothyroidism; 2) a similar microarray analysis on primary culture of cerebellum neurons; and 3) a bioinformatics screen of conserved putative-binding sites in the mouse genome. This identifies surprisingly a small set of target genes, which, for some of them, might be key regulators of cerebellum development and neuronal differentiation. C1 Univ Lyon, Ecole Normale Super Lyon, Inst Genome Fonctionnelle Lyon, UMR INRA CNRS 5242, F-69364 Lyon 7, France. Autonomous Univ Madrid, CSIC, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain. Ctr Biomed Res Rare Dis, Madrid 28029, Spain. Inst Genet & Biol Mol Cellulaire, Illkirch Graffenstaden, France. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. Univ Montreal, Inst Rech Immunol & Ctr, Montreal, PQ H3C 3J7, Canada. RP Flamant, F (reprint author), Univ Lyon, Ecole Normale Super Lyon, Inst Genome Fonctionnelle Lyon, UMR INRA CNRS 5242, IFR128 46 Allee Italie, F-69364 Lyon 7, France. EM frederic.flamant@ens-lyon.fr RI Compe, Emmanuel/N-8718-2016; OI Compe, Emmanuel/0000-0002-9189-7444 NR 65 TC 28 Z9 28 U1 0 U2 1 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0952-5041 J9 J MOL ENDOCRINOL JI J. Mol. Endocrinol. PD JUL-AUG PY 2007 VL 39 IS 1-2 BP 17 EP 28 DI 10.1677/JME-06-0054 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 205CX UT WOS:000249091900003 PM 17601882 ER PT J AU Spuches, AM Argiros, HJ Lee, KH Haas, LL Perch, SC Krag, DN Roller, PP Wilcox, DE Lyons, BA AF Spuches, A. M. Argiros, H. J. Lee, K. H. Haas, L. Lowell Perch, S. C. Krag, D. N. Roller, P. P. Wilcox, D. E. Lyons, B. A. TI Calorimetric investigation of phosphorylated and non-phosphorylated peptide ligand binding to the human Grb7-SH2 domain SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article DE erbB2; Grb7; SH2 domain; isothermal titration calorimetry; thermodynamics; ligand binding; protein recognition ID AFFINITY PHOSPHOTYROSYL PEPTIDE; GROWTH-FACTOR RECEPTOR; ADAPTER PROTEIN GRB10; FOCAL ADHESION KINASE; SRC HOMOLOGY-2 DOMAIN; SH2 DOMAIN; STRUCTURAL BASIS; GRB2-SH2 DOMAIN; CELL-MIGRATION; BREAST-CANCER AB Grb7 is a member of the Grb7 family of proteins, which also includes Grb10 and Grb14. All three proteins have been found to be overexpressed in certain cancers and cancer cell lines. In particular, Grb7 (along with the receptor tyrosine kinase erbB2) is overexpressed in 20-30% of breast cancers. In general, growth factor receptor bound (Grb) proteins bind to activated membrane-bound receptor tyrosine kinases (RTKs; e.g., the epidermal growth factor receptor, EGFR) through their Src homology 2 (SH2) domains. In particular, Grb7 binds to erbB2 (a.k.a. EGFR2) and may be involved in cell signaling pathways that promote the formation of metastases and inflammatory responses. In previous studies, we reported the solution structure and the backbone relaxation behavior of the Grb7-SH2/erbB2 peptide complex. In this study, isothermal titration calorimetry studies have been completed by measuring the thermodynamic binding parameters of several phosphorylated and non-phosphorylated peptides representative of natural Grb7 receptor ligands as well as ligands developed through combinatorial peptide screening methods. The entirety of these calorimetric studies is interpreted in an effort to describe the specific ligand binding characteristics of the Grb7 protein. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 New Mexico State Univ, Dept Chem & Biochem, Las Cruces, NM 88003 USA. NCI, Med Chem Lab, Frederick, MD 21702 USA. Univ Vermont, Coll Med, Dept Surg, Burlington, VT 05405 USA. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. RP Lyons, BA (reprint author), New Mexico State Univ, Dept Chem & Biochem, MSC 3C,POB 30001, Las Cruces, NM 88003 USA. EM blyons@nmsu.edu FU NCI NIH HHS [U56 CA096286, U56 CA096286-05]; NCRR NIH HHS [RR 016480]; NIGMS NIH HHS [S06 GM008136-31] NR 44 TC 13 Z9 13 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD JUL-AUG PY 2007 VL 20 IS 4 BP 245 EP 252 DI 10.1002/jmr.834 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 220UZ UT WOS:000250184100005 PM 17705331 ER PT J AU Meragelman, TL Willis, RH Woldemichael, GM Heaton, A Murphy, PT Snader, KM Newman, DJ Van Soest, R Boyd, MR Cardellina, JH McKee, TC AF Meragelman, Tamara L. Willis, Richard H. Woldemichael, Girma M. Heaton, Andrew Murphy, Peter T. Snader, Kenneth M. Newman, David J. Van Soest, Rob Boyd, Michael R. Cardellina, John H., II McKee, Tawnya C. TI Candidaspongiolides, distinctive analogues of tedanolide from sponges of the genus Candidaspongia SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID ANTITUMOR MACROLIDE; MYCALE-ADHAERENS; LIPASE; 13-DEOXYTEDANOLIDE; IMMOBILIZATION; TRIGLYCERIDE; SPIROSTANOL; SCREEN; TUBERS; POTENT AB Fractionation of cytotoxic extracts of specimens of a newly described sponge genus, Candidaspongia, has yielded the candidaspongiolides (3), a complex mixture of acyl esters of a macrolide related to tedanolide. The general structure of the candidaspongiolides was determined by analyses of various 2D NMR and MS data sets. The acyl ester components were identified by GC-MS analysis of the derived fatty acid methyl esters. The mixture could be selectively converted to the deacylated macrolide core (4) by enzymolysis with immobilized porcine lipase, with the structure of the candidaspongiolide core then secured by NMR and MS analysis. The candidaspongiolide mixture was potently cytotoxic, exhibiting a mean panel 50% growth inhibition (GI(50)) of 14 ng/mL in the National Cancer Institute's 60-cell-line in vitro antitumor screen. C1 NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD 21701 USA. NCI, Mol Targets Dev Program, Canc Res Ctr, Frederick, MD 21701 USA. Univ Amsterdam, Museum Zool, NL-1090 GT Amsterdam, Netherlands. NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Frederick, MD USA. Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. RP McKee, TC (reprint author), Australian Inst Marine Sci, PMB 3, Townsville Mail Ctr, Qld 4810, Australia. EM mckee@ncifcrf.gov FU Intramural NIH HHS [Z99 CA999999] NR 25 TC 19 Z9 19 U1 1 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD JUL PY 2007 VL 70 IS 7 BP 1133 EP 1138 DI 10.1021/np0700974 PG 6 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 194LB UT WOS:000248344800013 PM 17564468 ER PT J AU Bagic, A Lupu, VD Kessler, CM Tornatore, C AF Bagic, Anto Lupu, Vitalie D. Kessler, Craig M. Tornatore, Carlo TI Isolated Richter's transformation of the brain SO JOURNAL OF NEURO-ONCOLOGY LA English DT Review DE chronic lymphocytic leukemia; diffuse large cell lymphoma; non-Hodgkin's lymphoma; rituximab ID CENTRAL-NERVOUS-SYSTEM; CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPHOMA; INVOLVEMENT AB Patients with B-cell chronic lymphocytic leukemia (CLL) have an increased risk of second malignancy and may develop diffuse large-cell non-Hodgkin's lymphoma (DLCL) also known as Richter's syndrome (RS). Only seven cases of isolated brain RS without evidence of systemic lymphoma have been reported to date. We describe a case of isolated DLCL of the brain in a 58-year-old female patient with a 3 year history of B-cell CLL. The patient presented with falls due to left leg paresis and showed non-specific neuroimaging findings. Brain biopsy confirmed the diagnosis of DLCL and CLL restaging failed to demonstrate evidence of RS outside the CNS. The patient was treated with whole brain radiation therapy and was discharged 4 weeks later on weekly rituximab infusions. This report extends the previous experience by providing a detailed clinical, neuroradiological and pathological description of isolated RS of the brain. Early identification and timely CNS directed treatment may alter morbidity and positively influence quality of life. C1 E Portland Neurol Clin, Portland, OR 97201 USA. Univ Pittsburgh, Sch Med, Dept Neurol & Neurosurg, Pittsburgh, PA 15213 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Dept Internal Med, Washington, DC 20007 USA. Georgetown Univ Hosp, Dept Neurol, Washington, DC 20007 USA. RP Lupu, VD (reprint author), E Portland Neurol Clin, 10000 SE Main St,Ste 307, Portland, OR 97201 USA. EM LUPUV@ninds.nih.gov NR 13 TC 10 Z9 10 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD JUL PY 2007 VL 83 IS 3 BP 325 EP 328 DI 10.1007/s11060-007-9334-2 PG 4 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 179GP UT WOS:000247278000016 PM 17570037 ER PT J AU Greggio, E Lewis, PA van der Brug, MP Ahmad, R Kaganovich, A Ding, JH Beilina, A Baker, AK Cookson, MR AF Greggio, Elisa Lewis, Patrick A. van der Brug, Marcel P. Ahmad, Rili Kaganovich, Alice Ding, Jinhui Beilina, Alexandra Baker, Acacia K. Cookson, Mark R. TI Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cell culture; kinase; Parkinson disease; protein aggregation; toxicity AB Several mutations have been found in the leucine-rich repeat kinase 2 gene (LRRK2), encoding the protein dardarin, which are associated with autosomal dominant Parkinson disease. We have previously shown that mutant LRRK2/dardarin is toxic to neurons and neuron-like cell lines in culture and that some mutations are also associated with an inclusion-body phenotype. There is a homologous kinase, LRRK1, which has a similar domain structure but is not known to carry mutations causing Parkinson disease. In the current study, we introduced mutations at equivalent residues in both LRRK2 and LRRK1 to determine their effects in cells. We show that mutations in dardarin are more prone to form inclusion bodies in transfected cells and are more toxic than equivalent mutations in LRRK1. This work suggests that dardarin/LRRK2 is inherently more damaging than LRRK1. C1 NIA, Neurogenet Lab, NIH, Bioinformat Facil, Bethesda, MD 20892 USA. NIA, Cell Biol & Gene Express Unit, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bioinformat Facil, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov RI Lewis , Patrick/C-3674-2009; Greggio, Elisa/H-6119-2013; OI Greggio, Elisa/0000-0002-8172-3598; Lewis, Patrick/0000-0003-4537-0489 FU Intramural NIH HHS NR 15 TC 58 Z9 60 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2007 VL 102 IS 1 BP 93 EP 102 DI 10.1111/j.1471-4159.2007.04523.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 178FD UT WOS:000247205700008 PM 17394548 ER PT J AU Liu, LY Hoffman, GE Fei, XW Li, Z Zhang, ZH Mei, YA AF Liu, Lin-Yun Hoffman, Gloria E. Fei, Xiao-Wei Li, Zheng Zhang, Zhi-Hong Mei, Yan-Ai TI Delayed rectifier outward K+ current mediates the migration of rat cerebellar granule cells stimulated by melatonin SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cerebellar granule neurons; cerebellar slice cultures; K+ channel; melatonin; migration ID 2-IODOMELATONIN PREVENTS APOPTOSIS; NEURONAL MIGRATION; BINDING-SITES; OXIDATIVE STRESS; RECEPTORS; CHANNELS; BRAIN; MODULATION; ACTIVATION; INHIBITION AB Melatonin (MT) may work as a neuromodulator through the associated MT receptors in the central nervous system. Previously, our studies have shown that MT increased the I-K current via a G protein-related pathway. In the present study, patch-clamp whole-cell recording, transwell migration assays and organotypic cerebellar slice cultures were used to examine the effect of MT on granule cell migration. MT increased the I-K current amplitude and migration of granule cells. Meanwhile, TEA, the I-K channel blocker, decreased the I-K current and slowed the migration of granule cells. Furthermore, the effects of MT on the I-K current and cell migration were not abolished by pre-incubation with P7791, a specific antagonist of MT3R, but were eliminated by the application of the MT2R antagonists K185 and 4-P-PDOT. I-K current and cell migration were decreased by the application of dibutyryl cyclic AMP (dbcAMP), which was in contrast to the MT effect on the I-K current and cell migration. Incubation with dbcAMP essentially blocked the MT-induced increasing effect. Moreover, incubation of isolated cell cultures in the MT-containing medium also decreased the cAMP immunoreactivity in the granule cells. It is concluded, therefore, that I-K current, downstream of a cAMP transduction pathway, mediates the migration of rat cerebellar granule cells stimulated by MT. C1 Fudan Univ, Sch Life Sci, Dept Physiol & Biophys, Shanghai 200433, Peoples R China. Fudan Univ, State Key Lab Med Neurobiol, Shanghai 200433, Peoples R China. Univ Maryland, Sch Med, Dept Anat, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Neurobiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. NIMH, Unit Synapse Dev & Plastic Gene, Gognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. RP Mei, YA (reprint author), Fudan Univ, Sch Life Sci, Dept Physiol & Biophys, Shanghai 200433, Peoples R China. EM yamei@fudan.edu.cn NR 48 TC 27 Z9 28 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2007 VL 102 IS 2 BP 333 EP 344 DI 10.1111/j.1471-4159.2007.04669.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 183OE UT WOS:000247581300005 PM 17561939 ER PT J AU Lolait, SJ Stewart, LQ Roper, JA Harrison, G Jessop, DS Young, WS O'Carroll, AM AF Lolait, S. J. Stewart, L. Q. Roper, J. A. Harrison, G. Jessop, D. S. Young, W. S., III O'Carroll, A.-M. TI Attenuated stress response to acute lipopolysaccharide challenge and ethanol administration in vasopressin V1b receptor knockout mice SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE Avp 1b receptor; hypothalamic-pituitary-adrenal axis; lipopolysaccharide; ethanol ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; MESSENGER-RIBONUCLEIC-ACID; INSULIN-INDUCED HYPOGLYCEMIA; CENTRAL-NERVOUS-SYSTEM; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CRF GENE-EXPRESSION; ARGININE-VASOPRESSIN; ADRENOCORTICOTROPIN SECRETION; OXYTOCIN SECRETION AB The arginine vasopressin (Avp) 1b receptor (Avpr1b) present on anterior pituitary corticotrophs is involved in the stimulation of adrenocorticotrophic hormone (ACTH) secretion, especially during times of stress. Corticotrophin-releasing hormone (CRH) is considered the major ACTH secretagogue during acute stress whereas Avp appears to be the more dominant mediator of the hypothalamic-pituitary-adrenal (HPA) axis response during chronic stress situations. To investigate the role of the Avpr1b in the HPA axis response to acute stress, we measured ACTH and corticosterone (CORT) plasma levels in Avpr1b knockout (KO) mice and wild-type controls in response to bacterial lipopolysaccharide (LPS) challenge and ethanol (EtOH) administration. Mice deficient in Avpr1b had markedly compromised plasma ACTH and CORT responses to acute (30 min) LPS, but normal ACTH and CORT response to more extended exposure (4 h) to the immune system activator. The plasma ACTH and CORT levels stimulated by intoxicating, sedative doses of EtOH (3.2 and 4 g/kg) were significantly decreased in the Avpr1b KO mice compared to wild-type littermates. Significantly higher EtOH-induced plasma ACTH and CORT secretion was measured in female than in male Avpr1b wild-type mice. There were no differences in the blood alcohol levels following acute EtOH administration in Avpr1b KO or wild-type mice of either gender. Our results clearly suggest that Avpr1b plays a significant role in the HPA axis response to acute immune stress and EtOH intoxication. C1 Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Bristol BS1 3NY, Avon, England. Southmead Gen Hosp, Lewis Labs, Dept Clin Biochem, Bristol, Avon, England. NIMH, Sect Neural Gene Express, NIH, DHHS, Bethesda, MD 20892 USA. RP Lolait, SJ (reprint author), Univ Bristol, Henry Wellcome Labs Integrat Neurosci & Endocrino, Dorothy Hodgkin Bldg,Whitson St, Bristol BS1 3NY, Avon, England. EM s.j.lolait@bristol.ac.uk RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002498]; Wellcome Trust [, 063049, 074690] NR 69 TC 31 Z9 33 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD JUL PY 2007 VL 19 IS 7 BP 543 EP 551 DI 10.1111/j.1365-2826.2007.01560.x PG 9 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 177EC UT WOS:000247135400007 PM 17561882 ER PT J AU Salajegheh, M Raju, R Schmidt, J Dalakas, MC AF Salajegheh, Mohammad Raju, Raghavan Schmidt, Jens Dalakas, Marinos C. TI Upregulation of thrombospondin-1(TSP-1) and its binding partners, CD36 and CD47, in sporadic inclusion body myositis SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE inclusion body myositis; dermatomyositis; thrombospondin; CD47; CD36; amyloid ID CELL-ADHESION MOLECULES; IDIOPATHIC INFLAMMATORY MYOPATHIES; T-CELLS; COSTIMULATORY MOLECULE; EXPRESSION PROFILE; PROTEIN CD47; MUSCLE; BETA; RECEPTOR; DERMATOMYOSITIS AB The TSPI/CD36/CD47-complex is involved in T cell expansion and inflammatory responses to beta-amyloid, both relevant to IBM. We report on the mRNA and protein expression of TSP1/CD36/CD47-complex in IBM muscles and in human myoblasts after cytokine stimulation. The TSP1/CD36/CD47 was upregulated in IBM. TSPI immunolocalized to the connective tissue contiguous to inflammation and CD36/CD47 on the myofibers and CD8+ cells. Further, TNF-alpha upregulated the production of TSP1 and CD47 by myoblasts. The TSP-complex is another inflammatory mediator associated with chronic inflammation in IBM that may perpetuate the immune responses to local antigens in response to TNF-alpha. (c) 2007 Elsevier B.V. All rights reserved. C1 Brigham & Womens Hosp, Div Neuromusc Dis, Dept Neurol, Boston, MA 02115 USA. Ctr Surg Res, Dept Surg, Birmingham, AL 35294 USA. Univ Gottingen, Inst Expt & Clin, Muscle Immunobiol Sect, D-37073 Gottingen, Germany. NINDS, Neuromusc Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), Brigham & Womens Hosp, Div Neuromusc Dis, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM mdalakas@nonds.nih.gov RI Raju, Raghavan/E-9219-2011; Schmidt, Jens/B-5791-2013 FU Intramural NIH HHS NR 43 TC 8 Z9 8 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 2007 VL 187 IS 1-2 BP 166 EP 174 DI 10.1016/j.jneuroim.2007.04.022 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 196EC UT WOS:000248463500018 PM 17572512 ER PT J AU Schymick, JC Yang, Y Andersen, PM Vonsattel, JP Greenway, M Momeni, P Elder, J Chio, A Restagno, G Robberecht, W Dahlberg, C Mukherjee, O Goate, A Graff-Radford, N Caselli, RJ Hutton, M Gass, J Cannon, A Rademakers, R Singleton, AB Hardiman, O Rothstein, J Hardy, J Traynor, BJ AF Schymick, J. C. Yang, Y. Andersen, P. M. Vonsattel, J. P. Greenway, M. Momeni, P. Elder, J. Chio, A. Restagno, G. Robberecht, W. Dahlberg, C. Mukherjee, O. Goate, A. Graff-Radford, N. Caselli, R. J. Hutton, M. Gass, J. Cannon, A. Rademakers, R. Singleton, A. B. Hardiman, O. Rothstein, J. Hardy, J. Traynor, B. J. TI Progranulin mutations and amyotrophic lateral sclerosis or amyotrophic lateral sclerosis-frontotemporal dementia phenotypes SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID LOBAR DEGENERATION; CRITERIA AB Objective: Mutations in the progranulin (PGRN) gene were recently described as the cause of ubiquitin positive frontotemporal dementia (FTD). Clinical and pathological overlap between amyotrophic lateral sclerosis (ALS) and FTD prompted us to screen PGRN in patients with ALS and ALS-FTD. Methods: The PGRN gene was sequenced in 272 cases of sporadic ALS, 40 cases of familial ALS and in 49 patients with ALS-FTD. Results: Missense changes were identified in an ALS-FTD patient (p.S120Y) and in a single case of limb onset sporadic ALS (p.T182M), although the pathogenicity of these variants remains unclear. Conclusion: PGRN mutations are not a common cause of ALS phenotypes. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD USA. Johns Hopkins Univ, Dept Neurol & Neurosci, Baltimore, MD USA. Umea Univ Hosp, Dept Neurol & Clin Neurosci, S-90185 Umea, Sweden. Columbia Univ Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY USA. Beaumont Hosp, Dept Neurol, Dublin, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Univ Turin, Dept Neurosci, Turin, Italy. Childrens Hosp, Dept Clin Pathol, Mol Genet Unit, Turin, Italy. Katholieke Univ Leuven, Neurobiol Lab, Louvain, Belgium. Washington Univ, Sch Med, Alzheimers Dis Res Ctr, St Louis, MO USA. Mayo Clin, Coll Med, Dept Neurol, Jacksonville, FL USA. Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ USA. Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL USA. NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. RP Traynor, BJ (reprint author), Porter Neurosci Bldg,Room 1A-1014,35 Convent Dr, Bethesda, MD 20892 USA. EM traynorb@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Traynor, Bryan/G-5690-2010; OI Ingre, Caroline/0000-0001-5327-7204; Chio, Adriano/0000-0001-9579-5341; Hardiman, Orla/0000-0003-2610-1291 FU Intramural NIH HHS; Medical Research Council [G0701075]; NIA NIH HHS [P50 AG008702, P50 AG08702] NR 12 TC 80 Z9 82 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2007 VL 78 IS 7 BP 754 EP 756 DI 10.1136/jnnp.2006.109553 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 182TR UT WOS:000247527400025 PM 17371905 ER PT J AU Machner, B Gottschalk, S Sander, T Helmchen, C Rambold, H AF Machner, B. Gottschalk, S. Sander, T. Helmchen, C. Rambold, H. TI Intralabyrinthine schwannoma affecting the low but not high frequency function of the vestibulo-ocular reflex: implications for the clinical diagnosis of chronic peripheral vestibular deficits SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Letter C1 Univ Hosp Schleswig Holstein, Dept Neurol, D-23538 Lubeck, Germany. Univ Hosp Schleswig Holstein, Dept Neuroradiol, D-23538 Lubeck, Germany. NEI, Bethesda, MD 20892 USA. RP Helmchen, C (reprint author), Univ Hosp Schleswig Holstein, Dept Neurol, Campus Luebeck,Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM christoph.helmchen@neuro.uni-luebeck.de NR 5 TC 12 Z9 12 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2007 VL 78 IS 7 BP 772 EP 774 DI 10.1136/jnnp.2006.106179 PG 5 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 182TR UT WOS:000247527400034 PM 17575027 ER PT J AU Weinberger, DR AF Weinberger, D. R. TI Schizophrenia: Genes and the brain - A programme for the 21st century SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Meeting Abstract CT Annual Meeting of the British-Neuropsychiatry-Association CY FEB 22-23, 2007 CL Inst Child Hlth, London, ENGLAND SP British Neuropsychiat Assoc HO Inst Child Hlth C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2007 VL 78 IS 7 MA 005 BP 780 EP 780 PG 1 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 182TR UT WOS:000247527400044 ER PT J AU Cassiani-Ingoni, R Muraro, PA Magnus, T Reichert-Scrivner, S Schmidt, J Huh, J Quandt, JA Bratincsak, A Shahar, T Eusebi, F Sherman, LS Mattson, MP Martin, R Rao, MS AF Cassiani-Ingoni, Riccardo Muraro, Paolo A. Magnus, Tim Reichert-Scrivner, Susan Schmidt, Jens Huh, Jaebong Quandt, Jacqueline A. Bratincsak, Andras Shahar, Tal Eusebi, Fabrizio Sherman, Larry S. Mattson, Mark P. Martin, Roland Rao, Mahendra S. TI Disease progression after bone marrow transplantation in a model of multiple sclerosis is associated with chronic microglial and glial progenitor response SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE autoimmune disease; bone marrow transplantation; CD44; glial progenitor; microglia; Olig2; reactive astrocyte ID STEM-CELL TRANSPLANTATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; CENTRAL-NERVOUS-SYSTEM; FIBRILLARY ACIDIC PROTEIN; SPINAL-CORD; IMMATURE OLIGODENDROGLIA; DEMYELINATED LESIONS; PRECURSOR CELLS; THYMIC OUTPUT; EXPRESSION AB Multiple sclerosis (MS), the most common nontraumatic cause of neurologic disability in young adults in economically developed countries, is characterized by inflammation, gliosis, demyelination, and neuronal degeneration in the CNS. Bone marrow transplantation (BMT) can suppress inflammatory disease in a majority of patients with MS but retards clinical progression only in patients treated in the early stages of the disease. Here, we applied BMT in a mouse model of neuroinflammation, experimental autoimmune encephalomyelitis (EAE), and investigated the kinetics of reconstitution of the immune system in the periphery and in the CNS using bone marrow cells isolated from syngeneic donors constitutively expressing green fluorescent protein. This approach allowed us to dissect the contribution of donor cells to the turnover of resident microglia and to the pathogenesis of observed disease relapses after BMT. BMT effectively blocked or delayed EAE development when mice were treated early in the course of the disease but was without effect in mice with chronic disease. We found that there is minimal overall replacement of host microglia with donor cells in the CNS and that newly transplanted cells do not appear to contribute to disease progression. In contrast, EAE relapses are accompanied by the robust activation of endogenous microglial and macroglial cells, which further involves the maturation of endogenous Olig2 glial progenitor cells into reactive astrocytes through the cytoplasmic translocation of Olig2 and the expression of CD44 on the cellular membrane. The observed maturation of large numbers of reactive astrocytes from glial progenitors and the chronic activation of host microglial cells have relevance for our understanding of the resident glial response to inflammatory injury in the CNS. Our data indicate that reactivation of a local inflammatory process after BMT is sustained predominantly by endogenous microglia/macrophages. C1 Imperial Coll London, Fac Med, Dept Cellular & Mol Neurosci, London W68 RP, England. Imperial Coll London, Fac Med, Div Neurosci & Mental Hlth, London W68 RP, England. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, NIH, Bethesda, MD USA. Univ Roma La Sapienza, Ctr Excellence Biol & Mol Med, Rome, Italy. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Rome, Italy. NIA, Lab Neurosci, Stem Cell Biol Unit, NIH, Baltimore, MD USA. Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Div Neurosci, Beaverton, OR USA. Invitrogen Corp, Corp Res Labs, Carlsbad, CA USA. RP Cassiani-Ingoni, R (reprint author), Imperial Coll London, Fac Med, Dept Cellular & Mol Neurosci, Charing Cross Campus,Lab Block,12th Floor,St Duns, London W68 RP, England. EM cassianiingoni@gmail.com; p.muraro@imperial.ac.uk RI Mattson, Mark/F-6038-2012; Schmidt, Jens/B-5791-2013 FU Intramural NIH HHS NR 48 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD JUL PY 2007 VL 66 IS 7 BP 637 EP 649 DI 10.1097/nen.0b013e318093f3ef PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 189YQ UT WOS:000248025200008 PM 17620989 ER PT J AU Berman, RA Heiser, LM Dunn, CA Saunders, RC Colby, CL AF Berman, Rebecca A. Heiser, Laura M. Dunn, Catherine A. Saunders, Richard C. Colby, Carol L. TI Dynamic circuitry for updating spatial representations. III. From neurons to behavior SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; SACCADIC EYE-MOVEMENTS; SUPERIOR COLLICULUS ABLATIONS; POSTERIOR PARIETAL CORTEX; SPLIT-BRAIN MACAQUE; COROLLARY DISCHARGE; INTERHEMISPHERIC-TRANSFER; COGNITIVE ACTIVATION; PERCEPTUAL DECISION; SINGLE NEURONS AB Each time the eyes move, the visual system must adjust internal representations to account for the accompanying shift in the retinal image. In the lateral intraparietal cortex ( LIP), neurons update the spatial representations of salient stimuli when the eyes move. In previous experiments, we found that split-brain monkeys were impaired on double-step saccade sequences that required updating across visual hemifields, as compared to within hemifield. Here we describe a subsequent experiment to characterize the relationship between behavioral performance and neural activity in LIP in the split-brain monkey. We recorded from single LIP neurons while split-brain and intact monkeys performed two conditions of the double-step saccade task: one required acrosshemifield updating and the other required within-hemifield updating. We found that, despite extensive experience with the task, the splitbrain monkeys were significantly more accurate for within-hemifield than for across-hemifield sequences. In parallel, we found that population activity in LIP of the split-brain monkeys was significantly stronger for the within-hemifield than for the across-hemifield condition of the double-step task. In contrast, in the normal monkey, both the average behavioral performance and population activity showed no bias toward the within-hemifield condition. Finally, we found that the difference between within-hemifield and across-hemifield performance in the split-brain monkeys was reflected at the level of single-neuron activity in LIP. These findings indicate that remapping activity in area LIP is present in the split-brain monkey for the double-step task and covaries with spatial behavior on within-hemifield compared to across-hemifield sequences. C1 Univ Pittsburgh, Ctr Neural Basis Cognit, Dept Neurosci, Pittsburgh, PA USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Colby, CL (reprint author), Mellon Inst, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM ccolby@cnbc.cmu.edu FU NCRR NIH HHS [P41 RR003631-120005, P41 RR003631-150005, P41 RR03631, P41 RR003631-140005, P41 RR003631-130005]; NEI NIH HHS [EY08908, R01 EY012032-04, R01 EY012032, R01 EY012032-08, R01 EY012032-07, R01 EY012032-05, R01 EY012032-03, EY12032, R01 EY012032-06, R01 EY012032-09, R01 EY012032-02]; NIMH NIH HHS [MH45156, P50 MH045156-18, P50 MH045156] NR 64 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2007 VL 98 IS 1 BP 105 EP 121 DI 10.1152/jn.00330.2007 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188SA UT WOS:000247938400012 PM 17493922 ER PT J AU Tsaneva-Atanasova, K Sherman, A van Goor, F Stojilkovic, SS AF Tsaneva-Atanasova, Krasimira Sherman, Arthur van Goor, Frederick Stojilkovic, Stanko S. TI Mechanism of spontaneous and receptor-controlled electrical activity in pituitary somatotrophs: Experiments and theory SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID GROWTH-HORMONE-SECRETION; RAT ANTERIOR-PITUITARY; GATED CALCIUM INFLUX; SPONTANEOUS ACTION-POTENTIALS; CYTOSOLIC-FREE CALCIUM; PANCREATIC BETA-CELL; INTRACELLULAR CALCIUM; CA2+ OSCILLATIONS; TUMOR CELLS; K+ CHANNELS AB Cultured pituitary somatotrophs release growth hormone in response to spontaneous Ca2+ entry through voltage-gated calcium channels (VGCCs) that is governed by plateau-bursting electrical activity and is regulated by several neurohormones, including GH-releasing hormone ( GHRH) and somatostatin. Here we combine experiments and theory to clarify the mechanisms underlying spontaneous and receptor-controlled electrical activity. Experiments support a role of a Na+ -conducting and tetrodotoxin-insensitive channel in controlling spontaneous and GHRH-stimulated pacemaking, the latter in a cAMP-dependent manner; an opposing role of spontaneously active inwardly rectifying K+ (K-ir) channels and G-protein-regulated K-ir channels in somatostatin-mediated inhibition of pacemaking; as well as a role of VGCCs in spiking and large conductance (BK-type) Ca2+ -activated K+ channels in plateau bursting. The mathematical model is compatible with a wide variety of experimental data involving pharmacology and extracellular ion substitution and supports the importance of constitutively active tetrodotoxin-insensitive Na+ and K-ir channels in maintaining spontaneous pacemaking in pituitary somatotrophs. The model also suggests that these channels are involved in the up-and downregulation of electrical activity by GHRH and somatostatin. In the model, the plateau bursting is controlled by two functional populations of BK channels, characterized by distance from the VGCCs. The rapid activation of the proximal BK channels is critical for the establishment of the plateau, whereas slow recruitment of the distal BK channels terminates the plateau. C1 NIDDK, NIH, Lab Biol Modeling, Bethesda, MD 20892 USA. NICHHD, NIH, Natl Inst Diabet & Digest & Kidney Dis, Lab Biol Modeling, Bethesda, MD 20892 USA. NICHHD, NIH, Sect Cellular Signaling, Bethesda, MD 20892 USA. RP Sherman, A (reprint author), NIDDK, NIH, Lab Biol Modeling, 12 S Dr Rm 4007, Bethesda, MD 20892 USA. EM asherman@nih.gov RI Tsaneva-Atanasova, Krasimira/A-7153-2011; OI Tsaneva-Atanasova, Krasimira/0000-0002-6294-7051 FU Intramural NIH HHS NR 62 TC 53 Z9 53 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2007 VL 98 IS 1 BP 131 EP 144 DI 10.1152/jn.00872.2006 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 188SA UT WOS:000247938400014 PM 17493919 ER PT J AU Morrison, PF Lonser, RR Oldfield, EH AF Morrison, Paul F. Lonser, Russell R. Oldfield, Edward H. TI Convective delivery of glial cell line-derived neurotrophic factor in the human putamen SO JOURNAL OF NEUROSURGERY LA English DT Article DE convection-enhanced delivery; glial cell line-derived neurotrophic factor; Parkinson disease ID ENHANCED DELIVERY; PARKINSON-DISEASE; FACTOR GDNF; INTRAPUTAMENAL INFUSION; INTERSTITIAL INFUSION; FUNCTIONAL RECOVERY; NONHUMAN-PRIMATES; SPINAL-CORD; IN-VIVO; BRAIN AB Object. The authors conducted an analysis of the distribution of glial cell line-derived neurotrophic factor in the human striatum following convection-enhanced delivery. Methods. Computational examinations of the effects of differing catheters, infusion rates, infusate concentrations, and target placement on distribution were completed based on the protocols of three recent clinical trials. Results. Similar drug distributions around on-target end-hole catheters were predicted in two of the trials (AmgenUT study and Bristol study), although there was slightly deeper penetration for one of the trials (Bristol) due to a higher infusate concentration. However, when positioning uncertainly located catheter tips close to gray-white matter interfaces. backflow Could diminish delivery, shunting infusate across the interfaces. For delivery via a multiport catheter at a constant base infusion rate plus a periodic bolus inflow rate (Kentucky study), base inflow alone generated a somewhat smaller distribution volume relative to those in the other trials, was positioned more anteriorly in the putamen, and was,somewhat elongated axially; the bolus component extended this putaminal distribution to a larger relative volume but may have been reduced by backflow loss. Conclusions. Results of these computations indicated that for catheters placed exactly on the intended target, ideal drug distributions were similar for two of the trials (AmgenUT and Bristol) and different in terms of location and extent in the third study (Kentucky); yet the pattern of trial outcornes did not reflect these same groupings. This finding suggests that other factors are at play, widely varying statistical power and the possible effects of not excluding data from patients who experienced large drug losses across gray tissue boundaries due to variation in catheter placement. C1 NINDS, Div Bioengn & Phys Sci, ORS, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Morrison, PF (reprint author), NINDS, Div Bioengn & Phys Sci, ORS, NIH, Bldg 13,Room 3N17, Bethesda, MD 20892 USA. EM Morrison@mail.nih.gov FU Intramural NIH HHS NR 34 TC 41 Z9 42 U1 0 U2 5 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 JUL PY 2007 VL 107 IS 1 BP 74 EP 83 DI 10.3171/JNS-07/07/0074 PG 10 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 186TA UT WOS:000247799900013 PM 17639877 ER PT J AU Lonser, RR Warren, KE Butman, JA Quezado, Z Robison, A Walbridge, S Schiffman, R Merrill, M Walker, ML Park, DM Croteau, D Brady, RO Oldfield, EH AF Lonser, Russell R. Warren, Katherine E. Butman, John A. Quezado, Zenaide Robison, Aaron Walbridge, Stuart Schiffman, Raphael Merrill, Marsha Walker, Marion L. Park, Deric M. Croteau, David Brady, Roscoe O. Oldfield, Edward H. TI Real-time image-guided direct convective perfusion of intrinsic brainstem lesions SO JOURNAL OF NEUROSURGERY LA English DT Article DE brainstem; convection-enhanced delivery; glioma; intraoperative imaging; magnetic resonance imaging ID INHERITED ENZYME DEFICIENCY; ENHANCED DELIVERY; REPLACEMENT THERAPY; MALIGNANT GLIOMA; GAUCHERS-DISEASE; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; DRUG-DELIVERY; PRIMATE BRAIN; INFUSION AB Recent preclinical studies have demonstrated that convection-enhanced delivery (CED) can be used to perfuse the brain and brainstem with therapeutic agents while simultaneously tracking their distribution using coinfusion of a surrogate magnetic resonance (MR) imaging tracer. The authors describe a technique for the successful clinical application of this drug delivery and monitoring paradigm to the brainstem. Two patients with progressive intrinsic brainstem lesions (one with Type 2 Gaucher disease and one with a diffuse pontine glioma) were treated with CED of putative therapeutic agents mixed with Gd-diethylenetriamene pentaacetic acid (DTPA). Both patients underwent frameless stereotactic placement of MR imaging-compatible outer guide-inner infusion cannulae. Using intraoperative MR imaging, accurate cannula placement was confirmed and real-time imaging during infusion clearly demonstrated progressive filling of the targeted region with the drug and Gd-DTPA infusate. Neither patient had clinical or imaging evidence of short- or long-term infusate-related toxicity. Using this technique, CED can be used to safely perfuse targeted regions of diseased brainstern with therapeutic agents. Coinfused imaging surrogate tracers can be used to monitor and control the distribution of therapeutic agents in vivo. Patients with a variety of intrinsic brainstern and other central nervous system disorders may benefit from a similar treatment paradigm. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Neuroradiol Sect, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Dept Anesthesia & Surg Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Utah, Hlth Sci Ctr, Div Pediat Neurosurg, Dept Neurosurg,Primary Childrens Med Ctr, Salt Lake City, UT USA. NeoPharm Inc, Lake Forest, IL USA. RP Lonser, RR (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM lonserr@ninds.nih.gov RI Butman, John/A-2694-2008; Park, Deric/C-5675-2013; Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 FU Intramural NIH HHS [ZIA CL009009-02] NR 37 TC 67 Z9 68 U1 0 U2 5 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 JUL PY 2007 VL 107 IS 1 BP 190 EP 197 DI 10.3171/JNS-07/07/0190 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 186TA UT WOS:000247799900030 PM 17639894 ER PT J AU Hadi, M Chen, CC Whatley, M Pacak, K Carrasquillo, JA AF Hadi, Mohiuddin Chen, Clara C. Whatley, Millie Pacak, Karel Carrasquillo, Jorge A. TI Brown fat imaging with (18)F6-fluorodopamine PET/CT, F-18-FDG PET/CT, and I-123-MIBG SPECT a study of patients being evaluated for pheochromocytoma SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; PET/CT; brown fat; F-18-FDG; I-123-MIBG; F-18-fluorodopamine ID CARDIAC SYMPATHETIC INNERVATION; UPPER CHEST REGION; ADIPOSE-TISSUE; BETA-ADRENOCEPTOR; GLUCOSE-UPTAKE; USA-FAT; NECK; VISUALIZATION; I-123-METAIODOBENZYLGUANIDINE; TEMPERATURE AB Several radiopharmaceuticals such as F-18-FDG, I-123-metaiodobenzylguanidine (MIBG), and Tc-99m-tetrofosmin have demonstrated uptake in brown adipose tissue (BAT). It is important to recognize these normal variants so that they are not misinterpreted as a significant pathologic state. In addition, these radiopharmaceuticals may shed light on BAT physiology. F-18-6-fluorodopamine (F-DA) is being used as a PET radiopharmaceutical to image adrenergic innervation and suspected pheochromocytoma. Past reports have suggested that BAT is increased in pheochromocytoma patients. Methods: The images of 96 patients evaluated with F-18-F-DA or F-18-FDG PET/ CT for known or suspected pheochromocytoma were reviewed retrospectively to determine whether localized uptake of a pattern typically associated with BAT was present. When available, contemporaneous images obtained using I-123-MIBG were also reviewed for the presence of BAT. Results: Of 67 patients imaged with F-18-F-DA, BAT was found in 17.9%. Of 83 patients imaged with F-18-FDG, 19.2% had BAT. Discordant findings related to uptake in BAT were often seen in patients studied with F-18-FDG, F-18-F-DA, or I-123-MIBG. Overall, 26 (27.0%) of 96 patients showed BAT on at least 1 of the 3 imaging modalities. Conclusion: F-18-F-DA can image BAT, most likely by localizing to sympathetic innervations in a manner similar to I-123-MIBG. Patients with pheochromocytoma may have a greater BAT tissue mass or activation because of elevated levels of circulating catecholamines. Quantitative PET with F-18-FDG and F-18-F-DA may have a role in in vivo studies of BAT physiology in humans or animal models. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), 1275 York Ave, New York, NY 10021 USA. EM carrasj1@mskcc.org RI Carrasquillo, Jorge/E-7120-2010; Hadi, Mohiuddin/H-5682-2012; OI Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural NIH HHS NR 38 TC 54 Z9 56 U1 0 U2 6 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 2007 VL 48 IS 7 BP 1077 EP 1083 DI 10.2967/jnumed.106.035915 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187KK UT WOS:000247846300021 PM 17574980 ER PT J AU Ryu, YH Liow, JS Zoghbi, S Fujita, M Collins, J Tipre, D Sangare, J Hong, J Pike, VW Innis, RB AF Ryu, Yong Hoon Liow, Jeih-San Zoghbi, Sami Fujita, Masahiro Collins, Jerry Tipre, Dnyanesh Sangare, Janet Hong, Jinsoo Pike, Victor W. Innis, Robert B. TI Disulfiram inhibits defluorination of F-18-FCWAY, reduces bone radioactivity, and enhances visualization of radioligand binding to serotonin 5-HT1A receptors in human brain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE metabolism; F-18-FCWAY; 5HT(1A) receptor; PET; disulfiram; defluorination; serotonin ID P-GLYCOPROTEIN; CYTOCHROME-P450 2E1; DRUGS; BLOOD AB F-18-trans-4-Fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]N-(2-pyridyl)cyclohexanecarboxamide (F-18-FCWAY) is a PET radioligand for imaging serotonin 5-hydroxytryptamine-1A receptors in brain. F-18-FCWAY undergoes significant defluorination, with high uptake of radioactivity in the skull and resulting spillover contamination in the underlying neocortex. The cytochrome P450 enzyme CYP2E1 defluorinates many drugs. We previously showed that miconazole, an inhibitor of CYP2E1, blocks defluorination of FCWAY in rats. Here, we used F-18-FCWAY to test the ability of the less toxic agent disulfiram to inhibit defluorination in humans. Methods: Eight healthy volunteers underwent a PET scan before and after administration of 500 mg of disulfiram (n = 6) or 2,000 mg of cimetidine (n = 2). Seven of the subjects had arterial blood sampling during both scans. Results: Although cimetidine had relatively small and variable effects on 2 subjects, disulfiram reduced skull radioactivity by about 70% and increased peak brain uptake by about 50% (n = 5). Disulfiram decreased plasma-free F-18-fluoride ion (from peak levels of 340% +/- 62% standardized uptake value (SUV) to 62% +/- 43% SUV; P < 0.01) and increased the concentration of the parent F-18-FCWAY (with a corresponding decrease of clearance from 14.8 +/- 7.8 L.h(-1) at baseline to 7.9 +/- 2.8 L.h(-1) after drug treatment (P < 0.05). Using compartmental modeling with input of both F-18-FCWAY and the radiometabolite F-18-FC (trans-4-fluorocyclohexanecarboxylic acid), distribution volumes attributed to the parent radioligand unexpectedly decreased about 40%-60% after disulfiram, but the accuracy of the radiometabolite correction is uncertain. Disulfiram changed the shape of the brain time-activity curves in a manner that could occur with inhibition of the efflux transporter P-glycoprotein (P-gp). However, disulfiram showed no in vivo efficacy in monkeys to enhance the uptake of the known P-gp substrate C-11-loperamide, suggesting that the effects of disulfiram in humans were mediated entirely by inhibition of CYP2E1. Conclusion: A single oral dose of disulfiram inhibited about 70% of the defluorination of F-18-FCWAY, increased the plasma concentration of F-18-FCWAY, increased brain uptake of activity, and resulted in better visualization of 5-HT1A receptor in the brain. Disulfiram is a safe and well-tolerated drug that may be useful for other radioligands that undergo defluorination via CYP2E1. C1 NIH, Mol Imaging Branch, NIMH, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Nucl Med, Seoul 120749, South Korea. NIH, NCI, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), NIH, Mol Imaging Branch, NIMH, Bldg 31,Room B2B37,31 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov FU Intramural NIH HHS; NIMH NIH HHS [Z01-MH-002795-04] NR 25 TC 34 Z9 34 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD JUL PY 2007 VL 48 IS 7 BP 1154 EP 1161 DI 10.2967/jnumed.107.039933 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 187KK UT WOS:000247846300032 PM 17574977 ER PT J AU Howerton, MW Bell, BS Dodd, KW Berrigan, D Stolzenberg-Solomon, R Nebeling, L AF Howerton, Mollie W. Bell, B. Sue Dodd, Kevin W. Berrigan, David Stolzenberg-Solomon, Rachael Nebeling, Linda TI School-based nutrition programs produced a moderate increase in fruit and vegetable consumption: Meta and pooling analyses from 7 studies SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE child; adolescent; schools; interventions; fruit and vegetable; pooled analysis; nutrition; diet; meta-analysis ID RESOURCE TEACHERS; CANCER; COHORT; OUTCOMES; EPIDEMIOLOGY; BIOMARKER; REVIEWS; ADULTS; CATCH; DIET AB Objective: To evaluate, through study- and individual-level analyses of data from 7 studies, the effectiveness of school-based nutrition interventions on child fruit and vegetable (FV) consumption. Design: To find original studies on school-based nutrition interventions, the authors searched electronic databases from 1990 to 2002. First authors of the 13 eligible Studies were contacted to request their data. Data from 7 studies were received for inclusion in this pooled analysis. Setting: Schools. Participants: 8156 children were matched from pretest to posttest. Participants were primarily elementary school-aged (75.5%) and white (66%), and 50.4% were males. Main Outcome Measures: Net FV difference and net FV relative change MY Analysis: Data were analyzed at both the study and individual levels. A fitted multivariable fixed-effects model was used to analyze the role of potential covariates on FV intake. Statistical significance was set at alpha = .05. Results: At the individual level, the net difference in FV consumption was 0.45 (95% Cl 0.33-0.59) servings; the net relative change was 19% (95% Cl 0.15-0.23) servings. Conclusions and implications: School-based nutrition interventions produced a moderate increase in FV intake among children. These results may have implications for chronic disease prevention efforts, including cardiovascular disease and cancer. C1 NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Howerton, MW (reprint author), NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN4080, Bethesda, MD 20892 USA. EM mhowert2@jhmi.edu NR 33 TC 55 Z9 55 U1 3 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD JUL-AUG PY 2007 VL 39 IS 4 BP 186 EP 196 DI 10.1016/j.jneb.2007.01.010 PG 11 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 189ZO UT WOS:000248027700003 PM 17606244 ER PT J AU Fineberg, IC Grant, M Aziz, NM Payne, R Kagawa-Singer, M Dunn, GP Kinzbrunner, BM Palos, G Shinagawa, SM Krouse, RS AF Fineberg, Iris Cohen Grant, Marcia Aziz, Noreen M. Payne, Richard Kagawa-Singer, Marjorie Dunn, Geoffrey P. Kinzbrunner, Barry M. Palos, Guadalupe Shinagawa, Susan Matsuko Krouse, Robert S. TI Prospective integration of cultural consideration in biomedical research for patients with advanced cancer: Recommendations from an International Conference on Malignant Bowel Obstruction in palliative care SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article; Proceedings Paper CT International Conference on Malignant Bowel Obstruction CY NOV 12-13, 2004 CL Pasadena, CA DE culture; palliative care; research methods; multidisciplinary research; mixed method; approaches ID OF-LIFE; HEALTH; PAIN; END; STROKE AB In the setting of an international conference on malignant bowel obstruction as a model for randomized controlled trials (RCTs) in palliative care, we discuss the importance of incorporating prospective cultural considerations into research design. The approach commonly used in biomedical research has traditionally valued the RCT as the ultimate "way of knowing" about how to best treat a medical condition. The foremost limitation of this approach is the lack of recognition of the impact of cultural viewpoints on research outcomes. We propose that interest relevant to cultural viewpoints should be emphasized in conceptualizing and interpreting research questions, designs, and results. In addition to recognizing our cultural biases as individuals and researchers, we recommend two major shifts in designing and implementing RCTs: 1) inclusion of a multidisciplinary team of researchers to inform the diversity of perspectives and expertise brought to the research, and 2) use of mixed methods of inquiry, reflecting both deductive and inductive modes of inference. C1 City Hope Natl Med Ctr, Dept Nursing Res & Educ, Duarte, CA 91010 USA. Univ Lancaster, Inst Hlth Res, Int Observ End Life Care, Lancaster LA1 4YQ, England. NCI, Off Canc Survivorship, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Duke Univ, Divin Sch, Duke Inst Care End Life, Durham, England. Univ Calif Los Angeles, Sch Publ Hlth, Asian Amer Studies Dept, Community Hlth Sci Dept, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Ctr Hlth Disparities, Los Angeles, CA 90024 USA. Amer Coll Surgeons, Surg Palliat Care Task Force, Erie, PA USA. VITAS Healthcare Corp, Miami, FL USA. Univ Texas, MD Anderson Canc Ctr, Div Anesthesiol & Crit Care, Houston, TX 77025 USA. Univ Texas, MD Anderson Canc Ctr, Dept Sympton Res, Houston, TX 77025 USA. Asian Amer Network Canc Awareness Res & Training, Spring Valley, CA USA. So Arizona Vet Affairs Hlth Care Syst, Tucson, AZ USA. Univ Arizona, Coll Med, Tucson, AZ 85721 USA. RP Grant, M (reprint author), City Hope Natl Med Ctr, Dept Nursing Res & Educ, 1500 E Duarte Rd, Duarte, CA 91010 USA. EM mgrant@coh.org FU NCI NIH HHS [R13 CA110771, R13 CA110771-01] NR 37 TC 2 Z9 2 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD JUL PY 2007 VL 34 IS 1 SU S BP S28 EP S39 DI 10.1016/j.jpainsymman.2007.04.009 PG 12 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 190JN UT WOS:000248055200004 PM 17532174 ER PT J AU Meert, KL Eggly, S Pollack, M Anand, KJS Zimmerman, J Carcillo, J Newth, CJL Dean, JM Willson, DF Nicholson, C AF Meert, Kathleen L. Eggly, Susan Pollack, Murray Anand, K. J. S. Zimmerman, Jerry Carcillo, Joseph Newth, Christopher J. L. Dean, J. Michael Willson, Douglas F. Nicholson, Carol CA Natl Inst Child Hlth Human Dev Col TI Parents' perspectives regarding a physician-parent conference after their child's death in the pediatric intensive care unit SO JOURNAL OF PEDIATRICS LA English DT Article ID OF-LIFE CARE; PALLIATIVE CARE; FAMILY PERSPECTIVES; BEREAVED PARENTS; HOSPITAL STAFF; FOLLOW-UP; END; QUALITY; RECOMMENDATIONS; WITHDRAWAL AB Objective To investigate parents' perspectives on the desirability, content, and conditions of a physician-parent conference after their child's death in the pediatric intensive care unit (PICU). Study design Audio-recorded telephone interviews were conducted with 56 parents of 48 children. All children died in the PICU of one of six children's hospitals in the National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network (CPCCRN) 3 to 12 months before the study. Results Only seven (13%) parents had a scheduled meeting with any physician to discuss their child's death; 33 (59%) wanted to meet with their child's intensive care physician. Of these, 27 (82%) were willing to return to the hospital to meet. Topics that parents wanted to discuss included the chronology of events leading to PICU admission and death, cause of death, treatment, autopsy, genetic risk, medical documents, withdrawal of life support, ways to help others, bereavement support, and what to tell family. Parents sought reassurance and the opportunity to voice complaints and express gratitude. Conclusions Many bereaved parents want to meet with the intensive care physician after their child's death. Parents seek to gain information and emotional support, and to give feedback about their PICU experience. C1 Childrens Hosp Michigan, Detroit, MI 48201 USA. Karmanos Canc Inst, Detroit, MI USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Seattle Childrens Hosp, Seattle, WA USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Utah, Salt Lake City, UT USA. Univ Virginia, Childrens Hosp, Charlottesville, VA USA. NICHHD, Bethesda, MD 20892 USA. RP Meert, KL (reprint author), Childrens Hosp Michigan, 3901 Beaubien Blvd, Detroit, MI 48201 USA. EM kmeert@med.wayne.edu OI Anand, Kanwaljeet/0000-0001-6498-1483 FU NICHD NIH HHS [U10 HD049945, U01 HD049934, U01HD049934, U10 HD049981, U10 HD049983, U10 HD050012, U10 HD050096, U10 HD050096-01, U10 HD050096-02, U10 HD050096-03, U10HD049945, U10HD049981, U10HD049983, U10HD050012, U10HD050096, U10HD500009, UG1 HD050096] NR 36 TC 49 Z9 52 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2007 VL 151 IS 1 BP 50 EP 55 DI 10.1016/j.jpeds.2007.01.050 PG 6 WC Pediatrics SC Pediatrics GA 187MM UT WOS:000247851900013 PM 17586190 ER PT J AU Lakhani, NJ Sparreboom, A Xu, X Veenstra, TD Venitz, J Dahut, WL Figg, WD AF Lakhani, Nehal J. Sparreboom, Alex Xu, Xia Veenstra, Timothy D. Venitz, Juergen Dahut, William L. Figg, William D. TI Pharmacokinetics, pharmacodynamics and drug metabolism - Characterization of in vitro and in vivo metabolic pathways of the investigational anticancer agent, 2-methoxyestradiol SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE 2-methoxyestradiol (2ME2); metabolism; enzyme kinetics ID HUMAN LIVER-MICROSOMES; UDP-GLUCURONOSYLTRANSFERASE; MAMMALIAN METABOLITE; BREAST-CANCER; TUMOR-GROWTH; GLUCURONIDATION; ANGIOGENESIS; ESTRADIOL; PLASMA; CELLS AB The aim of this study was to characterize the metabolic pathways of 2-methoxyestradiol (2ME2), an investigational anticancer drug. In vitro metabolism studies were performed by incubation of 2ME2 with human liver microsomes under various conditions and metabolite identification was performed using liquid chromatography-tandem mass spectrometry. In microsomal mixtures, four major oxidative metabolites and two glucuronic acid conjugates were observed originating from 2ME2. Human liver S9 protein fraction was used to screen for in vitro sulfation but no prominent conjugates were observed. The total hepatic clearance as estimated using the well-stirred model was approximately 712 mL/min. In vivo metabolism, assessed using 24-h collections of urine from cancer patients treated with 2ME2 revealed that < 0.01% of the total administered dose of 2ME2 is excreted unchanged in urine and about 1% excreted as glucuronides. Collectively, this suggests that glucuronidation and subsequent urinary excretion are elimination pathways for 2ME2. (c) 2007 Wiley-Liss, Inc. C1 NCI, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. NCI Frederick, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD USA. RP Figg, WD (reprint author), NCI, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 33 TC 24 Z9 25 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2007 VL 96 IS 7 BP 1821 EP 1831 DI 10.1002/jps.20837 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 185DO UT WOS:000247691800013 PM 17252610 ER PT J AU Ma, XC Shah, YM Guo, GL Wang, T Krausz, KW Idle, JR Gonzalez, FJ AF Ma, Xiaochao Shah, Yatrik M. Guo, Grace L. Wang, Ting Krausz, Kristopher W. Idle, Jeffrey R. Gonzalez, Frank J. TI Rifaximin is a gut-specific human pregnane X receptor activator SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; BILIRUBIN DETOXIFICATION; DIVERTICULAR-DISEASE; COMBINATION THERAPY; DRUG-INTERACTIONS; SMALL-INTESTINE; GENE; INDUCTION; PHARMACOKINETICS; METABOLISM AB Rifaximin, a rifamycin analog approved for the treatment of travelers' diarrhea, is also beneficial in the treatment of multiple chronic gastrointestinal disorders. However, the mechanisms contributing to the effects of rifaximin on chronic gastrointestinal disorders are not fully understood. In the current study, rifaximin was investigated for its role in activation of the pregnane X receptor ( PXR), a nuclear receptor that regulates genes involved in xenobiotic and limited endobiotic deposition and detoxication. PXR- humanized ( hPXR), Pxr- null, and wild- type mice were treated orally with rifaximin, and rifampicin, a well characterized human PXR ligand. Rifaximin was highly concentrated in the intestinal tract compared with rifampicin. Rifaximin treatment resulted in significant induction of PXR target genes in the intestine of hPXR mice, but not in wild- type and Pxr- null mice. However, rifaximin treatment demonstrated no significant effect on hepatic PXR target genes in wild- type, Pxr- null, and hPXR mice. Consistent with the in vivo data, cell- based reporter gene assay revealed rifaximin- mediated activation of human PXR, but not the other xenobiotic nuclear receptors constitutive androstane receptor, peroxisome proliferator- activated receptor ( PPAR)alpha, PPAR gamma, and farnesoid X receptor. Pretreatment with rifaximin did not affect the pharmacokinetics of the CYP3A substrate midazolam, but it increased the C max and decreased T-max of 1'- hydroxymidazolam. Collectively, the current study identified rifaximin as a gut- specific human PXR ligand, and it provided further evidence for the utility of hPXR mice as a critical tool for the study of human PXR activators. Further human studies are suggested to assess the potential role of rifaximin- mediated gut PXR activation in therapeutics of chronic gastrointestinal disorders. C1 NCI, Met Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66103 USA. Charles Univ Prague, Fac Med 1, Inst Pharmacol, Prague, Czech Republic. RP Gonzalez, FJ (reprint author), NCI, Met Lab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov OI Idle, Jeff/0000-0002-6143-1520 FU Intramural NIH HHS NR 40 TC 67 Z9 68 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 2007 VL 322 IS 1 BP 391 EP 398 DI 10.1124/jpet.107.121913 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 180FO UT WOS:000247348100047 PM 17442842 ER PT J AU Diamond, JS AF Diamond, Jeffrey S. TI A light switch controlling Ca2+-permeable AMPA receptors in the retina SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Editorial Material ID PERMEATION; CHANNELS; RELEASE; RAT C1 NIH, NINDS, Porter Neurosci Res Ctr, Synapt Physiol Unit, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NIH, NINDS, Porter Neurosci Res Ctr, Synapt Physiol Unit, 35 Convent Dr,Bldg 35,Room 3C-1000, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 NR 9 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 1 PY 2007 VL 582 IS 1 BP 3 EP 3 DI 10.1113/jphysiol.2007.135145 PG 1 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 183GY UT WOS:000247561900002 PM 17463033 ER PT J AU Sakamoto, T Unno, T Kitazawa, T Taneike, T Yamada, M Wess, J Nishimura, M Komori, S AF Sakamoto, Takashi Unno, Toshihiro Kitazawa, Takio Taneike, Tetsuro Yamada, Masahisa Wess, Jurgen Nishimura, Masakazu Komori, Seiichi TI Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cells SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GUINEA-PIG ILEUM; RECEPTOR KNOCKOUT MICE; ACETYLCHOLINE-RECEPTOR; G-PROTEIN; GASTRIC MYOCYTES; PHOSPHOLIPASE-C; SMALL-INTESTINE; SUBTYPES; CARBACHOL; TRANSDUCTION AB Using mutant mice genetically lacking certain subtypes of muscarinic receptor, we have studied muscarinic signal pathways mediating cationic channel activation in intestinal smooth muscle cells. In cells from M-2 subtype-knockout (M-2-KO) or M-3-KO mice, carbachol (100 mu M) evoked a muscarinic cationic current (mI(Cat)) as small as similar to 10% of mI(Cat) in wild-type (WT) cells. No appreciable current was evoked in M-2/M-3 double-KO cells. All mutant type cells preserved normal G-protein-cationic channel coupling. The M-3-KO and WT mI(Cat) each showed a U-shaped current-voltage (I-V) relationship, whereas the M-2-KO mI(Cat) displayed a linear I-V relationship. Channel analysis in outside-out patches recognized 70-pS and 120-pS channels as the major muscarinic cationic channels. Active patches of M-2-KO cells exhibited both 70-pS and 120-pS channel activity usually together, either of which consisted of brief openings (the respective mean open times O-tau = 0.55 and 0.23 ms). In contrast, active M-3-KO patches showed only 70-pS channel activity, which had three open states (O-tau = 0.55, 3.1 and 17.4 ms). In WT patches, besides the M-2-KO and M-3-KO types, another type of channel activity was also observed that consisted of 70-pS channel openings with four open states (O-tau = 0.62, 2.7, 16.9 and 121.1 ms), and patch current of this channel activity showed a U-shaped I-V curve similar to the WT mI(Cat). The present results demonstrate that intestinal myocytes are endowed with three distinct muscarinic pathways mediating cationic channel activation and that the M-2/M-3 pathway targeting 70-pS channels, serves as the major contributor to mI(Cat) generation. The delineation of this pathway is consistent with the formation of a functional unit by the M-2-G(o) protein and the M-3-PLC systems predicted to control cationic channels. C1 Gifu Univ, United Grad Sch Vet Sci, Dept Pahtogenet Vet Sci, Gifu 50111, Japan. Gifu Univ, Fac Appl Biol Sci, Dept Vet Med, Pharmacol Lab, Gifu 50111, Japan. Rakuno Gakuen Univ, Fac Vet Med, Dept Pharmacol, Ebetsu, Hokkaido 069, Japan. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Komori, S (reprint author), Gifu Univ, United Grad Sch Vet Sci, Dept Pahtogenet Vet Sci, Gifu 50111, Japan. EM skomori@gifu-u.ac.jp NR 55 TC 23 Z9 23 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 1 PY 2007 VL 582 IS 1 BP 41 EP 61 DI 10.1113/jphysiol.2007.133165 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 183GY UT WOS:000247561900011 PM 17463038 ER PT J AU Sternberg, EM Silverman, MN Cizza, G AF Sternberg, Esther M. Silverman, Marni N. Cizza, Giovanni TI The neuroendocrine system and rheumatoid arthritis: Insights from anti-tumor necrosis factor-alpha therapy SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID VIRAL-INFECTION; CORTISOL; PATHWAY; AXIS; DHEA C1 NIH, NIMH, Sect Neuroendocrine Immunol & Behav, Rockville, MD 20852 USA. NIH, NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, Rockville, MD USA. NIH, Prince Wales Natl Ctr Complementary & Alternat Me, Sect Neuroendocrine Immunol & Behav, Rockville, MD USA. NIH, NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIH, NIMH, Sect Neuroendocrine Immunol & Behav, 5625 Fishers Lane,Rm 4N-13, Rockville, MD 20852 USA. EM sternbee@mail.nih.gov FU Intramural NIH HHS NR 20 TC 7 Z9 7 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2007 VL 34 IS 7 BP 1443 EP 1445 PG 3 WC Rheumatology SC Rheumatology GA 189VW UT WOS:000248017700002 PM 17611960 ER PT J AU Stewart, JH Tran, TL Levi, N Tsai, WS Schrump, DS Nguyen, DM AF Stewart, John H., IV Tran, Thai-Lan Levi, Nicole Tsai, Wilson S. Schrump, David S. Nguyen, Dao M. TI The essential role of the mitochondria and reactive oxygen species in cisplatin-mediated enhancement of fas ligand-induced apoptosis in malignant pleural mesothelioma SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE malignant pleural mesothelioma; Fas ligand; cisplatin; reactive oxygen species; apoptosis; caspase; mitochondria ID CYTOCHROME-C RELEASE; THORACIC CANCER-CELLS; CASPASE ACTIVATION; OXIDATIVE STRESS; APO2L/TRAIL-MEDIATED CYTOTOXICITY; CONFORMATIONAL-CHANGE; HYDROGEN-PEROXIDE; BCL-2 FAMILY; DNA DAMAGE; BAX AB Cytotoxic chemotherapeutic drugs such as cisplatin (CDDP) synergistically interact with soluble Fas ligand (sFasL) to mediate profound induction of apoptosis in cancer cells, particularly those refractory to this death-inducing ligand. The goal of this study was to evaluate the roles of the mitochondria-dependent apoptotic cascade and the CDDP-generated reactive oxygen species (ROS) in mediating the supra-additive enhancement of cytotoxicity and apoptosis in combination-treated malignant pleural mesothelioma (MPM) cells. MPM cells were treated with sequential CDDP/sFasL in vitro. Cell viability and apoptosis were determined by MITT and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assays. Stable transfectants expressing high levels of Bcl2 were created by retroviral gene transfer. Specific proteolytic activity of caspases 3, 8, and 9 were measured using fluorescent substrates. Pretreating MPM cells with CDDP increased their susceptibility to sFasL by 2- to more than 20-fold. Overexpression of either Bcl-2, the selective caspase 9 inhibitor z-LEHD-fmk, or the antioxidant N-acetyl-cysteine significantly abrogated combination-induced cytotoxicity and apoptosis. Moreover, the robust activation of caspase 8 in combination-treated cells was completely suppressed by Bcl-2 overexpression, thus implicating a mitochondria-mediated amplification feedback loop. As an in vivo correlate, sequential intraperitoneal administration of CDDP and sFasL significantly inhibited the growth of intraperitoneal MPM human xenografts in nude mice. Our data indicate that the mitochondria-dependent feedback loop of the caspase activation cascade and the generation of ROS are both essential in mediating profound cytotoxicity and apoptosis of MPM cells treated with CDDP and sFasL. This mechanistic study establishes a the translational framework for the clinical application of sequential CDDP/sFasL in the treatment of MPM. (C) 2007 Elsevier Inc. All rights reserved. C1 NCI, Canc Res Ctr, NIH, Sect Thorac Oncol,Surg Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Surg, Winston Salem, NC 27109 USA. RP Nguyen, DM (reprint author), NCI, Canc Res Ctr, NIH, Sect Thorac Oncol,Surg Branch, Room 4W-4-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM dao_nguyen@nih.gov FU Intramural NIH HHS; NCI NIH HHS [K08 CA131482] NR 52 TC 18 Z9 18 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD JUL PY 2007 VL 141 IS 1 BP 120 EP 131 DI 10.1016/j.jss.2007.03.048 PG 12 WC Surgery SC Surgery GA 182ES UT WOS:000247488500018 PM 17574045 ER PT J AU May, DE Hallin, MJ Kratochvil, CJ Puumala, SE Smith, LS Reinecke, MA Silva, SG Weller, EB Vitiello, B Breland-Noble, A March, JS AF May, Diane E. Hallin, Mary J. Kratochvil, Christopher J. Puumala, Susan E. Smith, Lynette S. Reinecke, Mark A. Silva, Susan G. Weller, Elizabeth B. Vitiello, Benedetto Breland-Noble, Alfiee March, John S. TI Factors associated with recruitment and screening in the Treatment for Adolescents with Depression Study (TADS) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE depression; Treatment for Adolescents with Depression Study; recruitment; eligibility ID PLACEBO-CONTROLLED TRIAL; GENDER-DIFFERENCES; CLINICAL-TRIAL; DOUBLE-BLIND; RETENTION; CHILDREN; CARE; PARTICIPATION; DISORDERS; SYMPTOMS AB Objective: To examine factors associated with eligibility and randomization and consider the efficiency of recruitment methods. Method: Adolescents, ages 12 to 17 years, were telephone screened (N = 2,804) followed by in-person evaluation (N = 1,088) for the Treatment for Adolescents With Depression Study. Separate logistic regression models, controlling for site, examined whether sex, age, race, or source of recruitment was associated with eligibility, providing written consent, or randomization. Efficiency was calculated from the number of completed telephone screens per each enrolled participant. Results: Older adolescents were less likely to be eligible at telephone screening (odds ratio [OR] 0.81). Regardless of race, eligible adolescents who were referred by a professional had higher odds of presenting in-person for consent (OR 1.56). African Americans had statistically lower odds of providing consent (OR 0.67), particularly if recruited by advertisement (OR 0.54). Females were more likely to be diagnosed with major depressive disorder (OR 1.69). No significant differences were found between randomized participants and eligible adolescents who withdrew from the study before randomization. Conclusions: These findings underscore the importance of using multiple strategies to recruit adolescents for clinical trial participation and enhancing sensitivity to cultural variations, especially when reaching out to depressed African Americans. C1 Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Duke Univ, Med Ctr, Durham, NC USA. Northwestern Univ, Chicago, IL 60611 USA. NIMH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Childrens Hosp, Philadelphia, PA 19104 USA. RP May, DE (reprint author), 985581 Nebraska Med Ctr, Omaha, NE 68198 USA. EM dmay@unmc.edu RI Breland-Noble, Alfiee/E-9789-2010 FU NIMH NIH HHS [N01 MH80008]; NIMHD NIH HHS [L60 MD000389, L60 MD000389-03] NR 28 TC 9 Z9 9 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2007 VL 46 IS 7 BP 801 EP 810 DI 10.1097/CHI.0b013e3180582019 PG 10 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 181NE UT WOS:000247442600004 PM 17581444 ER PT J AU Perdue, KA Green, KY Copeland, M Barron, E Mandel, M Faucette, LJ Williams, EM Sosnovtsev, SV Elkins, WR Ward, JM AF Perdue, Kathy A. Green, Kim Y. Copeland, Michelle Barron, Elyssa Mandel, Myrna Faucette, Lawrence J. Williams, Elizabeth M. Sosnovtsev, Stanislav V. Elkins, William R. Ward, Jerrold M. TI Naturally occurring murine norovirus infection in a large research institution SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Article ID BEDDING SENTINEL SYSTEM; MURINE-NOROVIRUS-1 INFECTION; MICE; EFFICACY; VIRUS; CELLS AB Murine norovirus (MNV) is a recently discovered infectious agent in mice and may be the most common naturally occurring infection of laboratory mice in North America. In 2005, we surveyed the Swiss Webster female sentinel mice in our institute's research facilities. Of the 4 facilities surveyed, 3 had sentinel mice that were positive for MNV antibodies, whereas our largest facility (which only receives mice directly from select vendors or by embryo rederivation directly into the facility) was apparently MNV-free. However, testing of sentinel mice in this large facility 1 y later found that 2% of the animals had developed MNV-specific antibodies. In a recently opened fifth facility, a serologic survey in 2006 identified MNV-antibody-positive Tac:SW sentinel mice that had received bedding from experimental mice on the same rack quadrant. Reverse transcription-polymerase chain reaction analysis of feces from the cages of these mice showed evidence for shedding of MNV. These sentinel mice were used to study the fecal excretion, antibody development, gross lesions upon necropsy, histopathology, and immunohistochemistry of the viral infection. None of the MNV-antibody-positive sentinel mice exhibited clinical signs or gross lesions, but these mice excreted virus in feces and developed antibodies to MNV. Histopathologic lesions consisted only of a few hepatic inflammatory foci in each liver section, some of which were immunoreactive with antibodies to MNV. MNV viral antigens also were present in the mesenteric lymph nodes. C1 NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Lab Mol Genet & Microbiol, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Perdue, KA (reprint author), NIAID, Comparat Med Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM kperdue@niaid.nih.gov FU Intramural NIH HHS NR 17 TC 36 Z9 38 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 39 EP 45 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000005 PM 17645294 ER PT J AU Kurtz, DM Thigpen, JE Wolf, JC AF Kurtz, D. M. Thigpen, J. E. Wolf, J. C. TI Disease due to acid-fast bacilli septicemia in a colony of African clawed frogs (Xenopus laevis) and Japanese medaka (Oryzias latipes) SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 Expt Pathol Labs Inc, Res Triangle Pk, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs Inc, Sterling, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 90 EP 90 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000043 ER PT J AU Wiltrout, ER Cyril, R AF Wiltrout, E. R. Cyril, R. TI Special care and rearing techniques to successfully raise GULO KO mouse pups SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 SoBran Inc, Burtonsville, MD USA. NIAAA, OLAS FLAC, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 118 EP 118 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000128 ER PT J AU Thigpen, JE Padilla-Banks, E Little, S Orosz, SE Whiteside, T Caviness, G Locklear, J Grant, M Forsythe, DB AF Thigpen, J. E. Padilla-Banks, E. Little, S. Orosz, S. E. Whiteside, T. Caviness, G. Locklear, J. Grant, M. Forsythe, D. B. TI Survey of commercially available fish, frog, and bird diets for phytoestrogen and zearalanone SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NCSU, Raleigh, NC USA. Bird & Exot Pet Wellness Ctr, Toledo, OH USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 135 EP 135 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000180 ER PT J AU Whiteside, T Thigpen, JE Grant, MF Forsythe, DB AF Whiteside, T. Thigpen, J. E. Grant, M. F. Forsythe, D. B. TI Survey of various types of rodent bedding for lipopolysaccharide (endotoxin) and dust content SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 135 EP 136 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000181 ER PT J AU Kilts, TM Inkson, CI Bi, Y Young, MF AF Kilts, T. M. Inkson, C. I. Bi, Y. Young, M. F. TI In vivo tracking of distribution, growth, and survival of luminescence-labeled prostate cancer cells after transplantation SO JOURNAL OF THE AMERICAN ASSOCIATION FOR LABORATORY ANIMAL SCIENCE LA English DT Meeting Abstract C1 NIH, NIDCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1559-6109 J9 J AM ASSOC LAB ANIM JI J. Amer. Assoc. Lab. Anim. Sci. PD JUL PY 2007 VL 46 IS 4 BP 143 EP 144 PG 2 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196ZK UT WOS:000248522000205 ER PT J AU Anderson, DE Parsons, BA McNeely, JD Miller, ER AF Anderson, David E. Parsons, Beverly A. McNeely, Jessica D. Miller, Edgar R. TI Salt sensitivity of blood pressure is accompanied by slow respiratory rate: results of a clinical feeding study SO JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION LA English DT Article DE Blood pressure; hypertension; respiration; sodium ID PERIPHERAL ARTERIAL CHEMORECEPTORS; ESSENTIAL-HYPERTENSION; SODIUM; SYSTEM; HYPOVENTILATION; DETERMINANT; INHIBITION; PARADIGM; HUMANS; TIME AB Sleep-disordered breathing has been implicated in hypertension, but whether daytime breathing is a factor in blood pressure (BP) regulation has not been investigated to date. The present study sought to determine the role of breathing pattern in salt sensitivity of BP. Thirty-six women, ages 40 to 70, were placed on a 6-day low-sodium/low-potassium diet followed by a 6-day high-sodium/low-potassium diet. Breathing pattern at rest and 24-hour ambulatory BP were monitored at baseline and after each 6-day diet period. Respiratory rate (but not tidal volume or minute ventilation) was an inverse predictor of systolic (r = -0.50; P < .001) and diastolic (r = -0.59; P < .001) blood pressure sensitivity to high sodium intake. Respiratory rate was positively associated with hemoglobin (r = + 0.38; P < .01), and the salt-induced change in hemoglobin was associated with salt-induced change in BP (r = -0.35; P < .05). These findings indicate that a pattern of slow breathing not compensated by increased tidal volume is associated with salt sensitivity of BP in women. Breathing patterns could play a role in the hypertensive response via sustained effects on blood gases and acid-base balance, and/or be a marker for other biological factors mediating the cardiovascular response to dietary salt intake. (C) 2007 American Society of Hypertension. All rights reserved. C1 [Anderson, David E.; Parsons, Beverly A.; McNeely, Jessica D.; Miller, Edgar R.] NIA, US Dept HHS, Publ Hlth Serv, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Anderson, DE (reprint author), NIA, US Dept HHS, Publ Hlth Serv, Cardiovasc Sci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Andersod@grc.nia.nih.gov FU NIH National Institute on Aging FX This research was supported by the Intramural Research Program of the NIH National Institute on Aging. NR 28 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-1711 J9 J AM SOC HYPERTENS JI J. Am. Soc. Hypertens. PD JUL-AUG PY 2007 VL 1 IS 4 BP 256 EP 263 DI 10.1016/j.jash.2007.05.002 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA V18KO UT WOS:000208003900005 PM 18591996 ER PT J AU Rossetti, S Consugar, MB Chapman, AB Torres, VE Guay-Woodford, LM Grantham, JJ Bennett, WM Meyers, CM Walker, DL Bae, K Zhang, QJ Thompson, PA Miller, JP Harris, PC AF Rossetti, Sandro Consugar, Mark B. Chapman, Arlene B. Torres, Vicente E. Guay-Woodford, Lisa M. Grantham, Jared J. Bennett, William M. Meyers, Catherine M. Walker, Denise L. Bae, Kyongtae Zhang, Qin Jean Thompson, Paul A. Miller, J. Philip Harris, Peter C. CA Crisp Consortium TI Comprehensive molecular diagnostics in autosomal dominant polycystic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PKD1 GENE; MUTATION DETECTION; PROTEIN; DOMAIN; KIDNEY-DISEASE-1; SUBSTITUTIONS; ENCODES; BRCA1; ADPKD; IDENTIFICATION AB Mutation-based molecular diagnostics of autosomal dominant polycystic kidney disease (ADPKD) is complicated by genetic and allelic heterogeneity, large multi-exon genes, duplication of PKD1, and a high level of unclassified variants (UCV). Present mutation detection levels are 60 to 70%, and PKD1 and PKD2 UCV have not been systematically classified. This study analyzed the uniquely characterized Consortium for Radiologic Imaging Study of PKD (CRISP) ADPKD population by molecular analysis. A cohort of 202 probands was screened by denaturing H PLC, followed by direct sequencing using a clinical test of 121 with no definite mutation (plus controls). A subset was also screened for larger deletions, and reverse transcription-PCR was used to test abnormal splicing. Definite mutations were identified in 127 (62.9%) probands, and all UCV were assessed for their potential pathogenicity. The Grantham Matrix Score was used to score the significance of the substitution and the conservation of the residue in orthologs and defined domains. The likelihood for aberrant splicing and contextual information about the UCV within the patient (including segregation analysis) was used in combination to define a variant score. From this analysis, 44 missense plus two atypical splicing and seven small in-frame changes were defined as probably pathogenic and assigned to a mutation group. Mutations were thus defined in 180 (89.1%) probands: 153 (85.0%) PKD1 and 27 (15.0%) PKD2. The majority were unique to a single family, but recurrent mutations accounted for 30.0% of the total. A total of 190 polymorphic variants were identified in PKD1 (average of 10.1 per patient) and eight in PKD2. Although nondefinite mutation data must be treated with care in the clinical setting, this study shows the potential for molecular diagnostics in ADPKD that is likely to become increasingly important as therapies become available. C1 Mayo Clin, Coll Med, Div Nephrol & Hypertens, Rochester, MN USA. Emory Univ, Div Nephrol, Atlanta, GA 30322 USA. Univ Alabama, Div Genet & Translat Med, Birmingham, AL USA. Univ Kansas, Med Ctr, Kidney Inst, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. NW Renal Clin, Portland, OR USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RP Harris, PC (reprint author), Mayo Clin, Div Nephrol, 200 1st St SW, Rochester, MN 55905 USA. EM harris.peter@mayo.edu OI Miller, J Philip/0000-0003-4568-6846 FU NIDDK NIH HHS [DK56957, DK56934, DK56956, DK56957-S1, DK58816, DK56961] NR 51 TC 169 Z9 182 U1 2 U2 12 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2007 VL 18 IS 7 BP 2143 EP 2160 DI 10.1681/ASN.2006121387 PG 18 WC Urology & Nephrology SC Urology & Nephrology GA 200JA UT WOS:000248758500023 PM 17582161 ER PT J AU Bieliauskas, LA Back-Madruga, C Lindsay, KL Wright, EC Kronfol, Z Lok, ASF Fontana, RJ AF Bieliauskas, Linas A. Back-Madruga, Carla Lindsay, Karen L. Wright, Elizabeth C. Kronfol, Ziad Lok, Anna S. F. Fontana, Robert J. CA HALT C TRIAL GRP TI Cognitive reserve and neuropsychological functioning in patients infected with hepatitis C SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Article DE liver diseases; hepatic insufficiency; intelligence; IQ; cognitive manifestations; neurobehavioral manifestations ID PREMORBID INTELLIGENCE; ADVANCED FIBROSIS; WAIS-R; IQ; EDUCATION; DISEASE; SCORES; TRIAL AB This study evaluated the influence of cognitive reserve on neuropsychological test performance in 198 patients infected with the hepatitis C Virus. IQ scores, educational level, and occupational rating were combined to calculate a Cognitive Reserve Score (CRS) for each patient. Similar to studies of infection with the human immunodeficiency virus. there was a significantly increased risk of impairment in neuropsychological test performance in individuals with lower CRSs. It is important to account for CRS when assessing cognitive findings in large-scale clinical trials. C1 Ann Arbor Vet Affairs Healthcare Syst, Psychol Serv 116B, Ann Arbor, MI 48105 USA. Univ Michigan, Med Ctr, Dept Psychiat, Neuropsychol Sect, Ann Arbor, MI 48109 USA. Univ So Calif, Dept Psychiat & Behav Sci, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA 90089 USA. New England Res Inst, Watertown, MA 02172 USA. NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. RP Bieliauskas, LA (reprint author), Ann Arbor Vet Affairs Healthcare Syst, Psychol Serv 116B, 2215 Fuller Rd, Ann Arbor, MI 48105 USA. EM linas@umich.edu RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU NCRR NIH HHS [M01-RR-00042, M01-RR-00043]; NIDDK NIH HHS [N01-DK-9-2323, N01-DK-9-2325, N01-DK-9-2328] NR 23 TC 13 Z9 13 U1 1 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD JUL PY 2007 VL 13 IS 4 BP 687 EP 692 DI 10.1017/S1355617707070877 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 186GJ UT WOS:000247766800015 PM 17521478 ER PT J AU Cogdill, KW AF Cogdill, Keith W. TI Public health information outreach SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Editorial Material ID LIBRARY-OF-MEDICINE; COLLABORATION; ACCESS; NEEDS; COMMUNITY; WORKFORCE; IMPROVE; WORKERS C1 Natl Lib Med, Natl Network Lib Med Natl Network Off, Bethesda, MD 20894 USA. RP Cogdill, KW (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Reg Informat Serv, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cogdillk@uthscsa.edu OI Cogdill, Keith/0000-0002-9863-1657 NR 22 TC 3 Z9 3 U1 1 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 290 EP 292 DI 10.3163/1536-5050.95.3.290 PG 3 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300017 ER PT J AU Humphreys, BL AF Humphreys, Betsy L. TI Building better connections: the National Library of Medicine and public health SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID INFORMATION INFRASTRUCTURE; CARE; TECHNOLOGY; WORKFORCE; SERVICES; NETWORK AB Purpose: The paper describes the expansion of the public health programs and services of the National Library of Medicine (NLM) in the 1990s and provides the context in which NLM's public health outreach programs arose and exist today. Brief Description: Although NLM has always had collections and services relevant to public health, the US public health workforce made relatively little use of the library's information services and programs in the twentieth century. In the 1990s, intensified emphases on outreach to health professionals, building national information infrastructure, and promoting health data standards provided NLM with new opportunities to reach the public health community. A seminal conference cosponsored by NLM in 1995 produced an agenda for improving public health access to and use of advanced information technology and electronic information services. NLM actively pursued this agenda by developing new services and outreach programs and promoting public health informatics initiatives. Method: Historical analysis is presented. Results/Outcome: NLM took advantage of a propitious environment to increase visibility and understanding of public health information challenges and opportunities. The library helped create partnerships that produced new information services, outreach initiatives, informatics innovations, and health data policies that benefit the public health workforce and the diverse populations it serves. C1 NIH, Natl Lib Med, US Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Humphreys, BL (reprint author), NIH, Natl Lib Med, US Dept Hlth & Human Serv, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM Betsy.Humphreys@nih.hhs.gov NR 37 TC 9 Z9 10 U1 1 U2 7 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 293 EP 300 DI 10.3163/1536-5050.95.3.293 PG 8 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300018 PM 17641764 ER PT J AU Cahn, MA Auston, I Selden, CR Cogdill, K Baker, S Cavanaugh, D Elliott, S Foster, AJ Leep, CJ Perez, DJ Pomietto, BR AF Cahn, Marjorie A. Auston, Ione Selden, Catherine R. Cogdill, Keith Baker, Stacy Cavanaugh, Debra Elliott, Sterling Foster, Allison J. Leep, Carolyn J. Perez, Debra Joy Pomietto, Blakely R. TI The Partners in Information Access for the Public Health Workforce: a collaboration to improve and protect the public's health, 1995-2006 SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID OUTREACH FORUM; POLICY; NEEDS; RESOURCES; MEDICINE; LESSONS; QUALITY AB Objective: The paper provides a complete accounting of the Partners in Information Access for the Public Health Workforce (Partners) initiative since its inception in 1997, including antecedent activities since 1995. Methods: A descriptive overview is provided that is based on a review of meeting summaries, published reports, Websites, project reports, databases, usage statistics, and personal experiences from offices in the National Library of Medicine (NLM), six organizations that collaborate formally with NLM on the Partners initiative, and one outside funding partner. Results: With ten years of experience, the initiative is an effective and unique public-private collaboration that builds on the strengths and needs of the organizations that are involved and the constituencies that they serve. Partners-supported and sponsored projects include satellite broadcasts or Webcasts, training initiatives, Web resource development, a collection of historical literature, and strategies for workforce enumeration and expansion of public health systems research, which provide excellent examples of the benefits realized from collaboration between the public health community and health sciences libraries. Conclusions: With continued funding, existing and new Partners-sponsored projects will be able to fulfill many public health information needs. This collaboration provides excellent opportunities to strengthen the partnership between library science and public health in the use of health information and tools for purposes of improving and protecting the public's health. C1 Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, Bethesda, MD 20894 USA. Univ Texas, Hlth Sci Ctr, S Texas Reg Informat Serv, San Antonio, TX USA. Natl Lib Med, Natl Network Lib Med Natl Network Off, Bethesda, MD 20894 USA. Publ Hlth Fdn, Washington, DC 20005 USA. Med Lib Assoc, Chicago, IL 60601 USA. Assoc State & Terr Hlth Officials, Arlington, VA 22202 USA. Assoc Sch Publ Hlth, Washington, DC 20005 USA. Natl Assoc Cty & City Hlth Officials, Washington, DC 20036 USA. Robert Wood Johnson Fdn, Princeton, NJ 08543 USA. Soc Publ Hlth Educ, Washington, DC 20002 USA. RP Cahn, MA (reprint author), Natl Lib Med, Natl Informat Ctr Hlth Serv Res & Hlth Care Techn, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM nichsr@nlm.nih.gov; auston@nlm.nih.gov; selden@nlm.nih.gov; cogdillk@uthscsa.edu; sbaker@phf.org; mlapd3@mlahq.org; selliott@astho.org; afoster@asph.org; cleep@naccho.org; dperez@rwjf.org; blakely@umd.edu OI Cogdill, Keith/0000-0002-9863-1657 FU PHS HHS [U50/CCU302718] NR 34 TC 9 Z9 9 U1 0 U2 4 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 301 EP 309 DI 10.3163/1536-5050.95.3.301 PG 9 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300019 PM 17641765 ER PT J AU Cogdill, KW Ruffin, AB AF Cogdill, Keith W. Ruffin, Angela B. TI The National Network of Libraries of Medicine's outreach to the public health workforce: 2001-20060 SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Objective: The paper provides an overview of the National Network of Libraries of Medicine's (NN/LM's) outreach to the public health workforce from 2001 to 2006. Description: NN/LM conducts outreach through the activities of the Regional Medical Library (RML) staff and RML-sponsored projects led by NN/LM members. Between 2001 and 2006, RML staff provided training on information resources and information management for public health personnel at national, state, and local levels. The RMLs also contributed significantly to the Partners in Information Access for the Public Health Workforce collaboration. Methods: Data were extracted from telephone interviews with directors of thirty-seven NN/LM-sponsored outreach projects directed. at the public health sector. A review of project reports informed the interviews, which were transcribed and subsequently coded for emergent themes using qualitative analysis software. Results: Analysis of interview data led to the identification of four major themes: training, collaboration, evaluation of outcomes, and challenges. Sixteen subthemes represented specific lessons learned from NN/LM members' outreach to the public health sector. Conclusions: NN/LM conducted extensive information-oriented outreach to the public health workforce during the 2001-to-2006 contract period. Lessons learned from this experience, most notably the value of collaboration and the need for flexibility, continue to influence outreach efforts in the current contract period. C1 Univ Texas, Hlth Sci Ctr, S Texas Reg Informat Serv, San Antonio, TX 78284 USA. Natl Lib Med, Natl Network Off, Bethesda, MD USA. RP Cogdill, KW (reprint author), Univ Texas, Hlth Sci Ctr, S Texas Reg Informat Serv, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM cogdillk@uthscsa.edu; ruffina@mail.nlm.nih.gov NR 16 TC 4 Z9 5 U1 1 U2 6 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 310 EP 315 DI 10.3163/1536-5050.95.3.310 PG 6 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300020 PM 17641766 ER PT J AU Arnesen, SJ Cid, VH Scott, JC Perez, R Zervaas, D AF Arnesen, Stacey J. Cid, Victor H. Scott, John C. Perez, Ricardo Zervaas, Dave TI The Central American Network for Disaster and Health Information SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Purpose: This paper describes an international outreach program to support rebuilding Central America's health information infrastructure after several natural disasters in the region, including Hurricane Mitch in 1998 and two major earthquakes in 2001. Setting, Participants, and Description: The National Library of Medicine joined forces with the Pan American Health Organization/World Health Organization, the United Nations International Strategy for Disaster Reduction, and the Regional Center of Disaster Information for Latin America and the Caribbean (CRID) to strengthen libraries and information centers in Central America and improve the availability of and access to health and disaster information in the region by developing the Central American Network for Disaster and Health Information (CANDHI). Through CRID, the program created ten disaster health information centers in medical libraries and disaster-related organizations in six countries. Results/Outcome: This project served as a catalyst for the modernization of several medical libraries in Central America. The resulting CANDHI provides much needed electronic access to public health "gray literature" on disasters, as well as access to numerous health information resources. CANDHI members assist their institutions and countries in a variety of disaster preparedness activities through collecting and disseminating information. C1 Natl Lib Med, Bethesda, MD 20892 USA. Ctr Publ Serv Commun, Arlington, VA 22207 USA. Pan Amer Hlth Org, Panama City, Panama. United Nat Int Strategy Disaster Reduct, Panama City, Panama. Ctr Reg Informac Desastres Amer Latina & Caribe C, San Jose, Costa Rica. RP Arnesen, SJ (reprint author), Natl Lib Med, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA. EM stacey-arnesen@nlm.nih.gov; victor_cid@nlm.nih.gov; jcscott@cpsc.com; perez.tato@gmail.com; dzervaas@eird.org NR 15 TC 2 Z9 2 U1 2 U2 9 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 316 EP 322 DI 10.3163/1536-5050.95.3.316 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300021 PM 17641767 ER PT J AU Dancy, NC Dutcher, GA AF Dancy, Nicole C. Dutcher, Gale A. TI HIV/AIDS information outreach: a community-based approach SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Objective: The paper provides an overview of the National Library of Medicine's (NLM's) AIDS Community Information Outreach Program during the years 1994 to 2005, discusses the impact of previously funded projects, and explores future implications for HIV/AIDS information outreach to communities in need. Methods: A qualitative assessment was conducted to provide information on the impact of projects funded by the AIDS Community Information Outreach Program during fiscal year 2002. Interviews were conducted and final reports were analyzed, resulting in themes based on roles and responsibilities of participants and the impact of the projects in the communities. Results: Results from the assessment suggest that access to HIV/AIDS information led to improved communication between patients and their health care providers and encouraged better health care decision making. Feedback from reports and interviews included examples of impact such as an increase in services provided to communities, national and global recognition of HIV/AIDS services, sustainability of projects, and improved communication. Conclusion: Community-based health information outreach projects may empower the HIV/AIDS community to become more involved in health care and improve communication with providers. NLM will continue to promote the AIDS Community Information Outreach Program to encourage community organizations to design local projects for their specific communities. C1 Natl Lib Med, Off Outreach & Special Populat, Div Specialized Informat Serv, Bethesda, MD 20892 USA. RP Dancy, NC (reprint author), Natl Lib Med, Off Outreach & Special Populat, Div Specialized Informat Serv, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA. EM dancyn1@mail.nih.gov; dutcherg@mail.nlm.nih.gov NR 13 TC 4 Z9 4 U1 1 U2 3 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 323 EP 329 DI 10.3163/1536-5050.95.3.323 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300022 PM 17641768 ER PT J AU Dutcher, GA Spann, M Gaines, C AF Dutcher, Gage A. Spann, Melvin Gaines, Cynthia TI Addressing health disparities and environmental justice: the National Library of Medicine's Environmental Health Information Outreach Program SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Purpose: Disparities in health between minority and majority populations have become a topic of high interest in the health care and information communities. This paper describes the National Library of Medicine's (NLM's) oldest outreach program to a minority population, a project that has been going on for over fifteen years. Setting/Participants/Resources: The overview is based on internal documentation and reports, interviews, personal communications, and project reports. Brief Description: This is a historical overview of the Environmental Health Information Outreach Program, from its beginnings in 1991 as the Toxicology Information Outreach Project. The initial collaboration began with nine historically black colleges and universities (HBCUs) that had graduate programs in biomedicine. The current program includes representation from HBCUs, institutions serving Hispanic students, and tribal colleges. In addition to working with these institutions to promote the use of and access to electronic health information and related technology, this program brings attention to scientific research related to health issues that disproportionately affect minorities. Results/Outcome: The program expanded due to its perceived success by the initial participants and NLM's management. Not only have faculty, staff, and students at the participating institutions received training in using NLM's toxicology, environmental health, and other electronic resources, but the participants ascribe other successes to their collaboration with NLM. C1 Natl Lib Med, Off Outreach & Special Populat, Div Specialized Informat Serv, Bethesda, MD 20892 USA. Natl Lib Med, Div Specialized Informat Serv, Bethesda, MD 20892 USA. Natl Lib Med, Div Specialized Informat Serv, Bethesda, MD 20892 USA. RP Dutcher, GA (reprint author), Natl Lib Med, Off Outreach & Special Populat, Div Specialized Informat Serv, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA. EM dutdierg@mail.nlm.nih; melspann7@aol.com; gainesc@mail.nlm.nih.gov NR 12 TC 1 Z9 1 U1 1 U2 4 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2007 VL 95 IS 3 BP 330 EP 336 DI 10.3163/1536-5050.95.3.330 PG 7 WC Information Science & Library Science SC Information Science & Library Science GA 187KU UT WOS:000247847300023 PM 17641769 ER PT J AU Shavers, VL AF Shavers, Vickie L. TI Racial/ethnic variation in the anatomic subsite location of in situ and invasive cancers of the colon SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE race/ethnicity; colon; cancer; prevention ID SCREENING FLEXIBLE SIGMOIDOSCOPY; COLORECTAL-CANCER; UNITED-STATES; MEDICARE BENEFICIARIES; ENDOSCOPIC CAPACITY; RACIAL-DIFFERENCES; FEMALE SEX; AGE; COLONOSCOPY; RISK AB Introduction: Approximately 145,000 Americans were diagnosed with colorectal cancer and 56,000 died from colorectal cancer in 2006. Although colorectal screening can reduce mortality and incidence, U.S. screening rates are particularly low for racial/ethnic minorities. Racial differences in the subsite location of colon cancers could have implications for colorectal screening. This study examines the anatomic subsite distribution of tumors among African-American, Hispanic, Asian-American/Pacific-Islander and non-Hispanic white (NHW) patients with colon cancer. Methods: Surveillance and End Results program data for 254,469 primary in situ and invasive colon cancers for patients from 1973-2002 are included in this analysis. Descriptive analyses and logistic regression are used to describe and examine variations in the proportion of colon cancers diagnosed at sites proximal to the sigmoid colon or proximal to the splenic flexure over three successive time periods. Results: The proportion of colon cancers diagnosed at the sigmoid colon was 15.6-21.3% lower, while diagnoses at the descending colon were 40.5.0-45.3.0% higher for African Americans than NHWs over the three time periods. In logistic regression analyses adjusted for gender, age group and year of diagnosis, the odds of a diagnosis of cancer proximal to the sigmoid colon or proximal to the splenic flexure was significantly higher for African Americans but lower for Hispanics and Asian Americans/Pacific Islanders compared to NHWs. Discussion: The higher proportion of cancers among African Americans diagnosed at sites that are generally attempted but not always reached with a sigmoidscope suggest that African Americans may benefit from screening colonoscopy. They also highlight the need for systems that collect data that would allow a direct examination of the role that the differential use of specific colon screening tests and polypectomy play in racial/ethnic variation in colon cancer incidence and in the anatomic subsite distribution of colon cancers. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Appl Res Program, Econ Branch, Bethesda, MD 20892 USA. RP Shavers, VL (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv, 6130 Execut Blvd,Room 4005, Bethesda, MD 20892 USA. EM shaversv@mail.nih.gov NR 43 TC 44 Z9 45 U1 1 U2 1 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD JUL PY 2007 VL 99 IS 7 BP 733 EP 748 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 191CU UT WOS:000248108300004 PM 17668639 ER PT J AU Antonellis, A Vinton, R McCallion, A Green, ED Pavan, WJ AF Antonellis, A. Vinton, R. McCallion, A. Green, E. D. Pavan, W. J. TI Transcriptional regulation of the sry-box 10 locus: Implications for diseases of the peripheral nerve SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Annual Meeting of the Peripheral-Nerve-Society CY JUL 14-18, 2007 CL Snowbird, UT SP Peripheral Nerve Soc C1 NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUL PY 2007 VL 12 SU 1 BP 5 EP 5 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 207IA UT WOS:000249243600014 ER PT J AU Lee, CJ Chandrasekaran, V Duke, RE Perera, L Pedersen, LG AF Lee, C. J. Chandrasekaran, V. Duke, R. E. Perera, L. Pedersen, L. G. TI A proposed structural model of human protein Z SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID BLOOD-COAGULATION FACTOR; CRYSTAL-STRUCTURE; GLA DOMAIN; PLASMA; DEFICIENCY; INHIBITOR; MUTATION; COMPLEX; SUBSTITUTION; SEQUENCE C1 Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Pedersen, LG (reprint author), Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. EM lee_pedersen@unc.edu RI perera, Lalith/B-6879-2012; Pedersen, Lee/E-3405-2013 OI perera, Lalith/0000-0003-0823-1631; Pedersen, Lee/0000-0003-1262-9861 NR 30 TC 7 Z9 7 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2007 VL 5 IS 7 BP 1558 EP 1561 DI 10.1111/j.1538-7836.2007.02597.x PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 189HM UT WOS:000247980000035 PM 17456189 ER PT J AU Thompson, IM Lucia, MS Redman, MW Darke, A La Rosa, FG Parnes, HL Lippman, SM Coltman, CA AF Thompson, Ian M. Lucia, M. Scott Redman, Mary W. Darke, Amy La Rosa, Francisco G. Parnes, Howard L. Lippman, Scott M. Coltman, Charles A. TI Finasteride decreases the risk of prostatic intraepithelial neoplasia SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostatic neoplasms; finasteride; risk; prevention and control ID CANCER PREVENTION TRIAL; NEEDLE BIOPSIES; BREAST-CANCER; ADENOCARCINOMA; OUTCOMES; CHEMOPREVENTION; TAMOXIFEN; MEN AB Purpose: High grade prostatic intraepithelial neoplasia is likely a premalignant lesion of the prostate. Decreasing the frequency of high grade PIN may decrease the risk of prostate cancer. In the Prostate Cancer Prevention Trial we evaluated the impact of finasteride on the risk of a needle biopsy diagnosis of high grade prostatic intraepithelial neoplasia. Materials and Methods: The Prostate Cancer Prevention Trial was a randomized, placebo controlled clinical trial that enrolled 18,882 men without evidence of prostate cancer, prostate specific antigen less than 3.0 ng/ml and normal digital rectal examination, and randomized them to 5 mg finasteride daily or placebo. Subjects were followed for 7 years with biopsy recommended for prostate specific antigen greater than 4.0 ng/ml, adjusted in the finasteride group to achieve an equal number of biopsy recommendations or for abnormal digital rectal examination. All cancer-free subjects were recommended to undergo biopsy after 7 years on study. We evaluated the diagnosis of high grade prostatic intraepithelial neoplasia with or without concomitant prostate cancer in these 2 study groups. Results: The number of men evaluable for high grade prostatic intraepithelial neoplasia was 4,568 in the finasteride group and 4,886 in the placebo group. High grade prostatic intraepithelial neoplasia alone was diagnosed in 276 men (6.0%) in the finasteride group vs 347 (7.1%) in the placebo group (RR 0.85, 95% CI 0.73-0.99, p = 0.04). High grade prostatic intraepithelial neoplasia accompanied by prostate cancer was diagnosed in 144 men (3.2%) in the finasteride group vs 223 (4.6%) in the placebo group (RR 0.69, 95% CI 0.56-0.85, p = 0.0004). Finasteride significantly decreased the overall risk of high grade prostatic intraepithelial neoplasia (alone and with cancer) from 570 cases (11.7%) in the placebo group to 420 (9.2%) in the finasteride group (HR 0.79, 95% CI 0.70-0.89, p <0.001). Conclusions: Finasteride significantly decreased the risk of high grade PIN. This observation may explain how finasteride decreased prostate cancer in the Prostate Cancer Prevention Trial, supporting the notion that high grade prostatic intraepithelial neoplasia is a premalignant lesion of the prostate, and it provides new information relevant to the consideration of finasteride for prostate cancer prevention. C1 Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctrd, Dept Urol, SW Oncol Grp, San Antonio, TX USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Natl Canc Inst, Div Canc Prevent, Bethesda, MD 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 [CA35178, CA45808, CA37429] NR 26 TC 32 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUL PY 2007 VL 178 IS 1 BP 107 EP 109 DI 10.1016/j.juro.2007.03.012 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 178BU UT WOS:000247197000029 PM 17499284 ER PT J AU McDermott, MM Guralnik, JM Ferrucci, L Tian, L Pearce, WH Hoff, F Liu, K Liao, YH Criqui, MH AF McDermott, Mary McGrae Guralnik, Jack M. Ferrucci, Luigi Tian, Lu Pearce, William H. Hoff, Frederick Liu, Kiang Liao, Yihua Criqui, Michael H. TI Physical activity, walking exercise, and calf skeletal muscle characteristics in patients with peripheral arterial disease SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID LOWER-EXTREMITY ISCHEMIA; ANKLE BRACHIAL INDEX; FUNCTIONAL DECLINE; CRITERIA; QUESTIONNAIRES; CLASSIFICATION; OSTEOARTHRITIS; ACCELEROMETER; CLAUDICATION; ASSOCIATION AB Objective: This cross-sectional study was set in an academic medical center and conducted to identify associations of physical activity level and walking exercise frequency with calf skeletal muscle characteristics in individuals with lower extremity peripheral arterial disease (PAD). Methods. Calf muscle characteristics in 439 men and women with PAD were measured with computed tomography at 66.67% of the distance between the distal and proximal tibia. Physical activity was measured continuously during 7 days with a vertical accelerometer. Patient report was used to determine the number of blocks walked during the past week and walking exercise frequency. Results were adjusted for age, sex, race, comorbidities, ankle-brachial index, body mass index, smoking, and other confounders. Results. For both objective and subjective measures, more physically active PAD participants had higher calf muscle area and muscle density. Calf muscle area across tertiles of accelerometer-measured physical activity were first activity tertile, 5071 mm(2); second activity tertile: 5612 mm(2); and third activity tertile, 5869 mm(2) (p < .001). Calf muscle density across tertiles of patient-reported blocks walked during the past week were first activity tertile, 31.4 mg/cm(3); second activity tertile, 33.0 mg/cm(3); and third activity tertile, 33.8 mg/cm(3) (P < .001). No significant associations were found between walking exercise frequency and calf muscle characteristics. Conclusion: Among participants with PAD, higher physical activity levels, measured by accelerometer and by patient-reported blocks walked per week, were associated with more favorable calf muscle characteristics. In contrast, more frequent patient-reported walking exercise was not associated with more or less favorable calf muscle characteristics. Results suggest that clinicians should encourage their patients to increase their walking activity during daily life. C1 Northwestern Univ, Feinberg Sch Med, Dept Med, Evanston, IL 60208 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Evanston, IL 60208 USA. Northwestern Univ, Feinberg Sch Med, Dept Surg, Evanston, IL 60208 USA. Northwestern Univ, Feinberg Sch Med, Dept Radiobiol, Evanston, IL 60208 USA. NIA, Labs Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RP McDermott, MM (reprint author), 676 N St Clair,Suite 200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU Intramural NIH HHS [Z99 AG999999]; NCRR NIH HHS [M01 RR000048-456853, M01 RR000048-440425, M01 RR000048-380366, RR 00048, M01 RR000048-430425, M01 RR000048]; NHLBI NIH HHS [R01 HL 58099, R01 HL 64739, R01 HL071223, R01 HL071223-02, R01 HL064739-01A1, R01 HL071223-03, R01 HL 71223, R01 HL064739, R01 HL071223-04, R01 HL071223-01] NR 28 TC 18 Z9 19 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD JUL PY 2007 VL 46 IS 1 BP 87 EP 93 DI 10.1016/j.jvs.2007.02.064 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 185JO UT WOS:000247707500015 PM 17540532 ER PT J AU Wakamatsu, N King, DJ Seal, BS Brown, CC AF Wakamatsu, Nobuko King, Daniel J. Seal, Bruce S. Brown, Corrie C. TI Detection of Newcastle disease virus RNA by reverse transcription-polymerase chain reaction using formalin-fixed, paraffin-embedded tissue and comparison with immunohistochemistry and in situ hybridization SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Article DE formalin-fixed; Newcastle disease virus; paraffin-embedded tissue; RT-PCR ID MOLECULAR EPIDEMIOLOGIC ANALYSIS; DOMESTIC CHICKENS; PATHOGENESIS; INFECTION; DIAGNOSIS; VIRULENCE; SEQUENCE; ORGANS; ASSAY; PCR AB The usefulness of reverse transcription-polymerase chain reaction (RT-PCR) from formalin-fixed, paraffin-embedded (FFPE) tissues was examined and compared to the immunohistochemistry (IHC) and in situ hybridization (ISH) assays for detection of Newcastle disease virus (NDV). Spleen and lung tissues were collected from chickens experimentally infected with either of 2 NDV isolates: a low virulent virus (LaSota) and a virulent virus (from the 2002-2003 California outbreak). The tissues were harvested immediately postmortem and fixed in 10% neutral buffered formalin for approximately 52 hours. Also, just before euthanasia, oral and cloacal swabs were collected for virus isolation. RNA was obtained from the FFPE tissues by digestion with proteinase K and subsequent extraction with phenol, chloroform, and isoamyl alcohol. By seminested RT-PCR with primers for the NDV matrix gene, a 232-base pair (bp) product was generated and visualized by electrophoresis. The results of PCR were compared to those of IHC for viral nucleoprotein and ISH for matrix gene (850 bp) on 3-mu m sections and to those of virus isolation from swabs. All samples from infected chickens were positive by RT-PCR, including samples that were negative by both IHC and ISH. The RT-PCR positives included tissue from chickens that were no longer shedding virus detectable by virus isolation. The RT-PCR was an effective and sensitive method to detect NDV in FFPE tissues. To the authors' knowledge, this is the first report of NDV detection in FFPE tissues as a diagnostic approach possibly suitable for archival materials. C1 Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. USDA ARS, SE Poultry Res Lab, Athens, GA 30605 USA. USDA ARS, Russell Res Ctr, Poultry Microbiol Safety Res Unit, Athens, GA 30605 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Brown, CC (reprint author), Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. EM corbrown@vet.uga.edu NR 17 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD JUL PY 2007 VL 19 IS 4 BP 396 EP 400 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 189MZ UT WOS:000247994300010 PM 17609350 ER PT J AU Barthold, SW Borowsky, AD Brayton, C Bronson, R Cardiff, RD Griffey, SM Ince, TA Nikitin, AY Sundberg, J Valli, VET Ward, JM AF Barthold, Stephen W. Borowsky, Alexander D. Brayton, Cory Bronson, Rod Cardiff, Robert D. Griffey, Steven M. Ince, Tan A. Nikitin, Alexander Yu Sundberg, John Valli, V. E. Ted Ward, Jerrold M. TI From whence will they come? - A perspective on the acute shortage of pathologists in biomedical research SO JOURNAL OF VETERINARY DIAGNOSTIC INVESTIGATION LA English DT Letter C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Cornell Univ, Dept Biomed Sci, Ithaca, NY 14853 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Illinois, Coll Vet Med, Dept Pathobiol, Urbana, IL 61802 USA. NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, SoBran Inc,NIH, Bethesda, MD 20892 USA. RP Barthold, SW (reprint author), Univ Calif Davis, Ctr Comparat Med, Davis Cty Rd 98 & Hutchinson Dr, Davis, CA 95616 USA. NR 0 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC VETERINARY LABORATORY DIAGNOSTICIANS INC PI TURLOCK PA PO BOX 1522, TURLOCK, CA 95381 USA SN 1040-6387 J9 J VET DIAGN INVEST JI J. Vet. Diagn. Invest. PD JUL PY 2007 VL 19 IS 4 BP 455 EP 456 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 189MZ UT WOS:000247994300025 PM 17609364 ER PT J AU Dunn, ST Allen, RA Wang, S Walker, J Schiffman, M AF Dunn, S. Terence Allen, Richard A. Wang, Sophia Walker, Joan Schiffman, Mark TI DNA extraction: An understudied and important aspect of HPV genotyping using PCR-based methods SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HPV; virus; DNA extraction; genotyping; linear array ID HUMAN-PAPILLOMAVIRUS HPV; CERVICAL-CANCER; ROCHE-AMPLICOR; RISK; WORLDWIDE; SAMPLES; WOMEN; ASSAY; SPECIMENS; CELLS AB Testing for the group of similar to 15 carcinogenic human papillomavirus (HPV) genotypes is an important adjunct to cytology. Because carcinogenic strengths of HPV types differ greatly, assays that permit identification of individual HPV genotypes are being introduced. Most HPV genotyping systems proposed for clinical use are PCR-based, depending heavily for validity on careful attention to numerous details. One understudied detail is the effect of different sample preparation methods including DNA extraction. This study examines the influence of DNA extraction on performance of a new PCR-based genotyping kit, the Roche LINEAR ARRAY(R) HPV assay. When volume of sample extracted, DNA extraction methods and/or amount of DNA tested were varied, the HPV type results were reproducible for strong viral bands but not weak ones. Moreover, although the experiments were not comprehensive, they showed that the manufacturer-approved DNA extraction method might not be the best method for use in this assay. Because different "front end" protocols introduce variability into genotyping results, the authors urge laboratories not to vary methods for this assay without due consideration. The results suggest that companies carefully optimize DNA extraction methods prior to commercial introduction of their PCR-based genotyping assays destined for widespread clinical use. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Dunn, ST (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, BMSB Rm 451,POB 26901, Oklahoma City, OK 73190 USA. EM terry-dunn@ouhsc.edu FU Intramural NIH HHS; NCI NIH HHS [N02CP31102]; NCRR NIH HHS [M01 RR14467] NR 22 TC 35 Z9 35 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUL PY 2007 VL 143 IS 1 BP 45 EP 54 DI 10.1016/j.jviromet.2007.02.006 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 179NT UT WOS:000247297300007 PM 17399803 ER PT J AU Wang, K Mahalingam, G Hoover, SE Mont, EK Holland, SM Cohen, JI Straus, SE AF Wang, Kening Mahalingam, Gowtharn Hoover, Susan E. Mont, Erik K. Holland, Steven M. Cohen, Jeffrey I. Straus, Stephen E. TI Diverse herpes simplex virus type 1 thymidine kinase mutants in individual human neurons and ganglia SO JOURNAL OF VIROLOGY LA English DT Article ID RESISTANT GENITAL HERPES; ACYCLOVIR-RESISTANT; TRIGEMINAL GANGLIA; GENOTYPIC CHARACTERIZATION; IMMUNOCOMPETENT PATIENT; TRANSPLANT RECIPIENTS; DNA-POLYMERASE; HIGH-FREQUENCY; LATENCY; REACTIVATION AB Mutations in the thymidine kinase gene (tk) of herpes simplex virus type 1 (HSV-1) explain most cases of virus resistance to acyclovir (ACV) treatment Mucocutaneous lesions of patients with ACV resistance contain mixed populations of tk mutant and wild-type virus. However, it is unknown whether human ganglia also contain mixed populations since the replication of HSV tk mutants in animal neurons is impaired. Here we report the detection of mutated HSV tk sequences in human ganglia. Trigerninal and dorsal root ganglia were obtained at autopsy from an immunocompromised woman with chronic mucocutaneous infection with ACV-resistant HSV-1. The HSV-1 tk open reading frames from ganglia were amplified by PCR, cloned, and sequenced. tk mutations were detected in a seven-G homopolymer region in 11 of 12 ganglia tested, with clonal frequencies ranging from 4.2 to 769/v HSV-1 tk mutants per ganglion. In 8 of 11 ganglia, the mutations were heterogeneous, varying from a deletion of one G to an insertion of one to three G residues, with the two-G insertion being the most common. Each ganglion had its own pattern of mutant populations. When individual neurons from one ganglion were analyzed by laser capture microdissection and PCR, 6 of 14 HSV-1-positive neurons were coinfected with HSV tk mutants and wild-type virus, 4 of 14 were infected with wild-type virus alone, and 4 of 14 were infected with tk mutant virus alone. These data suggest that diverse tk mutants arise independently under drug selection and establish latency in human sensory ganglia alone or together with wild-type virus. C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathogenesis Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N-234,10 Ctr Dr, Bethesda, MD 20892 USA. EM kwang@niaid.nih.gov RI Hoover, Susan/F-8580-2015 FU Intramural NIH HHS NR 41 TC 22 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 6817 EP 6826 DI 10.1128/JVI.00166-07 PG 10 WC Virology SC Virology GA 180YW UT WOS:000247404900005 PM 17459924 ER PT J AU Delviks-Frankenberry, KA Nikolenko, GN Barr, R Pathak, VK AF Delviks-Frankenberry, Krista A. Nikolenko, Galina N. Barr, Rebekah Pathak, Vinay K. TI Mutations in human immunodeficiency virus type 1 RNase H primer grip enhance 3-Azido-3'-deoxythymidine resistance SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; DOUBLE-STRANDED DNA; TEMPLATE-PRIMER; DRUG-RESISTANCE; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; IN-VIVO; POLYMERASE; FREQUENCY; COMPLEX AB We recently observed that mutations in the human immunodeficiency type 1 (HIV-1) reverse transcriptase (RT) connection domain significantly increase 3'-azido-3'-deoxythyrnidine (AZT) resistance up to 536 times over wildtype (WT) RT in the presence of thymidine analog resistance mutations (TAMs). These mutations also decreased RT template switching, suggesting that they altered the balance between nucleotide excision and template RNA degradation, which in turn increased AZT resistance. Several residues in the HIV-1 connection domain contact the primer strand and form an RNase H primer grip structure that helps to position the primer-template at the RNase H and polymerase active sites. To test the hypothesis that connection domain mutations enhanced AZT resistance by influencing the RNase H primer grip, we determined the effects of alanine substitutions in RNase H primer grip residues on nucleoside RT inhibitor resistance in the context of a Wr, TAM-containing, or K65R-containing polymerase domain. Ten of the 11 RNase H primer grip mutations increased AZT resistance 20 to 243 times above WT levels in the context of a TAM-containing polymerase domain. Furthermore, all mutations in the RNase H primer grip decreased template switching, suggesting that they reduced RNase H activity. These results demonstrate that mutations in the RNase H primer grip region can significantly enhance AZT resistance and support the hypothesis that mutations in the connection and RNase H domains can increase resistance by altering the RNase H primer grip region, changing interactions between RT and the template-primer complex and/or shifting the balance between the polymerase and RNase H activities. C1 NCI, HIV Drug Resistance Program, Viral Mutat Sect, Frederick, MD 21702 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, Viral Mutat Sect, Bldg 535,Room 334, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov RI Delviks-Frankenberry, Krista/M-4822-2013 FU Intramural NIH HHS NR 29 TC 62 Z9 63 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 6837 EP 6845 DI 10.1128/JVI.02820-06 PG 9 WC Virology SC Virology GA 180YW UT WOS:000247404900007 PM 17428874 ER PT J AU Luque, D Saugar, I Rodriguez, JF Verdaguer, N Garriga, D Martin, C Velazquez-Muriel, JA Trus, BL Carrascosa, JL Caston, JR AF Luque, Daniel Saugar, Irene Rodriguez, Jos F. Verdaguer, Nuria Garriga, Damia San Martin, Carmen Velazquez-Muriel, Javier A. Trus, Benes L. Carrascosa, Jos L. Caston, Jose R. TI Infectious bursal disease virus capsid assembly and maturation by structural rearrangements of a transient molecular switch SO JOURNAL OF VIROLOGY LA English DT Article ID ICOSAHEDRAL ANIMAL VIRUS; DEPENDENT RNA-POLYMERASE; C-TERMINAL DOMAIN; CRYOELECTRON MICROSCOPY; CRYSTAL-STRUCTURE; FUNCTIONAL IMPLICATIONS; SCAFFOLDING PROTEIN; CATALYTIC DYAD; RESOLUTION; VP2 AB Infectious bursal disease virus (IBDV), a double-stranded RNA (dsRNA) virus belonging to the Birnaviridae family, is an economically important avian pathogen. The IBDV capsid is based on a single-shelled T=13 lattice, and the only structural subunits are VP2 trimers. During capsid assembly, VP2 is synthesized as a protein precursor, called pVP2, whose 71-residue C-terminal end is proteollytically processed. The conformational flexibility of pVP2 is due to an amphipathic alpha-helix located at its C-terminal end. VP3, the other IBDV major structural protein that accomplishes numerous roles during the viral cycle, acts as a scaffolding protein required for assembly control. Here we address the molecular mechanism that defines the multimeric state of the capsid protein as hexamers or pentamers. We used a combination of three-dimensional cryo-ellectron microscopy maps at or close to subnanometer resolution with atomic models. Our studies suggest that the key polypeptide element, the C-terminal amphipathic alpha-helix, which acts as a transient conformational switch, is bound to the flexible VP2 C-terminal end. In addition, capsid protein olligomerization is also controlled by the progressive trimming of its C-terminal domain. The coordination of these molecular events correlates viral capsid assembly with different conformations of the amphipathic alpha-helix in the precursor capsid, as a five-alpha-helix bundle at the pentamers or an open star-like conformation at the hexamers. These results, reminiscent of the assembly pathway of positive single-stranded RNA viruses, such as nodavirus and tetravirus, add new insights into the evolutionary relationships of dsRNA viruses. C1 CSIC, Dept Struct Macromol, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. CSIC, Dept Mol & Cellular Biol, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. CSIC, Inst Biol Mol Barcelona, E-08028 Barcelona, Spain. NIH, CIT, Imaging Sci Lab, Bethesda, MD 20892 USA. RP Caston, JR (reprint author), CSIC, Dept Struct Macromol, Ctr Nacl Biotecnol, Plaza Murillo 2, E-28049 Madrid, Spain. EM jrcaston@cnb.uam.es RI San Martin, Carmen/A-4074-2010; Caston, Jose/L-5896-2014; Luque, Daniel/I-6467-2015; OI San Martin, Carmen/0000-0001-9799-175X; Caston, Jose/0000-0003-2350-9048; Luque, Daniel/0000-0002-0151-6020; Garriga, Damia/0000-0003-0410-538X FU Intramural NIH HHS NR 49 TC 32 Z9 35 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 6869 EP 6878 DI 10.1128/JVI.00077-07 PG 10 WC Virology SC Virology GA 180YW UT WOS:000247404900010 PM 17442720 ER PT J AU Park, GS Morris, KL Hallett, RG Bloom, ME Best, SM AF Park, Gregory S. Morris, Keely L. Hallett, Roselyn G. Bloom, Marshall E. Best, Sonja M. TI Identification of residues critical for the interferon antagonist function of langat virus NS5 reveals a role for the RNA-dependent RNA polymerase dornainv SO JOURNAL OF VIROLOGY LA English DT Article ID TICK-BORNE FLAVIVIRUS; DENGUE VIRUS; JAPANESE ENCEPHALITIS; CRYSTAL-STRUCTURE; ALPHA-INTERFERON; INHIBITION; INFECTION; VIRULENCE; BLOCKING; SEQUENCE AB All pathogenic flaviviruses examined thus far inhibit host interferon (IFN) responses by suppressing the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Both Langat virus (LGTV; a member of the tick-borne encephalitis virus serogroup) and Japanese encephalitis virus use the nonstructural protein NS5 to suppress JAK-STAT signaling. However, NS5 is also critical to virus replication, contributing methyltransferase and RNA-dependent RNA polymerase (RdRP) activities. The specific amino acid residues of NS5 involved in IFN antagonism are not known. Here, we demonstrate that the LGTV NS5 JAK-STAT inhibitory domain is contained between amino acids 355 and 735 (of 903), a range which lies within the RdRP domain. Furthermore, we identified two noncontiguous stretches of specific amino acids within the RdRP, 374 to 380 and 624 to 647, as critical for inhibition of JAK-STAT signaling. Despite considerable separation on the linear NS5 sequence, these residues localized adjacent to each other when modeled on the West Nile virus RdRP crystal structure. Due to the general conservation of RdRP structures, these results suggest that the specific residues identified act cooperatively to form a unique functional site on the RdRP responsible for JAK-STAT inhibition. This insight into the mechanism underlying flavivirus IFN evasion strategies will facilitate the design of antiviral therapeutics that potentiate the action of IFN during infection. C1 NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, Hamilton, MT 59840 USA. RP Best, SM (reprint author), NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov FU Intramural NIH HHS NR 26 TC 42 Z9 46 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 6936 EP 6946 DI 10.1128/JVI.002830-07 PG 11 WC Virology SC Virology GA 180YW UT WOS:000247404900017 PM 17459929 ER PT J AU Nie, Z Bren, GD Vlahakis, SR Schimnich, AAE Brenchley, JM Trushin, SA Warren, S Schnepple, DJ Kovacs, CM Loutfy, MR Douek, DC Badley, AD AF Nie, Zilin Bren, Gary D. Vlahakis, Stacey R. Schimnich, Alicia Al Eciras Brenchley, Jason M. Trushin, Sergey A. Warren, Sarah Schnepple, David J. Kovacs, Colin M. Loutfy, Mona R. Douek, Daniel C. Badley, Andrew D. TI Human immunodeficiency virus type 1 protease cleaves procaspase 8 in vivo SO JOURNAL OF VIROLOGY LA English DT Article ID CD4(+) T-CELLS; HIV-1 PROTEASE; GASTROINTESTINAL-TRACT; INFECTIOUS HIV-1; APOPTOSIS; PROTEINS; LYMPHOCYTES; CYTOSKELETAL; MACROPHAGES; ACTIVATION AB Human immunodeficiency virus type 1 (HIV-1) infection causes apoptosis of infected CD4 T cells as well as uninfected (bystander) CD4 and CD8 T cells. It remains unknown what signals cause infected cells to die. We demonstrate that HIV-1 protease specifically cleaves procaspase 8 to create a novel fragment termed casp8p41, which independently induces apoptosis. casp8p41 is specific to HIV-1 protease-induced death but not other caspase 8-dependent death stimuli. In HIV-1-infected patients, casp8p41 is detected only in CD4(+) T cells, predominantly in the CD27(+) memory subset, its presence increases with increasing viral load, and it colocalizes with both infected and apoptotic cells. These data indicate that casp8p41 independently induces apoptosis and is a specific product of HIV-1 protease which may contribute to death of HIV-1-infected cells. C1 Mayo Clin & Mayo Fdn, Coll Med, Div Infect Dis, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Coll Med, Program Translat Immunovirol & Biodef, Rochester, MN 55905 USA. NIAID, VRC, NIH, Human Immunol Sect, Bethesda, MD 20892 USA. Univ Toronto, Dept Med, Toronto, ON M5B 1L6, Canada. RP Badley, AD (reprint author), Mayo Clin & Mayo Fdn, Coll Med, Div Infect Dis, 200 1st St SW, Rochester, MN 55905 USA. EM badley.andrew@mayo.edu RI badley, andrew/O-9022-2014 FU NIAID NIH HHS [R01 AI040384, R01 AI62261, R01 AI062261, R01 AI40384] NR 38 TC 35 Z9 35 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 6947 EP 6956 DI 10.1128/JVI.02798-07 PG 10 WC Virology SC Virology GA 180YW UT WOS:000247404900018 PM 17442709 ER PT J AU Larsen, LSZ Zhang, M Beliakova-Bethell, N Bilanchone, V Lamsa, A Nagashima, K Najdi, R Kosaka, K Kovacevic, V Cheng, J Baldi, P Hatfield, GW Sandmeyer, S AF Larsen, Liza S. Z. Zhang, Min Beliakova-Bethell, Nadejda Bilanchone, Virginia Lamsa, Anne Nagashima, Kunio Najdi, Rani Kosaka, Kathryn Kovacevic, Vuk Cheng, Jianlin Baldi, Pierre Hatfield, G. Wesley Sandmeyer, Suzanne TI Ty3 capsid mutations reveal early and late functions of the amino-terminal domainv SO JOURNAL OF VIROLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HOMOLOGY REGION; CYTOPLASMIC PROCESSING BODIES; RETROVIRAL GAG PROTEINS; PFIZER MONKEY VIRUS; HIV-1 GAG; INTRACELLULAR TRAFFICKING; CRYSTAL-STRUCTURE; REVERSE TRANSCRIPTION; PERICENTRIOLAR REGION AB The Ty3 retrotransposon assembles into 50-nm virus-like particles that occur in large intracellular clusters in the case of wild-type (wt) Ty3. Within these particles, maturation of the Gag3 and Gag3-Pol3 polyproteins by Ty3 protease produces the structural proteins capsid (CA), spacer, and nucleocapsid. Secondary and tertiary structure predictions showed that, like retroviral CA, Ty3 CA contains a large amount of helical structure arranged in amino-terminal and carboxyl-terminal bundles. Twenty-six mutants in which alanines were substituted for native residues were used to study CA subdomain functions. Transposition was measured, and particle morphogenesis and localization were characterized by analysis of protein processing, cDNA production, genomic RNA protection, and sedimentation and by fluorescence and electron microscopy. These measures defined five groups of mutants. Proteins from each group could be sedimented in a large complex. Mutations in the amino-terminal domain reduced the formation of fluorescent Ty3 protein foci. In at least one major homology region mutant, Ty3 protein concentrated in foci but no wt clusters of particles were observed. One mutation in the carboxyl-terminal domain shifted assembly from spherical particles to long filaments. Two mutants formed foci separate from P bodies, the proposed sites of assembly, and formed defective particles. P-body association was therefore found to be not necessary for assembly but correlated with the production of functional particles. One mutation in the amino terminus blocked transposition after cDNA synthesis. Our data suggest that Ty3 proteins are concentrated first, assembly associated with P bodies occurs, and particle morphogenesis concludes with a post-reverse transcription, CA-dependent step. Particle formation was generally resistant to localized substitutions, possibly indicating that multiple domains are involved. C1 Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Univ Calif Irvine, Sch Informat & Comp Sci, Irvine, CA 92697 USA. Univ Calif Irvine, Inst Genom & Bioinformat, Irvine, CA 92697 USA. SAIC Frederick Inc, Image Anal Lab, NCI, Frederick, MD 21702 USA. RP Sandmeyer, S (reprint author), Univ Calif Irvine, Dept Biol Chem, Irvine, CA 92697 USA. EM sbsandme@uci.edu RI zhang, min/C-6300-2011; Cheng, Jianlin/N-8209-2013 FU NCI NIH HHS [R01 CA112560, CA112560, N01CO12400, N01-CO12400]; NIAID NIH HHS [T32-AI07319, T32 AI007319]; NIGMS NIH HHS [R01 GM068903, R01 GM033281, GM68903, GM33281]; NLM NIH HHS [T15 LM007443, LM07443-01] NR 103 TC 21 Z9 21 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 6957 EP 6972 DI 10.1128/JVI.02207-07 PG 16 WC Virology SC Virology GA 180YW UT WOS:000247404900019 PM 17442718 ER PT J AU Mbisa, JL Barr, R Thomas, JA Vandegraaff, N Dorweiler, IJ Svarovskaia, ES Brown, WL Mansky, LM Gorelick, RJ Harris, RS Engelman, A Pathak, VK AF Mbisa, Jean L. Barr, Rebekah Thomas, James A. Vandegraaff, Nick Dorweiler, Irene J. Svarovskaia, Evguenia S. Brown, William L. Mansky, Louis M. Gorelick, Robert J. Harris, Reuben S. Engelman, Alan Pathak, Vinay K. TI Human immunodeficiency virus type 1 cDNAs produced in the presence of APOBEC3G exhibit defects in plus-strand DNA transfer and integration SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE TRANSCRIPTION; IN-VIVO; VIF PROTEIN; VIRAL-DNA; RETROVIRAL INFECTION; CYTIDINE DEAMINATION; ANTIVIRAL ACTIVITY; RIBONUCLEASE-H; HIV-1 VIRION; HYPERMUTATION AB Encapsidation of host restriction factor APOBEC3G (A3G) into vif-deficient human immunodeficiency virus type I (HIV-1) blocks virus replication at least partly by C-to-U deamination of viral minus-strand DNA, resulting in G-to-A hypermutation. A3G may also inhibit HIV-1 replication by reducing viral DNA synthesis and inducing viral DNA degradation. To gain further insight into the mechanisms of viral inhibition, we examined the metabolism of A3G-exposed viral DNA. We observed that an overall 35-fold decrease in viral infectivity was accompanied by a five- to sevenfold reduction in viral DNA synthesis. Wild-type A3G induced an additional fivefold decrease in the amount of viral DNA that was integrated into the host cell genome and similarly reduced the efficiency with which HIV-1 preintegration complexes (PICs) integrated into a target DNA in vitro. The A3G C-terminal catalytic domain was required for both of these antiviral activities. Southern blotting analysis of PICs showed that A3G reduced the efficiency and specificity of primer tRNA processing and removal, resulting in viral DNA ends that are inefficient substrates for integration and plus-strand DNA transfer. However, the decrease in plus-strand DNA transfer did not account for all of the observed decrease in viral DNA synthesis associated with A3G. These novel observations suggest that HIV-1 cDNA produced in the presence of A3G exhibits defects in primer tRNA processing, plus-strand DNA transfer, and integration. C1 NCI, AIDS Vaccine Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Univ Minnesota, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Microbiol, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Biochem Mol Biol & Biophys, Arnold & Mabel Beckman Ctr Transposon Res, Minneapolis, MN 55455 USA. RP Pathak, VK (reprint author), NCI, HIV Drug Resistance Program, SAIC Frederick Inc, POB B,Bldg 535, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov OI Thomas, James/0000-0002-2509-490X FU Intramural NIH HHS; NCI NIH HHS [N01-CO12400, N01CO12400]; NIAID NIH HHS [AI064046, AI39394, AI57735, K02 AI057735, R01 AI039394, R01 AI064046, R37 AI039394, R37 AI064046, R56 AI064046]; NIGMS NIH HHS [GM56615, R01 GM056615, R29 GM056615] NR 54 TC 191 Z9 197 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 7099 EP 7110 DI 10.1128/JVI.00272-07 PG 12 WC Virology SC Virology GA 180YW UT WOS:000247404900033 PM 17428871 ER PT J AU Sakai, A Takikawa, S Thimme, R Meunier, JC Spangenberg, HC Govindarajan, S Farci, P Emerson, SU Chisari, FV Purcell, RH Bukh, J AF Sakai, Akito Takikawa, Shingo Thimme, Robert Meunier, Jean-Christophe Spangenberg, Hans Christian Govindarajan, Sugantha Farci, Patrizia Emerson, Suzanne U. Chisari, Francis V. Purcell, Robert H. Bukh, Jens TI In vivo study of the HC-TN strain of hepatitis C virus recovered from a patient with fulminant hepatitis: RNA transcripts of a molecular clone (pHC-TN) are infectious in chimpanzees but not in Huh7.5 cells SO JOURNAL OF VIROLOGY LA English DT Article ID HYPERVARIABLE REGION-1; ANTIBODY-RESPONSE; IMMUNE-RESPONSES; CDNA-CLONE; NON-A; NON-B; SEQUENCE; IDENTIFICATION; GENOME; DETERMINANTS AB Both viral and host factors are thought to influence the pathogenesis of hepatitis C virus (HCV) infection. We studied strain HC-TN (genotype 1a), which caused fulminant hepatic failure in a patient and, subsequently, severe hepatitis in a chimpanzee (CH1422), to analyze the relationship between disease severity, host immune response, viral evolution, and outcome. A second chimpanzee (CH1581) was infected from CH1422 plasma, and a third chimpanzee (CH1579) was infected from RNA transcripts of a consensus cDNA of HC-TN (pHC-TN). RNA transcripts of pHC-TN did not replicate in Huh7.5 cells, which were recently found to be susceptible to infection with another fulminant HCV strain (JFH1). The courses of viremia were similar in the three animals. However, CH1581 and CH1579 developed a less severe acute hepatitis than CH1422. CH1579 and CH1422 resolved the infection, whereas CH1581 became persistently infected. CH1579 and CH1581, despite their differing outcomes, both developed significant intrahepatic cellular immune responses, but not antibodies to the envelope glycoproteins or neutralizing antibodies, during the acute infection. We analyzed the polyprotein sequences of virus recovered at five and nine time points from CH1579 and CH1581, respectively, during the first year of follow-up. High mutation rates and high proportions of nonsynonymous mutations suggested immune pressure and positive selection in both animals. Changes were not selected until after the initial decrease in virus titers and after the development of immune responses and hepatitis. Subsequently, however, mutations emerged repeatedly in both animals. Overall, our results indicate that disease severity and outcome of acute HCV infection depend primarily on the host response. C1 NIAID, Hepatitis Viruses Sect, Lab Infect Dis, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol & Expt Med, Div Expt Pathol, La Jolla, CA USA. Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA USA. Univ Copenhagen Hosp, Dept Infect Dis, Hvidovre, Denmark. Univ Copenhagen, Panum Inst, Dept Int Hlth Immunol & Microbiol, DK-1123 Copenhagen, Denmark. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Lab Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbukh@niaid.nih.gov RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU Intramural NIH HHS; NCI NIH HHS [CA76403, R01 CA076403] NR 50 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 7208 EP 7219 DI 10.1128/JVI.01774-06 PG 12 WC Virology SC Virology GA 180YW UT WOS:000247404900044 PM 17409145 ER PT J AU Berglund, P Finzi, D Bennink, JR Yewdell, JW AF Berglund, Peter Finzi, Diana Bennink, Jack R. Yewdell, Jonathan W. TI Viral alteration of cellular translational machinery increases defective ribosomal products SO JOURNAL OF VIROLOGY LA English DT Article ID SEMLIKI-FOREST-VIRUS; ENDOPLASMIC-RETICULUM; SINDBIS VIRUS; SEQUENCES DOWNSTREAM; EXPRESSION SYSTEM; IMMUNE-RESPONSES; GENE-EXPRESSION; MESSENGER-RNA; VECTORS; CELLS AB Here we show that cells expressing genes inserted into Semliki Forest virus (SFV) vectors generate a large fraction of defective ribosomal products (DRiPs) due to frequent initiation on downstream Met residues. In monopolizing the host cell translational machinery, SFV reduces levels of translation eukaryotic initiation factor 4E (eIF4E), diminishes phosphorylation of ribosome subunit S6, and phosphorylates translation initiation factor eIF2 alpha. We show that the last event is required for SFV mistranslation of inserted genes. Downstream initiation is suppressed by fusing inserted genes with the open reading frame encoding the SFV capsid, demonstrating that one function of the capsid element is to enable ribosomes to initiate translation in the proper location. These results show that in modifying translation, viral vectors can unpredictably increase the generation of truncated polypeptides and thereby the DRiP fraction of inserted gene products, which can potentially affect their yield, therapeutic efficacy, and immunogenicity. C1 NIAID, Lab Viral Dis, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Lab Viral Dis, NIH, 4 Ctr Dr, Bethesda, MD 20892 USA. EM jyewdell@niaid.nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Intramural NIH HHS NR 37 TC 20 Z9 21 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2007 VL 81 IS 13 BP 7220 EP 7229 DI 10.1128/JVI.00137-07 PG 10 WC Virology SC Virology GA 180YW UT WOS:000247404900045 PM 17459927 ER PT J AU Obias-Manno, D Scott, PE Kaczmarczyk, J Miller, M Pinnow, E Lee-Bishop, L Jones-London, M Chapman, K Kallgren, D Uhl, K AF Obias-Manno, Dulce Scott, Pamela E. Kaczmarczyk, Joseph Miller, Margaret Pinnow, Ellen Lee-Bishop, Lynda Jones-London, Michelle Chapman, Kennerly Kallgren, Deborah Uhl, Kathleen TI The food and drug administration office of Women's Health: Impact of science on regulatory policy SO JOURNAL OF WOMENS HEALTH LA English DT Article ID BREAST IMPLANT RUPTURE; TORSADES-DE-POINTES; CLINICAL-TRIALS; SEX-DIFFERENCES; QT INTERVAL; INDUCED PROLONGATION; GENDER DIFFERENCES; SILICONE; PHARMACOKINETICS; PHARMACODYNAMICS AB In 1994, the Food and Drug Administration Office of Women's Health (FDA-OWH) was created to provide leadership and policy direction for the Agency regarding issues of women's health. Within its first year, the FDA-OWH established a science program for women's health research, promoting the development of sound policy and regulation. In a little over a decade, the program has provided approximately $14 million to fund more than 100 women's health research studies covering a broad range of health topics affecting women across their lifespan. Some studies, such as those elucidating drug effects on QT prolongation in women and drug-dietary supplement interaction, have had significant influence on regulatory decisions. Other studies have provided sound scientific data on sex and gender differences supporting FDA guidelines to protect women's health. This paper describes the science program at the FDA-OWH, providing examples of how funded research impacts regulatory policy. C1 US FDA, OC, Off Womes Hlth, Rockville, MD 20857 USA. World Hlth Org, Dept Food Safety, Geneva, Switzerland. Hlth Resources & Serv Adm, Div Hlth Ctr Management, Dept Hlth & Human Serv, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Off Minor Hlth & Res, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Scott, PE (reprint author), US FDA, OC, Off Womes Hlth, 5600 Fishers Lane,Room 16-65 HF-8, Rockville, MD 20857 USA. EM Pamela.Scott@FDA.hhs.gov NR 76 TC 6 Z9 6 U1 4 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL PY 2007 VL 16 IS 6 BP 807 EP 817 DI 10.1089/jwh.2006.0135 PG 11 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 197JR UT WOS:000248551600004 PM 17678451 ER PT J AU Bergman, H Ferrucci, L Guralnik, J Hogan, DB Hummel, S Karunananthan, S Wolfson, C AF Bergman, Howard Ferrucci, Luigi Guralnik, Jack Hogan, David B. Hummel, Silvia Karunananthan, Sathya Wolfson, Christina TI Frailty: An emerging research and clinical paradigm - Issues and controversies SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID FUNCTIONAL DECLINE; GERIATRIC SYNDROME; METABOLIC SYNDROME; ELDERLY PERSONS; WOMENS HEALTH; OLDER PERSONS; BIRTH COHORT; CARDIOVASCULAR-DISEASE; DEVELOPMENTAL ORIGINS; PHYSICAL PERFORMANCE AB Clinicians and researchers have shown increasing interest in frailty. Yet, there is still considerable uncertainty regarding the concept and its definition. In this article, we present perspectives on key issues and controversies discussed by scientists from 13 different countries, representing a diverse range of disciplines, at the 2006 Second International Working Meeting on Frailty and Aging. The following fundamental questions are discussed: What is the distinction, if any, between frailty and aging? What is its relationship with chronic disease? Is frailty a syndrome or a series of age-related impairments that predict adverse outcomes? What are the critical domains in its operational definition? Is frailty a useful concept? The implications of different models and approaches are examined. Although consensus has yet to be attained, work accomplished to date has opened exciting new horizons. The article concludes with suggested directions for future research. C1 [Bergman, Howard] McGill Univ, Jewish Gen Hosp, Div Geriatr Med, Montreal, PQ H3T 1E2, Canada. [Ferrucci, Luigi] NIA, Clin Res Branch, Baltimore, MD 21224 USA. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Hogan, David B.] Univ Calgary, Div Geriatr Med, Calgary, AB T2N 1N4, Canada. [Hummel, Silvia; Karunananthan, Sathya] McGill Univ Montreal, Solidage Res Grp, Canadian Initiat Frailty & Aging, Jewish Gen Hosp, Quebec City, PQ, Canada. [Wolfson, Christina] McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. RP Bergman, H (reprint author), McGill Univ, Jewish Gen Hosp, Div Geriatr Med, 3755 Cote Ste Catherine, Montreal, PQ H3T 1E2, Canada. EM howard.bergman@mcgill.ca RI Hogan, David/I-4360-2013 OI Hogan, David/0000-0002-9462-5460 FU Intramural NIH HHS [Z99 AG999999] NR 70 TC 384 Z9 392 U1 1 U2 22 PU GERONTOLOGICAL SOC AMER PI WASHINGTON PA 1030 15TH ST NW, STE 250, WASHINGTON, DC 20005202-842 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2007 VL 62 IS 7 BP 731 EP 737 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 272AB UT WOS:000253828700007 PM 17634320 ER PT J AU Garcia, GN McCardle, P Nixon, SM AF Garcia, Gil Narro McCardle, Peggy Nixon, Stephanie M. TI Development of English literacy in Spanish-speaking children: Transforming research into practice SO LANGUAGE SPEECH AND HEARING SERVICES IN SCHOOLS LA English DT Editorial Material DE English language learners; reading; bilingual; education C1 NICHHD, Rockville, MD 20852 USA. US Dept Educ, Inst Sci Educ, Washington, DC USA. RP McCardle, P (reprint author), NICHHD, 6100 Execut Blvd,Suite 4B05, Rockville, MD 20852 USA. EM PM43Q@nih.gov FU Intramural NIH HHS NR 13 TC 0 Z9 0 U1 1 U2 2 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 0161-1461 J9 LANG SPEECH HEAR SER JI Lang. Speech Hear. Serv. Sch. PD JUL PY 2007 VL 38 IS 3 BP 213 EP 215 DI 10.1044/0161-1461(2007/022) PG 3 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 194UM UT WOS:000248369300006 PM 17625047 ER PT J AU Nixon, SM McCardle, P Leos, K AF Nixon, Stephanie M. McCardle, Peggy Leos, Kathleen TI Implications of research on English language learners for classroom and clinical practice SO LANGUAGE SPEECH AND HEARING SERVICES IN SCHOOLS LA English DT Editorial Material DE English language learners; reading; bilingual; education C1 NICHHD, Rockville, MD 20852 USA. US Dept Educ, Off English Language Acquisit, Washington, DC USA. RP McCardle, P (reprint author), NICHHD, 6100 Execut Blvd,Suite 4B05, Rockville, MD 20852 USA. EM PM43Q@nih.gov NR 34 TC 1 Z9 1 U1 0 U2 0 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 0161-1461 J9 LANG SPEECH HEAR SER JI Lang. Speech Hear. Serv. Sch. PD JUL PY 2007 VL 38 IS 3 BP 272 EP 277 DI 10.1044/0161-1461(2007/028) PG 6 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 194UM UT WOS:000248369300012 PM 17625053 ER PT J AU Hayun, M Okun, E Hayun, R Gafter, U Albeck, M Longo, DL Sredni, B AF Hayun, M. Okun, E. Hayun, R. Gafter, U. Albeck, M. Longo, D. L. Sredni, B. TI Synergistic effect of AS101 and Bryostatin-1 on myeloid leukemia cell differentiation in vitro and in an animal model SO LEUKEMIA LA English DT Article DE differentiation; HL-60; Bryostatin-1; PMA; AS101; gene array ID PROTEIN-KINASE-C; IMMUNOMODULATOR AS101; MONOCYTIC DIFFERENTIATION; ACTIVATES RAF-1; MURINE MODEL; EXPRESSION; INDUCTION; PATHWAY; ALPHA; HL-60 AB We evaluated the synergistic activity of AS101 (ammonium trichloro-(dioxoethylene-0-0')-tellurate) with the protein kinase C (PKC) activators, Bryostatin-1 and phorbol-12-myristate-13-acetate (PMA), on human myelocytic leukemia cell differentiation in vitro, and in a mouse model. Use of AS101 with Bryostatin-1 or with a low concentration of PMA resulted in the differentiation of HL-60 cell line to cells with characteristics of macrophages. A similar synergistic effect was found in vivo. Compared with mice treated with AS101 alone or with Bryostatin-1 alone, the infiltration of leukemic cells into the spleen and the peritoneum of mice treated with both compounds, as well as the number of the HL-60 colonies extracted from those organs, were markedly reduced. The antitumor effects were associated with significantly prolonged survival (100% for 125 days) of the treated mice. Finally, the mechanism of action of this antitumor effect was explored, and was found to involve the Ras/extracellular signal-regulated kinase signaling pathway. Combined treatment with AS101 and Bryostatin-1 synergistically increased p21(waf1) expression levels independently of p53. Upregulation of p21(waf1) was necessary for HL-60 cell differentiation, which was found to be both c-raf-1 and mitogen-activated protein kinase dependent. This study may have implications for the development of strategies to induce differentiation in myeloid leukemias, myelodysplasias and possibly in other malignancies. C1 Bar Ilan Univ, Safdie Inst AIDS & Immunol Res, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel. NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Rabin Med Ctr, Dept Nephrol, Petah Tiqwa, Israel. Rabin Med Ctr, Dept Pathol, Petah Tiqwa, Israel. RP Sredni, B (reprint author), Bar Ilan Univ, Safdie Inst AIDS & Immunol Res, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel. EM srednib@mail.biu.ac.il FU Intramural NIH HHS NR 37 TC 13 Z9 15 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2007 VL 21 IS 7 BP 1504 EP 1513 DI 10.1038/sj.leu.2404746 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 182HC UT WOS:000247494700021 PM 17508000 ER PT J AU Pfeuffer, J Shmuel, A Keliris, GA Steudel, T Merkle, H Logothetis, NK AF Pfeuffer, Josef Shmuel, Amir Keliris, Georgios A. Steudel, Thomas Merkle, Hellmut Logothetis, Nikos K. TI Functional MR imaging in the awake monkey: effects of motion on dynamic off-resonance and processing strategies SO MAGNETIC RESONANCE IMAGING LA English DT Article; Proceedings Paper CT International School on Magnetic Resonance and Brain Function CY MAY 21-28, 2006 CL Erice, ITALY DE functional imaging; monkey brain; high-field MR system ID ECHO-PLANAR; HUMAN BRAIN; 7 TESLA; FMRI; SPECTROSCOPY; RESPIRATION; ACQUISITION; ALGORITHMS; RESOLUTION; DISTORTION AB Functional MR imaging of the alert, behaving monkey is being used more and more often to detect activation patterns and guide electrophysiological research investigating the neural basis of behavior. Several labs have reported fMRI data from the awake monkey, but none of them has studied and systematically corrected the effects of monkeys' motion on fMRI time series. In this study, a significant refinement of acquisition and correction strategies is reported that can be used to minimize magnetic susceptibility artifacts induced by respiration and by jaw and body movement. Real-time acquisition of sensor signals (e.g., signals induced by jaw and body movement) and MR navigator data were combined to optimize fMRI signal-correction strategies. Within trials, the artifact-induced off-resonance changes were small and mainly reflected the effects of respiration; between trials, movements caused major changes of global frequency and shim (> 20 Hz/cm). Several methods were used to assess the stability of the fMRI series: k-space analysis ('dynamic intensity and off-resonance changes in k-space', dubbed DICK and DORK) and image analysis using a Laplace operator and a center-of-mass metric. The variability between trials made it essential to correct for inter-trial variations. On the other hand, images were sufficiently stable with our approach to perform fMRI evaluations on single trials before averaging of trials. Different motion correction strategies were compared: DORK, McFLIRT (rigid body model with three translations and three rotations) and 2D image alignment based on a center-of-mass detection (in-plane translation). The latter yielded the best results and proved to be fast and robust for intra- and inter-trial alignment. Finally, fMRI in the behaving monkey was tested for spatial and temporal reproducibility on a trial-to-trial basis. Highly activated voxels also displayed good reproducibility between trials. On average, the BOLD amplitude response to a short 3-s visual stimulus was close to 2%. (c) 2007 Elsevier Inc. All rights reserved. C1 Siemens Med Solut, MR Applicat Dev, D-91052 Erlangen, Germany. Max Planck Inst Biol Cybernet, Dept Physiol Cognit Proc, D-72076 Tubingen, Germany. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Pfeuffer, J (reprint author), Siemens Med Solut, MR Applicat Dev, Karl Schall Str 6, D-91052 Erlangen, Germany. EM josef.pfeuffer@siemens.com RI Shmuel, Amir/G-8690-2013; Keliris, Georgios A/B-6692-2008 OI Keliris, Georgios A/0000-0001-6732-1261 FU Intramural NIH HHS NR 29 TC 17 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD JUL PY 2007 VL 25 IS 6 SI SI BP 869 EP 882 DI 10.1016/j.mri.2007.03.002 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 197BV UT WOS:000248529200017 PM 17451900 ER PT J AU Galban, CJ Spencer, RG AF Galban, Craig J. Spencer, Richard G. TI Measurement of spin-lattice relaxation times and chemical exchange rates in multiple-site systems using progressive saturation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE T-1 measurement; chemical exchange; progressive saturation; creatine kinase; exchange rate measurement ID MAGNETIZATION-TRANSFER EXPERIMENTS; TRANSFER KINETIC MEASUREMENTS; RESONANCE-SPECTROSCOPY; INCOMPLETE SATURATION; QUANTITATION ERRORS; CREATINE-KINASE; RATE CONSTANTS; NMR; OPTIMIZATION; PARAMETERS AB A new method for measuring spin-lattice relaxation times and chemical exchange (CE) rate constants in multiple-site exchanging systems is described. The method, chemical exchange and T-1 measurement using progressive saturation (CUPS), was applied to determine T(1)s and analyze phosphorus exchange among phosphocreatine (PCr), ATP, and inorganic phosphate (Pi), mediated by creatine kinase (CK) and ATP synthase, using P-31-MRS. Two-site exchange was analyzed in vitro and in the rat leg, and three-site exchange was analyzed in the rat heart. Data were fitted to a model of progressive saturation incorporating T, relaxation and CE. For the in vitro system at 8.45T, we found T-1(PCr) = 2.86 s and T-1(gamma-ATP) = 1.72 s. Forthe rat gastrocnemius at 1.9T, we found T-1(PCr) = 6.60 s and T-1(gamma-ATP) = 2.06 s. For the rat heart at 9.4T, we found T-1(PCr) = 3.35 s, T-1(gamma-ATP) = 0.69 s, and T-1(Pi) = 1.83 s. All of these values were within 20% of literature values. Similarly, the determined exchange rates were in the same range as published values. Using simulations, we compared CUPS with transient saturation transfer as a method for measuring T(1)s and rates. The two methods showed similar sensitivity to noise. We conclude that CUPS is a viable alternative for measuring T(1)s and CE rates in exchanging systems. Magn Reson Med 58:8-18, 2007. (c) 2007 Wiley-Liss, Inc. C1 NIA, NMR Unit, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. RP Spencer, RG (reprint author), NIA, NMR Unit, Clin Invest Lab, NIH, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov FU Intramural NIH HHS NR 26 TC 5 Z9 5 U1 1 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 2007 VL 58 IS 1 BP 8 EP 18 DI 10.1002/mrm.21185 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196ND UT WOS:000248488400002 PM 17659623 ER PT J AU Zhang, Y Marenco, S Shen, J AF Zhang, Yan Marenco, Stefano Shen, Jun TI Correction of frequency and phase variations induced by eddy currents in localized spectroscopy with multiple echo times SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE in vivo spectroscopy; eddy currents; frequency and phase correction; water reference; measurement of glutamate ID TE-AVERAGED PRESS; HUMAN BRAIN; REFERENCE DECONVOLUTION; PROTON SPECTROSCOPY; REFERENCE SIGNALS; NMR-SPECTROSCOPY; B0 FIELD; QUANTITATION; WATER; COMPENSATION AB As a consequence of the time-varying magnetic field induced by eddy currents, frequency drifting occurs when the sampling window of localized spectroscopy continuously shifts. The frequency drifting and the concomitant phase variations can severely affect spectroscopy results when data are acquired with multiple echo times (TEs), such as in the measurement of glutamate (GIu) concentration using the TE-averaged method. Specifically, the averaged spectra are further broadened and distorted in the presence of residual eddy currents, and editing of the coupled spins of Glu C4 protons is affected, resulting in errors in the measured relative intensity ratio. Postacquisition correction using unsuppressed water as reference can effectively minimize this detrimental effect, as manifested by the significantly enhanced signal intensity. Also, it is demonstrated that the methyll signals of creatine (Cr) at 3.0 ppm and choline (Cho) at 3.2 ppm can be used as internal references in finding frequency and phase disparities between different TEs. Magn Reson Med 58:174-178, 2007. (c) 2007 Wiley-Liss, Inc. C1 NIMH, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 27 TC 9 Z9 9 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 2007 VL 58 IS 1 BP 174 EP 178 DI 10.1002/mrm.21265 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196ND UT WOS:000248488400020 PM 17659625 ER PT J AU Derbyshire, JA Sampath, S McVeigh, ER AF Derbyshire, J. Andrew Sampath, Smita McVeigh, Elliot R. TI Phase-sensitive cardiac tagging - REALTAG SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE myocardial function; cardiac imaging; myocardial tagging; contrast; phase sensitive reconstruction ID MOTION; HEART; CONTRAST; IMAGES; SSFP AB Fully inverting spins, instead of merely saturating them, provides superior contrast for tagging procedures. The resulting improvement in tag contrast-to-noise ratio (CNR) yields higher-precision tag detection. Also, thinner slices and hence reduced tag separations can be employed, providing displacement and strain measurements with better spatial resolution. Alternatively, the improved tag contrast can be used to obtain cine images covering a greater portion of the cardiac cycle. The use of standard magnitude reconstruction for images of these inversion tags causes rectification of the negative-valued signals from the tags, confounding the image interpretation. Therefore, a phase-sensitive reconstruction scheme of the inverted tags must be employed. Here we demonstrate the implementation of inverted tags with phase-sensitive reconstruction in a ramped-flip-angle, steady-state free precession (SSFP) sequence. Magn Reson Med 58:206-210, 2007. (c) 2007 Wiley-Liss, Inc. C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP McVeigh, ER (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM emcveigh@nih.gov FU Intramural NIH HHS NR 13 TC 3 Z9 3 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD JUL PY 2007 VL 58 IS 1 BP 206 EP 210 DI 10.1002/mrm.21264 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 196ND UT WOS:000248488400025 PM 17659612 ER PT J AU Berezovskaya, FS Novozhilov, AS Karev, GP AF Berezovskaya, Faina S. Novozhilov, Artem S. Karev, Georgy P. TI Population models with singular equilibrium SO MATHEMATICAL BIOSCIENCES LA English DT Article DE non-analytic equilibrium; ratio-dependent response; pathogen transmission; elliptic sector; population extinction ID PREDATOR-PREY SYSTEM; DETERMINISTIC EXTINCTION; INFECTIOUS-DISEASES; BIOLOGICAL-CONTROL; ONCOLYTIC VIRUSES; DYNAMICS; TRANSMISSION; PARASITES; GROWTH AB A class of models of biological population and communities with a singular equilibrium at the origin is analyzed; it is shown that these models can possess a dynamical regime of deterministic extinction, which is crucially important from the biological standpoint. This regime corresponds to the presence of a family of homoclinics to the origin, so-called elliptic sector. The complete analysis of possible topological structures in a neighborhood of the origin, as well as asymptotics to orbits tending to this point, is given. An algorithmic approach to analyze system behavior with parameter changes is presented. The developed methods and algorithm are applied to existing mathematical models of biological systems. In particular, we analyze a model of anticancer treatment with oncolytic viruses, a parasite-host interaction model, and a model of Chagas' disease. Published by Elsevier Inc. C1 Natl Inst Hlth, Bethesda, MD 20894 USA. Howard Univ, Washington, DC 20059 USA. RP Karev, GP (reprint author), Natl Inst Hlth, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM karev@ncbi.nlm.nih.gov RI Novozhilov, Artem/D-7544-2012; Novozhilov, Artem/C-9248-2013 OI Novozhilov, Artem/0000-0001-5469-2557 NR 45 TC 20 Z9 23 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JUL PY 2007 VL 208 IS 1 BP 270 EP 299 DI 10.1016/j.mbs.2006.10.006 PG 30 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 192JC UT WOS:000248196400016 PM 17174347 ER PT J AU Bohr, VA Vijg, J AF Bohr, Vilhelm A. Vijg, Jan TI Ageing advances - Opinion section - Preface SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Editorial Material C1 NIA, NIH, Lab Mol Gerontol, Baltimore, MD 21224 USA. Buck Inst Age Res, Novato, CA 94945 USA. RP Bohr, VA (reprint author), NIA, NIH, Lab Mol Gerontol, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov 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 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD JUL-AUG PY 2007 VL 128 IS 7-8 BP 455 EP 455 DI 10.1016/j.mad.2007.05.006 PG 1 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 212MB UT WOS:000249599500006 ER PT J AU Sato, Y Buchholz, DR Paul, BD Shi, YB AF Sato, Yukiyasu Buchholz, Daniel R. Paul, Bindu D. Shi, Yun-Bo TI A role of unliganded thyroid hormone receptor in postembryonic development in Xenopus laevis SO MECHANISMS OF DEVELOPMENT LA English DT Article DE Xenopus laevis; thyroid hormone receptor; transcriptional regulation; amphibian metamorphosis; derepression ID NUCLEAR RECEPTOR; N-COR; AMPHIBIAN METAMORPHOSIS; COREPRESSOR COMPLEX; FROG METAMORPHOSIS; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; HISTONE ACETYLATION; GENE-EXPRESSION; MUTANT MICE AB A fascinating feature of thyroid hormone (T3) receptors (TR) is that they constitutively bind to promoter regions of T3-response genes, providing dual functions. In the presence of T3, TR activates T3-inducible genes, while unliganded TR represses these same genes. Although this dual function model is well demonstrated at the molecular level, few studies have addressed the presence or the role of unliganded TR-induced repression in physiological settings. Here, we analyze the role of unliganded TR in Xenopus laevis development. The total dependence of amphibian metamorphosis upon T3 provides us a valuable opportunity for studying TR function in vivo. First, we designed a dominant negative form of TR-binding corepressor N-CoR (dnN-CoR) consisting of its receptor interacting domain. We confirmed its dominant negative activity by showing that dnN-CoR competes away the binding of endogenous N-CoR to unliganded TR and relieves unliganded TR-induced gene repression in frog oocytes. Next, we overexpressed dnN-CoR in tadpoles through transgenesis and analyzed its effect on gene expression and development. Quantitative RT-PCR revealed significant derepression of T3-response genes in transgenic animals. In addition, transgenic tadpoles developed faster than wild type siblings, with an acceleration of as much as 7 days out of the 30-day experiment. These data thus provide in vivo evidence for the presence and a role of unliganded TR-induced gene repression in physiological settings and strongly support our earlier model that unliganded TR represses T3-response genes in premetamorphic tadpoles to regulate the progress of development. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cell Regulat & Metab,NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Lab Gene Regulat & Dev, Program Cell Regulat & Metab,NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM Shi@helix.nih.gov FU Intramural NIH HHS [Z01 HD001901-12] NR 66 TC 40 Z9 40 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUL PY 2007 VL 124 IS 6 BP 476 EP 488 DI 10.1016/j.mod.2007.03.006 PG 13 WC Developmental Biology SC Developmental Biology GA 179EX UT WOS:000247273600007 PM 17482434 ER PT J AU Yabroff, KR McNeel, TS Waldron, WR Davis, WW Brown, ML Clauser, S Lawrence, WF AF Yabroff, K. Robin McNeel, Timothy S. Waldron, William R. Davis, William W. Brown, Martin L. Clauser, Steven Lawrence, William F. TI Health limitations and quality of life associated with cancer and other chronic diseases by phase of care SO MEDICAL CARE LA English DT Article DE health status; quality of life; health services research; neoplasms/epidemiology; chronic disease ID SEER-MEDICARE DATA; MAINTENANCE ORGANIZATION; MYOCARDIAL-INFARCTION; UNITED-STATES; COST; POPULATION; VALIDITY; INDEX; COMORBIDITY; UTILITIES AB Objective: To estimate health limitations and health-related quality of life (HRQL) associated with cancer and other chronic conditions in a nationally representative sample within a phase-of-care framework. Study Design and Setting: We used a nested case-control design to assess health limitations and HRQL in individuals reporting a breast, colorectal, prostate, or lung cancer diagnosis, or a diagnosis of arthritis, diabetes, heart disease, or hypertension compared with similar controls without these conditions. All subjects were selected from the 1986-1994 National Health Interview Surveys linked to mortality files in 1995, and classified into the initial, continuing, or last year of life phase of care. Health limitations and HRQL were compared for cases and controls for each condition with 2-sided statistical tests. Results: Across all conditions, individuals in the last year of life phase of care reported greater health limitations and lower HRQL, as measured by the Health Activities and Limitations Index (HALex), than did individuals in the initial and continuing phases of care. Compared with their matched controls, individuals with cancer or other chronic conditions were more likely to report health limitations and lower mean HALex values in the initial, continuing, and last year of life phases of care (P < 0.05). Conclusions: We observed greater health limitations and lower HRQL associated with cancer and other chronic diseases compared with similar individuals without these conditions. The phase-of-care framework used in this study seems to be applicable to the assessment of HRQL for cancer and other chronic diseases. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Agcy Healthcare Res & Qual, Rockville, MD USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 39 TC 24 Z9 24 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2007 VL 45 IS 7 BP 629 EP 637 DI 10.1097/MLR.0b013e318045576a PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 186OR UT WOS:000247788500007 PM 17571011 ER PT J AU Couto, FM Minn, AH Pise-Masison, CA Radonovich, M Brady, JN Hanson, M Fernandez, LA Wang, P Kendziorski, C Shalev, A AF Couto, Francesca M. Minn, Alexandra H. Pise-Masison, Cynthia A. Radonovich, Mike Brady, John N. Hanson, Matthew Fernandez, Luis A. Wang, Ping Kendziorski, Christina Shalev, Anath TI Exenatide blocks JAK1-STAT1 in pancreatic beta cells SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID GLUCAGON-LIKE PEPTIDE-1; EXENDIN-4; EXPRESSION; PROTEIN; APOPTOSIS; INCRETIN; PATHWAY; RATS AB Exenatide (Ex-4) is an antidiabetic drug that acts through the glucagon-like peptide 1 receptor and has recently been approved for the treatment of type 2 diabetes mellitus. Ex-4 also has been shown to affect beta cell gene expression and increase beta cell mass in rodent models of type 1 diabetes mellitus, but the mechanisms are not fully understood. We therefore analyzed the pathways affected by Ex-4 in human islets by using oligonucleotide microarrays and the PathwayStudio software (Ariadne Genomics, Rockville, MD). We identified the JAK1-STAT1 pathway as a novel target of Ex-4 and confirmed the Ex-4-mediated down-regulation of JAK1 and STAT1 by quantitative reverse transcription-polymerase chain reaction in human islets and INS-1 cells. JAK1-STAT1 is the major signaling pathway mediating the interferon gamma effects on beta cell apoptosis in type 1 diabetes mellitus. Thus, these findings suggest that Ex-4 treatment may also be beneficial in type 1 diabetes mellitus, where it may help protect beta cells from cytokine-induced cell death by inhibiting JAK1-STAT1. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Dept Med, Madison, WI 53706 USA. NIH, NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Surg, Madison, WI 53706 USA. Univ Wisconsin, Madison, WI 53706 USA. RP Shalev, A (reprint author), H4-526 Clin Sci Ctr, Madison, WI 53792 USA. EM as7@medicine.wisc.edu FU NIA NIH HHS [AG000265-08] NR 15 TC 10 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2007 VL 56 IS 7 BP 915 EP 918 DI 10.1016/j.metabol.2007.02.004 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 182ZK UT WOS:000247542300010 PM 17570252 ER PT J AU Womack, J Tien, PC Feldman, J Shin, JH Fennie, K Anastos, K Cohen, MH Bacon, MC Minkoff, H AF Womack, Julie Tien, Phyllis C. Feldman, Joseph Shin, Ja Hyun Fennie, Kristopher Anastos, Kathryn Cohen, Mardge H. Bacon, Melanie C. Minkoff, Howard TI Obesity and immune cell counts in women SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PERIPHERAL-BLOOD; INTERAGENCY HIV; LYMPHOCYTE SUBSETS; ADIPOSE-TISSUE; TNF-ALPHA; OVERWEIGHT; WEIGHT; LEPTIN; PREVALENCE; METABOLISM AB Obesity is common in women and is associated with a number of adverse health outcomes including cardiovascular disease, infectious diseases, and cancer. We explore the relationship between obesity and immune cell counts in women in a longitudinal study of 322 women from 1999 through 2003 enrolled as HIV-negative comparators in the Women's Interagency HIV Study. Body mass index (BMI, kg/m(2)) was categorized as normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), obese (BMI 30-34.9), and morbidly obese (BMI >= 35). CD4 and CD8 counts and percents and total lymphocyte and white blood cell (WBC) counts were measured annually using standardized techniques. A mixed model repeated measures analysis was performed using an autoregressive correlation matrix. At the index visit, 61% of women were African American; mean age was 35 years, and median BMI was 29 kg/m(2). Immunologic parameters were in the reference range (median CD4 count, 995 cells/mm(3); CD8 count, 488 cells/mm(3); total lymphocyte count, 206 cells/min(3); median WBC, 6 x 10(3) cells/mm(3)) .In multivariate analyses, being overweight, obese, or morbidly obese were independently associated with higher CD4, total lymphocyte, and WBC counts than being normal weight; morbid obesity was associated with a higher CD8 count. The strongest associations between body weight and immune cell counts were demonstrated in the morbidly obese. Increasing body weight is associated with higher CD4, CD8, total lymphocyte, and WBC counts in women. Investigation into the impact of obesity on immune function and long-term adverse outcomes is needed. (c) 2007 Elsevier Inc. All rights reserved. C1 Yale Univ, Sch Nursing, New Haven, CT 06536 USA. Univ Calif San Francisco, Dept Med, San Francisco & Infect Dis Sect, San Francisco, CA 94121 USA. Suny Downstate Med Ctr, Dept Prevent Med, Brooklyn, NY 11203 USA. Montefiore Med Ctr, Dept Med, Dept Epidemiol & Publ Hlth, Bronx, NY 10467 USA. Cook Cty Hosp, CORE Ctr, Dept Med, Bur Hlth Serv, Chicago, IL 60612 USA. NIH, NIAID, Div Aids, Bethesda, MD 20817 USA. Suny Downstate Med Ctr, Maimonides Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. RP Womack, J (reprint author), Yale Univ, Sch Nursing, New Haven, CT 06536 USA. EM julie.womack@yale.edu FU NCRR NIH HHS [MO1-RR-00079, M01 RR000083, M01 RR000079, MO1-RR-00083, MO1-RR-00071, M01 RR000071]; NIAID NIH HHS [U01 AI034994, UO1-AI-42590, UO1-AI-34994, U01 AI035004-14, U01 AI035004, K23 AI066943-02, U01 AI034989, UO1-AI-34989, U01 AI034993, K23 AI066943, UO1-AI-31834, U01 AI034993-14, U01 AI031834, U01 AI031834-15, U01 AI042590-10, UO1-AI-34993, U01 AI034989-14, UO1-AI-35004, U01 AI042590, U01 AI034994-14]; NICHD NIH HHS [UO1-HD-23632, U01 HD032632-14]; NINR NIH HHS [F31 NR009886-02, F31 NR009886] NR 31 TC 49 Z9 53 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2007 VL 56 IS 7 BP 998 EP 1004 DI 10.1016/j.metabol.2007.03.008 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 182ZK UT WOS:000247542300022 PM 17570264 ER PT J AU Zhang, Y Adams, IP Ratledge, C AF Zhang, Ying Adams, Ian P. Ratledge, Colin TI Malic enzyme: the controlling activity for lipid production? Overexpression of malic enzyme in Mucor circinelloides leads to a 2.5-fold increase in lipid accumulation SO MICROBIOLOGY-SGM LA English DT Article ID FATTY-ACID BIOSYNTHESIS; ATP-CITRATE LYASE; MORTIERELLA-ALPINA; CARNITINE ACETYLTRANSFERASE; OLEAGINOUS MICROORGANISMS; RHODOSPORIDIUM-TORULOIDES; ASPERGILLUS-NIDULANS; FILAMENTOUS FUNGI; GENOME SEQUENCE; GENE-EXPRESSION AB Malic enzyme (ME; NADP(+)-dependent; EC 1.1.1.40) has been postulated to be the rate-limiting step for fatty acid biosynthesis in oleaginous fungi in which the extent of lipid accumulation is below the maximum possible. The genes encoding the isoform of ME involved in fatty acid synthesis were identified in Mucor circinelloides and Mortierella alpina, two commercially useful oil-producing fungi, using degenerate primers. Both showed high similarity with ME genes from other micro-organ isms. The whole-length ME gene from each source was cloned into a leucine auxotroph of Mc. circinelloides and placed under the control of the constitutive glyceralclehyde-3-phosphate dehydrogenase gene (gpd1) promoter. After confirming correct expression of the ME genes, the two recombinant strains were grown in fully controlled, submerged-culture bioreactors using a high C : N ratio medium for lipid accumulation. Activities of ME were increased by two- to threefold and the lipid contents of the cells, in both recombinants, were increased from 12 % of the biomass to 30 %. Simultaneously, the degree of fatty acid desaturation increased slightly. Thus, increased expression of the ME gene leads to both increased biosynthesis of fatty acids and formation of unsaturated fatty acids, including gamma-linolenic acid (18 : 3 n-6). At the end of lipid accumulation (96 h), ME activity in the recombinant strains had ceased, as it had done in the parent wild-type cells, indicating that additional, but unknown, controls over its activity must be in place to account for this loss of activity: this may be due to the presence of a specific ME-cleaving enzyme. The hypothesis that the rate-limiting step of fatty acid biosynthesis is therefore the supply of NADPH, as generated specifically and solely by ME, is therefore considerably strengthened by these results. C1 Univ York, Ctr Novel Agr Prod, Dept Biol, York YO10 5DD, N Yorkshire, England. Univ Hull, Dept Biol Sci, Kingston Upon Hull HU6 7RX, N Humberside, England. RP Ratledge, C (reprint author), NIDCR, NIH, 9000 Rockville Oike, Bethesda, MD 20892 USA. EM c.ratledge@hull.ac.uk NR 55 TC 107 Z9 123 U1 1 U2 31 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUL PY 2007 VL 153 BP 2013 EP 2025 DI 10.1099/mic.0.2006/002683-0 PN 7 PG 13 WC Microbiology SC Microbiology GA 191TM UT WOS:000248154900003 PM 17600047 ER PT J AU Smith, KA Rex, EB Komuniecki, RW AF Smith, Katherine A. Rex, Elizabeth B. Komuniecki, Richard W. TI Are Caenorhabditis elegans receptors useful targets for drug discovery: Pharmacological comparison of tyramine receptors with high identity from C-elegans (TYRA-2) and Brugia malayi (Bm4) SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE tyramine receptor; nematode; Brugia malayi; Caenorhabditis elegans ID PROTEIN-COUPLED RECEPTORS; MOLLUSCAN OCTOPAMINE RECEPTOR; BOMBYX-MORI; AMINO-ACID; FUNCTIONAL EXPRESSION; ADENYLATE-CYCLASE; MOLECULAR-CLONING; NERVOUS-SYSTEM; SEROTONIN; DROSOPHILA AB The biogenic amine, tyramine (TA), modulates a number of key processes in nematodes and a number of TA-specific receptors have been identified. In the present study, we have identified a putative TA receptor (Bm4) in the recently completed Brugia malayi genome and compared its pharmacology to its putative Caenorhabditis elegans orthologue, TYRA-2, under identical expression and assay conditions. TYRA-2 and Bm4 are the most closely related C elegans and B. malayi BA receptors and differ by only 14 aa in the TM regions directly involved in ligand binding. Membranes from HEK-293 cells stably expressing Bm4 exhibited specific, saturable, high affinity, [H-3]LSD and [H-3]TA binding with K(d)s of 18.1 +/- 0.93 and 15.1 +/- 0.2 nM, respectively. More importantly, both TYRA-2 and Bm4 TA exhibited similar rank orders of potencies for a number of potential tyraminergic ligands. However, some significant differences were noted. For example, chloropromazine exhibited an order of magnitude higher affinity for Bm4 than TYRA-2 (pK(i)s of 7.6 +/- 0.2 and 6.49 +/- 0.1, respectively). In contrast, TYRA-2 had significantly higher affinity for phentolamine than Bm4. These results highlight the utility of the nearly completed B. malayi genome and the importance of using receptors from individual parasitic nematodes for drug discovery. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Toledo, Dept Biol Sci, Toledo, OH 43606 USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Komuniecki, RW (reprint author), Univ Toledo, Dept Biol Sci, 2801 W Bancroft St, Toledo, OH 43606 USA. EM rkomuni@uoft02.utoledo.edu FU NIAID NIH HHS [R01 AI072644, R01 AI045147, AI045147] NR 47 TC 7 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 2007 VL 154 IS 1 BP 52 EP 61 DI 10.1016/j.molbiopara.2007.04.004 PG 10 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 190LH UT WOS:000248059800006 PM 17537528 ER PT J AU Woynarowski, JM Krugliak, M Ginsburg, H AF Woynarowski, Jan M. Krugliak, Miriam Ginsburg, Hagai TI Pharmacogenomic analyses of targeting the AT-rich malaria parasite genome with AT-specific alkylating drugs SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; malaria; A/T-rich; AT islands; matrix attachment regions (MARs, S/MARs); Centromeres; nucleosome-free regions; anti-malarial activity; adozelesin; bizelesin ID QUINOLINE-CONTAINING DRUGS; PLASMODIUM-FALCIPARUM; IN-VITRO; PHASE-I; ATTACHMENT-REGIONS; ANTICANCER DRUGS; CELLULAR-DNA; BIZELESIN; ADOZELESIN; SEQUENCE AB Human malaria parasites, including the most lethal Plasmodium,falciparum, are increasingly resistant to existing antimalarial drugs. One remarkable opportunity to selectively target P falciparum stems from the unique AT-richness of its genome (80% A/T, relative to 60% in human DNA). To rationally explore this opportunity, we used drugs (adozelesin and bizelesin) which distinctly target AT-rich minisatellites and an in silico approach for genome-wide analysis previously experimentally validated in human cells [Woynarowski JM, Trevino AV, Rodriguez KA, Hatches SC, Benham CJ. AT-rich islands in genomic DNA as a novel target for AT-specific DNA-reactive antitumor drugs. J Biol Chem 2001;276:40555-66]. Both drugs demonstrate a potent, rapid and irreversible inhibition of the cultured P.falciparum (50% inhibition at 110 and 10 +/- 2.3 pM, respectively). This antiparasital activity reflects most likely drug binding to specific super-AT-rich regions. Relative to the human genome, the P. falciparum genome shows 3.9- and 7-fold higher frequency of binding sites for adozelesin and bizelesin, respectively. The distribution of these sites is non-random with the most prominent clusters found in large unique minisatellites [median size 3.5 kbp of nearly pure A/T, with multiple converging repeats but no shared consensus other than (A/T)(n)]. Each of the fourteen P. falciparum chromosomes contains only one such "super-AT island" located within similar to 3-7.5 kbp of gene-free and nucleosome-free loci. Important functions of super-AT islands are suggested by their exceptional predicted potential to serve as matrix attachment regions (MARs) and a precise co-localization with the putative centromeres. Conclusion: Super-AT islands, identified as unique domains in the P.falciparum genome with presumably crucial functions, offer therapeutically exploitable opportunity for new antimalarial strategies. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Radiat Oncol, San Antonio, TX 78245 USA. Hebrew Univ Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel. RP Woynarowski, JM (reprint author), NCI, DEA PCRB, 6116 Execut Blvd, Bethesda, MD 20892 USA. EM woynarowskij@mail.nih.gov; hagai@vms.huji.ac.il NR 52 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 2007 VL 154 IS 1 BP 70 EP 81 DI 10.1016/j.molbiopara.2007.04.009 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 190LH UT WOS:000248059800008 PM 17524501 ER PT J AU Yedjou, CG Tchounwou, PB AF Yedjou, Clement G. Tchounwou, Paul B. TI In-vitro cytotoxic and genotoxic effects of arsenic trioxide on human leukemia (HL-60) cells using the MTT and alkaline single cell gel electrophoresis (Comet) assays SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Recent Advances in Environmental Health Research CY SEP 18-21, 2005 CL Jackson, MS DE arsenic trioxide; cytotoxixity; genotoxicity; HL-60 cells; promyelocytic leukemia ID ACUTE PROMYELOCYTIC LEUKEMIA; TRANSCRIPTIONAL ACTIVATION; STRESS GENES; DNA-DAMAGE; CARCINOGENESIS; APOPTOSIS; TOXICITY; METABOLITES; MECHANISMS; EXPRESSION AB Although arsenic trioxide (ATO) has been the subject of toxicological research, in vitro cytotoxicity and genotoxicity studies using relevant cell models and uniform methodology are not well elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by ATO in a human leukemia (HL-60) cell line using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and alkaline single cell gel electrophoresis (Comet) assays, respectively. HL-60 cells were treated with different doses of ATO for 24 h prior to cytogenetic assessment. Data obtained from the MTT assay indicated that ATO significantly (P < 0.05) reduced the viability of HL-60 cells in a dose-dependent manner, showing a LD50 value of 6.4 +/- 0.6 mu g/mL. Data generated from the comet assay also indicated a significant dose-dependent increase in DNA damage in HL-60 cells associated with ATO exposure. We observed a significant increase (P < 0.05) in comet tall length, tall arm and tall moment, as well as in percentages of DNA cleavage at all doses tested, showing an evidence of ATO-induced genotoxic damage in HL60 cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by heavy metals like arsenic. Taken together, our findings suggest that ATO exposure significantly (P < 0.05) reduces cellular viability and induces DNA damage in HL-60 cells as assessed by MTT and alkaline single cell gel electrophoresis assays, respectively. C1 Jackson State Univ, Coll Sci Engn & Technol, Ctr Environm Hlth, Mol Toxicol Res Lab,NIH, Jackson, MS USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Ctr Environm Hlth, Mol Toxicol Res Lab,NIH, 1400 Lynch St,Box 18540, Jackson, MS USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [1 G12 RR13459, G12 RR013459] NR 34 TC 30 Z9 31 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD JUL PY 2007 VL 301 IS 1-2 BP 123 EP 130 DI 10.1007/s11010-006-9403-4 PG 8 WC Cell Biology SC Cell Biology GA 184YV UT WOS:000247679400012 PM 17216127 ER PT J AU Kinyamu, HK Archer, TK AF Kinyamu, H. Karimi Archer, Trevor K. TI Proteasome activity modulates chromatin modifications and RNA polymerase II phosphorylation to enhance glucocorticoid receptor-mediated transcription SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE H3; REGULATED TRANSCRIPTION; DEPENDENT TRANSCRIPTION; NUCLEAR RECEPTORS; 26S PROTEASOME; HUMAN GENOME; IN-VIVO; ASSOCIATION; CELLS; PROGESTERONE AB The 26S proteasome modulates steroid hormone receptor-dependent gene transcription at least in part by regulating turnover and recycling of receptor/transcriptional DNA complexes, thereby ensuring continued hormone response. For the glucocorticoid receptor (GR), inhibition of proteasome-mediated proteolysis or RNA interference-mediated depletion of specific proteasome subunits results in an increase in gene expression. To facilitate transcription, proteasome inhibition alters at least two features associated with modification of chromatin architecture and gene transcription. First, proteasome inhibition increases trimethyl histone H3K4 levels with a corresponding accumulation of this modification on GR-regulated promoters in vivo. Secondly, global levels of phosphorylated RNA polymerase II (Pol II) increase, together with hormone-dependent association of the phosphorylated Pol II, with the promoter and the body of the activated gene. We propose that apart from modulating receptor turnover, the proteasome directly influences both the transcription machinery and chromatin structure, factors integral to nuclear receptor-regulated gene transcription. C1 Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Chromatin & Gene Express Sect, Lab Mol Carcinogenesis,NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Natl Inst Environm Hlth Sci, Mol Carcinogenesis Lab, Chromatin & Gene Express Sect, Lab Mol Carcinogenesis,NIH, 111 Alexander Dr,POB 12233,MD C4-01, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov FU Intramural NIH HHS NR 54 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2007 VL 27 IS 13 BP 4891 EP 4904 DI 10.1128/MCB.02162-06 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183JN UT WOS:000247569200024 PM 17438138 ER PT J AU Frydrychova, RC Biessmann, H Konev, AY Golubovsky, MD Johnson, J Archer, TK Mason, JM AF Frydrychova, Radmila Capkova Biessmann, Harald Konev, Alexander Y. Golubovsky, Mikhail D. Johnson, Jessica Archer, Trevor K. Mason, James M. TI Transcriptional activity of the telomeric retrotransposon HeT-A in Drosophila melanogaster is stimulated as a consequence of subterminal deficiencies at homologous and nonhomologous telomeres SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID POSITION EFFECT VARIEGATION; NUCLEAR-ORGANIZATION; CHROMATIN-STRUCTURE; MAINTAIN TELOMERES; CHROMOSOME ENDS; WHITE LOCUS; EXPRESSION; ELONGATION; MECHANISM; ELEMENTS AB Drosophila melanogaster telomeres have two DNA domains: a terminal array of retrotransposons and a subterminal repetitive telomere-associated sequence (TAS), a source of telomere position effect (TPE). We reported previously that deletion of the 2L TAS array leads to dominant suppression of TPE by stimulating in trans expression of a telomeric transgene. Here, we compared the transcript activities of a w transgene inserted between the retrotransposon and TAS arrays at the 2L telomere in genotypes with different lengths of the 2L TAS. In contrast to individuals bearing a wild-type 2L homologue, flies with a TAS deficiency showed a significant increase in the level of telomeric w transcript during development, especially in pupae. Moreover, we identified a read-through w transcript initiated from a retrotransposon promoter in the terminal array. Read-through transcript levels also significantly increased with the presence of a 2L TAS deficiency in trans, indicating a stimulating force of the TAS deficiency on retrotransposon promoter activity. The read-through transcript contributes to total w transcript, although most w transcript originates at the w promoter. While silencing of transgenes in nonhomologous telomeres is suppressed by 2L TAS deficiencies, suggesting a global effect, the overall level of HeT-A transcripts is not increased under similar conditions. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Calif Irvine, Dev Biol Ctr, Irvine, CA 92697 USA. NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. RP Mason, JM (reprint author), NIEHS, Mol Genet Lab, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM masonj@niehs.nih.gov RI Capkova Frydrychova, Radmila/H-4187-2014; Konev, Alexander/J-4401-2015 OI Konev, Alexander/0000-0002-4497-6377 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM056729, GM56729] NR 54 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2007 VL 27 IS 13 BP 4991 EP 5001 DI 10.1128/MCB.00515-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 183JN UT WOS:000247569200032 PM 17470550 ER PT J AU Berthet, C Rodriguez-Galan, MC Hodge, DL Gooya, J Pascal, V Young, HA Keller, J Bosselut, R Kaldis, P AF Berthet, Cyril Rodriguez-Galan, Maria Cecilia Hodge, Deborah L. Gooya, John Pascal, Veronique Young, Howard A. Keller, Jonathan Bosselut, Remy Kaldis, Philipp TI Hematopoiesis and thymic apoptosis are not affected by the loss of Cdk2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DEPENDENT KINASE INHIBITORS; CELL-CYCLE ENTRY; THYMOCYTE APOPTOSIS; PROGENITOR CELLS; DIFFERENTIATION; PROLIFERATION; STEM; ACTIVATION; PROTEIN; GENE AB Cell cycle regulation is essential for proper homeostasis of hematopoietic cells. Cdk2 is a major regulator of S phase entry, is activated by mitogenic cytokines, and has been suggested to be involved in antigen-induced apoptosis of T lymphocytes. The role of Cdk2 in hematopoietic cells and apoptosis in vivo has not yet been addressed. To determine whether Cdk2 plays a role in these cells, we performed multiple analyses of bone marrow cells, thymocytes, and splenocytes from Cdk2 knockout mice. We found that Cdk2 is not required in vivo to induce apoptosis in lymphocytes, a result that differs from previous pharmacological in vitro studies. Furthermore, thymocyte maturation was not affected by the lack of Cdk2. We then analyzed the hematopoietic stem cell compartment and found similar proportions of stem cells and progenitors in Cdk2(-/-) and wild-type animals. Knockouts of Cdk2 inhibitors (p21, p27) affect stem cell renewal, but a competitive graft experiment indicated that renewal and multilineage differentiation are normal in the absence of Cdk2. Finally, we stimulated T lymphocytes or macrophages to induce proliferation and observed normal reactivation of Cdk2(-/-) quiescent cells. Our results indicate that Cdk2 is not required for proliferation and differentiation of hematopoietic cells in vivo, although in vitro analyses consider Cdk2 to be a major player in proliferation and apoptosis in these cells and a potential target for therapy. C1 NCI, Canc Res Ctr, Mouse Canc Genet Program, Frederick, MD 21702 USA. NCI, Canc Res Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp, Basic Res Program, Frederick, MD 21702 USA. NCI, Natl Inst Hlth, Lab Immune Cell Biol, Cellular Immunol Lab, Bethesda, MD 20892 USA. RP Kaldis, P (reprint author), Medimmune Inc, Gaithersburg, MD 20878 USA. EM kaldis@ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU Intramural NIH HHS NR 37 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2007 VL 27 IS 14 BP 5079 EP 5089 DI 10.1128/MCB.00029-07 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 189TB UT WOS:000248010300002 PM 17485443 ER PT J AU Miller-Butterworth, CM Murphy, WJ O'Brien, SJ Jacobs, DS Springer, MS Teeling, EC AF Miller-Butterworth, Cassandra M. Murphy, William J. O'Brien, Stephen J. Jacobs, David S. Springer, Mark S. Teeling, Emma C. TI A family matter: Conclusive resolution of the taxonomic position of the long-fingered bats, Miniopterus SO MOLECULAR BIOLOGY AND EVOLUTION LA English DT Article DE Miniopterus; long-fingered bats; Vespertilionidae; Molossidae; Chiroptera; phylogeny; molecular dating ID PHYLOGENETIC-RELATIONSHIPS; REPRODUCTIVE-CYCLE; VOMERONASAL ORGAN; VESPERTILIONIDAE; CHIROPTERA; EVOLUTION; SCHREIBERSII; MORPHOLOGY; ECHOLOCATION; BIOGEOGRAPHY AB The long-fingered bats (Miniopterus sp.) are among the most widely distributed mammals in the world. However, despite recent focus on the systematics of these bats, their taxonomic position has not been resolved. Traditionally, they are considered to be sole members of Miniopterinae, I of 5 subfamilies within the largest family of bats, the Vespertilionidae. However, this classification has increasingly been called into question. Miniopterines differ extensively from other vespertilionids in numerous aspects of morphology, embryology, immunology, and, most recently, genetics. Recent molecular studies have proposed that the miniopterines are sufficiently distinct from vespertilionids that Miniopterinae should be elevated to full familial status. However, controversy remains regarding the relationship of the putative family, Miniopteridae to existing Vespertilionidae and to the closely related free-tailed bats, the Molossidae. We report here the first conclusive analysis of the taxonomic position of Miniopterus relative to all other bat families. We generated one of the largest chiropteran data sets to date, incorporating similar to 11 kb of sequence data from 16 nuclear genes, from representatives of all bat families and 2 Miniopterus species. Our data confirm the distinctiveness of Miniopterus, and we support previous recommendations to elevate these bats to full familial status. We estimate that they diverged from all other bat species approximately 49-38 MYA, which is comparable to most other bat families. Furthermore, we find very strong support from all phylogenetic methods for a sister group relationship between Miniopteridae and Vespertilionidae. The Molossidae diverged from these lineages approximately 54-43 MYA and form a sister group to the Miniopteridae-Vespertilionidae clade. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA. Texas A&M Univ, Coll Vet Med, College Stn, TX 77843 USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. Univ Cape Town, Dept Zool, ZA-7700 Rondebosch, South Africa. Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. Univ Coll Dublin, Sch Biol & Environm Sci, Dublin 2, Ireland. RP Miller-Butterworth, CM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15260 USA. EM cbutterworth@hgen.pitt.edu; emma.teeling@ucd.ie RI Self, Casey/B-6871-2011; Miller-Butterworth, Cassandra/H-5994-2013; Jacobs, David/L-9118-2013 FU NCI NIH HHS [N01-CO-12400] NR 66 TC 96 Z9 102 U1 2 U2 30 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0737-4038 J9 MOL BIOL EVOL JI Mol. Biol. Evol. PD JUL PY 2007 VL 24 IS 7 BP 1553 EP 1561 DI 10.1093/molbev/msm076 PG 9 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 188TV UT WOS:000247943100012 PM 17449895 ER PT J AU Scarzello, AJ Romero-Weaver, AL Maher, SG Veenstra, TD Zhou, M Qin, A Donnelly, RP Sheikh, F Gamero, AM AF Scarzello, Anthony J. Romero-Weaver, Ana L. Maher, Stephen G. Veenstra, Timothy D. Zhou, Ming Qin, Angel Donnelly, Raymond P. Sheikh, Faruk Gamero, Ana M. TI A mutation in the SH2 domain of STAT2 prolongs tyrosine phosphorylation of STAT1 and promotes type IIFN-induced apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID STIMULATED-GENE FACTOR-3; SERINE PHOSPHORYLATION; DNA-BINDING; INTERFERON-ALPHA; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; I INTERFERONS; CELL-LINES; GAMMA; ACTIVATION AB Type I interferons (IFN-alpha/beta) induce apoptosis in certain tumor cell lines but not others. Here we describe a mutation in STAT2 that confers an apoptotic effect in tumor cells in response to type I IFNs. This mutation was introduced in a conserved motif, PYTK, located in the STAT SH2 domain, which is shared by STAT1, STAT2, and STAT3. To test whether the tyrosine in this motif might be phosphorylated and affect signaling, Y631 of STAT2 was mutated to phenylalanine (Y631F). Although it was determined that Y631 was not phosphorylated, the Y631F mutation conferred sustained signaling and induction of IFN-stimulated genes. This prolonged IFN response was associated with sustained tyrosine phosphorylation of STAT1 and STAT2 and their mutual association as heterodimers, which resulted from resistance to dephosphorylation by the nuclear tyrosine phosphatase TcPTP. Finally, cells bearing the Y631F mutation in STAT2 underwent apoptosis after IFN-alpha stimulation compared with wild-type STAT2. Therefore, this mutation reveals that a prolonged response to IFN-alpha could account for one difference between tumor cell lines that undergo IFN-alpha-induced apoptosis compared with those that display an antiproliferative response but do not die. C1 NCI, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. Ctr Drug Evaluat & Res, Div Therapeut Prot, Food & Drug Adm, Bethesda, MD 20892 USA. RP Gamero, AM (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. EM gameroa@ncifcrf.gov OI Maher, Stephen/0000-0003-0126-7906 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400] NR 36 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2007 VL 18 IS 7 BP 2455 EP 2462 DI 10.1091/mbc.E06-09-0843 PG 8 WC Cell Biology SC Cell Biology GA 183WV UT WOS:000247604000007 PM 17442890 ER PT J AU Wang, J Sun, HQ Macia, E Kirchhausen, T Watson, H Bonifacino, JS Yin, HL AF Wang, Jing Sun, Hui-Qiao Macia, Eric Kirchhausen, Tomas Watson, Hadiya Bonifacino, Juan S. Yin, Helen L. TI PIP promotes the recruitment of the GGA adaptor proteins to the trans-Golgi TS recognition of the ubiquitin network and regulates their sorting signal SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; FACTOR-BINDING PROTEINS; AMINO-TERMINAL DOMAIN; SACCHAROMYCES-CEREVISIAE; MOLECULAR-MECHANISM; GAT DOMAIN; MEMBRANE; CLATHRIN; ARF; TRAFFICKING AB Phosphatidylinositol 4 phosphate (PI4P) is highly enriched in the trans-Golgi network (TGN). Here we establish that PI4P is a key regulator of the recruitment of the GGA clathrin adaptor proteins to the TGN and that PI4P has a novel role in promoting their recognition of the ubiquitin (Ub) sorting signal. Knockdown of PI4KII alpha by RNA interference (RNAi), which depletes the TGN's PI4P, impaired the recruitment of the GGAs to the TGN. GGAs bind PI4P primarily through their GAT domain, in a region called C-GAT, which also binds Ub but not Arf1. We identified two basic residues in the GAT domain that are essential for PI4P binding in vitro and for the recruitment of GGAs to the TGN in vivo. Unlike wild-type GGA, GGA with mutated GATs failed to rescue the abnormal TGN phenotype of the GGA RNAi-depleted cells. These residues partially overlap with those that bind Ub, and PI4P increased the affinity of the GAT domain for Ub. Because the recruitment of clathrin adaptors and their cargoes to the TGN is mediated through a web of low-affinity interactions, our results show that the dual roles of PI4P can promote specific GGA targeting and cargo recognition at the TGN. C1 Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res Inst Biomed Res, Boston, MA 02115 USA. Natl Inst Child Hlth & Human Dev, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Yin, HL (reprint author), Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. EM Yin@UTSouthwestern.edu FU NIGMS NIH HHS [GM055562, GM36548, R01 GM036548, R01 GM055562] NR 40 TC 84 Z9 86 U1 0 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2007 VL 18 IS 7 BP 2646 EP 2655 DI 10.1091/mbc.E06-10-0897 PG 10 WC Cell Biology SC Cell Biology GA 183WV UT WOS:000247604000025 PM 17494868 ER PT J AU Rao, VA Conti, C Guirouilh-Barbat, J Nakamura, A Miao, ZH Davies, SL Sacca, B Hickson, ID Bensimon, A Pommier, Y AF Rao, V. Ashutosh Conti, Chiara Guirouilh-Barbat, Josee Nakamura, Asako Miao, Ze-Hong Davies, Sally L. Sacca, Barbara Hickson, Ian D. Bensimon, Aaron Pommier, Yves TI Endogenous gamma-H2AX-ATM-Chk2 checkpoint activation in Bloom's syndrome helicase-deficient cells is related to DNA replication arrested forks SO MOLECULAR CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-III-ALPHA; SYNDROME GENE-PRODUCT; DOUBLE-STRAND BREAKS; S-PHASE ARREST; SISTER CHROMATID EXCHANGES; CHK2 PROTEIN-KINASE; HISTONE H2AX; GENOMIC INSTABILITY; RECQ HELICASES; NUCLEAR FOCI AB The Bloom syndrome helicase (BLM) is critical for genomic stability. A defect in BLM activity results in the cancer-predisposing Bloom syndrome (BS). Here, we report that BLM-deficient cell lines and primary fibroblasts display an endogenously activated DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (gamma-H2AX), Chk2 (p(T68)Chk2), and ATM (p(S1981)ATM) colocalizing in nuclear foci. Interestingly, the mitotic fraction of gamma-H2AX foci did not seem to be higher in BLM-deficient cells, indicating that these lesions form transiently during interphase. Pulse labeling with iododeoxyuridine and immunofluorescence microscopy showed the colocalization of gamma-H2AX, ATM, and Chk2 together with replication foci. Those foci costained for Rad51, indicating homologous recombination at these replication sites. We therefore analyzed replication in BS cells using a single molecule approach on combed DNA fibers. In addition to a higher frequency of replication fork barriers, BS cells displayed a reduced average fork velocity and global reduction of interorigin distances indicative of an elevated frequency of origin firing. Because BS is one of the most penetrant cancer-predisposing hereditary diseases, it is likely that the lack of BLM engages the cells in a situation similar to precancerous tissues with replication stress. To our knowledge, this is the first report of high ATM-Chk2 kinase activation and its linkage to replication defects in a BS model. C1 NCI, US Dept Hlth & Human Serv, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. Inst Pasteur, Genome Stabil Lab, Paris, France. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Canc Res UK Labs, Oxford OX3 9DU, England. RP Pommier, Y (reprint author), NIH, 37 Convent Dr, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sacca, Barbara/B-9554-2015 OI Sacca, Barbara/0000-0003-2708-2272 FU Intramural NIH HHS NR 87 TC 56 Z9 58 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUL PY 2007 VL 5 IS 7 BP 713 EP 724 DI 10.1158/1541-7786.MCR-07-0028 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 192KN UT WOS:000248200700007 PM 17634426 ER PT J AU Lubet, RA Yang, CS Lee, MJ Hara, Y Kapetanovic, IM Crowell, JA Steele, VE Juliana, MM Grubbs, CJ AF Lubet, Ronald A. Yang, Chung S. Lee, Mao-Jung Hara, Yukihiko Kapetanovic, Izet M. Crowell, James A. Steele, Vernon E. Juliana, M. Margaret Grubbs, Clinton J. TI Preventive effects of Polyphenon E on urinary bladder and mammary cancers in rats and correlations with serum and urine levels of tea polyphenols SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID GREEN TEA; SIGNALING PATHWAYS; BREAST-CANCER; CARCINOGENESIS; INHIBITION; TUMORS; CHEMOPREVENTION; EXPRESSION; MICE; N-BUTYL-N-(4-HYDROXYBUTYL)-NITROSAMINE AB Polyphenon E, a standardized mixture of green tea polyphenols, was examined for its chemopreventive efficacy against chemically induced urinary bladder and mammary cancers. In the present study, Polyphenon E was administered after the last dose of 4-hydroxybutyl(butyl)nitrosamine, or roughly 30% of the way into the experiment. Polyphenon E (100 or 250 mg/kg body weight/d) caused a dose-dependent decrease in palpable urinary bladder tumors [low dose, 14 of 34; high dose, 6 of 35; controls, 20 of 34 (P < 0.01)]. In the mammary cancer model, Polyphenon E [333 or 1,000 mg/kg body weight (BW)/d] was administered beginning 5 days after a single dose of methylnitrosourea. In contrast to its significant efficacy in bladder tumor prevention, Polyphenon E had a minimal effect in the prevention of mammary cancers. Levels of polyphenols were determined in the urine and serum of rats. Relatively high levels of various polyphenols (and metabolites) were found in the urine. However, virtually no epigallocatechin-3-gallate was observed in the urine because of low systemic bioavailability; although it represents almost 65% of the polyphenols in Polyphenon E. Levels of polyphenols in serum were 50 x to 1,000 x less than were observed in urine. The bioavailability of these tea polyphenols to different organ sites may contribute to the differing preventive efficacy of Poly-phenon E against urinary bladder and mammary cancers. C1 NCI, Div Canc Prevent, Bethesda, MD 20852 USA. Rutgers State Univ, Dept Biol Chem, Piscataway, NJ USA. Mitsui Norin LTD, Food Res Labs, Shizuoka, Japan. Univ Alabama, Dept Genet, Birmingham, AL USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Lubet, RA (reprint author), NCI, Div Canc Prevent, Execut Plaza N,Suite 2110,6130 Execut Blvd, Bethesda, MD 20852 USA. EM lubetr@mail.nih.gov FU NCI NIH HHS [N01-CN-43308, N01-CN-25115, P01-CA88961, R01-CA096131, R01-CA101240] NR 29 TC 26 Z9 27 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2007 VL 6 IS 7 BP 2022 EP 2028 DI 10.1158/1535-7163.MCT-07-0058 PG 7 WC Oncology SC Oncology GA 191TG UT WOS:000248154300012 PM 17620432 ER PT J AU Manoukis, NC AF Manoukis, Nicholas C. TI FORMATOMATIC: a program for converting diploid allelic data between common formats for population genetic analysis SO MOLECULAR ECOLOGY NOTES LA English DT Article DE allele; conversion; data file; format; genotype; population genetic ID MULTILOCUS GENOTYPE DATA; INFERENCE AB There has been a great increase in both the number of population genetic analysis programs and the size of data sets being studied with them. Since the file formats required by the most popular and useful programs are variable, automated reformatting or conversion between them is desirable. (FORMATOMATIC) is an easy to use program that can read allelic data files in (GENEPOP), (RAW ( CSV)) or (CONVERT) formats and create data files in nine formats: RAW (( CSV), ARLEQUIN, GENEPOP, IMMANC / BAYESASS +, MIGRATE, NEWHYBRIDS, MSVAR, BAPS) and (STRUCTURE.) Use of formatomatic should greatly reduce time spent reformatting data sets and avoid unnecessary errors. C1 Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA. RP Manoukis, NC (reprint author), NIAID, Sect Vector Biol, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM manoukis@taylor0.biology.ucla.edu OI Manoukis, Nicholas/0000-0001-5062-7256 FU NIAID NIH HHS [R01 AI040308, R01 AI040308-10, R01 AI051633, R01 AI051633-05] NR 11 TC 14 Z9 14 U1 2 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1471-8278 J9 MOL ECOL NOTES JI Mol. Ecol. Notes PD JUL PY 2007 VL 7 IS 4 BP 592 EP 593 DI 10.1111/j.1471-8286.2007.01784.x PG 2 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 186DA UT WOS:000247758100012 PM 19789658 ER PT J AU Tingay, RE Dawson, DA Pandhal, J Clarke, ML David, VA Hailer, F Culver, M AF Tingay, Ruth E. Dawson, Deborah A. Pandhal, Jagroop Clarke, Michele L. David, Victor A. Hailer, Frank Culver, Melanie TI Isolation of 22 new Haliaeetus microsatellite loci and their characterization in the critically endangered Madagascar fish-eagle (Haliaeetus vociferoides) and three other Haliaeetus eagle species SO MOLECULAR ECOLOGY NOTES LA English DT Article DE Accipitridae; cross-species utility; eagle; Falconiformes; Haliaeetus; microsatellite ID DNA AB We isolated a total of 22 microsatellite loci from two Haliaeetus species: the Madagascar fish-eagle (Haliaeetus vociferoides) and the bald eagle (Haliaeetus leucocephalus). Five loci were monomorphic in both the Madagascar fish-eagle (n = 24-43) and the bald eagle (n = 2-8) but were found to be polymorphic in other Haliaeetus species. Haliaeetus loci have proved useful for investigating gene flow in Haliaeetus and Aquila eagles. Ten loci were polymorphic in the critically endangered Madagascar fish-eagle and will be used to investigate the genetic population structure and mating system in this species. C1 Nat Resources Ltd, Burn Obennie Rd, Banchory AB31 5ZU, Kincardine, Scotland. Univ Nottingham, Sch Geog, Nottingham NG7 2RD, England. Univ Sheffield, Mol Genet Facil, Dept Anim & Plant Sci, Sheffield S10 2TN, S Yorkshire, England. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Uppsala Univ, Dept Evolutionary Biol, Evolutionary Biol Ctr, S-75236 Uppsala, Sweden. Univ Arizona, Arizona Cooperat Fish & Wildlife Res Unit, USGS, Tucson, AZ 85721 USA. RP Tingay, RE (reprint author), Nat Resources Ltd, Burn Obennie Rd, Banchory AB31 5ZU, Kincardine, Scotland. EM dimlylit100@hotmail.com RI Hailer, Frank/C-9114-2012 OI Hailer, Frank/0000-0002-2340-1726 NR 14 TC 4 Z9 4 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1471-8278 J9 MOL ECOL NOTES JI Mol. Ecol. Notes PD JUL PY 2007 VL 7 IS 4 BP 711 EP 715 DI 10.1111/j.1471-8286.2007.01690.x PG 5 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 186DA UT WOS:000247758100048 ER PT J AU Kino, T Ichijo, T Amin, ND Kesavapany, S Wang, Y Kim, N Rao, S Player, A Zheng, YL Garabedian, MJ Kawasaki, E Pant, HC Chrousos, GP AF Kino, Tomoshige Ichijo, Takamasa Amin, Niranjana D. Kesavapany, Sashi Wang, Yonghong Kim, Nancy Rao, Sandesh Player, Audrey Zheng, Ya-Li Garabedian, Michael J. Kawasaki, Ernest Pant, Harish C. Chrousos, George P. TI Cyclin-dependent kinase 5 differentially regulates the transcriptional activity of the glucocorticoid receptor through phosphorylation: Clinical implications for the nervous system response to glucocorticoids and stress SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID N-TERMINAL KINASE; CDK5 ACTIVATION; ADRENAL AXIS; MOUSE MODEL; PROTEIN; GENE; P35; P25; DISEASE; NEUROFILAMENT AB Glucocorticoids, major end effectors of the stress response, play an essential role in the homeostasis of the central nervous system and influence diverse functions of neuronal cells. We found that cyclin-dependent kinase 5 (CDK5), which plays important roles in the morphogenesis and functions of the nervous system and whose aberrant activation is associated with development of neurodegenerative disorders, interacted with the ligand-binding domain of the glucocorticoid receptor (GR) through its activator p35 or its active proteolytic fragment p25. CDK5 phosphorylated GR at multiple serines, including Ser203 and Ser211 of its N-terminal domain, and suppressed the transcriptional activity of this receptor on glucocorticoid-responsive promoters by attenuating attraction of transcriptional cofactors to DNA. In microarray analyses using rat cortical neuronal cells, the CDK5 inhibitor roscovitine differentially regulated the transcriptional activity of the GR on more than 90% of the endogenous glucocorticoid-responsive genes tested. Thus, CDK5 exerts some of its biological activities in neuronal cells through the GR, dynamically modulating GR transcriptional activity in a target promoter-dependent fashion. C1 NINDS, NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Microarray Facil, Gaithersburg, MD 20877 USA. NYU, Sch Med, Inst Canc, Dept Microbiol & Urol, New York, NY 10016 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kino, T (reprint author), NINDS, NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov FU Intramural NIH HHS NR 65 TC 80 Z9 83 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUL PY 2007 VL 21 IS 7 BP 1552 EP 1568 DI 10.1210/me.2006-0345 PG 17 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 183GD UT WOS:000247559800005 PM 17440046 ER PT J AU Hassan, M Riley, J Chernomordk, V Smith, P Pursley, R Lee, SB Capala, J Gandjbakhche, AH AF Hassan, Moinuddin Riley, Jason Chernomordk, Victor Smith, Paul Pursley, Randall Lee, Sang Bong Capala, Jacek Gandjbakhche, Amir H. TI Fluorescence lifetime Imaging system for in vivo studies SO MOLECULAR IMAGING LA English DT Article ID TURBID MEDIUM; CANCER; CELLS; TOMOGRAPHY; MEDIA; FLIM AB In this article, a fluorescence lifetime imaging system for small animals is presented. Data were collected by scanning a region of interest with a measurement head, a linear fiber array with fixed separations between a single source fiber and several detection fibers. The goal was to localize tumors and monitor their progression using specific fluorescent markers. We chose a near-infrared contrast agent, Alexa Fluor 750 (Invitrogen Corp., Carlsbad, CA). Preliminary results show that the fluorescence lifetime for this dye was sensitive to the immediate environment of the fluorophore (in particular, pH), making it a promising candidate for reporting physiologic changes around a fluorophore. To quantify the intrinsic lifetime of deeply embedded fluorophores, we performed phantom experiments to investigate the contribution of photon migration effects on observed lifetime by calculating the fluorescence intensity decay time. A previously proposed theoretical model of migration, based on random walk theory, is also substantiated by new experimental data. The developed experimental system has been used for in vivo mouse imaging with Alexa Fluor 750 contrast agent conjugated to tumor-specific antibodies (trastuzumab [Herceptin]). Three-dimensional mapping of the fluorescence lifetime indicates lower lifetime values in superficial breast cancer tumors in mice. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Off Res Serv, Bethesda, MD USA. Ctr Informat Technol, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Hassan, M (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, 9 Mem Dr,Bldg 9,Rm B1E11, Bethesda, MD 20892 USA. EM hassanm@mail.nih.gov FU Intramural NIH HHS [Z99 CT999999] NR 22 TC 64 Z9 64 U1 3 U2 13 PU B C DECKER INC PI HAMILTON PA 50 KING STREET EAST, 2ND FLOOR, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1535-3508 J9 MOL IMAGING JI Mol. Imaging PD JUL-AUG PY 2007 VL 6 IS 4 BP 229 EP 236 DI 10.2310/7290.2007.00019 PG 8 WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical Imaging GA 208WE UT WOS:000249349100002 PM 17711778 ER PT J AU Park, IK Letterio, JJ Gorham, JD AF Park, Il-Kyoo Letterio, John J. Gorham, James D. TI TGF-beta 1 inhibition of IFN-gamma-induced signaling and Th1 gene expression in CD4(+) T cells is Smad3 independent but MAP kinase dependent SO MOLECULAR IMMUNOLOGY LA English DT Article DE IFN-gamma; TGF-beta; T helper cell; Th1 ID GROWTH-FACTOR-BETA; TGF-BETA; TARGETED DISRUPTION; PATHWAYS; DISEASE; MICE; INVOLVEMENT; RESPONSES; RAS AB In addition to classic Smad signaling pathways, the pleiotropic immunoregulatory cytokine TGF-beta 1 can activate MAP kinases, but a role for TGF-beta 1-MAP kinase pathways in T cells has not been defined heretofore. We have shown previously that TGF-beta 1 inhibits Th1 development by inhibiting IFN-gamma's induction of T-bet and other Th1 differentiation genes, and that TGF-beta 1 inhibits receptor-proximal IFN-gamma-Jak-Stat signaling responses. We now show that these effects of TGF-beta 1 are independent of the canonical TGF-beta 1 signaling module Smad3, but involve a specific MAP kinase pathway. In primary T cells, TGF-beta 1 activated the MEK/ERK and p38 MAP kinase pathways, but not the JNK pathway. Inhibition of the MEK/ERK pathway completely eliminated the inhibitory effects of TGF-beta 1 on IFN-gamma responses in T cells, whereas inhibition of the p38 pathway had no effect. Thus, TGF-beta 1's inhibition of IFN-gamma signaling in T cells is mediated through a highly specific Smad3 independent, MEK/ERK-dependent signaling pathway. (c) 2007 Elsevier Ltd. All rights reserved. C1 Dartmouth Coll Sch Med, Dept Pathol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. NIH, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NIH, Lab Mol Biol, Ctr Canc Biol, Bethesda, MD 20892 USA. RP Gorham, JD (reprint author), Dartmouth Coll Sch Med, Dept Pathol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM James.D.Gorham@Dartmouth.edu FU NCRR NIH HHS [P20 RR016437-020002, P20RR16437, P20 RR016437]; NIAID NIH HHS [R01 AI053056-04, AI053056, R01 AI053056]; NIDDK NIH HHS [DK073904, R21 DK073904, R21 DK073904-02] NR 29 TC 16 Z9 19 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD JUL PY 2007 VL 44 IS 13 BP 3283 EP 3290 DI 10.1016/j.molimm.2007.02.024 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 179EK UT WOS:000247272200002 PM 17403540 ER PT J AU Burtnick, MN Downey, JS Brett, PJ Boylan, JA Frye, JG Hoover, TR Gherardini, FC AF Burtnick, Mary N. Downey, Jennifer S. Brett, Paul J. Boylan, Julie A. Frye, Jonathan G. Hoover, Timothy R. Gherardini, Frank C. TI Insights into the complex regulation of rpoS in Borrelia burgdorferi SO MOLECULAR MICROBIOLOGY LA English DT Article ID OXIDATIVE STRESS-RESPONSE; BINDING PROTEIN NTRC; LYME-DISEASE; ESCHERICHIA-COLI; TRANSCRIPTIONAL ACTIVATOR; GENE-EXPRESSION; RNA-POLYMERASE; IN-VITRO; DIFFERENTIAL EXPRESSION; SURFACE PROTEIN AB Co-ordinated regulation of gene expression is required for the transmission and survival of Borrelia burgdorferi in different hosts. The sigma factor RpoS (as), as regulated by RpoN (3 4), has been shown to regulate key virulence factors (e.g. OspC) required for these processes. As important, multiple signals (e.g. temperature, pH, cell density, oxygen) have been shown to increase the expression of as-dependent genes; however, little is known about the signal transduction mechanisms that modulate the expression of rpoS. In this report we show that: (i) rpoS has a (;14dependent promoter that requires Rrp2 to activate transcription; (ii) Rrp2A123, a constitutively active form of Rrp2, activated U54 -dependent transcription of rpoSIP-lacZ reporter constructs in Escherichia coli; (iii) quantitative reverse transcription polymerase chain reaction (QRT-PCR) experiments with reporter cat constructs in B. burgdorferi indicated that Rrp2 activated transcription of rpoS in an enhancerindependent fashion; and finally, (iv) rpoN is required for cell density- and temperature-dependent expression of rpoS in B. burgdorferi, but histidine kinase Hk2, encoded by the gene immediately upstream of rrp2, is not essential. Based on these findings, a model for regulation of rpoS has been proposed which provides mechanisms for multiple signalling pathways to modulate the expression of the as regulon in B. burgdorteri. C1 NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. Univ So Calif, Norris Sch Dent, Div Diagnost Sci, Los Angeles, CA 90089 USA. USDA ARS, SAA RRC, Bacterial Epidemiol & Antimicrobial Resistance Re, Athens, GA 30613 USA. Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. RP Gherardini, FC (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT USA. EM fgherardini@niaid.nih.gov RI Frye, Jonathan/I-6382-2013; OI Frye, Jonathan/0000-0002-8500-3395; Hoover, Timothy/0000-0003-1101-8030 FU Intramural NIH HHS NR 54 TC 72 Z9 74 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2007 VL 65 IS 2 BP 277 EP 293 DI 10.1111/j.1365-2958.2007.05813.x PG 17 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 196LV UT WOS:000248484300005 PM 17590233 ER PT J AU Semsey, S Krishna, S Sneppen, K Adhya, S AF Semsey, Szabolcs Krishna, Sandeep Sneppen, Kim Adhya, Sankar TI Signal integration in the galactose network of Escherichia coli SO MOLECULAR MICROBIOLOGY LA English DT Article ID METHYLGALACTOSIDE TRANSPORT-SYSTEM; OPEN COMPLEX-FORMATION; RNA-POLYMERASE; GAL REPRESSOR; OPERON PROMOTERS; RECEPTOR PROTEIN; DNA-SEQUENCE; SPOT-42 RNA; CYCLIC-AMP; GENE AB The gal regulon of Escherichia coli contains genes involved in galactose transport and metabolism. Transcription of the gal regulon genes is regulated in different ways by two iso-regulatory proteins, Gal repressor (GaIR) and Gal isorepressor (GaIS), which recognize the same binding sites in the absence of D-galactose. DNA binding by both GaIR and GaIS is inhibited in the presence Of D-galactose. Many of the gal regulon genes are activated in the presence of the adenosine cyclic-3',5'-monophosphate (cAMP)-cAMP receptor protein (CRP) complex. We studied transcriptional regulation of the gal regulon promoters simultaneously in a purified system and attempted to integrate the two small molecule signals, D-galactose and cAMP, that modulate the isoregulators and CRP respectively, at each promoter, using Boolean logic. Results show that similarly organized promoters can have different input functions. We also found that in some cases the activity of the promoter and the cognate gene can be described by different logic gates. We combined the transcriptional network of the galactose regulon, obtained from our experiments, with literature data to construct an integrated map of the galactose network. Structural analysis of the network shows that at the interface of the genetic and metabolic network, feedback loops are by far the most common motif. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Niels Bohr Inst, Ctr Models Life, DK-2100 Copenhagen, Denmark. Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov RI Semsey, Szabolcs/L-6329-2013; OI Semsey, Szabolcs/0000-0002-4522-5495; Sneppen, Kim/0000-0001-9820-3567 FU Intramural NIH HHS NR 63 TC 32 Z9 33 U1 0 U2 7 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2007 VL 65 IS 2 BP 465 EP 476 DI 10.1111/j.1365-2958.2007.05798.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 196LV UT WOS:000248484300019 PM 17630975 ER PT J AU Zhang, MH Goswami, M Sawai, S Cox, EC Hereld, D AF Zhang, Minghang Goswami, Mousumi Sawai, Satoshi Cox, Edward C. Hereld, Dale TI Regulation of G protein-coupled cAMP receptor activation by a hydrophobic residue in transmembrane helix 3 SO MOLECULAR MICROBIOLOGY LA English DT Article ID CONSTITUTIVELY ACTIVE MUTANTS; SITE-DIRECTED MUTAGENESIS; DICTYOSTELIUM-DISCOIDEUM; CHEMOATTRACTANT RECEPTOR; MEDIATED ACTIVATION; GENETIC-ANALYSIS; CELLS; ERK2; PHOSPHORYLATION; RHODOPSIN AB cAR1, a G protein-coupled cAMP receptor, is essential for multicellular development of Dictyostelium. We previously identified a cAR1-Ile(104) mutant that appeared to be constitutively activated based on its constitutive phosphorylation, elevated affinity for cAMP, and dominant-negative effects on development as well as specific cAR1 pathways that are subject to adaptation. To investigate how Ile(104) might regulate cAR1 activation, we assessed the consequences of substituting it with all other amino acids. Constitutive phosphorylation of these Ile(104) mutants varied broadly, suggesting that they are activated to varying extents, and was correlated with polarity of the substituting amino acid residue. Remarkably, all Ile(104) substitutions, except for the most conservative, dramatically elevated the receptor's cAMP affinity. However, only a third of the mutants (those with the most polar substitutions) blocked development. These findings are consistent with a model in which polar Ile(104) substitutions perturb the equilibrium between inactive and active cAR1 conformations in favour of the latter. Based on homology with rhodopsin, Ile(104) is likely buried within inactive cAR1 and exposed to the cytoplasm upon activation. We propose that the hydrophobic effect normally promotes burial of Ile(104) and hence cAR1 inactivation, while polar substitution of Ile(104) mitigates this effect, resulting in activation. C1 Univ Texas, Hlth Sci Ctr, Dept Microbiol & Mol Genet, Houston, TX 77030 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. RP Hereld, D (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM hereldd@niaid.nih.gov FU NIGMS NIH HHS [GM 63677] NR 40 TC 3 Z9 4 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD JUL PY 2007 VL 65 IS 2 BP 508 EP 520 DI 10.1111/j.1365-2958.2007.05803.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 196LV UT WOS:000248484300022 PM 17630977 ER PT J AU Jefferson, WN Padilla-Banks, E Newbold, RR AF Jefferson, Wendy N. Padilla-Banks, Elizabeth Newbold, Retha R. TI Disruption of the developing female reproductive system by phytoestrogens: Genistein as an example SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE fertility; ovary; ovulation; reproductive tract; transgenerational effects ID ESTROGEN-RECEPTOR-BETA; SPRAGUE-DAWLEY RATS; SOY-BASED FORMULA; NEONATAL EXPOSURE; POLYOVULAR FOLLICLES; DIETARY GENISTEIN; MAMMARY-GLAND; UDP-GLUCURONOSYLTRANSFERASE; DEVELOPMENTAL EXPOSURE; DIETHYLSTILBESTROL DES AB Studies in our laboratory have shown that exposure to genistein causes deleterious effects on the developing female reproductive system. Mice treated neonatally on days 1-5 by subcutaneous injection of genistein (0.5-50 mg/kg) exhibited altered ovarian differentiation leading to multioocyte follicles (MOFs) at 2 months of age. Ovarian function and estrous cyclicity were also disrupted by neonatal exposure to genistein with increasing severity observed over time. Reduced fertility was observed in mice treated with genistein (0.5, 5, or 25 mg/kg) and infertility was observed at 50 mg/ kg. Mammary gland and behavioral endpoints were also affected by neonatal genistein treatment. Further, transgenerational effects were observed; female offspring obtained from breeding genistein treated females (25 mg/kg) to control males had increased MOFs. Thus, neonatal treatment with genistein at environmentally relevant doses caused adverse consequences on female development which is manifested in adulthood. Whether adverse effects occur in human infants exposed to soy-based products such as soy infant formulas is unknown but the neonatal murine model may help address some of the current uncertainties since we have shown that many effects obtained from feeding genistin, the glycosolated form of genistein found in soy formula, are similar to those obtained from injecting genistein. C1 NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, NIH, DHHS, Lab Mol Toxicol,Dev Endocrinol & Endocrine D, Res Triangle Pk, NC USA. RP Jefferson, WN (reprint author), NIEHS, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM jeffers1@niehs.nih.gov NR 98 TC 61 Z9 62 U1 2 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUL PY 2007 VL 51 IS 7 BP 832 EP 844 DI 10.1002/mnfr.200600258 PG 13 WC Food Science & Technology SC Food Science & Technology GA 192JF UT WOS:000248196700008 PM 17604387 ER PT J AU Newbold, RR Padilla-Banks, E Snyder, RJ Jefferson, WN AF Newbold, Retha R. Padilla-Banks, Elizabeth Snyder, Ryan J. Jefferson, Wendy N. TI Perinatal exposure to environmental estrogens and the development of obesity SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE adipocytes; epigenetic; leptin; metabolic disease; obesogens ID BODY-FAT DISTRIBUTION; BISPHENOL-A; ENDOCRINE DISRUPTORS; 3T3-L1 CELLS; RISK-FACTORS; DIETHYLSTILBESTROL; EPIDEMIC; ADIPOCYTES; RECEPTOR; DIFFERENTIATION AB Dietary substances and xenobiotic compounds with hormone-like activity can disrupt the programming of endocrine signaling pathways that are established during perinatal differentiation. The consequences of this disruption may not be apparent until later in life but increasing evidence implicates developmental exposure to environmental hormone-mimics with a growing list of adverse health effects including reproductive problems and increased cancer risks. Obesity has recently been proposed to be yet another adverse health consequence of exposure to endocrine disrupting substances during development. There is a renewed focus on identifying contributions of environmental factors to the development of obesity since it is reaching worldwide epidemic proportions, and this disease has the potential to overwhelm healthcare systems with associated illnesses such as diabetes and cardiovascular disease. Here, we review the literature that proposes an association of perinatal exposure to endocrine disrupting chemicals, in particular those with estrogenic activity, with the development of obesity later in life. We further describe an animal model of developmental exposure to diethylstilbestrol (DES) to study mechanisms involved in programming for obesity. Our experimental data support the idea that adipocytes and the mechanisms involved in weight homeostasis are novel targets of abnormal programming of environmental estrogens, some of which are found in our foods as naturally occurring substances or inadvertently as contaminants. C1 NIH, DHHS, Natl Inst Environm Hlth Sci, Dev Endocrinol & Endocrine Disruptor Sect Lab Mol, Res Triangle Pk, NC USA. RP Newbold, RR (reprint author), Natl Inst Environm Hlth Sci, Dev Endocrinol & Endocrine Sect, Mail Stop E4-02, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov FU Intramural NIH HHS NR 28 TC 74 Z9 75 U1 4 U2 15 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUL PY 2007 VL 51 IS 7 BP 912 EP 917 DI 10.1002/mnfr.200600259 PG 6 WC Food Science & Technology SC Food Science & Technology GA 192JF UT WOS:000248196700016 PM 17604389 ER PT J AU Lazo, JS Brady, LS Dingledine, R AF Lazo, John S. Brady, Linda S. Dingledine, Ray TI Building a pharmacological lexicon: Small molecule discovery in academia SO MOLECULAR PHARMACOLOGY LA English DT Review ID TOO LATE; NIH; LIBRARIES; TIMES AB Small molecules are powerful pharmacological tools to dissect biological events. There is now considerable interest in expanding efforts to identify and use small molecules targeting proteins encoded in the genomes of humans and pathogenic organisms. Integration of the principles of molecular pharmacology with contemporary high-throughput and high-content screening technologies is essential for the success of these discovery activities. We present some of the challenges and opportunities provided by the Molecular Library Screening Centers Network (MLSCN), which is a National Institutes of Health Roadmap Initiative. C1 Univ Pittsburgh, Dept Pharmacol, Pittsburgh Mol Lib Screening Ctr, Drug Discovery Inst, Pittsburgh, PA 15261 USA. NIMH, Mol Screening Ctr Network, Div Neurosci & Basic Behav Sci, Bethesda, MD 20892 USA. Emory Univ, Dept Pharmacol, Emory Chem Biol Discovery Ctr, Atlanta, GA 30322 USA. RP Lazo, JS (reprint author), Univ Pittsburgh, Dept Pharmacol, Pittsburgh Mol Lib Screening Ctr, Drug Discovery Inst, Biomed Sci Tower 3,Suite 10040, Pittsburgh, PA 15261 USA. EM lazo@pitt.edu; rdingledine@pharm.emory.edu RI dingledine, Ray/F-5173-2011 FU NHGRI NIH HHS [5U54-HG003918]; NIMH NIH HHS [5U54-MH074411] NR 14 TC 37 Z9 37 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2007 VL 72 IS 1 BP 1 EP 7 DI 10.1124/mol.107.035113 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 182AN UT WOS:000247477600001 PM 17405872 ER PT J AU Mooberry, SL Weiderhold, KN Dakshanamurthy, S Hamel, E Banner, EJ Kharlamova, A Hempel, J Gupton, JT Brown, ML AF Mooberry, Susan L. Weiderhold, Kimberly N. Dakshanamurthy, Sivanesan Hamel, Ernest Banner, Edith J. Kharlamova, Anastasia Hempel, Jonathan Gupton, John T. Brown, Milton L. TI Identification and characterization of a new tubulin-binding tetrasubstituted brominated pyrrole SO MOLECULAR PHARMACOLOGY LA English DT Article ID LEUKEMIA-CELLS; BETA-TUBULIN; COLCHICINE; CYTOTOXICITY; SITE; DISCOVERY; ANALOGS; EFFLUX; SCREEN; DRUGS AB We studied the mechanism of action of 3,5-dibromo-4-(3,4dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester (JG03-14) and found that it is a potent microtubule depolymerizer. JG-03-14 caused a dose-dependent loss of cellular microtubules, formation of aberrant mitotic spindles, accumulation of cells in the G(2)/M phase of the cell cycle, and Bcl-2 phosphorylation. These events culminated in the initiation of apoptosis, as evidenced by the caspase 3-dependent cleavage of poly(ADP-ribose) polymerase ( PARP). JG-03-14 has antiproliferative activity against a wide range of cancer cell lines, with an average IC50 value of 62 nM, and it is a poor substrate for transport by P-glycoprotein. JG-03-14 inhibited the polymerization of purified tubulin in vitro, consistent with a direct interaction between the compound and tubulin. JG-03-14 potently inhibited the binding of [H-3] colchicine to tubulin, suggesting that it bound to tubulin at a site overlapping the colchicine site. JG-03-14 had antitumor effects in the PC3 xenograft model, in which it caused greater than 50% reduction in tumor burden after 14 days of treatment. Molecular modeling studies indicated that the dimethoxyphenyl group of JG-03-14 occupies a space similar to that of the trimethoxyphenyl group of colchicine. However, the 2,3,5-trisubstituted pyrrole group, which is connected to the dimethoxyphenyl moiety, interacted with both alpha and beta tubulin in space not shared with colchicine, suggesting significant differences compared with colchicine in the mechanism of binding to tubulin. Our results suggest that this tetra-substituted pyrrole represents a new, biologically active chemotype for the colchicine site on tubulin. C1 SW Fdn Biomed Res, Dept Physiol & Med, San Antonio, TX 78245 USA. Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr,Drug Discovery Progr, Washington, DC 20007 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21701 USA. Univ Richmond, Gottwald Ctr Sci, Dept Chem, Richmond, VA 23173 USA. RP Mooberry, SL (reprint author), SW Fdn Biomed Res, Dept Physiol & Med, POB 760549, San Antonio, TX 78245 USA. EM smooberry@sfbr.org FU NCI NIH HHS [R15-CA67236] NR 39 TC 22 Z9 22 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2007 VL 72 IS 1 BP 132 EP 140 DI 10.1124/mol.107.034876 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 182AN UT WOS:000247477600014 PM 17456786 ER PT J AU Zandi, PP Badner, JA Steele, J Willour, VL Miao, K MacKinnon, DF Mondimore, FM Schweizer, B McInnis, MG DePaulo, JR Gershon, E McMahon, FJ Potash, JB AF Zandi, P. P. Badner, J. A. Steele, J. Willour, V. L. Miao, K. MacKinnon, D. F. Mondimore, F. M. Schweizer, B. McInnis, M. G. DePaulo, J. R., Jr. Gershon, E. McMahon, F. J. Potash, J. B. TI Genome-wide linkage scan of 98 bipolar pedigrees and analysis of clinical covariates SO MOLECULAR PSYCHIATRY LA English DT Article DE bipolar disorder; genetic linkage; covariates; age at onset; psychosis; anxiety disorder ID MAJOR AFFECTIVE-DISORDER; I AFFECTIVE-DISORDER; SUSCEPTIBILITY LOCI; FAMILIAL AGGREGATION; DARIERS-DISEASE; PANIC DISORDER; SHARED SUSCEPTIBILITY; CHROMOSOME 12Q23-Q24; DIAGNOSTIC INTERVIEW; PSYCHOTIC SYMPTOMS AB Despite compelling evidence that genetic factors contribute to bipolar disorder ( BP), attempts to identify susceptibility genes have met with limited success. This may be due to the genetic heterogeneity of the disorder. We sought to identify susceptibility loci for BP in a genome-wide linkage scan with and without clinical covariates that might reflect the underlying heterogeneity of the disorder. We genotyped 428 subjects in 98 BP families at the Center for Inherited Disease Research with 402 microsatellite markers. We first carried out a non-parametric linkage analysis with MERLIN, and then reanalyzed the data with LODPAL to incorporate clinical covariates for age at onset (AAO), psychosis and comorbid anxiety. We sought to further examine the top findings in the covariate analysis in an independent sample of 64 previously collected BP families. In the non-parametric linkage analysis, three loci were nominally significant under a narrow diagnostic model and seven other loci were nominally significant under a broader model. The top findings were on chromosomes 2q24 and 3q28. The covariate analyses yielded additional evidence for linkage on 3q28 with AAO in the primary and independent samples. Although none of the linked loci were genome-wide significant, their congruence with prior results and, for the covariate analyses, their identification in two separate samples increases the likelihood that they are true positives and deserve further investigation. These findings further demonstrate the value of considering clinical features that may reflect the underlying heterogeneity of disease in order to facilitate gene mapping. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21205 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. NIMH, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Zandi, PP (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Hampton House,Room 857,624 N Broadway, Baltimore, MD 21205 USA. EM pzandi@jhsph.edu RI McMahon, Francis/A-7290-2009; McInnis, Melvin/F-6963-2012; OI McInnis, Melvin/0000-0002-0375-6247; McMahon, Francis/0000-0002-9469-305X FU NCRR NIH HHS [RR03655]; NIMH NIH HHS [K01-MH072866, K01 MH072866, K01 MH072866-01] NR 46 TC 25 Z9 26 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 2007 VL 12 IS 7 BP 630 EP 639 DI 10.1038/sj.mp.4002027 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 184CW UT WOS:000247619700006 PM 17505464 ER PT J AU Hayward, AR AF Hayward, Anthony R. TI Remodeling the NGVL program to meet contemporary needs SO MOLECULAR THERAPY LA English DT Editorial Material C1 NIH, Div Clin Res Resources, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Hayward, AR (reprint author), NIH, Div Clin Res Resources, Natl Ctr Res Resources, Bldg 10, Bethesda, MD 20892 USA. EM haywarda@mail.nih.gov NR 1 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2007 VL 15 IS 7 BP 1223 EP 1224 DI 10.1038/sj.mt.6300229 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 184MS UT WOS:000247646400002 PM 17579590 ER PT J AU Adewumi, O Aflatoonian, B Ahrlund-Richter, L Amit, M Andrews, PW Beighton, G Bello, PA Benvenisty, N Berry, LS Bevan, S Blum, B Brooking, J Chen, KG Choo, ABH Churchill, GA Corbel, M Damjanov, I Draper, JS Dvorak, P Emanuelsson, K Fleck, RA Ford, A Gertow, K Gertsenstein, M Gokhale, PJ Hamilton, RS Hampl, A Healy, LE Hovatta, O Hyllner, J Imreh, MP Itskovitz-Eldor, J Jackson, J Johnson, JL Jones, M Kee, K King, BL Knowles, BB Lako, M Lebrin, F Mallon, BS Manning, D Mayshar, Y Mckay, RDG Michalska, AE Mikkola, M Mileikovsky, M Minger, SL Moore, HD Mummery, CL Nagy, A Nakatsuji, N O'Brien, CM Oh, SKW Olsson, C Otonkoski, T Park, KY Passier, R Patel, H Patel, M Pedersen, R Pera, MF Piekarczyk, MS Pera, RAR Reubinoff, BE Robins, AJ Rossant, J Rugg-Gunn, P Schulz, TC Semb, H Sherrer, ES Siemen, H Stacey, GN Stojkovic, M Suemori, H Szatkiewicz, J Turetsky, T Tuuri, T van den Brink, S Vintersten, K Vuoristo, S Ward, D Weaver, TA Young, LA Zhang, WD AF Adewumi, Oluseun Aflatoonian, Behrouz Ahrlund-Richter, Lars Amit, Michal Andrews, Peter W. Beighton, Gemma Bello, Paul A. Benvenisty, Nissim Berry, Lorraine S. Bevan, Simon Blum, Barak Brooking, Justin Chen, Kevin G. Choo, Andre B. H. Churchill, Gary A. Corbel, Marie Damjanov, Ivan Draper, Jon S. Dvorak, Petr Emanuelsson, Katarina Fleck, Roland A. Ford, Angela Gertow, Karin Gertsenstein, Marina Gokhale, Paul J. Hamilton, Rebecca S. Hampl, Ales Healy, Lyn E. Hovatta, Outi Hyllner, Johan Imreh, Marta P. Itskovitz-Eldor, Joseph Jackson, Jamie Johnson, Jacqueline L. Jones, Mark Kee, Kehkooi King, Benjamin L. Knowles, Barbara B. Lako, Majlinda Lebrin, Franck Mallon, Barbara S. Manning, Daisy Mayshar, Yoav Mckay, Ronald D. G. Michalska, Anna E. Mikkola, Milla Mileikovsky, Masha Minger, Stephen L. Moore, Harry D. Mummery, Christine L. Nagy, Andras Nakatsuji, Norio O'Brien, Carmel M. Oh, Steve K. W. Olsson, Cia Otonkoski, Timo Park, Kye-Yoon Passier, Robert Patel, Hema Patel, Minal Pedersen, Roger Pera, Martin F. Piekarczyk, Marian S. Pera, Renee A. Reijo Reubinoff, Benjamin E. Robins, Allan J. Rossant, Janet Rugg-Gunn, Peter Schulz, Thomas C. Semb, Henrik Sherrer, Eric S. Siemen, Henrike Stacey, Glyn N. Stojkovic, Miodrag Suemori, Hirofumi Szatkiewicz, Jin Turetsky, Tikva Tuuri, Timo van den Brink, Steineke Vintersten, Kristina Vuoristo, Sanna Ward, Dorien Weaver, Thomas A. Young, Lesley A. Zhang, Weidong CA Int Stem Cell Initiative TI Characterization of human embryonic stem cell lines by the International Stem Cell Initiative SO NATURE BIOTECHNOLOGY LA English DT Article ID HUMAN TERATOCARCINOMA CELLS; X-CHROMOSOME INACTIVATION; GENE-EXPRESSION; CARCINOMA-CELLS; MONOCLONAL-ANTIBODIES; SURFACE-ANTIGENS; ES CELLS; MOUSE EMBRYOGENESIS; GLOBO-SERIES; DIFFERENTIATION AB The International Stem Cell Initiative characterized 59 human embryonic stem cell lines from 17 laboratories worldwide. Despite diverse genotypes and different techniques used for derivation and maintenance, all lines exhibited similar expression patterns for several markers of human embryonic stem cells. They expressed the glycolipid antigens SSEA3 and SSEA4, the keratan sulfate antigens TRA-1-60, TRA-1-81, GCTM2 and GCT343, and the protein antigens CD9, Thy1 (also known as CD90), tissue- nonspecific alkaline phosphatase and class 1 HLA, as well as the strongly developmentally regulated genes NANOG, POU5F1 (formerly known as OCT4), TDGF1, DNMT3B, GABRB3 and GDF3. Nevertheless, the lines were not identical: differences in expression of several lineage markers were evident, and several imprinted genes showed generally similar allele-specific expression patterns, but some gene-dependent variation was observed. Also, some female lines expressed readily detectable levels of XIST whereas others did not. No significant contamination of the lines with mycoplasma, bacteria or cytopathic viruses was detected. C1 Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. Natl Inst Biol Stand & Controls, UK Stem Cell Bank, Div Cell Biol & Imaging, S Mimms EN6 3QG, Herts, England. Univ Sheffield, Ctr Stem Cell Biol, Dept Mol Biol & Biotechnol, Sheffield S10 2TN, S Yorkshire, England. Karolinska Inst, Dept Lab Med, Unit Mol Embryol, S-14157 Huddinge, Sweden. Technion Israel Inst Technol, Rambam Med Ctr, IL-31096 Haifa, Israel. St James Univ Hosp, Canc Res UK Genotyping Facil, Leeds LS9 3LP, W Yorkshire, England. Geneservice Ltd, Cambridge CB3 0FE, England. Monash Univ, Stem Cell Sci Ltd, Clayton, Vic 3800, Australia. Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. Thermo Fisher Sci, Matrix Technol, Handforth SK9 3LP, England. NIH, NIH Stem Cell Unit, Bethesda, MD 20892 USA. Bioproc Technol Inst, Singapore 138668, Singapore. Jackson Lab, Bar Harbor, ME 04609 USA. Univ Cambridge, Addenbrookes Hosp, Dept Surg, Cambridge CB2 2XY, England. Univ Kansas, Sch Med, Dept Pathol, Kansas City, KS 66160 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Masaryk Univ, Fac Med, Dept Biol, Brno, Czech Republic. Acad Sci Czech Republic, Inst Expt Med, Dept Mol Embryol, Brno, Czech Republic. Cellartis AB, S-41346 Gothenburg, Sweden. Monash Univ, MISCL, Clayton, Vic 3800, Australia. Karolinska Univ Hosp, Karolinska Inst, Dept Clin Sci Intervent & Technol, Div Obstet Gynecol, S-14186 Huddinge, Sweden. Karolinska Inst, Dept Lab Med, Clin Res Ctr, S-14157 Huddinge, Sweden. Uppsala Univ, Dept Genet & Dev, SE-7523236 Uppsala, Sweden. Stanford Univ, Ctr Human Embryon Stem Cell Res & Educ, Inst Stem Cell Biol & Regenerat Med, Dept Obstet & Gynecol, Palo Alto, CA 94304 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Inst Mol Biophys, Bar Harbor, ME 04609 USA. Newcastle Univ, Inst Human Genet, Int Ctr Life, Newcastle Upon Tyne NE1 3BZ, Tyne & Wear, England. Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. Univ Paris 06, INSERM, UR 525, Paris, France. WiCell Res Inst, Madison, WI 53707 USA. WiCell Res Inst, St Louis, MO 63131 USA. Monash Univ, Monash Inst Med Res, Lab Embryon Stem Cell Biol, Clayton, Vic 3800, Australia. Australian Stem Cell Ctr, Clayton, Vic 3800, Australia. Univ Helsinki, Biomedicum Stem Cell Ctr, Biomedicum Helsinki, FIN-00014 Helsinki, Finland. Kings Coll London, Wolfson Ctr Age Related Dis, London SE1 1UL, England. Kyoto Univ, Inst Frontier Med Sci, Kyoto 6068507, Japan. UCL, Univ Coll London, Regenerat Med Bioproc Unit, Adv Ctr Biochem Engn,Dept Biochem Engn, London WC1E 7JE, England. Monash Univ, Monash Inst Med Res, Ctr Reprod & Dev, Clayton, Vic 3800, Australia. Univ So Calif, Keck Sch Med, Ctr Stem Cell & Regenerat Med, CO Zilkha Neurogenet Inst, Los Angeles, CA 90089 USA. Hadassah Univ, Med Ctr, Hadassah Human Embryon Stem Cell Res Ctr, Goldyne Savad Inst Gene Therapy, IL-91120 Jerusalem, Israel. Hadassah Univ, Med Ctr, Dept Obstet & Gynecol, IL-91120 Jerusalem, Israel. Novocell, Athens, GA 30606 USA. Hosp Sick Children, Dev Biol Program, Toronto, ON M5G 1L7, Canada. Hosp Sick Children, Dev Biol Program, Toronto, ON M5G 1X8, Canada. Lund Univ, Stem Cell Ctr, SE-22184 Lund, Sweden. Ctr Invest Principe Felipe, Valencia, Spain. RP Andrews, PW (reprint author), Univ Sheffield, Dept Biomed Sci, Ctr Stem Cell Biol, Sheffield S10 2TN, S Yorkshire, England. EM p.w.andrews@sheffield.ac.uk RI Chen, Kevin/D-6769-2011; Otonkoski, Timo/F-1189-2011; PERA, MARTIN/A-9812-2012; Ahrlund-Richter, Lars/C-6226-2012; Lako, Majlinda/B-6297-2013; Nagy, Andras/G-6465-2013; Dvorak, Petr/G-2509-2013; Hampl, Ales/N-1632-2016; Dvorak, Petr/N-8936-2016; OI King, Benjamin/0000-0001-6463-1336; Chen, Kevin/0000-0003-2983-6330; PERA, MARTIN/0000-0001-6239-0428; Dvorak, Petr/0000-0002-3229-140X; Dvorak, Petr/0000-0002-3229-140X; Gokhale, Paul/0000-0001-7225-4403; lebrin, franck/0000-0002-1650-6757 NR 75 TC 602 Z9 630 U1 8 U2 89 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 EI 1546-1696 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2007 VL 25 IS 7 BP 803 EP 816 DI 10.1038/nbt1318 PG 14 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 189MW UT WOS:000247994000032 ER PT J AU Jimenez-Baranda, S Gomez-Mouton, C Rojas, A Martinez-Prats, L Mira, E Lacalle, RA Valencia, A Dimitrov, DS Viola, A Delgado, R Martinez, C Manes, S AF Jimenez-Baranda, Sonia Gomez-Mouton, Concepcion Rojas, Ana Martinez-Prats, Lorena Mira, Emilia Lacalle, Rosa Ana Valencia, Alfonso Dimitrov, Dimiter S. Viola, Antonella Delgado, Rafael Martinez, Carlos Manes, Santos TI Filamin-A regulates actin-dependent clustering of HIV receptors SO NATURE CELL BIOLOGY LA English DT Article ID CHEMOKINE RECEPTORS; LIPID RAFTS; VIRUS ENTRY; HOST-CELLS; CD4; INFECTION; TYPE-1; CHOLESTEROL; BINDING; ROCK AB Human immunodeficiency virus ( HIV)-1 infection requires envelope ( Env) glycoprotein gp120-induced clustering of CD4 and coreceptors (CCR5 or CXCR4) on the cell surface; this enables Env gp41 activation and formation of a complex that mediates fusion between Env-containing and target-cell membranes(1). Kinetic studies show that viral receptors are actively transported to the Env-receptor interface in a process that depends on plasma membrane composition and the actin cytoskeleton(2-7). The mechanisms by which HIV-1 induces F-actin rearrangement in the target cell remain largely unknown. Here, we show that CD4 and the coreceptors interact with the actin-binding protein filamin-A, whose binding to HIV-1 receptors regulates their clustering on the cell surface. We found that gp120 binding to cell receptors induces transient cofilin-phosphorylation inactivation through a RhoA-ROCK-dependent mechanism. Blockade of filamin-A interaction with CD4 and/or coreceptors inhibits gp120-induced RhoA activation and cofilin inactivation. Our results thus identify filamin-A as an adaptor protein that links HIV-1 receptors to the actin cytoskeleton remodelling machinery, which may facilitate virus infection. C1 CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, E-28049 Madrid, Spain. CSIC, Ctr Nacl Biotecnol, Bioinformat Unit, E-28049 Madrid, Spain. Hosp 12 Octubre, Microbiol Serv, E-28041 Madrid, Spain. NCI, CCR Nanobiol Program, NIH, Ft Detrick, MD 21702 USA. Univ Padua, Venetian Inst Mol Med, I-35100 Padua, Italy. RP Manes, S (reprint author), CSIC, Ctr Nacl Biotecnol, Dept Immunol & Oncol, Darwin 3,Campus Cantoblanco, E-28049 Madrid, Spain. EM smanes@cnb.uam.es RI Rojas, Ana/C-3022-2008; Rojas, Ana /D-5777-2011; MIRA, EMILIA/K-2456-2014; Manes, Santos/E-4725-2011; Valencia, Alfonso/I-3127-2015; Delgado, Rafael/C-4910-2016; IBIS, BIOINFORMATICA/O-1882-2015; Agatea, Lisa/L-8267-2016 OI Rojas, Ana /0000-0003-0750-9099; MIRA, EMILIA/0000-0002-4226-1829; Valencia, Alfonso/0000-0002-8937-6789; Delgado, Rafael/0000-0002-6912-4736; Agatea, Lisa/0000-0002-8380-9619 FU Intramural NIH HHS NR 32 TC 104 Z9 105 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUL PY 2007 VL 9 IS 7 BP 838 EP + DI 10.1038/ncb1610 PG 22 WC Cell Biology SC Cell Biology GA 186EA UT WOS:000247760700020 PM 17572668 ER PT J AU Schmidt, BM Ribnicky, DM Lipsky, PE Raskin, I AF Schmidt, Barbara M. Ribnicky, David M. Lipsky, Peter E. Raskin, Ilya TI Revisiting the ancient concept of botanical therapeutics SO NATURE CHEMICAL BIOLOGY LA English DT Editorial Material ID DRUG DISCOVERY; NATURAL-PRODUCTS; TRIPTERYGIUM-WILFORDII; ARTEMISIA-DRACUNCULUS; PLANTS; INHIBITORS; CHEMISTRY; EXTRACT AB Mixtures of interacting compounds produced by plants may provide important combination therapies that simultaneously affect multiple pharmacological targets and provide clinical efficacy beyond the reach of single compound-based drugs. Developing innovative scientific methods for discovery, validation, characterization and standardization of these multicomponent botanical therapeutics is essential to their acceptance into mainstream medicine. C1 Rutgers State Univ, Sch Biol & Environm Sci, Biotech Ctr, New Brunswick, NJ 08901 USA. Natl Inst Arthritis & Musculosketal & Skin Dis, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Schmidt, BM (reprint author), Rutgers State Univ, Sch Biol & Environm Sci, Biotech Ctr, 59 Dudley Rd, New Brunswick, NJ 08901 USA. EM raskin@AESOP.Rutgers.edu FU FIC NIH HHS [U01 TW006674]; NCCIH NIH HHS [1-P50 AT002776-01] NR 37 TC 157 Z9 164 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD JUL PY 2007 VL 3 IS 7 BP 360 EP 366 DI 10.1038/nchembio0707-360 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181UY UT WOS:000247462800005 PM 17576417 ER PT J AU Levy-Clarke, G Reed, G Nussenblatt, R AF Levy-Clarke, Grace Reed, George Nussenblatt, Robert TI Is anti-tumor necrosis factor therapy effective in reducing uveitis flares in patients with spondyloarthropathies? SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Editorial Material C1 NEI, NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Levy-Clarke, G (reprint author), NEI, NIH, Immunol Lab, Bldg 10,Room 10N112,10 Ctr Dr,MSC-1857, Bethesda, MD 20892 USA. EM clarkeg@nei.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD JUL PY 2007 VL 3 IS 7 BP 376 EP 377 DI 10.1038/ncprheum0512 PG 2 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 184NS UT WOS:000247649300005 PM 17502888 ER PT J AU Hunter, DJ Kraft, P Jacobs, KB Cox, DG Yeager, M Hankinson, SE Wacholder, S Wang, ZM Welch, R Hutchinson, A Wang, JW Yu, K Chatterjee, N Orr, N Willett, WC Colditz, GA Ziegler, RG Berg, CD Buys, SS McCarty, CA Feigelson, HS Calle, EE Thun, MJ Hayes, RB Tucker, M Gerhard, DS Fraumeni, JF Hoover, RN Thomas, G Chanock, SJ AF Hunter, David J. Kraft, Peter Jacobs, Kevin B. Cox, David G. Yeager, Meredith Hankinson, Susan E. Wacholder, Sholom Wang, Zhaoming Welch, Robert Hutchinson, Amy Wang, Junwen Yu, Kai Chatterjee, Nilanjan Orr, Nick Willett, Walter C. Colditz, Graham A. Ziegler, Regina G. Berg, Christine D. Buys, Saundra S. McCarty, Catherine A. Feigelson, Heather Spencer Calle, Eugenia E. Thun, Michael J. Hayes, Richard B. Tucker, Margaret Gerhard, Daniela S. Fraumeni, Joseph F., Jr. Hoover, Robert N. Thomas, Gilles Chanock, Stephen J. TI A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer SO NATURE GENETICS LA English DT Article ID LOCI; PREMENOPAUSAL; FREQUENCIES; COHORT; BRCA1 AB We conducted a genome- wide association study ( GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 ( which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant ( P(trend) for the most strongly associated SNP ( rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. MIT, Broad Inst, Cambridge, MA 02142 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Bioinformed Consulting Serv, Gaithersburg, MD 20877 USA. SAIC Frederick, NCI FCRDC, Frederick, MD 21702 USA. NCI, Pediat Oncol Branch, Canc Res Ctr, NIH,DHHS, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Washington Univ, Sch Med, St Louis, MO 63130 USA. NCI, Div Canc Prevent, NIH, DHHS, Bethesda, MD 20892 USA. Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. Marshfield Clin Fdn Med Res & Educ, Ctr Human Genet, Marshfield, WI 54449 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. NCI, Off Canc Genom, NIH, DHHS, Bethesda, MD 20892 USA. RP Hunter, DJ (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 75 Francis St, Boston, MA 02115 USA. EM dhunter@hsph.harvard.edu RI Cox, David/A-2023-2009; Wang, Junwen/C-4432-2009; Tucker, Margaret/B-4297-2015; Wang, Junwen/D-3700-2011; Colditz, Graham/A-3963-2009; OI Cox, David/0000-0002-2152-9259; Wang, Junwen/0000-0002-4432-4707; Colditz, Graham/0000-0002-7307-0291; Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS; NCI NIH HHS [R01 CA065725, 5U01CA098233, CA49449, CA50385, CA65725, CA67262, CA87969, P01 CA087969, R01 CA049449, R01 CA050385, R01 CA067262, U01 CA049449, U01 CA067262, U01 CA098233, U01 CA098710] NR 23 TC 957 Z9 988 U1 5 U2 64 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2007 VL 39 IS 7 BP 870 EP 874 DI 10.1038/ng2075 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 184CX UT WOS:000247619800017 PM 17529973 ER PT J AU Guarda, G Hons, M Soriano, SF Huang, AY Polley, R Martin-Fontecha, A Stein, JV Germain, RN Lanzavecchia, A Sallusto, F AF Guarda, Greta Hons, Miroslav Soriano, Silvia F. Huang, Alex Y. Polley, Rosalind Martin-Fontecha, Alfonso Stein, Jens V. Germain, Ronald N. Lanzavecchia, Antonio Sallusto, Federica TI L-selectin-negative CCR7(-) effector and memory CD8(+) T cells enter reactive lymph nodes and kill dendritic cells SO NATURE IMMUNOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; IN-VIVO; NK CELLS; LISTERIA-MONOCYTOGENES; DEPENDENT ELIMINATION; LEUKOCYTE ADHESION; PERIPHERAL-TISSUES; IFN-GAMMA; LYMPHOCYTES; MIGRATION AB T lymphocytes lacking the lymph node-homing receptors L-selectin and CCR7 do not migrate to lymph nodes in the steady state. Instead, we found here that lymph nodes draining sites of mature dendritic cells or adjuvant inoculation recruited L-selectin- negative CCR7(-) effector and memory CD8(+) T cells. This recruitment required CXCR3 expression on T cells and occurred through high endothelial venules in concert with lumenal expression of the CXCR3 ligand CXCL9. In reactive lymph nodes, recruited T cells established stable interactions with and killed antigen-bearing dendritic cells, limiting the ability of these dendritic cells to activate naive CD4(+) and CD8(+) T cells. The inducible recruitment of blood-borne effector and memory T cells to lymph nodes may represent a mechanism for terminating primary and limiting secondary immune responses. C1 Inst Res Biomed, CH-6500 Bellinzona, Switzerland. Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland. NIAID, NIH, Bethesda, MD 20892 USA. RP Sallusto, F (reprint author), Inst Res Biomed, CH-6500 Bellinzona, Switzerland. EM federica.sallusto@irb.unisi.ch RI Guarda, Greta/G-1921-2011 OI Huang, Alex/0000-0002-5701-4521; FU Intramural NIH HHS NR 54 TC 142 Z9 144 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2007 VL 8 IS 7 BP 743 EP 752 DI 10.1038/ni1469 PG 10 WC Immunology SC Immunology GA 185NQ UT WOS:000247718100015 PM 17529983 ER PT J AU Darrah, PA Patel, DT De Luca, PM Lindsay, RWB Davey, DF Flynn, BJ Hoff, ST Andersen, P Reed, SG Morris, SL Roederer, M Seder, RA AF Darrah, Patricia A. Patel, Dipti T. De Luca, Paula M. Lindsay, Ross W. B. Davey, Dylan F. Flynn, Barbara J. Hoff, Soren T. Andersen, Peter Reed, Steven G. Morris, Sheldon L. Roederer, Mario Seder, Robert A. TI Multifunctional T(H)1 cells define a correlate of vaccine-mediated protection against Leishmania major SO NATURE MEDICINE LA English DT Article ID NECROSIS-FACTOR-ALPHA; CD8(+) T-CELLS; INTERFERON-GAMMA; MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSE; FLOW-CYTOMETRY; MEMORY CD4(+); NITRIC-OXIDE; IN-VIVO; INFECTION AB CD4(+) T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4(+) T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4(+) T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4(+) T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (T(H)1) cells. C1 NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen S, Denmark. Infect Dis Res Inst, Seattle, WA 98104 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS NR 49 TC 784 Z9 790 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2007 VL 13 IS 7 BP 843 EP 850 DI 10.1038/nm1592 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 188EU UT WOS:000247902800031 PM 17558415 ER PT J AU Roberts, JN Buck, CB Thompson, CD Kines, R Bernardo, M Choyke, PL Lowy, DR Schiller, JT AF Roberts, Jeffrey N. Buck, Christopher B. Thompson, Cynthia D. Kines, Rhonda Bernardo, Marcelino Choyke, Peter L. Lowy, Douglas R. Schiller, John T. TI Genital transmission of HPV in a mouse model is potentiated by nonoxynol-9 and inhibited by carrageenan SO NATURE MEDICINE LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; HUMAN-PAPILLOMAVIRUS TYPE-16; MINOR CAPSID PROTEIN; VAGINAL EPITHELIUM; CONTROLLED-TRIAL; PREVENTION; L2; NEUTRALIZATION; SPERMICIDE; EFFICACY AB Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection, and virtually all cases of cervical cancer are attributable to infection by a subset of HPVs (reviewed in ref. 1). Despite the high incidence of HPV infection and the recent development of a prophylactic vaccine that confers protection against some HPV types, many features of HPV infection are poorly understood. It remains worthwhile to consider other interventions against genital HPVs, particularly those that target infections not prevented by the current vaccine. However, productive papillomavirus infection is species- and tissue-restricted, and traditional models use animal papillomaviruses that infect the skin or oral mucosa. Here we report the development of a mouse model of cervicovaginal infection with HPV16 that recapitulates the establishment phase of papillomavirus infection. Transduction of a reporter gene by an HPV16 pseudovirus was characterized by histology and quantified by whole-organ, multispectral imaging. Disruption of the integrity of the stratified or columnar genital epithelium was required for infection, which occurred after deposition of the virus on the basement membrane underlying basal keratinocytes. A widely used vaginal spermicide, nonoxynol-9 (N-9), greatly increased susceptibility to infection. In contrast, carrageenan, a polysaccharide present in some vaginal lubricants, prevented infection even in the presence of N-9, suggesting that carrageenan might serve as an effective topical HPV microbicide. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. SAIC Frederick, Frederick, MD 21702 USA. NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schiller, JT (reprint author), NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. EM schillej@mail.nih.gov OI Buck, Christopher/0000-0003-3165-8094 FU Intramural NIH HHS NR 26 TC 253 Z9 260 U1 2 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2007 VL 13 IS 7 BP 857 EP 861 DI 10.1038/nm1598 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 188EU UT WOS:000247902800033 PM 17603495 ER PT J AU Connor, KM SanGiovanni, JP Lofqvist, C Aderman, CM Chen, J Higuchi, A Hong, S Pravda, EA Majchrzak, S Carper, D Hellstrom, A Kang, JX Chew, EY Salem, N Serhan, CN Smith, LEH AF Connor, Kip M. SanGiovanni, John Paul Lofqvist, Chatarina Aderman, Christopher M. Chen, Jing Higuchi, Akiko Hong, Song Pravda, Elke A. Majchrzak, Sharon Carper, Deborah Hellstrom, Ann Kang, Jing X. Chew, Emily Y. Salem, Norman, Jr. Serhan, Charles N. Smith, Lois E. H. TI Increased dietary intake of omega-3-polyunsaturated fatty acids reduces pathological retinal angiogenesis SO NATURE MEDICINE LA English DT Article ID NF-KAPPA-B; DOCOSAHEXAENOIC ACID; ISCHEMIC RETINOPATHY; RESOLVIN E1; IN-VIVO; INFLAMMATION; RECEPTOR; NEOVASCULARIZATION; INHIBITION; PROLIFERATION AB Many sight-threatening diseases have two critical phases, vessel loss followed by hypoxia-driven destructive neovascularization. These diseases include retinopathy of prematurity and diabetic retinopathy, leading causes of blindness in childhood and middle age affecting over 4 million people in the United States. We studied the influence of omega-3- and omega-6-polyunsaturated fatty acids (PUFAs) on vascular loss, vascular regrowth after injury, and hypoxia-induced pathological neovascularization in a mouse model of oxygen-induced retinopathy. We show that increasing omega-3-PUFA tissue levels by dietary or genetic means decreased the avascular area of the retina by increasing vessel regrowth after injury, thereby reducing the hypoxic stimulus for neovascularization. The bioactive omega-3-PUFA-derived mediators neuroprotectinD1, resolvinD1 and resolvinE1 also potently protected against neovascularization. The protective effect of omega-3-PUFAs and their bioactive metabolites was mediated, in part, through suppression of tumor necrosis factor-alpha. This inflammatory cytokine was found in a subset of microglia that was closely associated with retinal vessels. These findings indicate that increasing the sources of omega-3-PUFA or their bioactive products reduces pathological angiogenesis. Western diets are often deficient in omega-3-PUFA, and premature infants lack the important transfer from the mother to the infant of omega-3-PUFA that normally occurs in the third trimester of pregnancy. Supplementing omega-3-PUFA intake may be of benefit in preventing retinopathy. C1 Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, Boston, MA 02115 USA. NEI, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Univ Gothenburg, Sahlgrenska Acad, Dept Pediat, Gothenburg, Sweden. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesiol Perioperat & Pain Med,Ctr Expt T, Boston, MA 02115 USA. NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. NEI, Off Director, Bethesda, MD 20892 USA. Univ Gothenburg, Sahlgrenska Acad, Dept Clin Neurosci, Gothenburg, Sweden. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Smith, LEH (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Dept Ophthalmol, 300 Longwood Ave, Boston, MA 02115 USA. EM lois.smith@childrens.harvard.edu RI SanGiovanni, John Paul/A-7605-2008; Majchrzak, Sharon/F-1830-2013; OI Majchrzak, Sharon/0000-0001-8934-7294; Lofqvist, Chatarina/0000-0003-4371-5164; Connor, Kip/0000-0002-2048-9080; Hellstrom, Ann/0000-0002-9259-1244 FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [1F32 EY017789, 5 T32 EY07145, EY008670, EY017017, EY14811, F32 EY017789, R01 EY008670, R01 EY017017, R21 EY014811, T32 EY007145]; NICHD NIH HHS [P01 HD18655, P30 HD018655]; NIDCR NIH HHS [P50 DE016191, P50-DE016191]; NIGMS NIH HHS [GM38765, R01 GM038765, R37 GM038765] NR 30 TC 327 Z9 344 U1 4 U2 23 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2007 VL 13 IS 7 BP 868 EP 873 DI 10.1038/nm1591 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 188EU UT WOS:000247902800035 PM 17589522 ER PT J AU Micu, I Ridsdale, A Zhang, LQ Woulfe, J McClintock, J Brantner, CA Andrews, SB Stys, PK AF Micu, Ileana Ridsdale, Andrew Zhang, Lingqing Woulfe, John McClintock, Jeff Brantner, Christine A. Andrews, S. Brian Stys, Peter K. TI Real-time measurement of free Ca2+ changes in CNS myelin by two-photon microscopy SO NATURE MEDICINE LA English DT Article ID CORD WHITE-MATTER; SHEATH THICKNESS; ION CHANNELS; OPTIC-NERVE; CALCIUM; MECHANISMS; ACTIVATION; RECEPTORS; GLYCINE; CELLS AB Here we describe a technique for measuring changes in Ca2+ in the cytosolic domain of mature compact myelin of live axons in the central nervous system (CNS). We label the myelin sheath of optic nerve and dorsal column axons by using the Ca2+ indicator X-rhod-1 coupled with DiOC(6)(3) to produce bright myelin counterstaining, thereby providing unambiguous identification of the myelin sheath for analysis of two-photon excited fluorescence. We present evidence for localization of the Ca2+ reporter to the cytosolic domain of myelin, obtained by using fluorescence lifetime, spectral measurements and Mn2+ quenching. Chemical ischemia increased myelinic X-rhod-1 fluorescence (similar to 50% after 30 min) in a manner dependent on extracellular Ca2+. Inhibiting Na+-dependent glutamate transporters (with TBOA) or glycine transporters (with sarcosine and ALX-1393) reduced the ischemia-induced increase in Ca2+. We show that myelinic N-methyl-D-aspartate (NMDA) receptors are activated by the two conventional coagonists glutamate and glycine, which are released by specific transporters under conditions of cellular Na+ loading and depolarization in injured white matter. This new technique facilitates detailed studies of living myelin, a vital component of the mammalian CNS. C1 Univ Ottawa, Div Neurosci, Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Ctr Canc Therapeut, Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. Univ Ottawa, Childrens Hosp Eastern Ontario, Ottawa, ON K1H 8L1, Canada. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Stys, PK (reprint author), Univ Ottawa, Div Neurosci, Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. EM pstys@ucalgary.ca RI Micu, Ileana/M-9468-2016 OI Brantner, Christine/0000-0001-8172-901X; Micu, Ileana/0000-0001-7112-0075 FU Intramural NIH HHS NR 30 TC 39 Z9 40 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2007 VL 13 IS 7 BP 874 EP 879 DI 10.1038/nm1568 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 188EU UT WOS:000247902800036 PM 17603496 ER PT J AU Agarwal, N Pacher, P Tegeder, I Amaya, F Constantin, CE Brenner, GJ Rubino, T Michalski, CW Marsicano, G Monory, K Mackie, K Marian, C Batkai, S Parolaro, D Fischer, MJ Reeh, P Kunos, G Kress, M Lutz, B Woolf, CJ Kuner, R AF Agarwal, Nitin Pacher, Pal Tegeder, Irmgard Amaya, Fumimasa Constantin, Cristina E. Brenner, Gary J. Rubino, Tiziana Michalski, Christoph W. Marsicano, Giovanni Monory, Krisztina Mackie, Ken Marian, Claudiu Batkai, Sandor Parolaro, Daniela Fischer, Michael J. Reeh, Peter Kunos, George Kress, Michaela Lutz, Beat Woolf, Clifford J. Kuner, Rohini TI Cannabinoids mediate analgesia largely via peripheral type 1 cannabinoid receptors in nociceptors SO NATURE NEUROSCIENCE LA English DT Article ID IN-SITU HYBRIDIZATION; DORSAL-ROOT GANGLIA; NEUROPATHIC PAIN; ENDOGENOUS CANNABINOIDS; SPINAL NEURONS; KNOCKOUT MICE; WIN 55,212-2; RATS; CB1; HYPERALGESIA AB Although endocannabinoids constitute one of the first lines of defense against pain, the anatomical locus and the precise receptor mechanisms underlying cannabinergic modulation of pain are uncertain. Clinical exploitation of the system is severely hindered by the cognitive deficits, memory impairment, motor disturbances and psychotropic effects resulting from the central actions of cannabinoids. We deleted the type 1 cannabinoid receptor (CB1) specifically in nociceptive neurons localized in the peripheral nervous system of mice, preserving its expression in the CNS, and analyzed these genetically modified mice in preclinical models of inflammatory and neuropathic pain. The nociceptor-specific loss of CB1 substantially reduced the analgesia produced by local and systemic, but not intrathecal, delivery of cannabinoids. We conclude that the contribution of CB1-type receptors expressed on the peripheral terminals of nociceptors to cannabinoid-induced analgesia is paramount, which should enable the development of peripherally acting CB1 analgesic agonists without any central side effects. C1 Univ Heidelberg, Inst Pharmacol, D-69120 Heidelberg, Germany. NIH, NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. Univ Frankfurt Klinikum, D-60590 Frankfurt, Germany. Massachusetts Gen Hosp, Harvard Med Sch, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Med Univ Innsbruck, Dept Physiol & Med Phys, Div Physiol, A-6020 Innsbruck, Austria. Univ Mainz, Dept Physiol Chem, D-55099 Mainz, Germany. Univ Washington, Sch Med, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Erlangen Nurnberg, Inst Physiol & Pathophysiol, D-91054 Erlangen, Germany. RP Kuner, R (reprint author), Univ Heidelberg, Inst Pharmacol, Im Neuenheimer Feld, D-69120 Heidelberg, Germany. EM rohini.kuner@pharma.uni-heidelberg.de RI Fischer, Michael/F-7976-2010; Mackie, Kenneth/B-7358-2011; Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Reeh, Peter/J-8981-2012; Mackie, Ken/E-3715-2013; Batkai, Sandor/H-7983-2014; OI Pacher, Pal/0000-0001-7036-8108; Reeh, Peter/0000-0002-4367-094X; Mackie, Ken/0000-0001-8501-6199; Tegeder, Irmgard/0000-0001-7524-8025 FU Intramural NIH HHS [Z01 AA000375-02]; NIDA NIH HHS [DA00286, DA11322, K02 DA000286, K02 DA000286-04, R01 DA011322, R01 DA011322-02]; NINDS NIH HHS [NS 038253, NS039518, R01 NS038253, R01 NS038253-01S1, R01 NS039518, R01 NS039518-01A2, R37 NS039518] NR 46 TC 285 Z9 289 U1 2 U2 20 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUL PY 2007 VL 10 IS 7 BP 870 EP 879 DI 10.1038/nn1916 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 183GH UT WOS:000247560200017 PM 17558404 ER PT J AU Kelloff, GJ Sigman, CC AF Kelloff, Gary J. Sigman, Caroline C. TI Assessing intraepithelial neoplasia and drug safety in cancer-preventive drug development SO NATURE REVIEWS CANCER LA English DT Review ID SURROGATE END-POINTS; ESTROGEN-RECEPTOR MODULATORS; SURGICAL ADJUVANT BREAST; BOWEL PROJECT P-1; PROSTATE-CANCER; COLORECTAL ADENOMAS; CHEMOPREVENTION TRIALS; CARDIOVASCULAR EVENTS; BIOMARKER DEVELOPMENT; CLINICAL-TRIAL AB Despite significant interest from the research community and the population in general, drug approvals for cancer prevention and/ or cancer risk reduction are few. This is due, in part, to the requirement that new cancer-preventive drugs must first be shown to be efficacious in reducing cancer incidence or mortality. Moreover, such drugs need to have proven safety for long-term administration. This process can be improved by focusing on precancer ( intraepithelial neoplasia) to identify subjects at risk and prove efficacy in shorter, smaller trials as well as on detecting early markers of potential toxicities of chronic exposure to cancer-preventive drug regimens. C1 Natl Inst Hlth, Natl Canc Inst, Div Canc Treatment & Diag, Rockville, MD 20852 USA. CCS Assoc, Mountain View, CA 94043 USA. RP Kelloff, GJ (reprint author), Natl Inst Hlth, Natl Canc Inst, Div Canc Treatment & Diag, Execut Plaza N Rm 6058,6130 Execut Blvd, Rockville, MD 20852 USA. EM kelloffg@mail.nih.gov NR 79 TC 12 Z9 12 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD JUL PY 2007 VL 7 IS 7 BP 508 EP 518 DI 10.1038/nrc2154 PG 11 WC Oncology SC Oncology GA 181UW UT WOS:000247462600012 PM 17568791 ER PT J AU Su, XZ Hayton, K Wellems, TE AF Su, Xinzhuan Hayton, Karen Wellems, Thomas E. TI Genetic linkage and association analyses for trait mapping in Plasmodium falciparum SO NATURE REVIEWS GENETICS LA English DT Review ID CHLOROQUINE-RESISTANCE LOCUS; TRANSMEMBRANE PROTEIN PFCRT; PAPUA-NEW-GUINEA; RED-BLOOD-CELLS; MALARIA PARASITES; IN-VITRO; DRUG-RESISTANCE; LIFE-CYCLE; FERRIPROTOPORPHYRIN-IX; MEFLOQUINE RESISTANCE AB Genetic studies of Plasmodium falciparum laboratory crosses and field isolates have produced valuable insights into determinants of drug responses, antigenic variation, disease virulence, cellular development and population structures of these virulent human malaria parasites. Full-genome sequences and high-resolution haplotype maps of SNPs and microsatellites are now available for all 14 parasite chromosomes. Rapidly increasing genetic and genomic information on Plasmodium parasites, mosquitoes and humans will combine as a rich resource for new advances in our understanding of malaria, its transmission and its manifestations of disease. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS NR 118 TC 50 Z9 50 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD JUL PY 2007 VL 8 IS 7 BP 497 EP 506 DI 10.1038/nrg2126 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 180EJ UT WOS:000247344800012 PM 17572690 ER PT J AU Nabel, GJ AF Nabel, Gary J. TI Mapping the future of HIV vaccines SO NATURE REVIEWS MICROBIOLOGY LA English DT Editorial Material ID AIDS VACCINE; NEUTRALIZATION; VIREMIA; GP120 AB Efforts to develop an HIV vaccine have been slower than expected, but significant progress has been made in recent years. Gary Nabel provides an update on this progress, and describes how the field is now poised to begin translating scientific understanding into improved vaccine candidates. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 13 TC 10 Z9 11 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD JUL PY 2007 VL 5 IS 7 BP 482 EP U14 DI 10.1038/nrmicro1713 PG 4 WC Microbiology SC Microbiology GA 180EH UT WOS:000247344600009 PM 17571457 ER PT J AU Whitehead, SS Blaney, JE Durbin, AP Murphy, BR AF Whitehead, Stephen S. Blaney, Joseph E. Durbin, Anna P. Murphy, Brian R. TI Prospects for a dengue virus vaccine SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID ANTIBODY-DEPENDENT ENHANCEMENT; GLYCOPROTEIN PROTECT MICE; HEMORRHAGIC-FEVER; RHESUS-MONKEYS; DISEASE SEVERITY; YELLOW-FEVER; NEUTRALIZING ANTIBODIES; MONOCLONAL-ANTIBODIES; VERO CELLS; NONSTRUCTURAL PROTEINS AB The number of cases of severe dengue disease continues to grow in endemic areas of southeast Asia, Central and South America, and other subtropical regions. Children bear the greatest burden of disease, and the development of an effective vaccine remains a global public health priority. A tetravalent vaccine is urgently needed and must be effective against all four dengue virus serotypes, be cost-effective and provide long-term protection. In this Review we discuss the unique immunological concerns in dengue virus vaccine development and the current prospects for the development of an acceptable vaccine, a goal that is likely to be reached in the near future. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Ctr Immunizat Res, Dept Int Hlth, Baltimore, MD 21205 USA. RP Whitehead, SS (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM swhitehead@niaid.nih.gov FU Intramural NIH HHS NR 116 TC 289 Z9 300 U1 6 U2 52 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD JUL PY 2007 VL 5 IS 7 BP 518 EP 528 DI 10.1038/nrmicro1690 PG 11 WC Microbiology SC Microbiology GA 180EH UT WOS:000247344600014 PM 17558424 ER PT J AU Ferrier, MC Sarin, H Fung, SH Schatlo, B Pluta, RM Gupta, SN Choyke, PL Oldfield, EH Thomasson, D Butman, JA AF Ferrier, Moira C. Sarin, Hemant Fung, Steve H. Schatlo, Bawarjan Pluta, Ryszard M. Gupta, Sandeep N. Choyke, Peter L. Oldfield, Edward H. Thomasson, David Butman, John A. TI Validation of dynamic contrast-enhanced magnetic resonance imaging-derived vascular permeability measurements using quantitative autoradiography in the RG2 rat brain tumor model SO NEOPLASIA LA English DT Article DE blood brain barrier; tumor permeability; anti-angiogenesis ID TRANSCYTOLEMMAL WATER EXCHANGE; EXPERIMENTAL RG-2 GLIOMAS; REGIONAL MEASUREMENTS; ADJACENT BRAIN; INPUT FUNCTION; BREAST-CANCER; BLOOD-BRAIN; MRI; REPRODUCIBILITY; ANGIOGENESIS AB Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is widely used to evaluate tumor permeability, yet measurements have not been directly validated in brain tumors. Our purpose was to compare estimates of forward leakage K-trans derived from DCE-MRI to the estimates K obtained using [C-14] aminoisobutyric acid quantitative autoradiography ([C-14] AIB QAR), an established method of evaluating blood - tumor barrier permeability. Both DCE- MRI and [C-14] AIB QAR were performed in five rats 9 to 11 days following tumor implantation. K trans in the tumor was estimated from DCE- MRI using the threeparameter general kinetic model and a measured vascular input function. Ki was estimated from QAR data using regions of interest (ROI) closely corresponding to those used to estimate K trans. K trans and Ki correlated with each other for two independent sets of central tumor ROI (R = 0.905, P =.035; R = 0.933, P =.021). In an additional six rats, K trans was estimated on two occasions to show reproducibility (intraclass coefficient = 0.9993; coefficient of variance = 6.07%). In vivo blood - tumor permeability parameters derived from DCE-MRI are reproducible and correlate with the gold standard for quantifying blood tumor barrier permeability, [C-14] AIB QAR. C1 NIH, Dept Diagnost Radiol, Ctr Natl Inst Hlth, Imaging Sci Program, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Dept Expt Neurol, Berlin, Germany. Gen Elect Med Syst, Appl Sci Lab, Baltimore, MD USA. NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA. RP Butman, JA (reprint author), NIH, Dept Diagnost Radiol, Ctr Natl Inst Hlth, Imaging Sci Program, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbutmana@cc.nih.gov RI SCHATLO, Bawarjan/F-4285-2010; Butman, John/A-2694-2008; OI Fung, Steve/0000-0002-1177-682X; Butman, John/0000-0002-1547-9195 NR 35 TC 46 Z9 48 U1 0 U2 2 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL PY 2007 VL 9 IS 7 BP 546 EP 555 DI 10.1593/neo.07289 PG 10 WC Oncology SC Oncology GA 196PS UT WOS:000248495100003 PM 17710157 ER PT J AU Lovvorn, HN Westrup, J Opperman, S Boyle, S Shi, G Anderson, J Perlman, EJ Perantoni, AO Wills, M de Caestecker, M AF Lovvorn, Harold N., III Westrup, Jenifer Opperman, Shaun Boyle, Scott Shi, Genbin Anderson, James Perlman, Elizabeth J. Perantoni, Alan O. Wills, Marcia de Caestecker, Mark TI CITED1 expression in Wilms' tumor and embryonic kidney SO NEOPLASIA LA English DT Article DE CITED1; Wilms' tumor; metanephric mesenchyme; nephroblastoma; nuclear localization ID BETA-CATENIN; NUCLEAR-PROTEIN; GENE-EXPRESSION; RODENT MODEL; HISTOLOGY; MUTATIONS; REVEALS; CELLS; MSG1; ORGANOGENESIS AB Wilms' tumors, or nephroblastomas, are thought to arise from abnormal postnatal retention and dysregulated differentiation of nephrogenic progenitor cells that originate as a condensed metanephric mesenchyme within embryonic kidneys. We have previously shown that the transcriptional regulator CITED1 (CBP/ p300 -interacting transactivators with glutamic acid [E]/ aspartic acid [D]-rich C-terminal domain) is expressed exclusively in these nephrogenic progenitor cells and is downregulated as they differentiate to form nephronic epithelia. In the current study, we show that CITED1 expression persists in blastemal cell populations of both experimental rat nephroblastomas and human Wilms' tumors, and that primary human Wilms' tumors presenting with disseminated disease show the highest level of CITED1 expression. Unlike the predominantly cytoplasmic subcellular localization of CITED1 in the normal developing kidney, CITED1 is clearly detectable in the nuclear compartment of Wilms' tumor blastema. These findings indicate that CITED1 is a marker of primitive blastema in Wilms' tumors and suggest that persistent expression and/ or altered subcellular localization of CITED1 in the condensed metanephric mesenchyme could play a role in Wilms' tumor initiation and pathogenesis. C1 Vanderbilt Univ, Sch Med, Dept Pediat Surg, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Div Nephrol & Cell & Dev Biol, Nashville, TN 37212 USA. Univ Nebraska Med Ctr, Omaha, NE 68198 USA. Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA. Natl Canc Inst, Lab Comparat Carcinogenesis, Frederick, MD USA. Vanderbilt Univ, Sch Med, Sect Pediat Pathol, Nashville, TN 37212 USA. RP Lovvorn, HN (reprint author), Suite 4150,2200 Childrens Way, Nashville, TN 37232 USA. EM harold.lovvorn@vanderbilt.edu FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK061558, R01DK61558] NR 45 TC 24 Z9 24 U1 0 U2 2 PU NEOPLASIA PRESS PI ANN ARBOR PA 1150 W MEDICAL CENTER DR, MSRB III, RM 9303, ANN ARBOR, MI 48109-0648 USA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD JUL PY 2007 VL 9 IS 7 BP 589 EP 600 DI 10.1593/neo.07358 PG 12 WC Oncology SC Oncology GA 196PS UT WOS:000248495100008 PM 17710162 ER PT J AU Sampson, JH Raghavan, R Brady, ML Provenzale, JM Herndon, JE Croteau, D Friedman, AH Reardon, DA Coleman, RE Wong, T Bigner, DD Pastan, I Rodriguez-Ponce, MI Tanner, P Puri, R Pedain, C AF Sampson, John H. Raghavan, Raghu Brady, Martin L. Provenzale, James M. Herndon, James E., II Croteau, David Friedman, Allan H. Reardon, David A. Coleman, R. Edward Wong, Terence Bigner, Darell D. Pastan, Ira Rodriguez-Ponce, Maria Inmaculada Tanner, Philipp Puri, Raj Pedain, Christoph TI Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions SO NEURO-ONCOLOGY LA English DT Article DE brain neoplasms; computer simulation; convection; drug delivery systems; single-photon emission computed tomography ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; RAT-BRAIN; TOXIN; MODEL; MOLECULES; EFFICACY AB Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (I-123-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal in plane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique. C1 Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Therataxis LLC, Baltimore, MD 21210 USA. NeoPharm Inc, Waukegan, IL 60085 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. BrainLAB, D-85622 Feldkirchen, Germany. Univ Munich, Klinikum Grosshadern, Dept Neurosurg, D-81377 Munich, Germany. US FDA, CBER, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Box 3050, Durham, NC 27710 USA. EM john.sampson@duke.edu RI Coleman, Ralph/A-7865-2009 FU Intramural NIH HHS; NCI NIH HHS [5P50-CA108786, P50 CA108786, R01 CA097611]; NCRR NIH HHS [K23 RR016065, K23 RR16065, S10 RR15697]; NINDS NIH HHS [2P50-NS20023, P50 NS020023] NR 44 TC 72 Z9 74 U1 0 U2 6 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2007 VL 9 IS 3 BP 343 EP 353 DI 10.1215/15228517-2007-007 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 189UL UT WOS:000248014000014 PM 17435179 ER PT J AU Jin, JK Ahn, BH Na, YJ Kim, JI Kim, YS Choi, EK Ko, YG Chung, KC Kozlowski, PB Min, DS AF Jin, Jae-Kwang Ahn, Bong-Hyun Na, Yeo-Jung Kim, Jae-Il Kim, Yong-Sun Choi, Eun-Kyoung Ko, Young-Gyu Chung, Kwang Chul Kozlowski, Piotr B. Min, Do Sik TI Phospholipase D1 is associated with amyloid precursor protein in Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE Alzheimer's disease; amyloid precursor protein; beta-amyloid; phospholipase D; reactive astrocytes; caveolin ID UP-REGULATION; CEREBRAL-CORTEX; BETA; EXPRESSION; D1; MEMBRANE; RATS; SYNAPTOSOMES; ACTIVATION; HYPOTHESIS AB Amyloid precursor protein (APP) is a widely expressed transmembrane protein of unknown function that is involved in the pathogenesis of Alzheimer's disease (AD). We investigated the involvement of phospholipase D (PLD) in the pathophysiology of AD. We showed dramatic upregulation of PLD1 immunoreactivity in reactive astroglial cells in brain tissue sections from authentic AD patients. Expression and activity of PLD1 were up-regulated in brain tissues from AD patients, especially caveolae membrane fraction, compared with those of control brains. Interestingly, PLD1 physically interacts and colocalizes with APP and caveolin-3. We found that APP was associated with the pleckstrin homology domain of PLD I, and the arnyloid region of APP interacted with PLD. Elevated expression of APP stimulated PLD activity in human astroglioma cells. These results suggest that up-regulation of PLD might have a role in the neuronal pathology associated with AD. (C) 2006 Elsevier Inc. All rights reserved. C1 Pusan Natl Univ, Dept Mol Biol, Coll Nat Sci, Pusan 609735, South Korea. Hallym Univ, Ilsong Inst Life Sci, Anyang 431060, Kyonggi Do, South Korea. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. New York State Inst Basic Res Dev Disabil, Staten Isl, NY 10314 USA. Korea Univ, Coll Life Sci & Biotechnol, Seoul 136701, South Korea. Yonsei Univ, Dept Biol, Coll Sci, Seoul 120752, South Korea. RP Min, DS (reprint author), Pusan Natl Univ, Dept Mol Biol, Coll Nat Sci, 30 Jangjeon Dong, Pusan 609735, South Korea. EM minds@pusan.ac.kr NR 39 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2007 VL 28 IS 7 BP 1015 EP 1027 DI 10.1016/j.neurobiolaging.2006.05.022 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 167ZV UT WOS:000246492400005 PM 16797788 ER PT J AU Iribarren, P Chen, K Gong, W Cho, EH Lockett, S Uranchimeg, B Wang, JM AF Iribarren, Pablo Chen, Keqiang Gong, Wanghua Cho, Edward H. Lockett, Stephen Uranchimeg, Badarch Wang, Ji Ming TI Interleukin 10 and TNF alpha synergistically enhance the expression of the G protein-coupled formylpeptide receptor 2 in microglia SO NEUROBIOLOGY OF DISEASE LA English DT Article DE cytokines; chemotaxis; inflammation; protein kinases; neuroimmunology ID CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PEPTIDE; ALZHEIMERS-DISEASE; ACTIVATED MICROGLIA; MULTIPLE-SCLEROSIS; SCAVENGER RECEPTOR; TRANSGENIC MICE; CELLS; MACROPHAGES; ASTROCYTES AB Microglia are important participants in inflammatory responses in the central nervous system. We previously observed that tumor necrosis factor alpha (TNF alpha) induces the expression of the formylpeptide receptor mFPR2 on microglial cells. This chemoattractant receptor mediates microglial cell chemotaxis in response to a variety of peptides, including amyloid 0 peptide (A beta(42)), a major pathogenic factor in Alzheimer's disease (AD). In search for agents that regulate microglial activation, we unexpectedly found that IL-10 enhanced the expression of mFPR2 on TNF alpha-activated microglia. This was associated with a markedly increased microglial chemotaxis to A beta(42) and its endocytosis via mFPR2. Mechanistic studies revealed that the synergistic effect of IL-10 on TNF alpha-induction of mFPR2 in microglia was dependent on activation of p38 MAPK. Our results suggest that IL-10 may affect the pathogenic process of AD by up-regulating mFPR2 and thus favoring the recognition and internalization of A beta(42) by activated microglial cells. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, CIBICI CONICET, RA-5000 Cordoba, Argentina. NCI, Ctr Canc Res, Mol Immunoregulat Lab, Frederick, MD 21702 USA. SAIC Frederick, Tumor Hypoxia Lab, Basic Res Program, Frederick, MD 21702 USA. SAIC Frederick, Tumor Hypoxia Lab, Dev Therapeut Program, Frederick, MD 21702 USA. SAIC Frederick, Image Anal Lab, Frederick, MD 21702 USA. RP Iribarren, P (reprint author), Univ Nacl Cordoba, Fac Ciencias Quim, Dept Bioquim Clin, CIBICI CONICET, RA-5000 Cordoba, Argentina. EM piribarr@mail.fcq.unc.edu.ar RI Cho, Edward/B-3727-2012 OI Cho, Edward/0000-0002-0278-334X FU NCI NIH HHS [N01CO12400, N01 CO012400, N01 CO12400] NR 51 TC 7 Z9 7 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUL PY 2007 VL 27 IS 1 BP 90 EP 98 DI 10.1016/j.nbd.2007.04.010 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 187PL UT WOS:000247860200009 PM 17544285 ER PT J AU Yamamoto, H Kamegaya, E Hagino, Y Imai, K Fujikawa, A Tamura, K Enokiya, T Yamamoto, T Takeshima, T Koga, H Uhl, GR Ikeda, K Sora, I AF Yamamoto, Hideko Kamegaya, Etsuko Hagino, Yoko Imai, Kazuhide Fujikawa, Akihiro Tamura, Kohei Enokiya, Tomoyuki Yamamoto, Toshifumi Takeshima, Takao Koga, Hisashi Uhl, George R. Ikeda, Kazutaka Sora, Ichiro TI Genetic deletion of vesicular monoamine transporter-2 (VMAT2) reduces dopamine transporter activity in mesencephalic neurons in primary culture SO NEUROCHEMISTRY INTERNATIONAL LA English DT Article DE vMAT2-KO; DAT; primary brain stem culture; mKIAA gene ID KNOCKOUT MICE; CHROMAFFIN GRANULES; PARKINSONS-DISEASE; EXPRESSION CLONING; AMPHETAMINE; COCAINE; PROTEIN; BRAIN; CDNA; NEUROTOXICITY AB Our aim was to investigate whether a defect in vesicular monoamine transporter-2 (VMAT2) activities would affect dopaminergic cell functions or not. We examined mesencephalon dopamimergic cultures prepared from VMAT2 wild-type, heterozygous or homozygous knockout (KO) 14-day-old mouse fetuses to determine the number of tyrosine hydroxylase (TH)-positive cells and dopamine transporter activity. The number of TH-positive cells remained unchanged in the VMAT2-KO cultures. Of interest, the dopamine transporter activity in the homozygous cells was significantly decreased, but not in the heterozygous cells, suggesting that complete deletion of VMAT2 inhibited dopamine transporter function. Furthermore, dopamine transporter activity was prominently decreased in the synaptosomal fraction of neonatal homozygous VMAT2-KO mice compared with that of wild-type/heterozygous VMAT2-KO ones, indicating that VMAT2 activity might be one of the factors regulating dopamine transporter activities. To test this possibility, we used reserpine, a VMAT2 inhibitor. Reserpine (1 mu M) decreased dopamine transporter activity (approx. 50%) in wild-type and heterozygous VMAT2-KO cultures but not in homozygous ones, indicating that blockade of VMAT2 activity reduced dopamine transporter activity. To investigate possible mechanisms underlying the decreased dopamine transporter activity in VMAT2-KO mice, we measured dopamine transporter activities after 24-48 It exposure of primary cultures of mesencephalic neurons to dopamine receptor antagonists, PKC inhibitor, PI3K inhibitor, and L-DOPA. Among these drugs, L-DCPA slightly reduced the dopamine transporter activities of all genotypes, but the other drugs could not. Since the ratios of reduction in dopamine transporter activity of each genotype treated with L-DOPA were similar, substrate inhibition of dopamine transporters was not the main mechanism underlying the reduced dopamine transporter activity due to genetic deletion of VMAT2. Our results demonstrate that genetic deletion of VMAT2 did not induce immediate cell death but did markedly inhibit dopamine transporter activity. (C) 2007 Elsevier Ltd. All rights reserved. C1 Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, Tokyo 1568585, Japan. Kazusa DNA Res Inst, Dept Human Genome Technol, Chiba, Japan. Natl Inst Basic Biol, Div Mol Neurobiol, Okazaki, Aichi 444, Japan. Yokohama City Univ, Yokohama, Kanagawa 232, Japan. Tottori Univ, Fac Med, Inst Neurol Sci, Tottori 680, Japan. NIDA, Mol Neurobiol Branch, Baltimore, MD USA. Tohoku Univ, Sch Med, Dept Psychobiol, Sendai, Miyagi 980, Japan. RP Yamamoto, H (reprint author), Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM yamahide@prit.go.jp RI Ikeda, Kazutaka/I-4694-2013; Fujikawa, Akihiro/K-9805-2015 OI Ikeda, Kazutaka/0000-0001-8342-0278; Fujikawa, Akihiro/0000-0002-3950-0550 NR 26 TC 7 Z9 10 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0197-0186 J9 NEUROCHEM INT JI Neurochem. Int. PD JUL-SEP PY 2007 VL 51 IS 2-4 BP 237 EP 244 DI 10.1016/j.neuint.2007.06.022 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 204WX UT WOS:000249075800020 PM 17664021 ER PT J AU Stein, JL Wiedholz, LM Bassett, DS Weinberger, DR Zink, CF Mattay, VS Meyer-Lindenberg, A AF Stein, Jason L. Wiedholz, Lisa M. Bassett, Danielle S. Weinberger, Daniel R. Zink, Caroline F. Mattay, Venkata S. Meyer-Lindenberg, Andreas TI A validated network of effective amygdalla connectivity SO NEUROIMAGE LA English DT Article ID ORBITOFRONTAL CORTEX; STRUCTURAL EQUATION; PREFRONTAL CORTEX; RHESUS-MONKEY; HIPPOCAMPAL-FORMATION; CORTICAL PROJECTIONS; FACIAL EXPRESSIONS; NEURAL MECHANISMS; BRAIN; EMOTION AB Regulatory interactions with the amygdala are thought to be critical for emotional processing in the extended limbic system. Structural equation modeling (path analysis) is a widely used method to quantify interactions among brain regions based on connectivity models, but is often limited by lack of precise anatomical and functional constraints. To address this issue, we developed an automated elaborative path analysis procedure guided by known anatomical connectivity in the macaque. We applied this technique to a large human fMRI data set acquired during perceptual processing of angry or fearful facial stimuli. The derived models were inferentially validated using a bootstrapping split-half approach in pairs of 500 independent groups. Significant paths across the groups were used to form a rigorously validated and consistent path model. We confirm and extend previous observations of amygdala regulation by an extended prefrontal network encompassing cingulate, orbitofrontal, insular, and dorsolateral prefrontal cortex, as wen as strong interactions between amygdala and parahippocampal gyrus. This validated model can be used to study neurocognitive correlates as wen as genotype or disease-related alterations of functional interactions in the limbic system. Published by Elsevier Inc. C1 Unit Syst Neurosci Psychiat, Bethesda, MD 20892 USA. Neuroimaging Core Facil, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,DHHS, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), 10-3C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasm@mail.nih.gov RI Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 60 TC 232 Z9 235 U1 1 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2007 VL 36 IS 3 BP 736 EP 745 DI 10.1016/j.neuroimage.2007.03.022 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 184IJ UT WOS:000247634400023 PM 17475514 ER PT J AU Kleber, B Birbaumer, N Veit, R Trevorrow, T Lotze, M AF Kleber, B. Birbaumer, N. Veit, R. Trevorrow, T. Lotze, M. TI Overt and imagined singing of an Italian aria SO NEUROIMAGE LA English DT Review DE auditory imagery; singing; audio-motor; musicians; tMRI ID AUDITORY VERBAL IMAGERY; VISUAL MENTAL-IMAGERY; PRIMARY MOTOR CORTEX; FUNCTIONAL-ANATOMY; HAND MOVEMENTS; SPEECH PRODUCTION; INVESTIGATING EMOTION; MUSIC PERCEPTION; BRAIN ACTIVATION; WORKING-MEMORY AB Activation maps of 16 professional classical singers were evaluated during overt singing and imagined singing of an Italian aria utilizing a sparse sampling functional magnetic imaging (fMRI) technique. Overt singing involved bilateral primary and secondary sensorimotor and auditory cortices but also areas associated with speech and language production. Activation magnitude within the gyri of Heschl (A1) was comparable in both hemispheres. Subcortical motor areas (cerebellum, thalamus, medulla and basal ganglia) were active too. Areas associated with emotional processing showed slight (anterior cingulate cortex, anterior insula) activation. Cerebral activation sites during imagined singing were centered on fronto-parietal areas and involved primary and secondary sensorimotor areas in both hemispheres. Areas processing emotions showed intense activation (ACC and bilateral insula, hippocampus and anterior temporal poles, bilateral amygdala). Imagery showed no significant activation in A1. Overt minus imagined singing revealed increased activation in cortical (bilateral primary motor; M1) and subcortical (right cerebellar hemisphere, medulla) motor as well as in sensory areas (primary somatosensory cortex, bilateral A1). Imagined minus overt singing showed enhanced activity in the medial Brodmann's area 6, the ventrolateral and medial prefrontal cortex (PFC), the anterior cingulate cortex and the inferior parietal lobe. Additionally, Wernicke's area and Brocca's area and their homologues were increasingly active during imagery. We conclude that imagined and overt singing involves partly different brain systems in professional singers with more prefrontal and limbic activation and a larger network of higher order associative functions during imagery. (c) 2007 Published by Elsevier Inc. C1 Univ Tubingen, Inst Med Psychol & Verhaltensneurobiol, D-72074 Tubingen, Germany. NINDS, NIH, Human Cortial Physiol Sect, Bethesda, MD USA. Chaminade Univ Honolulu, Honolulu, HI USA. Univ Greifswald, Ctr Radiol, Dept Funct Imaging, Greifswald, Germany. RP Kleber, B (reprint author), Univ Tubingen, Inst Med Psychol & Verhaltensneurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM boris.kleber@uni-tuebingen.de RI Veit, Ralf/F-8907-2012 OI Veit, Ralf/0000-0001-9860-642X NR 105 TC 72 Z9 72 U1 3 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2007 VL 36 IS 3 BP 889 EP 900 DI 10.1016/j.neuroimage.2007.02.053 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 184IJ UT WOS:000247634400035 PM 17478107 ER PT J AU Goldstein, M Brendel, G Tuescher, O Pan, H Epstein, J Beutel, M Yang, YH Thomas, K Levy, K Silverman, M Clarkin, J Posner, M Kernberg, O Stern, E Silbersweig, D AF Goldstein, Martin Brendel, Gary Tuescher, Oliver Pan, Hong Epstein, Jane Beutel, Manfred Yang, Yihong Thomas, Katherine Levy, Kenneth Silverman, Michael Clarkin, Jonathon Posner, Michael Kernberg, Otto Stern, Emily Silbersweig, David TI Neural substrates of the interaction of emotional stimulus processing and motor inhibitory control: An emotional linguistic go/no-go fMRI study SO NEUROIMAGE LA English DT Review ID ANTERIOR CINGULATE CORTEX; VENTROMEDIAL PREFRONTAL CORTEX; EVENT-RELATED FMRI; BORDERLINE PERSONALITY-DISORDER; FUNCTIONAL MRI; ORBITOFRONTAL CORTEX; RESPONSE-INHIBITION; WORKING-MEMORY; INDIVIDUAL-DIFFERENCES; EXECUTIVE FUNCTIONS AB Neural substrates of behavioral inhibitory control have been probed in a variety of animal model, physiologic, behavioral, and imaging studies, many emphasizing the role of prefrontal circuits. Likewise, the neurocircuitry of emotion has been investigated from a variety of perspectives. Recently, neural mechanisms mediating the interaction of emotion and behavioral regulation have become the focus of intense study. To further define neurocircuitry specifically underlying the interaction between emotional processing and response inhibition, we developed an emotional linguistic go/no-go fMRI paradigm with a factorial block design which joins explicit inhibitory task demand (i.e., go or no-go) with task-unrelated incidental emotional stimulus valence manipulation, to probe the modulation of the former by the latter. In this study of normal subjects focusing on negative emotional processing, we hypothesized activity changes in specific frontal neocortical and limbic regions reflecting modulation of response inhibition by negative stimulus processing. We observed common fronto-limbic activations (including orbitofrontal cortical and amygdalar components) associated with the interaction of emotional stimulus processing and response suppression. Further, we found a distributed cortico-limbic network to be a candidate neural substrate for the interaction of negative valence-specific processing and inhibitory task demand. These findings have implications for elucidating neural mechanisms of emotional modulation of behavioral control, with relevance to a variety of neuropsychiatric disease states marked by behavioral dysregulation within the context of negative emotional processing. (c) 2007 Elsevier Inc. All rights reserved. C1 CUNY Mt Sinai Sch Med, Dept Neurol, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Psychiat, Funct Neuroimaging Lab, Ithaca, NY 14853 USA. Univ Freiburg, Dept Neurol, D-7800 Freiburg, Germany. Univ Mainz, Dept Psychosomat Med & Psychotherapy, Giessen, Germany. NIDA, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Inst Child Dev, Minneapolis, MN 55455 USA. Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. Penn State Univ, Dept Psychol, University Pk, PA 16802 USA. RP Goldstein, M (reprint author), CUNY Mt Sinai Sch Med, Dept Neurol, 1 Gustave L Levy Pl, New York, NY 10021 USA. EM martin.goldstein@mssm.edu RI Silverman, Michael/A-5688-2008; Stern, Emily/E-6035-2011 FU NIMH NIH HHS [R25 MH060478] NR 134 TC 88 Z9 96 U1 7 U2 37 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2007 VL 36 IS 3 BP 1026 EP 1040 DI 10.1016/j.neuroimage.2007.01.056 PG 15 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 184IJ UT WOS:000247634400047 PM 17509899 ER PT J AU Riegel, AC Zapata, A Shippenberg, TS French, ED AF Riegel, Arthur C. Zapata, Agustin Shippenberg, Toni S. French, Edward D. TI The abused inhalant toluene increases dopamine release in the nucleus accumbens by directly stimulating ventral tegmental area neurons SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE inhalant abuse; ventral tegmental area (VTA); nucleus accumbens (ACB); electrophysiology; microdialysis; dopamine (DA) ID VESICULAR CATECHOLAMINE RELEASE; CONDITIONED PLACE PREFERENCE; DUAL-PROBE MICRODIALYSIS; GAMMA-AMINOBUTYRIC-ACID; FREELY MOVING RATS; IN-VITRO; INTERPEDUNCULAR NUCLEUS; EXTRACELLULAR DOPAMINE; REGIONAL HETEROGENEITY; SELF-STIMULATION AB Recreational abuse of toluene-containing volatile inhalants by adolescents is a significant public health problem. The mechanisms underlying the abuse potential of such substances remain unclear, but could involve increased activity in mesoaccumbal dopamine (DA) afferents innervating the nucleus accumbens (ACB). Here, using in vitro electrophysiology, we show that application of behaviorally relevant concentrations of toluene directly stimulates DA neurons in the ventral tegmental area (VTA), but not surrounding midbrain regions. Toluene stimulation of VTA neurons persists when synaptic transmission is reduced. Moreover, unlike non-DA neurons, the magnitude of VTA DA neuron firing does not decline during longer exposures designed to emulate 'huffing'. Using dual-probe in vivo microdialysis, we show that perfusion of toluene directly into the VTA increases DA concentrations in the VTA (somatodendritic release) and its terminal projection site, the ACB. These results provide the first demonstration that even brief exposure to toluene increases action potential drive onto mesoaccumbal VTA DA neurons, thereby enhancing DA release in the ACB. The finding that toluene stimulates mesoaccumbal neurotransmission by activating VTA DA neurons directly (independently of transynaptic inputs) provide insights into the neural substrates that may contribute to the initiation and pathophysiology of toluene abuse. C1 Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR USA. Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA. NIDA, Intramural Res Program, Integrat Neurosci Sect, US Dept Hlth & Human Serv,NIH, Baltimore, MD USA. RP Riegel, AC (reprint author), Oregon Hlth & Sci Univ, Vollum Inst, 3181 SW Sam Jackson Pk Rd,Mail Stop L474, Portland, OR USA. EM Riegela@OHSU.edu FU Intramural NIH HHS NR 96 TC 51 Z9 52 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2007 VL 32 IS 7 BP 1558 EP 1569 DI 10.1038/sj.npp.1301273 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 179NV UT WOS:000247297500011 PM 17213847 ER PT J AU Horng, SH Miller, FG AF Horng, Sam H. Miller, Franklin G. TI Placebo-controlled procedural trials for neurological conditions SO NEUROTHERAPEUTICS LA English DT Review DE placebo-controlled trials; sham surgery; cross-over; ethics; neurological procedures; deception ID TRANSCRANIAL MAGNETIC STIMULATION; RANDOMIZED CONTROLLED-TRIAL; MAMMARY-ARTERY LIGATION; DEEP-BRAIN-STIMULATION; PARKINSONS-DISEASE; CLINICAL-RESEARCH; SHAM SURGERY; SURGICAL TRIALS; ETHICS; TRANSPLANTATION AB Neurological disease has been a central focus in the ongoing ethical debate over the use of invasive placebo controls, especially sham surgery. The risk to research subjects and necessary use of deception involved in these procedures must be balanced against the methodological need to control for bias and the placebo effect. We review a framework formulated for the ethical assessment of sham surgery in the context of research evaluating novel procedures for neurological conditions. Special issues raised include the growing evidence of expectation and conditioning effects in a number of neurological diseases, the escalating scale of risk from different types of invasive placebo interventions, and the increasing use of cross-over designs, which allow a switch from placebo to active intervention without additional procedures. C1 NIH, Dept Bioeth Clin, Bethesda, MD 20892 USA. MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. RP Miller, FG (reprint author), NIH, Dept Bioeth Clin, Rm 1C118, Bethesda, MD 20892 USA. EM FMiller@ce.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 44 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1933-7213 J9 NEUROTHERAPEUTICS JI Neurotherapeutics PD JUL PY 2007 VL 4 IS 3 BP 531 EP 536 DI 10.1016/j.nurt.2007.03.001 PG 6 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 214UD UT WOS:000249762800021 PM 17599718 ER PT J AU Brown, RA Niaura, R Lloyd-Richardson, EE Strong, DR Kahler, CW Abrantes, AM Abrams, D Miller, IW AF Brown, Richard A. Niaura, Raymond Lloyd-Richardson, Elizabeth E. Strong, David R. Kahler, Christopher W. Abrantes, Ana M. Abrams, David Miller, Ivan W. TI Bupropion and cognitive-behavioral treatment for depression in smoking cessation SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID SUSTAINED-RELEASE BUPROPION; LONGITUDINAL DATA-ANALYSIS; NICOTINE DEPENDENCE; CONTROLLED-TRIAL; COMBINED PSYCHOTHERAPY; RELAPSE PREVENTION; CIGARETTE-SMOKING; MAJOR DEPRESSION; DOUBLE-BLIND; SMOKERS AB This study is a randomized, double-blind, placebo-controlled clinical trial examining the effects of an intensive cognitive-behavioral mood management treatment (CBTD) and of bupropion, both singularly and in combination, on smoking cessation in adult smokers. As an extension of our previous work, we planned to examine the synergistic effects of CBTD and bupropion on smoking cessation outcomes in general and among smokers with depression vulnerability factors. Participants were 524 smokers (47.5% female, Mag,=44.27 years) who were randomized to one of four 12-week treatments: (a) standard, cognitive-behavioral smoking cessation treatment (ST) plus bupropion (BUP), (b) ST plus placebo (PLAC, (c) standard cessation treatment combined with cognitive-behavioral treatment for depression (CBTD) plus BUP, and (d) CBTD plus PLAC. Follow-up assessments were conducted 2, 6, and 12 months after treatment, and self-reported abstinence was verified biochemically. Consistent with previous studies, bupropion, in comparison with placebo, resulted in better smoking outcomes in both intensive group treatments. Adding CBTD to standard intensive group treatment did not result in improved smoking cessation outcomes. In addition, neither CBTD nor bupropion, either alone or in combination, was differentially effective for smokers with single-past-episode major depressive disorder (MDD), recurrent MDD, or elevated depressive symptoms. However, findings with regard to recurrent MDD and elevated depressive symptoms should be interpreted with caution given the low rate of recurrent MDD and the low level of depressive symptoms in our sample. An a priori test of treatment effects in smokers with these depression vulnerability factors is warranted in future clinical trials. C1 Brown Univ, Butler Hosp, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Miriam Hosp, Providence, RI 02906 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02906 USA. NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA. RP Brown, RA (reprint author), Brown Univ, Butler Hosp, Sch Med, Dept Psychiat & Human Behav, 345 Blackstone Blvd, Providence, RI 02906 USA. EM richard_brown@brown.edu FU NHLBI NIH HHS [HL32318]; NIDA NIH HHS [DA08511, R01 DA008511, R01 DA008511-08] NR 56 TC 67 Z9 68 U1 1 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD JUL PY 2007 VL 9 IS 7 BP 721 EP 730 DI 10.1080/14622200701416955 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 189GR UT WOS:000247977900002 PM 17577801 ER PT J AU Kann, MG Sheetlin, SL Park, Y Bryant, SH Spouge, JL AF Kann, Maricel G. Sheetlin, Sergey L. Park, Yonil Bryant, Stephen H. Spouge, John L. TI The identification of complete domains within protein sequences using accurate E-values for semi-global alignment SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HIDDEN MARKOV-MODELS; PSI-BLAST; SIMILARITY SEARCHES; NUCLEIC-ACID; DATABASE; PERFORMANCE; STATISTICS; FAMILIES; MOTIFS; MEME AB The sequencing of complete genomes has created a pressing need for automated annotation of gene function. Because domains are the basic units of protein function and evolution, a gene can be annotated from a domain database by aligning domains to the corresponding protein sequence. Ideally, complete domains are aligned to protein subsequences, in a 'semi-global alignment'. Local alignment, which aligns pieces of domains to subsequences, is common in high-throughput annotation applications, however. It is a mature technique, with the heuristics and accurate E-values required for screening large databases and evaluating the screening results. Hidden Markov models (HMMs) provide an alternative theoretical framework for semi-global alignment, but their use is limited because they lack heuristic acceleration and accurate E-values. Our new tool, GLOBAL, overcomes some limitations of previous semi-global HMMs: it has accurate E-values and the possibility of the heuristic acceleration required for high-throughput applications. Moreover, according to a standard of truth based on protein structure, two semi-global HMM alignment tools (GLOBAL and HMMer) had comparable performance in identifying complete domains, but distinctly outperformed two tools based on local alignment. When searching for complete protein domains, therefore, GLOBAL avoids disadvantages commonly associated with HMMs, yet maintains their superior retrieval performance. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Dept Hlth & Human Serv, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov RI Kann, Maricel/E-5701-2012 FU Intramural NIH HHS NR 40 TC 12 Z9 12 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2007 VL 35 IS 14 BP 4678 EP 4685 DI 10.1093/nar/gkm414 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 212QP UT WOS:000249612200010 PM 17596268 ER PT J AU Bao, Y Bolotov, P Dernovoy, D Kiryutin, B Tatusova, T AF Bao, Yiming Bolotov, Pavel Dernovoy, Dmitry Kiryutin, Boris Tatusova, Tatiana TI FLAN: a web server for influenza virus genome annotation SO NUCLEIC ACIDS RESEARCH LA English DT Article AB FLAN (short for FLu ANnotation), the NCBI web server for genome annotation of influenza virus (http://www.ncbi.nlm.nih.gov/genomes/FLU/Database/annotation.cgi) is a tool for user-provided influenza A virus or influenza B virus sequences. It can validate and predict protein sequences encoded by an input flu sequence. The input sequence is BLASTed against a database containing influenza sequences to determine the virus type (A or B), segment (1 through 8) and subtype for the hemagglutinin and neuraminidase segments of influenza A virus. For each segment/subtype of the viruses, a set of sample protein sequences is maintained. The input sequence is then aligned against the corresponding protein set with a 'Protein to nucleotide alignment tool' (ProSplign). The translated product from the best alignment to the sample protein sequence is used as the predicted protein encoded by the input sequence. The output can be a feature table that can be used for sequence submission to GenBank (by Sequin or tbl2asn), a GenBank flat file, or the predicted protein sequences in FASTA format. A message showing the length of the input sequence, the predicted virus type, segment and subtype for the hemagglutinin and neuraminidase segments of Influenza A virus will also be displayed. C1 [Bao, Yiming; Bolotov, Pavel; Dernovoy, Dmitry; Kiryutin, Boris; Tatusova, Tatiana] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Tatusova, T (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM tatiana@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 7 TC 20 Z9 21 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2007 VL 35 SU S BP W280 EP W284 DI 10.1093/nar/gkm354 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293CD UT WOS:000255311500052 PM 17545199 ER PT J AU Dogan, RI Getoor, L Wilbur, WJ Mount, SM AF Dogan, Rezarta Islamaj Getoor, Lise Wilbur, W. John Mount, Stephen M. TI SplicePort - An interactive splice-site analysis tool SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PRE-MESSENGER-RNA; SEQUENCE INFORMATION; PREDICTION; ENHANCERS; IDENTIFICATION; CLASSIFICATION; SILENCERS; DNA AB SplicePort is a web-based tool for spliceanalysis that allows the user to make splicepredictions for submitted sequences. In the user can also browse the rich catalog of that underlies these predictions, and which we found capable of providing high accuracy on human splice sites. Feature is optimized for human splice sites, but the features are likely to be predictive for mammals as well. With our interactive browsing and visualization tool, the user can and explore subsets of features used in spliceprediction (either the features that account for classification of a specific input sequence or complete collection of features). Selected sets can be searched, ranked or displayed The user can group features into clusters frequency plot WebLogos can be generated each cluster. The user can browse the clusters and their contributing elements, for new interesting signals, or can validate observed signals. The SplicePort server can be accessed athttp://www.cs.umd.projects/SplicePort and http://www.spliceport.org. C1 [Dogan, Rezarta Islamaj; Getoor, Lise] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Dogan, Rezarta Islamaj; Wilbur, W. John] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Mount, Stephen M.] Univ Maryland, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. [Mount, Stephen M.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. RP Dogan, RI (reprint author), Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. EM rezarta@cs.umd.edu OI Mount, Steve/0000-0003-2748-8205 NR 16 TC 101 Z9 101 U1 1 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2007 VL 35 SU S BP W285 EP W291 DI 10.1093/nar/gkm407 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293CD UT WOS:000255311500053 PM 17576680 ER PT J AU Huang, DW Sherman, BT Tan, Q Kir, J Liu, D Bryant, D Guo, Y Stephens, R Baseler, MW Lane, HC Lempicki, RA AF Huang, Da Wei Sherman, Brad T. Tan, Qina Kir, Joseph Liu, David Bryant, David Guo, Yongjian Stephens, Robert Baseler, Michael W. Lane, H. Clifford Lempicki, Richard A. TI DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ONTO-TOOLS; PROTEIN INFORMATION; ART.; EXPRESSION; SETS; ASSOCIATIONS; CATEGORIES; UNIPROT; DESIGN AB All tools in the DAVID Bioinformatics Resources aim to provide functional interpretation of large lists of genes derived from genomic studies. The newly updated DAVID Bioinformatics Resources consists of the DAVID Knowledgebase and five integrated, web-based functional annotation tool suites: the DAVID Gene Functional Classification Tool, the DAVID Functional Annotation Tool, the DAVID Gene ID Conversion Tool, the DAVID Gene Name Viewer and the DAVID NIAID Pathogen Genome Browser. The expanded DAVID Knowledgebase now integrates almost all major and well-known public bioinformatics resources centralized by the DAVID Gene Concept, a single-linkage method to agglomerate tens of millions of diverse gene/protein identifiers and annotation terms from a variety of public bioinformatics databases. For any uploaded gene list, the DAVID Resources now provides not only the typical gene-term enrichment analysis, but also new tools and functions that allow users to condense large gene lists into gene functional groups, convert between gene/protein identifiers, visualize many-genes-to-many-terms relationships, cluster redundant and heterogeneous terms into groups, search for interesting and related genes or terms, dynamically view genes from their lists on bio-pathways and more. With DAVID (http://david.niaid.nih.gov), investigators gain more power to interpret the biological mechanisms associated with large gene lists. C1 [Huang, Da Wei; Sherman, Brad T.; Tan, Qina; Kir, Joseph; Lempicki, Richard A.] NCI, SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. [Liu, David; Bryant, David; Stephens, Robert] NCI, SAIC Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. [Baseler, Michael W.] NCI, SAIC Frederick Inc, Clin Serv Program, Frederick, MD 21702 USA. [Lane, H. Clifford] NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. [Guo, Yongjian] NIAID, NIH, NIAID Off Technol Informat Syst, Bioinformat & Sci IT Program, Bethesda, MD 20892 USA. RP Lempicki, RA (reprint author), NCI, SAIC Frederick Inc, Lab Immunopathogenesis & Bioinformat, Frederick, MD 21702 USA. EM rlempicki@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU NCI NIH HHS [N01- CO-12400, N01CO12400] NR 28 TC 417 Z9 425 U1 6 U2 34 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2007 VL 35 SU S BP W169 EP W175 DI 10.1093/nar/gkm415 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293CD UT WOS:000255311500033 PM 17576678 ER PT J AU Khaladkar, M Bellofatto, V Wang, JTL Tian, B Shapiro, BA AF Khaladkar, Mugdha Bellofatto, Vivian Wang, Jason T. L. Tian, Bin Shapiro, Bruce A. TI RADAR: a web server for RNA data analysis and research SO NUCLEIC ACIDS RESEARCH LA English DT Article ID SECONDARY STRUCTURE PREDICTION; ALGORITHM; STABILITY; SEQUENCES AB RADAR is a web server that provides a multitude of functionality for RNA data analysis and research. It can align structure-annotated RNA sequences so that both sequence and structure information are taken into consideration during the alignment process. This server is capable of performing pair-wise structure alignment, multiple structure alignment, database search and clustering. In addition, RADAR provides two salient features: (i) constrained alignment of RNA secondary structures, and (ii) prediction of the consensus structure for a set of RNA sequences. RADAR will be able to assist scientists in performing many important RNA mining operations, including the understanding of the functionality of RNA sequences, the detection of RNA structural motifs and the clustering of RNA molecules, among others. The web server together with a software package for download is freely accessible at http://datalab.njit.edu/biodata/rna/RSmatch/server.htm and http://www.ccrnp.ncifcrf.gov/similar to bshapiro/. C1 [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. [Khaladkar, Mugdha; Wang, Jason T. L.] New Jersey Inst Technol, Bioinformat Program, Newark, NJ 07102 USA. [Khaladkar, Mugdha; Wang, Jason T. L.] New Jersey Inst Technol, Dept Comp Sci, Newark, NJ 07102 USA. [Bellofatto, Vivian] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Microbiol & Mol Genet, Int Ctr Publ Hlth, Newark, NJ 07103 USA. [Tian, Bin] Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07101 USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov OI Tian, Bin/0000-0001-8903-8256 FU Intramural NIH HHS NR 23 TC 9 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2007 VL 35 SU S BP W300 EP W304 DI 10.1093/nar/gkm253 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293CD UT WOS:000255311500056 PM 17517784 ER PT J AU Khatri, P Voichita, C Kattan, K Ansari, N Khatri, A Georgescu, C Tarca, AL Draghici, S AF Khatri, Purvesh Voichita, Calin Kattan, Khalid Ansari, Nadeem Khatri, Avani Georgescu, Constantin Tarca, Adi L. Draghici, Sorin TI Onto-Tools: new additions and improvements in 2006 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION DATA; MICROARRAY DATA; BIOLOGICAL PATHWAYS; NETWORKS; TRANSLATE; DATABASES; COMPARE; GENMAPP; DESIGN; MODELS AB Onto-Tools is a freely available web-accessible software suite, composed of an annotation database and nine complementary data-mining tools. This article describes a new tool, Onto-Express-to-go (OE2GO), as well as some new features implemented in Pathway-Express and Onto-Miner over the past year. Pathway-Express (PE) has been enhanced to identify significantly perturbed pathways in a given condition using the differentially expressed genes in the input. OE2GO is a tool for functional profiling using custom annotations. The development of this tool was aimed at the researchers working with organisms for which annotations are not yet available in the public domain. OE2GO allows researchers to use either annotation data from the Onto-Tools database, or their own custom annotations. By removing the necessity to use any specific database, OE2GO makes the functional profiling available for all organisms, with annotations using any ontology. The Onto-Tools are freely available at http://vortex.cs.wayne.edu/projects.htm. C1 [Khatri, Purvesh; Voichita, Calin; Kattan, Khalid; Ansari, Nadeem; Khatri, Avani; Georgescu, Constantin; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48202 USA. [Tarca, Adi L.] NICHD, NIH, Perinatol Res Branch, Detroit, MI 48201 USA. RP Draghici, S (reprint author), Wayne State Univ, Dept Comp Sci, 431 State Hall, Detroit, MI 48202 USA. EM sorin@wayne.edu RI Draghici, Sorin/B-3074-2013 OI Draghici, Sorin/0000-0002-0786-8377 FU NCI NIH HHS [1R21CA100740-01, 2P30 CA022453-24, U01 CA117478, 1U01CA117478-01, P30 CA022453, R21 CA100740]; NCRR NIH HHS [S10 RR017857, 1S10 RR017857-01]; NHGRI NIH HHS [1R01HG003491-01A1, R01 HG003491]; NIBIB NIH HHS [5R21EB000990-03, R21 EB000990]; NINDS NIH HHS [1R01NS045207-01, R01 NS045207] NR 24 TC 67 Z9 68 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2007 VL 35 SU S BP W206 EP W211 DI 10.1093/nar/gkm327 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 293CD UT WOS:000255311500039 PM 17584796 ER PT J AU Gardner, DB AF Gardner, Deborah B. TI Immigration and health care reform: Shared struggles SO NURSING ECONOMICS LA English DT Article AB The connection between health care and immigration share overlaping key areas in policy reform. General concern, anger, and fear about immigration has been spreading nationwide. While illegal immigrants' use of expensive emergency department services does add to the cost for uncompensated care, this expenditure is not a primary cost driver but more a symptom of little or no access to preventative or primary health care. As a result of federal inaction, more state politicians are redefining how America copes with illegal residents including how or whether they have access to health care. The overlap of immigration and health care reform offers an opportunity for us to enter the next round of debate from a more informed vantage point. C1 Natl Inst Hlth Clin Ctr, Bethesda, MD USA. RP Gardner, DB (reprint author), Natl Inst Hlth Clin Ctr, Bethesda, MD USA. NR 12 TC 3 Z9 3 U1 0 U2 5 PU JANNETTI PUBLICATIONS, INC PI PITMAN PA EAST HOLLY AVENUE, BOX 56, PITMAN, NJ 08071-0056 USA SN 0746-1739 J9 NURS ECON JI Nurs. Econ. PD JUL-AUG PY 2007 VL 25 IS 4 BP 235 EP 237 PG 3 WC Nursing SC Nursing GA 198ZY UT WOS:000248667200009 PM 17847662 ER PT J AU Grady, PA AF Grady, Patricia A. TI Intramural research and training at NINR SO NURSING OUTLOOK LA English DT Editorial Material AB There are a variety of outstanding scientific resources available on the National Institutes of Health (NIH) campus in Bethesda, Maryland. The National Institute of Nursing Research (NINR) has been devoting effort in recent years to developing and enhancing our intramural research program, in order to maximize these opportunities for our community. C1 NINR, Bethesda, MD 20892 USA. RP Grady, PA (reprint author), NINR, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JUL-AUG PY 2007 VL 55 IS 4 BP 208 EP 209 DI 10.1016/j.outlook.2007.05.001 PG 2 WC Nursing SC Nursing GA 200TC UT WOS:000248784700010 PM 17678687 ER PT J AU Giger, JN Davidhizar, R Purnell, L Harden, JT Phillips, J Strickland, O AF Giger, Joyce Newman Davidhizar, Ruth Purnell, Larry Harden, J. Taylor Phillips, Janice Strickland, Ora TI Understanding cultural language to enhance cultural competence SO NURSING OUTLOOK LA English DT Editorial Material C1 Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. Bethel Coll, Sch Nursing, Mishawaka, IN USA. Univ Delaware, Sch Nursing, Newark, DE USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Chicago Hosp, Chicago, IL 60637 USA. Emory Univ, Nell Hodgson Woodruff Sch Nursing, Dept Family & Community Nursing, Atlanta, GA 30322 USA. RP Giger, JN (reprint author), Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. EM JGiger@sonnet.ucla.edu; RDavidhiza@aol.com NR 0 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-6554 J9 NURS OUTLOOK JI Nurs. Outlook PD JUL-AUG PY 2007 VL 55 IS 4 BP 212 EP 214 DI 10.1016/j.outlook.2007.05.004 PG 3 WC Nursing SC Nursing GA 200TC UT WOS:000248784700012 ER PT J AU Almasy, L Goring, HHH Diego, V Cole, S Laston, S Dyke, B Howard, BV Lee, ET Best, LG Devereux, R Fabsitz, RR MacCluer, JW AF Almasy, Laura Goering, Harald H. H. Diego, Vincent Cole, Shelley Laston, Sandra Dyke, Bennett Howard, Barbara V. Lee, Elisa T. Best, Lyle G. Devereux, Richard Fabsitz, Richard R. MacCluer, Jean W. TI A novel obesity locus on chromosome 4q: The strong heart family study SO OBESITY LA English DT Article DE linkage; genome-wide scan; BMI; weight ID BODY-MASS INDEX; LINKAGE ANALYSIS; AMERICAN-INDIANS; GENETIC-LINKAGE; CARDIOVASCULAR-DISEASE; LEPTIN LEVELS; PIMA-INDIANS; HUMAN GENOME; MAP; SCAN AB Objective: Obesity is a growing and important public health problem in Western countries and worldwide. There is ample evidence that both environmental and genetic factors influence the risk of developing obesity. Although a number of genes influencing obesity and obesity-related measures have been localized, it is clear that others remain to be identified. The rate of obesity is particularly high in American Indian populations. This study reports the results of a genome-wide scan for loci influencing BMI and weight in 963 individuals in 58 families from three American Indian populations in Arizona, Oklahoma, and North and South Dakota participating in the Strong Heart Family Study. Research Methods and Procedures: Short tandem repeat markers were genotyped, resulting in a marker map with an average spacing of 10 centimorgans. Standard multipoint variance component linkage methods were used. Results: Significant evidence of linkage was observed in the overall sample, including all three study sites, for a locus on chromosome 4q35 [logarithm of the odds (LOD) = 5.17 for weight, 5.08 for BMI]. Analyses of the three study sites individually showed that the greatest linkage support for the chromosome 4 locus came from Arizona (LOD = 2.6 for BMI), but that LOD scores for weight were > 1 in all three samples. Suggestive linkage signals (LOD > 2) were also observed on chromosomes 5, 7, 8, and 10. Discussion: The chromosome 4 locus detected in this scan is in a region lacking any obvious positional candidate genes with known functions related to obesity. This locus may represent a novel obesity gene. C1 SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. MedStar Res Inst, Washington, DC USA. Univ Oklahoma, Hlth Sci Ctr, Dept Biostat & Epidemiol, Oklahoma City, OK USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. Cornell Univ Med Coll, Dept Med, New York, NY USA. NHLBI, Div Prevent & Populat Sci, Bethesda, MD 20892 USA. RP Almasy, L (reprint author), SW Fdn Biomed Res, Dept Genet, POB 760549, San Antonio, TX 78245 USA. EM almasy@sfbrgenetics.org OI Diego, Vincent/0000-0002-0007-2085 FU NHLBI NIH HHS [U01 HL41654, U01 HL41642, U01 HL65521, U01 HL41652, U01 HL65520] NR 28 TC 10 Z9 10 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2007 VL 15 IS 7 BP 1741 EP 1748 DI 10.1038/oby.2007.207 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 192ZO UT WOS:000248242900015 PM 17636092 ER PT J AU Treuth, MS Catellier, DJ Schmitz, KH Pate, RR Elder, JP McMurray, RG Blew, RM Yang, S Webber, L AF Treuth, Margarita S. Catellier, Diane J. Schmitz, Kathryn H. Pate, Russell R. Elder, John P. McMurray, Robert G. Blew, Robert M. Yang, Song Webber, Larry TI Weekend and weekday patterns of physical activity in overweight and normal-weight adolescent girls SO OBESITY LA English DT Article DE activity monitors; physical activity assessment; sedentary activity; accelerometry ID RISK BEHAVIOR SURVEY; CHILDREN; SCHOOL; YOUTH; AGE AB Objective: To describe the patterns (specifically comparing weekdays and weekends classified by intensities) of physical activity (PA) measured by accelerometry in adolescent girls. Research Methods and Procedures: Healthy sixth grade girls (n = 1603), 11 to 12 years old, were randomly recruited from 36 schools participating in the Trial of Activity in Adolescent Girls. Age, ethnicity, socioeconomic status, weight, and height were taken. PA patterns were measured for 6 days using accelerometry. Results: Adolescent girls spend most of their time in sedentary (52% to 57% of the day) and light activity (40% to 45% of the day) on weekdays and weekends. In all girls, total PA comprised 44.5% of the day (41.7% light, 2.2% moderate, and 0.7% vigorous) with sedentary activity comprising 55.4%. Moderate-to-vigorous PA (MVPA) was higher (p < 0.001) on weekdays than weekends in all girls, but MVPA was lower in at-risk of overweight + overweight girls (p < 0.001) on both weekdays and weekends compared with normal-weight girls. Discussion: Adolescent girls are more active at moderate and vigorous intensities on weekdays than on weekends, and at-risk of overweight and those overweight spend less time engaging in MVPA than normal-weight girls. C1 Johns Hopkins Univ, Sch Publ Hlth, Ctr Human Nutr, Baltimore, MD 21205 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ S Carolina, Dept Exercise Sci, Columbia, SC 29208 USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. Univ Arizona, Dept Physiol, Tucson, AZ USA. NHLBI, Bethesda, MD 20892 USA. Tulane Univ, Sch Publ Hlth & Trop Med, Dept Biostat, New Orleans, LA USA. RP Treuth, MS (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Ctr Human Nutr, 615 N Wolfe St, Baltimore, MD 21205 USA. EM mtreuth@jhsph.edu RI Schmitz, Kathryn/B-7154-2011 FU NHLBI NIH HHS [U01 HL066855, U01 HL066845, U01 HL066852, U01 HL066853, U01 HL066853-07, U01 HL066856, U01 HL066857, U01 HL066858, U01HL66845, U01HL66852, U01HL66853, U01HL66855, U01HL66856, U01HL66857, U01HL66858] NR 27 TC 77 Z9 77 U1 1 U2 8 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1930-7381 J9 OBESITY JI Obesity PD JUL PY 2007 VL 15 IS 7 BP 1782 EP 1788 DI 10.1038/oby.2007.212 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 192ZO UT WOS:000248242900020 PM 17636097 ER PT J AU Reddy, UM AF Reddy, Uma M. TI The evolving prenatal screening scene SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID DOWN-SYNDROME C1 NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. RP Reddy, UM (reprint author), NICHHD, Dept Hlth & Human Serv, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 6 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2007 VL 110 IS 1 BP 2 EP 4 DI 10.1097/01.AOG.0000269044.84174.fc PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 183KW UT WOS:000247572700001 PM 17601887 ER PT J AU Zyczynski, RM Lloyd, LK Kenton, K Menefee, S Boreham, M Stoddard, AM AF Zyczynski, Ralina M. Lloyd, L. Keith Kenton, Kimberly Menefee, Shawn Boreham, Muriel Stoddard, Anne M. CA UITN TI Correlation of Q-tip values and point Aa in stress-incontinent women SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the International-Continence-Society CY AUG 28-SEP 02, 2005 CL Montreal, CANADA SP Int Continence Soc ID PELVIC ORGAN PROLAPSE; URINARY-INCONTINENCE; URETHRAL MOBILITY; TAPE PROCEDURE; FEMALE; STANDARDIZATION; SYSTEM AB OBJECTIVE: To estimate the relationship between pelvic organ prolapse quantification (POP-Q) point Aa and straining Q-tip angle. METHODS: We compared preoperative straining Q-tip angles and Aa measurements from 655 women with predominant stress incontinence and urethral hypermobility (defined as a resting or straining angle of greater than 301) using Pearson correlations and linear regression. Point Aa is 3 cm deep to the urethral meatus in the midline of the anterior vagina and corresponds to the urethrovesical crease. RESULTS: The median for point Aa was -1 cm (range -3 to +3 cm) and for straining Q-tip was 60 degrees (30-130 degrees). Twenty-nine percent of participants had an Aa at least 2 cm deep to the hymen, whereas in 69%, Aa was at or below -1 cm. The straining Q-tip angle was significantly different between these respective groups: 51.5 degrees and 64 degrees (P<.001). Linear regression analysis indicates that point Aa and straining Q-tip were moderately correlated (r=0.35, P<.001). As straining point Aa increased by 1 cm, Q-tip angle increased 4.6 degrees (P<.001). Age and prior anterior vaginal or incontinence surgery had no significant effect on the correlation (P=.08 and P=.64, respectively). CONCLUSION: Nearly a third of stress-incontinent women with urethral mobility by Q-tip test visually appeared to have a well-supported urethrovesical junction with POP-Q point Aa values of -2 cm or less. The position of the urethrovesical crease (point Aa) on POP-Q and straining angle on Q-tip test do not appear to reflect the same anatomic support and cannot be used to predict one another. No Aa value can rule out urethral hypermobility. C1 Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. Univ Alabama, Div Urol, Birmingham, AL USA. Loyola Univ, Med Ctr, Dept Obstet & Gynecol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Urol, Maywood, IL 60153 USA. So Calif Permanente Med Grp, Dept Obstet & Gynecol, San Diego, CA 92120 USA. Baylor Univ, Med Ctr, Dept Obstet & Gynecol, Dallas, TX USA. NIDDKD, Bethesda, MD 20892 USA. New England Res Inst, Watertown, MA 02172 USA. RP Zyczynski, RM (reprint author), Magee Womens Hosp, Div Urogynecol & Reconstruct Pelv Surg, 300 Halket St, Pittsburgh, PA 15213 USA. EM hzyczynski@mail.magee.edu NR 20 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2007 VL 110 IS 1 BP 39 EP 43 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 183KW UT WOS:000247572700008 ER PT J AU Troisi, R Titus-Ernstoff, L Hyer, M Hatch, EE Robboy, SJ Strohsnitter, W Palmer, JR Ogloend, B Adam, E Kaufman, R Herbst, AL Hoover, RN AF Troisi, Rebecca Titus-Ernstoff, Linda Hyer, Marianne Hatch, Elizabeth E. Robboy, Stanley J. Strohsnitter, William Palmer, Julie R. Ogloend, Bjorn Adam, Ervin Kaufman, Raymond Herbst, Arthur L. Hoover, Robert N. TI Preeclampsia risk in women exposed in utero to diethylstilbestrol SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FEMALE REPRODUCTIVE-TRACT; ADENOSIS DESAD PROJECT; MEDICAL RECORDS; BREAST-CANCER; FOLLOW-UP; PREGNANCY; INUTERO; MOTHERS; RECALL AB OBJECTIVE: To assess whether preeclampsia risk is elevated in pregnancies of diethylstilbestrol (DES)-exposed daughters. METHODS: This study used data from the National Cancer Institute DES Combined Cohorts Follow-up Study. A total of 285 preeclampsia cases (210 exposed and 75 unexposed) occurred in 7,313 live births (4,759 DES exposed and 2,554 unexposed). Poisson regression analysis estimated relative risks and 95% confidence intervals (CI) for preeclampsia adjusted for age at the index pregnancy, parity, education, smoking, body mass index, year of diagnosis, and cohort. RESULTS: In utero DES exposure was associated with nearly a 50% elevation in preeclampsia risk. Adjustment for preeclampsia risk factors attenuated the relative risk slightly (1.42, 95% CI 1.04-1.94). The excess risk with DES was concentrated among women who developed preeclampsia in their first pregnancies (relative risk 1.81, 95% CI 1.17-2.79), who were exposed before 15 weeks of gestation (relative risk 1.57, 95% CI 1.11-2.23), and who were treated with magnesium sulfate (relative risk 2.10, 95% Cl 0.82-5.42). Among DES-exposed women who had a prior hysterosalpingogram, preeclampsia prevalence was higher in those with uterine abnormalities (12.4%) than in those without (7.7%). CONCLUSION: These data suggest that in utero exposure to DES is associated with a slightly elevated risk of preeclampsia, and that one possible biological mechanism involves uterine abnormalities. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. Informat Management Serv Inc, Rockville, MD USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Boston Univ, Slone Epidemiol Unit, Boston, MA 02215 USA. Stavanger Univ Hosp, Div Gynaecol Obstet & Paediat, Stavanger, Norway. Methodist Hosp, Obstet & Gynecol Phys Org, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. RP Troisi, R (reprint author), Dartmouth Hitchcock Med Ctr, Room 854,7297 Rubin Bldg,1 Med Ctr Dr, Lebanon, NH 03756 USA. EM troisir@mail.nih.gov NR 22 TC 10 Z9 10 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUL PY 2007 VL 110 IS 1 BP 113 EP 120 DI 10.1097/01.AOG.0000268796.75591.02 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 183KW UT WOS:000247572700019 PM 17601905 ER PT J AU Berthet, C Kaldis, P AF Berthet, C. Kaldis, P. TI Cell-specific responses to loss of cyclin-dependent kinases SO ONCOGENE LA English DT Review DE cyclin; cyclin-dependent kinase; cell cycle; embryonic stem cells; tumor cells; differentiated cells ID EMBRYONIC STEM-CELLS; SKIN TUMOR-DEVELOPMENT; CANCER-CELLS; DNA-DAMAGE; TARGETED DISRUPTION; THYMOCYTE APOPTOSIS; MOUSE MODELS; MICE LACKING; G(1) CONTROL; IN-VIVO AB Inactivation of cyclin-dependent kinases (Cdks) and/or cyclins in mice has changed our view of cell cycle regulation. In general, cells are far more resistant to the loss of Cdks than originally anticipated, suggesting widespread compensation among the Cdks. Early embryonic cells are, so far, not sensitive to the lack of multiple Cdks or cyclins. In contrast, differentiated cells are more dependent on Cdk/cyclin complexes and the functional redundancy is more limited. Our challenge is to better understand these cell-type specific differences in cell cycle regulation that can be used to design efficient cancer therapy. Indeed, tumor cells seem to respond to inhibition of Cdk activities, however, with different outcome depending on the tumor cell type. Tumor cells share some proliferation features with stem cells, but appear more sensitive to loss of Cdk activity, somewhat resembling differentiated cells. We summarize the current knowledge of cell cycle regulation in different cell types and highlight their sensitivity to the lack of Cdk activities. C1 NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Bldg 560-22-26,1050 Boyles St, Frederick, MD 21702 USA. EM kaldis@ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU Intramural NIH HHS NR 81 TC 53 Z9 55 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2007 VL 26 IS 31 BP 4469 EP 4477 DI 10.1038/sj.onc.1210243 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 187GR UT WOS:000247836100001 PM 17297466 ER PT J AU Angeloni, D Danilkovitch-Miagkova, A Ivanova, T Braga, E Zabarovsky, E Lerman, MI AF Angeloni, D. Danilkovitch-Miagkova, A. Ivanova, T. Braga, E. Zabarovsky, E. Lerman, M. I. TI Hypermethylation of Ron proximal promoter associates with lack of full-length Ron and transcription of oncogenic short-Ron from an internal promoter SO ONCOGENE LA English DT Article DE 3p21.3; differentiation; erythroleukemia; lung cancer; promoter methylation; Ron (MST1R) ID RECEPTOR TYROSINE KINASE; ACTIVATION; FAMILY; CANCER; GENE; MET; PROGRESSION; DOMAIN; MOUSE; CELLS AB The gene for tyrosine-kinase receptor Ron (MST1R) resides in the chromosome 3p21.3 region, frequently affected in common human malignancies. The gene generates two transcripts, 5 and 2 kb-long, full-length Ron (flRon) and short-form Ron (sfRon), respectively. Here, we show for the first time that the variegated Ron expression is associated with variations in the methylation patterns of two distinct CpG islands in Ron proximal promoter. Widespread hypermethylation associates with lack of flRon whereas hypermethylation of the distal island associates with transcription of sfRon, a constitutively active tyrosine-kinase that drives cell proliferation. sfRon inhibition with kinase-dead transgenes decreases cancer cell growth and induces cellular differentiation. sfRon could be a new drug target in cancer types in which it contributes to tumor progression. C1 NCI, Ctr Canc Res, Immunol Lab, Frederick, MD USA. Karolinska Inst, MTC, Stockholm, Sweden. Russian Acad Med Sci, Blokhin Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia. CNR, Scuola Super St Anna, Inst Clin Physiol, Pisa, Italy. Russian State Genet Ctr, Lab Mol Diagnost, Moscow, Russia. Osiris Therapeut Inc, Baltimore, MD USA. RP Angeloni, D (reprint author), Scuola Super Sant Anna, Inst Clin Physiol, Via Mourzzi,1, I-56124 Pisa, Italy. EM angeloni@ifc.cnr.it RI Zabarovsky, Eugene/A-6645-2010; Braga, Eleonora/P-5574-2016 FU Intramural NIH HHS NR 29 TC 29 Z9 32 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2007 VL 26 IS 31 BP 4499 EP 4512 DI 10.1038/sj.onc.1210238 PG 14 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 187GR UT WOS:000247836100004 PM 17297469 ER PT J AU Leupold, JH Yang, HS Colburn, NH Asangani, I Post, S Allgayer, H AF Leupold, J. H. Yang, H-S Colburn, N. H. Asangani, I. Post, S. Allgayer, H. TI Tumor suppressor Pdcd4 inhibits invasion/intravasation and regulates urokinase receptor (u-PAR) gene expression via Sp-transcription factors SO ONCOGENE LA English DT Article DE Pdcd4; Sp1; Sp3; invasion; intravasation; u-PAR ID PLASMINOGEN-ACTIVATOR RECEPTOR; PROGRAMMED CELL-DEATH; INVASIVE COLON-CANCER; INITIATION-FACTOR 4A; TRANSFORMATION SUPPRESSOR; PROTEIN-2-ALPHA-RELATED FACTOR; TOPOISOMERASE INHIBITORS; AP-1 TRANSACTIVATION; PROGNOSTIC IMPACT; BINDING-PROTEIN AB Tumor suppressor Pdcd4 has recently been shown to inhibit invasion by activating activator protein-1 (AP-1); however, little is known of the functionally significant Pdcd4-target genes. The urokinase receptor (u-PAR) promotes invasion/metastasis, and is associated with poor cancer-patient survival. The present study was conducted (1) to investigate a role for Pdcd4 in intravasation, invasion and u-PAR regulation, and (2) to describe mechanisms by which this is achieved. Fourteen cell lines showed reciprocal expression of u-PAR/Pdcd4. Resected tumor/normal tissues of 29 colorectal cancer patients demonstrated a significant inverse correlation between Pdcd4/u-PAR. siRNA-Pdcd4-transfected GEO cells significantly increased endogenous u-PAR mRNA/protein. A u-PAR-promoter-chloramphenicol acetyl transferase (CAT)-reporter was reduced in activity with increasing Pdcd4 expression in RKO. Deletion of a putative Sp-1-binding site (-402/-350) inhibited u-PAR promoter regulation by Pdcd4, this being paralleled by a reduction of Sp1 binding to this region in pdcd4-transfected cells. Pdcd4-transfected cells showed an increase in Sp3 binding to u-PAR promoter region -152/-135, the deletion of which reduces the ability of Pdcd4 to suppress u- PAR promoter activity. Surprisingly, the u-PAR-AP-1 site was not targeted by Pdcd4. Finally, RKO cells overexpressing Pdcd4 showed an inhibition of invasion/intravasation (chicken embryo metastasis assay). These data suggest Pdcd4 as a new negative regulator of intravasation, and qas the invasion-related gene u-PAR. It is the first study to implicate Pdcd4 regulation of gene expression via Sp1/Sp3. C1 Univ Heidelberg, DKFZ Heidelberg, Med Fac Mannheim, Dept Expt Surg & Mol Oncol Solid Tumors, D-6900 Heidelberg, Germany. NCI, Basic Res Lab, Gene Regulat Sect, Frederick, MD USA. Univ Heidelberg, Med Fac Mannheim, Dept Surg, Heidelberg, Germany. RP Allgayer, H (reprint author), Univ Heidelberg, Med Fac Mannheim, Dept Expt Surg Mol Oncol Solid Tumors, Collaborat Unit German Canc Res Ctr DKFZ Heidelbe, D-68167 Mannheim, Germany. EM heike.allgayer@chir.ma.uni-heidelberg.de RI Yang, Hsin-Sheng/A-6419-2008 NR 61 TC 103 Z9 106 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2007 VL 26 IS 31 BP 4550 EP 4562 DI 10.1038/sj.onc.1210234 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 187GR UT WOS:000247836100009 PM 17297470 ER PT J AU Durkin, ME Ullmannova, V Guan, M Popescu, NC AF Durkin, M. E. Ullmannova, V. Guan, M. Popescu, N. C. TI Deleted in liver cancer 3 (DLC-3), a novel Rho GTPase-activating protein, is downregulated in cancer and inhibits tumor cell growth SO ONCOGENE LA English DT Article DE tumor suppressor gene; Rho GTPase-activating protein; prostate cancer; breast cancer ID HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; CRANIOFRONTONASAL SYNDROME; RECOGNITION DOMAINS; SUPPRESSOR FUNCTION; PROSTATE-CANCER; GENE-EXPRESSION; IDENTIFICATION; TUMORIGENICITY; PROLIFERATION AB Two related Rho GTPase-activating proteins, DLC-1 (deleted in liver cancer 1) and DLC-2, are emerging as bona. de tumor suppressor genes that inhibit cancer cell growth. In this report, we characterized a gene on chromosome Xq13 that encodes DLC-3 (also known as KIAA0189 and STARD8), a third member of the DLC family. The DLC-3 gene has transcripts with alternative 50 ends, one of which, DLC-3a, encodes an 1103-amino acid polypeptide highly similar to DLC-1 and DLC-2. A second isoform (DLC-3b) would yield a protein lacking the N-terminal sterile alpha motif domain. The DLC-3 gene is widely expressed in normal tissues, but DLC-3 mRNA levels were low or absent in a significant number of breast, ovarian, liver and prostate cancer cell lines. Using a cancer pro. ling array to compare matched tumor and normal human tissues, downregulation of DLC-3 mRNA was observed in kidney, lung, ovarian, uterine and breast cancer samples. By quantitative reverse transcriptase polymerase chain reaction, DLC-3 expression was reduced in primary prostate carcinomas relative to normal prostate tissue. Transfection of human breast and prostate cancer cells with a DLC-3a expression vector inhibited cell proliferation, colony formation and growth in soft agar. These results indicate that deregulation of DLC-3 may contribute to breast and prostate tumorigenesis. C1 NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI Benson, Veronika/D-9942-2014 OI Benson, Veronika/0000-0003-4770-9909 FU Intramural NIH HHS NR 47 TC 43 Z9 44 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUL PY 2007 VL 26 IS 31 BP 4580 EP 4589 DI 10.1038/sj.onc.1210244 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 187GR UT WOS:000247836100012 PM 17297465 ER PT J AU Hoffman, AJ Given, BA von Eye, A Gift, AG Given, CW AF Hoffman, Amy J. Given, Barbara A. von Eye, Alexander Gift, Audrey G. Given, Charles W. TI Relationships among pain, fatigue, insomnia, and gender in persons with lung cancer SO ONCOLOGY NURSING FORUM LA English DT Article ID ADULTS RECEIVING TREATMENT; SYMPTOM DISTRESS; DIAGNOSIS; MECHANISM; SURVIVAL; CLUSTERS; TIME AB Purpose/Objectives: To examine the relationships among pain, fatigue, insomnia, and gender while controlling for age, comorbidities, and stage of cancer in patients newly diagnosed with lung cancer within 56 days of receiving chemotherapy. Design: Secondary data analysis. Setting: Accrual from four sites: two clinical community oncology programs and two comprehensive cancer centers. Sample: 80 patients newly diagnosed with lung cancer. Methods: Analysis from baseline observation of a randomized clinical intervention trial. Multinomial log-linear modeling was performed to explain the relationships among pain, fatigue, insomnia, and gender. Main Research Variables: Pain, fatigue, insomnia, and gender. Findings: For all people with lung cancer, fatigue (97%) and pain (69%) were the most frequently occurring symptoms; insomnia occurred 51% of the time. A model containing all main effects (two-way interactions of pain and fatigue, pain and insomnia, and insomnia and gender; and the three-way interaction of pain, fatigue, and insomnia, along with three covariates [age, comorbidities, and stage of cancer]) was a good fit to the data. Parameter estimates indicated that a statistically significant effect from the model was the three-way interaction of pain, fatigue, and insomnia. Gender did not make a difference. Age, comorbidities, and stage of cancer were not significant covariates. Conclusions: For people newly diagnosed with lung cancer undergoing chemotherapy, multiple symptoms occur simultaneously rather than in isolation; a symptom cluster exists, consisting of pain, fatigue, and insomnia; and no relationship was found among gender, pain, fatigue, and insomnia. Implications for Nursing: By understanding this symptom cluster, healthcare providers can target specific troublesome symptoms to optimize symptom management and achieve the delivery of high-quality cancer care. C1 NINR, NIH, Bethesda, MD 20892 USA. Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. Michigan State Univ, Coll Nursing, E Lansing, MI 48824 USA. Michigan State Univ, Psychol Dept, E Lansing, MI 48824 USA. Michigan State Univ, Dept Family Practice, E Lansing, MI 48824 USA. RP Hoffman, AJ (reprint author), NINR, NIH, Bethesda, MD 20892 USA. EM ahoffman32@aol.com FU NINR NIH HHS [1F31 NR009621-01A1, F31 NR009621] NR 37 TC 42 Z9 43 U1 7 U2 19 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JUL PY 2007 VL 34 IS 4 BP 785 EP 792 DI 10.1188/07.ONF.785-792 PG 8 WC Oncology; Nursing SC Oncology; Nursing GA 189TC UT WOS:000248010400007 PM 17723980 ER PT J AU Farhat, GN Newman, AB Sutton-Tyrrell, K Matthews, KA Boudreau, R Schwartz, AV Harris, T Tylavsky, F Visser, M Cauley, JA AF Farhat, G. N. Newman, A. B. Sutton-Tyrrell, K. Matthews, K. A. Boudreau, R. Schwartz, A. V. Harris, T. Tylavsky, F. Visser, M. Cauley, J. A. CA Hlth ABC Study TI The association of bone mineral density measures with incident cardiovascular disease in older adults SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE areal BMD; incident cardiovascular disease; inflammatory cytokines; oxidized LDL; volumetric BMD ID HUMAN ATHEROSCLEROTIC PLAQUES; CORONARY-ARTERY-DISEASE; POSTMENOPAUSAL WOMEN; AORTIC CALCIFICATION; ELDERLY-WOMEN; US ADULTS; INFLAMMATORY MARKERS; HEALTH ABC; OSTEOPOROSIS; MORTALITY AB The associations of volumetric and areal bone mineral density (BMD) measures with incident cardiovascular disease (CVD) were studied in a biracial cohort of 2,310 older adults. BMD measures were inversely related to CVD in women and white men, independent of age and shared risk factors for osteoporosis and CVD. Introduction We investigated the associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with incident cardiovascular disease (CVD) in older adults enrolled in the Health, Aging, and Body Composition study. Methods The incidence of CVD was ascertained in 2,310 well-functioning white and black participants (42% black; 55% women), aged 68 - 80 years. aBMD measures of the hip were assessed using DXA. Spine trabecular, integral, and cortical vBMD measures were obtained using QCT. Results During an average follow-up of 5.4 years, 23% of men and 14% of women had incident CVD. Spine vBMD measures were inversely associated with incident CVD in white men [HR( integral)= 1.39, 95% CI 1.03 - 1.87; HR ( cortical)= 1.38, 95% CI 1.03 - 1.84], but not in black men. In women, aBMD measures of the total hip (HR= 1.36, 95% CI 1.03 - 1.78), femoral neck ( HR= 1.44, 95% CI 1.10 - 1.90), and trochanter (HR= 1.34, 95% CI 1.04 - 1.72) exhibited significant associations with CVD in blacks, but not in whites. All associations were independent of age and shared risk factors between osteoporosis and CVD, and were not explained by inflammatory cytokines or oxidized LDL. Conclusion Our results provide support for an inverse association between BMD and incident CVD. Further research should elucidate possible pathophysiological mechanisms linking osteoporosis and CVD. C1 Univ Pittsburgh, Div Canc Prevent & Populat Sci, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15232 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, 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. Vrije Univ Amsterdam, Inst Res Extramural Med, VU Med Ctr, Amsterdam, Netherlands. Vrije Univ Amsterdam, Inst Res Extramural Med, Inst Hlth Sci, Amsterdam, Netherlands. RP Farhat, GN (reprint author), Univ Pittsburgh, Div Canc Prevent & Populat Sci, UPMC Canc Pavil,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM farhatg@upmc.edu RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015; OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408; Boudreau, Robert/0000-0003-0162-5187 FU Intramural NIH HHS; NIA NIH HHS [5 T32 AG00181, N01 AG62101, N01 AG62103, N01 AG62106] NR 44 TC 43 Z9 44 U1 0 U2 3 PU SPRINGER LONDON LTD PI ARTINGTON PA ASHBOURNE HOUSE, THE GUILDWAY, OLD PORTSMOUTH ROAD, ARTINGTON GU3 1LP, GUILDFORD, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JUL PY 2007 VL 18 IS 7 BP 999 EP 1008 DI 10.1007/s00198-007-0338-8 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 178ET UT WOS:000247204700012 PM 17285350 ER PT J AU Wilcox, AJ AF Wilcox, Allen J. TI The analysis of recurrence risk as an epidemiological tool SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Successive Pregnancy Outcomes - A Decade of Progress CY AUG 19-20, 2005 CL New Brunswick, NJ SP Ctr Dis Control & Prevent, March Dimes DE recurrence; outcome of pregnancy; aetiology; genetics; environment; interpretation ID BIRTH-DEFECTS AB Recurrence risk provides information on the heterogeneity of risk in the population, and thus is useful for aetiological studies. While recurrence risk is observable in many areas of epidemiology, it is particularly accessible in the study of perinatal events. High recurrence rates of pregnancy problems suggest genetic causes, but can also reflect the presence of persistent environmental causes. Specific patterns of recurrence risk can provide further clues about the relative importance of genetic vs. environmental factors, for example through comparisons of recurring pregnancy problems in women who change their male partner and women who keep the same partner. Interpretation of recurrence risk is subject to confusion from bias and confounding, and some examples are discussed. In addition to providing information on causality, recurrence risk offers a means for more efficient design of aetiological studies. C1 NIEHS, Epidemiol Branch, NIH, Durham, NC 27709 USA. RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, NIH, MD A3-05,POB 12233, Durham, NC 27709 USA. EM wilcox@niehs.nih.gov OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 11 TC 9 Z9 9 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2007 VL 21 SU 1 BP 4 EP 7 DI 10.1111/j.1365-3016.2007.00830.x PG 4 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 193XL UT WOS:000248308400002 PM 17593190 ER PT J AU Basso, O AF Basso, Olga TI Options and limitations in studies of successive pregnancy outcomes: an overview SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Successive Pregnancy Outcomes - A Decade of Progress CY AUG 19-20, 2005 CL New Brunswick, NJ SP Ctr Dis Control & Prevent, March Dimes DE recurrence; outcome of pregnancy; birthweight; interpretation ID BIRTH-WEIGHT; RISK; PREECLAMPSIA; IMPACT; FETAL AB This paper provides a brief overview of options and limitations in studies of successive pregnancy outcomes, largely derived from the author's personal experience on Danish registries. The issues discussed here by no means constitute an exhaustive list, but aim at providing an introduction for researchers interested in this topic. C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Basso, O (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bassoo2@niehs.nih.gov RI Basso, Olga/E-5384-2010 OI Basso, Olga/0000-0001-9298-4921 FU Intramural NIH HHS NR 14 TC 5 Z9 5 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2007 VL 21 SU 1 BP 8 EP 12 DI 10.1111/j.1365-3016.2007.00831.x PG 5 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 193XL UT WOS:000248308400003 PM 17593191 ER PT J AU Zhang, J AF Zhang, Jun TI Partner change, birth interval and risk of pre-eclampsia: a paradoxical triangle SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Successive Pregnancy Outcomes - A Decade of Progress CY AUG 19-20, 2005 CL New Brunswick, NJ SP Ctr Dis Control & Prevent, March Dimes DE pre-eclampsia; change in partner; paternity; statistical artefact; pregnancy; interval ID ANTIRETROVIRAL THERAPY; SUBSEQUENT PREGNANCY; WOMEN; EPIDEMIOLOGY; COMPONENTS; INFECTION; PATERNITY; ECLAMPSIA; COHORT; FETAL AB Immunology has been hypothesised to play a critical role in the development of pre-eclampsia. A number of epidemiological studies have shown that multiparous women who changed partner had an increased risk of pre-eclampsia in the following pregnancy compared with multiparous women with the same partner. However, partner change is often associated with a long birth interval. Two recent papers using data from the same birth registry reported that, after controlling for birth interval, partner change was associated with a reduced risk of pre-eclampsia. Based on a causal diagram, the author argues conceptually that birth interval is not a confounder but more likely to be a collider. Controlling for or stratifying birth interval in the association between partner change and risk of pre-eclampsia could be inappropriate and may have produced a spurious association. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov NR 28 TC 21 Z9 23 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2007 VL 21 SU 1 BP 31 EP 35 DI 10.1111/j.1365-3016.2007.00835.x PG 5 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 193XL UT WOS:000248308400007 PM 17593195 ER PT J AU Zhang, J Patel, G AF Zhang, Jun Patel, Geeta TI Partner change and perinatal outcomes: a systematic review SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 2nd International Symposium on Successive Pregnancy Outcomes - A Decade of Progress CY AUG 19-20, 2005 CL New Brunswick, NJ SP Ctr Dis Control & Prevent, March Dimes DE change in partner; paternity; pre-eclampsia; preterm delivery; low birthweight; congenital malformations ID SUBSEQUENT PREGNANCY; PRETERM DELIVERY; RECURRENCE RISK; LAST PREGNANCY; PREECLAMPSIA; PATERNITY; BIRTH; DEFECTS; DENMARK; WOMEN AB Epidemiological studies suggest that partner change may affect perinatal outcomes in subsequent pregnancies. We conducted a systematic review on the association between paternity change and perinatal outcomes. We searched the literature in MEDLINE using keywords 'paternity', 'partner', 'pre-eclampsia', 'preterm birth', 'low birth weight', and 'birth defects' from 1966 to 2005. We identified 19 studies that examined the association between partner change and specific perinatal outcomes: 12 on preeclampsia or hypertension in pregnancy, three on birth defects, three on preterm birth, and two on low birthweight. Partner change was consistently associated with an increased risk of pre-eclampsia or hypertension in pregnancy in 11 of 12 studies (the unadjusted relative risk [RR] ranging from 1.2 to 8.3). However, after controlling for birth interval as a confounder in multivariate analysis, two studies using the same birth registry data showed a modestly reduced risk in relation to partner change (RR = 0.84 and 0.73, respectively), while two studies found a slightly increased risk (both RR = 1.3). Retrospective cohort studies presented inconsistent findings on the association between partner change and risk of preterm birth and low birthweight. Finally, three population-based cohort studies demonstrated that partner change significantly reduced the recurrence of the same or similar birth defects in subsequent births (RRs ranging from 0.1 to 0.76). We conclude that partner change reduces the risk of recurrent same birth defects. However, epidemiological evidence on the effect of partner change on pre-eclampsia, preterm birth and low birthweight is inconclusive. Whether birth interval should be controlled for in the association between partner change and pre-eclampsia warrants caution. C1 NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov NR 27 TC 15 Z9 16 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2007 VL 21 SU 1 BP 46 EP 57 DI 10.1111/j.1365-3016.2007.00837.x PG 12 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 193XL UT WOS:000248308400009 PM 17593197 ER PT J AU Astone, NM Misra, D Lynch, C AF Astone, Nan Marie Misra, Dawn Lynch, Courtney TI The effect of maternal socio-economic status throughout the lifespan on infant birthweight SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE maternal childhood socio-economic status; maternal socio-economic status; maternal education; grandmaternal education; maternal age; birthweight ID CHILDREN; SPLINES; GROWTH; RECALL; INCOME; AGES; RACE AB The objective of this study was to investigate whether maternal socio-economic status during childhood and at the time of pregnancy each have unique associations with infant birthweight when biological determinants of birthweight are controlled. The data are from a three-generation study which contains information on the mothers and grandmothers of 987 singleton infants, collected over a period of 25 years. We used simple and multivariable regression to assess the association between indicators of a woman's socio-economic status and her offspring's birthweight. Women who grew up in poor households had smaller babies than those who did not, and a unit increase in the income/needs ratio (analogous to the poverty index), in non-poor households only, was associated with a 185 g [95% CI 70, 200] increase in infant birthweight. Maternal age at the index infant's birth had a positive association with birthweight that diminished as women reached their mid-twenties. Among mothers with low education, high grandmaternal education was associated with a 181 g [95% CI 71, 292] increase in infant birthweight, while high grandmaternal education had no effect among infants whose mothers were relatively well-educated. This interaction between grandmaternal and maternal education is consistent with claims that cumulative stress is an important mechanism connecting maternal socio-economic status and infant health. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD 21205 USA. Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA. NICHD, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Astone, NM (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, 615 N Wolfe, Baltimore, MD 21205 USA. EM nastone@jhsph.edu NR 18 TC 36 Z9 36 U1 3 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2007 VL 21 IS 4 BP 310 EP 318 DI 10.1111/j.1365-3016.2007.00821.x PG 9 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 177SW UT WOS:000247173800004 PM 17564587 ER PT J AU Hitti, J Nugent, R Boutain, D Gardella, C Hillier, SL Eschenbach, DA AF Hitti, Jane Nugent, Robert Boutain, Doris Gardella, Carolyn Hillier, Sharon L. Eschenbach, David A. TI Racial disparity in risk of preterm birth associated with lower genital tract infection SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article DE vaginal infection; preterm delivery; low birthweight; Chlamydia trachomatis; Trichomonas vaginalis; ethnic group; bacterial vaginosis ID BACTERIAL VAGINOSIS; VAGINAL INFECTIONS; PREGNANT-WOMEN; GRAM STAIN; DELIVERY; WEIGHT; COLONIZATION; PREMATURITY; MISCARRIAGE; MORTALITY AB The objective of this study was to examine the associations between lower genital tract infection, racial group and preterm birth in the Vaginal Infections and Prematurity Study, a large prospective cohort study conducted between 1984 and 1989. This analysis included 11 910 women enrolled at 23-26 weeks' gestation with equal representation from self-identified African American, Hispanic and white women. Subjects were screened for Chlamydia trachomatis, Trichomonas vaginalis and bacterial vaginosis at study entry, and their pregnancy outcomes were ascertained after delivery. The primary outcome of interest was preterm delivery of a low-birthweight infant (< 37 weeks and < 2500 g). The associations between lower genital tract infection and preterm delivery of a low-birthweight infant were examined within each racial group, with adjustment for potential confounders using multivariable logistic regression. In this cohort, 6.4% of African Americans, 3.8% of Hispanics, and 4.4% of whites had a preterm delivery of a low-birthweight infant (P < 0.001). Lower genital tract infection was significantly associated with preterm delivery of a low-birthweight infant among African Americans, but not among other racial groups. The proportion of preterm birth associated with lower genital tract infection was 21% among African Americans and 5% among whites. The increase in infection-associated preterm birth among African Americans appears to be related both to an increased prevalence of lower genital tract infection, and also to an increased risk of preterm delivery of a low-birthweight infant in the context of lower genital tract infection. C1 Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Obstet & Reprod Serv, Pittsburgh, PA 15260 USA. RP Hitti, J (reprint author), Univ Washington, Dept Obstet Gynecol, Box 356460, Seattle, WA 98195 USA. EM jhitti@u.washington.edu FU NIAID NIH HHS [AI-2532]; NICHD NIH HHS [HD-3-2832-2836, HD-41682] NR 24 TC 38 Z9 39 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD JUL PY 2007 VL 21 IS 4 BP 330 EP 337 DI 10.1111/j.1365-3016.2007.00807.x PG 8 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 177SW UT WOS:000247173800006 PM 17564589 ER PT J AU Edwards, RR Klick, B Buenaver, L Max, MB Haythornthwaite, JA Keller, RB Atlas, SJ AF Edwards, Robert R. Klick, Brendan Buenaver, Luis Max, Mitchell B. Haythornthwaite, Jennifer A. Keller, Robert B. Atlas, Steven J. TI Symptoms of distress as prospective predictors of pain-related sciatica treatment outcomes SO PAIN LA English DT Article DE sciatica; pain; disability; discectomy; mood; distress; psychosocial ID MAINE LUMBAR SPINE; LOW-BACK-PAIN; HEALTH SURVEY SF-36; QUALITY-OF-LIFE; NONSURGICAL MANAGEMENT; PERSISTENT PAIN; BIOPSYCHOSOCIAL PERSPECTIVE; GENERAL-POPULATION; LONGITUDINAL DATA; DISC HERNIATION AB Prior studies evaluating predictors of pain-related outcomes following treatment for sciatica have been limited by methodological problems, including retrospective study design, use of unvalidated outcome measures, and short-term follow-up periods. Despite these limitations, some reports have suggested that symptoms of psychological distress may predict individual differences in pain treatment-related outcomes (e.g., higher levels of depressive and anxious symptomatology are associated with greater pain and disability after treatment). In this study, we sought to determine whether acute symptoms of depression and anxiety were prospectively associated with treatment outcomes over a 3-year follow-up period in surgically treated and non-surgically treated patients with sciatica. Patients were recruited from the practices of community-based physicians throughout the state of Maine, and underwent in-person baseline assessments, with mailed follow-up questionnaires at 3, 6, 12, 24, and 36 months. Study outcomes included patient-reported symptoms of pain and disability. For each outcome variable, we examined whether baseline mood (i.e., mood assessed prior to the initiation of treatment), as well as mood at the immediately preceding assessment point, prospectively predicted outcomes over 3 years in multivariate repeated-measures analyses. Tn most analyses, symptoms of depression and anxiety, both at baseline and at the preceding time point, were significant independent predictors of worse pain and function after controlling for relevant covariates. Collectively, elevated distress appears to be a significant risk factor for reduced treatment benefit (i.e., less improvement in pain and disability) over short and medium-term follow-up periods in patients with sciatica. Future research should determine whether the prospective identification and treatment of patients with high levels of distress (a "yellow flag") is associated with improved treatment outcomes. (C) 2006 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. NIH, Natl Inst Dent & Cranofacial Res, DHHS, Div Intramural Res, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Ctr Evaluat Clin Sci, Hanover, NH USA. Massachusetts Gen Hosp, Harvard Med Sch, Med Serv, Gen Med Div,Clin Epidemiol Unit, Boston, MA 02114 USA. RP Edwards, RR (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 1-108, Baltimore, MD 21287 USA. EM redwar10@jhmi.edu FU AHRQ HHS [HS-06344, HS-08194, HS-09804]; NIAMS NIH HHS [K23-AR051315, P60-AR048094-01A1]; NINDS NIH HHS [K24-NS02225, R21-NS048593] NR 47 TC 35 Z9 35 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2007 VL 130 IS 1-2 BP 47 EP 55 DI 10.1016/j.pain.2006.10.026 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 186BO UT WOS:000247754300009 PM 17156925 ER PT J AU Khoromi, S Cui, L Nackers, L Max, MB AF Khoromi, Suzan Cui, Lihong Nackers, Lisa Max, Mitchell B. TI Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain SO PAIN LA English DT Article DE opioids; tricyclic antidepressants; chronic sciatica; lumbar radicular pain; clinical trial ID RANDOMIZED CONTROLLED-TRIAL; RELIEVES POSTHERPETIC NEURALGIA; CONTROLLED-RELEASE OXYCODONE; LOW-BACK-PAIN; NEUROPATHIC PAIN; DIABETIC-NEUROPATHY; CLINICAL-TRIAL; EFFICACY; AMITRIPTYLINE; PREGABALIN AB Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine "active placebo" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. The primary outcome was the mean daily leg pain score on a 0-10 scale during the maintenance period. Secondary outcomes included a 6-point ordinal global pain relief scale, the Beck Depression Inventory (BDI), the Oswestry Back Pain Disability Index (ODI) and the SF-36. In the 28 out of 61 patients who completed the study, none of the treatments produced significant reductions in average leg pain or other leg or back pain scores. Pain reduction, relative to placebo treatment was, 14% for nortriptyline (95% CI = [-2%, 30%]), 7% for morphine (95% CI = [-8%, 22%]), and NO for the combination treatment (95% CI = [-4%, 18%]). Mean doses were: nortriptyline alone, 84 24.44 (SD) mg/day; morphine alone, 62 +/- 29 mg/day; and combination, morphine, 49 27 mg/day plus nortriptyline, 55 mg 33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica. Published by Elsevier B.V. on behalf of International Association for the Study of Pain. C1 NIMH, Dept Hlth & Human Serv, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. Natl Ctr Complementary & Alternat Med, Dept Hlth & Human Serv, Div Intramural Res, Clin Invest Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Dept Hlth & Human Serv, Clin Pain Res Sect, Bethesda, MD 20892 USA. RP Khoromi, S (reprint author), NIMH, Dept Hlth & Human Serv, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. EM khoromisu@mail.nih.gov FU Intramural NIH HHS [Z01 DE000366-25] NR 45 TC 100 Z9 101 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JUL PY 2007 VL 130 IS 1-2 BP 66 EP 75 DI 10.1016/j.pain.2006.10.029 PG 10 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 186BO UT WOS:000247754300011 PM 17182183 ER PT J AU Subbiah, V Chanock, SJ AF Subbiah, Vivek Chanock, Stephen J. TI Modifiers of risk for infectious complications of cancer therapy in children: The long road ahead SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID MANNOSE-BINDING LECTIN; CHEMOTHERAPY-RELATED INFECTIONS; GENE POLYMORPHISMS; INDUCTION THERAPY; ASSOCIATION; DEFICIENCY; MBL; NO; TRANSPLANTATION; LEUKEMIA C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Internal Med Pediat, Sch Med, Cleveland, OH 44106 USA. RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Canc Res Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov NR 16 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2007 VL 49 IS 1 BP 3 EP 5 DI 10.1002/pbc.21164 PG 3 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 172EO UT WOS:000246787100002 PM 17330833 ER PT J AU Savage, SA Burdett, L Troisi, R Douglass, C Hoover, RN Chanock, SJ AF Savage, Sharon A. Burdett, Laura Troisi, Rebecca Douglass, Chester Hoover, Robert N. Chanock, Stephen J. TI Germ-line genetic variation of TP53 in osteosarcoma SO PEDIATRIC BLOOD & CANCER LA English DT Article DE genetic variation; osteosarcoma; single nucleotide polymorphism; TP53 ID CELL LUNG-CANCER; ESTROGEN-RECEPTOR; CANDIDATE GENES; BREAST-CANCER; BONE CANCER; POLYMORPHISMS; MUTATIONS; SURVIVAL; DISEASE; P53 AB Background Osteosarcoma (OS) has been well described in individuals with germ-line TP53 mutations (Li-Fraumeni Syndrome) but typically occurs sporadically in adolescents and young adults. Single nucleotide polymorphisms (SNPs), the most common germline genetic variation, have been associated with risk for other types of cancer. We hypothesized that genetic variation in TP53 could be associated with OS risk based on its critical role in cell growth and effect of somatic mutations in OS tumors. Procedure. Twelve common SNPs in TP53 were genotyped in a case-control study of sporadic OS. These SNPs spanned the TP53 locus and captured common haplotypes. Genotype data were analyzed using contingency tables for additive, dominant, and recessive genetic models. PHASEv2.1 and HaploStats were used to evaluate haplotypes. Results. The recessive model suggested an increased risk of OS when two copies of TP53-34 C > G variant (IVS2+38, rs1642785) were present, P=0.041, odds ratio (OR) 6.70 (95% confidence interval [CI] 1,06-41.6). The TP53-01 variant C > G (Pro72Arg, rs1042522) may also be associated with increased risk for OS, P=0.028, OR 7.5 (95% CI 1.20-46.3). Common TP53 haplotypes as well as the remaining 10 SNPs were not associated with risk for OS. Conclusions. These data do not indicate a strong link between variation in TP53 and OS risk, although they provide preliminary evidence of an increased risk of OS associated with variants at IVS2+38 and Pro72Arg. The findings warrant replication in further studies. C1 NCI, Pediat Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Natl Canc Inst, Gaithersburg, MD USA. NCI, Epidemiol & Biostat Program, DCEG, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 7018, Rockville, MD 20852 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 43 TC 24 Z9 26 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUL PY 2007 VL 49 IS 1 BP 28 EP 33 DI 10.1002/pbc.21077 PG 6 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 172EO UT WOS:000246787100007 PM 17096406 ER PT J AU D'Ippolito, M Read, JS Korelitz, J Joao, EC Mussi-Pinhata, M Rocha, N AF D'Ippolito, Marcos Read, Jennifer S. Korelitz, James Joao, Esau Custodio Mussi-Pinhata, Marisa Rocha, Neiva CA NISDI Perinatal Study Grp TI Missed opportunities for prevention of mother-to-child transmission of human immunodeficiency virus type 1 in Latin America and the Caribbean: The NISDI Perinatal Study SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE HIV-1; mother-to-child transmission; prevention ID INTRAPARTUM TRANSMISSION; HIV TRANSMISSION AB Cases of mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) in a prospective cohort study in Latin America and the Caribbean were analyzed. Eight of 820 eligible infants became infected [transmission rate, 0.98% (95% CI = 0.45-1.96%)]. Five cases (62%) represented missed opportunities for prevention of MTCT of HIV-1, suggesting the need for ongoing training and education of clinicians regarding prevention of MTCT of HIV-1. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Hosp Servidores Estado, Rio De Janeiro, Brazil. Westat Corp, Rockville, MD USA. Fac Med Ribeirao Preto, Sao Paulo, Brazil. Ambulatorio Municipal DST AIDS, Caxias Do Sul, Brazil. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd MSC 7510, Bethesda, MD 20892 USA. EM jennifer_read@nih.gov RI Mussi-Pinhata, Marisa/G-6568-2012 FU NICHD NIH HHS [N01-HD-3-3345] NR 10 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 2007 VL 26 IS 7 BP 649 EP 653 DI 10.1097/INF.0b013e3180618bd6 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 185FS UT WOS:000247697400021 PM 17596813 ER PT J AU Heller, CD O'Shea, M Yao, Q Langer, J Ehrenkranz, RA Phelps, DL Poole, WK Stoll, B Duara, S Oh, W Lemons, J Poindexter, B AF Heller, Cherrie D. O'Shea, Michael Yao, Qing Langer, John Ehrenkranz, Richard A. Phelps, Dale L. Poole, W. Kenneth Stoll, Barbara Duara, Shahnaz Oh, William Lemons, James Poindexter, Brenda CA NICHD Neonatal Res Network TI Human milk intake and retinopathy of prematurity in extremely low birth weight infants SO PEDIATRICS LA English DT Article DE human milk; retinopathy of prematurity; premature ID NEONATAL RESEARCH NETWORK; FULL-TERM INFANTS; BRONCHOPULMONARY DYSPLASIA; NATIONAL-INSTITUTE; MULTICENTER TRIAL; RANDOMIZED-TRIAL; PRETERM INFANTS; CHILD-HEALTH; BREAST-MILK; RISK AB OBJECTIVES. Our goal was to analyze the association between human milk intake and severe retinopathy of prematurity in extremely low birth weight infants. PATIENTS AND METHODS. This study is a secondary analysis of data collected for a trial of glutamine supplementation in extremely low birth weight infants (birth weight < 1000 g). Among the 1433 participants in that trial, data are available regarding human milk intake and the occurrence of severe retinopathy of prematurity (defined in this study as retinopathy of prematurity treated surgically) for 1057 infants. The volume of human milk intake was expressed as the mean volume (milliliters per kilogram per day) and the mean proportional volume (proportion of total nutritional intake) from birth to discharge or transfer. Using logistic regression, we estimated odds ratios and 95% confidence intervals for any human milk intake and, among infants who received human milk, for each 10 mL/kg per day and each 10% increase in volume. RESULTS. Of the 1057 infants included in this cohort, 788 infants (75%) received at least some human milk. Among these milk-fed infants, the median volume of human milk intake was 30 mL/kg per day (interquartile range: 6-83 mL/kg per day), and the median proportional volume of human milk intake was 0.18 (interquartile range: 0.03-0.66). One hundred sixty-three infants (135%) developed severe retinopathy of prematurity. CONCLUSIONS. In extremely low birth weight infants, human milk intake was not associated with a decreased risk of severe retinopathy of prematurity. C1 Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. RTI Int, Res Triangle Pk, NC USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Rochester, NY 14642 USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA. Women & Infants Hosp Rhode Isl, Dept Pediat, Providence, RI USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. NICHHD, Rockville, MD USA. RP Heller, CD (reprint author), Wake Forest Univ, Sch Med, Dept Pediat, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM cheller@wfubmc.edu FU NCRR NIH HHS [M01 RR00997, M01 RR 08084, M01 RR 06022, M01 RR 00070, M01 RR 00750]; NICHD NIH HHS [U01 HD36790, U10 HD27904, U10 HD34216, U10 HD27880, U10 HD27871, U10 HD27856, U10 HD27853, U10 HD21415, U10 HD21397, U10 HD21385, U10 HD21373, U10 HD21364, U10 HD40689, U10 HD40461, U10 HD27881, U10 HD27851] NR 33 TC 14 Z9 15 U1 1 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2007 VL 120 IS 1 BP 1 EP 9 DI 10.1542/peds.2006-1465 PG 9 WC Pediatrics SC Pediatrics GA 185OC UT WOS:000247719300001 PM 17606555 ER PT J AU Nesheim, SR Kapogiannis, BG Soe, MM Sullivan, KM Abrams, E Farley, J Palumbo, P Koenig, LJ Bulterys, M AF Nesheim, Steven R. Kapogiannis, Bill G. Soe, Minn M. Sullivan, Kevin M. Abrams, Elaine Farley, John Palumbo, Paul Koenig, Linda J. Bulterys, Marc TI Trends in opportunistic infections in the pre- and post-highly active antiretroviral therapy eras among HIV-infected children in the Perinatal AIDS Collaborative Transmission Study, 1986-2004 SO PEDIATRICS LA English DT Article DE pediatric HIV/AIDS; opportunistic infections; highly active antiretroviral therapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; BACTERIAL-INFECTIONS; INTRAVENOUS IMMUNOGLOBULIN; RISK-FACTORS; PROPHYLAXIS; ZIDOVUDINE; DISEASE; REDUCTION; MORTALITY; ILLNESSES AB OBJECTIVE. We sought to determine the impact of highly active antiretroviral therapy on the incidence and prevalence of opportunistic infections in HIV-infected children. METHODS. Children born from 1986 to 1998 were monitored until 2004 in the Perinatal AIDS Collaborative Transmission Study, sponsored by the Centers for Disease Control and Prevention. We determined the pre-highly active antiretroviral therapy and post-highly active antiretroviral therapy (before and after January 1, 1997, respectively) incidence rates of opportunistic infections among HIV-infected children and characterized the temporal decreases in percentages of CD4(+) cells and the mortality rates among patients with and those without incident opportunistic infections. RESULTS. The overall opportunistic infection incidence declined from 14.4 to 1.1 cases per 100 patient-years; statistically significant reductions were seen in the incidence of the most common opportunistic infections, including Pneumocystis jiroveci pneumonia (5.8 vs 0.3 cases per 100 patient-years), recurrent bacterial infections (4.7 vs 0.2 cases per 100 patient-years), extraocular cytomegalovirus infection (1.4 vs 0.1 cases per 100 patient-years), and disseminated nontuberculous mycobacterial infection (1.3 vs 0.2 cases per 100 patient-years). Kaplan-Meier analysis of time from birth to the first opportunistic infection illustrated more-rapid acquisition of opportunistic infections by HIV-infected children born in the pre-highly active antiretroviral therapy era than by those born later. In the first 3 years of life, there was a faster decline in the percentage of CD4(+) cells among children with opportunistic infections. The mortality rate was significantly higher among children with opportunistic infections. CONCLUSIONS. Reduction in the incidence of opportunistic infections and prolongation of the time to the first opportunistic infection were noted during the post highly active antiretroviral therapy era. Children who experienced opportunistic infections had higher mortality rates than did those who did not. Younger children (< 3 years) who experienced opportunistic infections had faster declines in percentages of CD4(+) T cells. C1 Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pediat, Div Infect Dis, Atlanta, GA USA. Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA. Harlem Hosp Med Ctr, Dept Pediat, New York, NY USA. Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Univ Med & Dent New Jersey, Dept Pediat, Newark, NJ 07103 USA. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA USA. RP Kapogiannis, BG (reprint author), NICHHD, Pediat Adolescent & maternal AIDS Branch, 6100 Execut Blvd,Room 4B11J, Bethesda, MD 20892 USA. EM kapogiannisb@mail.nih.gov FU PHS HHS [U64/CCU306825, U64/CCU207228, U64/CCU202219, U64/CCU404456] NR 30 TC 37 Z9 40 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2007 VL 120 IS 1 BP 100 EP 109 DI 10.1542/peds.2006-2052 PG 10 WC Pediatrics SC Pediatrics GA 185OC UT WOS:000247719300013 PM 17606567 ER PT J AU Bocchini, JA Baltimore, RS Bernstein, HH Bradley, JS Brady, MT Dennehy, PH Fisher, MC Frenck, RW Kimberlin, DW Long, SS McMillan, JA Rubin, LG Clover, RD Fischer, MA Gorman, RL Pratt, DR Schuchat, A Schwartz, B Starke, JR Swanson, J Pickering, LK Baker, CJ Ledbetter, EO Siwek, A AF Bocchini, Joseph A., Jr. Baltimore, Robert S. Bernstein, Henry H. Bradley, John S. Brady, Michael T. Dennehy, Penelope H. Fisher, Margaret C. Frenck, Robert W., Jr. Kimberlin, David W. Long, Sarah S. McMillan, Julia A. Rubin, Lorry G. Clover, Richard D. Fischer, Marc A. Gorman, Richard L. Pratt, Douglas R. Schuchat, Anne Schwartz, Benjamin Starke, Jeffrey R. Swanson, Jack Pickering, Larry K. Baker, Carol J. Ledbetter, Edgar O. Siwek, Alison CA Comm Infectious Dis TI Prevention of varicella: Recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule SO PEDIATRICS LA English DT Article DE chickenpox; varicella; immunization; Varivax; ProQuad ID HUMORAL IMMUNE-RESPONSES; ZOSTER VIRUS-INFECTIONS; HEALTH-CARE WORKERS; UNITED-STATES; HERPES-ZOSTER; ELEMENTARY-SCHOOL; ANTIBODY-RESPONSE; LONG-TERM; FOLLOW-UP; ADULTS AB National varicella immunization coverage using the current 1-dose immunization strategy has increased among vaccine-eligible children 19 through 35 months of age from 27% in 1997 to 88% by 2005. These high immunization rates have resulted in a 71% to 84% decrease in the reported number of varicella cases, an 88% decrease in varicella-related hospitalizations, a 59% decrease in varicella-related ambulatory care visits, and a 92% decrease in varicella-related deaths in 1- to 4-year-old children when compared with data from the prevaccine era. Despite this significant decrease, the number of reported cases of varicella has remained relatively constant during the past 5 to 6 years. Since vaccine effectiveness for prevention of disease of any severity has been 80% to 85%, a large number of cases of varicella continue to occur among people who already have received the vaccine ( breakthrough varicella), and outbreaks of varicella have been reported among highly immunized populations of schoolchildren. The peak age-specific incidence has shifted from 3- to 6-year-old children in the prevaccine era to 9- to 11-year-old children in the postvaccine era for cases in both immunized and unimmunized children during these outbreaks. Outbreaks of varicella are likely to continue with the current 1-dose immunization strategy. After administration of 2 doses of varicella vaccine in children, the immune response is markedly enhanced, with > 99% of children achieving an antibody concentration (determined by glycoprotein enzyme-linked immunosorbent assay) of >= 5 U/mL (an approximate correlate of protection) and a marked increase in geometric mean antibody titers after the second vaccine dose. The estimated vaccine efficacy over a 10-year observation period of 2 doses for prevention of any varicella disease is 98% (compared with 94% for 1 dose), with 100% efficacy for prevention of severe disease. Recipients of 2 doses of varicella vaccine are 3.3-fold less likely to have breakthrough varicella, compared with those who are given 1 dose, during the first 10 years after immunization. To achieve greater levels of immunity with fewer serosusceptible people, greater protection against breakthrough varicella disease, and reduction in the number of outbreaks that occur nationwide among school-aged populations, a 2-dose varicella immunization strategy is now recommended for children >= 12 months of age. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. OI Dennehy, Penelope/0000-0002-2259-5370 NR 79 TC 36 Z9 39 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2007 VL 120 IS 1 BP 221 EP 231 DI 10.1542/peds.2007-1089 PG 11 WC Pediatrics SC Pediatrics GA 185OC UT WOS:000247719300028 ER PT J AU Zaykin, DV Zhivotovsky, LA Czika, W Shao, S Wolfinger, RD AF Zaykin, Dmitri V. Zhivotovsky, Lev A. Czika, Wendy Shao, Susan Wolfinger, Russell D. TI Combining p-values in large-scale genomics experiments SO PHARMACEUTICAL STATISTICS LA English DT Article DE multiple testing; p-value ranking; p-value combination; truncated product method; genetic association testing; microarray statistical testing ID GENOMEWIDE ASSOCIATION; TRUNCATED PRODUCT; TESTS; COMBINATION; SCANS AB In large-scale genomics experiments involving thousands of statistical tests, such as association scans and microarray expression experiments, a key question is: Which of the L tests represent true associations (TAs)? The traditional way to control false findings is via individual adjustments. In the presence of multiple TAs, p-value combination methods offer certain advantages. Both Fishers and Lancaster's combination methods use an inverse gamma transformation. We identify the relation of the shape parameter of that distribution to the implicit threshold value; p-values below that threshold are favored by, the inverse gamma method (GM). We explore this feature to improve power over Fisher's method when L is large and the number of TAs is moderate. However, the improvement in power provided by combination methods is at the expense of a weaker claim made upon rejection of the null hypothesis - that there are some TAs among the L tests. Thus, GM remains a global test. To allow a stronger claim about a subset of p-values that is smaller than L, we investigate two methods with an explicit truncation: the rank truncated product method (RTP) that combines the first K-ordered p-values, and the truncated product method (TPM) that combines p-values that are smaller than a specified threshold. We conclude that TPM allows claims to be made about subsets of p-values, while the claim of the RTP is, like GM, more appropriately about all L tests. GM gives somewhat higher power than TPM, RTP, Fisher, and Simes methods across a range of simulations. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. Inst Gen Genet RAS, Moscow, Russia. SAS Inst Inc, Cary, NC USA. RP Zaykin, DV (reprint author), Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. EM zaykind@niehs.nih.gov FU Intramural NIH HHS [Z01 ES101866-03] NR 19 TC 33 Z9 35 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2007 VL 6 IS 3 BP 217 EP 226 DI 10.1002/pst.304 PG 10 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 210TA UT WOS:000249477300008 PM 17879330 ER PT J AU Chignell, CF Sik, RH Watson, MA Wielgus, AR AF Chignell, Colin F. Sik, Robert H. Watson, Mary A. Wielgus, Albert R. TI Photochemistry and photocytotoxicity of alkaloids from Goldenseal (Hydrastis canadensis L.) 3: Effect on human lens and retinal pigment epithelial cells SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ISOQUINOLINE ALKALOIDS; UVEAL MELANOCYTES; AQUEOUS-HUMOR; ROOT POWDER; BERBERINE; RAT; EYE; DNA; QUANTITATION; EXPRESSION AB The dried root or rhizome of Goldenseal (Hydrastis canadensis L.) contains several alkaloids including berberine, hydrastine, palmatine and lesser amounts of canadine and hydrastinine. Preparations derived from Goldenseal have been used to treat skin and eye ailments. Berberine, the major alkaloid in Goldenseal root powder, has been used in eye drops to treat trachoma, a disease characterized by keratoconjunctivitis. Berberine and palmatine are also present in extracts from Berberis amurensis Ruprecht (Berberidaceae) which are used to treat ocular disorders. We have previously shown that Goldenseal alkaloids are phototoxic to keratinocytes (Chem Res Toxicol. 14, 1529, 2001; ibid 19, 739, 2006) and now report their effect on human lens and retinal pigment epithelial cells. Human lens epithelial cells (HLE-B3) were severely damaged when incubated with berberine (25 mu M and exposed to UVA (5 J cm(-2)). Under the same conditions, palmatine was less phototoxic and hydrastine, canadine and hydrastinine were inactive. Moderate protection against berberine phototoxicity was afforded by the antioxidants ascorbate (2 mM and N-acetylcysteine (5 mM). When exposed to UVA (5 J cm(-2)) both berberine (10 mu M and palmatine (10 mu M caused mild DNA damage as determined by the alkaline comet assay which measures single strand breaks. Berberine and palmatine are the only Goldenseal alkaloids with appreciable absorption above 400 nm. Because light at wavelengths below 400 nm is cut off by the anterior portion of the adult human eye only berberine and palmatine were tested for phototoxicity to human retinal pigment epithelial (hRPE) cells. Although berberine did damage hRPE cells when irradiated with visible light (lambda > 400 nm) approximately 10 times higher concentrations were required to produce the same amount of damage as seen in lens cells. Pallmatine was not phototoxic to hRPE cells. Neither berberine nor palmatine photodamaged DNA in hRPE. Infusions of Goldenseal are estimated to contain similar to 1 mM berberine, while in tinctures the alkaloid concentration may be more than 10 times higher. Our findings show that eyewashes and lotions derived from Goldenseal or containing C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM chignell@niehs.nih.gov FU Intramural NIH HHS [NIH0010085416, Z01 ES050046-29] NR 39 TC 7 Z9 7 U1 0 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL-AUG PY 2007 VL 83 IS 4 BP 938 EP 943 DI 10.1111/j.1751-1097.2007.00086.x PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 197EK UT WOS:000248537200022 PM 17645667 ER PT J AU Rajter, RF Podgornik, R Parsegian, VA French, RH Ching, WY AF Rajter, Rick F. Podgornik, Rudi Parsegian, V. Adrian French, Roger H. Ching, W. Y. TI van der Waals-London dispersion interactions for optically anisotropic cylinders: Metallic and semiconducting single-wall carbon nanotubes SO PHYSICAL REVIEW B LA English DT Article ID ELECTRONIC-STRUCTURE; HAMAKER CONSTANTS; FORCES; CERAMICS; VACUUM; WATER AB We investigate the van der Waals-London dispersion interactions between a single-walled carbon nanotube immersed in water and interacting with three different objects: an optically isotropic planar substrate, an optically anisotropic planar substrate, and another single-walled carbon nanotube of identical chirality. These interactions were derived from ab initio optical properties and an appropriate formulation of the Lifshitz theory. We derive two analytically tractable limits for the van der Waals interaction: the far limit at separations much larger than the cylinder radius, and the near or Derjaguin limit where surface-cylinder separation is much smaller than the radius. We investigate in detail the effect of relative geometry and the relative separation on the magnitude of the dispersion interaction. C1 MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Ljubljana, Fac Math & Phys, SI-1000 Ljubljana, Slovenia. Jozef Stefan Inst, Dept Theoret Phys, Ljubljana 1000, Slovenia. DuPont Co Inc, Cent Res, Expt Stn, Wilmington, DE 19880 USA. Univ Missouri, Dept Phys, Kansas City, MO 64110 USA. RP Rajter, RF (reprint author), MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. RI Ching, Wai-Yim/B-4686-2009; French, Roger/E-1986-2011; Podgornik, Rudolf/C-6209-2008 OI Ching, Wai-Yim/0000-0001-7738-8822; French, Roger/0000-0002-6162-0532; Podgornik, Rudolf/0000-0002-3855-4637 NR 34 TC 44 Z9 45 U1 1 U2 21 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1098-0121 J9 PHYS REV B JI Phys. Rev. B PD JUL PY 2007 VL 76 IS 4 AR 045417 DI 10.1103/PhysRevB.76.045417 PG 16 WC Physics, Condensed Matter SC Physics GA 197FM UT WOS:000248540000111 ER PT J AU Becker, ED AF Becker, Edwin D. TI Paul Christian Lauterbur SO PHYSICS TODAY LA English DT Biographical-Item C1 NIH, Bethesda, MD 20892 USA. RP Becker, ED (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0031-9228 J9 PHYS TODAY JI Phys. Today PD JUL PY 2007 VL 60 IS 7 BP 77 EP 78 DI 10.1063/1.2761815 PG 2 WC Physics, Multidisciplinary SC Physics GA 187LB UT WOS:000247848100031 ER PT J AU Anderson, SJ Stone, CL Boore, JL Neelam, BA Stephens, RM Luster, DG Frederick, RD Pedley, KF AF Anderson, S. J. Stone, C. L. Boore, J. L. Neelam, B. A. Stephens, R. M. Luster, D. G. Frederick, R. D. Pedley, K. F. TI Phenotypic and genetic variation among soybean rust isolates SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 NCI, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. US DOE, Joint Genome Inst, Walnut Creek, CA USA. USDA ARS, Foreign Dis Weed Sci Res Unit, Ft Detrick, MD USA. RI Moreira, Eder/B-2309-2010 NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUL PY 2007 VL 97 IS 7 SU S BP S4 EP S4 PG 1 WC Plant Sciences SC Plant Sciences GA 181XP UT WOS:000247470000020 ER PT J AU Yap, M Kim, H Charkowski, AO AF Yap, M. Kim, H. Charkowski, A. O. TI The response regulator HrpY of Dickeya dadantii 3937 regulates virulence genes not linked to the hrp cluster SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 Univ Wisconsin, Dept Plant Pathol, Madison, WI 53706 USA. NIDDK, Natl Inst Hlth, Genet & Biochem Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUL PY 2007 VL 97 IS 7 SU S BP S127 EP S127 PG 1 WC Plant Sciences SC Plant Sciences GA 181XP UT WOS:000247470001188 ER PT J AU Scuteri, A Sanna, S Chen, WM Uda, M Albai, G Strait, J Najjar, S Nagaraja, R Orru, M Usala, G Dei, M Lai, S Maschio, A Busonero, F Mulas, A Ehret, GB Fink, AA Weder, AB Cooper, RS Galan, P Chakravarti, A Schlessinger, D Cao, A Lakatta, E Abecasis, GR AF Scuteri, Angelo Sanna, Serena Chen, Wei-Min Uda, Manuela Albai, Giuseppe Strait, James Najjar, Samer Nagaraja, Ramaiah Orru, Marco Usala, Gianluca Dei, Mariano Lai, Sandra Maschio, Andrea Busonero, Fabio Mulas, Antonella Ehret, Georg B. Fink, Ashley A. Weder, Alan B. Cooper, Richard S. Galan, Pilar Chakravarti, Aravinda Schlessinger, David Cao, Antonio Lakatta, Edward Abecasis, Goncalo R. TI Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits SO PLOS GENETICS LA English DT Article ID BODY-MASS INDEX; UNITED-STATES; ANTIOXIDANT VITAMINS; QUANTITATIVE TRAITS; PROSPECTIVE COHORT; BLOOD-PRESSURE; ADULT OBESITY; US ADULTS; LINKAGE; DISEASE AB The obesity epidemic is responsible for a substantial economic burden in developed countries and is a major risk factor for type 2 diabetes and cardiovascular disease. The disease is the result not only of several environmental risk factors, but also of genetic predisposition. To take advantage of recent advances in gene-mapping technology, we executed a genome-wide association scan to identify genetic variants associated with obesity-related quantitative traits in the genetically isolated population of Sardinia. Initial analysis suggested that several SNPs in the FTO and PFKP genes were associated with increased BMI, hip circumference, and weight. Within the FTO gene, rs9930506 showed the strongest association with BMI (p = 8.6 x 10(-7)), hip circumference (p = 3.4 x 10(-8)), and weight (p = 9.1 x 10(-7)). In Sardinia, homozygotes for the rare "G'' allele of this SNP (minor allele frequency 0.46) were 1.3 BMI units heavier than homozygotes for the common "A'' allele. Within the PFKP gene, rs6602024 showed very strong association with BMI (p = 4.9 x 10(-6)). Homozygotes for the rare "A'' allele of this SNP ( minor allele frequency 0.12) were 1.8 BMI units heavier than homozygotes for the common "G'' allele. To replicate our findings, we genotyped these two SNPs in the GenNet study. In European Americans (N = 1,496) and in Hispanic Americans (N = 839), we replicated significant association between rs9930506 in the FTO gene and BMI (p-value for meta-analysis of European American and Hispanic American follow-up samples, p = 0.001), weight (p = 0.001), and hip circumference (p =0.0005). We did not replicate association between rs6602024 and obesity-related traits in the GenNet sample, although we found that in European Americans, Hispanic Americans, and African Americans, homozygotes for the rare "A'' allele were, on average, 1.0-3.0 BMI units heavier than homozygotes for the more common "G'' allele. In summary, we have completed a whole genome association scan for three obesity-related quantitative traits and report that common genetic variants in the FTO gene are associated with substantial changes in BMI, hip circumference, and body weight. These changes could have a significant impact on the risk of obesity-related morbidity in the general population. C1 Ist patol Endocrina & Metabol, Unita Operat Geriat, Rome, Italy. NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. Cittadella Univ Monserrato, Ist Neurogenet & Neurofarmacol, Consiglio Nazl Ric, Cagliari, Italy. Presidio Osped Santa Barbara, Div Med, UNita Operat Semplice Cardiol, Iglesias, Italy. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Loyola Stritch Sch Med, Dept Prevent Med & Epidemiol, Chicago, IL USA. Inst Sci & Tech Nutr & Alimentat, Paris, France. INSERM, INRA, CNAM, U557, Paris, France. RP Schlessinger, D (reprint author), Ist patol Endocrina & Metabol, Unita Operat Geriat, Rome, Italy. EM schlessingerd@grc.nia.nih.gov; goncalo@umich.edu RI EHRET, Georg/A-9532-2009; Chen, Wei-Min/A-8469-2009; Abecasis, Goncalo/B-7840-2010; OI EHRET, Georg/0000-0002-5730-0675; sanna, serena/0000-0002-3768-1749; Abecasis, Goncalo/0000-0003-1509-1825 FU Intramural NIH HHS; NHGRI NIH HHS [R01 HG002651, HG02651]; NHLBI NIH HHS [HL084729, U01 HL084729]; NIA NIH HHS [N01-AG-1-2109]; PHS HHS [263-MA-410953] NR 55 TC 785 Z9 806 U1 14 U2 68 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2007 VL 3 IS 7 BP 1200 EP 1210 AR e115 DI 10.1371/journal.pgen.0030115 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 194NB UT WOS:000248350000007 PM 17658951 ER PT J AU Horvath, MM Wang, X Resnick, MA Bell, DA AF Horvath, Monica M. Wang, Xuting Resnick, Michael A. Bell, Douglas A. TI Divergent evolution of human p53 binding sites: Cell cycle versus apoptosis SO PLOS GENETICS LA English DT Article ID NF-KAPPA-B; GENOME BROWSER DATABASE; TARGET GENES; SEQUENCES; MOUSE; IDENTIFICATION; MUTATION; ELEMENTS; REGIONS; CONSERVATION AB The p53 tumor suppressor is a sequence-specific pleiotropic transcription factor that coordinates cellular responses to DNA damage and stress, initiating cell-cycle arrest or triggering apoptosis. Although the human p53 binding site sequence (or response element [RE]) is well characterized, some genes have consensus-poor REs that are nevertheless both necessary and sufficient for transactivation by p53. Identification of new functional gene regulatory elements under these conditions is problematic, and evolutionary conservation is often employed. We evaluated the comparative genomics approach for assessing evolutionary conservation of putative binding sites by examining conservation of 83 experimentally validated human p53 REs against mouse, rat, rabbit, and dog genomes and detected pronounced conservation differences among p53 REs and p53-regulated pathways. Bona fide NRF2 (nuclear factor [erythroid-derived 2]-like 2 nuclear factor) and NF kappa B (nuclear factor of kappa light chain gene enhancer in B cells) binding sites, which direct oxidative stress and innate immunity responses, were used as controls, and both exhibited high interspecific conservation. Surprisingly, the average p53 RE was not significantly more conserved than background genomic sequence, and p53 REs in apoptosis genes as a group showed very little conservation. The common bioinformatics practice of filtering RE predictions by 80% rodent sequence identity would not only give a false positive rate of similar to 19%, but miss up to 57% of true p53 REs. Examination of interspecific DNA base substitutions as a function of position in the p53 consensus sequence reveals an unexpected excess of diversity in apoptosis-regulating REs versus cell-cycle controlling REs ( rodent comparisons: p < 1.0 e-12). While some p53 REs show relatively high levels of conservation, REs in many genes such as BAX, FAS, PCNA, CASP6, SIVA1, and P53AIP1 show little if any homology to rodent sequences. This difference suggests that among mammalian species, evolutionary conservation differs among p53 REs, with some having ancient ancestry and others of more recent origin. Overall our results reveal divergent evolutionary pressure among the binding targets of p53 and emphasize that comparative genomics methods must be used judiciously and tailored to the evolutionary history of the targeted functional regulatory regions. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA. RP Bell, DA (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC USA. EM BELL1@niehs.nih.gov OI Wang, Xuting/0000-0001-6781-8008 FU Intramural NIH HHS NR 46 TC 62 Z9 62 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD JUL PY 2007 VL 3 IS 7 BP 1284 EP 1295 AR e127 DI 10.1371/journal.pgen.0030127 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 194NB UT WOS:000248350000015 PM 17677004 ER PT J AU Paukner, A Anderson, JR Fogassi, L Ferrari, PF AF Paukner, Annika Anderson, James R. Fogassi, Leonardo Ferrari, Pier F. TI Do facial gestures, visibility or speed of movement influence gaze following responses in pigtail macaques? SO PRIMATES LA English DT Article DE gaze-following; social cognition; joint attention; visual co-orientation; pigtail macaque; facial expression ID EYE GAZE; ATTENTION; MONKEYS AB This study investigated whether a human model's facial gestures, speed of head turn and visibility of face influenced gaze-following responses (GFR) in pigtail macaques. A human provided gaze cues by turning her head 90 degrees in one of four directions. Head turns were immediately followed by a facial movement (pucker, eyebrow raise, tongue protrusion, neutral), or were executed swiftly (< 0.5 s), slowly (3 s) or whilst facing away from the monkeys. All monkeys reliably followed the gaze in all conditions with no differences between conditions. A greater frequency of GFR was found in females compared to males, and two hypotheses for this finding are discussed. C1 Univ Stirling, Dept Psychol, Stirling FK9 4LA, Scotland. Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. NIH, Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. RP Paukner, A (reprint author), Univ Stirling, Dept Psychol, Stirling FK9 4LA, Scotland. EM pauknera@mail.nih.gov NR 15 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 0032-8332 J9 PRIMATES JI Primates PD JUL PY 2007 VL 48 IS 3 BP 241 EP 244 DI 10.1007/s10329-006-0024-z PG 4 WC Zoology SC Zoology GA 182TZ UT WOS:000247528200008 PM 17119866 ER PT J AU Negrete, A Ling, TC Lyddiatt, A AF Negrete, Alejandro Ling, Tau Chuan Lyddiatt, Andrew TI Production of adenoviral vectors and its recovery SO PROCESS BIOCHEMISTRY LA English DT Article DE adenoviral vectors; HEK 293; ATPS; yield; recovery ID AQUEOUS 2-PHASE SYSTEMS; GENE-THERAPY; BED CHROMATOGRAPHY; CELL-CULTURE; SERUM-FREE; PURIFICATION; INFECTIVITY; TYPE-5; VIRUS AB The current demands for adenoviral vectors are increasing to satisfy pre-clinical and clinical gene therapy protocols. Consequently, there is a necessity of methodologies to improve production and recovery of intact particles with the minimum effect upon bioactivity. The production of adenoviral vectors in HEK 293 cells and the potential of an alternative aqueous two-phase system (ATPS) composed of PEG 300-phosphate in recovery of adenoviral vectors were investigated. The production of adenoviral vectors was carried out using a 2 L bioreactor equipped with two Rushton impellers. Different parameters including initial cell density, harvesting time and the addition of a buffer (HEPES) were studied in order to improve the production of adenoviral vectors in HEK 293 cells. A yield of 8 x 10(11) infective particles was achieved under the conditions characterized by the addition of Pluronic F-68, inoculation at an initial cell density of 3.5 x 10(5) cells/mL and harvest of infected cells at 48 h post infection (hpi). This material was used for the evaluation of the ATPS recovery processes. It was demonstrated that the chemical components of the ATPS did not have a significant effect upon the infectivity of the adenoviral vectors and a total recovery of approximately 90% was obtained. These findings contribute to the process development for the manufacture of adenoviral vectors and other nanoparticulate bioproducts. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Birmingham, Biochem Recovery Grp, Dept Chem Engn, Sch Engn, Birmingham B15 2TT, W Midlands, England. RP Negrete, A (reprint author), NHLBI, US Natl Inst Hlth, 9000 Rockville Pike Bldg 10,Rm 7D04, Bethesda, MD 20892 USA. EM negretea@nhlbi.nih.gov RI Ling, Tau Chuan/F-5137-2011 NR 34 TC 6 Z9 8 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-5113 J9 PROCESS BIOCHEM JI Process Biochem. PD JUL PY 2007 VL 42 IS 7 BP 1107 EP 1113 DI 10.1016/j.procbio.2007.05.004 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Engineering, Chemical SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Engineering GA 196GX UT WOS:000248470800010 ER PT J AU Ziolkowska, NE Shenoy, SR O'Keefe, BR Wlodawer, A AF Ziolkowska, Natasza E. Shenoy, Shilpa R. O'Keefe, Barry R. Wlodawer, Alexander TI Crystallographic studies of the complexes of antiviral protein griffithsin with glucose and N-acetylglucosamine SO PROTEIN SCIENCE LA English DT Article DE lectins; monosaccharide binding; antiviral activity; cocrystallization ID MODE AB Crystal structures of complexes of an antiviral lectin griffithsin (GRFT) with glucose and N-acetylglucosamine were solved and refined at high resolution. In both complexes, all six monosaccharide-binding sites of GRFT were occupied and the mode of binding was similar to that of mannose. In our previous attempts to obtain a complex with N-acetylglucosamine by soaking, only a single site was occupied; thus, cocrystallization was clearly superior despite lower concentration of the ligand. Isothermal titration calorimetric experiments with N-acetylglucosamine, glucose, and mannose provided enthalpic evidence of distinct binding differences between the three monosaccharides. A comparison of the mode of binding of different monosaccharides is discussed in the context of the antiviral activity of GRFT, based on specific binding to high-mannose-containing complex carbohydrates found on viral envelopes. C1 NCI, Frederick Canc Res & Dev Ctr, Macromol Crystallog Lab, Prot Struct Sect, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC, Mol Targets Dev Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Mol Targets Dev Program, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 11 TC 19 Z9 19 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUL PY 2007 VL 16 IS 7 BP 1485 EP 1489 DI 10.1110/ps.072889407 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181VX UT WOS:000247465400025 PM 17567736 ER PT J AU Tsai, CJ Zheng, J Zanuy, D Haspel, N Wolfson, H Aleman, C Nussinov, R AF Tsai, Chung-Jung Zheng, Jie Zanuy, David Haspel, Nurit Wolfson, Haim Aleman, Carlos Nussinov, Ruth TI Principles of nanostructure design with protein building blocks SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Review DE nanostructure design; protein building blocks; self-assembly; protein folding; repeat proteins ID ANKYRIN REPEAT PROTEIN; MOLECULAR-DYNAMICS; CYCLOPROPANE ANALOG; NANOFIBER SCAFFOLD; CRYSTAL-STRUCTURE; ENERGY LANDSCAPE; SOLID-STATE; SIDE-CHAIN; PEPTIDE; PHENYLALANINE AB Currently there is increasing interest in nanostructures and their design. Nanostructure design involves the ability to predictably manipulate the properties of the self-assembly of autonomous units. Autonomous units have preferred conformational states. The units can be synthetic material science-based or derived from functional biological macromolecules. Autonomous biological building blocks with available structures provide an extremely rich and useful resource for design. For proteins, the structural databases contain large libraries of protein molecules and their building blocks with a range of shapes, surfaces, and chemical properties. The introduction of engineered synthetic residues or short peptides into these can expand the available chemical space and enhance the desired properties. Here we focus on the principles of nanostructure design with protein building blocks. C1 SAIC Frederick Inc, Ctr Canc Res NAnobiol Program, NCI Frederick, Basic Res Program, Frederick, MD 21702 USA. Univ Politecn Catalunya, Dept Engn Quim, ETS Engn Ind, E-08028 Barcelona, Spain. Tel Aviv Univ, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), SAIC Frederick Inc, Ctr Canc Res NAnobiol Program, NCI Frederick, Basic Res Program, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011; Zheng, Jie/B-5057-2013; Zanuy, David/G-3930-2014; Haspel, Nurit/D-1961-2017 OI Zheng, Jie/0000-0003-1547-3612; Zanuy, David/0000-0001-7704-2178; FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 57 TC 42 Z9 43 U1 2 U2 25 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUL PY 2007 VL 68 IS 1 BP 1 EP 12 DI 10.1002/prot.21413 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 173TG UT WOS:000246894800001 PM 17407160 ER PT J AU Fernandez, MM Bhattacharya, S De Marzi, MC Brown, PH Kerzic, M Schuck, P Mariuzza, RA Malchiodi, EL AF Fernandez, Marisa M. Bhattacharya, Suparna De Marzi, Mauricio C. Brown, Patrick H. Kerzic, Melissa Schuck, Peter Mariuzza, Roy A. Malchiodi, Emilio L. TI Superantigen natural affinity maturation revealed by the crystal structure of staphylococcal enterotoxin g and its binding to T-cell receptor v beta 8.2 SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE bacterial superantigen; Staphylococcus aureus; SEG; T-cell receptor; MHC; class II ID MHC CLASS-II; TOXIC-SHOCK-SYNDROME; STREPTOCOCCAL PYROGENIC EXOTOXIN; TUMOR-NECROSIS-FACTOR; BETA-CHAIN; 3-DIMENSIONAL STRUCTURE; BACTERIAL SUPERANTIGENS; PROTEIN STRUCTURES; IN-VITRO; AUREUS AB The illnesses associated with bacterial superantigens (SAgs) such as food poisoning and toxic shock syndrome, as well as the emerging threat of purpura fulminans and community-associated methicillin-resistant S. aureus producer of SAgs, emphasize the importance of a better characterization of SAg binding to their natural ligands, which would allow the development of drugs or biological reagents able to neutralize their action. SAgs are toxins that bind major histocompatibility complex class II molecules (MHC-II) and T-cell receptors (TCR), in a nonconventional manner, inducing T-cell activation that leads to production of cytokines such as tumor necrosis factor and interleukin-2, which may result in acute toxic shock. Previously, we cloned and expressed a new natural variant of staphylococcal enterotoxin G (SEG) and evaluated its ability to stimulate in vivo murine T-cell subpopulations. We found an early, strong, and widespread stimulation of mouse V beta 8.2 T-cells when compared with other SAgs member of the SEB subfamily. In search for the reason of the strong mitogenic potency, we determined the SEG crystal structure by X-ray crystallography to 2.2 angstrom resolution and analyzed SEG binding to mV beta 8.2 and MHC-II. Calorimetry and SPR analysis showed that SEG has an affinity for mV beta 8.2 40 to 100-fold higher than that reported for other members of SEB subfamily, and the highest reported for a wild type SAg-TCR couple. We also found that mutations introduced in mV beta 8.2 to produce a high affinity mutant for other members of the SEB subfamily do not greatly affect binding to SEG. Crystallographic analysis and docking into mV beta 8.2 in complex with SEB, SEC3, and SPEA showed that the deletions and substitution of key amino acids remodeled the putative surface of the mV beta 8.2 binding site without affecting the binding to MHC-II. This results in a SAg with improved binding to its natural ligands, which may confer a possible evolutionary advantage for bacterial strains expressing SEG. C1 Univ Buenos Aires, Fac Farm & Bioquim, Catedra Inmunol, RA-1113 Buenos Aires, DF, Argentina. Univ Buenos Aires, Fac Farm & Bioquim, IDEHU, CONICET,Lab Inmunol Estruct, RA-1113 Buenos Aires, DF, Argentina. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD 20850 USA. ORS, OD, Div Bioengn & Phys Sci, NIH, Bethesda, MD USA. RP Malchiodi, EL (reprint author), Univ Buenos Aires, Fac Farm & Bioquim, Catedra Inmunol, Junin 956 4 P, RA-1113 Buenos Aires, DF, Argentina. EM emalchio@ffyb.uba.ar OI Schuck, Peter/0000-0002-8859-6966 FU NIAID NIH HHS [AI36900] NR 50 TC 14 Z9 16 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 JUL PY 2007 VL 68 IS 1 BP 389 EP 402 DI 10.1002/prot.21388 PG 14 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 173TG UT WOS:000246894800039 PM 17427250 ER PT J AU Stinson, FS Dawson, DA Chou, SP Smith, S Goldstein, RB Ruan, WJ Grant, BF AF Stinson, Frederick S. Dawson, Deborah A. Chou, S. Patricia Smith, Sharon Goldstein, Rise B. Ruan, W. June Grant, Bridget F. TI The epidemiology of DSM-IV specific phobia in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions SO PSYCHOLOGICAL MEDICINE LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; MENTAL-HEALTH SURVEY; COMORBIDITY SURVEY REPLICATION; GENERALIZED ANXIETY DISORDER; SUBSTANCE USE DISORDERS; TE-RAU-HINENGARO; UNITED-STATES; PSYCHIATRIC-DISORDERS; SOCIAL PHOBIA; LIFETIME PREVALENCE AB Background. There is a lack of current detailed national data on the prevalence, correlates, disability and co-morbidity of DSM-IV specific phobia (SP), the prevalence of specific objects and situations feared, and associations between impairment, treatment and co-morbidity and the number of specific situations and objects feared, among adults in the USA. Method. The data were derived from a large (43093) representative sample of the adult population in the USA. Results. Prevalences of 12-month and lifetime DSM-IV SP were 7-1 % and 9.4% respectively. Being female, Young, and low income increased risk, while being Asian or Hispanic decreased risk (p < 0.05). The mean age at onset of SP was 9.7 years. the mean duration of episode was 20.1 years and only 8.0 % reported treatment specifically for SP. Most specific phobias involved multiple fears, and an increasing, number of fears, regardless of content, was associated with greater disability and impairment, treatment seeking and co-morbidity with other Axis I and II disorders. Conclusions. SP is a highly prevalent, disabling and co-morbid disorder in the US adult population. The early onset of SP and the disorders most strongly associated with it highlights the need for longitudinal studies beginning in early childhood. Results suggest the existence of a generalized Subtype Of SP Much like social phobia, which, once revealed, may lead to a classification of SP that is more etiologically and therapeutically meaningful. C1 Natl Inst Alcohol Abuse & Alcoholism, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry, Dept Hlth & Human Serv NIH, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry, Dept Hlth & Human Serv NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU Intramural NIH HHS NR 79 TC 114 Z9 115 U1 5 U2 30 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2007 VL 37 IS 7 BP 1047 EP 1059 DI 10.1017/S0033291707000086 PG 13 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 189JE UT WOS:000247984400014 PM 17335637 ER PT J AU Fukushima, S Shen, HW Hata, H Ohara, A Ohmi, K Ikeda, K Numachi, Y Kobayashi, H Hall, FS Uhl, GR Sora, I AF Fukushima, Setsu Shen, Haowei Hata, Harumi Ohara, Arihisa Ohmi, Kayo Ikeda, Kazutaka Numachi, Yohtaro Kobayashi, Hideaki Hall, F. Scott Uhl, George R. Sora, Ichiro TI Methamphetamine-induced locomotor activity and sensitization in dopamine transporter and vesicular monoamine transporter 2 double mutant mice SO PSYCHOPHARMACOLOGY LA English DT Article DE sensitization; dopamine transporter; vesicular monoamine transporter 2; methamphetamine; knockout mice; locomotor activity; heterozygote ID PARANOID PSYCHOTIC STATE; KNOCKOUT MICE; EXTRACELLULAR DOPAMINE; INTRAVENOUS COCAINE; AMPHETAMINE ACTION; NUCLEUS-ACCUMBENS; PLACE PREFERENCE; 129/J MICE; RELEASE; SEROTONIN AB Rationale The dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2) play pivotal roles in the action of methamphetamine (MAP), including acute locomotor effects and behavioral sensitization. However, the relative impact of heterozygous DAT and VMAT2 knockouts (KOs) on the behavioral effects of MAP remains unknown. Objectives To evaluate the roles of DAT and VMAT2 in MAP-induced locomotor behavior, we examined locomotor activity and sensitization in heterozygous DAT KO (DAT+/-), heterozygous VMAT2 KO (VMAT2+/-), double heterozygous DAT/VMAT2 KO (DAT+/-VMAT2+/-), and wild-type (WT) mice. Results Acute 1 mg/kg MAP injection induced significant locomotor increases in WT and VMAT2+/- mice but not in DAT+/- and DAT+/-VMAT2+/- mice. Acute 2 mg/kg MAP significantly increased locomotor activity in all genotypes. Repeated 1 mg/kg MAP injections revealed a delayed and attenuated development of sensitization in DAT+/- and DAT+/-VMAT2+/- mice compared to WT mice and delayed development in VMAT2+/- mice. In repeated 2 mg/kg MAP injections, DAT+/- and DAT+/-VMAT2+/- mice showed delayed but not attenuated development of sensitization, while there was no difference in the onset of sensitization between VMAT2+/- and WT mice. In DAT+/-VMAT2+/- mice, all of MAP-induced behavioral responses were similar to those in DAT+/- but not VMAT2+/- mice. Conclusions Heterozygous deletion of DAT attenuates the locomotor effects of MAP and may play larger role in behavioral responses to MAP compared to heterozygous deletion of VMAT2. C1 Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan. Tokyo Inst Psychiat, Div Psychobiol, Tokyo, Japan. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Sora, I (reprint author), Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan. EM isora@mail.tains.tohoku.ac.jp RI Kobayashi, Hideaki/C-8617-2009; Ikeda, Kazutaka/I-4694-2013; Hall, Frank/C-3036-2013; OI Kobayashi, Hideaki/0000-0003-3599-0465; Ikeda, Kazutaka/0000-0001-8342-0278; Hall, Frank/0000-0002-0822-4063; Shen, Hao-wei/0000-0002-2766-5139 FU Intramural NIH HHS NR 34 TC 26 Z9 27 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2007 VL 193 IS 1 BP 55 EP 62 DI 10.1007/s00213-007-0749-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 178TX UT WOS:000247244100005 PM 17377774 ER PT J AU Blumenthal, JA Babyak, MA Ironson, G Thoresen, C Powell, L Czajkowski, S Burg, M Keefe, FJ Steffen, P Catellier, D AF Blumenthal, James A. Babyak, Michael A. Ironson, Gail Thoresen, Carl Powell, Lynda Czajkowski, Susan Burg, Matthew Keefe, Francis J. Steffen, Patrick Catellier, Diane CA ENRICHD Investigators TI Spirituality, religion, and clinical outcomes in patients recovering from an acute myocardial infarction SO PSYCHOSOMATIC MEDICINE LA English DT Article DE coronary heart disease; religion; spirituality; depression; social support ID DISEASE PATIENTS ENRICHD; ILL ELDERLY-PATIENTS; CORONARY-CARE UNIT; HEART-DISEASE; INTERCESSORY PRAYER; ENHANCING RECOVERY; BLOOD-PRESSURE; HEALTH; MORTALITY; SURVIVAL AB Objective: To assess the prospective relationship between spiritual experiences and health in a sample of patients surviving an acute myocardial infarction (AMI) with depression or low social support. Methods: A subset of 503 patients participating in the enhancing recovery in coronary heart disease (ENRICHD) trial completed a Daily Spiritual Experiences (DSE) questionnaire within 28 days from the time of their AMI. The questionnaire assessed three spirituality variables-worship service/church attendance, prayer/meditation, and total DSE score. Patients also completed the Beck Depression Inventory to assess depressive symptoms and the ENRICHD Social Support Inventory to determine perceived social support. The sample was subsequently followed prospectively every 6 months for an average of 18 months to assess all-cause mortality and recurrent AMI. Results: Of the 503 participants who completed the DSE questionnaire at the time of index AMI, 61 (12%) participants either died or sustained a recurrent MI during the follow-up period. After adjustment for gender, education level, ethnicity, and a composite medical prognosis risk score derived specifically for the ENRICHD trial, we observed no relationship between death or nonfatal AMI and total spirituality as measured by the DSE (p = .446), worship service attendance (p = .120), or frequency of prayer/meditation (p = .679). Conclusion: We found little evidence that self-reported spirituality, frequency of church attendance, or frequency of prayer is associated with cardiac morbidity or all-cause mortality post AMI in patients with depression and/or low perceived support. C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. Univ Miami, Dept Psychiat, Miami, FL 33152 USA. Stanford Univ, Sch Educ, Stanford, CA 94305 USA. Rush Presbyterian Hosp, Dept Community Med, Chicago, IL USA. Yale Univ, New Haven Vet Adm Hosp, Dept Psychol, New Haven, CT USA. NHLBI, Bethesda, MD 20892 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Blumenthal, JA (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Box 3119, Durham, NC 27710 USA. EM Blume003@mc.duke.edu RI Steffen, Patrick/D-7264-2013 OI Steffen, Patrick/0000-0002-3647-0456 FU NHLBI NIH HHS [N01-HC-55145, N01-HC-55141, N01-HC-55143, N01-HC-55147, N01-HC-55140, N01-HC-55142, N01-HC-55144, N01-HC-55146, N01-HC-55148]; NIMH NIH HHS [MH 49679] NR 48 TC 30 Z9 32 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2007 VL 69 IS 6 BP 501 EP 508 DI 10.1097/PSY.0b013e3180cab76c PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 197EA UT WOS:000248535600004 PM 17636153 ER PT J AU Eaker, ED Sullivan, LM Kelly-Hayes, M D'Agostino, RB Benjamin, EJ AF Eaker, Elaine D. Sullivan, Lisa M. Kelly-Hayes, Margaret D'Agostino, Ralph B., Sr. Benjamin, Emelia J. TI Marital status, marital strain, and risk of coronary heart disease or total mortality: The Framingham Offspring Study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE coronary heart disease; mortality; cohort study; marital strain; epidemiology ID MEN; WOMEN; SELF; PREDICT; STRESS; SCALE AB Objective: To determine if marriage and marital strain are related to the 10-year coronary heart disease (CHD) incidence or total mortality. Research has demonstrated associations between marital strain and prognosis of heart disease, but little research has addressed the association between specific aspects of marital strain and incident CHD. Methods: From 1984 to 1987, 3682 participants (mean age 48.5 +/- 10.1 (standard deviation) years; 52% women) of the Framingham Offspring Study were examined; measures of marital status, marital strain, and risk factors for CHD were collected at the baseline examination. The present study describes the 10-year follow-up for incident CHD and total mortality. Results: After adjusting for age, systolic blood pressure, body mass index, cigarette smoking, diabetes, and total cholesterol/high density cholesterol, the married men compared with unmarried men were almost half as likely to die during follow-up (hazard ratio (HR) = 0.54; 95% confidence interval (CI): 0.34-0.83). Women who "self-silenced" during conflict with their spouse, compared with women who did not, had four times the risk of dying (HR = 4.01; 95% CI: 1.75-9.20). Men with wives who were upset by work were 2.7 times more likely to develop CHD (HR = 2.71; 95% Cl: 1.22-6.03). Marital happiness, satisfaction, and disagreements were not related to the development of CHD or death in men or women. Conclusions: Our study suggests that marital communication, conflict, and strain are associated with adverse health outcomes. Further research into the influence of marital stress on health is merited. C1 Eaker Epidemiol Enterprises LLC, Gaithersburg, MD 20882 USA. Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Eaker, ED (reprint author), Eaker Epidemiol Enterprises LLC, 25015 Dunterry Court, Gaithersburg, MD 20882 USA. EM eakerepi@tznet.com OI Benjamin, Emelia/0000-0003-4076-2336; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-25195, R03 HL67426] NR 23 TC 97 Z9 100 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2007 VL 69 IS 6 BP 509 EP 513 DI 10.1097/PSY.0b013e3180f62357 PG 5 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 197EA UT WOS:000248535600005 PM 17634565 ER PT J AU Roca, AL Georgiadis, N O'Brien, SJ AF Roca, Alfred L. Georgiadis, Nicholas O'Brien, Stephen J. TI Cyto-nuclear genomic dissociation and the African elephant species question SO QUATERNARY INTERNATIONAL LA English DT Article; Proceedings Paper CT 2nd World of Elephants Congress CY SEP 22-25, 2005 CL Mammoth Site Hot Spring, Hot Spring, SD HO Mammoth Site Hot Spring ID MITOCHONDRIAL GENOME; POPULATIONS; EVOLUTION; LOCI AB Studies of skull morphology and of nuclear DNA have strongly concluded that African elephants comprise two species. Nonetheless, a recent article [Debruyne (2005). A case study of apparent conflict between molecular phylogenies: the interrelationships of African elephants. Cladistics 21, 31-50] has suggested a single-species model for Loxodonta based on the polyphyly of a single genetic locus, mitochondrial DNA (mtDNA). Discordant patterns between mitochondrial and nuclear DNA markers were subsequently reported in some African savanna elephant populations, further supporting a two-species model, and prompting us to re-examine here the geographic distribution of different elephant morphotypes and their relationship to nuclear and mtDNA phylogeographic patterns. We used exact tests to compare the distribution of forest elephant-typical and savanna elephant-typical characteristics across eight published datasets containing morphological, mtDNA or nuclear DNA data for African elephants. Among the elephants examined by Debruyne (2005), we found that patterns of forest vs. savanna characteristics were significantly different (P < 10-5) between mtDNA and morphology, suggesting the presence of cyto-nuclear genomic dissociation. We show that the eight African elephant continent-wide datasets compared, including that of Debruyne (2005), together support a two-species model with cyto-nuclear genomic dissociation rather than a one-species model, and together indicate that Africa harbors two species of elephant. (C) 2006 Elsevier Ltd and INQUA. All rights reserved. C1 SAIC Frederick, Lab Genom Diversity, Basic Res Program, Frederick, MD 21702 USA. NCI, Lab Genom Diversity, Frederick, MD 21702 USA. Mpala Res Ctr, Nanyuki, Kenya. RP Roca, AL (reprint author), SAIC Frederick, Lab Genom Diversity, Basic Res Program, Bldg 560-6, Frederick, MD 21702 USA. EM roca@ncifcrf.gov FU NCI NIH HHS [N01 CO12400/CO/NCI, N01CO12400] NR 25 TC 26 Z9 27 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1040-6182 J9 QUATERN INT JI Quat. Int. PD JUL PY 2007 VL 169 BP 4 EP 16 DI 10.1016/j.quaint.2006.08.008 PG 13 WC Geography, Physical; Geosciences, Multidisciplinary SC Physical Geography; Geology GA 198KX UT WOS:000248628100002 PM 18591997 ER PT J AU Simon, SL Bailiff, I Bouville, A Fattibene, P Kleinerman, RA Lloyd, DC McKeever, SWS Romanyukha, A Sevan'kaev, AV Tucker, JD Wieser, A AF Simon, Steven L. Bailiff, Ian Bouville, Andre Fattibene, Paola Kleinerman, Ruth A. Lloyd, David C. McKeever, Stephen W. S. Romanyukha, Alexander Sevan'kaev, Alexander V. Tucker, James D. Wieser, Albrecht TI BiodosEPR-2006 consensus committee report on biodosimetric methods to evaluate radiation doses at long times after exposure SO RADIATION MEASUREMENTS LA English DT Article; Proceedings Paper CT Joint Meeting of the 2nd International Conference on Biodosimetry/7th International Symposium on Electron Paramagnetic Resonance Dosimetry and Applications CY JUL 10-13, 2007 CL Bethesda, MD SP Uniformed Serv Univ DE dosimetry; biodosimetry; retrospective dosimetry ID NUCLEAR TEST-SITE; CHERNOBYL CLEANUP WORKERS; SOMATIC-CELL MUTATIONS; ATOMIC-BOMB SURVIVORS; RETROSPECTIVE LUMINESCENCE DOSIMETRY; ELECTRON-PARAMAGNETIC-RESONANCE; GLYCOPHORIN-A LOCUS; HUMAN TOOTH ENAMEL; STABLE CHROMOSOME-ABERRATIONS; CYTOGENETIC FOLLOW-UP AB The requirements for biodosimetric techniques used at long times after exposure, i.e., 6 months to more than 50 years, are unique compared to the requirements for methods used for immediate dose estimation. In addition to the fundamental requirement that the assay measures a physical or biologic change that is proportional to the energy absorbed, the signal must be highly stable over time to enable reasonably precise determinations of the absorbed dose decades later. The primary uses of these biodosimetric methods have been to support long-term health risk (epidemiologic) studies or to support compensation (damage) claims. For these reasons, the methods must be capable of estimating individual doses, rather than group mean doses. Even when individual dose estimates can be obtained, inter-individual variability remains as one of the most difficult problems in using biodosimetry measurements to rigorously quantify individual exposures. Other important criteria for biodosimetry methods include obtaining samples with minimal invasiveness, low detection limits, and high precision. Cost and other practical limitations generally prohibit biodosimetry measurements on a large enough sample to replace analytical dose reconstruction in epidemiologic investigations. However, these measurements can be extremely valuable as a means to corroborate analytical or model-based dose estimates, to help reduce uncertainty in individual doses estimated by other methods and techniques, and to assess bias in dose reconstruction models. There has been extensive use of three biodosimetric techniques in irradiated populations: EPR (using tooth enamel), FISH (using blood lymphocytes), and GPA (also using blood); these methods have been supplemented with luminescent methods applied to building materials and artifacts. A large number of investigations have used biodosimetric methods many years after external and, to a lesser extent, internal exposure to reconstruct doses received from accidents, from occupational exposures, from environmental releases of radioactive materials, and from medical exposures. In most applications, the intent has been to either identify highly exposed persons or confirmed suspected exposures. Improvements in methodology, however, have led many investigators to attempt quantification of whole-body doses received, or in a few instances, to estimate organ doses. There will be a continued need for new and improved biodosimetric techniques not only to assist in future epidemiologic investigations but to help evaluate the long-term consequences following nuclear accidents or events of radiologic terrorism. (c) 2007 Elsevier Ltd. All rights reserved. C1 NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Durham, Luminescence Dating & Dosimetry Lan, Durham, England. Ist Super Sanita, I-00161 Rome, Italy. Ist Nazl Fis Nucl, Rome, Italy. Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England. Oklahoma State Univ, Off Vice President Res & Technol Transfer, Stillwater, OK 74078 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol, Bethesda, MD 20814 USA. Med Radiol Res Ctr, Obninsk, Russia. Wayne State Univ, Dept Biol Sci, Detroit, MI 48202 USA. Inst Radiat Protect, GSF Natl Res Ctr, Neuherberg, Germany. RP Simon, SL (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov RI fattibene, paola/E-9041-2015; OI fattibene, paola/0000-0002-8204-0414; Kleinerman, Ruth/0000-0001-7415-2478 NR 172 TC 23 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD JUL-AUG PY 2007 VL 42 IS 6-7 BP 948 EP 971 DI 10.1016/j.radmeas.2007.05.036 PG 24 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 224AH UT WOS:000250416900002 ER PT J AU Sholom, S Desrosiers, M Bouville, A Luckyanov, N Chumak, V Simon, SL AF Sholom, Sergey Desrosiers, Marc Bouville, Andre Luckyanov, Nicholas Chumak, Vadim Simon, Steven L. TI EPR tooth dosimetry of SNTS area inhabitants SO RADIATION MEASUREMENTS LA English DT Article; Proceedings Paper CT Joint Meeting of the 2nd International Conference on Biodosimetry/7th International Symposium on Electron Paramagnetic Resonance Dosimetry and Applications CY JUL 10-13, 2007 CL Bethesda, MD SP Uniformed Serv Univ ID NUCLEAR TEST-SITE; DOLON VILLAGE; FALLOUT; POPULATION; VICINITY AB The determination of external dose to teeth of inhabitants of settlements near the Semipalatinsk Nuclear Test Site (SNTS) was conducted using the EPR dosimetry technique to assess radiation doses associated with exposure to radioactive fallout from the test site. In this study, tooth doses have been reconstructed for 103 persons with all studied teeth having been formed before the first nuclear test in 1949. Doses above those received from natural background radiation, termed "accident doses", were found to lie in the range from zero to approximately 2 Gy, with one exception, a dose for one person from Semipalatinsk city was approximately 9 Gy. The variability of reconstructed doses within each of the settlements demonstrated heterogeneity of the deposited fallout as well as variations in lifestyle. The village mean external gamma doses for residents of nine settlements were in the range from a few tens of mGy to approximately 100 mGy. (c) 2007 Elsevier Ltd. All rights reserved. C1 NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. Sci Ctr Radiat Med, Kiev, Ukraine. RP Simon, SL (reprint author), NCI, Natl Inst Hlth, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov RI Chumak, Vadim/N-6960-2015 OI Chumak, Vadim/0000-0001-6045-9356 FU NCI NIH HHS [CO5117, Y03 CO5117]; NIAID NIH HHS [Y02 AI005077] NR 15 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD JUL-AUG PY 2007 VL 42 IS 6-7 SI SI BP 1037 EP 1040 DI 10.1016/j.radmeas.2007.05.007 PG 4 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 224AH UT WOS:000250416900011 PM 19590746 ER PT J AU Sholom, S O'Brien, M Bakhanova, E Chumak, V Desrosiers, M Bouville, A AF Sholom, S. O'Brien, M. Bakhanova, E. Chumak, V. Desrosiers, M. Bouville, A. TI X-ray and gamma-ray absorbed dose profiles in teeth: An EPR and modeling study SO RADIATION MEASUREMENTS LA English DT Article; Proceedings Paper CT Joint Meeting of the 2nd International Conference on Biodosimetry/7th International Symposium on Electron Paramagnetic Resonance Dosimetry and Applications CY JUL 10-13, 2007 CL Bethesda, MD SP Uniformed Serv Univ ID SPIN-RESONANCE DOSIMETRY; TOOTH ENAMEL; CONVERSION AB Dose profiles in teeth have been experimentally and theoretically studied for different energies and geometries of incident X- and gamma-rays. The experiments were conducted with teeth inside of an Alderson phantom using monodirectional radiation beams at selected energies; they revealed two effects: an apparent lack of dose attenuation between the buccal and the lingual sides of the teeth for energies higher than 120 keV and an attenuation between first and last tooth layers for low-energy beams in the range from 0.28 to 0.57. Monte Carlo simulations confirmed the experimental data and provided dose profiles for other energies and geometries. In particular, exposure in the rotational radiation field produces pronounced dose profiles only for energies lower than 60 keV. The usefulness of these data to estimate the average energy of accidental radiation field is discussed. (c) 2007 Elsevier Ltd. All rights reserved. C1 Sci Ctr Radiat Med, Kiev, Ukraine. Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Sholom, S (reprint author), Sci Ctr Radiat Med, Melnikova St 53, Kiev, Ukraine. EM sholom@leed1.kiev.ua RI Chumak, Vadim/N-6960-2015 OI Chumak, Vadim/0000-0001-6045-9356 NR 8 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD JUL-AUG PY 2007 VL 42 IS 6-7 SI SI BP 1196 EP 1200 DI 10.1016/j.radmeas.2007.05.037 PG 5 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 224AH UT WOS:000250416900038 ER PT J AU Yukihara, EG Mittani, J McKeever, SWS Simon, SL AF Yukihara, E. G. Mittani, J. McKeever, S. W. S. Simon, S. L. TI Optically stimulated luminescence (OSL) of dental enamel for retrospective assessment of radiation exposure SO RADIATION MEASUREMENTS LA English DT Article; Proceedings Paper CT Joint Meeting of the 2nd International Conference on Biodosimetry/7th International Symposium on Electron Paramagnetic Resonance Dosimetry and Applications CY JUL 10-13, 2007 CL Bethesda, MD SP Uniformed Serv Univ ID DOSIMETRY AB This paper briefly reviews the optically stimulated luminescence (OSL) properties of dental enamel and discusses the potential and challenges of OSL for filling the technology gap in biodosimetry required for medical triage following a radiological/nuclear accident or terrorist event. The OSL technique uses light to stimulate a radiation-induced luminescence signal from materials previously exposed to ionizing radiation. This luminescence originates from radiation-induced defects in insulating crystals and is proportional to the absorbed dose of ionizing radiation. In our research conducted to date, we focused on fundamental investigations of the OSL properties of dental enamel using extracted teeth and tabletop OSL readers. The objective was to obtain information to support the development of the necessary instrumentation for retrospective dosimetry using dental enamel in laboratory, or for in situ and non-invasive accident dosimetry using dental enamel in emergency triage. An OSL signal from human dental enamel was detected using blue, green, or IR stimulation. Blue/green stimulation associated with UV emission detection seems to be the most appropriate combination in the sense that there is no signal from un-irradiated samples and the shape of the OSL decay is clear. Improvements in the minimum detection level were achieved by incorporating an ellipsoidal mirror in the OSL system to maximize light collection. Other possibilities to improve the sensitivity and research steps necessary to establish the feasibility of the technique for retrospective assessment of radiation exposure are also discussed. (c) 2007 Elsevier Ltd. All rights reserved. C1 Oklahoma State Univ, Dept Phys, Stillwater, OK 74078 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Yukihara, EG (reprint author), Oklahoma State Univ, Dept Phys, Stillwater, OK 74078 USA. EM eduardo.yukihara@okstate.edu RI Yukihara, Eduardo/F-1345-2014 OI Yukihara, Eduardo/0000-0002-4615-6698 FU NCI NIH HHS [CO5117, Y03 CO5117]; NIAID NIH HHS [Y02 AI005077] NR 11 TC 24 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD JUL-AUG PY 2007 VL 42 IS 6-7 SI SI BP 1256 EP 1260 DI 10.1016/j.radmeas.2007.05.03 PG 5 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 224AH UT WOS:000250416900049 PM 19623269 ER PT J AU Preston, DL Ron, E Tokuoka, S Funamoto, S Nishi, N Soda, M Mabuchi, K Kodama, K AF Preston, D. L. Ron, E. Tokuoka, S. Funamoto, S. Nishi, N. Soda, M. Mabuchi, K. Kodama, K. TI Solid cancer incidence in atomic bomb survivors: 1958-1998 SO RADIATION RESEARCH LA English DT Review ID HEPATITIS-C VIRUS; NONCANCER DISEASE INCIDENCE; SALIVARY-GLAND TUMORS; FEMALE BREAST-CANCER; 2 SWEDISH COHORTS; X-RAY THERAPY; RADIATION-THERAPY; INCIDENCE RATES; POOLED ANALYSIS; RISK-FACTORS AB This is the second general report on radiation effects on the incidence of solid cancers (cancers other than malignancies of the blood or blood-forming organs) among members of the Life Span Study (LSS) cohort of Hiroshima and Nagasaki atomic bomb survivors. The analyses were based on 17,448 first primary cancers (including non-melanoma skin cancer) diagnosed from 1958 through 1998 among 105,427 cohort members with individual dose estimates who were alive and not known to have had cancer prior to 1958. Radiation-associated relative risks and excess rates were considered for all solid cancers as a group, for 19 specific cancer sites or groups of sites, and for five histology groups. Poisson regression methods were used to investigate the magnitude of the radiation-associated risks, the shape of the dose response, how these risks vary with gender, age at exposure, and attained age, and the evidence for inter-site variation in the levels and patterns of the excess risk. For all solid cancers as a group, it was estimated that about 850 (about 11%) of the cases among cohort members with colon doses in excess of 0.005 Gy were associated with atomic bomb radiation exposure. The data were consistent with a linear dose response over the 0-to 2-Gy range, while there was some flattening of the dose response at higher doses. Furthermore, there is a statistically significant dose response when analyses were limited to cohort members with doses of 0.15 Gy or less. The excess risks for all solid cancers as a group and many individual sites exhibit significant variation with gender, attained age, and age at exposure. It was estimated that, at age 70 after exposure at age 30, solid cancer rates increase by about 35% per Gy (90% CI 28 %; 43 %) for men and 58 % per Gy (43 %; 69 %) for women. For all solid cancers as a group, the excess relative risk (ERR per Gy) decreases by about 17% per decade increase in age at exposure (90% CI 7%; 25%) after allowing for attained-age effects, while the ERR decreased in proportion to attained age to the power 1.65 (90% CI 2.1; 1.2) after allowing for age at exposure. Despite the decline in the ERR with attained age, excess absolute rates appeared to increase throughout the study period, providing further evidence that radiation-associated increases in cancer rates persist throughout life regardless of age at exposure. For all solid cancers as a group, women had somewhat higher excess absolute rates than men (F:M ratio 1.4; 90% CI 1.1; 1.8), but this difference disappears when the analysis was restricted to non-gender-specific cancers. Significant radiation-associated increases in risk were seen for most sites, including oral cavity, esophagus, stomach, colon, liver, lung, non-melanoma skin, breast, ovary, bladder, nervous system and thyroid. Although there was no indication of a statistically significant dose response for cancers of the pancreas, prostate and kidney, the excess relative risks for these sites were also consistent with that for all solid cancers as a group. Dose-response estimates for cancers of the rectum, gallbladder and uterus were not statistically significant, and there were suggestions that the risks for these sites may be lower than those for all solid cancers combined. However, there was emerging evidence from the present data that exposure as a child may increase risks of cancer of the body of the uterus. Elevated risks were seen for all of the five broadly classified histological groups considered, including squamous cell carcinoma, adenocarcinoma, other epithelial cancers, sarcomas and othernon-epithelial cancers. Although the data were limited, there was a significant radiation-associated increase in the risk of cancer occurring in adolescence and young adulthood. In view of the persisting increase in solid cancer risks, the LSS should continue to provide important new information on radiation exposure and solid cancer risks for at least another 15 to 20 years. (c) 2007 by Radiation Research Society C1 Hirosoft Int, Eureka, CA 95501 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Radiat Effects Res Fdn, Hiroshima, Japan. Radiat Effects Res Fdn, Nagasaki, Japan. RP Preston, DL (reprint author), Hirosoft Int, 1335 H St, Eureka, CA 95501 USA. EM preston@hirosoft.net FU Intramural NIH HHS; NCI NIH HHS [N01-CP-31021] NR 129 TC 709 Z9 750 U1 8 U2 62 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2007 VL 168 IS 1 BP 1 EP 64 DI 10.1667/RR0763.1 PG 64 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 183YI UT WOS:000247607900001 PM 17722996 ER PT J AU Papadopoulou, MV Bloomer, WD Taylor, AP Hernandez, M Blumenthal, RD Hollingshead, MG AF Papadopoulou, Maria V. Bloomer, William D. Taylor, Alice P. Hernandez, Marisol Blumenthal, Rosalyn D. Hollingshead, Melinda G. TI Advantage of combining NLCQ-1 (NSC 709257) with radiation in treatment of human head and neck xenografts SO RADIATION RESEARCH LA English DT Article ID LOCALLY ADVANCED HEAD; HYPOXIA-SELECTIVE CYTOTOXIN; CELL LUNG-CANCER; RANDOMIZED-TRIAL; TUMOR HYPOXIA; SOLID TUMORS; PHASE-II; HYDROCHLORIDE NLCQ-1; BIOREDUCTIVE AGENT; EXPLOITING HYPOXIA AB NLCQ-1 (NSC 709257), a hypoxia-selective cytotoxin that targets DNA through weak intercalation, was investigated for efficacy in combination with single or fractionated radiotherapy of human head and neck xenografts. A staged tumor experiment was performed in tumor-bearing female athymic nude mice that were locally irradiated with or without NLCQ-1. Tumor hypoxia was assessed by immunohistochemistry for pimonidazole adducts in tumors of varying weight. Fractionated radiation, depending on the dose, was administered either once daily for 4 days or once daily for 4 days followed by a 7-day rest and repeat. NLCQ-1 was administered i.p. at 15 mg/kg alone or 45 min before each radiation dose. Hypoxia (1-52%) was detected in all tumors and was positively correlated with tumor size. NLCQ-1 alone resulted in about 10 days of tumor growth delay, measured at sixfold the tumor's original size, without causing toxicity. All combination treatments with NLCQ-1 were more effective than treatments with radiation alone. Radiation at 1 Gy given once daily for 4 days on days 20 and 30 caused 3.5 days of tumor growth delay, whereas in combination with NLCQ-1 it caused 14.5 days of growth delay. Radiation at 5 Gy given in two doses 10 days apart resulted in 3.5 days of tumor growth delay, whereas more than 20 additional days of delay were observed in combination with NLCQ-1. Radiation given as a single dose of 10 Gy resulted in about 7 days of tumor growth delay, whereas in combination with NLCQ-1 about 30 additional days of delay were seen. These results suggest a significant advantage in combining radiation with NLCQ-1 in treatment of human head and neck tumors, which are known to have hypoxic areas. (c) 2007 by Radiation Research Society. C1 Evanston NW Healthcare, Dept Radiat Med, Evanston, IL 60201 USA. NCI, Biol Testing Branch, DTP, DCTC, Frederick, MD 21702 USA. Garden State Canc Ctr, Belleville, NJ 07109 USA. RP Papadopoulou, MV (reprint author), Evanston NW Healthcare, Dept Radiat Med, 2650 Ridge Ave, Evanston, IL 60201 USA. EM m-papadopoulou@northwestern.edu FU NCI NIH HHS [N01-CM-12400] NR 34 TC 6 Z9 6 U1 1 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUL PY 2007 VL 168 IS 1 BP 65 EP 71 DI 10.1667/RR0539.1 PG 7 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 183YI UT WOS:000247607900002 PM 17722994 ER PT J AU Brinton, L AF Brinton, Louise TI Long-term effects of ovulation-stimulating drugs on cancer risk SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article; Proceedings Paper CT 1st World Congress on Natural Cycle Minimal Stimulation IVF CY DEC 15-16, 2006 CL London, ENGLAND DE cancer; epidemiology; fertility drugs; infertility; ovulation stimulation; risk ID IN-VITRO FERTILIZATION; EPITHELIAL OVARIAN-CANCER; HORMONE-REPLACEMENT THERAPY; STATES CASE-CONTROL; BREAST-CANCER; FERTILITY DRUGS; INFERTILE WOMEN; UNITED-STATES; COLLABORATIVE ANALYSIS; BORDERLINE MALIGNANCY AB Although nulliparity has been extensively related to the risk of ovarian, breast and endometrial cancers, with many studies showing the relationship largely attributable to infertility, treatment effects on cancer risk are poorly understood. Two early studies raised substantial concern when ovulation-stimulating drugs were linked with large increases in ovarian cancer, supporting the notion of an important aetiological role of incessant ovulation. Subsequent studies have been mainly reassuring, although some have suggested possible risk increases among nulligravid women, those with extensive follow-up, and those developing borderline tumours. Results regarding effects of fertility drugs on breast cancer risk are conflicting, with some showing no associations and others demonstrating possible risk increases, although for varying subgroups. In contrast, endometrial cancer results are more consistent, with two recent studies showing increased risks related to clomiphene usage. This is of interest given that clomiphene is structurally similar to tamoxifen, a drug extensively linked with this cancer. Given the recent marketing of fertility drugs and the fact that exposed women are only beginning to reach the cancer age range, further follow-up is necessary. This will also be important to fully resolve effects of exposures such as gonadotrophins, used more recently in conjunction with IVF. C1 NCI, Hormonal & Reproduct Epidemiol Branch, Rockville, MD 20852 USA. RP Brinton, L (reprint author), NCI, Hormonal & Reproduct Epidemiol Branch, 6120 Execut Blvd,Suite 550,Room 5018, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 71 TC 27 Z9 27 U1 0 U2 9 PU REPRODUCTIVE HEALTHCARE LTD PI CAMBRIDGE PA DUCK END FARM, DRY DRAYTON, CAMBRIDGE, CB3 8DB, ENGLAND SN 1472-6483 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD JUL PY 2007 VL 15 IS 1 BP 38 EP 44 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 191UQ UT WOS:000248157900009 PM 17623533 ER PT J AU Kornyshev, AA Lee, DJ Leikin, S Wynveen, A AF Kornyshev, Alexei A. Lee, Dominic J. Leikin, Sergey Wynveen, Aaron TI Structure and interactions of biological helices SO REVIEWS OF MODERN PHYSICS LA English DT Review ID DNA DOUBLE HELICES; X-RAY-DIFFRACTION; CHOLESTERIC LIQUID-CRYSTALS; POISSON-BOLTZMANN EQUATION; COLLAGEN TRIPLE HELICES; DIVALENT METAL-IONS; DOUBLE-STRANDED DNA; STABILIZED COLLOIDAL SUSPENSIONS; CYLINDRICAL POLY-ELECTROLYTE; GUANOSINE 4-STRANDED HELICES AB Helices are essential building blocks of living organisms, be they molecular fragments of proteins (alpha-helices), macromolecules (DNA and collagen), or multimolecular assemblies (microtubules and viruses). Their interactions are involved in packing of meters of genetic material within cells and phage heads, recognition of homologous genes in recombination and DNA repair, stability of tissues, and many other processes. Helical molecules form a variety of mesophases in vivo and in vitro. Recent structural studies, direct measurements of intermolecular forces, single-molecule manipulations, and other experiments have accumulated a wealth of information and revealed many puzzling physical phenomena. It is becoming increasingly clear that in many cases the physics of biological helices cannot be described by theories that treat them as simple, unstructured polyelectrolytes. The present article focuses on the most important and interesting aspects of the physics of structured macromolecules, highlighting various manifestations of the helical motif in their structure, elasticity, interactions with counterions, aggregation, and poly- and mesomorphic transitions. C1 Univ London Imperial Coll Sci Technol & Med, Dept Chem, Fac Nat Sci, London SW7 2AZ, England. DHHS, Natl Inst Hlth, Natl Inst Child Hlth & Human Dev, Sec Phys Biochem, Bethesda, MD 20892 USA. RP Kornyshev, AA (reprint author), Univ London Imperial Coll Sci Technol & Med, Dept Chem, Fac Nat Sci, London SW7 2AZ, England. EM a.kornyshev@imperial.ac.uk; dj.lee@imperial.ac.uk; leikins@mail.nih.gov; a.wynveen@imperial.ac.uk RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 421 TC 177 Z9 181 U1 12 U2 83 PU AMER PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0034-6861 J9 REV MOD PHYS JI Rev. Mod. Phys. PD JUL-SEP PY 2007 VL 79 IS 3 BP 943 EP 996 DI 10.1103/RevModPhys.79.943 PG 54 WC Physics, Multidisciplinary SC Physics GA 201XX UT WOS:000248867000006 ER PT J AU Ellis, JC Barnes, J Brown, JW AF Ellis, J. Chris Barnes, Jeffrey Brown, James W. TI Is Alba an RNase P subunit? SO RNA BIOLOGY LA English DT Article DE ribonuclease P; archaea; rihozyme; Methanothermobacter thermoautotrophicus; Mth1483; Rpp25 ID ARCHAEAL CHROMATIN PROTEIN; PYROCOCCUS-HORIKOSHII OT3; RIBONUCLEASE-P; CRYSTAL-STRUCTURE; DNA-BINDING; MECHANISM; SIR2; RECONSTITUTION; ACETYLATION; HOLOENZYME AB It has been suggested that Alba, a well-established chromatin protein in Archaea, is also a subunit of the archaeal RNase P holoenzyme, based on the observation that the homolog of this protein in humans has been shown to be associated with RNase P activity. Using the same biochemical methods we used previously to show that four other proteins homologous to eukaryotic RNase P proteins are bona fide RNase P subunits in Archaea, we could not detect any association of the Alba homolog in Methanothermobacter thermoautotrophicus (Mth 1483p) with the RNase P holoenzyme. In addition, the presence of Mth 1483p did not enhance the activity of RNase P holoenzyme reconstituted from recombinant subunits. In conclusion, we find no evidence that Alba is an RNase P subunit. C1 [Brown, James W.] N Carolina State Univ, Dept Microbiol, Raleigh, NC 27695 USA. [Ellis, J. Chris] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. [Barnes, Jeffrey] Appl Biosyst Inc, Foster City, CA USA. RP Brown, JW (reprint author), N Carolina State Univ, Dept Microbiol, Campus Box 7615, Raleigh, NC 27695 USA. EM james_brown@ncsu.edu RI Ellis, Joseph/G-6335-2011 NR 29 TC 7 Z9 7 U1 1 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1547-6286 EI 1555-8584 J9 RNA BIOL JI RNA Biol. PD JUL-DEC PY 2007 VL 4 IS 3 BP 169 EP 172 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 265WG UT WOS:000253391900009 PM 18347433 ER PT J AU Pletneva, NV Pletnev, SV Chudakov, DM Tikhonova, TV Popov, VO Martynov, VI Wlodawer, A Dauter, Z Pletnev, VZ AF Pletneva, N. V. Pletnev, S. V. Chudakov, D. M. Tikhonova, T. V. Popov, V. O. Martynov, V. I. Wlodawer, A. Dauter, Z. Pletnev, V. Z. TI Three-dimensional structure of yellow fluorescent protein zYFP538 from Zoanthus sp at the resolution 1.8 angstrom SO RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY LA English DT Article DE GFP-like proteins; crystal structure; chromophore structure; tetramer structure; intersubunit interfaces; yellow fluorescent protein; Zoanthus sp ID MONOMERIC RED; CHROMOPHORE; DECARBOXYLATION; FRAGMENTATION; MATURATION; CONVERSION; MECHANISM; EXTENSION; PROGRAM; ZFP538 AB The three-dimensional structure of yellow fluorescent proteins zYFP538 (zFP538) from the button polyp Zoanthus sp. was determined at a resolution of 1.8 angstrom by X-ray analysis. The monomer of zYFP538 adopts a structure characteristic of the green fluorescent protein (GFP) family, a beta-barrel formed from 11 antiparallel beta segments and one internal alpha helix with a chromophore embedded into it. Like the TurboGFP, the beta-barrel of zYFP538 contains a water-filled pore leading to the chromophore Tyr67 residue, which presumably provides access of molecular oxygen necessary for the maturation process. The post-translational modification of the chromophore-forming triad Lys66-Tyr67-Gly68 results in a tricyclic structure consisting of a five-membered imidazolinone ring, a phenol ring of the Tyr67 residue, and an additional six-membered tetrahydropyridine ring. The chromophore formation is completed by cleavage of the protein backbone at the C-alpha-N bond of Lys66. It was suggested that the energy conflict between the buried positive charge of the intact Lys66 side chain in the hydrophobic pocket formed by the Ile44, Leu46, Phe65, Leu204 and Leu219 side chains is the most probable trigger that induces the transformation of the bicyclic green form to the tricyclic yellow form. A stereochemical analysis of the contacting surfaces at the intratetramer interfaces helped reveal a group of conserved key residues responsible for the oligomerization. Along with others, these residues should be taken into account in designing monomeric forms suitable for practical application as markers of proteins and cell organelles. C1 Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. Russian Acad Sci, Bach Inst Biochem, Moscow 119071, Russia. Natl Canc Inst, Lab Macromol Crystallog, Synchrotron Radiat Res Sect, Argonne, IL 60439 USA. NCI, Prot Struct Sect, Lab Macromol Crystallog, Frederick, MD 21702 USA. RP Pletneva, NV (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Ul Miklukho Maklaya 16-10, Moscow 117997, Russia. EM nadand@mail.ru RI Chudakov, Dmitriy/G-7741-2014; Pletneva, Nadya/F-7839-2014; Pletnev, Vladimir/Q-6151-2016; Martynov, Vladimir/S-3483-2016 OI Chudakov, Dmitriy/0000-0003-0430-790X; Martynov, Vladimir/0000-0003-4923-6842 NR 41 TC 9 Z9 9 U1 0 U2 2 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 1068-1620 J9 RUSS J BIOORG CHEM+ JI Russ. J. Bioorg. Chem. PD JUL PY 2007 VL 33 IS 4 BP 390 EP 398 DI 10.1134/S1068162007040048 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 194FG UT WOS:000248329200004 ER PT J AU Elvevag, B Foltz, PW Weinberger, DR Goldberg, TE AF Elvevag, Brita Foltz, Peter W. Weinberger, Daniel R. Goldberg, Terry E. TI Quantifying incoherence in speech: An automated methodology and novel application to schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE psychosis; language; semantic; thought disorder ID LATENT SEMANTIC ANALYSIS; THOUGHT-DISORDER; LANGUAGE PRODUCTION; COMMUNICATION; FLUENCY AB Incoherent discourse, with a disjointed flow of ideas, is a cardinal symptom in several psychiatric and neurological conditions. However, measuring incoherence has often been complex and subjective. We sought to validate an objective, intrinsically reliable, computational approach to quantifying speech incoherence. Patients with schizophrenia and healthy control volunteers were administered a variety of language tasks. The speech generated was transcribed and the coherence computed using Latent Semantic Analysis (LSA). The discourse was also analyzed with a standard clinical measure of thought disorder. In word association and generation tasks LSA derived coherence scores were sensitive to differences between patients and controls, and correlated with clinical measures of thought disorder. In speech samples LSA could be used to localize where in sentence production incoherence occurs, predict levels of incoherence as well as whether discourse "belonged" to a patient or control. In conclusion, LSA can be used to assay disordered language production so as to both complement human clinical ratings as well as experimentally parse this incoherence in a theory-driven manner. (c) 2007 Elsevier B.V. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. New Mexico State Univ, Dept Psychol, Las Cruces, NM 88003 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. EM brita@elvevaag.net FU Intramural NIH HHS [Z01 MH002712-13] NR 34 TC 37 Z9 37 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 EI 1573-2509 J9 SCHIZOPHR RES JI Schizophr. Res. PD JUL PY 2007 VL 93 IS 1-3 BP 304 EP 316 DI 10.1016/j.schres.2007.03.001 PG 13 WC Psychiatry SC Psychiatry GA 184SU UT WOS:000247663200035 PM 17433866 ER PT J AU Girlanda, R Mannon, RB Kirk, AD AF Girlanda, Raffbele Mannon, Roslyn B. Kirk, Allan D. TI Diagnostic tools for monitoring kidney transplant recipients SO SEMINARS IN NEPHROLOGY LA English DT Review DE kidney transplantation; monitoring; protocol biopsy; allograft rejection; immunosuppression ID RENAL-ALLOGRAFT REJECTION; GLOMERULAR-FILTRATION-RATE; URINE FLOW-CYTOMETRY; INTERCELLULAR-ADHESION MOLECULE-1; CYTOKINE GENE-EXPRESSION; SERUM CYSTATIN C; PERIPHERAL-BLOOD LYMPHOCYTES; CREATININE REDUCTION RATIO; LIMITING DILUTION ANALYSIS; DEAMINASE-BINDING-PROTEIN C1 NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Kirk, AD (reprint author), Room 5-5752,Bldg 10CRC,Ctr Dr, Bethesda, MD 20892 USA. EM lank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 FU Intramural NIH HHS NR 180 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD JUL PY 2007 VL 27 IS 4 BP 462 EP 478 DI 10.1016/j.semnephrol.2007.03.007 PG 17 WC Urology & Nephrology SC Urology & Nephrology GA 192MP UT WOS:000248206400008 PM 17616277 ER PT J AU Zheng, P Dean, J AF Zheng, Ping Dean, Jurrien TI Oocyte-specific genes affect folliculogenesis, fertilization, and early development SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE oocyte-specific genes; folliculogenesis; fertilization; preimplantation embryonic development ID MATERNAL-EFFECT GENE; GROWTH-DIFFERENTIATION FACTOR-9; ZONA-PELLUCIDA GLYCOPROTEIN; GERM-CELL DIFFERENTIATION; SPERM-EGG RECOGNITION; LIM-HOMEOBOX GENE; MOUSE OOCYTES; TRANSCRIPTION FACTOR; KNOCKOUT MICE; EMBRYONIC-DEVELOPMENT AB Although cell-autonomous genetic programs pursued by germ and somatic cells are of critical import, intimate interplays between the two cell types are also essential for normal development of the female gonad. Recent studies demonstrate that oocytes play active roles in coordinating the growth and differentiation of somatic cells during folliculogenesis and affect successful outcomes at fertilization and early development. Mouse transgenesis has been particularly useful in defining germ-cell specific genes and their roles in folliculogenesis (e.g., Dazla, Figla, Nobox, Sohlh1, Ybx2, Cpeb1, Gdf9), pl, Zp2, Zp3), and preimplantation embryonic development (e.g., fertilization (e.g., Zp1 Npm2, Zar1, Nalp5, Dppa3). Continued identification of novel oocyte-specific genes and the annotation of their functions will provide additional insight into the genetic pathways regulating ovarian development. The knowledge gained from mouse models will no doubt benefit the understanding of human biology and treatment of reproductive failure. C1 NIH, NIDDK, Cellular & Dev Biol Lab, Bethesda, MD 20892 USA. RP Zheng, P (reprint author), NIH, NIDDK, Cellular & Dev Biol Lab, 50 S Dr, Bethesda, MD 20892 USA. EM zhengp@niddk.nih.gov FU Intramural NIH HHS NR 90 TC 55 Z9 58 U1 0 U2 13 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JUL PY 2007 VL 25 IS 4 BP 243 EP 251 DI 10.1055/s-2007-980218 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 185UU UT WOS:000247736700005 PM 17594605 ER PT J AU Ottolenghi, C Colombino, M Crisponi, L Cao, A Forabosco, A Schlessinger, D Uda, M AF Ottolenghi, Chris Colombino, Maria Crisponi, Laura Cao, Antonio Forabosco, Antonino Schlessinger, David Uda, Manuela TI Transcriptional control of ovarian development in somatic cells SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE ovary; development; premature ovarian failure; follicle formation; follicle dynamics; sex determination; transcription factors; forkhead domain; granulosa cells ID DOUBLESEX-RELATED GENES; SEX DETERMINATION; FOLLICLE DEVELOPMENT; MOUSE OVARY; OOCYTE DEVELOPMENT; INVERSUS SYNDROME; MAMMALIAN OVARY; EMBRYONIC GONAD; FACTOR FOXL2; IN-VITRO AB Developmental transitions of the bipotential gonad to the embryonic ovary and thence to the follicle-filled mature ovary are expected to be coordinated by sets of transcription factors. We infer candidate lists here, focusing on somatic cell fate and function. For the mouse, developmental stages of ovary differentiation are relatively discretely phased, and provide a unique tool to investigate the intricate mechanisms that lead to the acquisition of female reproductive competence. Cross-platform gene expression profiles supplement functional studies of specific genes and comparative information about human biology. Available data suggest that: (1) peak transcription activity just precedes the two most decisive steps of early ovary differentiation (i.e., entry into meiosis and follicle formation); (2) alternating peak gene activities in oocytes and somatic cells may reflect reciprocal interactions; and (3) in addition to stable states of chromatin modification associated with morphogenesis, some features of differentiation are labile, contingent on the expression state of critical factors. Examples are the maintenance of somatic sex determination by continued Fox12 action and the reversible maintenance of follicles in a quiescent state by nuclear Foxo3. C1 Natl Inst Aging, Genet Lab, Baltimore, MD USA. Osped Microcitem, Consiglio Nazl Ric, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. Univ Modena & Reggio Emilia, Policlinico, Dipartimento Materno Infantile, I-41100 Modena, Italy. RP Schlessinger, D (reprint author), TRIAD Bldg,333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM SchlessingerD@grc.nia.nih.gov FU Intramural NIH HHS; Telethon [GP0049Y01] NR 85 TC 3 Z9 3 U1 1 U2 5 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD JUL PY 2007 VL 25 IS 4 BP 252 EP 263 DI 10.1055/s-2007-980219 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 185UU UT WOS:000247736700006 PM 17594606 ER PT J AU Rodriguez, AC Burk, R Herrero, R Hildesheim, A Bratti, C Sherman, ME Solomon, D Guillen, D Alfaro, M Viscidi, R Morales, J Hutchinson, M Wacholder, S Schiffman, M AF Rodriguez, Ana Cecilia Burk, Robert Herrero, Rolando Hildesheim, Allan Bratti, Concepcion Sherman, Mark E. Solomon, Diane Guillen, Diego Alfaro, Mario Viscidi, Raphael Morales, Jorge Hutchinson, Martha Wacholder, Sholom Schiffman, Mark TI The natural history of human papillomavirus infection and cervical Intraepithelial neoplasia among young women in the guanacaste cohort shortly after initiation of sexual life SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID FEMALE UNIVERSITY-STUDENTS; COSTA-RICA; POPULATION; CANCER; RISK; CARCINOGENESIS; DURATION; LESIONS; DNA AB Objective: Cross-sectional analyses of our 10,000-woman, population-based Guanacaste cohort suggest a lag of >= 10 years between the peak of human papillomavirus (HPV) infection and the later peak of cervical intraepithelial neoplasia grade 3 (CIN 3). We wanted to explore early HPV natural history and CIN 3 prospectively. Study Design: As part of the Guanacaste cohort, we followed 206 initially virginal women aged 18 to 26 semiannually for a median of 3.6 years after initiation of sexual life. Results: A total of 53.4% of women tested positive during the study for 1 HPV type. Very few infections persisted for >1 to 2 years. Three women had histologically confirmed CIN 3, of which 2 showed persistent HPV 16. The other had serologic evidence of HPV 31. Conclusions: HPV infection occurs frequently and clears rapidly in most young women initiating sexual intercourse. Persistent HPV 16 can cause early CIN 3. The peak age for CIN 3 will decline with the increased screening intensity and sensitivity typical of longitudinal studies. C1 DHHS, Natl Inst Hlth, Div Canc Epidemiol & Genet, Rockville, MD 20859 USA. DHHS, Natl Inst Hlth, Natl Canc Inst, Div Canc Prevent, Rockville, MD USA. INCIENSA Fdn, Proyecto Epidemiol Guanacastle, San Jose, Costa Rica. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. RP Rodriguez, AC (reprint author), DHHS, Natl Inst Hlth, Div Canc Epidemiol & Genet, 6120 Executive Blvd,EPS Suite 550, Rockville, MD 20859 USA. EM rodrigac@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA-78527, N01-CP-21081, N01-CP-33061, N01-CP-40542, N01-CP-50535, N01-CP-81023] NR 30 TC 37 Z9 39 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JUL PY 2007 VL 34 IS 7 BP 494 EP 502 DI 10.1097/01.olq.0000251241.03088.a0 PG 9 WC Infectious Diseases SC Infectious Diseases GA 182SJ UT WOS:000247524000014 PM 17237737 ER PT J AU Fokianos, K Troendle, JF AF Fokianos, Konstantinos Troendle, James F. TI Inference for the relative treatment effect with the density ratio model SO STATISTICAL MODELLING LA English DT Article DE Box-Cox transformation; empirical likelihood; likelihood ratio test; nonparametric Behrens-Fisher hypothesis; power; simulation ID BEHRENS-FISHER PROBLEM AB Consider the problem of estimating and testing the relative treatment effect between two populations based on a random sample from each distribution. Under the well-established normal theory, inference is based on analysis of variance methods. However, there are many examples of skewed data which show that normal theory is not applicable. Then the problem of inference regarding the treatment effect can be attacked by standard nonparametric methods. In this paper, we propose a serniparametric model, the so-called density ratio model, which specifies that the log-likelihood ratio of two densities is linear in some parameters. For testing hypotheses regarding the relative treatment effect, a robust test is obtained by employing the density ratio model for a suitable Box-Cox transformation of the data. The transformation, along with the density ratio model, are estimated by maximum empirical likelihood. The new test procedure is studied theoretically and it is applied to real and simulated data. It is further compared with some nonparametric competitors, and it is found to have relatively high power across a wide variety of distributions, including those outside the density ratio family. C1 NICHHD, Biometry & Math Stat Branch, Bethesda, MD 20892 USA. Univ Cyprus, Dept Math & Stat, Nicosia, Cyprus. RP Troendle, JF (reprint author), NICHHD, Biometry & Math Stat Branch, Bld 6100,Room 7B05, Bethesda, MD 20892 USA. EM jt3t@nih.gov NR 16 TC 5 Z9 5 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1471-082X EI 1477-0342 J9 STAT MODEL JI Stat. Model. PD JUL PY 2007 VL 7 IS 2 BP 155 EP 173 DI 10.1177/1471082X0700700203 PG 19 WC Statistics & Probability SC Mathematics GA 215EF UT WOS:000249790400003 ER PT J AU Yang, S Zhao, Y AF Yang, Song Zhao, Yichuan TI Testing treatment effect by combining weighted log-rank tests and using empirical likelihood SO STATISTICS & PROBABILITY LETTERS LA English DT Article DE clinical trials; crossing survival curves; survival analysis; weighted log-rank tests ID RIGHT CENSORED-DATA; REGRESSION-ANALYSIS; SURVIVAL FUNCTIONS; CONFIDENCE BANDS; RATIO; TABLES; TERM AB For testing treatment effect with time to event data, combinations of several tests are often desired when the hazard functions of the two groups are nonproportional. Yang and Prentice [2005. Serniparametric analysis of short term and long term hazard ratios with two sample survival data. Biometrika 92, 1-17.] defined a new two-sample semiparametric model that accommodates nonproportional hazard functions and contains the Cox model and the proportional odds model as two submodels. They also obtained a x(2) test on the parameter that reduces to the x(2) test based on weighted log-rank tests for testing the null hypothesis of no treatment effect. In this paper, we consider a new x(2) test using the empirical likelihood method. Extensive simulation studies were conducted to compare the performance of the test with other related ones, for a variety of combinations of the short-term and long-term treatment effects. (c) 2007 Elsevier B.V. All rights reserved. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Georgia State Univ, Dept Math & Stat, Atlanta, GA 30303 USA. RP Yang, S (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr MSC 7938, Bethesda, MD 20892 USA. EM yangso@nhlbi.nili.gov NR 23 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7152 J9 STAT PROBABIL LETT JI Stat. Probab. Lett. PD JUL 1 PY 2007 VL 77 IS 12 BP 1385 EP 1393 DI 10.1016/j.spl.2007.03.025 PG 9 WC Statistics & Probability SC Mathematics GA 187GK UT WOS:000247835400027 ER PT J AU Brenner, S Ryser, MF Whiting-Theobald, NL Gentsch, M Linton, GF Malech, HL AF Brenner, Sebastian Ryser, Martin F. Whiting-Theobald, Narda L. Gentsch, Marcus Linton, Gilda F. Malech, Harry L. TI The late dividing population of gamma-retroviral vector transduced human mobilized peripheral blood progenitor cells contributes most to gene-marked cell engraftment in nonobese diabetic/severe combined immunodeficient mice SO STEM CELLS LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CHRONIC GRANULOMATOUS-DISEASE; CD34(+) CELLS; CYCLE KINETICS; CORD BLOOD; IN-VITRO; FUNCTIONAL DIFFERENCES; OXIDASE DEFECT; MARROW-CELLS; VIVO AB We used the nonobese diabetic/severe combined immunodeficient (NOD/SCID) mouse model to assess the repopulation potential of subpopulations of mobilized human CD34+ peripheral blood progenitor cells (PBPC). First, PBPC were transduced with gamma-retrovirus vector RD114-MFGS-CFP, which requires cell division for successful transduction, at 24 hours, 48 hours, and 72 hours to achieve 96% cyan fluorescent protein (CFP)-positive cells. Cells were sorted 12 hours after the last transduction into CFP-positive (divided cells) and CFP-negative populations. CFP-positive cells were transplanted postsort, whereas the CFP-negative cells were retransduced and injected at 120 hours. The CFP-negative sorted and retransduced cells contained markedly fewer vector copies and resulted in a 32-fold higher overall engraftment and in a 13-fold higher number of engrafted transgene positive cells. To assess cell proliferation as an underlying cause for the different engraftment levels, carboxyfluorescein succinimidyl ester-labeling of untransduced PBPC was performed to track the number of cell divisions. At 72 hours after initiation of culture, when 95% of all cells have divided, PBPC were sorted into nondivided and divided fractions and transplanted into NOD/SCID mice. Non-divided cells demonstrated 45-fold higher engraftment than divided cells. Late dividing PBPC in ex vivo culture retain high expression of the stem cell marker CD133, whereas rapidly proliferating cells lose CD133 in correlation to the number of cell divisions. Our studies demonstrate that late dividing progenitors transduced with gamma-retroviral vectors contribute most to NOD/SCID engraftment and transgene marking. Confining the gamma-retroviral transduction to CD133-positive cells on days 3 and 4 could greatly reduce the number of transplanted vector copies, limiting the risk of leukemia from insertional mutagenesis. C1 Univ Clin Carl Gustav Carus, Dept Pediat, D-01307 Dresden, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Brenner, S (reprint author), Univ Clin Carl Gustav Carus, Dept Pediat, Bldg 21,Fetscherstr 74, D-01307 Dresden, Germany. EM sebastian.brenner@uniklinikum-dresden.de RI Brenner, Sebastian/D-7456-2013; OI Malech, Harry/0000-0001-5874-5775 NR 21 TC 11 Z9 11 U1 0 U2 0 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 2007 VL 25 IS 7 BP 1807 EP 1813 DI 10.1634/stemcells.2006-0581 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 185PE UT WOS:000247722100026 PM 17464090 ER PT J AU Kuznetsov, SA Mankani, MH Leet, AI Ziran, N Gronthos, S Robey, PG AF Kuznetsov, Sergei A. Mankani, Mahesh H. Leet, Arabella I. Ziran, Navid Gronthos, Stan Gehron Robey, Pamela TI Circulating connective tissue precursors: Extreme rarity in humans and chondrogenic potential in guinea pigs SO STEM CELLS LA English DT Article DE blood cells; cell culture; cell transplantation; chondrogenesis ID UMBILICAL-CORD BLOOD; MESENCHYMAL STEM-CELLS; MARROW STROMAL CELLS; FIBROBLAST COLONY FORMATION; DIFFUSION CHAMBER IMPLANTS; BUFFY COAT CULTURES; BONE-MARROW; IN-VITRO; PROGENITOR CELLS; PERIPHERAL-BLOOD AB Using a variety of cell separation techniques and cultivation conditions, circulating, adherent, connective tissue, clonogenic cells were found in just 3 donors out of 66, demonstrating that these precursors are extremely rare in postnatal human blood. Contrary to humans, guinea pig blood shows much more reproducible connective tissue colony formation; it was therefore chosen to study the differentiation potential of adherent blood-derived clonogenic cells. Out of 22 single colony-derived strains of various morphologies, only 5 spindle-shaped strains showed extensive proliferative capacity in vitro. None of these strains formed bone upon in vivo transplantation, whereas two strains formed cartilage in high-density pellet cultures in vitro. Both chondrogenic strains included cells expressing aggrecan, whereas nonchondrogenic strains did not. Out of four polyclonal strains studied, one formed both cartilage and abundant bone accompanied by hematopoiesis-supporting stroma. Evidently, there are cells in adult guinea pig blood capable of both extensive proliferation and differentiation toward cartilage: circulating chondrogenic precursors. Although some of these cells lack osteogenic potential and therefore represent committed chondrogenic precursors, others may be multipotential and consequently belong to the family of skeletal stem cells. This is the first demonstration of postnatal circulating chondrogenic precursors, as well as of precursor cells with chondrogenic but not osteogenic potential. C1 Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RP Kuznetsov, SA (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Bldg 30,Room 228,30 Convent Dr MSC 4370, Bethesda, MD 20892 USA. EM skuznets@mail.nih.gov RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 63 TC 37 Z9 40 U1 1 U2 8 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD JUL PY 2007 VL 25 IS 7 BP 1830 EP 1839 DI 10.1634/stemcells.2007-0140 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 185PE UT WOS:000247722100029 PM 17464083 ER PT J AU Baker, ML Larsen, EKM Kuller, LH Klein, R Klein, BEK Siscovick, DS Bernick, C Manolio, TA Wong, TY AF Baker, Michelle L. Larsen, Emily K. Marino Kuller, Lewis H. Klein, Ronald Klein, Barbara E. K. Siscovick, David S. Bernick, Charles Manolio, Teri A. Wong, Tien Yin TI Retinal microvascular signs, cognitive function, and dementia in older persons - The cardiovascular health study SO STROKE LA English DT Article DE cognitive impairment; dementia; hypertension; retinal microvascular disease; retinopathy ID POPULATION-BASED COHORT; WHITE-MATTER LESIONS; MIDDLE-AGED ADULTS; ALZHEIMERS-DISEASE; ATHEROSCLEROSIS RISK; BLOOD-PRESSURE; ABNORMALITIES; BRAIN; COMMUNITIES; IMPAIRMENT AB Background and Purpose - Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals. Methods - In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded. Results - After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit - Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P = 0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension. Conclusions - In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons. C1 Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia. Univ Washington, Dept Biostat, Washington, DC USA. Univ Washington, Dept Epidemiol, Washington, DC USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Univ Nevada, Sch Med, Div Neurol, Las Vegas, NV 89154 USA. NHLBI, Bethesda, MD 20892 USA. Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore Eye Res Inst, Singapore 117548, Singapore. RP Wong, TY (reprint author), Univ Melbourne, Ctr Eye Res Australia, 32 Gisborne St, Melbourne, Vic 3002, Australia. EM twong@unimelb.edu.au FU NHLBI NIH HHS [N01-HC-45133, N01 HC-15103, N01 HC-55222, N01-HC-35129, N01-HC-75150, N01-HC-85079, N01-HC-85086, R21-HL077166, U01 HL080295] NR 35 TC 58 Z9 62 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2007 VL 38 IS 7 BP 2041 EP 2047 DI 10.1161/STROKEAHA.107.483586 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 182OG UT WOS:000247513300024 PM 17525385 ER PT J AU Messe, SR Kasner, SE Chalela, JA Cucchiara, B Demchuk, AM Hill, MD Warach, S AF Messe, Steven R. Kasner, Scott E. Chalela, Julio A. Cucchiara, Brett Demchuk, Andrew M. Hill, Michael D. Warach, Steven TI CT-NIHSS mismatch does not correlate with MRI diffusion-perfusion mismatch SO STROKE LA English DT Article DE cerebral infarct; computed tomography; ischemic penumbra; magnetic resonance imaging; mismatch; neuroradiology; thrombolysis ID ACUTE ISCHEMIC-STROKE; COMPUTED-TOMOGRAPHY; INTRAVENOUS THROMBOLYSIS; SCORE; DESMOTEPLASE; MULTICENTER; INFARCTION; THERAPY; PREDICT; TISSUE AB Background and Purpose - MRI diffusion-perfusion mismatch may identify patients for thrombolysis beyond 3 hours. However, MRI has limited availability in many hospitals. We investigated whether mismatch between the Alberta Stroke Program Early CT Score (ASPECTS) and the NIH Stroke Scale (NIHSS) correlates with MRI diffusion-perfusion mismatch. Methods - We retrospectively analyzed a cohort of consecutive acute ischemic stroke patients who underwent MRI and CT at admission. NIHSS was performed by the admitting physician. MRI and CT were reviewed by 2 blinded expert raters. Degree of MRI mismatch was defined as present (> 25%) or absent (< 25%). Univariate and multivariate analyses were performed to determine characteristics associated with MRI mismatch. Probability of MRI mismatch was calculated for all combinations of ASPECTS and NIHSS cutoff scores. Results - Included in the analysis were 143 patients. Median NIHSS on admission was 4 (IQR, 2 to 10); median ASPECTS was 10 (IQR, 9 to 10). Median time to completion of MRI and CT was 4.5 (2.5 to 13.9) hours after onset. CT and MRI were separated by a median of 35 (IQR, 29 to 44) minutes. MRI mismatch was present in 41% of patients. In multivariate analysis, only shorter time-to-scan (OR, 0.96 per hour; 95% CI, 0.92 to 1.0; P = 0.043) was associated with MRI mismatch. There was no combination of NIHSS and ASPECTS thresholds that was significantly associated with MRI mismatch. Conclusions - ASPECTS-NIHSS mismatch did not correlate with MRI diffusion-perfusion mismatch in this clinical cohort. MRI mismatch was associated with decreasing time from stroke onset to scan. C1 Univ Penn, Med Ctr, Comprehens Stroke Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA 19104 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA. Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. NIH, Bethesda, MD 20892 USA. RP Messe, SR (reprint author), Univ Penn, Med Ctr, Comprehens Stroke Ctr, Dept Neurol, 3W Gates Building,3400 Spruce St, Philadelphia, PA 19104 USA. EM messe@mail.med.upenn.edu RI Kasner, Scott/C-6109-2011; Demchuk, Andrew/E-1103-2012; Hill, Michael/C-9073-2012 OI Demchuk, Andrew/0000-0002-4930-7789; Hill, Michael/0000-0002-6269-1543 FU Intramural NIH HHS; NINDS NIH HHS [NS02147] NR 26 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2007 VL 38 IS 7 BP 2079 EP 2084 DI 10.1161/STROKEAHA.106.480731 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 182OG UT WOS:000247513300030 PM 17540971 ER PT J AU Zhang, XY Yasuno, F Zoghbi, SS Liow, JS Hong, J McCarron, JA Pike, VW Innis, RB AF Zhang, Xiang-Yang Yasuno, Fumihiko Zoghbi, Sami S. Liow, Jeih-San Hong, Jinsoo McCarron, Julie A. Pike, Victor W. Innis, Robert B. TI Quantification of serotonin 5-HT1A receptors in humans with [C-11](R)-(-)-RWAY: Radiometabolite(s) likely confound brain measurements SO SYNAPSE LA English DT Article DE PET; kinetic analysis; serotonin 5-HT1A; [C-11](R)-(-)-RWAY; human ID POSITRON-EMISSION-TOMOGRAPHY; PET; RADIOLIGAND; DELINEATION; TRANSPORTER; MONKEY; BLOOD; MODEL AB [C-11](R)-(-)-RWAY has been shown to be a promising radioligand for kimaging brain 5-HT1A receptors with positron emission tomography in rodents and nonhuman primates. We now report the first use of [C-11](R)-(-)-RWAY in six healthy human subjects, using kinetic brain imaging and serial arterial measurements of plasma parent radiotracer. At 80 min after radiotracer injection, activity ratios were about three for brain receptor-rich regions compared with cerebellum. However, the washout from brain was unexpectedly slow relative to plasma clearance of the parent radiotracer. This disparity between brain and plasma activity was quantified with distribution volume calculated from increasingly truncated brain imaging data. In both receptor-rich regions and cerebellum, distribution volumes were unstable and increased continuously from 90 to 150 min by about 30%. This increasing distribution volume was unlikely due to the variations or errors of plasma input at later time points, since a similar truncation of plasma time points from 150 to 90 min did not significantly affect the analysis of the brain data. When the metabolites of [C-11](R)-(-)-RWAY in human and monkey were compared, a moderate lipophilic radiometabolite was present at a significantly higher percentage of total plasma radioactivity in human than in monkey. The relatively slow washout of activity from brain and the temporal instability of distribution volume likely reflect the accumulation of radiometabolite(s) in human brain. Although prior studies in rodents and nonhuman primates showed [C-11](R)-(-)-RWAY to be a promising radiotracer, we suspect that a species difference in metabolism caused this serious deficiency in humans. C1 Natl Inst Mental Hlth, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Innis, RB (reprint author), Natl Inst Mental Hlth, Mol Imaging Branch, NIH, Bldg 1,Room B3-10,1 Ctr Dr, Bethesda, MD 20892 USA. EM robert.innis@nih.gov FU NIMH NIH HHS [Z01-MH002795-04] NR 21 TC 14 Z9 15 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2007 VL 61 IS 7 BP 469 EP 477 DI 10.1002/syn.20392 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 167FG UT WOS:000246436200001 PM 17415792 ER PT J AU Moses-Kolko, EL Price, JC Thase, ME Meltzer, CC Kupfer, DJ Mathis, CA Bogers, WD Berman, SR Houck, PR Schneider, TN Drevets, WC AF Moses-Kolko, Eydie L. Price, Julie C. Thase, Michael E. Meltzer, Carolyn Cidis Kupfer, David J. Mathis, Chester A. Bogers, Wendy D. Berman, Susan R. Houck, Patricia R. Schneider, Trisha N. Drevets, Wayne C. TI Measurement of 5-HT(1A) receptor binding in depressed adults before and after antidepressant drug treatment using positron emission tomography and [(11)C]WAY-100635 SO SYNAPSE LA English DT Article DE raphe nucleus; hippocampus; major depression; selective serotonin reuptake inhibitor ID SEROTONIN 1A RECEPTOR; CENTRAL-NERVOUS-SYSTEM; MAJOR DEPRESSION; SUICIDE VICTIMS; CEREBRAL-CORTEX; RAT-BRAIN; NEUROTRANSMISSION; TRANSPORTER; PET; DESIPRAMINE AB Objective: To assess effects of chronic antidepressant drug treatment on serotonin type-1A receptor (5-HT(1A)R) binding potential. (BP) in major depressive disorder. Methods: Depressed subjects (n = 27) were imaged using PET and [(11)C]WAY-100635 at baseline and following a median of 9.4 weeks of treatment with selective serotonin reuptake inhibitor or dual reuptake inhibitor antidepressant agents. Fifteen subjects had complete pre- and post-treatment scan data. The 5-HT(1A)R BP was derived from the tissue time-radioactivity concentrations from regions-of-interest defined a priori, using a simplified reference tissue model (SRTM), and in a subset of subjects, compartmental modeling (CMOD). Results: Chronic treatment had no effect on pre- or post-synaptic 5-HT(1A)R BP, as confirmed by both the SRTM and CMOD analyses. These results were unaffected by treatment response status and were consistent across brain regions. Among the 22 subjects for whom the clinical response-to-treatment was established, the treatment nonresponders (n = 7) had higher baseline BP values in the left (P = 0.01) and right orbital cortex (P = 0.02) than the responders (n = 15). Conclusions: Chronic antidepressant drug treatment did not significantly change cerebral 5-HT(1A)R binding, consistent with preclinical evidence that the alterations in serotonergic function associated with antidepressant drag administration are not accompanied by changes in 5-HT(1A)R density. Higher baseline 5-HT(1A)R binding was associated with poorer response to treatment. C1 Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA USA. NIMH, Sect Neuroimaging Mood & Anxiety Disorders, NIH, Bethesda, MD USA. RP Moses-Kolko, EL (reprint author), 410 Oxford Bldg,3811 O Hara St, Pittsburgh, PA 15213 USA. EM MosesEL@upmc.edu RI Mathis, Chester/A-8607-2009 FU NIMH NIH HHS [K23 MH064561, MH59769, MH64561, R01 MH059769] NR 44 TC 41 Z9 41 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2007 VL 61 IS 7 BP 523 EP 530 DI 10.1002/syn.20398 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 167FG UT WOS:000246436200006 PM 17447260 ER PT J AU Seeman, P Hall, FS Uhl, G AF Seeman, Philip Hall, Frank Scott Uhl, George TI Increased dopamine D2(High) receptors in knockouts of the dopamine transporter and the vesicular monoamine transporter may contribute to spontaneous hyperactivity and dopamine lsupersensitivity SO SYNAPSE LA English DT Article ID PERTUSSIS TOXIN; PLACE PREFERENCE; COCAINE REWARD; RAT STRIATUM; MICE LACKING; AMPHETAMINE; SEROTONIN; SUPERSENSITIVITY; PSYCHOSTIMULANTS; PSYCHOSIS C1 Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. RP Seeman, P (reprint author), Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. EM philip.seeman@utoronto.ca RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 FU Intramural NIH HHS NR 21 TC 14 Z9 14 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2007 VL 61 IS 7 BP 573 EP 576 DI 10.1002/syn.20402 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 167FG UT WOS:000246436200012 PM 17447256 ER PT J AU Caggiari, L Rehermann, B Folgori, A De Re, V AF Caggiari, L. Rehermann, B. Folgori, A. De Re, V. TI Identification of four novel MHC-C alleles in chimpanzees SO TISSUE ANTIGENS LA English DT Editorial Material DE pan troglodytes; Patr-C; polymerase chain; reaction-sequence-based typing ID CLASS-I; POLYMORPHISM C1 Ctr Riferimento Oncol, Dipartimento Oncol Mol & Ric Traslaz, I-33081 Aviano, PN, Italy. NIDDKD, Immunol Sect, Liver Dis Branch, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Pomezia, Ist Ric Biol Mol, Rome, Italy. RP De Re, V (reprint author), Ctr Riferimento Oncol, Dipartimento Oncol Mol & Ric Traslaz, Via F Gallini 2, I-33081 Aviano, PN, Italy. EM vdere@cro.it FU Intramural NIH HHS NR 6 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD JUL PY 2007 VL 70 IS 1 BP 78 EP 79 DI 10.1111/j.1399-0039.2007.00846.x PG 2 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 177SR UT WOS:000247173300017 PM 17559591 ER PT J AU Lumelsky, NL AF Lumelsky, Nadya L. TI Commentary: Engineering of tissue healing and regeneration SO TISSUE ENGINEERING LA English DT Editorial Material ID LIVER-REGENERATION; INFLAMMATORY CELLS; IN-VITRO; GROWTH; RESOLUTION; REPAIR; SELF; DIFFERENTIATION; BIOMATERIALS; MACROPHAGES C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Lumelsky, NL (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 45 Ctr Dr,Bldg 45,Room 4An-18J, Bethesda, MD 20892 USA. EM nadyal@nidcr.nih.gov NR 55 TC 18 Z9 18 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD JUL PY 2007 VL 13 IS 7 BP 1393 EP 1398 DI 10.1089/ten.2007.0100 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 190CL UT WOS:000248035500001 PM 17550337 ER PT J AU Gopee, NV Roberts, DW Webb, P Cozart, CR Siitonen, PH Warbritton, AR Yu, WW Colvin, VL Walker, NJ Howard, PC AF Gopee, Neera V. Roberts, Dean W. Webb, Peggy Cozart, Christy R. Siitonen, Paul H. Warbritton, Alan R. Yu, William W. Colvin, Vicki L. Walker, Nigel J. Howard, Paul C. TI Migration of intradermally injected quantum dots to sentinel organs in mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE nanoparticles; nanoscale materials; quantum dots; sentinel organs; biodistribution ID TITANIUM-DIOXIDE; IN-VIVO; SEMICONDUCTOR PHOTOCATALYSIS; BACTERICIDAL ACTIVITY; NANOCRYSTALS; TIO2; SKIN; WATER; PENETRATION; PARTICLES AB Topical exposure to nanoscale materials is likely from a variety of sources including sunscreens and cosmetics. Because the in vivo disposition of nanoscale materials is not well understood, we have evaluated the distribution of quantum dots (QDs) following intradermal injection into female SKH-1 hairless mice as a model system for determining tissue localization following intradermal infiltration. The QD (CdSe core, US capped, poly[ethylene glycol] coated, 37 mn diameter, 621 nm fluorescence emission) were injected intradermally (ID) on the right dorsal flank. Within minutes following intradermal injection, the highly UV fluorescent QD could be observed moving from the injection sites apparently through the lymphatic duct system to regional lymph nodes. Residual fluorescent QD remained at the site of injection until necropsy at 24 h. Quantification of cadmium and selenium levels after 0, 4,8,12, or 24 h in multiple tissues, using inductively coupled plasma mass spectrometry (ICP-MS), showed a time-dependent loss of cadmium from the injection site, and accumulation in the liver, regional draining lymph nodes, kidney, spleen, and hepatic lymph node. Fluorescence microscopy corroborated the ICP-MS results regarding the tissue distribution of QD. The results indicated that (1) ID injected nanoscale QD remained as a deposit in skin and penetrated the surrounding viable subcutis, (2) QD were distributed to draining lymph nodes through the sc lymphatics and to the liver and other organs, and (3) sentinel organs are effective locations for monitoring transdermal penetration of nanoscale materials into animals. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Toxicol Program, Ctr Phototoxicol, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR 72079 USA. Rice Univ, Dept Chem, Houston, TX 77251 USA. Rice Univ, Ctr Biol & Environm Nanotechnol, Houston, TX 77251 USA. Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM paul.howard@fda.hhs.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [Y01 ES001027-35] NR 59 TC 102 Z9 112 U1 0 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2007 VL 98 IS 1 BP 249 EP 257 DI 10.1093/toxsci/kfm074 PG 9 WC Toxicology SC Toxicology GA 183VZ UT WOS:000247601800024 PM 17404394 ER PT J AU Xie, YX Liu, J Benbrahim-Tallaa, L Ward, JM Logsdon, D Diwan, BA Waalkes, MP AF Xie, Yaxiong Liu, Jie Benbrahim-Tallaa, Lamia Ward, Jerry M. Logsdon, Daniel Diwan, Bhalchandra A. Waalkes, Michael P. TI Aberrant DNA methylation and gene expression in livers of newborn mice transplacentally exposed to a hepatocarcinogenic dose of inorganic arsenic SO TOXICOLOGY LA English DT Article DE arsenic; transplacental exposure; newborn mouse liver; DNA methylation; gene expression ID IN-UTERO; DRINKING-WATER; POSTNATAL DIETHYLSTILBESTROL; HEPATOCELLULAR-CARCINOMA; MONOMETHYLARSONIC ACID; GESTATIONAL EXPOSURE; ADULT MICE; CARCINOGENESIS; HYPOMETHYLATION; INDUCTION AB Our prior work showed that brief exposure of pregnant C3H mice to inorganic arsenic-induced hepatocellular carcinoma (HCC) formation in adult mate offspring. The current study examined the early hepatic events associated with this oncogenic transformation. Pregnant mice were exposed to a known carcinogenic dose of arsenic (85 ppm) in the drinking water from gestation days 8 to 18. The darns were allowed to give birth and liver samples from newborn males were analyzed for arsenic content, global DNA methylation and aberrant expression of genes relevant to the carcinogenic process. Arsenic content in newborn liver reached 57 ng/g wet weight, indicating arsenic had crossed the placenta, reached the fetal liver and that significant amounts remained after birth. Global methylation status of hepatic DNA was not altered by arsenic in the newborn. However, a significant reduction in methylation occurred globally in GC-rich regions. Microarray and real-time RT-PCR analysis showed that arsenic exposure enhanced expression of genes encoding for glutathione production and caused aberrant expression of genes related to insulin growth factor signaling pathways and cytochrome P450 enzymes. Other expression alterations observed in the arsenic-treated male mouse newborn liver included the overexpression of cdk-inhibitors and stress response genes including increased expression of metallothionein-1 and decreased expression of betaine-homocysteine methyltransferase and thioether S-inethyltransferase. Thus, transplacental exposure to arsenic at a hepatocarcinogenic dose induces alterations in DNA methylation and a complex set of aberrant gene expressions in the newborn liver, a target of arsenic carcinogenesis. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. NIAID, NIH, Bethesda, MD 20892 USA. NCI, Off Lab Anim Sci, Frederick, MD 21701 USA. SAIC, Basic Res Lab, Frederick, MD USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. EM Waalkes@niehs.nih.gov FU Intramural NIH HHS [, NIH0011069698]; NCI NIH HHS [N01CO12400]; PHS HHS [NIH0011069698] NR 39 TC 90 Z9 95 U1 0 U2 15 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 1 PY 2007 VL 236 IS 1-2 BP 7 EP 15 DI 10.1016/j.tox.2007.03.021 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 180IB UT WOS:000247355200002 PM 17451858 ER PT J AU Sloand, EM Read, EJ Scheinberg, P Tang, Y More, K Leitman, SF Maciejewski, J Young, NS AF Sloand, Elaine M. Read, Elizabeth J. Scheinberg, Phillip Tang, Yong More, Kenneth Leitman, Susan F. Maciejewski, Jaroslaw Young, Neal S. TI Mobilization, collection, and immunomagnetic selection of peripheral blood CD34 cells in recovered aplastic anemia patients SO TRANSFUSION LA English DT Article ID COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELLS; PROGENITOR CELLS; HEALTHY DONORS; CYTOGENETIC ABNORMALITIES; ANTITHYMOCYTE GLOBULIN; CXCR4 ANTAGONIST; STEM; THROMBOPOIETIN; CYCLOSPORINE AB BACKGROUND: Most patients with severe aplastic anemia (sAA) respond to immunosuppression, but a significant number relapse or develop clonal abnormalities such as paroxysmal nocturnal hemoglobinuria, myelodysplasia, or leukemia. In principle, patients without matched sibling donors and older patients might benefit from transplantation of autologous hematopoietic peripheral blood progenitor cells (PBPCs) obtained during remission. Even patients who have clinically recovered from aplastic anemia have diminished hematopoietic progenitor cells, so the practicability of PBPC mobilization in these individuals is unknown. STUDY DESIGN AND METHODS: The feasibility of PBPC mobilization in nine patients with a history of sAA was evaluated. Granulocyte-colony-stimulating factor (10 mu g/kg) was administered subcutaneously for 5 days and followed by a 12-L leukapheresis procedure. RESULTS: Only two of the nine patients had sufficient mobilization of CD34 cells to merit collection; in these cases sufficient CD34 cells were obtained for autologous transplantation should the need arise. CONCLUSION: PBPC collection is feasible only in a fraction of recovered AA patients. C1 NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, NIH, Mark O Hartfield Clin Res Ctr, Hematol Branch, Bethesda, MD USA. RP Sloand, EM (reprint author), NHLBI, NIH, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA. EM sloande@nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 NR 19 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2007 VL 47 IS 7 BP 1250 EP 1253 DI 10.1111/j.1537-2995.2007.01258.x PG 4 WC Hematology SC Hematology GA 184YG UT WOS:000247677900020 PM 17581160 ER PT J AU Manoli, I Alesci, S Blackman, MR Su, YA Rennert, OM Chrousos, GP AF Manoli, Irini Alesci, Salvatore Blackman, Marc R. Su, Yan A. Rennert, Owen M. Chrousos, George P. TI Mitochondria as key components of the stress response SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID NF-KAPPA-B; SKELETAL-MUSCLE CELLS; TRANSCRIPTIONAL COACTIVATOR; OXIDATIVE STRESS; GENE-EXPRESSION; GLUCOCORTICOID-RECEPTOR; CALORIE RESTRICTION; INSULIN-RESISTANCE; INDUCED APOPTOSIS; CRITICALLY-ILL AB The exquisitely orchestrated adaptive response to stressors that challenge the homeostasis of the cell and organism involves important changes in mitochondrial function. A complex signaling networkenables mitochondria to sense internal milieu or environmental changes and to adjust their bioenergetic, thermogenic, oxidative and/or apoptotic responses accordingly, aiming at reestablishment of homeostasis. Mitochondrial dysfunction is increasingly recognized as a key component in both acute and chronic allostatic states, although the extent of its role in the pathogenesis of such conditions remains controversial. Genetic and environmental factors that determine mitochondrial function might contribute to the significant variation of the stress response. Understanding the often reciprocal interplay between stress mediators and mitochondrial function is likely to help identify potential therapeutic targets for many stress and mitochondria-related pathologies. C1 NHGRI, Human Biochem Genet Sect, MGB, NIH, Bethesda, MD 20892 USA. UOA, Dept Pediat 1, GR-11527 Athens, Greece. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NCCAM, Endocrine Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. George Washington Univ, Sch Med & Hlth Sci, Catherine Birch McCormick Genom Ctr, Washington, DC 20037 USA. NICHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. NICHD, Pediat Endocrinol Sect, RBMB, Bethesda, MD 20892 USA. RP Manoli, I (reprint author), NHGRI, Human Biochem Genet Sect, MGB, NIH, Bethesda, MD 20892 USA. EM manolii@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 FU Intramural NIH HHS; NIDDK NIH HHS [DK-06-925] NR 90 TC 106 Z9 109 U1 4 U2 16 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL PY 2007 VL 18 IS 5 BP 190 EP 198 DI 10.1016/j.tem.2007.04.004 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 190BX UT WOS:000248034000003 PM 17500006 ER PT J AU Barillas-Mury, C AF Barillas-Mury, Carolina TI CLIP proteases and Plasmodium melanization in Anopheles gambiae SO TRENDS IN PARASITOLOGY LA English DT Article ID SERINE PROTEINASE HOMOLOGS; MANDUCA-SEXTA; ACTIVATING PROTEINASE; REFRACTORY STRAIN; CYNOMOLGI B; ENCAPSULATION; HEMOLYMPH; IMMUNITY; MIDGUT; GENES AB Melanization is a potent immune response mediated by phenoloxidase (PO). Multiple Clip-domain serine proteases (CLIP) regulate PO activation as part of a complex cascade of proteases that are cleaved sequentially. The role of several CLIP as key activators or suppressors of the melanization responses of Anopheles gambiae to Plasmodium berghei (murine malaria) has been established recently using a genome-wide reverse genetics approach. Important differences in regulation of PO activation between An. gambiae strains were also identified. This review summarizes these findings and discusses our current understanding of the An. gambiae melanization responses to Plasmodium. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov FU Intramural NIH HHS NR 22 TC 32 Z9 33 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD JUL PY 2007 VL 23 IS 7 BP 297 EP 299 DI 10.1016/j.pt.2007.05.001 PG 3 WC Parasitology SC Parasitology GA 189BI UT WOS:000247963000002 PM 17512801 ER PT J AU Cheng, JY Riesz, P AF Cheng, Jason Y. Riesz, Peter TI Mechanism of the protective effects of long chain n-alkyl glucopyrano sides against ultrasound-induced cytolysis of HL-60 cells SO ULTRASONICS SONOCHEMISTRY LA English DT Article DE n-alkyl glucopyranosides; protection mechanism; ultrasound-induced cell killing; HL-60 cells ID SURFACTANT SOLUTIONS; CAVITATION BUBBLES; AQUEOUS-SOLUTION; SONOLUMINESCENCE; SONOCHEMISTRY; FREQUENCY AB Recently it has been shown that long chain (C5-C8) n-alkyl glucopyranosides completely inhibit ultra sound-induced cytolysis [J.Z. Sostaric, N. Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539]. This protective effect has possible applications in HIFU (high intensity focused ultrasound) for tumor treatment, and in ultrasound assisted drug delivery and gene therapy. n-Alkyl glueopyranosides with hexyl (5 mM), heptyl (3 mM), octyl (2 mM) n-alkyl chains protected 100% of HL-60 cells in vitro from 1.057 MHz ultrasound-induced cytolysis under a range of conditions that resulted in 35-100% cytolysis in the absence of glucopyranosides. However the hydrophilic methyl-beta-D-glucopyranoside did not protect cells. The surface active n-alkyl glucopyranosides accumulate at the gas-liquid interface of cavitation bubbles. The OH radicals and H atoms formed in collapsing cavitation bubbles react by H-atom abstraction from either the n-alkyl chain or the glucose moiety of the n-alkyl glucopyranosides. Owing to the high concentration of the long chain surfactants at the gas-liquid interface of cavitation bubbles, the initially formed carbon radicals on the alkyl chains are transferred to the glucose moieties to yield radicals which react with oxygen leading to the formation of hydrogen peroxide. In this work, we find that the sonochemically produced hydrogen peroxide yields from oxygen-saturated solutions of long chain (hexyl, octyl) n-alkyl glucopyranosides at 614 kHz and 1.057 MHz ultrasound increase with increasing n-alkyl glucopyranoside concentration but are independent of concentration for methyl-beta-D-glucopyrano side. These results are consistent with the previously proposed mechanism of sonoprotection [J.Z. Sostaric, N. Miyoshi, P. Riesz, W.G. DeGraff, and J.B. Mitchell, Free Radical Biol. Med., 39 (2005) 1539]. This sequence of events prevents sonodynamic cell killing by initiation of lipid peroxidation chain reactions in cellular membranes by peroxyl and/or alkoxyl radicals [V. Misik, P. Riesz, Ann. N.Y. Acad. Sci., 899 (2000) 335]. Published by Elsevier B.V. C1 NCI, NIH, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Riesz, P (reprint author), NCI, NIH, Ctr Canc Res, Radiat Biol Branch, Bethesda, MD 20892 USA. EM rieszp@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999, Z01 SC006358-23] NR 16 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1350-4177 J9 ULTRASON SONOCHEM JI Ultrason. Sonochem. PD JUL PY 2007 VL 14 IS 5 BP 667 EP 671 DI 10.1016/j.ultsonch.2006.10.011 PG 5 WC Acoustics; Chemistry, Multidisciplinary SC Acoustics; Chemistry GA 171RP UT WOS:000246753400028 PM 17224298 ER PT J AU Rapkiewicz, AV Patel, SY Holland, SM Kleiner, DE AF Rapkiewicz, Amy V. Patel, Smita Y. Holland, Steven M. Kleiner, David E. TI Hepatoportal venopathy due to disseminated Mycobacterium avium complex infection in a child with IFN-gamma receptor 2 deficiency SO VIRCHOWS ARCHIV LA English DT Article DE obliterative venopathy; interferon; mycobacteria ID INTERFERON-GAMMA RECEPTOR; PORTAL-HYPERTENSION; LIVER; SUSCEPTIBILITY; INTERLEUKIN-12; MUTATION; FIBROSIS; DEFECTS AB The control of intracellular microorganisms such as mycobacteria is largely dependent on the adaptive immune response, specifically the interaction of T helper cells and antigen presenting cells such as macrophages. The interferon gamma (IFN-gamma) pathway activation is crucial for containment and killing of mycobacteria, as evidenced by the fact that defects in this pathway often result in profound infections with both tuberculous and non-tuberculous mycobacteria. We herein report a case of a child with autosomal recessive IFN-gamma receptor 2 (IFN-gamma R2) deficiency who developed hepatic venopathy secondary to disseminated Mycobacterium avium complex (MAC) infection. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Rapkiewicz, AV (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM Rapkia01@med.nyu.edu NR 19 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD JUL PY 2007 VL 451 IS 1 BP 95 EP 100 DI 10.1007/s00428-007-0427-2 PG 6 WC Pathology SC Pathology GA 195LG UT WOS:000248413100012 PM 17554558 ER PT J AU Camalier, CR Gotler, A Murthy, A Thompson, KG Logan, GD Palmeri, TJ Schall, JD AF Camalier, C. R. Gotler, A. Murthy, A. Thompson, K. G. Logan, G. D. Palmeri, T. J. Schall, J. D. TI Dynamics of saccade target selection: Race model analysis of double step and search step saccade production in human and macaque SO VISION RESEARCH LA English DT Article DE saccade; race model; latency double step; search step; decision making ID FRONTAL EYE FIELD; CHOICE REACTION-TIME; SUPERIOR COLLICULUS; COUNTERMANDING SACCADES; VISUAL SELECTION; DIFFUSION-MODEL; CURVED SACCADES; PARIETAL CORTEX; STOP SIGNALS; NO-RETURN AB We investigated how saccade target selection by humans and macaque monkeys reacts to unexpected changes of the image. This was explored using double step and search step tasks in which a target, presented alone or as a singleton in a visual search array, steps to a different location on infrequent, random trials. We report that human and macaque monkey performance are qualitatively indistinguishable. Performance is stochastic with the probability of producing a compensated saccade to the final target location decreasing with the delay of the step. Compensated saccades to the final target location are produced with latencies relative to the step that are comparable to or less than the average latency of saccades on trials with no target step. Noncompensated errors to the initial target location are produced with latencies less than the average latency of saccades on trials with no target step. Noncompensated saccades to the initial target location are followed by corrective saccades to the final target location following an intersaccade interval that decreases with the interval between the target step and the initiation of the noncompensated saccade. We show that this pattern of results cannot be accounted for by a race between two stochastically independent processes producing the saccade to the initial target location and another process producing the saccade to the final target location. However, performance can be accounted for by a race between three stochastically independent processes-a GO process producing the saccade to the initial target location, a STOP process interrupting that GO process, and another GO process producing the saccade to the final target location. Furthermore, if the STOP process and second GO process start at the same time, then the model can account for the incidence and latency of mid-flight corrections and rapid corrective saccades. This model provides a computational account of saccade production when the image changes unexpectedly. (c) 2007 Elsevier Ltd. All riehts reserved. C1 Vanderbilt Univ, Ctr Integrat & Cognit Neurosci, Vanderbilt Vis Res Ctr, Dept Psychol, Nashville, TN 37203 USA. Nat Brain Res Ctr, Haryana, India. NEI, Bethesda, MD 20892 USA. RP Schall, JD (reprint author), Vanderbilt Univ, Ctr Integrat & Cognit Neurosci, Vanderbilt Vis Res Ctr, Dept Psychol, 111 21st Ave S,Wilson Hall, Nashville, TN 37203 USA. EM jeffrey.d.schall@vanderbilt.edu OI Palmeri, Thomas/0000-0001-7617-9797 FU NEI NIH HHS [P30 EY008126, P30 EY008126-19, P30-EY08126, R01 EY008890, R01 EY008890-17, R01-EY08890]; NICHD NIH HHS [P30 HD015052, P30 HD015052-27, P30-HD015052]; NIMH NIH HHS [T32 MH064913, T32 MH064913-07, T32-MH064913] NR 55 TC 50 Z9 51 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD JUL PY 2007 VL 47 IS 16 BP 2187 EP 2211 DI 10.1016/j.visres.2007.04.021 PG 25 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 202MO UT WOS:000248906000010 PM 17604806 ER PT J AU Raat, NJH Ince, C AF Raat, N. J. H. Ince, C. TI Oxygenating the microcirculation: the perspective from blood transfusion and blood storage SO VOX SANGUINIS LA English DT Review DE blood storage; blood transfusion; microcirculation; oxygenation ID CRITICALLY-ILL PATIENTS; BYPASS GRAFT-SURGERY; HUMAN RED-CELLS; NITRIC-OXIDE; TISSUE OXYGENATION; HUMAN ERYTHROCYTES; STORED-BLOOD; EXCHANGE; MODEL; RAT AB Tissue oxygen delivery depends on red blood cell (RBC) content and RBC flow regulation in the microcirculation. The important role of the RBC in tissue oxygenation is clear from anaemia and the use of RBC transfusion which has saved many lives. Whether RBC transfusion actually restores tissue oxygenation is difficult to determine due to the lack of appropriate clinical monitoring techniques. Some patients with restored haemoglobin levels and stable haemodynamics still develop tissue hypoxia, emphasizing that, in addition to global parameters, local microcirculatory control mechanisms are also important in the restoration of tissue oxygenation. Both clinical and animal experimental studies have indicated that storage of RBC diminishes their ability to oxygenate the tissue. Several intrinsic RBC parameters that change during storage and might influence tissue oxygenation will be mentioned. The release of vasodilators from RBC that will alter blood flow during hypoxia, mediated by haemoglobin in the RBC that functions as an oxygen sensor, could be impaired during storage. A better understanding of hypoxia-induced vasodilator release from RBC might become a potential target for drug development and improve tissue oxygenation after transfusion. C1 Univ Amsterdam, Acad Med Ctr, Dept Physiol, NL-1105 AZ Amsterdam, Netherlands. NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. RP Ince, C (reprint author), Univ Amsterdam, Acad Med Ctr, Dept Physiol, Meibergdreef 9, NL-1105 AZ Amsterdam, Netherlands. EM c.ince@amc.nl NR 62 TC 47 Z9 49 U1 3 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD JUL PY 2007 VL 93 IS 1 BP 12 EP 18 DI 10.1111/j.1423-0410.2007.00909.x PG 7 WC Hematology SC Hematology GA 177SZ UT WOS:000247174100002 PM 17547560 ER PT J AU Porter, CM Horvath-Arcidiacono, JA Singh, AK Horvath, KA Bloom, ET Mohiuddin, MM AF Porter, Cynthia M. Horvath-Arcidiacono, Judith A. Singh, Avneesh K. Horvath, Keith A. Bloom, Eda T. Mohiuddin, Muhammad M. TI Characterization and expansion of baboon CD4(+)CD25(+) Treg cells for potential use in a non-human primate xenotransplantation model SO XENOTRANSPLANTATION LA English DT Article DE baboon; immune tolerance; regulatory T cells; transplantation tolerance; xenotransplantation ID REGULATORY T-CELLS; TRANSPLANTATION TOLERANCE; IN-VITRO; CLINICAL XENOTRANSPLANTATION; CARDIAC XENOTRANSPLANTATION; INTERLEUKIN-2 PRODUCTION; B-CELLS; RAPAMYCIN; PIGS; XENOGRAFTS AB Background: It is well established that CD4(+)CD25(+) regulatory T (Treg) cells can modulate allogeneic immune responses. Xenotransplantation, proposed as a means to address the critical shortage of human organs, may also benefit from similar approaches to avert rejection. Baboons are a preferred preclinical animal model for xenogeneic organ transplantation experiments, and the characterization of baboon Treg cells will be beneficial to future tolerance studies in this animal model. Methods: We analyzed CD4(+) CD25(+) T cells from baboon lymph nodes, spleens, and blood by flow cytometry, then purified and expanded porcine antigen-specific baboon CD4(+) CD25(high) cells in vitro to evaluate their regulatory activity in the baboon anti-pig xenogeneic responses. Results: CD4(+) CD25(high) T cells were 1.7%, 3.1 %, and 1.9% of baboon splenic, lymph node, and blood T cells, respectively. The CD4(+) CD25(high) T cells expressed the Treg cell-associated transcription factor, FoxP3. Proliferation/suppression assays using irradiated pig peripheral blood mononuclear cells as stimulators showed that Treg cells suppressed the vigorous baboon CD4(+) CD25(-) T-cell anti-pig proliferation response and cytokine secretion. Expanded baboon Treg cells suppressed baboon anti-pig CD4(+) CD25(-) T-cell proliferation similar to 4- to 10-fold more than freshly isolated Treg cells. Expanded Treg cells suppressed proliferation to primary cells from the same pig used for expansion more effectively than proliferation to stimulators from a different strain of pig, suggesting a level of antigen specificity. Conclusion: We demonstrate that baboon Treg cells suppress immune responses to xenogeneic stimulation. These Studies suggest that adoptive transfer of expanded Treg cells into transplant recipients may provide an approach to prevent cell-mediated rejection of grafts and potentially induce tolerance in the pig to baboon xenotransplantation preclinical model. C1 US FDA, CBER, Div Cellular & Gene Therapy, Bethesda, MD 20892 USA. NIH, NHLBI, Cardiothorac Surg Res Program, Bethesda, MD 20892 USA. RP Porter, CM (reprint author), US FDA, CBER, Div Cellular & Gene Therapy, HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 49 TC 25 Z9 26 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2007 VL 14 IS 4 BP 298 EP 308 DI 10.1111/j.1399-3089.2007.00416.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 201QI UT WOS:000248847300003 PM 17669171 ER PT J AU Shin, A Kang, D Choi, JY Lee, KM Park, SK Noh, DY Ahn, SH Yoo, KY AF Shin, Aesun Kang, Daehee Choi, Ji-Yeob Lee, Kyoung-Mu Park, Sue Kyung Noh, Dong-Young Ahn, Sei-Hyun Yoo, Keun-Young TI Cytochrome P450 1A1 (CYP1A1) polymorphisms and breast cancer risk in Korean women SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE Asian continental ancestry group; breast; neoplasms; cytochrome P450CYP1A1; Korea; polymorphism; genetic ID GSTT1 POLYMORPHISMS; GENE POLYMORPHISMS; CIGARETTE-SMOKING; AFRICAN-AMERICAN; CARCINOMA RISK; CHINESE WOMEN; NURSES HEALTH; LUNG-CANCER; ESTROGEN; P4501A1 AB Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma. We evaluated the associations between two CYP1A1 polymorphisms [MspI (rs4646903); Ile462Val (rs1048943)] and breast cancer in a multicenter case-control study of 513 breast cancer cases and 447 controls in Korea. Women carrying the T allele of the CYP1A1 MspI polymorphism were found to have a 1.72-fold (95% Cl 1.11-2.68) greater risk of developing breast cancer. No association was found between any CYP1A1 Ile462Val polymorphism and breast cancer. Haplotype analysis of the two loci showed that the CA haplotype was associated with the lowest risk of breast cancer, and CA/CA diplotypes were associated with a lower risk of breast cancer [OR = 0.28 (0.13-0.61)] than others/others diplotypes. Moreover, this reduced risk was more pronounced among women with a lower body mass index (BMI) [OR = 0.18 (0.06-0.58)] or with a shorter lifetime exposure to estrogen [OR = 0.23 (0.07-0.81)]. The results obtained suggest that the CYP1A1 MspI polymorphisms could affect susceptibility to breast cancer. C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. Natl Canc Ctr, Res Inst Natl Canc Control & Evaluat, Goyang 410769, South Korea. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. NCI, Div Canc Epidemiol & Genet, US Dept HHS, NIH, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea. Univ Ulsan, Coll Med, Dept Surg, Seoul 138736, South Korea. Natl Canc Ctr, Goyang 410769, South Korea. RP Yoo, KY (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. EM kyyoo@plaza.snu.ac.kr RI Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Choi, Ji-Yeob/J-2796-2012; Yoo, Keun-Young/J-5548-2012; Park, Sue Kyung/J-2757-2012; Shin, Aesun/E-9145-2014 OI Shin, Aesun/0000-0002-6426-1969 NR 24 TC 26 Z9 29 U1 0 U2 0 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD JUN 30 PY 2007 VL 39 IS 3 BP 361 EP 366 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 186SP UT WOS:000247798800013 PM 17603290 ER PT J AU Aebig, JA Mullen, GED Dobrescu, G Rausch, K Lambert, L Ajose-Popoola, O Long, CA Saul, A Miles, AP AF Aebig, Joan A. Mullen, Gregory E. D. Dobrescu, Gelu Rausch, Kelly Lambert, Lynn Ajose-Popoola, Olubunmi Long, Carole A. Saul, Allan Miles, Aaron P. TI Formulation of vaccines containing CpG oligonucleotides and alum SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE vaccine; formulation; CPG 7909; IP-10 ID PLASMODIUM-FALCIPARUM MALARIA; APICAL MEMBRANE ANTIGEN-1; IN-VITRO; OLIGODEOXYNUCLEOTIDE; INDUCTION; ADJUVANTS; RESPONSES; PROTEINS; IMMUNITY; PVS25H AB CpG oligodeoxynucleotides are potent immunostimulants. For parenterally delivered alum-based vaccines, the immunostimulatory effect of CpG depends on the association of the CpG and antigen to the alum. We describe effects of buffer components on the binding of CPG 7909 to aluminum hydroxide (Alhydrogel), assays for measuring binding of CPG 7909 to alum and CPG 7909 induced dissociation of antigen from the alum. Free CPG 7909 is a potent inducer of IP-10 in mice. However the lack of IP-10 production from formulations containing bound CPG 7909 suggested that CPG 7909 does not rapidly dissociate from the alum after injection. It also suggests that IP-10 assays are not a good basis for potency assays for alum-based vaccines containing CPG 7909. (C) 2007 Elsevier B.V. All rights reserved. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Aebig, JA (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Line, Rockville, MD 20852 USA. EM jaebig@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 FU Intramural NIH HHS [Z99 AI999999] NR 17 TC 26 Z9 29 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD JUN 30 PY 2007 VL 323 IS 2 BP 139 EP 146 DI 10.1016/j.jim.2007.03.003 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 191ZC UT WOS:000248169500006 PM 17512533 ER PT J AU Sharma, A Raviv, Y Puri, A Viard, M Blumenthal, R Maheshwari, RK AF Sharma, Anuj Raviv, Yossef Puri, Anu Viard, Mathias Blumenthal, Robert Maheshwari, Radha K. TI Complete inactivation of Venezuelan equine encephalitis virus by 1,5-iodonaphthylazide SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE 1,5-iodonaphthyl-azide; Venezuelan equine encephalitis virus; photoactive; inactivation ID ENCEPHALOMYELITIS VIRUS; AIRBORNE CHALLENGE; EXPERIMENTAL INFECTION; BIOLOGICAL-MEMBRANES; ATTENUATED VACCINES; AEROSOL CHALLENGE; LIPID BILAYER; LIVE; PROTECTION; PROTEINS AB Hydrophobic alkylating compounds like 1,5-iodonaphthylazide (INA) partitions into biological membranes and accumulates selectively into the hydrophobic domain of the lipid bilayer. Upon irradiation with far UV light, INA binds selectively to transmembrane proteins in the viral envelope and renders them inactive. Such inactivation does not alter the ectodomains of the membrane proteins thus preserving the structural and conformational integrity of immunogens on the surface of the virus. In this study, we have used INA to inactivate Venezuelan equine encephalitis virus (VEEV). Treatment of VEEV with INA followed by irradiation with UV light resulted in complete inactivation of the virus. Immuno-fluorescence for VEEV and virus titration showed no virus replication in-vitro. Complete loss of infectivity was also achieved in mice infected with INA treated plus irradiated preparations of VEEV. No change in the structural integrity of VEEV particles were observed after treatment with INA plus irradiation as assessed by electron microscopy. This data suggest that such inactivation strategies can be used for developing vaccine candidates for VEEV and other enveloped viruses. Published by Elsevier Inc. C1 Uniformed Serv Univ Hlth Sci, Ctr Combat Casualty & Life Sustainment Res, Dept Pathol, Bethesda, MD 20814 USA. Birla Inst Technol & Sci, Pilani, Rajasthan, India. NCI, CCR Nanobiol Program, Ctr Canc Res, Frederick, MD 21701 USA. Basic Res Program SAIC, Frederick, MD USA. RP Maheshwari, RK (reprint author), Uniformed Serv Univ Hlth Sci, Ctr Combat Casualty & Life Sustainment Res, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM rmaheshwari@usuhs.mil FU NCI NIH HHS [N01-CO-12400] NR 39 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 29 PY 2007 VL 358 IS 2 BP 392 EP 398 DI 10.1016/j.bbrc.2007.04.115 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 174FM UT WOS:000246927300003 PM 17493582 ER PT J AU Thomas, R Paredes, CJ Mehrotra, S Hatzimanikatis, V Papoutsakis, ET AF Thomas, Reuben Paredes, Carlos J. Mehrotra, Sanjay Hatzimanikatis, Vassily Papoutsakis, Eleftherios T. TI A model-based optimization framework for the inference of regulatory interactions using time-course DNA microarray expression data SO BMC BIOINFORMATICS LA English DT Article ID BIOCHEMICAL SYSTEMS ANALYSIS; GENETIC NETWORKS; COMPOUND-MODE; IDENTIFICATION; PROTEOMICS; ALGORITHM; PROFILES; PATHWAYS; LAW AB Background: Proteins are the primary regulatory agents of transcription even though mRNA expression data alone, from systems like DNA microarrays, are widely used. In addition, the regulation process in genetic systems is inherently non- linear in nature, and most studies employ a time- course analysis of mRNA expression. These considerations should be taken into account in the development of methods for the inference of regulatory interactions in genetic networks. Results: We use an S- system based model for the transcription and translation process. We propose an optimization-based regulatory network inference approach that uses time- varying data from DNA microarray analysis. Currently, this seems to be the only model- based method that can be used for the analysis of time- course " relative" expressions (expression ratios). We perform an analysis of the dynamic behavior of the system when the number of experimental samples available is varied, when there are different levels of noise in the data and when there are genes that are not considered by the experimenter. Our studies show that the principal factor affecting the ability of a method to infer interactions correctly is the similarity in the time profiles of some or all the genes. The less similar the profiles are to each other the easier it is to infer the interactions. We propose a heuristic method for resolving networks and show that it displays reasonable performance on a synthetic network. Finally, we validate our approach using real experimental data for a chosen subset of genes involved in the sporulation cascade of Bacillus anthracis. We show that the method captures most of the important known interactions between the chosen genes. Conclusion: The performance of any inference method for regulatory interactions between genes depends on the noise in the data, the existence of unknown genes affecting the network genes, and the similarity in the time profiles of some or all genes. Though subject to these issues, the inference method proposed in this paper would be useful because of its ability to infer important interactions, the fact that it can be used with time- course DNA microarray data and because it is based on a non- linear model of the process that explicitly accounts for the regulatory role of proteins. C1 Ecole Polytech Fed Lausanne, Lab Computat Syst Biotechnol, CH-1015 Lausanne, Switzerland. NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. Northwestern Univ, Dept Ind Engn & Management Sci, Evanston, IL 60208 USA. Northwestern Univ, Dept Biol & Chem Engn, Evanston, IL 60208 USA. Gevo Inc, Pasadena, CA 91107 USA. Univ Delaware, Dept Chem Engn, Newark, DE 19711 USA. Univ Delaware, Delaware Biotechnol Inst, Newark, DE 19711 USA. RP Papoutsakis, ET (reprint author), Ecole Polytech Fed Lausanne, Lab Computat Syst Biotechnol, CH-1015 Lausanne, Switzerland. EM ThomasR3@niehs.nih.gov; cjparedes@gmail.com; mehrotra@iems.northwestern.edu; vassily.hatzimanikatis@epfl.ch; epaps@northwestern.edu RI Mehrotra, Sanjay/B-7477-2009; Hatzimanikatis, Vassily/B-7646-2009; Papoutsakis, Eleftherios/B-7612-2009; Papoutsakis, Eleftherios/A-5254-2010; Hatzimanikatis, Vassily/G-6505-2010 OI Hatzimanikatis, Vassily/0000-0001-6432-4694 FU NIGMS NIH HHS [R01 GM065476, R01-GM065476] NR 44 TC 18 Z9 18 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUN 29 PY 2007 VL 8 AR 228 DI 10.1186/1471-2105-8-228 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 197OH UT WOS:000248564700001 PM 17603872 ER PT J AU Landgraf, P Rusu, M Sheridan, R Sewer, A Iovino, N Aravin, A Pfeffer, S Rice, A Kamphorst, AO Landthaler, M Lin, C Socci, ND Hermida, L Fulci, V Chiaretti, S Foa, R Schliwka, J Fuchs, U Novosel, A Muller, RU Schermer, B Bissels, U Inman, J Phan, Q Chien, MC Weir, DB Choksi, R De Vita, G Frezzetti, D Trompeter, HI Hornung, V Teng, G Hartmann, G Palkovits, M Di Lauro, R Wernet, P Macino, G Rogler, CE Nagle, JW Ju, JY Papavasiliou, FN Benzing, T Lichter, P Tam, W Brownstein, MJ Bosio, A Borkhardt, A Russo, JJ Sander, C Zavolan, M Tuschl, T AF Landgraf, Pablo Rusu, Mirabela Sheridan, Robert Sewer, Alain Iovino, Nicola Aravin, Alexei Pfeffer, Sebastien Rice, Amanda Kamphorst, Alice O. Landthaler, Markus Lin, Carolina Socci, Nicholas D. Hermida, Leandro Fulci, Valerio Chiaretti, Sabina Foa, Robin Schliwka, Julia Fuchs, Uta Novosel, Astrid Mueller, Roman-Ulrich Schermer, Bernhard Bissels, Ute Inman, Jason Phan, Quang Chien, Minchen Weir, David B. Choksi, Ruchi De Vita, Gabriella Frezzetti, Daniela Trompeter, Hans-Ingo Hornung, Veit Teng, Grace Hartmann, Gunther Palkovits, Miklos Di Lauro, Robert Wernet, Peter Macino, Giuseppe Rogler, Charles E. Nagle, James W. Ju, Jingyue Papavasiliou, F. Nina Benzing, Thomas Lichter, Peter Tam, Wayne Brownstein, Michael J. Bosio, Andreas Borkhardt, Arndt Russo, James J. Sander, Chris Zavolan, Mihaela Tuschl, Thomas TI A mammalian microRNA expression atlas based on small RNA library sequencing SO CELL LA English DT Article ID MENTAL-RETARDATION PROTEIN; POSTTRANSCRIPTIONAL REGULATION; C-ELEGANS; CAENORHABDITIS-ELEGANS/; ANIMAL DEVELOPMENT; GENE-EXPRESSION; IDENTIFICATION; TARGETS; MIRNAS; ZEBRAFISH AB MicroRNAs (miRNAs) are small noncoding regulatory RNAs that reduce stability and/or translation of fully or partially sequence-complementary target mRNAs. In order to identify miRNAs and to assess their expression patterns, we sequenced over 250 small RNA libraries from 26 different organ systems and cell types of human and rodents that were enriched in neuronal as well as normal and malignant hematopoietic cells and tissues. We present expression profiles derived from clone count data and provide computational tools for their analysis. Unexpectedly, a relatively small set of miRNAs, many of which are ubiquitously expressed, account for most of the differences in miRNA profiles between cell lineages and tissues. This broad survey also provides detailed and accurate information about mature sequences, precursors, genome locations, maturation processes, inferred transcriptional units, and conservation patterns. We also propose a subclassification scheme for miRNAs for assisting future experimental and computational functional analyses. C1 Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA. Univ Roma La Sapienza, Dipartimento Biotecnol Cellulari & Ematol, New York, NY 10021 USA. Deutsch Krebsforschungszentrum, Div Mol Genet, D-69120 Heidelberg, Germany. Univ Munich, Dr Von Haunerschen Kinderspital, Dept Hematol & Oncol, D-80337 Munich, Germany. Univ Hosp Freiburg, Div Renal, D-79106 Freiburg, Germany. Miltenyi Biotec GmbH, D-50829 Cologne, Germany. Inst Genom Res, Rockville, MD 20850 USA. J Craig Venter Inst, Funct Genom, Rockville, MD 20850 USA. Columbia Genome Ctr, Russ Berrie Pavilion, New York, NY 10032 USA. Univ Dusseldorf, Med Ctr, Inst Transplantat Diagnost & Cell Therapeut, D-40225 Dusseldorf, Germany. Rockefeller Univ, Lab Lymphocyte Biol, New York, NY 10021 USA. Hungarian Acad Sci Semmelweis Univ, Lab Neuromorphol, Budapest, Hungary. Albert Einstein Coll Med, Bronx, NY 10461 USA. Cornell Univ, Joan & Sanford I Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. Univ Bonn, Univ Hosp, Div Clin Pharmacol, D-53105 Bonn, Germany. Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland. IRGS, Biogem Scarl, I-83031 Ariano Irpino, Italy. Columbia Univ, Dept Chem Engn, New York, NY 10027 USA. NIH, NINDS, DNA Sequencing Facil, Bethesda, MD 20892 USA. Univ Munich, Dept Internal Med, Div Clin Pharmacol, D-80366 Munich, Germany. Univ Massachusetts, Sch Med, Div Infect Dis & Immunol, Worcester, MA 01605 USA. IBM Corp, CNRS, F-678084 Strasbourg, France. Cold Spring Harbor Lab, Howard Hughes Med Inst, Sch Biol Sci, Cold Spring Harbor, NY 11724 USA. Rockefeller Univ, Lab Dev Neurogenet, New York, NY 10021 USA. Univ Dusseldorf, Med Ctr, Dept Pediat Oncol Hematol & Immunol, D-40225 Dusseldorf, Germany. Univ Lausanne, Dept Med Genet, Computat Biol Grp, CH-1005 Lausanne, Switzerland. RP Zavolan, M (reprint author), Univ Basel, Biozentrum, CH-4056 Basel, Switzerland. EM mihaela.zavolan@unibas.ch; ttuschl@rockefeller.edu RI Landthaler, Markus/A-1427-2010; Pfeffer, Sebastien/A-6512-2010; sander, chris/H-1452-2011; Di Lauro, Roberto/A-2746-2012; De Vita, Gabriella/H-4422-2011; Palkovits, Miklos/F-2707-2013; Schermer, Bernhard/E-9972-2014; fulci, valerio/J-1963-2015; Hornung, Veit/C-3565-2012 OI Palkovits, Miklos/0000-0003-0578-0387; Zavolan, Mihaela/0000-0002-8832-2041; Landthaler, Markus/0000-0002-1075-8734; Pfeffer, Sebastien/0000-0002-8458-348X; Di Lauro, Roberto/0000-0001-9493-3036; Schermer, Bernhard/0000-0002-5194-9000; fulci, valerio/0000-0002-1173-585X; Hornung, Veit/0000-0002-4150-194X FU NIGMS NIH HHS [P01 GM073047, P01 GM073047-01, P01 GM073047-03] NR 69 TC 2000 Z9 3161 U1 29 U2 222 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 29 PY 2007 VL 129 IS 7 BP 1401 EP 1414 DI 10.1016/j.cell.2007.04.040 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 188HQ UT WOS:000247911400024 PM 17604727 ER PT J AU Kim, HY AF Kim, Hee-Yong TI Novel metabolism of docosahexaenoic acid in neural cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; C6 GLIOMA-CELLS; RAT-BRAIN MICROSOMES; NEURONAL APOPTOSIS; PHOSPHATIDYLSERINE BIOSYNTHESIS; SUBSTRATE PREFERENCE; ALZHEIMERS-DISEASE; GENE-EXPRESSION; GLIAL-CELLS; N-3 AB Long-chain polyunsaturated fatty acids are highly enriched in the nervous system. Docosahexaenoic acid (DHA(2); 22: 6n-3), in particular, is the most abundant polyunsaturated fatty acid in the brain and is concentrated in aminophospholipids of cell membranes. Numerous studies have indicated that this concentration of DHA in the nervous system is essential for optimal neuronal and retinal functions (1). Although the underlying mechanisms of its essential function are still not clearly understood, emerging evidence suggests that unique metabolism of DHA in relation to its incorporation into neuronal membrane phospholipids plays an important role. In this review, biochemical mechanisms for enriching and metabolizing DHA in neural cells are discussed in the context of their biological significance in neuronal function. C1 NIAAA, Div Intramural Clin & Biol Res, Mol Signalling Lab, Bethesda, MD 20892 USA. RP Kim, HY (reprint author), NIAAA, Div Intramural Clin & Biol Res, Mol Signalling Lab, Bethesda, MD 20892 USA. EM hykim@nih.gov FU Intramural NIH HHS NR 57 TC 120 Z9 123 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 29 PY 2007 VL 282 IS 26 BP 18661 EP 18665 DI 10.1074/jbc.R700015200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181ZQ UT WOS:000247475300002 PM 17488715 ER PT J AU Barlic, J Zhang, Y Murphy, PM AF Barlic, Jana Zhang, Yuan Murphy, Philip M. TI Atherogenic lipids induce adhesion of human coronary artery smooth muscle cells to macrophages by up-regulating chemokine CX3CL1 on smooth muscle cells in a TNF alpha-NF kappa B-dependent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; FRACTALKINE RECEPTOR CX(3)CR1; AMERICAN-HEART-ASSOCIATION; NECROSIS-FACTOR-ALPHA; GENETIC RISK-FACTOR; OXIDIZED LDL; ENDOTHELIAL-CELLS; ATHEROSCLEROTIC LESIONS; HISTOLOGICAL CLASSIFICATION; MOLECULE EXPRESSION AB Recent genetic evidence has implicated the adhesive chemokine CX3CL1 and its leukocyte receptor CX3CR1 in atherosclerosis. We previously proposed a mechanism involving foam cell anchorage to vascular smooth muscle cells because: 1) CX3CL1 and CX3CR1 are expressed by both cell types in mouse and human atherosclerotic lesions; 2) foam cells are reduced in lesions in cx3cr1(-/-) apoE(-/-) mice; and 3) proatherogenic lipids ( oxidized low density lipoprotein [oxLDL] and oxidized linoleic acid derivatives) induce adhesion of primary human macrophages to primary human coronary artery smooth muscle cells (CASMCs) in vitro in a macrophage CX3CR1-dependent manner. Here we analyze this concept further by testing whether atherogenic lipids regulate expression and function of CX3CL1 and CX3CR1 on CASMCs. We found that both oxLDL and oxidized linoleic acid derivatives indirectly up-regulated CASMC CX3CL1 at both the protein and mRNA levels through an autocrine feedback loop involving tumor necrosis factor alpha production and NF-kappa B signaling. Oxidized lipids also up-regulated CASMC CX3CR1 but through a different mechanism. Oxidized lipid stimulation also increased adhesion of macrophages to CASMCs when CASMCs were stimulated prior to assay, and a synergistic pro-adhesive effect was observed when both cell types were prestimulated. Selective inhibition with a CX3CL1-specific blocking antibody indicated that adhesion was strongly CASMC CX3CL1-dependent. These findings support the hypothesis that CX3CR1 and CX3CL1 mediate heterotypic anchorage of foam cells to CASMCs in the context of atherosclerosis and suggest that this chemokine/chemokine receptor pair may be considered as a pro-inflammatory target for therapeutic intervention in atherosclerotic cardiovascular disease. C1 NIH, NIAID, Mol Signalling Sect, Lab Mol Immunol, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIH, Bldg 10,Rm 11N113,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Intramural NIH HHS NR 55 TC 35 Z9 38 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 29 PY 2007 VL 282 IS 26 BP 19167 EP 19176 DI 10.1074/jbc.M701642200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 181ZQ UT WOS:000247475300058 PM 17456471 ER PT J AU Robin, RW Gottesman, II Albaugh, B Goldman, D AF Robin, Robert W. Gottesman, Irving I. Albaugh, Bernard Goldman, David TI Schizophrenia and psychotic symptoms in families of two American Indian tribes SO BMC PSYCHIATRY LA English DT Article ID Y-CHROMOSOME HAPLOTYPE; PSYCHIATRIC-DISORDERS; DIAGNOSTIC INTERVIEW; BIPOLAR DISORDER; MENTAL-DISORDERS; SUBSTANCE-ABUSE; UNITED-STATES; PREVALENCE; POPULATION; COMMUNITY AB Background: The risk of schizophrenia is thought to be higher in population isolates that have recently been exposed to major and accelerated cultural change, accompanied by ensuing socio- environmental stressors/ triggers, than in dominant, mainstream societies. We investigated the prevalence and phenomenology of schizophrenia in 329 females and 253 males of a Southwestern American Indian tribe, and in 194 females and 137 males of a Plains American Indian tribe. These tribal groups were evaluated as part of a broader program of gene-environment investigations of alcoholism and other psychiatric disorders. Methods: Semi- structured psychiatric interviews were conducted to allow diagnoses utilizing standardized psychiatric diagnostic criteria, and to limit cultural biases. Study participants were recruited from the community on the basis of membership in pedigrees, and not by convenience. After independent raters evaluated the interviews blindly, DSM-III-R diagnoses were assigned by a consensus of experts well- versed in the local cultures. Results: Five of the 582 Southwestern American Indian respondents (prevalence = 8.6 per 1000), and one of the 331 interviewed Plains American Indians (prevalence = 3.02 per 1000) had a lifetime diagnosis of schizophrenia. The lifetime prevalence rates of schizophrenia within these two distinct American Indian tribal groups is consistent with lifetime expectancy rates reported for the general United States population and most isolate and homogeneous populations for which prevalence rates of schizophrenia are available. While we were unable to factor in the potential modifying effect that mortality rates of schizophrenia- suffering tribal members may have had on the overall tribal rates, the incidence of schizophrenia among the living was well within the normative range. Conclusion: The occurrence of schizophrenia among members of these two tribal population groups is consistent with prevalence rates reported for population isolates and in the general population. Vulnerabilities to early onset alcohol and drug use disorders do not lend convincing support to a diathesis- stressor model with these stressors, commonly reported with these tribes. Nearly one- fifth of the respondents reported experiencing psychotic- like symptoms, reaffirming the need to examine sociocultural factors actively before making positive diagnoses of psychosis or schizophrenia. C1 Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55454 USA. Univ Minnesota, Sch Med, Dept Psychol, Minneapolis, MN 55454 USA. Hopi Guidance Ctr, Second Mesa, AZ 86043 USA. Ctr Human Behav Studies, Weatherford, OK 73096 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Robin, RW (reprint author), Univ Minnesota, Sch Med, Dept Psychiat, F235-2A West,2450 Riverside Ave, Minneapolis, MN 55454 USA. EM rrobin@gci.net; gotte003@umn.edu; lhasa@classicnet.net; dgneuro@mail.nih.gov RI G, I/D-8042-2011; Gottesman, Irving/B-9303-2011; Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 61 TC 3 Z9 3 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD JUN 28 PY 2007 VL 7 AR 30 DI 10.1186/1471-244X-7-30 PG 8 WC Psychiatry SC Psychiatry GA 190WZ UT WOS:000248092700001 PM 17598920 ER PT J AU Tikhonova, IG Sum, CS Neumann, S Thomas, CJ Raaka, BM Costanzi, S Gershengorn, MC AF Tikhonova, Irina G. Sum, Chi Shing Neumann, Susanne Thomas, Craig J. Raaka, Bruce M. Costanzi, Stefano Gershengorn, Marvin C. TI Bidirectional, iterative approach to the structural delineation of the functional "Chemoprint" in GPR40 for agonist recognition SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED-RECEPTORS; INSULIN-SECRETION; LIGAND-BINDING; FATTY-ACIDS; DESIGN; ACTIVATION; RHODOPSIN; CONSTRUCTION; MUTAGENESIS; ANTAGONISTS AB GPR40, free fatty acid receptor 1 (FFAR1), is a member of the GPCR superfamily and a possible target for the treatment of type 2 diabetes. In this work, we conducted a bidirectional iterative investigation, including computational modeling and site-directed mutagenesis, aimed at delineating amino acid residues forming the functional "chemoprint" of GPR40 for agonist recognition. The computational and experimental studies revolved around the recognition of the potent synthetic agonist GW9508. Our experimentally supported model suggested that H137(4.56), R183(5.39), N244(6.55), and R258(7.35) are directly involved in interactions with the ligand. We have proposed a polarized NH-pi interaction between H137(4.56) and GW9508 as one of the contributing forces leading to the high potency of GW9508. The modeling approach presented in this work provides a general strategy for the exploration of receptor-ligand interactions in G-protein coupled receptors beginning prior to acquisition of experimental data. C1 NIDDK, Lab Biol Modeling, Clin Endocrinol Branch, Chem Biol Core Facil,NIH, Bethesda, MD 20892 USA. RP Costanzi, S (reprint author), NIDDK, Lab Biol Modeling, Clin Endocrinol Branch, Chem Biol Core Facil,NIH, Bethesda, MD 20892 USA. EM stefanoc@mail.nih.gov; marving@intra.niddk.nih.gov RI Costanzi, Stefano/G-8990-2013; OI Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z99 DK999999, Z01 DK013025-01, Z01 DK070005-04] NR 53 TC 61 Z9 62 U1 2 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 28 PY 2007 VL 50 IS 13 BP 2981 EP 2989 DI 10.1021/jm0614782 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 180VO UT WOS:000247394600005 PM 17552505 ER PT J AU Easton, DF Pooley, KA Dunning, AM Pharoah, PDP Thompson, D Ballinger, DG Struewing, JP Morrison, J Field, H Luben, R Wareham, N Ahmed, S Healey, CS Bowman, R Meyer, KB Haiman, CA Kolonel, LK Henderson, BE Le Marchand, L Brennan, P Sangrajrang, S Gaborieau, V Odefrey, F Shen, CY Wu, PE Wang, HC Eccles, D Evans, DG Peto, J Fletcher, O Johnson, N Seal, S Stratton, MR Rahman, N Chenevix-Trench, G Bojesen, SE Nordestgaard, BG Axelsson, CK Garcia-Closas, M Brinton, L Chanock, S Lissowska, J Peplonska, B Nevanlinna, H Fagerholm, R Eerola, H Kang, D Yoo, KY Noh, DY Ahn, SH Hunter, DJ Hankinson, SE Cox, DG Hall, P Wedren, S Liu, JJ Low, YL Bogdanova, N Schurmann, P Dork, T Tollenaar, RAEM Jacobi, CE Devilee, P Klijn, JGM Sigurdson, AJ Doody, MM Alexander, BH Zhang, JH Cox, A Brock, IW MacPherson, G Reed, MWR Couch, FJ Goode, EL Olson, JE Meijers-Heijboer, H van den Ouweland, A Uitterlinden, A Rivadeneira, F Milne, RL Ribas, G Gonzalez-Neira, A Benitez, J Hopper, JL McCredie, M Southey, M Giles, GG Schroen, C Justenhoven, C Brauch, H Hamann, U Ko, YD Spurdle, AB Beesley, J Chen, XQ Mannermaa, A Kosma, VM Kataja, V Hartikainen, J Day, NE Cox, DR Ponder, BAJ AF Easton, Douglas F. Pooley, Karen A. Dunning, Alison M. Pharoah, Paul D. P. Thompson, Deborah Ballinger, Dennis G. Struewing, Jeffery P. Morrison, Jonathan Field, Helen Luben, Robert Wareham, Nicholas Ahmed, Shahana Healey, Catherine S. Bowman, Richard Meyer, Kerstin B. Haiman, Christopher A. Kolonel, Laurence K. Henderson, Brian E. Le Marchand, Loic Brennan, Paul Sangrajrang, Suleeporn Gaborieau, Valerie Odefrey, Fabrice Shen, Chen-Yang Wu, Pei-Ei Wang, Hui-Chun Eccles, Diana Evans, D. Gareth Peto, Julian Fletcher, Olivia Johnson, Nichola Seal, Sheila Stratton, Michael R. Rahman, Nazneen Chenevix-Trench, Georgia Bojesen, Stig E. Nordestgaard, Borge G. Axelsson, Christen K. Garcia-Closas, Montserrat Brinton, Louise Chanock, Stephen Lissowska, Jolanta Peplonska, Beata Nevanlinna, Heli Fagerholm, Rainer Eerola, Hannaleena Kang, Daehee Yoo, Keun-Young Noh, Dong-Young Ahn, Sei-Hyun Hunter, David J. Hankinson, Susan E. Cox, David G. Hall, Per Wedren, Sara Liu, Jianjun Low, Yen-Ling Bogdanova, Natalia Schuermann, Peter Doerk, Thilo Tollenaar, Rob A. E. M. Jacobi, Catharina E. Devilee, Peter Klijn, Jan G. M. Sigurdson, Alice J. Doody, Michele M. Alexander, Bruce H. Zhang, Jinghui Cox, Angela Brock, Ian W. MacPherson, Gordon Reed, Malcolm W. R. Couch, Fergus J. Goode, Ellen L. Olson, Janet E. Meijers-Heijboer, Hanne van den Ouweland, Ans Uitterlinden, Andre Rivadeneira, Fernando Milne, Roger L. Ribas, Gloria Gonzalez-Neira, Anna Benitez, Javier Hopper, John L. McCredie, Margaret Southey, Melissa Giles, Graham G. Schroen, Chris Justenhoven, Christina Brauch, Hiltrud Hamann, Ute Ko, Yon-Dschun Spurdle, Amanda B. Beesley, Jonathan Chen, Xiaoqing Mannermaa, Arto Kosma, Veli-Matti Kataja, Vesa Hartikainen, Jaana Day, Nicholas E. Cox, David R. Ponder, Bruce A. J. CA SEARCH Collaborators kConFab AOCS Management Grp TI Genome-wide association study identifies novel breast cancer susceptibility loci SO NATURE LA English DT Article ID GROWTH-FACTOR RECEPTOR-2; OVARIAN-CANCER; BRCA2 MUTATIONS; PROSTATE-CANCER; GENE; DISEASE; CHEK2-ASTERISK-1100DELC; POPULATIONS; PATTERNS; DATABASE AB Breast cancer exhibits familial aggregation, consistent with variation in genetic susceptibility to the disease. Known susceptibility genes account for less than 25% of the familial risk of breast cancer, and the residual genetic variance is likely to be due to variants conferring more moderate risks. To identify further susceptibility alleles, we conducted a two-stage genome-wide association study in 4,398 breast cancer cases and 4,316 controls, followed by a third stage in which 30 single nucleotide polymorphisms (SNPs) were tested for confirmation in 21,860 cases and 22,578 controls from 22 studies. We used 227,876 SNPs that were estimated to correlate with 77% of known common SNPs in Europeans at r(2) > 0.5. SNPs in five novel independent loci exhibited strong and consistent evidence of association with breast cancer (P < 10(-7)). Four of these contain plausible causative genes (FGFR2, TNRC9, MAP3K1 and LSP1). At the second stage, 1,792 SNPs were significant at the P < 0.05 level compared with an estimated 1,343 that would be expected by chance, indicating that many additional common susceptibility alleles may be identifiable by this approach. C1 Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. Univ Cambridge, Dept Oncol, Cambridge CB1 8RN, England. Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic 3053, Australia. Univ Otago, Dept Prevent & Social Med, Dunedin 9001, New Zealand. Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Carlton, Vic 3053, Australia. Spanish Natl Canc Ctr CNIO, E-28029 Madrid, Spain. Erasmus Univ, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands. Mayo Clin, Coll Med, Rochester, MN 55905 USA. Univ Sheffield, Sch Med, Acad Unit Surg Oncol, Sheffield S10 2RX, S Yorkshire, England. Univ Sheffield, Sch Med, Inst Canc Studies, Sheffield S10 2RX, S Yorkshire, England. Univ Minnesota, Minneapolis, MN 55455 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Dept Med Oncol, Family Canc Clin, NL-3075 EA Rotterdam, Netherlands. Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Pathol, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Med Decis Making, NL-2333 ZA Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Surg, NL-2333 ZA Leiden, Netherlands. Hannover Med Sch, Dept Obstet & Gynecol, D-30625 Hannover, Germany. Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany. Genome Inst Singapore, Singapore 138672, Singapore. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Univ Ulsan, Coll Med, Ulsan 680749, South Korea. Natl Canc Ctr, Goyang 411769, South Korea. Seoul Natl Univ, Coll Med, Seoul 151742, South Korea. Univ Helsinki, Cent Hosp, Dept Oncol, Helsinki 00029, Finland. Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki 00029, Finland. Nofer Inst Occupat Med, PL-90950 Lodz, Poland. M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. Ctr Canc, PL-02781 Warsaw, Poland. NCI, Ctr Adv Technol, Gaithersburg, MD 20877 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Copenhagen, Herlev Univ Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark. Univ Copenhagen, Bispebjerg Univ Hosp, Dept Breast Surg, DK-2730 Herlev, Denmark. Queensland Inst Med Res, Brisbane, Qld 4006, Australia. Wellcome Trust Sanger Inst, Canc Genome Project, Cambridge CB10 1SA, England. Inst Canc Res, Sect Canc Genet, Sutton SM2 5NG, Surrey, England. Breakthrought Breast Canc Res Ctr, London SW3 6JB, England. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Univ London London Sch Hyg & Trop Med, London WC1E 7HT, England. St Marys Hosp, Reg Genet Serv, Manchester M13 0JH, Lancs, England. Princess Anne Hosp, Wessex Clin Genet Serv, Southampton SO16 5YA, Hants, England. Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan. NCI, Bangkok 10400, Thailand. Int Agcy Res Canc, F-69008 Lyon, France. Univ Hawaii, Canc Res Ctr Hawaii, Program Epidemiol, Honolulu, HI 96813 USA. Univ Calif Los Angeles, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. MRC, Dunn Clin Nutr Ctr, Cambridge CB2 0XY, England. Univ Cambridge, Dept Publ Hlth & Primary Care, EPIC, Cambridge CB1 8RN, England. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Perlegen Sci Inc, Mountain View, CA 94043 USA. Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Parkville, Vic 3052, Australia. Vaasa Cent Hosp, Dept Oncol, Vaasa 65130, Finland. Kuopio Univ Hosp, Dept Oncol, FIN-70211 Kuopio, Finland. Kuopio Univ Hosp, Dept Pathol, FIN-70211 Kuopio, Finland. Univ Kuopio, Inst Clin Med Pathol & Forens Med, FIN-70210 Kuopio, Finland. Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. Evangel Kliniken Bonn GGmbh, Johanniter Krankenhaus, D-53113 Bonn, Germany. Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. Univ Tubingen, D-72074 Tubingen, Germany. Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany. RP Easton, DF (reprint author), Univ Cambridge, Dept Publ Hlth & Primary Care, CR UK Genet Epidemiol Unit, Cambridge CB1 8RN, England. EM d.easton@srl.cam.ac.uk RI Hartikainen, Jaana/E-6256-2015; Struewing, Jeffery/I-7502-2013; Dork, Thilo/J-8620-2012; Bowtell, David/H-1007-2016; Rahman, Nazneen/D-2802-2013; Jenkins, Mark/P-7803-2015; Cox, David/A-2023-2009; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Spurdle, Amanda/A-4978-2011; Wang, Hui-Chun/C-5680-2009; Noh, Dong-Young/G-5531-2011; Peplonska, Beata/F-6004-2010; Shen, CY/F-6271-2010; Kang, Dae Hee/E-8631-2012; Yoo, Keun-Young/J-5548-2012; Rahman, Nazneen/B-8890-2012; Ward, Robyn/I-2313-2013; Gonzalez-Neira, Anna/C-5791-2015 OI Phillips, Kelly-Anne/0000-0002-0475-1771; Luben, Robert/0000-0002-5088-6343; Dunning, Alison Margaret/0000-0001-6651-7166; Rivadeneira, Fernando/0000-0001-9435-9441; Shelling, Andrew/0000-0002-5300-1934; Nevanlinna, Heli/0000-0002-0916-2976; Giles, Graham/0000-0003-4946-9099; Winship, Ingrid/0000-0001-8535-6003; Osborne, Richard/0000-0002-9081-2699; Saunders, Christobel/0000-0003-2281-9829; Evans, Gareth/0000-0002-8482-5784; Struewing, Jeffery/0000-0002-4848-3334; Bowtell, David/0000-0001-9089-7525; Callen, David/0000-0002-6189-9991; Lissowska, Jolanta/0000-0003-2695-5799; Rahman, Nazneen/0000-0003-4376-0440; Jenkins, Mark/0000-0002-8964-6160; Brown, Melissa/0000-0002-2830-9259; Cox, Angela/0000-0002-5138-1099; Webb, Penelope/0000-0003-0733-5930; Cox, David/0000-0002-2152-9259; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Spurdle, Amanda/0000-0003-1337-7897; Ward, Robyn/0000-0002-6877-8906; FU Cancer Research UK [A3353] NR 40 TC 1433 Z9 1492 U1 8 U2 144 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 28 PY 2007 VL 447 IS 7148 BP 1087 EP U7 DI 10.1038/nature05887 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 183HT UT WOS:000247564600032 PM 17529967 ER PT J AU Matsumoto, M Hikosaka, O AF Matsumoto, Masayuki Hikosaka, Okihide TI Lateral habenula as a source of negative reward signals in dopamine neurons SO NATURE LA English DT Article ID VENTRAL TEGMENTAL AREA; SUBSTANTIA-NIGRA; CAUDATE-NUCLEUS; COMPLEX; RATS; PREDICTION; MOTIVATION; SEROTONIN; RESPONSES; SACCADES AB Midbrain dopamine neurons are key components of the brain's reward system(1), which is thought to guide reward-seeking behaviours(2-4). Although recent studies have shown how dopamine neurons respond to rewards and sensory stimuli predicting reward(1,5,6), it is unclear which parts of the brain provide dopamine neurons with signals necessary for these actions. Here we show that the primate lateral habenula, part of the structure called the epithalamus, is a major candidate for a source of negative reward-related signals in dopamine neurons. We recorded the activity of habenula neurons and dopamine neurons while rhesus monkeys were performing a visually guided saccade task with positionally biased reward outcomes(7). Many habenula neurons were excited by a no-reward-predicting target and inhibited by a reward-predicting target. In contrast, dopamine neurons were excited and inhibited by reward-predicting and no-reward-predicting targets, respectively. Each time the rewarded and unrewarded positions were reversed, both habenula and dopamine neurons reversed their responses as the bias in saccade latency reversed. In unrewarded trials, the excitation of habenula neurons started earlier than the inhibition of dopamine neurons. Furthermore, weak electrical stimulation of the lateral habenula elicited strong inhibitions in dopamine neurons. These results suggest that the inhibitory input from the lateral habenula plays an important role in determining the reward-related activity of dopamine neurons. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Hikosaka, O (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM oh@lsr.nei.nih.gov NR 31 TC 467 Z9 481 U1 2 U2 34 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 28 PY 2007 VL 447 IS 7148 BP 1111 EP U11 DI 10.1038/nature05860 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 183HT UT WOS:000247564600037 PM 17522629 ER PT J AU Laine, C Horton, R DeAngelis, CD Drazen, JM Frizelle, FA Godlee, F Haug, C Hebert, PC Kotzin, S Marusic, A Sahni, P Schroeder, TV Sox, HC Van Der Weyden, MB Verheugt, FWA AF Laine, Christine Horton, Richard DeAngelis, Catherine D. Drazen, Jeffrey M. Frizelle, Frank A. Godlee, Fiona Haug, Charlotte Hebert, Paul C. Kotzin, Sheldon Marusic, Ana Sahni, Peush Schroeder, Torben V. Sox, Harold C. Van Der Weyden, Martin B. Verheugt, Freek W. A. TI Clinical trial registration - Looking back and moving ahead SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Natl Lib Med, MEDLINE, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; Verheugt, F.W.A./H-8105-2014; OI Marusic, Ana/0000-0001-6272-0917; Haug, Charlotte/0000-0001-8217-7376; Schroeder, Torben/0000-0002-9827-9438; Sahni, Peush/0000-0002-6910-062X NR 4 TC 87 Z9 94 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 JUN 28 PY 2007 VL 356 IS 26 BP 2734 EP 2736 DI 10.1056/NEJMe078110 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 183HS UT WOS:000247564500015 PM 17548427 ER PT J AU Curtis, D Xu, K AF Curtis, David Xu, Ke TI Minor differences in haplotype frequency estimates can produce very large differences in heterogeneity test statistics SO BMC GENETICS LA English DT Letter ID GENE AB Background: Tests for association between a haplotype and disease are commonly performed using a likelihood ratio test for heterogeneity between case and control haplotype frequencies. Using data from a study of association between heroin dependence and the DRD2 gene, we obtained estimated haplotype frequencies and the associated likelihood ratio statistic using two different computer programs, MLOCUS and GENECOUNTING. We also carried out permutation testing to assess the empirical significance of the results obtained. Results: Both programs yielded similar, though not identical, estimates for the haplotype frequencies. MLOCUS produced a p value of 1.8*10(-15) and GENECOUNTING produced a p value of 5.4*10(-4). Permutation testing produced a p value 2.8*10(-4). Conclusion: The fact that very large differences occur between the likelihood ratio statistics from the two programs may reflect the fact that the haplotype frequencies for the combined group are not constrained to be equal to the weighted averages of the frequencies for the cases and controls, as they would be if they were directly observed rather than being estimated. Minor differences in haplotype frequency estimates can result in very large differences in the likelihood ratio statistic and associated p value. C1 Queens Marys Sch Med & Dent, Acad Dept Psychiat, London E1 1BB, England. NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Curtis, D (reprint author), Queens Marys Sch Med & Dent, Acad Dept Psychiat, London E1 1BB, England. EM david.curtis@qmul.ac.uk; ke@mail.nih.gov OI Curtis, David/0000-0002-4089-9183 NR 6 TC 12 Z9 12 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD JUN 27 PY 2007 VL 8 AR 38 DI 10.1186/1471-2156-8-38 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 191IH UT WOS:000248124400001 PM 17597526 ER PT J AU Dabelea, D Bell, RA D'Agostino, RB Imperatore, G Johansen, JM Linder, B Liu, LL Loots, B Marcovina, S Mayer-Davis, EJ Pettitt, DJ Waitzfelder, B AF Dabelea, Dana Bell, Ronny A. D'Agostino, Ralph B., Jr. Imperatore, Giuseppina Johansen, Judith M. Linder, Barbara Liu, Lenna L. Loots, Beth Marcovina, Santica Mayer-Davis, Elizabeth J. Pettitt, David J. Waitzfelder, Beth CA Writing Grp SEARCH Diabet Youth St TI Incidence of diabetes in youth in the United States SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ACID DECARBOXYLASE GAD65; ALLEGHENY-COUNTY; AFRICAN-AMERICAN; MELLITUS; CHILDREN; ADOLESCENTS; TYPE-2; PREVALENCE; EPIDEMIC; TRENDS AB Context Data on the incidence of diabetes mellitus (DM) among US youth according to racial/ethnic background and DM type are limited. Objective To estimate DM incidence in youth aged younger than 20 years according to race/ethnicity and DM type. Design, Setting, and Participants A multiethnic, population-based study (The SEARCH for Diabetes in Youth Study) of 2435 youth with newly diagnosed, nonsecondary DM in 2002 and 2003, ascertained at 10 study locations in the United States, covering a population of more than 10 million person-years. Main Outcome Measure Incidence rates by age group, sex, race/ethnicity, and DM type were calculated per 100 000 person-years at risk. Diabetes mellitus type ( type 1/type 2) was based on health care professional assignment and, in a subset, further characterized with glutamicacid decarboxylase( GAD65) autoantibody and fasting C peptide measures. Results The incidence of DM ( per 100 000 person-years) was 24.3 (95% confidence interval [CI], 23.3-25.3). Among children younger than 10 years, most had type 1 DM, regardless of race/ethnicity. The highest rates of type 1 DM were observed in non-Hispanic white youth (18.6, 28.1, and 32.9 for age groups 0-4, 5-9, and 10-14 years, respectively). Even among older youth ( >= 10 years), type 1 DM was frequent among non-Hispanic white, Hispanic, and African American adolescents. Overall, type 2 DM was still relatively infrequent, but the highest rates (17.0 to 49.4 per 100 000 person-years) were documented among 15- to 19-year-old minority groups. Conclusions Our data document the incidence rates of type 1 DM among youth of all racial/ethnic groups, with the highest rates in non-Hispanic white youth. Overall, type 2 DM is still relatively infrequent; however, the highest rates were observed among adolescent minority populations. C1 Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NIDDK, Bethesda, MD USA. Univ Washington, Inst Child Hlth, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Univ S Carolina, Columbia, SC 29208 USA. Sansum Diabet Res Inst, Santa Barbara, CA USA. Pacific Hlth Res Inst, Honolulu, HI USA. RP Dabelea, D (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, 4200 E 9th Ave,Box C245, Denver, CO 80262 USA. EM dana.dabelea@uchsc.edu RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 NR 46 TC 464 Z9 471 U1 2 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2007 VL 297 IS 24 BP 2716 EP 2724 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 182UE UT WOS:000247528700021 ER PT J AU Pao, M Ballard, ED Rosenstein, DL AF Pao, Maryland Ballard, Elizabeth D. Rosenstein, Donald L. TI Growing up in the hospital SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CHRONIC ILLNESS; CHILDREN; DEPRESSION; ADOLESCENT; PREVALENCE; PSYCHIATRY; MECHANISMS; CHILDHOOD; ISSUES; CARE C1 NIMH, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Pao, M (reprint author), NIMH, NIH, Clin Res Ctr, 6-5340, Bethesda, MD 20892 USA. EM paom@mail.nih.gov NR 24 TC 11 Z9 11 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 27 PY 2007 VL 297 IS 24 BP 2752 EP 2755 DI 10.1001/jama.297.24.2752 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 182UE UT WOS:000247528700025 PM 17595276 ER PT J AU Lukacs, V Thyagarajan, B Varnai, P Balla, A Balla, T Rohacs, T AF Lukacs, Viktor Thyagarajan, Baskaran Varnai, Peter Balla, Andras Balla, Tamas Rohacs, Tibor TI Dual regulation of TRPV1 by phosphoinositides SO JOURNAL OF NEUROSCIENCE LA English DT Article DE TRPV1; TRP channel; phosphoinositides; PIP(2); vanilloid; desensitization ID DEPENDENT PROTEIN-KINASE; VANILLOID RECEPTOR TRPV1; SENSITIVE POTASSIUM CHANNELS; RECTIFYING K+ CHANNELS; ROOT GANGLION NEURONS; CAPSAICIN RECEPTOR; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; PHOSPHOLIPASE-C; ION CHANNELS; LIVING CELLS AB The membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5) P(2) or PIP(2)] regulates many ion channels. There are conflicting reports on the effect of PtdIns(4,5) P(2) on transient receptor potential vanilloid 1 (TRPV1) channels. We show that in excised patches PtdIns(4,5)P(2) and other phosphoinositides activate and the PIP(2) scavenger poly-Lys inhibits TRPV1. TRPV1 currents undergo desensitization on exposure to high concentrations of capsaicin in the presence of extracellular Ca(2+). We show that in the presence of extracellular Ca(2+), capsaicin activates phospholipase C (PLC) in TRPV1-expressing cells, inducing depletion of both PtdIns(4,5)P(2) and its precursor PtdIns(4)P (PIP). The PLC inhibitor U73122 and dialysis of PtdIns(4,5)P(2) or PtdIns(4)P through the patch pipette inhibited desensitization of TRPV1, indicating that Ca(2+)-induced activation of PLC contributes to desensitization of TRPV1 by depletion of PtdIns(4,5)P(2) and PtdIns(4) P. Selective conversion of PtdIns(4,5)P(2) to PtdIns(4)P by a rapamycin-inducible PIP2 5-phosphatase did not inhibit TRPV1 at high capsaicin concentrations, suggesting a significant role for PtdIns(4) P in maintaining channel activity. Currents induced by low concentrations of capsaicin and moderate heat, however, were potentiated by conversion of PtdIns(4,5)P(2) to PtdIns(4)P. Increasing PtdIns( 4,5)P(2) levels by coexpressing phosphatidylinositol-4-phosphate 5-kinase inhibited TRPV1 at low but not at saturating capsaicin concentrations. These data show that at low capsaicin concentrations and other moderate stimuli, PtdIns(4,5)P(2) partially inhibits TRPV1 in a cellular context, but this effect is likely to be indirect, because it is not detectable in excised patches. We conclude that phosphoinositides have both inhibitory and activating effects on TRPV1, resulting in complex and distinct regulation at various stimulation levels. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pharmacol & Physiol, Newark, NJ 07103 USA. NIH, NICHHD, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Rohacs, T (reprint author), Univ Med & Dent New Jersey, Dept Pharmacol & Physiol, New Jersey Med Sch, 185 S Orange Ave,MSB H631, Newark, NJ 07103 USA. EM tibor.rohacs@umdnj.edu OI Balla, Tamas/0000-0002-9077-3335; Balla, Andras/0000-0002-6450-2793; Lukacs, Viktor/0000-0003-3652-5469 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS055159] NR 51 TC 154 Z9 159 U1 2 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 27 PY 2007 VL 27 IS 26 BP 7070 EP 7080 DI 10.1523/JNEUROSCI.1866-07.2007 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 184CV UT WOS:000247619600023 PM 17596456 ER PT J AU Palaniappan, KK Gao, ZG Ivanov, AA Greaves, R Adachi, H Besada, P Kim, HO Kim, AY Choe, SA Jeong, LS Jacobson, KA AF Palaniappan, Krishnan K. Gao, Zhan-Guo Ivanov, Andrei A. Greaves, Rebecca Adachi, Hayamitsu Besada, Pedro Kim, Hea Ok Kim, Ae Yil Choe, Seung Ah Jeong, Lak Shin Jacobson, Kenneth A. TI Probing the binding site of the A(1) adenosine receptor reengineered for orthogonal recognition by tailored nucleosides SO BIOCHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; SMOOTH-MUSCLE-CELLS; DIRECTED MUTAGENESIS; LIGAND-BINDING; A(3) RECEPTOR; WILD-TYPE; ACTIVATION; AGONISTS; DERIVATIVES; MODULATION AB His272 (7.43) in the seventh transmembrane domain (TM7) of the human A(3) adenosine receptor (AR) interacts with the 3 ' position of nucleosides, based on selective affinity enhancement at a H272E mutant A(3) AR (neoceptor) of 3 '-ureido, but not 3 '-OH, adenosine analogues. Here, mutation of the analogous H278 of the human A(1) AR to Ala, Asp, Glu, or Leu enhanced the affinity of novel 2 '- and 3 '-ureido adenosine analogues, such as 10 (N-6-cyclopentyl-3 '-ureido-3 '-deoxyadenosine), by > 100-fold, while decreasing the affinity or potency of adenosine and other 3 '-OH adenosine analogues. His278 mutant receptors produced a similar enhancement regardless of the charge character of the substituted residue, implicating steric rather than electrostatic factors in the gain of function, a hypothesis supported by rhodopsin-based molecular modeling. It was also demonstrated that this interaction was orientationally specific; i.e., mutations at the neighboring Thr277 did not enhance the affinity for a series of 2 '- and 3 '-ureido nucleosides. Additionally, H-bonding groups placed on substituents at the N-6 or 5 ' position demonstrated no enhancement in the mutant receptors. These reengineered human A(1) ARs revealed orthogonality similar to that of the A(3) but not the A(2A) AR, in which mutation of the corresponding residue, His278, to Asp did not enhance nucleoside affinity. Functionally, the H278D A(1) AR was detectable only in a measure of membrane potential and not in calcium mobilization. This neoceptor approach should be useful for the validation of molecular modeling and the dissection of promiscuous GPCR signaling. C1 NIDDK, NIH, Mol Recognit Sect, LBC, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. RP Jacobson, KA (reprint author), NIDDK, NIH, Mol Recognit Sect, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063 FU Intramural NIH HHS [Z01 DK031115-24] NR 56 TC 9 Z9 9 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 26 PY 2007 VL 46 IS 25 BP 7437 EP 7448 DI 10.1021/bi7001828 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 180DI UT WOS:000247340300012 PM 17542617 ER PT J AU Sokolov, MV Neumann, RD Panyutin, IG AF Sokolov, Mykyta V. Neumann, Ronald D. Panyutin, Igor G. TI Effects of DNA-targeted ionizing radiation produced by 5-[I-125]iodo-2 '-deoxyuridine on global gene expression in primary human cells SO BMC GENOMICS LA English DT Article ID NORMAL HUMAN FIBROBLASTS; MAMMALIAN-CELLS; TRANSCRIPTIONAL RESPONSE; DAMAGE; EXPOSURE; STRESS; I-125; P53; RADIOTOXICITY; PHOSPHORYLATION AB Background: This study assesses the whole-genome gene expression changes in a panel of primary human cell lines in response to DNA damage mediated by decay of DNA-incorporated radioiodinated thymidine analog 5-[I-125] iodo-2'-deoxyuridine (I-125-IUdR). Three normal human cell lines of different origin, namely, gingival fibroblasts AG09319, fetal skin fibroblasts GM05388 and neonatal foreskin epidermal keratinocytes (NHFK) were used in this study. DNA molecules were radiolabeled by incubation of cells in culture in a medium supplemented with either 3.7 kBq/ml or 18.5 kBq/ml of 125I-IUdR for 24 h followed by incubation in IUdR-free medium for additional 24 hours. Each experiment was carried out in quadruplicate. 125I-IUdR uptake was monitored by measuring DNA-associated radioactivity. The whole-genome gene expression changes were evaluated using Agilent Human Whole Genome oligo microarrays containing 44,290 elements representing all known and predicted human genes. DNA microarray dataset was independently partially validated with quantitative real-time PCR (RT-PCR). Results: AG09319 gingival cells in culture responded to 125I-IUdR treatment by changing the expression level of 335 genes in total, whereas under the same conditions GM05388 and NHFK cells differentially expressed 49 genes and 27 genes, respectively. However, for GM05388 cells the number of differentially expressed genes increases with the rise of 125I-IUdR concentrations in cell culture media. The key up-regulated biological processes in a chosen panel of cell lines concern the regulation of protein kinase activities and/or cell death. Genes repressed in response to 125I-IUdR treatment are involved in cytokinesis, M phase of the cell cycle, chromosome architecture and organization, DNA metabolism, DNA packaging, DNA repair and response to DNA damage. Despite the disparate nature of the gene patterns elicited by 125I-induced DNA damage among the different cell lines, the differentially expressed transcripts reveal strikingly non-random chromosomal distribution in all the cell lines we used. /Conclusion: Our data suggest that DNA-targeted ionizing radiation produced by 125I-IUdR results in changes in expression of only a limited subset of genes in primary human cells. The responsive genes are distributed non-randomly among the chromosomes; and a significant fraction of them is p53-dependent in the transcriptional regulation. C1 Ctr Clin, Dept Nucl Med, NIH, Bethesda, MD 20892 USA. RP Panyutin, IG (reprint author), Ctr Clin, Dept Nucl Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM msokolov@mail.nih.gov; rneumann@mail.nih.gov; igorp@helix.nih.gov FU Intramural NIH HHS NR 43 TC 9 Z9 9 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUN 26 PY 2007 VL 8 AR 192 DI 10.1186/1471-2164-8-192 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 196KP UT WOS:000248480600001 PM 17594496 ER PT J AU Chen, W Dawsey, SM Qiao, YL Mark, SD Dong, ZW Taylor, PR Zhao, P Abnet, CC AF Chen, W. Dawsey, S. M. Qiao, Y-L Mark, S. D. Dong, Z-W Taylor, P. R. Zhao, P. Abnet, C. C. TI Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers SO BRITISH JOURNAL OF CANCER LA English DT Article DE vitamin D; oesophageal cancer; gastric cancer; cohort study; China ID VITAMIN-D STATUS; CASE-COHORT; CHINA; LINXIAN; MORTALITY; SPECIMENS; TRIALS; DIET; FOOD AB We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. The distribution of serum 25(OH) D was calculated using the known sampling weights. For the cohort as a whole, the 25th, 50th, and 75th percentile concentrations of 25(OH)-vitamin D were 19.6, 31.9, and 48.7 nmol l(-1), respectively, and we found that higher serum 25(OH) D concentrations were associated with monotonically increasing risk of ESCC in men, but not in women. Comparing men in the fourth quartile of serum 25(OH) D concentrations to those in the first, we found a hazard ratio (HR) (95% confidence interval (CI)) of 1.77 (1.16 - 2.70), P trend = 0.0033. The same comparison in women had a HR (95% CI) of 1.06 (0.71 - 1.59), P trend 0.70. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH) D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result. C1 NCI, Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. Chinese Acad Med Sci, Canc Inst Hosp, Dept Epidemiol, Beijing 100037, Peoples R China. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Prevent Med, Denver, CO 80206 USA. Univ Colorado, Hlth Sci Ctr, Dept Biometr, Denver, CO 80206 USA. RP Abnet, CC (reprint author), NIH, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM abnetc@mail.nih.gov 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 26 TC 65 Z9 67 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUN 26 PY 2007 VL 97 IS 1 BP 123 EP 128 DI 10.1038/sj.bjc.6603834 PG 6 WC Oncology SC Oncology GA 183UH UT WOS:000247597200019 PM 17551495 ER PT J AU Narayanan, A Ruyechan, WT Kristie, TM AF Narayanan, Aarthi Ruyechan, William T. Kristie, Thomas M. TI The coactivator host cell factor-1 mediates Set1 and MLL1 H3K4 trimethylation at herpesvirus immediate early promoters for initiation of infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin; histone methyltransferase; chromatin modifications; Sp1; transcription ID VIRUS VP16-INDUCED COMPLEX; TRANSCRIPTION FACTOR SP1; SIMPLEX-VIRUS; GENE-EXPRESSION; HISTONE H3; C1 FACTOR; PROTEIN; HCF-1; VP16; LYSINE-4 AB Originally identified as an essential component of the herpes simplex virus immediate early (IE) gene enhancer complex, the transcriptional coactivator host cell factor-1 (HCF-1) has been implicated in a broad range of cellular regulatory circuits. The protein mediates activation through multiple interactions with transcriptional activators, coactivators, and chromatin remodeling complexes. However, the mechanisms involved in HCF-1-dependent transcriptional stimulation were undefined. By using a minimal HCF-1-dependent promoter and a model activator, the varicella zoster IE62 protein, it was determined that HCF-1 was not required for the assembly of the RNAPII basal complex, which depended solely on IE62 in conjunction with the cellular factor Sp1. In contrast, HCF-1 was required for recruitment of the histone methyltransferases Set1 and MLL1 (mixed-lineage leukemia 1), leading to histone H3K4 trimethylation and transcriptional activation. Similarly, in a varicella zoster virus lytic infection, HCF-1, Set1, and MLL1 were recruited to the viral genomic IE promoter, suggesting an essential role for HCF-1 in chromatin modification and remodeling during initiation of lytic infection. The results indicate that one biological rationale for the incorporation of the viral IE activators in the viral particle is to recruit HCF-1/histone methyltransferase complexes and promote assembly of the viral IE gene promoters into transcriptionally active chromatin. These studies also contribute to the model whereby the induced nuclear transport of HCF-1 in sensory neurons may be critical to the reactivation of latent herpesviruses by promoting the activation of chromatin modifications. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14214 USA. RP Kristie, TM (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4-131,4 Ctr Dr, Bethesda, MD 20892 USA. EM thomas_kristie@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [AI18449, R01 AI018449, R21 AI018449, R56 AI018449] NR 41 TC 74 Z9 75 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 26 PY 2007 VL 104 IS 26 BP 10835 EP 10840 DI 10.1073/pnas.0704351104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 184LC UT WOS:000247641900018 PM 17578910 ER PT J AU Ha, L Ichikawa, T Anver, M Dickins, R Lowe, S Sharpless, NE Krimpenfort, P DePinho, RA Bennett, DC Sviderskaya, EV Merlino, G AF Ha, Linan Ichikawa, Takeshi Anver, Miriam Dickins, Ross Lowe, Scott Sharpless, Norman E. Krimpenfort, Paul DePinho, Ronald A. Bennett, Dorothy C. Sviderskaya, Elena V. Merlino, Glenn TI ARF functions as a melanoma tumor suppressor by inducing p53-independent senescence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetically engineered mice; MET; nevi; p16INK4A; rhabdomyosarcoma ID CELLULAR SENESCENCE; TRANSCRIPTION FACTOR; MALIGNANT-MELANOMA; MICE; P53; P16(INK4A); PATHWAYS; P14(ARF); RB; IMMORTALIZATION AB inactivation of the p53 pathway represents the most common molecular defect of human cancer. But in the setting of melanoma, a highly aggressive and invariably fatal malignancy in its advanced disseminated form, mutation/deletion of p53 is relatively rare, whereas its positive regulator ARF is often lost. Here, we show that genetic deficiency in Arf but not p53 facilitates rapid development of melanoma in a genetically engineered mouse model. This difference is accounted for, at least in part, by the unanticipated observation that, unlike fibroblasts, senescence control in melanocytes is strongly regulated by Arf and not p53. Moreover, oncogenic NRAS collaborates with deficiency in Arf, but not p53, to fully transform melanocytes. Our data demonstrate that ARF and p53, although linked in a common pathway, suppress tumorigenesis through distinct, lineage-dependent mechanisms and suggest that ARF helps restrict melanoma progression by executing the oncogene-induced senescence program in benign nevi. Thus, therapeutics designed to restore wild-type p53 function may be insufficient to counter melanoma and other malignancies in which ARF holds p53-independent tumor suppressor activity. C1 NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. Natl Canc Inst, Pathol Histotechnol Lab, SAIC, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Cold Spring Harbor Lab, Howard Hughes Med Inst, Cold Spring Harbor, NY 11724 USA. Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Genet, Chapel Hill, NC 27599 USA. Netherlands Canc Inst, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Appl Canc Sci, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Belfer Fdn Inst Innovat Canc Sci, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ London, Div Basic Med Sci, London SW17 0RE, England. RP Merlino, G (reprint author), NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. EM esviders@sgul.ac.uk; gmerlino@helix.nih.gov RI Sviderskaya, Elena/D-2419-2009; Bennett, Dorothy/C-2418-2008; Dickins, Ross/K-2852-2012 OI Bennett, Dorothy/0000-0002-3639-7527; Dickins, Ross/0000-0003-4112-5304 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400, P30 CA008748]; Wellcome Trust [064583, 078327] NR 36 TC 101 Z9 102 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 26 PY 2007 VL 104 IS 26 BP 10968 EP 10973 DI 10.1073/pnas.0611638104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 184LC UT WOS:000247641900041 PM 17576930 ER PT J AU Schiffman, M AF Schiffman, Mark TI Integration of human papillomavirus vaccination, cytology, and human papillomavirus testing SO CANCER CYTOPATHOLOGY LA English DT Review DE human papillomavirus; cytology; testing; cervical cancer ID CERVICAL INTRAEPITHELIAL NEOPLASIA; 2001 CONSENSUS GUIDELINES; FOLLOW-UP; PARTICLE VACCINE; ABSOLUTE RISK; WOMEN; TYPE-16; CANCER; ABNORMALITIES; EFFICACY AB There is justifiable excitement about the recent introduction of prophylactic vaccines against human papillornavirus (HPV) types 16 (HPV-16) and HPV-18. Preventing these infections theoretically could avert approximately 70% of cervical cancer cases worldwide. In the U.S., numerous influential advocates are calling for universal vaccination of adolescent females. Given the promise of the vaccines, perhaps it is inevitable that vaccine introduction is proceeding before full consideration of how universal vaccination would affect existing, successful cervical cancer prevention programs. Determining the impact and cost effectiveness of the vaccines unavoidably will require time. Nevertheless, it is worth describing in broad terms for the readers of Cancer Cytopathology how successful, broad HPV vaccination of adolescent girls may affect cytology and HPV testing. C1 NCI, Human Papillomavirus Res Unit, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RP Schiffman, M (reprint author), NCI, Human Papillomavirus Res Unit, Div Canc Epidemiol & Genet, Room 70666120,Execut Blvd, Rockville, MD 20852 USA. EM schiffmm@mail.nih.gov NR 45 TC 85 Z9 90 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUN 25 PY 2007 VL 111 IS 3 BP 145 EP 153 DI 10.1002/cncr.22751 PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 179LF UT WOS:000247290400004 PM 17487850 ER PT J AU Rapkiewicz, A Espina, V Zujewski, JA Lebowitz, PF Filie, A Wulfkuhle, J Camphausen, K Petricoin, EF Liotta, LA Abati, A AF Rapkiewicz, Amy Espina, Virginia Zujewski, Jo Anne Lebowitz, Peter F. Filie, Armando Wulfkuhle, Julia Camphausen, Kevin Petricoin, Emanuel F., III Liotta, Lance A. Abati, Andrea TI The needle in the haystack: Application of breast fine-needle aspirate samples to quantitative protein microarray technology SO CANCER CYTOPATHOLOGY LA English DT Article DE breast cancer; fine-needle aspiration; microarray; protein; proteomics ID GENE-EXPRESSION PROFILES; CLINICAL-APPLICATIONS; DIAGNOSTIC-ACCURACY; COST-EFFECTIVENESS; PROSTATE-CANCER; PTEN; BIOPSY; CARCINOMA; SURVIVAL; PROTEOMICS AB BACKGROUND. There is an unmet clinical need for economic, minimally invasive procedures that use a limited number of cells for the molecular profiling of tumors in individual patients. Reverse-phase protein microarray (RPPM) technology has been applied successfully to the quantitative analysis of breast, ovarian, prostate, and colorectal cancers using frozen surgical specimens. METHODS. For this report, the authors investigated the novel use of RPPM technology for the analysis of both archival cytology aspirate smears and frozen fine-needle aspiration (FNA) samples. RPPMs were printed with 63 breast FNA samples that were obtained before, during, and after treatment from 21 patients who were enrolled in a Phase 11 trial of neoadjuvant capecitabine and docetaxel therapy for breast cancer. RESULTS. Based on an MCF7 cell line model of breast adenocarcinoma, the sensitivity of the RPPM detection method was in the femtomolar range with a coefficient of variance < 13.50% for the most dilute sample. Assay linearity was noted from 1.0 mu g/mu L to 7.8 ng/mu L total protein/array spot (R-2 = 0.9887) for a membrane receptor protein (epidermal growth factor receptor; R-2 = 0.9935). CONCLUSIONS. The results from this study indicated that low-abundance analytes and phosphorylated and nonphosphorylated proteins in specimens that consist of a few thousand cells obtained through FNA can be quantified with RPPM technology. The ability to monitor the in vivo state of cell-signaling proteins before and after treatment potentially will augment the ability to design individualized therapy regimens through the mapping of aberrant cell-signaling phenotypes. The mapping of these protein pathways will further the development of rational drug targets. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA USA. NCI, Clin Invest Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Lombardi Comprehens Canc Ctr, Ctr Med, Washington, DC USA. RP Rapkiewicz, A (reprint author), NYU, Bellevue Hosp, Room 4S17A,462 1st Ave, New York, NY 10016 USA. EM rapkia01@med.nyu.edu OI Espina, Virginia/0000-0001-5080-5972 FU Intramural NIH HHS NR 48 TC 53 Z9 53 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUN 25 PY 2007 VL 111 IS 3 BP 173 EP 184 DI 10.1002/cncr.22686 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 179LF UT WOS:000247290400008 PM 17487852 ER PT J AU Zimmet, P Alberti, G Kaufman, F Tajima, N Silink, M Arslanian, S Wong, G Bennett, P Shaw, J Caprio, S AF Zimmet, Paul Alberti, George Kaufman, Francine Tajima, Naoko Silink, Martin Arslanian, Silva Wong, Gary Bennett, Peter Shaw, Jonathan Caprio, Sonia CA Int Diabet Federation Task Force E TI The metabolic syndrome in children and adolescents SO LANCET LA English DT Editorial Material ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CARDIOVASCULAR RISK-FACTORS; WAIST CIRCUMFERENCE; PREVALENCE; AMERICAN C1 St Marys Hosp, Dept Endocrinol & Metab Med, London W2 1NY, England. Int Diabet Inst, Melbourne, Vic, Australia. Univ London Imperial Coll Sci Technol & Med, London, England. Childrens Hosp, Los Angeles, CA USA. Jikei Univ, Sch Med, Tokyo, Japan. Westmead Hosp, Sydney, NSW, Australia. Childrens Hosp, Pittsburgh, PA 15213 USA. Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. Yale Univ, Sch Med, New Haven, CT USA. RP Alberti, G (reprint author), St Marys Hosp, Dept Endocrinol & Metab Med, Praed St, London W2 1NY, England. EM George.alberti@ncl.ac.uk RI Shaw, Jonathan/E-7388-2010 OI Shaw, Jonathan/0000-0002-6187-2203 NR 14 TC 384 Z9 428 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD JUN 23 PY 2007 VL 369 IS 9579 BP 2059 EP 2061 DI 10.1016/S0140-6736(07)60958-1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 182GM UT WOS:000247493100008 PM 17586288 ER PT J AU Nabel, EG Shurin, SB Simons-Morton, DG Gordon, D AF Nabel, Eliozabeth G. Shurin, Susan B. Simons-Morton, Denise G. Gordon, David TI Data and safety monitoring of rosiglitazone trials SO LANCET LA English DT Letter C1 NHLBI, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Bldg 31,Room 5A48,31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA. EM nabele@nhlbi.nih.gov NR 2 TC 2 Z9 2 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 23 PY 2007 VL 369 IS 9579 BP 2077 EP 2077 DI 10.1016/S0140-6736(07)60975-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 182GM UT WOS:000247493100023 PM 17586301 ER PT J AU Mukhopadhyay, P Rajesh, M Yoshihiro, K Hasko, G Pacher, P AF Mukhopadhyay, Partha Rajesh, Mohanraj Yoshihiro, Kashiwaya Hasko, Gyorgy Pacher, Pal TI Simple quantitative detection of mitochondrial superoxide production in live cells SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE superoxide; mitochondria; free radicals; MitoSOX; Antimycin A (AntA); Paraquat (PQ); Doxorubicin (DOX); cardiomyocytes; H9c2; human coronary artery endothelial cells (HCAECs) ID CARDIAC MITOCHONDRIA; OXIDATIVE DAMAGE; PROBES; ANTHRACYCLINES; RADICALS; DISEASE; OXIDASE; ANION; DEATH AB Experiments with isolated mitochondria have established that these organelles are pivotal intracellular sources of superoxide in a variety of pathophysiological conditions. Recently, a novel fluoroprobe MitoSOX Red was introduced for selective detection of superoxide in the mitochondria of live cells and was validated with confocal microscopy. Here we show similar to 3-7 fold dose- and time-dependent increase in mitochondrial superoxide production (measured by MitoSOX using flow cytometry and confocal microscopy) in rat cardiac derived H9c2 myocytes and/or in human coronary artery endothelial cells triggered by Antimycin A, Paraquat, Doxorubicin or high glucose. These results establish a novel, quantitative method for simple detection of mitochondrial superoxide generation simultaneously in a large population of live cells by flow cytometry. This method can also be adapted for immune cell studies with mixed population of T or B cells or their subsets to analyze mitochondrial superoxide levels using multiple labeled surface markers in individual populations. Published by Elsevier Inc. C1 NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Metab Control, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov RI MUKHOPADHYAY, PARTHA/G-3890-2010; Pacher, Pal/B-6378-2008 OI MUKHOPADHYAY, PARTHA/0000-0002-1178-1274; Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 23 TC 168 Z9 170 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 22 PY 2007 VL 358 IS 1 BP 203 EP 208 DI 10.1016/j.bbrc.2007.04.106 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 172FZ UT WOS:000246790800034 PM 17475217 ER PT J AU Skarlatos, SI AF Skarlatos, Sonia I. TI National Heart, Lung, and Blood Institute resources and programs for gene therapy in heart, lung, and blood diseases SO CIRCULATION RESEARCH LA English DT Editorial Material DE gene therapy; translational studies; clinical research; vector systems; gene transfer; NHLBI ID LENTIVIRAL VECTORS; MONKEYS; FETAL C1 NHLBI, Div Cardiovasc Dis, NIH, Bethesda, MD 20892 USA. RP Skarlatos, SI (reprint author), NHLBI, Div Cardiovasc Dis, NIH, Bldg 10, Bethesda, MD 20892 USA. EM skarlats@nhlbi.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 22 PY 2007 VL 100 IS 12 BP 1667 EP 1669 DI 10.1161/CIRCRESAHA.107.101201 PG 3 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 182UZ UT WOS:000247530800001 PM 17585073 ER PT J AU Lyashkov, AE Juhaszova, M Dobrzynski, H Vinogradova, TM Maltsev, VA Juhasz, O Spurgeon, HA Sollott, SJ Lakatta, EG AF Lyashkov, Alexey E. Juhaszova, Magdalena Dobrzynski, Halina Vinogradova, Tatiana M. Maltsev, Victor A. Juhasz, Ondrej Spurgeon, Harold A. Sollott, Steven J. Lakatta, Edward G. TI Calcium cycling protein density and functional importance to automaticity of isolated sinoatrial nodal cells are independent of cell size SO CIRCULATION RESEARCH LA English DT Article DE sinoatrial node; pacemaker cells; Na+/Ca2+ exchanger; ryanodine receptors; SERCA2 ID RABBIT SINUS NODE; DIASTOLIC DEPOLARIZATION; ELECTRICAL-ACTIVITY; RYANODINE RECEPTOR; PACEMAKER ACTIVITY; NA+-CA2+ EXCHANGER; CA2+; EXPRESSION; RELEASE AB Spontaneous, localized, rhythmic ryanodine receptor (RyRs) Ca2+ releases occur beneath the cell membrane during late diastolic depolarization in cardiac sinoatrial nodal cells (SANCs). These activate the Na+/Ca2+ exchanger (NCX1) to generate inward current and membrane excitation that drives normal spontaneous beating. The morphological background for the proposed functional of RyR and NCX crosstalk, however, has not been demonstrated. Here we show that the average isolated SANC whole cell labeling density of RyRs and SERCA2 is similar to atrial and ventricle myocytes, and is similar among SANCs of all sizes. Labeling of NCX1 is also similar among SANCs of all sizes and exceeds that in atrial and ventricle myocytes. Submembrane colocalization of NCX1 and cardiac RyR (cRyR) in all SANCs exceeds that in the other cell types. Further, the Cx43 negative primary pacemaker area of the intact rabbit sinoatrial node (SAN) exhibits robust positive labeling for cRyR, NCX1, and SERCA2. Functional studies in isolated SANCs show that neither the average action potential (AP) characteristics, nor those of intracellular Ca2+ releases, nor the spontaneous cycle length vary with cell size. Chelation of intracellular [Ca2+], or disabling RyRs or NCX1, markedly attenuates or abolishes spontaneous SANC beating in all SANCs. Thus, there is dense labeling of SERCA2, RyRs, and NCX1 in small-sized SANCs, thought to reside within the SAN center, the site of impulse initiation. Because normal automaticity of these cells requires intact Ca2+ cycling, interactions of SERCA, RyR2 and NCX molecules are implicated in the initiation of the SAN impulse. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Manchester, Div Cardiovasc & Endocrine Sci, Manchester M13 9XX, Lancs, England. RP Lakatta, EG (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM LakattaE@grc.nia.nih.gov OI Dobrzynski, Halina/0000-0003-4754-5975 FU Intramural NIH HHS NR 27 TC 52 Z9 53 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 22 PY 2007 VL 100 IS 12 BP 1723 EP 1731 DI 10.1161/CIRCRESAHA.107.153676 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 182UZ UT WOS:000247530800008 PM 17525366 ER PT J AU Mies, F Spriet, C Heliot, L Sariban-Sohraby, S AF Mies, Frederique Spriet, Corentin Heliot, Laurent Sariban-Sohraby, Sarah TI Epithelial Na+ channel stimulation by n-3 fatty acids requires proximity to a membrane-bound A-kinase-anchoring protein complexed with protein kinase A and phosphodiesterase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARACHIDONIC-ACID; LIVING CELLS; CA2+ CURRENT; CAMP; CURRENTS; ACTIVATION; PHOSPHORYLATION; AQUAPORIN-2; INHIBITION; TRANSPORT AB Essential polyunsatured fatty acids have been shown to modulate enzymes, channels and transporters, to interact with lipid bilayers and to affect metabolic pathways. We have previously shown that eicosapentanoic acid (EPA, C20:5, n-3) activates epithelial sodium channels (ENaCs) in a cAMP-dependent manner involving stimulation of cAMP-dependent protein kinase (PKA). In the present study, we explored further the mechanism of EPA stimulation of ENaC in A6 cells. Fluorescence resonance energy transfer experiments confirmed activation of PKA by EPA. Consistent with our previous studies, EPA had no further stimulatory effect on amiloride-sensitive transepithelial current (I-Na) in the presence of CPT-cAMP. Thus, we investigated the effect of EPA on cellular pathways which produce cAMP. EPA did not stimulate adenylate cyclase activity or total cellular cAMP accumulation. However, membrane-bound phosphodiesterase activity was inhibited by EPA from 2.46 pmol/mg of protein/min to 1.3 pmol/mg of protein/min. To investigate the potential role of an A-kinase-anchoring protein (AKAP), we used HT31, an inhibitor of the binding between PKA and AKAPs as well as cerulenin, an inhibitor of myristoylation and palmitoylation. Both agents prevented the stimulatory effect of EPA and CPT-cAMP on I-Na and drastically decreased the amount of PKA in the apical membrane. Colocalization experiments in A6 cells cotransfected with fluorescently labeled ENaC beta subunit and PKA regulatory subunit confirmed the close proximity of the two proteins and the membrane anchorage of PKA. Last, in A6 cells transfected with a dead mutant of Sgk, an enzyme which up-regulates ENaCs, EPA did not stimulate Na+ current. Our results suggest that stimulation of ENaCs by EPA occurs via SGK in membrane-bound compartments containing an AKAP, activated PKA, and a phosphodiesterase. C1 Univ Libre Bruxelles, Dept Phys, B-1070 Brussels, Belgium. Interdisciplinary Res Inst, Biophoton Cellulaire Fonctionnelle, F-59021 Lille, France. RP Sariban-Sohraby, S (reprint author), NIH, Bldg 31,Rm 6A22, Bethesda, MD 20892 USA. EM sohrabys@nei.nih.gov NR 39 TC 11 Z9 11 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 22 PY 2007 VL 282 IS 25 BP 18339 EP 18347 DI 10.1074/jbc.M611160200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 179PK UT WOS:000247302000040 PM 17478424 ER PT J AU Voloshin, ON Camerini-Otero, RD AF Voloshin, Oleg N. Camerini-Otero, R. Daniel TI The DinG protein from Escherichia coli is a structure-specific helicase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPLICATION FORK REVERSAL; DNA SUBSTRATE-SPECIFICITY; T-ANTIGEN HELICASE; SACCHAROMYCES-CEREVISIAE; BRANCH MIGRATION; HOMOLOGOUS RECOMBINATION; XERODERMA-PIGMENTOSUM; LEXA REPRESSOR; RECG HELICASE; GENE ENCODES AB The Escherichia coli DinG protein is a DNA damage-inducible member of the helicase superfamily 2. Using a panel of synthetic substrates, we have systematically investigated structural requirements for DNA unwinding by DinG. We have found that the helicase does not unwind blunt-ended DNAs or substrates with 3'-ss tails. On the other hand, the 5'-ss tails of 11-15 nucleotides are sufficient to initiate DNA duplex unwinding; bifurcated substrates further facilitate helicase activity. DinG is active on 5'-flap structures; however, it is unable to unwind 3'-flaps. Similarly to the homologous Saccharomyces cerevisiae Rad3 helicase, DinG unwinds DNA.RNA duplexes. DinG is active on synthetic D-loops and R-loops. The ability of the enzyme to unwind D-loops formed on superhelical plasmid DNA by the E. coli recombinase RecA suggests that D-loops may be natural substrates for DinG. Although the availability of 5'-ssDNA tails is a strict requirement for duplex unwinding by DinG, the unwinding of D-loops can be initiated on substrates without any ss tails. Since DinG is DNA damage-inducible and is active on D-loops and forked structures, which mimic intermediates of homologous recombination and replication, we conclude that this helicase may be involved in recombinational DNA repair and the resumption of replication after DNA damage. C1 NIDDK, NIH, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), Genet & Biochem Branch, 5 Mem Dr,Rm 201,MSC 0538, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov NR 69 TC 36 Z9 37 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 22 PY 2007 VL 282 IS 25 BP 18437 EP 18447 DI 10.1074/jbc.M700376200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 179PK UT WOS:000247302000050 PM 17416902 ER PT J AU Hwang, J Kalinin, A Hwang, M Anderson, DE Kim, MJ Stojadinovic, O Tomic-Canic, M Lee, SH Morasso, MI AF Hwang, Joonsung Kalinin, Alexandr Hwang, Meeyul Anderson, D. Eric Kim, Min Jung Stojadinovic, Olivera Tomic-Canic, Marjana Lee, Seung Hun Morasso, Maria I. TI Role of scarf and its binding target proteins in epidermal calcium homeostasis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CUTANEOUS BARRIER FUNCTION; CALMODULIN-LIKE PROTEIN; ENDOPLASMIC-RETICULUM; GROWTH-INHIBITION; MEMBRANE DYNAMICS; S100 PROTEINS; DIFFERENTIATION; EXPRESSION; LOCALIZATION; ANNEXINS AB The novel Ca2+-binding protein, Scarf ( skin calmodulin-related factor) belongs to the calmodulin-like protein family and is expressed in the differentiated layers of the epidermis. To determine the roles of Scarf during stratification, we set out to identify the binding target proteins by affinity chromatography and subsequent analysis by mass spectrometry. Several binding factors, including 14-3-3s, annexins, calreticulin, ERp72 ( endoplasmic reticulum protein 72), and nucleolin, were identified, and their interactions with Scarf were corroborated by co-immunoprecipitation and co-localization analyses. To further understand the functions of Scarf in epidermis in vivo, we altered the epidermal Ca2+ gradient by acute barrier disruption. The change in the expression levels of Scarf and its binding target proteins were determined by immunohistochemistry and Western blot analysis. The expression of Scarf, annexins, calreticulin, and ERp72 were up-regulated by Ca2+ gradient disruption, whereas the expression of 14-3-3s and nucleolin was reduced. Because annexins, calreticulin, and ERp72 have been implicated in Ca2+-induced cellular trafficking, including the secretion of lamellar bodies and Ca2+ homeostasis, we propose that the interaction of Scarf with these proteins might be crucial in the process of barrier restoration. On the other hand, down-regulation of 14-3-3s and nucleolin is potentially involved in the process of keratinocyte differentiation and growth inhibition. The calcium-dependent localization and up-regulation of Scarf and its binding target proteins were studied in mouse keratinocytes treated with ionomycin and during the wound-healing process. We found increased expression and nuclear presence of Scarf in the epidermis of the wound edge 4 and 7 days post-wounding, entailing the role of Scarf in barrier restoration. Our results suggest that Scarf plays a critical role as a Ca2+ sensor, potentially regulating the function of its binding target proteins in a Ca2+-dependent manner in the process of restoration of epidermal Ca2+ gradient as well as during epidermal barrier formation. C1 NIAMS, NIH, Dev Skin Biol Unit, Bethesda, MD 20892 USA. NIDDK, NIH, Proteom & Mass Spectrometry Fac, Bethesda, MD 20892 USA. Yonsei Univ, Coll Med, Dept Dermatol, Seoul 135720, South Korea. Cornell Univ, Weill Med Coll, Dept Dermatol, New York, NY 10021 USA. RP Morasso, MI (reprint author), NIAMS, NIH, Dev Skin Biol Unit, Bldg 50,Rm1525, Bethesda, MD 20892 USA. EM morassom@mail.nih.gov FU Intramural NIH HHS NR 54 TC 10 Z9 10 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 22 PY 2007 VL 282 IS 25 BP 18645 EP 18653 DI 10.1074/jbc.M702035200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 179PK UT WOS:000247302000069 PM 17470426 ER PT J AU Waterhouse, RM Kriventseva, EV Meister, S Xi, ZY Alvarez, KS Bartholomay, LC Barillas-Mury, C Bian, GW Blandin, S Christensen, BM Dong, YM Jiang, HB Kanost, MR Koutsos, AC Levashina, EA Li, JY Ligoxygakis, P MacCallum, RM Mayhew, GF Mendes, A Michel, K Osta, MA Paskewitz, S Shin, SW Vlachou, D Wang, LH Wei, WQ Zheng, LB Zou, Z Severson, DW Raikhel, AS Kafatos, FC Dimopoulos, G Zdobnov, EM Christophides, GK AF Waterhouse, Robert M. Kriventseva, Evgenia V. Meister, Stephan Xi, Zhiyong Alvarez, Kanwal S. Bartholomay, Lyric C. Barillas-Mury, Carolina Bian, Guowu Blandin, Stephanie Christensen, Bruce M. Dong, Yuemei Jiang, Haobo Kanost, Michael R. Koutsos, Anastasios C. Levashina, Elena A. Li, Jianyong Ligoxygakis, Petros MacCallum, Robert M. Mayhew, George F. Mendes, Antonio Michel, Kristin Osta, Mike A. Paskewitz, Susan Shin, Sang Woon Vlachou, Dina Wang, Lihui Wei, Weiqi Zheng, Liangbiao Zou, Zhen Severson, David W. Raikhel, Alexander S. Kafatos, Fotis C. Dimopoulos, George Zdobnov, Evgeny M. Christophides, George K. TI Evolutionary dynamics of immune-related genes and pathways in disease-vector mosquitoes SO SCIENCE LA English DT Article ID ANOPHELES-GAMBIAE; AEDES-AEGYPTI; DROSOPHILA-MELANOGASTER; SERINE PROTEASES; ANTIVIRAL RESPONSE; SEPHADEX BEADS; PLASMODIUM; MELANIZATION; PHAGOCYTOSIS; ACTIVATION AB Mosquitoes are vectors of parasitic and viral diseases of immense importance for public health. The acquisition of the genome sequence of the yellow fever and Dengue vector, Aedes aegypti (Aa), has enabled a comparative phylogenomic analysis of the insect immune repertoire: in Aa, the malaria vector Anopheles gambiae (Ag), and the fruit fly Drosophila melanogaster (Dm). Analysis of immune signaling pathways and response modules reveals both conservative and rapidly evolving features associated with different functional gene categories and particular aspects of immune reactions. These dynamics reflect in part continuous readjustment between accommodation and rejection of pathogens and suggest how innate immunity may have evolved. C1 Univ Geneva, Sch Med, Dept Struct Biol & Bioinformat, CH-1211 Geneva, Switzerland. Univ London Imperial Coll Sci Technol & Med, Fac Nat Sci, Div Cell & Mol Biol, London SW7 2AZ, England. Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Univ Calif Riverside, Dept Entomol, Riverside, CA 92521 USA. Univ Calif Riverside, Inst Integrat Genome Biol, Riverside, CA 92521 USA. Iowa State Univ, Dept Entomol, Ames, IA 50011 USA. NIAID, Lab Malaria & Vector Res, Twinbrook II Facil, NIH, Bethesda, MD 20892 USA. CNRS, Unite Propre Rech 9022, Avnir INSERM, Inst Mol & Cellulaire, Strasbourg, France. Univ Wisconsin, Dept Anim Hlth & Biomed Sci, Madison, WI 53706 USA. Oklahoma State Univ, Dept Entomol & Plant Pathol, Stillwater, OK 74078 USA. Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA. Virginia Tech, Dept Biochem, Blacksburg, VA 24061 USA. Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. Univ Wisconsin, Dept Entomol, Madison, WI 53706 USA. Yale Univ, Sch Med Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Fujian Ctr Prevent & Control Occupat Dis & Chem P, Fuzhou, Fujian, Peoples R China. Inst Plant Physiol & Ecol, Shanghai, Peoples R China. Univ Notre Dame, Ctr Global Hlth & Infect Dis, Dept Biol Sci, Notre Dame, IN 46556 USA. Swiss Inst Bioinformat, CH-1211 Geneva, Switzerland. RP Kafatos, FC (reprint author), Univ Geneva, Sch Med, Dept Struct Biol & Bioinformat, CH-1211 Geneva, Switzerland. EM f.kafatos@imperial.ac.uk; zdobnov@medecine.unige.ch; g.christophides@imperial.ac.uk RI Jiang, Haobo/A-6519-2008; Bian, Guowu /B-1572-2010; Michel, Kristin/F-3400-2011; Zdobnov, Evgeny/K-1133-2012; Meister, Stephan/M-6608-2014; Mayhew, George/B-4042-2016; zou, zhen/C-6134-2016; Waterhouse, Robert/A-1858-2010; Blandin, Stephanie/I-2786-2016; OI Dimopoulos, George/0000-0001-6755-8111; Christophides, George/0000-0002-3323-1687; Levashina, Elena/0000-0003-4605-906X; Shin, Sang Woon/0000-0001-9467-0803; Meister, Stephan/0000-0003-2436-7037; Mayhew, George/0000-0003-0609-6018; zou, zhen/0000-0003-3550-7656; Waterhouse, Robert/0000-0003-4199-9052; M. Mendes, Antonio/0000-0001-6562-5325; MacCallum, Robert/0000-0001-5070-4493; Vlachou, Dina/0000-0002-8305-3014 FU Medical Research Council [G0300170]; NIAID NIH HHS [1 R01 AI059492-01A1, 5 R01 AI61576-2, P01 AI044220-06A1, R01 AI037083]; NIGMS NIH HHS [GM41247, R01 GM058634, R01 GM058634-09]; Wellcome Trust [GR077229MA] NR 42 TC 283 Z9 298 U1 9 U2 62 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 22 PY 2007 VL 316 IS 5832 BP 1738 EP 1743 DI 10.1126/science.1139862 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 180XE UT WOS:000247400500045 PM 17588928 ER PT J AU Downs, JA Nussenzweig, MC Nussenzweig, A AF Downs, Jessica A. Nussenzweig, Michel C. Nussenzweig, Andre TI Chromatin dynamics and the preservation of genetic information SO NATURE LA English DT Review ID DOUBLE-STRAND BREAKS; CLASS-SWITCH RECOMBINATION; DNA-DAMAGE-RESPONSE; CEREVISIAE HISTONE H2A; SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; REMODELING COMPLEX; ATM ACTIVATION; MRE11-RAD50-NBS1 COMPLEX; HOMOLOGOUS RECOMBINATION AB The integrity of the genome is frequently challenged by double-strand breaks in the DNA. Defects in the cellular response to double-strand breaks are a major cause of cancer and other age-related pathologies; therefore, much effort has been directed at understanding the enzymatic mechanisms involved in recognizing, signalling and repairing double-strand breaks. Recent work indicates that chromatin - the fibres into which DNA is packaged with a proteinaceous structural polymer - has an important role in initiating, propagating and terminating this cellular response to DNA damage. C1 Univ Sussex, MRC, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Downs, JA (reprint author), Univ Sussex, MRC, Genome Damage & Stabil Ctr, Brighton BN1 9RQ, E Sussex, England. EM j.a.downs@sussex.ac.uk; andre_nussenzweig@nih.gov OI Downs, Jessica/0000-0002-6600-849X FU Intramural NIH HHS NR 98 TC 197 Z9 201 U1 0 U2 21 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 21 PY 2007 VL 447 IS 7147 BP 951 EP 958 DI 10.1038/nature05980 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 180NU UT WOS:000247373100037 PM 17581578 ER PT J AU Isaac, JTR Ashby, M McBain, CJ AF Isaac, John T. R. Ashby, Michael McBain, Chris J. TI The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity SO NEURON LA English DT Review ID LONG-TERM POTENTIATION; CALCIUM-PERMEABLE AMPA; IONOTROPIC GLUTAMATE RECEPTORS; INTERNEURON DIVERSITY SERIES; DOMAIN-CONTAINING PROTEINS; KINASE-C-ALPHA; HIPPOCAMPAL-NEURONS; CA2+-PERMEABLE AMPA; IN-VIVO; NEOCORTICAL NEURONS AB The AMPA receptor (AMPAR) GluR2 subunit dictates the critical biophysical properties of the receptor, strongly influences receptor assembly and trafficking, and plays pivotal roles in a number of forms of long-term synaptic plasticity. Most neuronal AMPARs contain this critical subunit; however, in certain restricted neuronal populations and under certain physiological or pathological conditions, AMPARs that lack this subunit are expressed. There is a current surge of interest in such GluR2-lacking Ca2(+)-permeable AMPARs in how they affect the regulation of synaptic transmission. Here, we bring together recent data highlighting the novel and important roles of GluR2 in synaptic function and plasticity. C1 NINDS, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Isaac, JTR (reprint author), NINDS, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM isaacj@ninds.nih.gov FU Intramural NIH HHS NR 152 TC 353 Z9 366 U1 2 U2 36 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 21 PY 2007 VL 54 IS 6 BP 859 EP 871 DI 10.1016/j.neuron.2007.06.001 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 184MK UT WOS:000247645600007 PM 17582328 ER PT J AU Kim, JY Jung, SC Clemens, AM Petralia, RS Hoffman, DA AF Kim, Jinhyun Jung, Sung-Cheri Clemens, Ann M. Petralia, Ronald S. Hoffman, Dax A. TI Regulation of dendritic excitability by activity-dependent trafficking of the A-type K+ channel subunit Kv4.2 in hippocampal neurons SO NEURON LA English DT Article ID CA1 PYRAMIDAL NEURONS; IONOTROPIC GLUTAMATE RECEPTORS; TEMPORAL-LOBE EPILEPSY; LONG-TERM DEPRESSION; AMPA RECEPTORS; SYNAPTIC PLASTICITY; POTASSIUM CHANNELS; NMDA RECEPTORS; DIFFERENTIAL EXPRESSION; EXCITATORY SYNAPSES AB Voltage-gated A-type K+ channel Kv4.2 sub-units are highly expressed in the dendrites of hippocampal CA1 neurons. However, little is known about the subcellular distribution and trafficking of Kv4.2-containing channels. Here we provide evidence for activity-dependent trafficking of Kv4.2 in hippocampal spines and dendrites. Live imaging and electrophysiological recordings showed that Kv4.2 internalization is induced rapidly upon glutamate receptor stimulation. Kv4.2 internalization was clathrin mediated and required NMDA receptor activation and Ca2+ influx. In dissociated hippocampal neurons, mEPSC amplitude depended on functional Kv4.2 expression level and was enhanced by stimuli that induced Kv4.2 internalization. Long-term potentiation (LTP) induced by brief glycine application resulted in synaptic insertion of GluR1-containing AMPA receptors along with Kv4.2 internalization. We also found evidence of Kv4.2 internalization upon synaptically evoked LTP in CA1 neurons of hippocampal slice cultures. These results present an additional mechanism for synaptic integration and plasticity through the activity-dependent regulation of Kv4.2 channel surface expression. C1 NICHHD, Mol Neurophysiol & Biophys Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. NIDCD, Sect Neurotransmitter Receptor Biol, NIH, Bethesda, MD 20892 USA. RP Kim, JY (reprint author), NICHHD, Mol Neurophysiol & Biophys Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. EM kimji@mail.nih.gov; hoffmand@mail.nih.gov RI Hoffman, Dax/E-5155-2011 OI Hoffman, Dax/0000-0001-6999-2157 FU Intramural NIH HHS [Z01 HD008755-05, Z99 HD999999] NR 56 TC 191 Z9 193 U1 2 U2 14 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD JUN 21 PY 2007 VL 54 IS 6 BP 933 EP 947 DI 10.1016/j.neuron.2007.05.026 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 184MK UT WOS:000247645600012 PM 17582333 ER PT J AU Manson, JE Allison, MA Rossouw, JE Carr, JJ Langer, RD Hsia, J Kuller, LH Cochrane, BB Hunt, JR Ludlam, SE Pettinger, MB Gass, M Margolis, KL Nathan, L Ockene, JK Prentice, RL Robbins, J Stefanick, ML Rossouw, JE Ludlam, S Cochrane, BB Hunt, JR Lund, B Prentice, R Carr, JJ O'Rourke, C Du, L Pillsbury, S Hightower, C Ellison, R Tan, J Wassertheil-Smoller, S Magnani, M Noble, DH Dellicarpini, T Manson, JE Bueche, M McGinnis, AD Rybicki, FJ Assaf, AR Sloane, G Phillips, LS Butler, V Huber, M Vitali, J Hsia, J LeBrun, C Palm, R Embersit, D Whitlock, E Arnold, K Sidney, S Cantrell, V Kotchen, JM Feltz, C Howard, BV Thomas-Geevarghese, A Boggs, G Jelinick, JS Greenland, P Neuman, A Carlson-Lund, G Giovanazzi, SM Stefanick, ML Swope, S Jackson, R Toussant, K Lewis, CE Pierce, P Stallings, C Wactawski-Wende, J Goel, S Laughlin, R Robbins, J Zaragoza, S Macias, D Belisle, D Nathan, L Voigt, B Goldin, J Woo, M Langer, RD Allison, MA Lien, X Wright, CM Gass, M Sheridan, S Robinson, JG Feddersen, D Kelly-Brake, K Carroll, J Ockene, J Churchill, L Lasser, NL Miller, B Maldjian, PD Pierre-Louis, J Fishman, J O'Sullivan, MJ Fernandez, D Margolis, KL Bjerk, CL Truwit, C Hearity, JA Hyslop, WB Darroch, K Murphy, C Heiss, G Kuller, LH Edmundowicz, D Ives, D Johnson, KC Satterfield, S Connelly, SA Jones, EL Brzyski, R Nashawati, MA Torchia, S Rodriguez, A Garza, R Nentwich, P Sarto, GE Broderick, L Sweitzer, NK Nabel, E Rossouw, JE Ludlam, SE Pottern, L McGowan, J Ford, L Geller, N Prentice, RL Anderson, G LaCroix, A Kooperberg, CL Patterson, RE McTiernan, A Shumaker, S Stein, E Cummings, S Wassertheil-Smoller, S Hays, J Manson, JE Assaf, AR Phillips, L Beresford, S Hsia, J Chlebowski, R Whitlock, E Caan, B Kotchen, JM Howard, BV Van Horn, L Black, H Stefanick, ML Lane, D Jackson, R Lewis, CE Bassford, T Wactawski-Wende, J Robbins, J Hubbell, FA Judd, H Langer, RD Gass, M Limacher, M Curb, D Wallace, R Ockene, J Lasser, N O'Sullivan, MJ Margolis, KL Brunner, R Heiss, G Kuller, LH Johnson, KC Brzyski, R Sarto, GE Bonds, D Hendrix, S AF Manson, JoAnn E. Allison, Matthew A. Rossouw, Jacques E. Carr, J. Jeffrey Langer, Robert D. Hsia, Judith Kuller, Lewis H. Cochrane, Barbara B. Hunt, Julie R. Ludlam, Shari E. Pettinger, Mary B. Gass, Margery Margolis, Karen L. Nathan, Lauren Ockene, Judith K. Prentice, Ross L. Robbins, John Stefanick, Marcia L. Rossouw, J. E. Ludlam, S. Cochrane, B. B. Hunt, J. R. Lund, B. Prentice, R. Carr, J. J. O'Rourke, C. Du, L. Pillsbury, S. Hightower, C. Ellison, R. Tan, J. Wassertheil-Smoller, S. Magnani, M. Noble, D. H. Dellicarpini, T. Manson, J. E. Bueche, M. McGinnis, A. D. Rybicki, F. J. Assaf, A. R. Sloane, G. Phillips, L. S. Butler, V. Huber, M. Vitali, J. Hsia, J. LeBrun, C. Palm, R. Embersit, D. Whitlock, E. Arnold, K. Sidney, S. Cantrell, V. Kotchen, J. M. Feltz, C. Howard, B. V. Thomas-Geevarghese, A. Boggs, G. Jelinick, J. S. Greenland, P. Neuman, A. Carlson-Lund, G. Giovanazzi, S. M. Stefanick, M. L. Swope, S. Jackson, R. Toussant, K. Lewis, C. E. Pierce, P. Stallings, C. Wactawski-Wende, J. Goel, S. Laughlin, R. Robbins, J. Zaragoza, S. Macias, D. Belisle, D. Nathan, L. Voigt, B. Goldin, J. Woo, M. Langer, R. D. Allison, M. A. Lien, X. Wright, C. M. Gass, M. Sheridan, S. Robinson, J. G. Feddersen, D. Kelly-Brake, K. Carroll, J. Ockene, J. Churchill, L. Lasser, N. L. Miller, B. Maldjian, P. D. Pierre-Louis, J. Fishman, J. O'Sullivan, M. J. Fernandez, D. Margolis, K. L. Bjerk, C. L. Truwit, C. Hearity, J. A. Hyslop, W. B. Darroch, K. Murphy, C. Heiss, G. Kuller, L. H. Edmundowicz, D. Ives, D. Johnson, K. C. Satterfield, S. Connelly, S. A. Jones, E. L. Brzyski, R. Nashawati, M. A. Torchia, S. Rodriguez, A. Garza, R. Nentwich, P. Sarto, G. E. Broderick, L. Sweitzer, N. K. Nabel, E. Rossouw, J. E. Ludlam, S. E. Pottern, L. McGowan, J. Ford, L. Geller, N. Prentice, R. L. Anderson, G. LaCroix, A. Kooperberg, C. L. Patterson, R. E. McTiernan, A. Shumaker, S. Stein, E. Cummings, S. Wassertheil-Smoller, S. Hays, J. Manson, J. E. Assaf, A. R. Phillips, L. Beresford, S. Hsia, J. Chlebowski, R. Whitlock, E. Caan, B. Kotchen, J. M. Howard, B. V. Van Horn, L. Black, H. Stefanick, M. L. Lane, D. Jackson, R. Lewis, C. E. Bassford, T. Wactawski-Wende, J. Robbins, J. Hubbell, F. A. Judd, H. Langer, R. D. Gass, M. Limacher, M. Curb, D. Wallace, R. Ockene, J. Lasser, N. O'Sullivan, M. J. Margolis, K. L. Brunner, R. Heiss, G. Kuller, L. H. Johnson, K. C. Brzyski, R. Sarto, G. E. Bonds, D. Hendrix, S. CA WHI WHI-CACS Investigators TI Estrogen therapy and coronary-artery calcification SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID POSTMENOPAUSAL HORMONE-THERAPY; RANDOMIZED CONTROLLED-TRIAL; ELECTRON-BEAM TOMOGRAPHY; COMPUTED-TOMOGRAPHY; REPLACEMENT THERAPY; HEART-DISEASE; CLINICAL-TRIAL; CALCIUM; WOMEN; ATHEROSCLEROSIS AB Background: Calcified plaque in the coronary arteries is a marker for atheromatous-plaque burden and is predictive of future risk of cardiovascular events. We examined the relationship between estrogen therapy and coronary-artery calcium in the context of a randomized clinical trial. Methods: In our ancillary substudy of the Women's Health Initiative trial of conjugated equine estrogens (0.625 mg per day) as compared with placebo in women who had undergone hysterectomy, we performed computed tomography of the heart in 1064 women aged 50 to 59 years at randomization. Imaging was conducted at 28 of 40 centers after a mean of 7.4 years of treatment and 1.3 years after the trial was completed (8.7 years after randomization). Coronary-artery calcium (or Agatston) scores were measured at a central reading center without knowledge of randomization status. Results: The mean coronary-artery calcium score after trial completion was lower among women receiving estrogen (83.1) than among those receiving placebo (123.1) (P=0.02 by rank test). After adjustment for coronary risk factors, the multivariate odds ratios for coronary-artery calcium scores of more than 0, 10 or more, and 100 or more in the group receiving estrogen as compared with placebo were 0.78 (95% confidence interval, 0.58 to 1.04), 0.74 (0.55 to 0.99), and 0.69 (0.48 to 0.98), respectively. The corresponding odds ratios among women with at least 80% adherence to the study estrogen or placebo were 0.64 (P=0.01), 0.55 (P<0.001), and 0.46 (P=0.001). For coronary-artery calcium scores of more than 300 (vs. <10), the multivariate odds ratio was 0.58 (P=0.03) in an intention-to-treat analysis and 0.39 (P=0.004) among women with at least 80% adherence. Conclusions: Among women 50 to 59 years old at enrollment, the calcified-plaque burden in the coronary arteries after trial completion was lower in women assigned to estrogen than in those assigned to placebo. However, estrogen has complex biologic effects and may influence the risk of cardiovascular events and other outcomes through multiple pathways. (ClinicalTrials.gov number, NCT00000611.). C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Geisinger Hlth Syst, Danville, PA USA. George Washington Univ, Washington, DC USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Cincinnati, Cincinnati, OH USA. Healthpartners Res Fdn, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif Los Angeles, Los Angeles, CA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Univ Calif Davis, Sacramento, CA 95817 USA. Stanford Univ, Palo Alto, CA 94304 USA. RP Manson, JE (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, 900 Commonwealth Ave E,3rd Fl, Boston, MA 02215 USA. EM jmanson@rics.bwh.harvard.edu RI Carr, John/A-1938-2012; OI Carr, John/0000-0002-4398-8237; Allison, Matthew/0000-0003-0777-8272 NR 41 TC 374 Z9 392 U1 0 U2 8 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 JUN 21 PY 2007 VL 356 IS 25 BP 2591 EP 2602 DI 10.1056/NEJMoa071513 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 180GN UT WOS:000247351200006 PM 17582069 ER PT J AU Dawson, DW Hong, JS Shen, RR French, SW Troke, JJ Wu, YZ Chen, SS Gui, D Regelson, M Marahrens, Y Morse, HC Said, J Plass, C Teitell, MA AF Dawson, D. W. Hong, J. S. Shen, R. R. French, S. W. Troke, J. J. Wu, Y-Z Chen, S-S Gui, D. Regelson, M. Marahrens, Y. Morse, H. C., III Said, J. Plass, C. Teitell, M. A. TI Global DNA methylation profiling reveals silencing of a secreted form of Epha7 in mouse and human germinal center B-cell lymphomas SO ONCOGENE LA English DT Article DE DNA methylation; B-cell lymphoma; TCL1 ID CHRONIC LYMPHOCYTIC-LEUKEMIA; COLORECTAL-CANCER; TCL1 EXPRESSION; RECEPTORS; EPHRINS; GENE; HYPERMETHYLATION; MALIGNANCIES; ADHESION; TISSUES AB Most human lymphomas originate from transformed germinal center (GC) B lymphocytes. While activating mutations and translocations of MYC, BCL2 and BCL6 promote specific GC lymphoma subtypes, other genetic and epigenetic modi. cations that contribute to malignant progression in the GC remain poorly defined. Recently, aberrant expression of the TCL1 proto-oncogene was identified in major GC lymphoma subtypes. TCL1 transgenic mice offer unique models of both aggressive GC and marginal zone B-cell lymphomas, further supporting a role for TCL1 in B-cell transformation. Here, restriction landmark genomic scanning was employed to discover tumor-associated epigenetic alterations in malignant GC and marginal zone B-cells in TCL1 transgenic mice. Multiple genes were identified that underwent DNA hypermethylation and decreased expression in TCL1 transgenic tumors. Further, we identified a secreted isoform of EPHA7, a member of the Eph family of receptor tyrosine kinases that are able to influence tumor invasiveness, metastasis and neovascularization. EPHA7 was hypermethylated and repressed in both mouse and human GC B-cell non-Hodgkin lymphomas, with the potential to influence tumor progression and spread. These data provide the first set of hypermethylated genes with the potential to complement TCL1-mediated GC B-cell transformation and spread. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA. Ohio State Univ, Div Human Canc Genet, Columbus, OH 43210 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA USA. NIAID, Natl Inst Hlth, Immunopathol Lab, Rockville, MD USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Stem Cell Biol & Med, Los Angeles, CA USA. Univ Calif Los Angeles, Calif Nanosyst Inst, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Cell Mimet Studies, Los Angeles, CA USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Teitell, MA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, 10833 LeConte Ave,Mail Code 173216, Los Angeles, CA 90095 USA. EM mteitell@ucla.edu RI Plass, Christoph/H-7192-2014; Dawson, David/I-5917-2014; OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS; NCI NIH HHS [T32CA009120, R01 CA107300, T32CA09056, T32 CA009120, T32 CA009056, R01 CA090571]; NEI NIH HHS [PN2 EY018228-02, PN2 EY018228]; NICHD NIH HHS [HD041451, R01 HD041451]; NIGMS NIH HHS [R01GM073981, R01 GM073981]; PHS HHS [T32A107126] NR 41 TC 23 Z9 32 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 21 PY 2007 VL 26 IS 29 BP 4243 EP 4252 DI 10.1038/sj.onc.1210211 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 184CY UT WOS:000247619900007 PM 17260020 ER PT J AU Chong, SY Egan, MA Kutzler, MA Megati, S Masood, A Roopchard, V Garcia-Hand, D Montefiori, DC Quiroz, J Rosati, M Schadeck, EB Boyer, JD Pavlakis, GN Weiner, DB Sidhu, M Eldridge, JH Israel, ZR AF Chong, Siew-Yen Egan, Michael A. Kutzler, Michele A. Megati, Shakuntala Masood, Amjed Roopchard, Vidia Garcia-Hand, Dorys Montefiori, David C. Quiroz, Jorge Rosati, Margherita Schadeck, Eva B. Boyer, Jean D. Pavlakis, George N. Weiner, David B. Sidhu, Maninder Eldridge, John H. Israel, Zimra R. TI Comparative ability of plasmid IL-12 and IL-15 to enhance cellular and humoral immune responses elicited by a SIVgag plasmid DNA vaccine and alter disease progression following SHIV89.6P challenge in rhesus macaques SO VACCINE LA English DT Article DE AIDS; vaccination; cytokines; SHIV89.6P ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD8(+) T-CELLS; IN-VIVO; ANTIBODY-RESPONSES; SEQUENTIAL IMMUNIZATION; RECOMBINANT PROTEIN; PRIMARY INFECTION; DENDRITIC CELLS; NATURAL-KILLER; MALARIA DNA AB Plasmid-based IL-12 has been demonstrated to successfully enhance the immunogenicity of DNA vaccines, thus enabling a reduction of the amount of DNA required for immunization. IL-15 is thought to affect the maintenance and enhance effector function of CD8(+) memory T cells. Since the ability to elicit a long-term memory response is a desirable attribute of a prophylactic vaccine, we sought to evaluate the ability of these plasmid-based cytokines to serve as vaccine adjuvants in rhesus macaques. Macaques were immunized with plasmid DNA encoding SIVgag in combination with plasmid IL-12, IL-15, or a combination of IL-12 and IL-15. The plasmid-based cytokines were monitored for their ability to augment SIVgag-specific cellular and humoral immune responses and to alter the clinical outcome following pathogenic SHIV89.6P challenge. Macaques receiving SIVgag pDNA in combination with plasmid IL-12 alone, or in combination with plasmid IL-12 and IL-15, demonstrated significantly elevated cell-mediated and humoral immune responses resulting in an improved clinical outcome following virus challenge compared to macaques receiving SIVgag pDNA alone. Macaques receiving SIVgag pDNA in combination with plasmid IL-15 alone demonstrated minor increases in cell-mediated and humoral immune responses, however, the clinical outcome following virus challenge was not improved. These results have important implications for the continued development of plasmid DNA vaccines for the prevention of HIV-1 infection. (c) 2007 Elsevier Ltd. All rights reserved. C1 Wyeth Vaccines Discovery, Pearl River, NY 10965 USA. Biometr Res, Pearl River, NY 10965 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NCI, Basic Res Lab, Human Retrovirus Sect, Frederick, MD 21702 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Chong, SY (reprint author), Wyeth Vaccines Discovery, 401N Middletown Rd,Bldg 180-214-04, Pearl River, NY 10965 USA. EM chongs@wyeth.com RI Weiner, David/H-8579-2014 FU NIAID NIH HHS [N01 AI 05397] NR 52 TC 61 Z9 61 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 21 PY 2007 VL 25 IS 26 BP 4967 EP 4982 DI 10.1016/j.vaccine.2006.11.070 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 183BJ UT WOS:000247547400013 PM 17335943 ER PT J AU Newell, ML Huang, S Fiore, S Thorne, C Mandelbrot, L Sullivan, JL Maupin, R Delke, I Watts, DH Gelber, RD Cunningham, CK AF Newell, Marie-Louise Huang, Sharon Fiore, Simona Thorne, Claire Mandelbrot, Laurent Sullivan, John L. Maupin, Robert Delke, Isaac Watts, D. Heather Gelber, Richard D. Cunningham, Coleen K. CA PACTG 316 Study Team TI Characteristics and management of HIV-1-infected pregnant women enrolled in a randomised trial: differences between Europe and the USA SO BMC INFECTIOUS DISEASES LA English DT Article ID MOTHER-TO-CHILD; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; PERINATAL HIV-1 TRANSMISSION; MATERNAL-INFANT TRANSMISSION; CLINICAL-TRIALS; VERTICAL TRANSMISSION; INFECTED WOMEN; UNITED-STATES; DRUG-USE AB Background: Rates of mother-to-child transmission of HIV-1 (MTCT) have historically been lower in European than in American cohort studies, possibly due to differences in population characteristics. The Pediatric AIDS Clinical Trials Group Protocol (PACTG) 316 trial evaluated the effectiveness of the addition of intrapartum/neonatal nevirapine in reducing MTCT in women already receiving antiretroviral prophylaxis. Participation of large numbers of pregnant HIV-infected women from the US and Western Europe enrolling in the same clinical trial provided the opportunity to identify and explore differences in their characteristics and in the use of non-study interventions to reduce MTCT. Methods: In this secondary analysis, 1350 women were categorized according to enrollment in centres in the USA (n = 978) or in Europe (n = 372). Factors associated with receipt of highly active antiretroviral therapy and with elective caesarean delivery were identified with logistic regression. Results: In Europe, women enrolled were more likely to be white and those of black race were mainly born in Sub-Saharan Africa. Women in the US were younger and more likely to have previous pregnancies and miscarriages and a history of sexually transmitted infections. More than 90% of women did not report symptoms of their HIV infection; however, more women from the US had symptoms (8%), compared to women from Europe (4%). Women in the US were less likely to have HIV RNA levels < 400 copies/ml at delivery than women enrolling in Europe, and more likely to receive highly active antiretroviral therapy, and to start therapy earlier in pregnancy. The elective caesarean delivery rate in Europe was 61%, significantly higher than that in the US (22%). Overall, 1.48% of infants were infected and there was no significant difference in the rate of transmission between Europe and the US despite the different approaches to treatment and delivery. Conclusion: These findings confirm that there are important historical differences between the HIV-infected pregnant populations in Western Europe and the USA, both in terms of the characteristics of the women and their obstetric and therapeutic management. Although highly active antiretroviral therapy predominates in pregnancy in both settings now, population differences are likely to remain. C1 UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Hop Louis Mourier, APHP, Serv Gynecol Obstet, F-75701 Colombes, France. Univ Paris 07, F-94276 Le Kremlin Bicetre, France. INSERM, U822, IFR69, F-94276 Le Kremlin Bicetre, France. Univ Massachusetts, Sch Med, Dept Pediat & Mol Med, Worcester, MA USA. Louisiana State Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, New Orleans, LA USA. Univ Florida, Coll Med, Dept Obstet & Gynecol, Jacksonville, FL USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27706 USA. RP Newell, ML (reprint author), UCL, Inst Child Hlth, Ctr Paediat Epidemiol & Biostat, London, England. EM m.newell@ich.ucl.ac.uk; sharon@sdac.harvard.edu; s.fiore@ich.ucl.ac.uk; c.thorne@ich.ucl.ac.uk; laurent.mandelbrot@lmr.aphp.fr; john.sullivan@umassmed.edu; rmaupi@lsuhsc.edu; isaac.delke@jax.ufl.edu; wattsh@exchange.nih.gov; gelber@jimmy.harvard.edu; coleen.cunningham@duke.edu RI Thorne, Claire/C-5943-2008; OI Thorne, Claire/0000-0003-0389-1956; Mofenson, Lynne/0000-0002-2818-9808; Newell, Marie-Louise/0000-0002-1074-7699 FU Medical Research Council [G84/5903, G9620552]; NIAID NIH HHS [U01 AI041110, U01 AI41110] NR 44 TC 15 Z9 16 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD JUN 20 PY 2007 VL 7 AR 60 DI 10.1186/1471-2334-7-60 PG 10 WC Infectious Diseases SC Infectious Diseases GA 187YY UT WOS:000247886500001 PM 17584491 ER PT J AU Lewis, MH Gohagan, JK Merenstein, DJ AF Huckaby Lewis, Michelle Gohagan, John K. Merenstein, Daniel J. TI The locality rule and the physician's dilemma - Local medical practices vs the national standard of care SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Johns Hopkins Berman Inst Bioeth, Greenwall Fellowship Program Bioeth & Hlth Policy, Baltimore, MD 21201 USA. Johns Hopkins Sch Med, Robert Wood Johnson Clin Scholars Program, Baltimore, MD USA. Georgetown Univ, Dept Family Med, Washington, DC USA. NCI, Div Canc Prevent, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Lewis, MH (reprint author), Johns Hopkins Berman Inst Bioeth, Greenwall Fellowship Program Bioeth & Hlth Policy, 100 N Charles St,Suite 740, Baltimore, MD 21201 USA. EM michellelewismd@yahoo.com NR 10 TC 22 Z9 22 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 20 PY 2007 VL 297 IS 23 BP 2633 EP 2637 DI 10.1001/jama.297.23.2633 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 180HB UT WOS:000247352600027 PM 17579232 ER PT J AU Adermark, L Lovinger, DM AF Adermark, Louise Lovinger, David M. TI Combined activation of L-type Ca2+ channels and synaptic transmission is sufficient to induce striatal long-term depression SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synaptic plasticity; basal ganglia; dopamine; glutamate; endocannabinoid; presynaptic mechanisms ID MEDIUM SPINY NEURONS; ENDOCANNABINOID RELEASE; BASAL GANGLIA; CHOLINERGIC INTERNEURONS; CORTICOSTRIATAL SYNAPSES; POSTNATAL-DEVELOPMENT; DISEASE MODELS; PLASTICITY; RAT; MODULATION AB Changes in synaptic strength at striatal synapses, such as long- term depression ( LTD), may be involved in striatal- based learning and memory. Several molecular mechanisms have been implicated in striatal LTD, but it is not clear which mechanisms are crucial for LTD induction. We found that the activation of L- type calcium channels by 2,5- dimethyl- 4-[ 2-( phenylmethyl) benzoyl]- 1H- pyrrole- 3carboxylic acid methylester ( FPL64176), combined with modest postsynaptic depolarization and synaptic activation, is sufficient to induce robust LTD ( FPL - LTD). The L- channel activator 1,4- dihydro- 2,6- dimethyl- 5- nitro- 4-[ 2( trifluoromethyl) phenyl] pyridine- 3carboxylic acid methyl ester ( Bay K 8644) has a similar action. FPL - LTD occludes LTD induced by high- frequency stimulation ( HFS LTD) and requires elevated postsynaptic calcium and retrograde endocannabinoid signaling, properties similar to those of HFS - LTD. In contrast, FPL - LTD does not require the activation of metabotropic glutamate receptors ( mGluRs), phospholipase C, or dopamine D-2 receptors. FPL - LTD induction also requires afferent stimulation. These findings suggest a scenario in which L- type calcium channel activation is a crucial switch for LTD induction, and mGluRs and D-2 receptors can be bypassed if this channel is activated. C1 NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov RI yu, yan/C-2322-2012; Adermark, Louise/D-2297-2014 OI Adermark, Louise/0000-0002-7165-9908 FU Intramural NIH HHS NR 41 TC 55 Z9 55 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 20 PY 2007 VL 27 IS 25 BP 6781 EP 6787 DI 10.1523/JNEUROSCI.0280-07.2007 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 180XK UT WOS:000247401100020 PM 17581965 ER PT J AU Lubin, JH Freeman, LEB Cantor, KP AF Lubin, Jay H. Freeman, Laura E. Beane Cantor, Kenneth P. TI Inorganic arsenic in drinking water: An evolving public health concern SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CANCER MORTALITY; SKIN-LESIONS; LUNG-CANCER; WEST-BENGAL; EXPOSURE; RISK; BLADDER; CHILE; CONTAMINATION; METHYLATION C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lubin, JH (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-8042, Bethesda, MD 20892 USA. EM lubinj@mail.nih.gov RI Beane Freeman, Laura/C-4468-2015 OI Beane Freeman, Laura/0000-0003-1294-4124 FU Intramural NIH HHS NR 26 TC 26 Z9 29 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 20 PY 2007 VL 99 IS 12 BP 906 EP 907 DI 10.1093/jnci/djm012 PG 2 WC Oncology SC Oncology GA 188KE UT WOS:000247918000001 PM 17565151 ER PT J AU Wacholder, S Loukissas, JK Hartge, P AF Wacholder, Sholorn Loukissas, Jennifer K. Hartge, Patricia TI Studies of genes and cancer survival: Pieces of the puzzle SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID PROSTATE-CANCER C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, EPN 8046, Bethesda, MD 20892 USA. EM wacholds@mail.nih.gov FU Intramural NIH HHS NR 12 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 20 PY 2007 VL 99 IS 12 BP 908 EP 909 DI 10.1093/jnci/djm013 PG 2 WC Oncology SC Oncology GA 188KE UT WOS:000247918000002 PM 17565150 ER PT J AU Biggar, RJ Chaturvedi, AK Goedert, JJ Engels, EA AF Biggar, Robert J. Chaturvedi, Anil K. Goedert, James J. Engels, Eric A. CA HIVAIDS CMS TI AIDS-Related cancer and severity of immunosuppression in persons with AIDS SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; SWISS HIV COHORT; KAPOSIS-SARCOMA; HUMAN-PAPILLOMAVIRUS; VIRUS; LYMPHOMA; RISK; HERPESVIRUS; INFECTION AB Background The incidence of Kaposi sarcoma, non-Hodgkin lymphoma, and cervical cancer has been declining among persons with AIDS. We investigated the association between cancer risk and CD4 cell count among such persons. Methods Data from US AIDS registries were linked to local cancer registry data. Cancer incidence per 100000 person-years was determined for the 4-27 months from the onset of AIDS from January 1, 1990, through December 31, 1995-before highly active antiretroviral therapy (HAART) became available-and from January 1, 1996, through December 31, 2002. The relationships between CD4 count at AIDS onset and cancer incidence were assessed by proportional hazards models. Results Among 325516 adults with AIDS, the incidence of Kaposi sarcoma was lower in 1996-2002 (334.6 cases per 100000 person-years) than in 1990-1995 (1838.9 cases per 100000 person-years), and the incidence of non-Hodgkin lymphoma followed a similar pattern (i.e., 390.1 cases per 100000 person-years in 1996-2002 and 1066.2 cases per 100000 person-years in 1990-1995). In 1996-2002, for each decline in CD4 cell count of 50 cells per microliter of blood, increased risks were found for Kaposi sarcoma (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.33 to 1.50), for central nervous system non-Hodgkin lymphoma subtypes (HR = 1.85, 95% Cl 1.58 to 2.16), and for non-central nervous system diffuse large B-cell lymphoma (HR = 1.12, 95% Cl 1.04 to 1.20) but not for non-central nervous system Burkitt lymphoma (HR = 0.93, 95% Cl = 0.81 to 1.06). Cervical cancer incidence was higher in 1996-2002 (86.5 per 100000 person-years) than in 1990-1995 (64.2 per 100000 person-years), although not statistically significantly so (relative risk [RR] = 1.41, 95% CI = 0.81 to 2.46). After adjustment for age, race, and sex or mode of HIV exposure, the risks for Kaposi sarcoma (RR = 0.22, 95% Cl = 0.20 to 0.24) and for non-Hodgkin lymphoma (RR = 0.40, 95% Cl = 0.36 to 0.44) were lower in the period of 1996-2002 than in 1990-1995. Similar relationships of these cancers to CD4 count were observed for 1990-1995. Conclusions Both before and after HAART was available, CD4 count was strongly associated with risks for Kaposi sarcoma and non-Hodgkin lymphoma but not for cervical cancer and Burkitt lymphoma. The decreasing incidences of most AIDS-associated cancers in persons with AIDS during the 1990s are consistent with improving CD4 counts after HAART introduction in 1996. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. State Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. RP Biggar, RJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room EPS 8014, Rockville, MD 20852 USA. EM biggarb@mail.nih.gov RI Chaturvedi, Anil/J-2024-2015 OI Chaturvedi, Anil/0000-0003-2696-8899 FU Intramural NIH HHS NR 30 TC 167 Z9 176 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 20 PY 2007 VL 99 IS 12 BP 962 EP 972 DI 10.1093/jnci/djm010 PG 11 WC Oncology SC Oncology GA 188KE UT WOS:000247918000011 PM 17565153 ER PT J AU Ganesh, SK Sharma, Y Dayhoff, J Fales, HM Van Eyk, J Kickler, TS Billings, EM Nabel, EG AF Ganesh, Santhi K. Sharma, Yugal Dayhoff, Judith Fales, Henry M. Van Eyk, Jennifer Kickler, Thomas S. Billings, Eric M. Nabel, Elizabeth G. TI Detection of Venous Thromboembolism by Proteomic Serum Biomarkers SO PLOS ONE LA English DT Article AB Background. Available blood assays for venous thromboembolism (VTE) suffer from diminished specificity. Compared with single marker tests, such as D-dimer, a multi-marker strategy may improve diagnostic ability. We used direct mass spectrometry (MS) analysis of serum from patients with VTE to determine whether protein expression profiles would predict diagnosis. Methods and Results. We developed a direct MS and computational approach to the proteomic analysis of serum. Using this new method, we analyzed serum from inpatients undergoing radiographic evaluation for VTE. In a balanced cohort of 76 patients, a neural network-based prediction model was built using a training subset of the cohort to first identify proteomic patterns of VTE. The proteomic patterns were then validated in a separate group of patients within the cohort. The model yielded a sensitivity of 68% and specificity of 89%, which exceeded the specificity of D-dimer assay tested by latex agglutination, ELISA, and immunoturbimetric methods (sensitivity/specificity of 63.2%/60.5%, 97.4%/21.1%, 97.4%/15.8%, respectively). We validated differences in protein expression between patients with and without VTE using more traditional gel-based analysis of the same serum samples. Conclusion. Protein expression analysis of serum using direct MS demonstrates potential diagnostic utility for VTE. This pilot study is the first such direct MS study to be applied to a cardiovascular disease. Differences in protein expression were identified and subsequently validated in a separate group of patients. The findings in this initial cohort can be evaluated in other independent cohorts, including patients with inflammatory conditions and chronic (but not acute) VTE, for the diagnosis of VTE. C1 [Ganesh, Santhi K.; Sharma, Yugal; Dayhoff, Judith; Fales, Henry M.; Billings, Eric M.; Nabel, Elizabeth G.] NHLBI, Bethesda, MD 20892 USA. [Ganesh, Santhi K.; Nabel, Elizabeth G.] NHGRI, Bethesda, MD 20892 USA. [Van Eyk, Jennifer; Kickler, Thomas S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Nabel, EG (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM nabele@nhlbi.nih.gov FU National Heart, Lung and Blood Institute; Division of Intramural Research; National Heart, Lung and Blood Institute Proteomic Initiative [NO-HV-28120]; Donald P. Amos Family Foundation FX This work was supported by the National Heart, Lung and Blood Institute, Division of Intramural Research, and in part by the National Heart, Lung and Blood Institute Proteomic Initiative (contract NO-HV-28120) (JVE) and the Donald P. Amos Family Foundation (JVE). We have no disclosures. NR 34 TC 10 Z9 10 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 20 PY 2007 VL 2 IS 6 AR e544 DI 10.1371/journal.pone.0000544 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10GE UT WOS:000207451700010 PM 17579716 ER PT J AU Choudhry, V Zhang, MY Sidorov, IA Louis, JM Harris, I Dimitrov, AS Bouma, P Cham, F Choudhary, A Rybak, SM Fouts, T Montefiori, DC Broder, CC Quinnan, GV Dimitrov, DS AF Choudhry, Vidita Zhang, Mei-Yun Sidorov, Igor A. Louis, John M. Harris, Ilia Dimitrov, Antony S. Bouma, Peter Cham, Fatim Choudhary, Anil Rybak, Susanna M. Fouts, Timothy Montefiori, David C. Broder, Christopher C. Quinnan, Gerald V., Jr. Dimitrov, Dimiter S. TI Cross-reactive HIV-1 neutralizing monoclonal antibodies selected by screening of an immune human phage library against an envelope glycoprotein (gp140) isolated from a patient (R2) with broadly HIV-1 neutralizing antibodies SO VIROLOGY LA English DT Article DE HIV; antibody; phage display; gp140; gp41; inhibitors; vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1; EPITOPE; GP120; GP41; INFECTION; DIVERSE; PROTEIN; SERA; 2G12 AB Elicitation of broadly cross-reactive neutralizing antibodies (bcnAbs) in HIV infections is rare. To test the hypothesis that such antibodies could be elicited by HIV envelope glycoproteins (Envs) with unusual immunogenic properties and to identify novel benAbs, we used a soluble Env ectodomain (gp 140) froin a donor (R2) with high level of bcnAbs as an antigen for panning of an immune phage-displayed antibody library. The panning with the R2 Env resulted in significantly higher number of cross-reactive antibody clones than by using Envs from two other isolates (89.6 and IIIB). Two of the identified human monoclonal antibodies (hmAbs), m22 and tn24, had sequences, neutralizing and binding activities similar or identical to those of the gp120-specific bcnAbs m 18 and m 14. The use of the R2 Env but not other Envs for panning resulted in the identification of a novel gp41-specific hmAb, m46. For several of the tested HIV-1 primary isolates its potency on molar basis was comparable to that of T20. It inhibited entry of primary isolates from different clades with an increased activity for cell lines with low CCR5 surface concentrations. The m46 neutralizing activity against a panel of clade C isolates was significantly higher in an assay based on peripheral blood mononuclear cells (4 out of 5 isolates were neutralized with an IC50 in the range from 1.5 to 25 mu g/ml) than in ail assay based on a cell line with relatively high concentration of cell-surface-associated CCR5. In contrast to 2175 and Z13, this antibody did not bind to denatured gp140 and gp41-derived peptides indicating a conformational nature of its epitope. It bound to a 5-helix bundle but not to N-heptad repeat coiled coils and a 6-helix bundle construct indicating contribution of both gp41 heptad repeats to its epitope and to a possible mechanism of neutralization. These results indicate that the R2 Env may contain unique exposed conserved epitopes that could contribute to its ability to elicit broadly cross-reactive antibodies in animals and humans; the newly identified antibodies may help in the development of novel vaccine immunogens and therapeutics. (C) 2007 Elsevier Inc. All rights reserved. C1 NCI, CCRNP, CCR, Prot Interact Grp,NIH, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, BRP, Frederick, MD 21702 USA. NCI, Biol Testing Branch, NIH, Frederick, MD 21702 USA. NIDDK, Phys Chem Lab, Bethesda, MD 20892 USA. Profectus BioSci Inc, Baltimore, MD 21227 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Duke Univ, Med Ctr, Lab AIDS Vaccine Res & Dev, Dept Surg, Durham, NC 27710 USA. RP Dimitrov, DS (reprint author), NCI, CCRNP, CCR, Prot Interact Grp,NIH, Bldg 469,Rm 105,POB B,Miller Dr, Frederick, MD 21702 USA. EM dimitrov@nciferf.gov OI Fouts, Timothy/0000-0002-2429-2859; Sidorov, Igor/0000-0001-6519-4983 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [AI37438, AI48280, AI64070, P01 AI048280, R01 AI037438, R01 AI064070, R21 AI037438] NR 43 TC 49 Z9 54 U1 1 U2 9 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 JUN 20 PY 2007 VL 363 IS 1 BP 79 EP 90 DI 10.1016/j.virol.2007.01.015 PG 12 WC Virology SC Virology GA 174IQ UT WOS:000246936000009 PM 17306322 ER PT J AU Fu, W Prasad, VVSP Chen, JB Nikolaitchik, O Hu, WS AF Fu, William Prasad, V. V. S. P. Chen, Jianbo Nikolaitchik, Olga Hu, Wei-Shau TI Molecular mechanisms of simian immunodeficiency virus SIVagm RNA encapsidation SO VIROLOGY LA English DT Article DE SIVagm; RNA packaging; NC; translation ID MURINE LEUKEMIA-VIRUS; PROTEIN ZINC-FINGER; ROUS-SARCOMA-VIRUS; NUCLEOCAPSID PROTEIN; GENOMIC RNA; PRIMATE LENTIVIRUS; HAIRPIN STRUCTURES; PACKAGING SIGNAL; GAG POLYPROTEIN; ACTINOMYCIN-D AB Primate lentiviruses are composed of several distinct lineages, including human immunodeficiency virus type 1 (HIV-1), HIV-2, and simian immunodeficiency virus SIVagm. HIV-1 and HIV-2 have significant differences in the mechanisms of viral RNA encapsidation. Therefore, the RNA packaging mechanisms of SIVagm cannot be predicted from the studies of HIV-1 and HIV-2. We examined the roles of the nucleocapsid (NC) zinc finger motifs on RNA packaging by mutating the conserved zinc finger (CCHC) motifs, and whether SIVagin has a preference to package RNA in cis by comparing the RNA packaging efficiencies of gag mutants in the presence of a wild-type vector. Our results indicate that the SIVagm NC domain plays an important role in Gag-RNA recognition; furthermore SIVagm. is distinct from the other currently known primate lentiviruses as destroying either zinc finger motif in the NC causes very drastic RNA packaging defects. Additionally, trans-packaging is a major mechanism for SIVagm RNA encapsidation. Published by Elsevier Inc. C1 Natl Canc Inst, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. RP Hu, WS (reprint author), Natl Canc Inst, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU Intramural NIH HHS [Z01 BC010506-05] NR 62 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 2007 VL 363 IS 1 BP 210 EP 219 DI 10.1016/j.virol.2007.01.030 PG 10 WC Virology SC Virology GA 174IQ UT WOS:000246936000021 PM 17321560 ER PT J AU Grivel, JC Elliott, J Lisco, A Biancotto, A Condack, C Shattock, RJ McGowan, I Margolis, L Anton, P AF Grivel, Jean-Charles Elliott, Julie Lisco, Andrea Biancotto, Angelique Condack, Cristian Shattock, Robin J. McGowan, Ian Margolis, Leonid Anton, Peter TI HIV-1 pathogenesis differs in rectosigmoid and tonsillar tissues infected ex vivo with CCR5-and CXCR4-tropic HIV-1 SO AIDS LA English DT Article DE co-receptor; gut-associated lymphoid tissue; HIV-1; mucosa; tonsil ID HUMAN LYMPHOID-TISSUE; T-CELL DEPLETION; GASTROINTESTINAL-TRACT; TYPE-1; REPLICATION; SPLEEN; CXCR4; HISTOCULTURES; MICROBICIDES; LYMPHOCYTES AB Gut-associated lymphoid tissue (GALT) has been identified as the primary target of HIV-1 infection. To investigate why GALT is especially vulnerable to HIV-1, and to determine whether the selective transmission of CCR5-using viral variants(R5)in vivo is the result of a greater susceptibility of GALT to this viral variant, we performed comparative studies of CXCR4-using (X4) and R5 HIV-1 infections of human lymphoid (tonsillar) and rectosigmoid tissues ex vivo under controlled laboratory conditions. We found that the relative level of R5 replication in rectosigmoid tissue is much greater than in tonsillar tissue. This difference is associated with the expression of the CCR5 co-receptor on approximately 70% of CD4 T cells in rectosigmoid tissue, whereas in tonsillar tissue it is expressed on fewer than 15% of CD4 T cells. Furthermore, tonsillar tissue responds to X4 HIV-1 infection by upregulating the secretion of CC-chemokines, providing a potential CCR5 blockade and further resistance to R5 infection, whereas gut tissue failed to increase such innate immune responses. Our results show that rectosigmoid tissue is more prone than tonsillar lymphoid tissue to R5 HIV-1 infection, primarily because of the high prevalence and availability of R5 cell targets and reduced chemokine blockade. The majority of CD4 T cells express CXCR4, however, and X4 HIV-1 readily replicates in both tissues, suggesting that although the differential expression of co-receptors contributes to the GALT vulnerability to R5 HIV-1, it alone cannot account for the selective R5 infection of the rectal mucosa in vivo. (C) 2007 Lippincott Williams & Wilkins. C1 NICHHD, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Daivd Geffen Sch Med, UCLA AIDS Inst, Ctr Prevent Res, Los Angeles, CA 90024 USA. Univ London St Georges Hosp, London SW17 0RE, England. RP Margolis, L (reprint author), 10 Ctr Dr,NIH Bldg 10,Room 9D58, Bethesda, MD 20892 USA. EM margolis@helix.nih.gov FU NIAID NIH HHS [AI 28697, U19 AI 060614] NR 36 TC 39 Z9 39 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 19 PY 2007 VL 21 IS 10 BP 1263 EP 1272 DI 10.1097/QAD.0b013e3281864667 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 183EZ UT WOS:000247556800005 PM 17545702 ER PT J AU Mannon, P AF Mannon, Peter TI GAIN for loss: Adalimumab for infliximab-refractory Crohn disease SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID RANDOMIZED-TRIAL; ANTIBODY; MAINTENANCE; EFFICACY C1 NIAID, Clin Inflammatory Bowel Dis Res Unit, Mucosal Immun Sect, Lab Host Def,NIH, Bethesda, MD 20892 USA. RP Mannon, P (reprint author), NIAID, Clin Inflammatory Bowel Dis Res Unit, Mucosal Immun Sect, Lab Host Def,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 3 Z9 3 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 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 19 PY 2007 VL 146 IS 12 BP 888 EP 890 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 180FF UT WOS:000247347100008 PM 17577009 ER PT J AU Moore, RA Hayes, SF Fischer, ER Priola, SA AF Moore, Roger A. Hayes, Stanley F. Fischer, Elizabeth R. Priola, Suzette A. TI Amyloid formation via supramolecular peptide assemblies SO BIOCHEMISTRY LA English DT Article ID ATOMIC-FORCE MICROSCOPY; IN-VITRO; ALZHEIMERS-DISEASE; FIBRIL FORMATION; PROTEIN; OLIGOMERS; FIBRILLOGENESIS; MECHANISM; AGGREGATION; PHENOTYPE AB Amyloid fibrils have been classically defined as linear, nonbranched polymeric proteins with a cross beta-sheet structure and the ability to alter the optical properties of the amyloid-specific dye Congo Red. Mounting evidence suggests that soluble oligomeric peptide assemblies similar to 2-20 nm in diameter are critical intermediates in amyloid formation. Using a pathogenic prion protein peptide comprised of residues 23-144, we demonstrate that, under quiescent but not agitated conditions, much larger globular assemblies up to 1 mu m in diameter are made. These globules precede fibril formation and directly interact with growing fibril bundles. Fibrils made via these large spherical peptide assemblies displayed a remarkable diversity of ultrastructural features. Fibrillization of the A beta 1-40 peptide under similar conditions yielded similar results, suggesting a mechanism of general amyloid formation that can proceed through intermediates much larger than those previously described. Our data suggest that simply changing the physical microenvironment can profoundly influence the mechanism of amyloid formation and yield fibrils with novel ultrastructural properties. C1 NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Microscopy Unit, Res Technol Sect, RTB,Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Lab Persistent Viral Dis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM spriola@nih.gov FU Intramural NIH HHS NR 40 TC 23 Z9 23 U1 1 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 JUN 19 PY 2007 VL 46 IS 24 BP 7079 EP 7087 DI 10.1021/bi700247y PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 177HV UT WOS:000247145100001 PM 17521170 ER PT J AU Levy, D Hwang, SJ Kayalar, A Benjamin, EJ Vasan, RS Parise, H Larson, MG Wang, TJ Selhub, J Jacques, PF Vita, JA Keyes, MJ Mitchell, GF AF Levy, Daniel Hwang, Shih-Jen Kayalar, Atilla Benjamin, Emelia J. Vasan, Ramachandran S. Parise, Helen Larson, Martin G. Wang, Thomas J. Selhub, Jacob Jacques, Paul F. Vita, Joseph A. Keyes, Michelle J. Mitchell, Gary F. TI Associations of plasma natriuretic peptide, adrenomedullin, and homocysteine levels with alterations in arterial stiffness the Framingham heart study SO CIRCULATION LA English DT Article DE arteries; elasticity; epidemiology; hemodynamics; homocysteine; natriuretic peptides ID BLOOD-PRESSURE TRACKING; AORTIC INPUT IMPEDANCE; PULSE-WAVE VELOCITY; CARDIOVASCULAR MORTALITY; MYOCARDIAL-INFARCTION; HORDALAND-HOMOCYSTEINE; ESSENTIAL-HYPERTENSION; INDEPENDENT PREDICTOR; LOADING SEQUENCE; RISK AB Background - Increased arterial stiffness and higher plasma natriuretic peptide and homocysteine levels are associated with elevated risk for cardiovascular disease. Little is known about the relations of natriuretic peptides and homocysteine to arterial wall stiffness in the community. Methods and Results - We assessed the relations of plasma N- terminal atrial natriuretic peptide, B- type natriuretic peptide, adrenomedullin, and homocysteine concentrations to arterial stiffness in participants in the Framingham Heart Study. Central pulse pressure, forward pressure wave, reflected pressure wave, carotid- femoral pulse wave velocity, and carotid- radial pulse wave velocity were assessed by tonometry in 1962 participants ( mean age, 61 years; 56% women) in the Framingham Heart Study. Central systolic and diastolic blood pressures were 123/75 mm Hg in men and 119/66 mm Hg in women. After adjustment for age and clinical covariates, N- terminal atrial natriuretic peptide and B- type natriuretic peptide were associated with carotid- femoral pulse wave velocity ( men: partial correlation, 0.069, P = 0.043 and r = 0.115, P = 0.001, respectively; women: r = -0.063, P = 0.037 and r = -0.062, P = 0.040), and carotid- radial pulse wave velocity ( men: r = -0.090, P = 0.009 and r = -0.083, P <= 0.015; women: r = -0.140, P <= 0.001 and r = -0.104, P = 0.001, respectively). In men, N- terminal atrial natriuretic peptide and B- type natriuretic peptide also were associated with forward and reflected wave and carotid pulse pressure. In men, adrenomedullin was associated with mean arterial pressure ( r = 0.089, P = 0.009), and homocysteine was associated with carotid- femoral pulse wave velocity ( r = 0.072, P = 0.036), forward pressure ( r = 0.079, P = 0.02), and central pulse pressure ( r = 0.072, P = 0.035). Interaction tests indicated sex differences in the relations of several biomarkers to measures of arterial stiffness. Conclusions - Plasma natriuretic peptide, adrenomedullin, and homocysteine levels are associated with alterations in conduit vessel properties that differ in men and women. C1 NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. MetroW Med Ctr, Dept Med, Framingham, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Tufts Univ, Freidman Sch Nutr Sci Policy, Boston, MA 02111 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Stat, Boston, MA 02215 USA. Boston Univ, Cardiol Sect, Boston, MA 02215 USA. Cardiovasc Engn Inc, Waltham, MA USA. RP Levy, D (reprint author), 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA. OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01-HL60040, 1R01-HL70100, N01-HC25195] NR 51 TC 35 Z9 38 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 19 PY 2007 VL 115 IS 24 BP 3079 EP 3085 DI 10.1161/CIRCULATIONAHA.106.652842 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 180GH UT WOS:000247350200009 PM 17533184 ER PT J AU Ostroumova, OS Kaulin, YA Gurnev, PA Schagina, LV AF Ostroumova, Olga S. Kaulin, Yuri A. Gurnev, Philip A. Schagina, Ludmila V. TI Effect of agents modifying the membrane dipole potential on properties of syringomycin E channels SO LANGMUIR LA English DT Article ID HYDROCARBON-WATER INTERFACE; LIPID BILAYER MEMBRANES; SYRINGAE PV SYRINGAE; ION CHANNELS; GRAMICIDIN CHANNEL; PHLORETIN; MODULATION; VESICLES; MONOLAYERS; TRANSPORT AB We evaluated the effect of agents modifying the membrane dipole potential: phloretin, 6-ketocholestanol and RH 421 on the properties of single channels formed by lipodepsipeptide syringomycin E (SRE) in planar lipid bilayers. SRE forms two conductive states in lipid bilayers: "small" and "large." Large SRE channels are clusters of several small ones, demonstrating synchronous openings and closures. The increase in the membrane dipole potential led to (i) an increase in SRE channel conductance, (ii) an increase in the channel's lifetime, and (iii) a decrease in a number of synchronously operating small channels in the clusters. Overall, the results support the model of the small SRE channel synchronization in the cluster as voltage-dependent orientation of the lipid dipoles associated with the channel pores. C1 Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. NICHHD, NIH, Bethesda, MD 20892 USA. RP Kaulin, YA (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, 1020 Locust St,Rm 239, Philadelphia, PA 19107 USA. EM Yuri.Kaulin@jefferson.edu RI Ostroumova, Olga/N-8636-2013 NR 39 TC 20 Z9 21 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD JUN 19 PY 2007 VL 23 IS 13 BP 6889 EP 6892 DI 10.1021/la7005452 PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 177HX UT WOS:000247145300005 PM 17508767 ER PT J AU Bae, DD Brown, PL Kiyatkin, EA AF Bae, David D. Brown, P. Leon Kiyatkin, Eugene A. TI Procedure of rectal temperature measurement affects brain, muscle, skin, and body temperatures and modulates the effects of intravenous cocaine SO BRAIN RESEARCH LA English DT Article DE body core temperature; thermorecording; stress; metabolic brain activation; skin hypothermia; rat ID INDUCED HYPERTHERMIA; STRESS HYPERTHERMIA; RATS; FEVER; FLUCTUATIONS; ACTIVATION; RESPONSES; BEHAVIOR AB Rectal probe thermometry is commonly used to measure body core temperature in rodents because of its ease of use. Although previous studies suggest that rectal measurement is stressful and results in long-lasting elevations in body temperatures, we evaluated how this procedure affects brain, muscle, skin, and core temperatures measured with chronically implanted thermocouple electrodes in rats. Our data suggest that the procedure of rectal measurement results in powerful locomotor activation, rapid and strong increases in brain, muscle, and deep body temperatures, as well as a biphasic, down-up fluctuation in skin temperature, matching the response pattern observed during tail-pinch, a representative stressful procedure. This response, moreover, did not habituate after repeated day-to-day testing. Repeated rectal probe insertions also modified temperature responses induced by intravenous cocaine. Under quiet resting conditions, cocaine moderately increased brain, muscle, and deep body temperatures. However, during repeated rectal measurements, which increased temperatures, cocaine induced both hyperthermic and hypothermic responses. Direct comparisons revealed that body temperatures measured by a rectal probe are typically lower (similar to 0.6 degrees C) and more variable than body temperatures recorded by chronically implanted electrodes; the difference is smaller at low and greater at high basal temperatures. Because of this difference and temperature increases induced by the rectal probe per se, cocaine had no significant effect on rectal temperatures compared to control animals exposed to repeated rectal probes. Therefore, although rectal temperature measurements provide a decent correlation with directly measured deep body temperatures, the arousing influence of this procedure may drastically modulate the effects of other arousing stimuli and drugs. Published by Elsevier B.V. C1 Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), Natl Inst Drug Abuse, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000445-07] NR 26 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD JUN 18 PY 2007 VL 1154 BP 61 EP 70 DI 10.1016/j.brainres.2007.03.078 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 187OK UT WOS:000247857400007 PM 17466279 ER PT J AU Muller, WG Rieder, D Karpova, TS John, S Trajanoski, Z McNally, JG AF Mueller, Waltraud G. Rieder, Dietmar Karpova, Tatiana S. John, Sam Trajanoski, Zlatko McNally, James G. TI Organization of chromatin and histone modifications at a transcription site SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MAMMARY-TUMOR VIRUS; RNA-POLYMERASE-II; ACTIVE GENES; LIVING CELLS; HUMAN NUCLEI; METHYLATION; GENOME; ACETYLATION; ELONGATION; PROMOTER AB According to the transcription factory model, localized transcription sites composed of immobilized polymerase molecules transcribe chromatin by reeling it through the transcription site and extruding it to form a surrounding domain of recently transcribed decondensed chromatin. Although transcription sites have been identified in various cells, surrounding domains of recently transcribed decondensed chromatin have not. We report evidence that transcription sites associated with a tandem gene array in mouse cells are indeed surrounded by or adjacent to a domain of decondensed chromatin composed of sequences from the gene array. Formation of this decondensed domain requires transcription and topoisomerase II alpha activity. The decondensed domain is enriched for the trimethyl H3K36 mark that is associated with recently transcribed chromatin in yeast and several mammalian systems. Consistent with this, chromatin immunoprecipitation demonstrates a comparable enrichment of this mark in transcribed sequences at the tandem gene array. These results provide new support for the pol II factory model, in which an immobilized polymerase molecule extrudes decondensed, transcribed sequences into its surroundings. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Graz Univ Technol, Christian Dappler Lab Genom & Bioinformat, Inst Genom & Bioinformat, A-8010 Graz, Austria. RP McNally, JG (reprint author), NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM mcnallyj@exchange.nih.gov FU Intramural NIH HHS NR 34 TC 25 Z9 26 U1 1 U2 2 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 JUN 18 PY 2007 VL 177 IS 6 BP 957 EP 967 DI 10.1083/jcb.200703157 PG 11 WC Cell Biology SC Cell Biology GA 180FH UT WOS:000247347400004 PM 17576795 ER PT J AU Lu, Z Je, HS Young, P Gross, J Lu, B Feng, G AF Lu, Zhonghua Je, Hyun-Soo Young, Paul Gross, Jimmy Lu, Bai Feng, Guoping TI Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MUSCLE-SPECIFIC KINASE; RECEPTOR TYROSINE KINASES; ACETYLCHOLINE-RECEPTOR; C-ELEGANS; GENE-EXPRESSION; MUTANT MICE; MUSK; AGRIN; PROTEIN; SYNAPTOGENESIS AB T he ubiquitin - proteasome pathway has been implicated in synaptic development and plasticity. However, mechanisms by which ubiquitination contributes to precise and dynamic control of synaptic development and plasticity are poorly understood. We have identified a PDZ domain containing RING finger 3 ( PDZRN3) as a synapse- associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of musclespecic receptor tyrosine kinase ( MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Regulation of cell surface levels of MuSK by PDZRN3 requires the ubiquitin ligase domain and is mediated by accelerated endocytosis. Gain- and loss- of function studies in cultured myotubes show that regulation of MuSK by PDZRN3 plays an important role in MuSKmediated nicotinic acetylcholine receptor clustering. Furthermore, overexpression of PDZRN3 in skeletal muscle of transgenic mice perturbs the growth and maturation of the neuromuscular junction. These results identify a synapseassociated E3 ubiquitin ligase as an important regulator of MuSK signaling. C1 Duke Univ, Ctr Med, Dept Neurobiol, Durham, NC 27710 USA. Duke Univ, Ctr Med, Dept Pathol, Durham, NC 27710 USA. NIMH, Sect Neural Dev & Plast, NICHD & Genes, GCAP, Bethesda, MD 20892 USA. RP Feng, G (reprint author), Duke Univ, Ctr Med, Dept Neurobiol, Durham, NC 27710 USA. EM feng@neuro.duke.edu RI Lu, Bai/A-4018-2012; Young, Paul/A-4874-2015; OI Young, Paul/0000-0002-1307-0249; Je, hyunsoo/0000-0002-2924-5621 NR 62 TC 36 Z9 41 U1 3 U2 7 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 JUN 18 PY 2007 VL 177 IS 6 BP 1077 EP 1089 DI 10.1083/jcb.200610060 PG 13 WC Cell Biology SC Cell Biology GA 180FH UT WOS:000247347400014 PM 17576800 ER PT J AU Laine, C Horton, R De Angelis, C Drazen, JM Frizelle, FA Godlee, F Haug, C Hebert, PC Kotzin, S Marusic, A Sahni, P Schroeder, TV Sox, HC Van der Weyden, MB Verheugt, FWA AF Laine, Christine Horton, Richard De Angelis, Catherine Drazen, Jeffrey M. Frizelle, Frank A. Godlee, Fiona Haug, Charlotte Hebert, Paul C. Kotzin, Sheldon Marusic, Ana Sahni, Peush Schroeder, Torben V. Sox, Harold C. Van der Weyden, Martin B. Verheugt, Freek W. A. TI Clinical trial registration: looking back and moving ahead SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Editorial Material C1 Natl Lib Med, MEDLINE, Bethesda, MD 20894 USA. EM medjaust@ampco.com.au RI Marusic, Ana/E-7683-2013; Verheugt, F.W.A./H-8105-2014; OI Marusic, Ana/0000-0001-6272-0917; Schroeder, Torben/0000-0002-9827-9438 NR 3 TC 2 Z9 2 U1 0 U2 2 PU AUSTRALASIAN MED PUBL CO LTD PI PYRMONT PA LEVEL 2, 26-32 PYRMONT BRIDGE RD, PYRMONT, NSW 2009, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD JUN 18 PY 2007 VL 186 IS 12 BP 612 EP 613 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 185UX UT WOS:000247737000002 PM 17576172 ER PT J AU Jeang, KT AF Jeang, Kuan-Teh TI Impact factor, H index, peer comparisons, and Retrovirology: is it time to individualize citation metrics? SO RETROVIROLOGY LA English DT Editorial Material AB There is a natural tendency to judge a gift by the attractiveness of its wrapping. In some respect, this reflects current mores of measuring the gravitas of a scientific paper based on the journal cover in which the work appears. Most journals have an impact factor (IF) which some proudly display on their face page. Although historically journal IF has been a convenient quantitative shorthand, has its (mis)use contributed to inaccurate perceptions of the quality of scientific articles? Is now the time that equally convenient but more individually accurate metrics be adopted? C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bethesda, MD 20892 USA. EM kjeang@niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 10 TC 25 Z9 25 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUN 18 PY 2007 VL 4 AR 42 DI 10.1186/1742-4690-4-42 PG 4 WC Virology SC Virology GA 184IB UT WOS:000247633600001 PM 17577403 ER PT J AU Freedman, ND Abnet, CC Leitzmann, MF Mouw, T Subar, AF Hollenbeck, AR Schatzkin, A AF Freedman, Neal D. Abnet, Christian C. Leitzmann, Michael F. Mouw, Traci Subar, Amy F. Hollenbeck, Albert R. Schatzkin, Arthur TI A prospective study of tobacco, alcohol, and the risk of esophageal and gastric cancer subtypes SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; cohort studies; esophageal neoplasms; prospective studies; smoking; stomach neoplasms ID HELICOBACTER-PYLORI INFECTION; UPPER AERODIGESTIVE TRACT; SQUAMOUS-CELL CARCINOMA; UNITED-STATES; ESOPHAGOGASTRIC JUNCTION; SMOKING; CONSUMPTION; ADENOCARCINOMA; CARDIA; STOMACH AB Rates of esophageal adenocarcinoma and gastric cardia adenocarcinoma have increased, while rates of esophageal squamous cell carcinoma (ESCC) and gastric noncardia adenocarcinoma have decreased, suggesting distinct etiologies. The authors prospectively investigated the associations of alcohol and tobacco with these cancers in 474,606 US participants using Cox models adjusted for potential confounders. Between 1995/1996 and 2000, 97 incident cases of ESCC, 205 of esophageal adenocarcinoma, 188 of gastric cardia, and 187 of gastric noncardia cancer occurred. Compared with nonsmokers, current smokers were at increased risk for ESCC (hazard ratio (HR) = 9.27, 95% confidence interval (CI): 4.04, 21.29), esophageal adenocarcinoma (HR = 3.70, 95% CI: 2.20, 6.22), gastric cardia (HR = 2.86, 95% CI: 1.73, 4.70), and gastric noncardia (HR = 2.04, 95% CI: 1.32, 3.16). Assuming causality, ever smoking had population attributable risks of 77% (95% CI: 0.55, 0.89) for ESCC, 58% (95% CI: 0.38, 0.72) for esophageal adenocarcinoma, 47% (95% CI: 0.27, 0.63) for gastric cardia, and 19% (95% CI: 0.00, 0.37) for gastric noncardia. For drinkers of more than three alcoholic beverages per day, compared with those whose intake was up to one drink per day, the authors found significant associations between alcohol intake and ESCC risk (HR = 4.93, 95% CI: 2.69, 9.03) but not risk for esophageal, gastric cardia, or gastric noncardia adenocarcinoma. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH Div Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, NIH, Dept Hlth & Human Serv, Rockville, MD USA. AARP, Washington, DC USA. RP Abnet, CC (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH Div Hlth & Human Serv, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM abnetc@mail.nih.gov RI Abnet, Christian/C-4111-2015; Freedman, Neal/B-9741-2015 OI Abnet, Christian/0000-0002-3008-7843; Freedman, Neal/0000-0003-0074-1098 FU Intramural NIH HHS NR 52 TC 155 Z9 165 U1 2 U2 15 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2007 VL 165 IS 12 BP 1424 EP 1433 DI 10.1093/aje/kwm051 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 178SP UT WOS:000247240700012 PM 17420181 ER PT J AU Alonso, WJ Viboud, C Simonsen, L Hirano, EW Daufenbach, LZ Miller, MA AF Alonso, Wladimir J. Viboud, Cecile Simonsen, Lone Hirano, Eduardo W. Daufenbach, Luciane Z. Miller, Mark A. TI Seasonality of influenza in Brazil: A traveling wave from the Amazon to the subtropics SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Brazil; climate; geographic locations; influenza, human; mortality; pneumonia; seasons ID INFECTIOUS-DISEASES; UNITED-STATES; SPATIAL HIERARCHIES; EPIDEMICS; MORTALITY; TRANSMISSION; VACCINATION; SPREAD; IMPACT; US AB Influenza circulation and mortality impact in tropical areas have not been well characterized. The authors studied the seasonality of influenza throughout Brazil, a geographically diverse country, by modeling influenza-related mortality and laboratory surveillance data. Monthly time series of pneumonia and influenza mortality were obtained from 1979 to 2001 for each of the 27 Brazilian states. Detrended time series were analyzed by Fourier decomposition to describe the amplitude and timing of annual and semiannual epidemic cycles, and the resulting seasonal parameters were compared across latitudes, ranging from the equator (+5 degrees N) to the subtropics (-35 degrees S). Seasonality in mortality was most pronounced in southern states (winter epidemics, June-July), gradually attenuated toward central states (15 degrees S) (p < 0.001), and remained low near the equator. A seasonal southward traveling wave of influenza was identified across Brazil, originating from equatorial and low-population regions in March-April and moving toward temperate and highly populous regions over a 3-month period. Laboratory surveillance data from recent years provided independent confirmation that mortality peaks coincided with influenza virus activity. The direction of the traveling wave suggests that environmental forces (temperature, humidity) play a more important role than population factors (density, travel) in driving the timing of influenza epidemics across Brazil. C1 Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Fed Santa Catarina, Dept Mech Engn, Florianopolis, SC, Brazil. Minist Hlth, Secretariat Hlth Surveillance, Brasilia, DF, Brazil. RP Alonso, WJ (reprint author), Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. EM alonsow@mail.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 FU NIMHD NIH HHS [MD516982] NR 31 TC 129 Z9 136 U1 2 U2 18 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 15 PY 2007 VL 165 IS 12 BP 1434 EP 1442 DI 10.1093/aje/kwm012 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 178SP UT WOS:000247240700013 PM 17369609 ER PT J AU Goedert, JJ Chen, BSE Preiss, L Aledort, LM Rosenberg, PS AF Goedert, James J. Chen, Bingshu E. Preiss, Liliana Aledort, Louis M. Rosenberg, Philip S. CA Second Multicenter Hemophilia TI Reconstruction of the hepatitis C virus epidemic in the US hemophilia population, 1940-1990 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE blood component transfusion; factor VIII; hemophilia A; Hepacivirus; hepatitis B virus; HIV; models, statistical; plasma ID UNITED-STATES; HIV-INFECTION; HEPATOCELLULAR-CARCINOMA; HUMAN-IMMUNODEFICIENCY; LIVER-DISEASE; RISK; AIDS; DEFICIENCY; HISTORY; ANTIGEN AB Hepatitis C virus (HCV) is a blood-borne infection readily transmitted by transfusion. Persons with hemophilia were at very high risk of acquiring HCV, but the chronology and correlates of HCV incidence in the US hemophilia population remain unknown. The authors used multiple data sources and new statistical methods to reconstruct HCV incidence in White males with hemophilia A from 1940 through 1990. HCV incidence was similar to 1%/year until 1950 but 2-3%/year by 1955. With mild hemophilia, HCV incidence increased in the 1960s, reaching a plateau of -8%/ year from 1969 to 1980. With moderate and severe hemophilia, HCV incidence increased steeply to peaks of 11.7%/year in 1970 and 17.2%/year in 1968, respectively. Overall, HCV incidence declined after 1970, steeply after 1984, to nearly zero by 1990. With improving and increasing use of plasma derivatives, the size of the hemophilia population increased 86% during these 50 years. Study results imply that these life-saving treatments also carried an increasing risk of HCV, particularly before clotting factor concentrates were licensed in the 1970s. They also suggest that multiple synergistic interventions since 1970, particularly donor deferral, screening for hepatitis B and human immunodeficiency virus, and viral inactivation of clotting factor concentrates, were needed to reduce transfusion of HCV prior to its discovery. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RTI Int, Rockville, MD USA. Mt Sinai Sch Med, New York, NY USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7066, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov FU Intramural NIH HHS NR 34 TC 18 Z9 21 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 JUN 15 PY 2007 VL 165 IS 12 BP 1443 EP 1453 DI 10.1093/aje/kwm030 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 178SP UT WOS:000247240700014 PM 17379617 ER PT J AU Anthi, A Machado, RF Jison, ML Taveira-DaSilva, AM Rubin, LJ Hunter, L Hunter, CJ Coles, W Nichols, J Avila, NA Sachdev, V Chen, CC Gladwin, MT AF Anthi, Anastasia Machado, Roberto F. Jison, Maria L. Taveira-DaSilva, Angelo M. Rubin, Lewis J. Hunter, Lori Hunter, Christian J. Coles, Wynona Nichols, James Avila, Nilo A. Sachdev, Vandana Chen, Clara C. Gladwin, Mark T. TI Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE sickle cell disease; pulmonary hypertension; six-minute walk; hemodynamics; echocardiogram ID 6-MINUTE WALK TEST; CARDIOPULMONARY BYPASS; RISK-FACTOR; MANSONIC SCHISTOSOMIASIS; ARTERIAL-HYPERTENSION; ATS STATEMENT; HEMOLYSIS; DEATH; HEMOGLOBIN; MORTALITY AB Rationale: Although pulmonary hypertension (PH) is a common complication of sickle cell disease (SCD) associated with high mortality, there exist few data characterizing hemodynamics and cardiopulmonary function in this population. Objectives: To characterize hemodynamics and cardiopulmonary function in patients with SCD with and without PH. Methods: Patients with SCD with PH (n = 26) were compared with control subjects with SCD but without PH (n = 17), matched for age, hemoglobin levels, and fetal hemoglobin levels. Measurements and Main Results: Upon catheterization, 54% of the patients with PH had pulmonary arterial hypertension, and 46% had pulmonary venous hypertension. When compared with control subjects, patients with PH exhibited lower six-minute-walk distance (435 +/- 31 vs. 320 +/- 20 m, p = 0.002) and oxygen consumption (50 +/- 3% vs. 41 +/- 2% of predicted, p = 0.02), and also had mild restrictive lung disease and more perfusion abnormalities on radio-nuclide lung scans. The six-minute-walk distance in this population inversely correlated with tricuspid regurgitant jet velocity (r = 0.55, p < 0.001), and mean pulmonary artery pressure (r = -0.57, p < 0.001), and directly correlated with maximal oxygen consumption (r = 0.49, p = 0.004), even after adjustment for hemoglobin, supporting an independent contribution of increasing pulmonary artery pressures to loss of exercise capacity. Conclusions: Patients with SCID-associated PH have both pulmonary arterial and venous PH associated with severe limitations in exercise capacity, likely compounded by interstitial lung fibrosis and severe anemia. These data support the use of the six-minute-walk distance as an index of PH and cardiopulmonary function in patients with SCD. C1 NHLBI, Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Med, Sch Med, La Jolla, CA 92093 USA. NIH, Dept Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Machado, RF (reprint author), NHLBI, Vasc Med Branch, Dept Crit Care Med, Ctr Clin,NIH, Bldg 10-CRC,Room 5-5140,10 Ctr Dr,MSC 1454, Bethesda, MD 20892 USA. EM robertom@nhlbi.nih.gov RI Hunter, Christian/G-4344-2010 FU Intramural NIH HHS NR 43 TC 123 Z9 128 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUN 15 PY 2007 VL 175 IS 12 BP 1272 EP 1279 DI 10.1164/rccm.200610-1498OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 179OA UT WOS:000247298000010 PM 17379852 ER PT J AU Bortner, CD Cidlowski, JA AF Bortner, Carl D. Cidlowski, John A. TI Cell shrinkage and monovalent cation fluxes: Role in apoptosis SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 3rd International Conference of the Collaborative Research Center Experimental Hepatology (SFB 575) CY OCT 13-14, 2006 CL Dusseldorf, GERMANY DE apoptosis; cell shrinkage; apoptotic volume decrease (AVD); ion channels; volume regulation; potassium; sodium; chloride ID CULTURED CORTICAL-NEURONS; PLASMA-MEMBRANE DEPOLARIZATION; SMOOTH-MUSCLE CELLS; HERG K+ CHANNEL; DEPENDENT POTASSIUM CHANNELS; ETOPOSIDE-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; X-RAY-MICROANALYSIS; THYMOCYTE APOPTOSIS; T-LYMPHOCYTES AB The loss of cell volume or cell shrinkage has been a morphological hallmark of the programmed cell death process known as apoptosis. This isotonic loss of cell volume has recently been term apoptotic volume decrease or AVID to distinguish it from inherent volume regulatory responses that occurs in cells under anisotonic conditions. Recent studies examining the intracellular signaling pathways that result in this unique cellular characteristic have determined that a fundamental movement of ions, particularly monovalent ions, underlie the AVID process and plays an important role on controlling the cell death process. An efflux of intracellular potassium was shown to be a critical aspect of the AVID process, as preventing this ion loss could protect cells from apoptosis. However, potassium plays a complex role as a loss of intracellular potassium has also been shown to be beneficial to the health of the cell. Additionally, the mechanisms that a cell employs to achieve this loss of intracellular potassium vary depending on the cell type and stimulus used to induce apoptosis, suggesting multiple ways exist to accomplish the same goal of AVID. Additionally, sodium and chloride have been shown to play a vital role during cell death in both the signaling and control of AVD in various apoptotic model systems. This review examines the relationship between this morphological change and intracellular monovalent ions during apoptosis. Published by Elsevier Inc. C1 NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Bortner, CD (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. EM bortner@neihs.nih.gov FU Intramural NIH HHS [Z01 ES090079-12] NR 135 TC 134 Z9 148 U1 1 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 15 PY 2007 VL 462 IS 2 BP 176 EP 188 DI 10.1016/j.abb.2007.01.020 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179OJ UT WOS:000247299100009 PM 17321483 ER PT J AU Carrick, DM Blackshear, PJ AF Carrick, Danielle M. Blackshear, Perry J. TI Comparative expression of tristetraprolin (TTP) family member transcripts in normal human tissues and cancer cell lines SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT 3rd International Conference of the Collaborative Research Center Experimental Hepatology (SFB 575) CY OCT 13-14, 2006 CL Dusseldorf, GERMANY DE AU-rich element; tandem zinc finger proteins; mRNA turnover; deadenylation ID ZINC-FINGER PROTEINS; MESSENGER-RNA TURNOVER; AU-RICH ELEMENTS; TNF-ALPHA; SEQUENCE; DEADENYLATION; DEGRADATION; DEFICIENCY; ARTHRITIS; NUCLEAR AB The tristetraprolin (TTP) family of tandem zinc finger proteins comprises three members in man and most other mammals, with a fourth expressed in rodents. In mice, gene disruption of TTP itself leads to a systemic inflammatory syndrome that is mediated in large part by over-expression of tumor necrosis factor alpha (TNF). This increased expression is secondary to stabilization of the TNF mRNA in the TTP KO mice, a finding that led to the characterization of TTP as an mRNA binding protein that can promote the removal of the poly(A) tail from selected mRNAs and facilitate their nucleolytic destruction. The other human family members behave similarly to TTP in over-expression studies of transfected cells, but gene disruption experiments have implicated them in different physiological processes. In the present study, we developed a real-time PCR assay for all three human family members that allowed for comparative measurements of all three family members in the same tissues and cells. We used this assay to quantitate expression levels of all three transcripts in a variety of normal human tissues, as well as in the "NCI 60", a well characterized panel of human tumor cell lines. Although studies in fibroblasts and macrophages derived from knockout mice have failed to demonstrate compensatory expression of the family members in terms of transcript levels, it remains possible that the different family members can function as "TTP equivalents" in certain physiological or pathological circumstances. (C) 2007 Published by Elsevier Inc. C1 NIEHS, Off Clin Res, Res Triangle Pk, NC 27709 USA. NIEHS, Neurobiol Lab, 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, Off Clin Res, MD A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM black009@nichs.nih.gov FU Intramural NIH HHS NR 31 TC 44 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 15 PY 2007 VL 462 IS 2 BP 278 EP 285 DI 10.1016/j.abb.2007.04.011 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 179OJ UT WOS:000247299100021 PM 17517366 ER PT J AU Mamyrova, G Kleiner, DE James-Newton, L Shaham, B Miller, FW Rider, LG AF Mamyrova, Gulnara Kleiner, David E. James-Newton, Laura Shaham, Bracha Miller, Frederick W. Rider, Lisa G. TI Late-onset gastrointestinal pain in juvenile dermatomyositis as a manifestation of ischemic ulceration from chronic endarteropathy SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID DUODENAL PERFORATION; CHILDHOOD; TRANSPLANTATION; VASCULOPATHY C1 Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ So Calif, Sch Med, Childrens Hosp, Los Angeles, CA USA. RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, NIH, CRC Room 4-2332,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA. EM rider1@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101074-06] NR 16 TC 15 Z9 15 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 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2007 VL 57 IS 5 BP 881 EP 884 DI 10.1002/art.22782 PG 4 WC Rheumatology SC Rheumatology GA 177BZ UT WOS:000247129900027 PM 17530691 ER PT J AU Gajewski, E Gaur, S Akman, SA Matsumoto, L van Balgooy, JNA Doroshow, JH AF Gajewski, Ewa Gaur, Shikha Akman, Steven A. Matsumoto, Linda van Balgooy, Josephus N. A. Doroshow, James H. TI Oxidative DNA base damage in MCF-10A breast epithelial cells at clinically achievable concentrations of doxorubicin SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE doxorubicin; DNA damage; reactive oxygen species; apoptosis; chemotherapy; secondary malignancy ID HYDROGEN-PEROXIDE; REPAIR ENZYME; FREE-RADICALS; IN-VITRO; CANCER; ANTHRACYCLINES; REDUCTION; LEUKEMIA; CYCLOPHOSPHAMIDE; CYTOTOXICITY AB The cellular metabolism of doxorubicin generates reactive oxygen species with significant potential to damage DNA. Such DNA damage can result in mutations if not adequately repaired by cellular DNA repair pathways. Secondary malignancies have been reported in patients who have received doxorubicin-containing chemotherapeutic regimens; however, the underlying molecular mechanism(s) to explain the development of these tumors remains under active investigation. We have previously demonstrated the presence of DNA bases modified by oxidation in the peripheral blood mononuclear cells of patients with breast cancer following treatment with doxorubicin. In those studies, doxorubicin was administered by continuous infusion over 96 h to minimize the risk of cardiac toxicity. To evaluate potential mechanisms underlying doxorubicin-induced DNA base oxidation in non-malignant tissues, MCF-10A breast epithelial cells were cultured for 96 h with the same doxorubicin concentration achieved in vivo (0.1 mu M). During doxorubicin exposure, MCF-10A cells underwent growth arrest and apoptosis, developed elevated levels of reactive oxygen species, and demonstrated a time-dependent and significant increase in the levels of 11 oxidized DNA bases, as determined by gas chromatography/mass spectroscopy. Diminished expression of DNA repair enzymes was also observed over the same time course. Thus, clinically achievable concentrations of doxorubicin induce a level of oxidative stress in MCF-10A cells that is capable of oxidizing DNA bases and significantly altering cellular proliferation. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. Wake Forest Univ, Ctr Comprehens Canc, Dept Canc Biol, Winston Salem, NC 27109 USA. City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA. RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, NIH, Bldg 31,Room 3A44,31 Ctr Dr, Bethesda, MD 20892 USA. EM doroshoj@mail.NIH.gov FU Intramural NIH HHS [Z01 BC010677-03]; NCI NIH HHS [CA33572, N01-CO-12400, N01CO12400, P30 CA033572] NR 32 TC 28 Z9 28 U1 0 U2 0 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 JUN 15 PY 2007 VL 73 IS 12 BP 1947 EP 1956 DI 10.1016/j.bcp.2007.03.022 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 177AU UT WOS:000247126800009 PM 17445777 ER PT J AU Jain, M Palacio, LG Castellanos, FX Palacio, JD Pineda, D Restrepo, MI Munoz, JF Lopera, F Wallis, D Berg, K Bailey-Wilson, JE Arcos-Burgos, M Muenke, M AF Jain, Mahim Palacio, Luis Guillermo Castellanos, F. Xavier Palacio, Juan David Pineda, David Restrepo, Maria I. Munoz, Juan F. Lopera, Francisco Wallis, Deeann Berg, Kate Bailey-Wilson, Joan E. Arcos-Burgos, Mauricio Muenke, Maximilian TI Attention-deficit/hyperactivity disorder and comorbid disruptive behavior disorders: Evidence of pleiotropy and new susceptibility loci SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; alcohol abuse/dependence; conduct disorder; nicotine dependence; oppositional defiant disorder; pleiotropy ID DEFICIT-HYPERACTIVITY DISORDER; PEDIGREE DISEQUILIBRIUM TEST; COMPLEX SEGREGATION ANALYSIS; LATENT CLASS ANALYSIS; DSM-IV ADHD; ALCOHOL DEPENDENCE; CONDUCT DISORDER; RESEARCH CRITERIA; PSYCHIATRIC COMORBIDITY; ENVIRONMENTAL-FACTORS AB Background: Attention-deficit/hyperactivity disorder (ADHD) comorbid with oppositional defiant disorder (ODD) or conduct disorder (CD) and substance abuse/dependence seems to represent a specific subset within the phenotypic ADHD spectrum. Methods: We applied complex segregation and linkage analyses in a set of multigenerational families densely segregating ADHD comorbid with ODD, CD, alcohol abuse/dependence, and nicotine dependence. Results: Our data suggest that ADHD cosegregates with disruptive behaviors as a unique, phenotypically variable trait as evidenced by highly significant pair-wise linkages among: ADHD and ODD (logarithm of odds [LOD] = 14.19), ADHD and CD (LOD = 5.34), ODD and CD (LOD = 6.68), and CD and alcohol abuse/dependence (LOD = 3.98). In addition to previously reported ADHD susceptibility loci, we found evidence of linkage for comorbid ADHD phenotypes to loci at 8q24, 2p21-22.3, 5p13.1-p13.3, 12p11.23-13.3, 8q15, and 14q21.1-22.2. These results were replicated with an affected status phenotype derived from latent class clusters. Conclusions: Patterns of cosegregation of ADHD with comorbidities can inform our understanding of the inheritance patterns not only of ADHD but also of disruptive behavioral disorders and alcohol abuse/dependence. Refining the comorbid ADHD phenotype by determining the cosegregation profile of specific comorbidities might be a powerful tool for defining significant regions of linkage. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. HHMI NIH Res Scholars Program, Chevy Chase, MD USA. NYU, Child Study Ctr, New York, NY USA. Univ Antioquia, Neurosci Grp, Medellin, Colombia. RP Arcos-Burgos, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr,MSC 3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM marcosbu@nhgri.nih.gov OI Palacio, Juan David/0000-0002-1584-4391; Bailey-Wilson, Joan/0000-0002-9153-2920; Castellanos, Francisco/0000-0001-9192-9437 FU Intramural NIH HHS NR 79 TC 44 Z9 44 U1 5 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2007 VL 61 IS 12 BP 1329 EP 1339 DI 10.1016/j.biopsych.2006.06.026 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 177AX UT WOS:000247127100003 PM 16950213 ER PT J AU Saksena, R Adamo, R Kovac, P AF Saksena, Rina Adamo, Roberto Kovac, Pavol TI Immunogens related to the synthetic tetrasaccharide side chain of the Bacillus anthracis exosporium SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE oligosaccharides; carbohydrates; glycoconjugates; synthetic carbohydrate antigens; conjugation by squaric acid chemistry ID ARTIFICIAL CARBOHYDRATE ANTIGENS; VIBRIO-CHOLERAE O-1; MAJOR GLYCOPROTEIN; CONJUGATE VACCINE; REPEATING-UNIT; SEROTYPE OGAWA; O-PS; OLIGOSACCHARIDES; DERIVATIVES; ANTIBODIES AB The known methyl 2-O-acetyl-3,4-di-O-benzyl-1-thio-alpha-L-rhamnopyranoside (3) was converted to the corresponding 5-methoxycarbonylpentyl glycoside 4 which was deacetylated. The product 5 was used as the initial glycosyl acceptor to construct two trirhamnoside glycosyl acceptors having HO-3(III) flanked by either benzoyl or benzyl groups, compounds 10 and 29, respectively [fully protected, except HO-3(III), alpha-L-Rha-(l -> 3)-alpha-L-Rha-(1 -> 2)-alpha-L-Rha-1-O-(CH2)(5)COOCH3]. When these were glycosylated with ethyl 4-azido-3-O-benzyl-4,6-dideoxy-2-O-bromoacetyl-1-thio-beta-D-glucopyranoside (18), only the benzylated glycosyl acceptor 29 gave good yield of the desired tetrasaccharide 30. The alpha- and P-linked products, together with the corresponding orthoester 23, were formed in almost equal amount when glycosylation of 10 was performed with the glycosyl donor carrying the 2-O-bromoacetyl protecting group. Deprotection at O-2 of 30, followed by further functionalization of the molecule and global deprotection, gave the 5-methoxycarbonylpentyl glycoside of the title tetrasaccharide, beta-Ant-(1 -> 3)-alpha-L-Rha-(1 -> 3)-alpha-L-Rha-(1 -> 2)-alpha-L-Rha (35). Except for differences due to presence of the anomeric 5-methoxycarbonylpentyl group, the fully assigned NMR spectra of glycoside 35 were found to be virtually identical to those reported for the parent tetrasaccharide isolated from Bacillus anthracis exosporium, thus proving the correct structure assigned to the naturally occurring substance. All theoretically possible structural fragments of 35, as well as analog of 35 lacking the 2-O-methyl group at the terminal 4,6-dideoxyglucosyl residue, compound 40, were also synthesized. Tetrasaccharide 35, its P-linked and non-methylated analogs 2 and 40, respectively, as well as the trirhamnoside fragment of 35, glycoside 12, were further functionalized and conjugated to BSA using squaric acid chemistry, to give neoglycoconjugates with a predetermined carbohydrate-protein ratio of similar to 3 and similar to 6. Published by Elsevier Ltd. C1 NIDDK, LBC, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov FU Intramural NIH HHS [Z01 DK059701-34] NR 35 TC 27 Z9 27 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 15 PY 2007 VL 15 IS 12 BP 4283 EP 4310 DI 10.1016/j.bme.2007.03.057 PG 28 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 173JX UT WOS:000246870400033 PM 17412599 ER PT J AU Finke, JM Jennings, PA Lee, JC Onuchic, JN Winkler, JR AF Finke, John M. Jennings, Patricia A. Lee, Jennifer C. Onuchic, Jose N. Winkler, Jay R. TI Equilibrium unfolding of the poly(glutamic acid)(20) helix SO BIOPOLYMERS LA English DT Article DE landscape theory; folding funnel; polyglutamic acid; fluorescence; protein folding; FRET; MD; circular dichroism; helix coil transition ID RESONANCE ENERGY-TRANSFER; MOLECULAR-DYNAMICS SIMULATIONS; ALANINE-BASED PEPTIDES; BETA-HAIRPIN FORMATION; CYTOCHROME-C; POLYPEPTIDE-CHAINS; FOLDING DYNAMICS; ALPHA-SYNUCLEIN; AMINO-ACIDS; SECONDARY STRUCTURE AB The equilibrium structural ensemble of a 20-residue polyglutamic acid peptide (E-20) was studied with FRET, circular dichroism, and molecular dynamics (MD) simulations. A FRET donor, o-aminobenzamide, and acceptor, 3-nitrotyrosine, were introduced at the N- and C-termini, respectively. circular dichroisrn, steady state FRET, and time-resolved FRET measurements were employed to characterize the fraction helix and end-to-end distance under different pH conditions: pH 4 (60% alpha -helix), pH 6 (0% alpha-helix), and pH 9 (0% a -helix). At pH 4, the end-to-end distance was measured at 24 angstrom and determined to be considerably less than the 31 angstrom predicted for an alpha-helix of the same length. At pH 6 and 91 the end-to-end distance was measured at > 31 and 39 A respectively, both which are determined to be considerably greater than the 27 A predicted for a freely jointed random coil of the same length. To better understand the physical forces underlying the unusual helix-coil transition in this peptide, three theoretical MD models of E-20 were constructed: (1) a pure alpha-helix, (2) an alpha-helix with equivalent attractive intramolecular contacts, and (3) a weak alpha-helix with termini-weighted intramolecular contacts ("sticky ends"). Using MD simulations, the bent helix structure calculated from Model 3 was found to be the closest in agreement with the experimental data. (C) 2007 Wiley Periodicals, Inc. Biopolymers 86: 193-211, 2007. C1 Oakland Univ, Dept Chem, Rochester, MI 48309 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. NHLBI, Mol Biophys Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Ctr Theoret Biol Phys, La Jolla, CA 92093 USA. CALTECH, Beckman Inst, Pasadena, CA 91125 USA. RP Finke, JM (reprint author), Oakland Univ, Dept Chem, Rochester, MI 48309 USA. EM finke@oakland.edu RI Lee, Jennifer/E-9658-2015 OI Lee, Jennifer/0000-0003-0506-8349 FU NIGMS NIH HHS [GM064936-01, GM068461, GM54038, R01 GM054038] NR 75 TC 14 Z9 14 U1 2 U2 15 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-3525 EI 1097-0282 J9 BIOPOLYMERS JI Biopolymers PD JUN 15 PY 2007 VL 86 IS 3 BP 193 EP 211 DI 10.1002/bip.20719 PG 19 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 173HV UT WOS:000246865000002 PM 17370320 ER PT J AU Pancrazio, JJ Wang, F Kelley, CA AF Pancrazio, Joseph J. Wang, Fei Kelley, Chfistine A. TI Enabling tools for tissue engineering SO BIOSENSORS & BIOELECTRONICS LA English DT Review DE bioreactors; cryopreservation; modeling; patterning; polymers; scaffolds ID OPTICAL COHERENCE TOMOGRAPHY; RAPID PROTOTYPING TECHNIQUES; COMPUTER-AIDED-DESIGN; IN-VITRO; MULTIPHOTON MICROSCOPY; COLLOIDAL LITHOGRAPHY; DRUG-DELIVERY; HUMAN SKIN; CELLS; BIOREACTOR AB Tissue engineering is a multidisciplinary field that combines engineering, physical sciences, biology, and medicine to restore or replace tissues and organs functions. In this review, enabling tools for tissue engineering are discussed in the context of four key areas or pillars: prediction, production, performance, and preservation. Prediction refers to the computational modeling where the ability to simulate cellular behavior in complex three-dimensional environments will be essential for design of tissues. Production refer imaging modalities that allow high resolution, non-invasive monitoring of the development and incorporation of tissue engineered constructs. Lastly, preservation includes biochemical tools that permit cryopreservation, vitrification, and freeze-drying of cells and tissues. Recent progress and future perspectives for development in each of these key areas are presented. (c) 2007 Elsevier B.V. All rights reserved. C1 NINDS, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Pancrazio, JJ (reprint author), NINDS, NIH, 6001 Execut Blvd,MSC 2205, Rockville, MD 20852 USA. EM pancrazj@ninds.nih.gov RI Pancrazio, Joseph/M-3206-2015 OI Pancrazio, Joseph/0000-0001-8276-3690 NR 90 TC 47 Z9 48 U1 0 U2 19 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD JUN 15 PY 2007 VL 22 IS 12 BP 2803 EP 2811 DI 10.1016/j.bios.2006.12.023 PG 9 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 183EK UT WOS:000247555300006 PM 17240132 ER PT J AU Raveche, ES Salerno, E Scaglione, BJ Manohar, V Abbasi, F Lin, YC Fredrickson, T Landgraf, P Ramachandra, S Huppi, K Toro, JR Zenger, VE Metcalf, RA Marti, GE AF Raveche, Elizabeth S. Salerno, Erica Scaglione, Brian J. Manohar, Vijaya Abbasi, Fatima Lin, Yi-Chu Fredrickson, Torgny Landgraf, Pablo Ramachandra, Sumant Huppi, Konrad Toro, Jorge R. Zenger, Vincent E. Metcalf, Robert A. Marti, Gerald E. TI Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MURINE MODEL; LYMPHOPROLIFERATIVE DISEASE; GENES; SEQUENCE; REGION; LUPUS; MOUSE; CELLS; SUSCEPTIBILITY AB New Zealand black (NZB) mice with autoimmune and B lymphoproliferative disease (B-LPD) are a model for human chronic lymphocytic leukemia (CLL). A genomewide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content, and microsatellite polymorphisms, 74 had disease. The CD5(+), IgM(+), B220(dim), hyperdiploid LPD was linked to 3 loci on chromosomes 14, 18, and 19 that are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs mir-15a16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3' flanking sequence of the identical microRNA, mir16-1, and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cellcycle alterations and increased apoptosis. Linkage of the mir-15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the mir-15a/16-1 is the molecular lesion in CLL. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ 07103 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIH, NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. Natl Inst Hlth, Natl Canc Inst, Gene Silencing Sect, Ctr Adv Technol, Gaithersburg, MD USA. NIH, NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Rockville, MD USA. Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA. RP Marti, GE (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, 185 S Orange Ave, Newark, NJ 07103 USA. EM gemarti@helix.nih.gov FU NIAID NIH HHS [CA/AI71478-07, F32 AI071478] NR 43 TC 178 Z9 193 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5079 EP 5086 DI 10.1182/blood-2007-02-071225 PG 8 WC Hematology SC Hematology GA 180JW UT WOS:000247360200012 PM 17351108 ER PT J AU Neelapu, SS Gause, BL Harvey, L Lee, ST Frye, AR Horton, J Robb, RJ Popescu, MC Kwak, LW AF Neelapu, Sattva S. Gause, Barry L. Harvey, Linda Lee, Seung-Tae Frye, Andrea Robin Horton, Jessie Robb, Richard J. Popescu, Mircea C. Kwak, Larry W. TI A novel proteoliposomal vaccine induces antitumor immunity against follicular lymphoma SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; NON-HODGKINS-LYMPHOMAS; RESPONSES; ANTIGEN; DELIVERY AB Clinical studies suggest that treatment with vaccines comprised of idlotype protein may be associated with improved clinical outcome in follicular lymphoma patients. The time-consuming process required to generate patient-specific vaccines is a major limitation, however. Here we report results of a pilot clinical trial with a novel autologous, tumor-derived proteoliposome vaccine formulation that could be rapidly produced within a single day. Vaccination was safe, induced autologous tumor-specific type 1 cytokine responses in 5 out of 10 follicular lymphoma patients, and was associated with induction of a sustained complete response in one patient. Other patients had large tumor burdens and progressed after a median duration of 8 months. These results suggest that further testing of this vaccine formulation, particularly in the setting of minimal disease, is warranted. Furthermore, the proteoliposome formulation may provide a model for vaccine development for other human cancers, for which tumor-associated antigens need not be defined. C1 Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. NIH, Ctr Canc Res, Expt & Transplantat Immunol Branch, Bethesda, MD 20892 USA. NCI, SAIC, Frederick, MD 21701 USA. XEME Biopharma Inc, Plainsboro, NJ USA. RP Neelapu, SS (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, 1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [N01 CO12400] NR 14 TC 19 Z9 21 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 JUN 15 PY 2007 VL 109 IS 12 BP 5160 EP 5163 DI 10.1182/blood-2006-12-063594 PG 4 WC Hematology SC Hematology GA 180JW UT WOS:000247360200024 PM 17339422 ER PT J AU Hsu, C Jones, SA Cohen, CJ Zheng, ZL Kerstann, K Zhou, JH Robbins, PF Peng, PD Shen, XL Gomes, TJ Dunbar, CE Munroe, DJ Stewart, C Cornetta, K Wangsa, D Ried, T Rosenberg, SA Morgan, RA AF Hsu, Cary Jones, Stephanie A. Cohen, Cyrille J. Zheng, Zhili Kerstann, Keith Zhou, Juhua Robbins, Paul F. Peng, Peter D. Shen, Xinglei Gomes, Theotonius J. Dunbar, Cynthia E. Munroe, David J. Stewart, Claudia Cornetta, Kenneth Wangsa, Danny Ried, Thomas Rosenberg, Steven A. Morgan, Richard A. TI Cytokine-independent growth and clonal expansion of a primary human CD8(+) T-cell clone following retroviral transduction with the IL-15 gene SO BLOOD LA English DT Article ID PERIPHERAL-BLOOD LYMPHOCYTES; TRANSCRIPTION START REGIONS; HEMATOPOIETIC STEM; TELOMERE LENGTH; PROGENITOR CELLS; INSERTIONAL MUTAGENESIS; ANTITUMOR-ACTIVITY; TRANSFER THERAPY; HUMAN TUMOR; LONG-TERM AB Malignancies arising from retrovirally transduced hernatopoietic stem cells have been reported in animal models and human gene therapy trials. Whether mature lymphocytes are susceptible to insertional mutagenesis is unknown. We have characterized a primary human CD8(+) Tcell clone, which exhibited logarithmic ex vivo growth in the absence of exogenous cytokine support for more than 1 year after transduction with a murine leukemia virus-based vector encoding the T-cell growth factor IL-15. Phenotypically, the clone was CD28(-), CD45RA(-), CD45RO(+), and CD62L(-), a profile consistent with effector memory T lymphocytes. After gene transfer with tumor-antigenspecific T-cell receptors, the clone secreted IFN-gamma upon encountering tumor targets, providing further evidence that they derived from mature lymphocytes. Gene-expression analyses revealed no evidence of insertional activation of genes flanking the retroviral insertion sites. The clone exhibited constitutive telomerase activity, and the presence of autocrine loop was suggested by impaired cell proliferation following knockdown of IL-15R alpha expression. The generation of this cell line suggests that nonphysiologic expression of IL-15 can result in the longterm in vitro growth of mature human T lymphocytes. The cytokine-independent growth of this line was a rare event that has not been observed in other IL-15 vector transduction experiments or with any other integrating vector system. It does not appear that the retroviral vector integration sites played a role in the continuous growth of this cell clone, but this remains under investigation. C1 Ctr Canc Res, Natl Canc Inst, NIH, Surg Branch, Bethesda, MD USA. Natl Canc Inst, Immunol Expt Branch, Bethesda, MD USA. NHLBI, NIH, Hematol Branch, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Natl Canc Inst, Lab Mol Technol, Frederick, MD USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46204 USA. Ctr Canc Res, Natl Canc Inst, NIH, Genet Branch, Bethesda, MD USA. RP Morgan, RA (reprint author), Ctr Canc Res, Natl Canc Inst, NIH, Surg Branch, Bethesda, MD USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS NR 54 TC 42 Z9 43 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 JUN 15 PY 2007 VL 109 IS 12 BP 5168 EP 5177 DI 10.1182/blood-2006-06-029173 PG 10 WC Hematology SC Hematology GA 180JW UT WOS:000247360200026 PM 17353346 ER PT J AU Solomou, EE Gibellini, F Stewart, B Malide, D Berg, M Visconte, V Green, S Childs, R Chanock, SJ Young, NS AF Solomou, Elena E. Gibellini, Federica Stewart, Brian Malide, Daniela Berg, Maria Visconte, Valeria Green, Spencer Childs, Richard Chanock, Stephen J. Young, Neal S. TI Perforin gene mutations in patients with acquired aplastic anemia SO BLOOD LA English DT Article ID HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; CELL-DEATH; LYMPHOCYTES; DIVERSITY; A91V AB Perforin is a cytolytic protein expressed mainly in activated cytotoxic lymphocytes and natural killer cells. Inherited perforin mutations account for 20% to 40% of familial hernophagocytic lymphohistiocytosis, a fatal disease of early childhood characterized by the absence of functional perforin. Aplastic anemia, the paradigm of immune-mediated bone marrow failure syndromes, is characterized by hematopoietic stem cell destruction by activated T cells and Th1 cytokines. We examined whether mutations in the perforin gene occurred in acquired aplastic anemia. Three nonsynonymous PRF1 mutations among 5 unrelated patients were observed. Four of 5 patients with the mutations showed some hemophagocytosis in the bone marrow at diagnosis. Perforin protein levels in these patients were very low or absent, and perforin granules were completely absent. Natural killer (NK) cell cytotoxicity from these patients was significantly decreased. Our data suggest that PRF1 genetic alterations help explain the aberrant proliferation and activation of cytotoxic T cells and may represent genetic risk factors for bone marrow failure. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Natl Canc Inst, NIH, Pediat Oncol Branch, Bethesda, MD USA. NHLBI, Light Microscopy Core Facil, Bethesda, MD 20892 USA. RP Solomou, EE (reprint author), NHLBI, Hematol Branch, Bldg 10, Bethesda, MD 20892 USA. EM solomoue@nhlbi.nih.gov FU Intramural NIH HHS NR 25 TC 19 Z9 26 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5234 EP 5237 DI 10.1182/blood-2006-12-063495 PG 4 WC Hematology SC Hematology GA 180JW UT WOS:000247360200035 PM 17311987 ER PT J AU Sundstrom, JB Ellis, JE Hair, GA Kirshenbaum, AS Metcalfe, DD Yi, H Cardona, AC Lindsay, MK Ansari, AA AF Sundstrom, J. Bruce Ellis, Jane E. Hair, Gregory A. Kirshenbaum, Arnold S. Metcalfe, Dean D. Yi, Hong Cardona, Adriana C. Lindsay, Michael K. Ansari, Aftab A. TI Human tissue mast cells are an inducible reservoir of persistent HIV infection SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CD4(+) T-CELLS; TYPE-1 INFECTION; VIRAL RESERVOIR; GENE-EXPRESSION; LYMPHOID-TISSUE; RESTORATION; INDIVIDUALS; REPLICATION AB We have proposed that, unlike other HIV-vulnerable cell lineages, progenitor mast cells (prMCs), cultured in vitro from undifferentiated bone marrow-derived CD34(+) pluripotent progenitors (PPPs), are susceptible to infection during a limited period of their ontogeny. As infected prMCs mature in culture, they lose expression of viral chemokine coreceptors necessary for viral entry and develop into long-lived, latently infected mature tissue mast cells (MCs), resistant to new infection. In vivo recruitment of prMCs to different tissue compartments occurs in response to tissue injury, growth, and remodeling or allergic inflammation, allowing populations of circulating and potentially HIV-susceptible prMCs to spread persistent infection to diverse tissue compartments. In this report, we provide in vivo evidence to confirm this model by demonstrating that HIV-Infected women have both circulating prMCs and placental tissue MCs (PLIVICs) that harbor inducible infectious HIV even after highly active antiretroviral therapy (HAART) during pregnancy. Fur- thermore, infectious virus, capable of infecting alloactivated fetal cord blood mononuclear cells (CBMCs), could be induced in isolated latently infected PLIVICs after weeks in culture in vitro. These data provide the first in vivo evidence that tissue IVICs, developed from infected circulating prMCs, comprise a long-lived inducible reservoir of persistent HIV in infected persons during HAART. C1 Emory Univ, Sch Med, Dept Pathol, Lab Med, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA USA. NIAID, NIH, Allerg Dis Res Lab, Bethesda, MD 20892 USA. Emory Univ, Sch Med Microscopy Core, Atlanta, GA USA. Emory Univ, Sch Med, Atlanta, GA USA. RP Sundstrom, JB (reprint author), Emory Univ, Sch Med, Dept Pathol, Lab Med, Atlanta, GA 30322 USA. EM jsundst@emory.edu FU NIAID NIH HHS [R01 AI062383, AI062383] NR 27 TC 48 Z9 49 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5293 EP 5300 DI 10.1182/blood-2006-11-058438 PG 8 WC Hematology SC Hematology GA 180JW UT WOS:000247360200043 PM 17351109 ER PT J AU Chen, G Ghosh, P Osawa, H Sasaki, CY Rezanka, L Yang, JD O'Farrell, TJ Longo, DL AF Chen, Gang Ghosh, Paritosh Osawa, Hiroshi Sasaki, Carl Y. Rezanka, Louis Yang, Jiandong O'Farrell, Thomas J. Longo, Dan L. TI Resistance to TGF-beta 1 correlates with aberrant expression of TGF-beta receptor II in human B-cell lymphoma cell lines SO BLOOD LA English DT Article ID GROWTH-FACTOR-BETA; MICROSATELLITE INSTABILITY; LUNG-CANCER; PROMOTER METHYLATION; PROSTATE-CANCER; COLON CANCERS; GENE; MUTATIONS; INACTIVATION; PROGRESSION AB Resistance to transforming growth factor (TGF)-beta 1-mediated growth suppression in tumor cells is often associated with the functional loss of TGF-beta receptors. Here we describe two B-cell lymphoma cell lines (DB and RL) that differ in their sensitivity to TGF-beta 1-mediated growth suppression. The TGF-beta 1-resistant cell line DB lacked functional TGF-beta receptor II (T beta RII) in contrast to the TGF-beta-responsive cell line RL, whereas both cell lines had comparable levels of receptor I (T beta RI). Lack of functional T beta RII was correlated with the lack of TGF-beta 1-induced nuclear translocation of phospho-Smad3 and phospho-Smad2, the lack of nuclear expression of p21(Cip1/WAF1), and the down-regulation of c-Myc in DB cells. Transfection of wild-type, but not a C-terminal-truncated, form of T beta RII rendered the DB cell line responsive to TGF-beta 1-mediated growth suppression. Analysis of the T beta RII gene in DB cells revealed the absence of T beta RII message, which was reversed upon 5'-azacytidine treatment, indicating that the promoter methylation might be the cause of gene silencing. Promoter analysis revealed CpG methylations at -25 and - 140 that correlated with the gene silencing. These data suggest that promoter methylation plays an important role in T beta RII gene silencing and subsequent development of a TGF-beta 1-resistant phenotype by some B-cell lymphoma cells. C1 NIA, Gerontol Res Ctr, NIH, Lymphocyte Cell Biol Unit,Lab Immunol, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, NIH, Genet Lab, Baltimore, MD 21224 USA. RP Ghosh, P (reprint author), NIA, Gerontol Res Ctr, NIH, Lymphocyte Cell Biol Unit,Lab Immunol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM ghoshp@grc.nia.nih.gov FU Intramural NIH HHS NR 36 TC 16 Z9 16 U1 0 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 JUN 15 PY 2007 VL 109 IS 12 BP 5301 EP 5307 DI 10.1182/blood-2006-06-032128 PG 7 WC Hematology SC Hematology GA 180JW UT WOS:000247360200044 PM 17339425 ER PT J AU Perez-Diez, A Joncker, NT Choi, K Chan, WFN Anderson, CC Lantz, O Matzinger, P AF Perez-Diez, Ainhoa Joncker, Nathalie T. Choi, Kyungho Chan, William F. N. Anderson, Colin C. Lantz, Olivier Matzinger, Polly TI CD4 cells can be more efficient at tumor rejection than CD8 cells SO BLOOD LA English DT Article ID T-HELPER-CELLS; ANTITUMOR IMMUNE-RESPONSE; BLOOD MONONUCLEAR-CELLS; DENDRITIC CELLS; METASTATIC MELANOMA; IFN-GAMMA; ADOPTIVE IMMUNOTHERAPY; IN-VIVO; ESTABLISHED TUMORS; TRANSGENIC MICE AB Researchers designing antitumor treatments have long focused on eliciting tumor-specific CD8 cytotoxic T lymphocytes (CTL) because of their potent killing activity and their ability to reject transplanted organs. The resulting treatments, however, have generally been surprisingly poor at inducing complete tumor rejection, both in experimental models and in the clinic. Although a few scattered studies suggested that CD4 T "helper" cells might also serve as antitumor effectors, they have generally been studied mostly for their ability to enhance the activity of CTL. In this mouse study, we compared monoclonal populations of tumor-specific CD4 and CD8 T cells as effectors against several different tumors, and found that CD4 T cells eliminated tumors that were resistant to CD8-mediated rejection, even in cases where the tumors expressed major histocompatibility complex (MHC) class I molecules but not MHC class II. MHC class II expression on host tissues was critical, suggesting that the CD4 T cells act indirectly. Indeed, the CD4 T cells partnered with INK cells to obtain the maximal antitumor effect. These findings suggest that CD4 T cells can be powerful antitumor effector cells that can, in some cases, outperform CD8 T cells, which are the current "gold standard" effector cell in tumor immunotherapy. C1 NIAID, NIH, Ghost Lab, Bethesda, MD 20892 USA. NIAID, NIH, Cellular & Mol Immunol Lab, Bethesda, MD USA. Inst Natl Sante & Rech Med, Inst Curie, U520, Immunol Lab, Paris, France. Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. RP Perez-Diez, A (reprint author), NIAID, NIH, Ghost Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM ainhoa@nih.gov RI Lantz, Olivier/J-4960-2012; Choi, Kyungho/J-5685-2012 OI Lantz, Olivier/0000-0003-3161-7719; FU Intramural NIH HHS NR 66 TC 214 Z9 219 U1 0 U2 6 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5346 EP 5354 DI 10.1182/blood-2006-10-051318 PG 9 WC Hematology SC Hematology GA 180JW UT WOS:000247360200049 PM 17327412 ER PT J AU Snyder, JT Shen, JJ Azmi, H Hou, J Fowler, DH Ragheb, JA AF Snyder, James T. Shen, Jijia Azmi, Hooman Hou, Jeannie Fowler, Daniel H. Ragheb, Jack A. TI Direct inhibition of CD40L expression can contribute to the clinical efficacy of daclizumab independently of its effects on cell division and Tb1/Th2 cytokine production SO BLOOD LA English DT Article ID VERSUS-HOST-DISEASE; REGULATORY T-CELLS; RECEPTOR ANTIBODY DACLIZUMAB; IN-VIVO BLOCKADE; LIGAND EXPRESSION; MULTIPLE-SCLEROSIS; AUTOIMMUNE-DISEASE; LETHAL AUTOIMMUNITY; MONOCLONAL-ANTIBODY; TH2 DIFFERENTIATION AB Humanized anti-CD25 antibodies (eg, daclizumab) have been successfully used to treat several autoimmune diseases. Paradoxically, IL-2 blockade in mice can induce autoimmunity. An interspecies; difference in the relative contribution of IL-2 to CD25(+) T regulatory cell (CD25(+)Treg) versus CD25(+) effector cell function might explain this conundrum. Consistent with this are reports that daclizumab inhibits human CD25(+) effector cell cytokine production by blocking the expression of CD40L. However, in mice, IL-4 and IL-12 regulate CD40L expression. As human Th1/Th2 cytokine production is also dependent on IL-2, daclizumab's inhibition of CD40L expression could be due to an indirect, rather than a direct, effect of IL-2. Here, we clarify the mechanisms underlying CD40L expression. In contrast to the mouse, human CD40L is regulated by CD28 signaling and IL-2, not the principal Th1/Th2-polarizing cytokines. We find that CD40L is expressed on naive and memory cells and inhibited by daclizumab independently of cell division. Collectively, our results indicate that daclizumab could inhibit CD25(+) effector T-cell function in vivo by directly blocking CD40L expression. This difference between mice and human may help explain the paradoxical effects of IL-2R blockade in the 2 species. C1 NEI, Immunol Lab, Bethesda, MD 20892 USA. Natl Canc Inst, Canc Res Ctr, Expt Transplant & Immunol Branch, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RP Ragheb, JA (reprint author), NEI, Immunol Lab, Bldg 10, Bethesda, MD 20892 USA. EM jr50b@nih.gov NR 58 TC 23 Z9 23 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 JUN 15 PY 2007 VL 109 IS 12 BP 5399 EP 5406 DI 10.1182/blood-2006-12-062943 PG 8 WC Hematology SC Hematology GA 180JW UT WOS:000247360200055 PM 17344465 ER PT J AU Popescu, MC Robb, RJ Batenjany, MM Boni, LT Neville, ME Pennington, RW Neelapu, SS Kwak, LW AF Popescu, Mircea C. Robb, Richard J. Batenjany, Michael M. Boni, Lawrence T. Neville, Mary E. Pennington, Robin W. Neelapu, Sattva S. Kwak, Larry W. TI A novel proteoliposomal vaccine elicits potent antitumor immunity in mice SO BLOOD LA English DT Article ID B-CELL LYMPHOMA; COLONY-STIMULATING FACTOR; IDIOTYPE VACCINATION; DENDRITIC CELLS; RESPONSES; ANTIGEN; TRIAL AB Therapeutic vaccination against idiotype is a promising strategy for immunotherapy of B-cell malignancies. Its feasibility, however, is limited by the requirement for a patient-specific product. Here we describe a novel vaccine formulation prepared by simply extracting cell-membrane proteins from lymphoma cells and incorporating them together with IL-2 into proteoliposomes. The vaccine was produced in 24 hours, compared with more labor-intensive and time-consuming hybridoma or recombinant DNA methods. The vaccine elicited T-cell immunity in vivo, as demonstrated by secretion of type 1 cytokines. It protected against tumor challenge at doses of tumor antigen 50 to 100 times lower than that previously observed using either liposomes formulated with IL-2 and secreted lymphoma immunoglobulin or a prototype vaccine consisting of lymphoma immunoglobulin conjugated to keyhole limpet hemocyanin. The increased potency justifies testing similar patient-specific human vaccines prepared using extracts from primary tumor samples. C1 XEME Biopharma, Plainsboro, NJ USA. Biomira USA, Cranbury, NJ USA. Natl Canc Inst, Canc Res Ctr, Expt & Transplant & Immunol Branch, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. RP Popescu, MC (reprint author), XEME Biopharma, Plainsboro, NJ USA. EM mpopescu@xemebiopharma.com NR 17 TC 12 Z9 12 U1 3 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 JUN 15 PY 2007 VL 109 IS 12 BP 5407 EP 5410 DI 10.1182/blood-2006-08-039446 PG 4 WC Hematology SC Hematology GA 180JW UT WOS:000247360200056 PM 17351111 ER PT J AU Cerhan, JR Wang, S Maurer, MJ Ansell, SM Geyer, SM Cozen, W Morton, LM Davis, S Severson, RK Rothman, N Lynch, CF Wacholder, S Chanock, SJ Habermann, TM Hartge, P AF Cerhan, James R. Wang, Sophia Maurer, Matthew J. Ansell, Stephen M. Geyer, Susan M. Cozen, Wendy Morton, Lindsay M. Davis, Scott Severson, Richard K. Rothman, Nathaniel Lynch, Charles F. Wacholder, Sholom Chanock, Stephen J. Habermann, Thomas M. Hartge, Patricia TI Prognostic significance of host immune gene polymorphisms, in follicular lymphoma survival SO BLOOD LA English DT Article ID NON-HODGKIN-LYMPHOMA; BIOLOGICAL IMPLICATIONS; CYTOKINE PRODUCTION; CANCER; EXPRESSION; RISK; SUSCEPTIBILITY; INTERLEUKIN-8; MODEL; TIME AB Recent gene-expression data have suggested that host immune genetic signatures may predict outcomes in patients with follicular lymphoma. We evaluated the hypothesis that germ line common variation in candidate immune genes is associated with survival. Cox models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals for individual SNPs after accounting for age, clinical, and other demographic factors. The median age at diagnosis of the 278 patients was 57 years, and 59 (21%) of the patients died during follow-up, with a median follow-up of 59 months (range, 27-78 months) for surviving patients. SNPs in IL8 (rs4073; HRTT = 2.14, 1.26 - 3.63), IL2(rs2069762; HRGT/TT = 11.80, 1.06 - 3.05), IL12B (rs3212227; HRAC/CC = 1.83, 1.06-3.06), and IL1RN (rs454078; HRAA = 1.93, 1.11-3.34) were the most robust predictors of survival. A summary score of the number of deleterious genotypes from these genes was strongly associated with survival (P =.001). A risk score that combined the 4 SNPs with the clinical and demographic factors was even more strongly associated with survival (P <.001); the 5-year KaplanMeier survival estimates were 96% (930/, 100%), 72% (62%-83%), and 58% (480/,72%) for groups at low, intermediate, and high risk, respectively. Common variation in host immune genes warrants further evaluation as a promising class of prognostic factors in follicular lymphoma. C1 Coll Med, Mayo Clin, Rochester, MN USA. Natl Canc Inst, Bethesda, MD USA. Univ So Calif, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Karmanos Canc Inst, Detroit, MI USA. Univ Iowa, Iowa City, IA USA. RP Cerhan, JR (reprint author), Coll Med, Mayo Clin, Rochester, MN USA. EM cerhan.james@mayo.edu RI Geyer, Susan/E-3112-2011; Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X FU Intramural NIH HHS; NCI NIH HHS [N01 PC067009, N01 PC065064, N01 PC067008, N01 PC067010, P50 CA097274, P50 CA97274, R01 CA096704, R01 CA96704] NR 53 TC 76 Z9 78 U1 1 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 JUN 15 PY 2007 VL 109 IS 12 BP 5439 EP 5446 DI 10.1182/blood-2006-11-058040 PG 8 WC Hematology SC Hematology GA 180JW UT WOS:000247360200060 PM 17327408 ER PT J AU Schardt, C Adams, MB Owens, T Keitz, S Fontelo, P AF Schardt, Connie Adams, Martha B. Owens, Thomas Keitz, Sheri Fontelo, Paul TI Utilization of the PICO framework to improve searching PubMed for clinical questions SO BMC MEDICAL INFORMATICS AND DECISION MAKING LA English DT Article ID MEDICINE RESIDENTS; PATIENT-CARE; ANSWER AB Background: Supporting 21st century health care and the practice of evidence-based medicine (EBM) requires ubiquitous access to clinical information and to knowledge-based resources to answer clinical questions. Many questions go unanswered, however, due to lack of skills in formulating questions, crafting effective search strategies, and accessing databases to identify best levels of evidence. Methods: This randomized trial was designed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system. Two of the search interfaces utilized a specific framework called PICO, which was designed to focus clinical questions and to prompt for publication type or type of question asked. The third interface was the standard PubMed interface readily available on the Web. Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US. Thirty-one subjects were randomized to one of the three interfaces, given 3 clinical questions, and asked to search PubMed for a set of relevant articles that would provide an answer for each question. The success of the search results was determined by a precision score, which compared the number of relevant or gold standard articles retrieved in a result set to the total number of articles retrieved in that set. Results: Participants using the PICO templates ( Protocol A or Protocol B) had higher precision scores for each question than the participants who used Protocol C, the standard PubMed Web interface. ( Question 1: A = 35%, B = 28%, C = 20%; Question 2: A = 5%, B = 6%, C = 4%; Question 3: A = 1%, B = 0%, C = 0%) 95% confidence intervals were calculated for the precision for each question using a lower boundary of zero. However, the 95% confidence limits were overlapping, suggesting no statistical difference between the groups. Conclusion: Due to the small number of searches for each arm, this pilot study could not demonstrate a statistically significant difference between the search protocols. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results. C1 Natl Lib Med, Bethesda, MD 20894 USA. Miami VAMC, Dept Med 111, Miami, FL 33125 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr Lib, Durham, NC 27710 USA. RP Fontelo, P (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM connie.schardt@duke.edu; martha.adams@duke.edu; thomas.owens@duke.edu; skeitz@med.miami.edu; fontelo@nlm.nih.gov NR 14 TC 146 Z9 149 U1 5 U2 21 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6947 J9 BMC MED INFORM DECIS JI BMC Med. Inform. Decis. Mak. PD JUN 15 PY 2007 VL 7 AR 16 DI 10.1186/1472-6947-7-16 PG 6 WC Medical Informatics SC Medical Informatics GA 184BR UT WOS:000247616600001 PM 17573961 ER PT J AU Sharma, S AF Sharma, Sudha TI Age-related nonhomologous end joining activity in rat neurons SO BRAIN RESEARCH BULLETIN LA English DT Article DE nonhomologous end joining; double strand breaks; DNA repair; neuron; aging ID DOUBLE-STRAND BREAKS; HUMAN CELL-EXTRACTS; RECOMBINATION-ACTIVATING GENE-1; MOUSE TESTICULAR EXTRACTS; KINASE CATALYTIC SUBUNIT; LIGASE IV DEFICIENCY; DNA-REPAIR; HOMOLOGOUS RECOMBINATION; CEREBRAL-CORTEX; DEFECTIVE NEUROGENESIS AB DNA double strand break (DSB) represents a potentially lethal form of DNA damage. Reports suggest that DSBs are introduced in neurons during the course of normal development, and repair of such DSBs is essential for neuronal survival. The molecular mechanisms of DSB repair by nonhomologous end joining (NHEJ) have been described in several cell types. The present study describes age-related NHEJ activity in the isolated neurons from rat cerebral cortex. Cell-free extracts prepared from rat cortical neurons support efficient NHEJ of linearized plasmid DNA in an in vitro DSB repair assay. End joining efficiency of young neurons is dependent on DNA end structure. A linear plasmid with blunt ends was joined less efficiently by the neuronal extracts than the cohesive or non-matching protruding DNA ends. NHEJ in neurons was blocked by the DNA-PKcs inhibitor wortmannin, and dNTP, and could occur in the absence of exogenously added ATP. The end joining process in young rat neurons is nonfaithful. In vitro NHEJ activity was considerably lower in adult brain, and neurons from old brain failed to support significant end joining. The age-dependent profile of neuronal NHEJ indicates that neurons in postnatal brain utilize error-prone NHEJ to repair DNA double strand breaks accumulated within the genome and this activity declines gradually with age. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Hyderabad, Sch Life Sci, Dept Biochem, ICMR Ctr Res Aging & Brain CRAB, Hyderabad 500046, Andhra Pradesh, India. RP Sharma, S (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sharmasu@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 NR 47 TC 14 Z9 14 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUN 15 PY 2007 VL 73 IS 1-3 BP 48 EP 54 DI 10.1016/j.brainresbull.2007.02.011 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 177DP UT WOS:000247134100006 PM 17499636 ER PT J AU Aid, S Bosetti, F AF Aid, Saba Bosetti, Francesca TI Gene expression of cyclooxygenase-1 and Ca2+-independent phospholipase A(2) is altered in rat hippocampus during normal aging SO BRAIN RESEARCH BULLETIN LA English DT Article DE cyclooxygenases; calcium-independent phospholipase A(2); hippocampus; thromboxane; prostaglandin ID AGE-RELATED-CHANGES; FIBRILLARY ACIDIC PROTEIN; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; MESSENGER-RNA; ALZHEIMERS-DISEASE; BRAIN ASTROCYTES; FRONTAL-CORTEX; IMMUNE-SYSTEM; BROWN-NORWAY AB Brain aging is associated with inflammatory changes. However, data on how the brain arachidonic acid (AA) metabolism is altered as a function of age are limited and discrepant. AA is released from membrane phospholipids by phospholipase A(2) (PLA(2)) and then further metabolized to bioactive prostaglandins and thromboxanes by cyclooxygenases (COX)-1 and -2. We examined the phospholipase A(2) (PLA(2))/COX-mediated AA metabolic pathway in the hippocampus and cerebral cortex of 4-, 12-, 24- and 30-month-old rats. A two-fold increase in brain thromboxane B-2 level in 24 and 30 months was accompanied by increased hippocampal COX-1 mRNA levels at 12, 24, and 30 months. COX-2 mRNA expression was significantly decreased only at 30 months. Hippocampal Ca2+-independent iPLA(2) mRNA levels were decreased at 24 and 30 months without any change in Ca2+-dependent PLA(2) expression. In the cerebral cortex, mRNA levels of COX and PLA(2) were not significantly changed. The specific changes in the AA cascade observed in the hippocampus may alter phospholipids homeostasis and possibly increase the susceptibility of the aging brain to neuroinflammation. Published by Elsevier Inc. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Bosetti, F (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9 Mem Dr,Bldg 9,Rm 1S126, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU Intramural NIH HHS [Z01 AG000424-04] NR 53 TC 29 Z9 32 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD JUN 15 PY 2007 VL 73 IS 1-3 BP 108 EP 113 DI 10.1016/j.brainresbull.2007.02.015 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 177DP UT WOS:000247134100014 PM 17499644 ER PT J AU Breen, N Cronin, KA Meissner, HI Taplin, SH Tangka, FK Tiro, JA McNeel, TS AF Breen, Nancy Cronin, Kathleen A. Meissner, Helen I. Taplin, Stephen H. Tangka, Florence K. Tiro, Jasmin A. McNeel, Timothy S. TI Reported drop in mammography - Is this cause for concern? SO CANCER LA English DT Article DE breast cancer incidence; mammography; cancer screening; National Health Interview Survey ID BREAST-CANCER AB BACKGROUND. Timely screening with mammography can prevent a substantial number of deaths from breast cancer. The objective of this brief was to ascertain whether recent use of mammography has dropped nationally. METHODS. The authors assessed the trend in mammography rates from 1987 through 2005. Then, they used the 2000 and 2005 National Health Interview Survey (NHIS) estimates to characterize trends and current patterns in mammography use. RESULTS. After robust, rapid increases in reported use of mammography by women in the U.S. since 1987, estimates from the 2005 NHIS showed a decline compared with 2000 (from 70% to 66%). Although it was small, this decline may be cause for concern, because it signals a change in direction. CONCLUSIONS. This report establishes for the nation what already has been observed in some local data. The results confirmed that the use of mammography may be falling. This change needs to be monitored carefully and also may call for intervention. C1 NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Bethesda, MD USA. Informat Management Serv Inc, Rockville, MD USA. RP Breen, N (reprint author), NCI, Div Canc Control & Populat Sci, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM breenn@mail.nih.gov OI Tiro, Jasmin/0000-0001-8300-0441 NR 19 TC 148 Z9 149 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 JUN 15 PY 2007 VL 109 IS 12 BP 2405 EP 2409 DI 10.1002/cncr.22723 PG 5 WC Oncology SC Oncology GA 176VR UT WOS:000247113500003 PM 17503429 ER PT J AU Owen, JE Goldstein, MS Lee, JH Breen, N Rowland, JH AF Owen, Jason E. Goldstein, Michael S. Lee, Jennifer H. Breen, Nancy Rowland, Julia H. TI Use of health-related and cancer-specific support groups among adult cancer survivors SO CANCER LA English DT Article DE cancer; support; adult; survivorship ID STAGE BREAST-CANCER; GROUP PARTICIPATION; INTERVIEW SURVEY; WOMEN; PREVALENCE; DIAGNOSIS; DISORDERS; MEDICINE; PROSTATE; LIFE AB BACKGROUND. Data from the National Health Inter-view Survey suggest that the utilization of mental health services among cancer survivors is low and unmet needs are high for some. However, to the authors' knowledge little is known regarding the prevalence and predictors of participation in health-related support groups. METHODS. A total of 9187 participants in the California Health Interview Survey Complementary and Alternative Medicine (CHIS-CAM) study completed a telephone interview in 2003 (1844 participants with cancer and 4951 participants with other chronic health problems). Participants were asked to describe previous/ current support group use, benefits of support group use, and physician involvement in decisions regarding support groups. Weighted logistic regression analyses were conducted using SUDAAN software to examine patterns of support group use. RESULTS. The prevalence of support group use was found to be higher among cancer survivors (23.7%) than those with another chronic health condition (14.5%). Predictors of support group use were found to be similar across groups and included female gender, greater education, use of complementary and alternative medicine (CAM), depression, and anxiety. Age, health insurance, and presence of depression predicted support group use differently for cancer survivors and those with other conditions. The percentages of those perceiving support groups to be beneficial varied from 35.1% for those with skin cancer to 96% for those with cervical cancer. The percentage of participants reporting that their physician recommended a support group was low (10.2%). CONCLUSIONS. Health-related support groups are used by nearly I in 4 cancer survivors, but levels of utilization differ across subgroups. An understanding of how cancer survivors use support groups highlights shortcomings in psychosocial care and suggests that additional efforts to overcome barriers to care are needed. C1 Loma Linda Univ, Dept Psychol, Loma Linda, CA 92350 USA. Univ Calif Los Angeles, Los Angeles Ctr Hlth Policy Res, Los Angeles, CA 90024 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Owen, JE (reprint author), Loma Linda Univ, Dept Psychol, 11130 Anderson St, Loma Linda, CA 92350 USA. EM jowen@llu.edu RI Lee, Jennifer/C-2698-2008 FU PHS HHS [263-MQ-418286-1] NR 32 TC 39 Z9 39 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2007 VL 109 IS 12 BP 2580 EP 2589 DI 10.1002/cncr.22719 PG 10 WC Oncology SC Oncology GA 176VR UT WOS:000247113500025 PM 17503435 ER PT J AU Verona, EV Elkahloun, AG Yang, JH Bandyopadhyay, A Yeh, IT Sun, LZ AF Verona, Erik V. Elkahloun, Abdel G. Yang, Junhua Bandyopadhyay, Abhik Yeh, I-Tien Sun, Lu-Zhe TI Transforming growth factor-beta signaling in prostate stromal cells supports prostate carcinoma growth by up-regulating stromal genes related to tissue remodeling SO CANCER RESEARCH LA English DT Article ID TGF-BETA; TUMOR-SUPPRESSOR; IN-VIVO; CANCER PROGRESSION; REACTIVE STROMA; XENOGRAFT MODEL; II RECEPTOR; MCF-7 CELLS; MYOFIBROBLAST; FIBROBLASTS AB Increasing evidence points to an active stromal involvement in cancer initiation and progression. Cytokines derived from tumor cells are believed to modulate stromal cells to produce growth and angiogenic factors, which in turn provide the tumor with the necessary microenvironment for expansion and invasion. Transforming growth factor beta (TGF beta) has been implicated as a candidate cytokine to mediate this communication. However, how its signaling in stromal cells regulates tumorigenesis and tumor progression remains unresolved. We show that normal, presenescent fibroblasts or prostate stromal cells cotransplanted with prostate carcinoma cells s.c. into nude mice reduced tumor latency and accelerated tumor growth. When their TGF beta signaling was blocked, the fibroblasts and stromal cells still stimulated tumor initiation but no longer supported tumor growth as control cells did. The loss of the tumor growth-promoting activity of the stromal cells with attenuated TGF beta signaling was not associated with altered cellular senescence or tumor angiogenicity. TGF beta and the medium conditioned by the prostate carcinoma cells stimulated myofibroblast differentiation of the intact stromal cells, but not the stromal cells with attenuated TGF beta signaling. Gene microarray and quantitative reverse transcription-PCR analyses showed that TGF beta upregulated a host of genes in stromal cells that are involved in tissue remodeling and wound healing. Thus, our study provides evidence for TGF beta as a supporting agent in tumor progression through the induction of a perpetual wound healing process in the tumor microenvironment. C1 Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio Canc Inst, San Antonio, TX USA. NIH, NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Sun, LZ (reprint author), Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, 7703 Floyd Curl Dr,Mail Code 7762, San Antonio, TX 78229 USA. EM sunl@uthscsa.edu FU Intramural NIH HHS; NCI NIH HHS [R01CA79683, R01CA75253] NR 48 TC 55 Z9 56 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2007 VL 67 IS 12 BP 5737 EP 5746 DI 10.1158/0008-5472.CAN-07-0444 PG 10 WC Oncology SC Oncology GA 180JV UT WOS:000247360100023 PM 17575140 ER PT J AU Huang, J Hu, JY Bian, XW Chen, KQ Gong, WH Dunlop, NM Howard, OMZ Wang, JM AF Huang, Jian Hu, Jinyue Bian, Xiuwu Chen, Keqiang Gong, Wanghua Dunlop, Nancy M. Howard, O. M. Zack Wang, Ji Ming TI Transactivation of the epidermal growth factor receptor by formylpeptide receptor exacerbates the malignant behavior of human glioblastoma cells SO CANCER RESEARCH LA English DT Article ID ACTIVATED PROTEIN-KINASE; FORMYL-PEPTIDE RECEPTORS; EGF RECEPTOR; ANGIOTENSIN-II; TRANSFORMING-GROWTH; SIGNALING PATHWAYS; GENE AMPLIFICATION; EPITHELIAL-CELLS; N-FORMYLPEPTIDE; CANCER CELLS AB The G protein-coupled formylpeptide receptor (FPR), which mediates leukocyte migration in response to bacterial and host-derived chemotactic peptides, promotes the chemotaxis, survival, and tumorigenesis of highly malignant human glioblastoma cells. Because glioblastoma cells may also express other receptors for growth signals, such as the epidermal growth factor (EGF) receptor (EGFR), we investigated the role of EGFR in the signaling cascade of FPR and how two receptors cross-talk to exacerbate tumor growth. We found that N-formyl-methionyl-leucyl-phenylatanine, an FPR agonist peptide, rapidly induced FGFR phosphorylation at tyrosine residue (Tyr) 992, but not residues 846, 1068, or 1173, in glioblastoma cells, whereas all these residues were phosphorylated after only EGF treatment. The FPR agonist-induced EGFR phosphorylation in tumor cells was dependent on the presence of FPR as well as G alpha i proteins, and was controlled by Src tyrosine kinase. The transactivation of FGFR contributes to the biological function of FPR in glioblastoma cells because inhibition of EGFR phosphorylation significantly reduced FPR agonist-induced tumor cell chernotaxis and proliferation. Furthermore, depletion of both FPR and EGFR by short interference RNA abolished the tumorigenesis of the glioblastorna cells. Our study indicates that the glioblastoma-promoting activity of FPR is mediated in part by transactivation of EGFR and the cross-talk between two receptors exacerbates the malignant phenotype of tumor cells. Thus, targeting both receptors may yield antiglioblastoma agents superior to those targeting one of them. C1 NCI, Canc & Inflammat Program, Ctr Canc Res, Lab Mol Immunoregulat, Ft Detrick, MD 21702 USA. NCI, Sci Applicat Int Corp Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. Cent S Univ, Xiang Ya Sch Med, Canc Res Inst, Changsha, Peoples R China. Third Mil Md Univ, Inst Pathol, SW Hosp, Chongqing, Peoples R China. RP Wang, JM (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, Lab Mol Immunoregulat, Bldg 560,Room 31-76, Ft Detrick, MD 21702 USA. EM wangji@mail.ncifcrf.gov RI Bian, Xiuwu/F-1569-2011; Howard, O M Zack/B-6117-2012; Bian, Xiu-wu/D-4736-2017 OI Howard, O M Zack/0000-0002-0505-7052; Bian, Xiu-wu/0000-0003-4383-0197 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 46 TC 37 Z9 37 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2007 VL 67 IS 12 BP 5906 EP 5913 DI 10.1158/0008-55472.CAN-07-0691 PG 8 WC Oncology SC Oncology GA 180JV UT WOS:000247360100043 PM 17575160 ER PT J AU Leonard, TA Hurley, JH AF Leonard, Thomas A. Hurley, James H. TI Two kinase family dramas SO CELL LA English DT Editorial Material ID TYROSINE KINASE; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; AUTOINHIBITION; RECEPTOR; SRC AB In this issue, Lietha and colleagues (2007) report the structure of focal adhesion kinase (FAK) and reveal how FAK maintains an autoinhibited state. Together with the structure of another tyrosine kinase, ZAP-70 (Deindl et al., 2007), this work highlights the diversity of mechanisms that nature has evolved within the kinase superfamily to regulate their activity through autoinhibition. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov RI Leonard, Thomas/A-5143-2013 OI Leonard, Thomas/0000-0001-6853-666X FU Intramural NIH HHS [Z01 DK036118-14] NR 9 TC 3 Z9 3 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 15 PY 2007 VL 129 IS 6 BP 1037 EP 1038 DI 10.1016/j.cell.2007.06.001 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180UA UT WOS:000247390400005 PM 17574014 ER PT J AU Mizuguchi, G Xiao, H Wisniewski, J Smith, MM Wu, C AF Mizuguchi, Gaku Xiao, Hua Wisniewski, Jan Smith, M. Mitchell Wu, Carl TI Nonhistone Scm3 and histones CenH3-H4 assemble the core of centromere-specific nucleosomes SO CELL LA English DT Article ID CHROMATIN REMODELING COMPLEX; BUDDING YEAST KINETOCHORE; A CENP-A; SACCHAROMYCES-CEREVISIAE; H3 VARIANT; IN-VITRO; PROTEIN; DNA; SITES; CSE4P AB The budding yeast histone H3 variant, Cse4, replaces conventional histone H3 in centromeric chromatin and, together with centromere-specific DNA-binding factors, directs assembly of the kinetochore, a multiprotein complex mediating chromosome segregation. We have identified Scm3, a nonhistone protein that colocalizes with Cse4 and is required for its centromeric association. Bacterially expressed Scm3 binds directly to and reconstitutes a stoichiometric complex with Cse4 and histone H4 but not with conventional histone H3 and H4. A conserved acidic domain of Scm3 is responsible for directing the Cse4-specific interaction. Strikingly, binding of Scm3 can replace histones H2A-H2B from preassembled Cse4-containing histone octamers. This incompatibility between Scm3 and histones H2A-H2B is correlated with diminished in vivo occupancy of histone H2B, H2A, and H2AZ at centromeres. Our findings indicate that nonhistone Scm3 serves to assemble and maintain Cse4-H4 at centromeres and may replace histone H2A-H2B dimers in a centromere-specific nucleosome core. C1 NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Virginia, Hlth Syst, Dept Microbiol, Charlottesville, VA 22908 USA. RP Wu, C (reprint author), NCI, Lab Biochem & Mol Biol, Ctr Canc Res, NIH, Bldg 37,Room 6068, Bethesda, MD 20892 USA. EM carlwu@helix.nih.gov FU Intramural NIH HHS; NIGMS NIH HHS [GM28930] NR 65 TC 183 Z9 192 U1 1 U2 14 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUN 15 PY 2007 VL 129 IS 6 BP 1153 EP 1164 DI 10.1016/j.cell.2007.04.026 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 180UA UT WOS:000247390400018 PM 17574026 ER PT J AU Nyaga, SG Jaruga, P Lohani, A Dizdaroglu, M Evans, MK AF Nyaga, Simon G. Jaruga, Pawel Lohani, Althaf Dizdaroglu, Miral Evans, Michele K. TI Accumulation of oxidatively induced DNA damage in human breast cancer cell lines following treatment with hydrogen peroxide SO CELL CYCLE LA English DT Article DE breast cancer; 8,5 '-cyclo-2 '-deoxyadenosine; DNA repair; formamidopyrimidines; oxidative DNA damage; reactive oxygen species ID RADICAL-INDUCED FORMATION; BASE-EXCISION-REPAIR; ESCHERICHIA-COLI; SUBSTRATE-SPECIFICITY; IONIZING-RADIATION; FEMALE BREAST; IN-VITRO; NUCLEOTIDE; PROTEIN; LESIONS AB Breast cancer is a leading cause of cancer deaths in women. Although the causes of this disease are largely unknown, inefficient repair of oxidatively induced DNA lesions has been thought to play a major role in the transformation of normal breast tissue to malignant breast tissue. Previous studies have revealed higher levels of 8-hydroxyguanine in malignant breast tissue compared to non-malignant breast tissue. Furthermore, some breast cancer cell lines have greatly reduced capacity to repair this lesion suggesting that oxidatively induced DNA lesions may be elevated in breast cancer cells. We used liquid chromatography/mass spectrometry and gas chromatography/mass spectrometry to measure the levels of 8-hydroxy-2'-deoxyadenosine, (5'S)-8,5'-cyclo-2'-deoxyadenosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, and 4,6-diamino-5-formamidopyrimidine in MCF-7 and HCC1937 breast cancer cell lines before and after exposure to H2O2 followed by a DNA repair period. We show that H2O2-treated HCC1937 and MCF-7 cell lines accumulate significantly higher levels of these lesions than the untreated cells despite a 1 h repair period. In contrast, the four lesions did not accumulate to any significant level in H2O2-treated non-malignant cell lines, AG11134 and HCC1937BL. Furthermore, MCF-7 and HCC1937 cell lines were deficient in the excision repair of all the four lesions studied. These results suggest that oxidatively induced DNA damage and its repair may be critical in the etiology of breast cancer. C1 Natl Inst Aging, NIH, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21201 USA. Nicholas Copernicus Univ, Coll Med, Dept Clin Biochem, Bydgoszce, Poland. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD USA. RP Evans, MK (reprint author), Natl Inst Aging, NIH, Lab Cellular & Mol Biol, 5600 Nathan Shock Dr,Mail Box 09, Baltimore, MD 21224 USA. EM me42v@nih.gov RI Jaruga, Pawel/M-4378-2015 FU Intramural NIH HHS NR 49 TC 27 Z9 29 U1 0 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 15 PY 2007 VL 6 IS 12 BP 1472 EP 1478 PG 7 WC Cell Biology SC Cell Biology GA 205CN UT WOS:000249090900014 PM 17568196 ER PT J AU Ramalingam, SS Parise, RA Ramananthan, RK Lagattuta, TF Musguire, LA Stoller, RG Potter, DM Argiris, AE Zwiebel, JA Egorin, MJ Belani, CP AF Ramalingam, Suresh S. Parise, Robert A. Ramananthan, Ramesh K. Lagattuta, Theodore F. Musguire, Lori A. Stoller, Ronald G. Potter, Douglas M. Argiris, Athanassios E. Zwiebel, James A. Egorin, Merrill J. Belani, Chandra P. TI Phase I and pharmacokinetic study of vorinostat, A histone deacetylase inhibitor, in combination with carboplatin and paclitaxel for advanced solid malignancies SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 42nd Annual Meeting of the American-Society-of-Clinical-Oncology CY JUN 02-06, 2006 CL Atlanta, GA SP Amer Soc Clin Oncol ID SUBEROYLANILIDE HYDROXAMIC ACID; CELL LUNG-CANCER; LEUKEMIA-CELLS; ONCOLOGY-GROUP; III TRIAL; SAHA; DIFFERENTIATION; APOPTOSIS; INDUCERS; QUANTITATION AB Purpose: The primary objective of this study was to determine the recommended phase 11 doses of the novel histone deacetylase inhibitor vorinostat when administered in combination with carboplatin and paclitaxel. Experimental Design: Patients (N = 28) with advanced solid malignancies were treated with vorinostat, administered orally once daily for 2 weeks or twice daily for 1 week, every 3 weeks. Carboplatin and paclitaxel were administered i.v. once every 3 weeks. Doses of vorinostat and paclitaxel were escalated in sequential cohorts of three patients. The pharmacokinetics of vorinostat, its metabolites, and paclitaxel were characterized. Results: Vorinostat was administered safely up to 400 mg qd or 300 mg bd with carboplatin and paclitaxel. Two of 12 patients at the 400 mg qd schedule experienced dose-limiting toxicities of grade 3 emesis and grade 4 neutropenia with fever. Non-dose-limiting toxicity included nausea, diarrhea, fatigue, neuropathy, thrombocytopenia, and anemia. Of 25 patients evaluable for response, partial responses occurred in 11 (10 non-small cell lung cancer and 1 head and neck cancer) and stable disease occurred in 7. Vorinostat pharmacokinetics were linear over the dose range studied. Vorinostat area under the concentration versus time curve and half-life increased when vorinostat was coadministered with carboplatin and paclitaxel, but vorinostat did not alter paclitaxel pharmacokinetics. Conclusions: Both schedules of vorinostat (400 mg oral qd x 14 days or 300 mg bd x 7 days) were tolerated well in combination with carboplatin (area under the concentration versus time curve = 6 mg/mL x min) and paclitaxel (200 mg/m(2)). Encouraging anticancer activity was noted in patients with previously untreated non-small cell lung cancer. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Inst Canc, Biostat Facil, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Ramalingam, SS (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, MD5150 Ctr Ave,Suite 555,UPMC Canc Pavil, Pittsburgh, PA 15232 USA. EM ramalingams@upmc.edu OI Belani, Chandra/0000-0001-5049-5329 FU NCATS NIH HHS [UL1 TR000005]; NCI NIH HHS [P30CA 47904, U01 CA099168-01]; NCRR NIH HHS [5M01RR 00056] NR 38 TC 130 Z9 133 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2007 VL 13 IS 12 BP 3605 EP 3610 DI 10.1158/1078-0432.CCR-07-0162 PG 6 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200023 PM 17510206 ER PT J AU Synold, TW Takimoto, CH Doroshow, JH Gandara, D Mani, S Remick, SC Mulkerin, DL Hamilton, A Sharma, S Ramanathan, RK Lenz, HJ Graham, M Longmate, J Kaufman, BM Ivy, P AF Synold, Timothy W. Takimoto, Chris H. Doroshow, James H. Gandara, David Mani, Sridhar Remick, Scot C. Mulkerin, Daniel L. Hamilton, Anne Sharma, Sunil Ramanathan, Ramesh K. Lenz, Heinz Josef Graham, Martin Longmate, Jeffrey Kaufman, Bennett M. Ivy, Percy TI Dose-escalating and pharmacologic study of oxaliplatin in adult cancer patients with impaired hepatic function: A National Cancer Institute Organ Dysfunction Working Group Study SO CLINICAL CANCER RESEARCH LA English DT Article AB Purpose: To determine the toxicities, pharmacokinetics, and maximally tolerated doses of oxaliplatin in patients with hepatic impairment and to develop formal guidelines for oxaliplatin dosing in this patient population. Experimental Design: Sixty adult cancer patients with variable hepatic function received i.v. oxaliplatin ranging from 60 to 130 mg/m(2) every 3 weeks. Patients were stratified by levels of total bilirubin, aspartate aminotransferase (AST), and alkaline phosphatase (AP) into five cohorts based on the degree of hepatic dysfunction: control group A [bilirubin, AST and AP <= upper limit of normal (ULN)], mild dysfunction group B (bilirubin <= ULN, ULN < AST <= 2.5 x ULN, or ULN < AP <= 5 x ULN), moderate dysfunction group C (ULN < bilirubin <= 3.0 mg/dL, AST > 2.5 x ULN, or AP > 5 x ULN), severe dysfunction group D (bilirubin > 3.0 mg/dL, anyAST, and any AP), and liver transplantation group E (any bilirubin, any AST, and any AP). Doses were escalated in cohorts of three patients, and urine and plasma ultrafiltrates were assayed for platinum concentrations. Results: Dose escalation of single-agent oxaliplatin to 130 mg/m(2) was well tolerated in all cohorts. Platinum clearance did not correlate with any liver function test. Two of 56 assessable patients with a diagnosis of laryngeal carcinoma and cervical adenocarcinoma experienced partial responses lasting 3 and 5.5 months. Conclusions: Oxaliplatin at 130 mg/m(2) every 3 weeks was well tolerated in all patients with impaired liver function. Dose reductions of single-agent oxaliplatin are not indicated in patients with hepatic dysfunction. C1 Canc Therapy & Res Ctr S Texas, Inst Drug Dev, San Antonio, TX 78245 USA. City Hope Comprehens Canc Ctr, Duarte, CA USA. Univ Calif Davis, Davis Canc Ctr, Sacramento, CA 95817 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Case Western Comprehens Canc Ctr, Cleveland, OH USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. NYU, Inst Canc, New York, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Ctr Comprehens Canc, Pittsburgh, PA USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Sanofi Synthelabo Inc, Dept Clin Pharmacokinet & Drug Metab, Malvern, PA USA. PSI Int Inc, Vienna, VA USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Takimoto, CH (reprint author), Canc Therapy & Res Ctr S Texas, Inst Drug Dev, 14960 Omicron Dr, San Antonio, TX 78245 USA. EM ctakimot@idd.org OI Longmate, Jeffrey/0000-0002-0869-7928 FU NCI NIH HHS [U01CA062502, U01CA069856, U01CA062491, U01CA076642, U01CA03330, U01 CA062491, U01CA033572, U01CA069855, U01CA062505, U01CA069853]; NCRR NIH HHS [RR00056, M01RR00080] NR 10 TC 24 Z9 27 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2007 VL 13 IS 12 BP 3660 EP 3666 DI 10.1158/1078-0432.CCR-06-2385 PG 7 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200031 PM 17575231 ER PT J AU Stockwin, LH Bumke, MA Yu, SX Webb, SP Collins, JR Hollingshead, MG Newton, DL AF Stockwin, Luke H. Bumke, Maja A. Yu, Sherry X. Webb, Simon P. Collins, Jack R. Hollingshead, Melinda G. Newton, Dianne L. TI Proteomic analysis identifies oxidative stress induction by adaphostin SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN LEUKEMIA-CELLS; CHRONIC MYELOGENOUS LEUKEMIA; PROTEIN DISULFIDE-ISOMERASE; IN-VITRO; INDUCED APOPTOSIS; BENZENE METABOLITES; PROGENITOR CELLS; BCR-ABL; INHIBITORS; HYDROQUINONE AB Purpose: Activities distinct from inhibition of Bcr/abl have led to adaphostin (NSC 680410) being described as "a drug in search of a mechanism." In this study, proteomic analysis of adaphostin-treated myeloid leukemia cell lines was used to further elucidate a mechanism of action. Experimental Design: HL60 and K562 cells treated with adaphostin for 6,12, or 24 h were analyzed using two-dimensional PAGE. Differentially expressed spots were excised, digested with trypsin, and analyzed by liquid chromatography - tandem mass spectrometry. The contribution of the redox-active hydroquinone group in adaphostin was also examined by carrying out proteomic analysis of HL60 cells treated with a simple hydroquinone (1,4-dihydroxybenzene) or H2O2. Results: Analysis of adaphostin-treated cells identified 49 differentially expressed proteins, the majority being implicated in the response to oxidative stress (e.g., CALM, ERP29, GSTP1, PDIA1) or induction of apoptosis (e.g., LAMA, FLNA,TPR, GDIS). Interestingly, modulation of these proteins was almost fully prevented by inclusion of an antioxidant, N-acetylcysteine. Validation of the proteomic data confirmed GSTP1 as an adaphostin resistance gene. Subsequent analysis of HL60 cells treated with 1,4-dihydroxybenzene or H2O2 showed similar increases in intracellular peroxides and an almost identical proteomic profiles to that of adaphostin treatment. Western blotting of a panel of cell lines identified Cu/Zn superoxide dismutase (SOD) as correlating with adaphostin resistance. The role of SOD as a second adaphostin resistance gene was confirmed by demonstrating that inhibition of SOD using diethyldithiocarbamate increased adaphostin sensitivity, whereas transfection of SOD I attenuated toxicity. Importantly, treatment with 1,4-dihydroxybenzene or H2O2 replicated adaphostin-induced Bcr/abl polypeptide degradation, suggesting that kinase inhibition is a ROS-dependent phenomenon. Conclusion: Adaphostin should be classified as a redox-active-substituted dihydroquinone. C1 NCI, Sci Applicat Int Corp Frederick Inc, Dev Therapeut Program, Frederick, MD 21702 USA. NCI, Sci Applicat Int Corp Frederick Inc, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Newton, DL (reprint author), NCI, Sci Applicat Int Corp Frederick Inc, Dev Therapeut Program, Room 6,Bldg 320, Frederick, MD 21702 USA. EM dnewton@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 60 TC 21 Z9 24 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 JUN 15 PY 2007 VL 13 IS 12 BP 3667 EP 3681 DI 10.1158/1078-0432.CCR-07-0025 PG 15 WC Oncology SC Oncology GA 180BZ UT WOS:000247336200032 PM 17575232 ER PT J AU Greene, RE Schlamm, HT Oestmann, JW Stark, P Durand, C Lortholary, O Wingard, JR Herbrecht, R Ribaud, P Patterson, TF Troke, PF Denning, DW Bennett, JE de Pauw, BE Rubin, RH AF Greene, Reginald E. Schlamm, Haran T. Oestmann, Joerg-W. Stark, Paul Durand, Christine Lortholary, Olivier Wingard, John R. Herbrecht, Raoul Ribaud, Patricia Patterson, Thomas F. Troke, Peter F. Denning, David W. Bennett, John E. de Pauw, Ben E. Rubin, Robert H. TI Halo sign and improved outcome - Reply to Verweij et al. SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID INVASIVE PULMONARY ASPERGILLOSIS C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Pfizer Global Res & Dev, New York, NY USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Florida, Coll Med, Gainesville, FL USA. Univ Texas, Hlth Sci Ctr San Antonio, San Antonio, TX 78285 USA. NIAID, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Berlin, Germany. Hop Bocage, Dijon, France. Inst Pasteur, Paris, France. Hop St Louis, Paris, France. Hop Hautepierre, Strasbourg, France. Pfizer Global Res & Dev, Sandwich, Kent, England. Univ Manchester, Manchester, Lancs, England. Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. RP Greene, RE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,Founders 202, Boston, MA 02114 USA. EM greene.reginald@mgh.harvard.edu RI Herbrecht, Raoul/D-3471-2013 NR 5 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 15 PY 2007 VL 44 IS 12 BP 1667 EP 1668 DI 10.1086/519700 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 170JA UT WOS:000246658200026 ER PT J AU Ohshima, T Hirasawa, M Tabata, H Mutoh, T Adachi, T Suzuki, H Saruta, K Iwasato, T Itohara, S Hashimoto, M Nakajima, K Ogawa, M Kulkarni, AB Mikoshiba, K AF Ohshima, Toshio Hirasawa, Motoyuki Tabata, Hidenori Mutoh, Tetsuji Adachi, Tomoko Suzuki, Hiromi Saruta, Keiko Iwasato, Takuji Itohara, Shigeyoshi Hashimoto, Mistuhiro Nakajima, Kazunori Ogawa, Masaharu Kulkarni, Ashok B. Mikoshiba, Katsuhiko TI Cdk5 is required for multipolar-to-bipolar transition during radial neuronal migration and proper dendrite development of pyramidal neurons in the cerebral cortex SO DEVELOPMENT LA English DT Article DE neuronal migration; cerebral cortex; mouse; Cdk5; Map2 (Mtap2) ID DEPENDENT KINASE 5/P35; DEVELOPING MOUSE-BRAIN; CORTICAL-NEURONS; CELL-MIGRATION; GENE-TRANSFER; MICE; PHOSPHORYLATION; DOUBLECORTIN; EXPRESSION; PROTEIN AB The mammalian cerebral cortex consists of six layers that are generated via coordinated neuronal migration during the embryonic period. Recent studies identified specific phases of radial migration of cortical neurons. After the final division, neurons transform from a multipolar to a bipolar shape within the subventricular zone-intermediate zone (SVZ-IZ) and then migrate along radial glial fibres. Mice lacking Cdk5 exhibit abnormal corticogenesis owing to neuronal migration defects. When we introduced GFP into migrating neurons at E14.5 by in utero electroporation, we observed migrating neurons in wild-type but not in Cdk5(-/-) embryos after 3-4 days. Introduction of the dominant-negative form of Cdk5 into the wild-type migrating neurons confirmed specific impairment of the multipolar-to-bipolar transition within the SVZ-IZ in a cell-autonomous manner. Cortex-specific Cdk5 conditional knockout mice showed inverted layering of the cerebral cortex and the layer V and callosal neurons, but not layer VI neurons, had severely impaired dendritic morphology. The amount of the dendritic protein Map2 was decreased in the cerebral cortex of Cdk5-deficient mice, and the axonal trajectory of cortical neurons within the cortex was also abnormal. These results indicate that Cdk5 is required for proper multipolar-to-bipolar transition, and a deficiency of Cdk5 results in abnormal morphology of pyramidal neurons. In addition, proper radial neuronal migration generates an inside-out pattern of cerebral cortex formation and normal axonal trajectories of cortical pyramidal neurons. C1 RIKEN, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama 3510198, Japan. NIDCR, Funct Genom Sect, NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Anat, Shinjuku Ku, Tokyo 1608582, Japan. RIKEN, Brain Sci Inst, Lab Cell Culture Dev, Wako, Saitama 3510198, Japan. RIKEN, Brain Sci Inst, Lab Behav Genet, Wako, Saitama 3510198, Japan. RIKEN, Brain Sci Inst, Hashimoto Res Unit, Wako, Saitama 3510198, Japan. Jikei Univ, Sch Med, Inst DNA Med, Dept Mol Neurobiol, Tokyo 1058641, Japan. Univ Tokyo, Inst Med Sci, Dept Mol Neurobiol, Minato Ku, Tokyo, Japan. RP Ohshima, T (reprint author), RIKEN, Brain Sci Inst, Dev Neurobiol Lab, Wako, Saitama 3510198, Japan. EM ohshima@brain.riken.go.jp RI Itohara, Shigeyoshi/I-8769-2012; Nakajima, Kazunori/L-3396-2013; Mikoshiba, Katsuhiko/N-7943-2015 OI Itohara, Shigeyoshi/0000-0002-2410-9989; Nakajima, Kazunori/0000-0003-1864-9425; NR 47 TC 103 Z9 108 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 15 PY 2007 VL 134 IS 12 BP 2273 EP 2282 DI 10.1242/dev.02854 PG 10 WC Developmental Biology SC Developmental Biology GA 185OJ UT WOS:000247720000008 PM 17507397 ER PT J AU Pajni-Underwood, S Wilson, CP Elder, C Mishina, Y Lewandoski, M AF Pajni-Underwood, Sangeeta Wilson, Catherine P. Elder, Cindy Mishina, Yuji Lewandoski, Mark TI BMP signals control limb bud interdigital programmed cell death by regulating FGF signaling SO DEVELOPMENT LA English DT Article DE apoptosis; BMP; FGF; interdigit; limb development; programmed cell death ID APICAL ECTODERMAL RIDGE; VERTEBRATE LIMB; MOUSE LIMB; DEVELOPMENTAL BASIS; GENE-EXPRESSION; APOPTOSIS; OUTGROWTH; MORPHOGENESIS; MUTANT; INDUCTION AB In vertebrate limbs that lack webbing, the embryonic interdigit region is removed by programmed cell death (PCD). Established models suggest that bone morphogenetic proteins (BMPs) directly trigger such PCD, although no direct genetic evidence exists for this. Alternatively, BMPs might indirectly affect PCD by regulating fibroblast growth factors (FGFs), which act as cell survival factors. Here, we inactivated the mouse BMP receptor gene Bmpr1a specifically in the limb bud apical ectodermal ridge (AER), a source of FGF activity. Early inactivation completely prevents AER formation. However, inactivation after limb bud initiation causes an upregulation of two AER-FGFs, Fgf4 and Fgf8, and a loss of interdigital PCD leading to webbed limbs. To determine whether excess FGF signaling inhibits interdigit PCD in these Bmpr1a mutant limbs, we performed double and triple AER-specific inactivations of Bmpr1a, Fgf4 and Fgf8. Webbing persists in AER-specific inactivations of Bmpr1a and Fgf8 owing to elevated Fgf4 expression. Inactivation of Bmpr1a, Fgf8 and one copy of Fgf4 eliminates webbing. We conclude that during normal embryogenesis, BMP signaling to the AER indirectly regulates interdigit PCD by regulating AER-FGFs, which act as survival factors for the interdigit mesenchyme. C1 NCI, Lab Canc & Dev Biol, NIH, Frederick, MD 21702 USA. NCI, SAIC, NIH, Frederick, MD 21702 USA. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. RP Lewandoski, M (reprint author), NCI, Lab Canc & Dev Biol, NIH, Frederick, MD 21702 USA. EM mlewandoski@mail.ncifcrf.gov FU Intramural NIH HHS NR 89 TC 79 Z9 80 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN 15 PY 2007 VL 134 IS 12 BP 2359 EP 2368 DI 10.1242/dev.001677 PG 10 WC Developmental Biology SC Developmental Biology GA 185OJ UT WOS:000247720000016 PM 17537800 ER PT J AU Saha, TD Stinson, FS Grant, BF AF Saha, Tulshi D. Stinson, Frederick S. Grant, Bridget F. TI The role of alcohol consumption in future classifications of alcohol use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol use disorder; IRT analysis; addiction; physical dependence; high-risk drinking patterns ID ITEM RESPONSE THEORY; NATIONAL EPIDEMIOLOGIC SURVEY; DSM-IV ALCOHOL; MARGINAL MAXIMUM-LIKELIHOOD; INTERVIEW SCHEDULE AUDADIS; SUBSTANCE USE DISORDERS; RISK-FUNCTION ANALYSIS; GENERAL-POPULATION; PARAMETER-ESTIMATION; PSYCHIATRIC-ILLNESS AB Background: Item response theory (IRT) was used to determine whether DSM-IV alcohol abuse and dependence and consumption criteria were arrayed along a continuum of severity. Methods: Data came from a large, nationally representative sample of the U.S. adult population. Results: DSM-IV alcohol abuse and dependence criteria formed a continuum of alcohol use disorder severity along with the drinking 5+/4+ at least once a week in the past year criterion. Criteria were invariant across sex, race-ethnicity, and age subgroups. Conclusion: The drinking 5+/4+ high-risk drinking pattern was identified as a suitable criterion for future classifications of DSM-IV alcohol use disorder. Some dependence criteria were among the least severe criteria, and some abuse criteria were among the most severe, findings that question the validity of DSM-IV abuse and dependence categories as distinct entities and that do not support the assumption of abuse as prodromal to dependence. Physical dependence and addiction were identified as defining elements of the continuum. Further research examining their dimensional properties and relationships to high-risk drinking patterns appears warranted. An approach highlighting a more important role of consumption in future classifications of alcohol use disorder defined broadly to encompass all alcohol-related harm, including addiction and physical dependence, is discussed. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Alcohol Abuse & Alcoholism, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry, NIH, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), Natl Inst Alcohol Abuse & Alcoholism, Div Intramural Clin & Biol Res, Lab Epidemiol & Biometry, NIH, Room 3077,MS 9304 5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU Intramural NIH HHS [Z01 AA000449-04] NR 78 TC 113 Z9 113 U1 6 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 15 PY 2007 VL 89 IS 1 BP 82 EP 92 DI 10.1016/j.drugalcdep.2006.12.003 PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 167IL UT WOS:000246445200010 PM 17240085 ER PT J AU Goldstein, RZ Woicik, PA Lukasik, T Maloney, T Volkow, ND AF Goldstein, R. Z. Woicik, P. A. Lukasik, T. Maloney, T. Volkow, N. D. TI Drug fluency: A potential marker for cocaine use disorders SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE semantic memory; cocaine; drug addiction; salience; cue-reactivity; craving; prefrontal cortex ID ATTENTIONAL BIAS; CUES; ADDICTION; INVENTORY; CINGULATE; CORTEX AB The goal of the current study was to tailor semantic fluency to increase its sensitivity and ecological validity in the study of drug use disorders. On a newly modified "drug" fluency task, individuals with cocaine use disorders who tested positive for cocaine at study day named more drug-related words than control subjects. The number of words provided on the classical semantic fluency task (animals and fruits/vegetables) did not differ between the groups. While the individuals with cocaine use disorders who tested negative for cocaine at study day did not differ from the control subjects in total words named on this task, a qualitative analysis indicated that both cocaine subgroups provided significantly more words pertaining to the experience of using drugs (paraphernalia, administration) than the matched control subjects. These results demonstrate that compared to classical neurocognitive assessment tools, newly tailored measures may be more sensitive to cocaine use disorders, psychopathologies that are often characterized by mild neuropsychological deficits but a well-circumscribed attentional bias to drug-related cues. Future studies are needed to probe the exact cognitive processes and neural circuitry underlying performance on this cue-sensitive 1-min measure. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Brookhaven Natl Lab, Med Dept, Upton, NY 11973 USA. Natl Inst Drug Abuse, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, Med Dept, POB 5000, Upton, NY 11973 USA. EM rgoldstein@bnl.gov FU NCRR NIH HHS [5-M01-RR-10710, M01 RR010710]; NIDA NIH HHS [1K23 DA1 5517-01, K23 DA015517] NR 21 TC 10 Z9 11 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUN 15 PY 2007 VL 89 IS 1 BP 97 EP 101 DI 10.1016/j.drugalcdep.2006.12.001 PG 5 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 167IL UT WOS:000246445200012 PM 17234364 ER PT J AU Pi, JB Bai, YS Reece, JM Williams, J Liu, DX Freeman, ML Fahl, WE Shugar, D Liu, J Qu, W Collins, S Waalkes, MP AF Pi, Jingbo Bai, Yushi Reece, Jeffrey M. Williams, Jason Liu, Dianxin Freeman, Michael L. Fahl, William E. Shugar, David Liu, Jie Qu, Wei Collins, Sheila Waalkes, Michael P. TI Molecular mechanism of human Nrf2 activation and degradation: Role of sequential phosphorylation by protein kinase CK2 SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Nrf7; CK2; pliosphorylation; oxidative stress; arsenic ID ANTIOXIDANT RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; CELL-SURVIVAL; GENE-EXPRESSION; STRESS; PROTEASOME; CALMODULIN; PATHWAY; MICE; IDENTIFICATION AB Nrf2 is a key transcription factor in the cellular response to oxidative stress. In this study we identify two phosphorylated forms of endogenous human Nrf2 after chemically induced oxidative stress and provide evidence that protein kinase CK2-mediated sequential phosphorylation plays potential roles in Nrf2 activation and degradation. Human Nrf2 has a predicted molecular mass of 66 kDa. However, immunoblots showed that two bands at 98 and 118 kDa, which are identified as phosphorylated forms, are increased in response to Nrf2 inducers. In addition, human Nrf2 was found to be a substrate for CK2 which mediated two steps of phosphorylation, resulting in two forms of Nrf2 migrating with differing M, at 98 kDa (Nrf2-98) and 118 kDa (Nrf2-118). Our results support a role in which calmodulin binding regulates CK2 activity, in that cold (25 degrees C) Ca2+-free media (cold/Ca2+-free) decreased both cellular calcium levels and CK2-calmodulin binding and induced Nrf2-118 formation, the latter of which was prevented by CK2-specific inhibitors. Gel shift assays showed that the Nrf2-118 generated under cold/Ca2+-free conditions does not bind to the antioxidant response element, indicating that Nrf2-98 has transcriptional activity. In contrast, Nrf2-118 is more susceptible to degradation. These results provide evidence for phosphorylation by CK2 as a critical controlling factor in Nrf2-mediated cellular antioxidant response. (c) 2007 Elsevier Inc. All rights reserved. C1 NCI, Comparat Carcinogenesis Lab, NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Hammer Inst Hlth Sci, Endocrine Biol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Radiat Oncol, Nashville, TN 37232 USA. Univ Wisconsin, McArdle Lab Canc Res, Madison, WI 53706 USA. Polish Acad Sci, Inst Biochem & Biophys, PL-02106 Warsaw, Poland. RP Waalkes, MP (reprint author), NCI, Comparat Carcinogenesis Lab, NIEHS, NIH, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov OI Freeman, Michael/0000-0003-1881-366X FU Intramural NIH HHS [Z01 BC005488-21] NR 41 TC 105 Z9 107 U1 0 U2 3 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 JUN 15 PY 2007 VL 42 IS 12 BP 1797 EP 1806 DI 10.1016/j.freeradbiomed.2007.03.001 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 174QL UT WOS:000246957300005 PM 17512459 ER PT J AU Entezam, A Biacsi, R Orrison, B Saha, T Hoffman, GE Grabczyk, E Nussbaum, RL Usdin, K AF Entezam, Ali Biacsi, Rea Orrison, Bonnie Saha, Tapas Hoffman, Gloria E. Grabczyk, Ed Nussbaum, Robert L. Usdin, Karen TI Regional FMRP deficits and large repeat expansions into the full mutation range in a new Fragile X permutation mouse model SO GENE LA English DT Article DE repeat expansion; DNA instability; full mutation ID CEREBELLAR-TREMOR/ATAXIA-SYNDROME; CGG-REPEAT; MESSENGER-RNA; TRANSGENIC MICE; INTRANUCLEAR INCLUSIONS; PREMUTATION ALLELES; ELEVATED LEVELS; SYNDROME FXTAS; GENE; CARRIERS AB Carriers of FMR1 alleles with 55-200 repeats in the 5'UTR are at risk for Fragile X associated tremor and ataxia syndrome. The cause of the neuropathology is unknown but is thought to be RNA-mediated. Maternally transmitted premutation alleles are also at risk of expansion of the repeat tract into the "full mutation" range (>200 repeats). The mechanism responsible for expansion is unknown. Full inutation alleles produce reduced amounts of the FMR I gene product, FMRP, which leads to Fragile X mental retardation syndrome. We have developed a murine model for Fragile X premutation carriers that recapitulates key features seen in humans including a direct relationship between repeat number and Fmr1 mRNA levels, an inverse relationship with FMRP levels and Purkinje cell dropout that have not been seen in a previously described knock-in mouse model. In addition, these mice also show a differential deficit of FMRP in different parts of the brain that might account for symptoms of the full mutation that are seen in premutation carriers. As in humans, repeat instability is high with expansions predominating and, for the first time in a mouse model, large expansions into the full mutation range are seen that occur within a single generation. Thus, contrary to what was previously thought, mice may be good models not only for the symptoms seen in human carriers of FMR1 premutation alleles but also for understanding the mechanism responsible for repeat expansion, a phenomenon that is responsible for a number of neurological and neurodevelopmental disorders. (c) 2007 Elsevier B.V. All rights reserved. C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Anat & Neurobiol, College Pk, MD 20742 USA. RP Usdin, K (reprint author), Bldg 8,Room 202,8 Ctr Dr, Bethesda, MD 20892 USA. EM ku@helix.nih.gov FU Intramural NIH HHS [Z01 DK057602-11] NR 30 TC 95 Z9 96 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 15 PY 2007 VL 395 IS 1-2 BP 125 EP 134 DI 10.1016/j.gene.2007.02.026 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 174HU UT WOS:000246933800014 PM 17442505 ER PT J AU Jin, CY Felsenfeld, G AF Jin, Chunyuan Felsenfeld, Gary TI Nucleosome stability mediated by histone variants H3.3 and H2A.Z SO GENES & DEVELOPMENT LA English DT Article DE histone H2A.Z; histone H3.3; nucleosome structure ID CHROMATIN REMODELING COMPLEX; BETA-GLOBIN LOCUS; TRANSCRIPTIONAL ACTIVATION; ACTIVE CHROMATIN; CORE PARTICLE; GENES; ACETYLATION; REPLACEMENT; PROMOTERS; MARKS AB Nucleosomes containing the histone variant H3.3 tend to be clustered in vivo in the neighborhood of transcriptionally active genes and over regulatory elements. It has not been clear, however, whether H3.3-containing nucleosomes possess unique properties that would affect transcription. We report here that H3.3 nucleosomes isolated from vertebrates, regardless of whether they are partnered with H2A or H2A.Z, are unusually sensitive to salt-dependent disruption, losing H2A/H2B or H2A.Z/H2B dimers. Immunoprecipitation studies of nucleosome core particles (NCPs) show that NCPs that contain both H3.3 and H2A.Z are even less stable than NCPs containing H3.3 and H2A. Intriguingly, NCPs containing H3 and H2A.Z are at least as stable as H3/H2A NCPs. These results establish an hierarchy of stabilities for native nucleosomes carrying different complements of variants, and suggest how H2A.Z could play different roles depending on its partners within the NCP. They also are consistent with the idea that H3.3 plays an active role in maintaining accessible chromatin structures in enhancer regions and transcribed regions. Consistent with this idea, promoters and enhancers at transcriptionally active genes and coding regions at highly expressed genes have nucleosomes that simultaneously carry both H3.3 and H2A.Z, and should therefore be extremely sensitive to disruption. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM gary.felsenfeld@nih.gov FU Intramural NIH HHS NR 40 TC 280 Z9 283 U1 3 U2 15 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 JUN 15 PY 2007 VL 21 IS 12 BP 1519 EP 1529 DI 10.1101/gad.1547707 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 182AW UT WOS:000247478500009 PM 17575053 ER PT J AU Ito, D Visus, C Hoffmann, TK Balz, V Bier, H Appella, E Whiteside, TL Ferris, RL Deleo, AB AF Ito, Daisuke Visus, Carmen Hoffmann, Thomas K. Balz, Vera Bier, Henning Appella, Ettore Whiteside, Theresa L. Ferris, Robert L. DeLeo, Albert B. TI Immunological characterization of missense mutations occurring within cytotoxic T cell-defined p53 epitopes in HLA-A*0201(+) squamous cell carcinomas of the head and neck SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE T cells; cytotoxic; peptides; p53; mutant ID SEQUENCE P53(264-272) PEPTIDE; WILD-TYPE; DENDRITIC CELLS; TUMOR-CELLS; IMMUNE-RESPONSE; CANCER-PATIENTS; BREAST-CANCER; LUNG CANCERS; LYMPHOCYTES; GENERATION AB Previous analyses of p53 in 40 HLA-A*0201(HLA-A2)(+) squamous cell carcinomas of the head and neck (SCCHN) indicated that 6/13 p53 missense mutations that were detected, S149C, T150R, V157F, Y220C, Y220H, and E271K, occurred within HLA-A2-restricted cytotoxic T lymphocyte (CTL)-defined p53 epitopes. Of the 6, the p53 S149C, Y220C and Y220H peptides were immunogenetic. Anti-p53 mutant S149C and Y220H effector cells cross-reacted against the parental wild type sequence (wt) p53 peptides, whereas anti-p53 Y220C cDNA-transfected HLA-A2(+) SaOS cells, and an HLA-A2(+) SCCHN cell line naturally expressing the mutation. These results indicate that the p53 Y220C mutation can be processed and presented for CD8(+) T cell recognition. Furthermore, using an autologous PBMC/tumor system, anti-p53 Y220C peptide-effector cells recognizing the autologous tumor could also be generated. Our analysis of p53 in 10 additional HLA-A2(+) SCCHN tumors detected the p53 Y220C in 2/10 tumors raising the overall frequency of the p53 Y220C mutation to 6/50 (12%) HLA-A2(+) SCCHN tumors. In contrast, independent of their HLA class I genotypes, the p53 Y220C mutation frequency for all human tumors analyzed to date is similar to 1.5%. This unexpectedly high frequency of the p53 Y220C mutation in HLA-A2(+) SCCHN suggests that vaccines targeting this mutation would not only be expected to induce robust anti-tumor immune responses in HLA-A2(+) subjects, but also be more widely applicable than previously envisioned for any given p53 missense mutation. (c) Wiley-Liss, Inc. C1 Univ Pittsburgh, Inst Canc, Div Basic Res, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Otolaryngol, Pittsburgh, PA USA. Univ Dusseldorf, Dept Otorhinolaryngol, D-4000 Dusseldorf, Germany. NCI, Bethesda, MD 20892 USA. RP Deleo, AB (reprint author), Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, 5117 Ctr Ave,Res Pavil, Pittsburgh, PA 15213 USA. EM deleo@imap.pitt.edu FU NCI NIH HHS [CA97190]; NIDCR NIH HHS [DE-12321] NR 36 TC 12 Z9 12 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2007 VL 120 IS 12 BP 2618 EP 2624 DI 10.1002/ijc.22584 PG 7 WC Oncology SC Oncology GA 159NO UT WOS:000245873000012 PM 17294448 ER PT J AU Lissowska, J Gaudet, MM Brinton, LA Chanock, SJ Peplonska, B Welch, R Zatonski, W Szeszenia-Dabrowska, N Park, S Sherman, M Garcia-Closas, M AF Lissowska, Jolanta Gaudet, Mia M. Brinton, Louise A. Chanock, Stephen J. Peplonska, Beata Welch, Robert Zatonski, Witold Szeszenia-Dabrowska, Neonila Park, Sue Sherman, Mark Garcia-Closas, Montserrat TI Genetic polymorphisms in the one-carbon metabolism pathway and breast cancer risk: A population-based case-control study and meta-analyses SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE folate metabolism; single nucleotide polymorphism; breast cancer ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; SYNTHASE D919G POLYMORPHISM; DIETARY-FOLATE INTAKE; MTHFR POLYMORPHISMS; C677T POLYMORPHISM; NO ASSOCIATION; SUSCEPTIBILITY; HOMOCYSTEINE; TAIWAN; WOMEN AB Epidemiological evidence suggests that intake of folate and other B-vitamins and genetic variants in the one-carbon metabolism pathway could influence the risk of breast cancer. Previous studies have focused on 2 polymorphisms in the methylenetetrahydrofolate gene (MTHFR A222V and E429A); however, findings are inconclusive. in a large population-based case-control study in Poland (2,386 cases, 2,502 controls), we investigated the association between breast cancer risk and 13 polymorphisms in 6 one-carbon metabolism genes (MTHFR, MTR, MTRR, CBS, SHMT1 and SLC19A1). Data suggested an association between a nonsynonymous change in the gene coding for methionine synthase (MTR D919G) and reduced breast cancer risk: OR (95% CI) = 0.84 (0.73-0.96) and 0.85 (0.62-1.15) for heterozygous and homozygote variant genotypes, respectively, compared with common homozygotes; p-trend = 0.01, false discovery rate = 0.14. We found no significant associations between other variants and breast cancer risk, including MTHFR A222V or E429A. Meta-analyses including published studies of MTHFR A222V (8,330 cases and 10,825 controls) and E429A (6,521 cases and 8,515 controls) supported the lack of an overall association; however, studies suggested an increase in risk among premenopausal women. In conclusion, this report does not support a substantial overall association between the evaluated polymorphisms in the one-carbon metabolism pathway and breast cancer risk. (c) 2007 Wiley-Liss, Inc. C1 Canc Inst & M Sklodowska Curie Inst Oncol, Dept Canc Epidemiol & Prevent, Inst Oncol, PL-02781 Warsaw, Poland. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Lissowska, J (reprint author), Canc Inst & M Sklodowska Curie Inst Oncol, Dept Canc Epidemiol & Prevent, Inst Oncol, WK Roentgena 5, PL-02781 Warsaw, Poland. EM lissowsj@coi.waw.p RI Peplonska, Beata/F-6004-2010; Park, Sue Kyung/J-2757-2012; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 37 TC 81 Z9 86 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2007 VL 120 IS 12 BP 2696 EP 2703 DI 10.1002/ijc.22604 PG 8 WC Oncology SC Oncology GA 159NO UT WOS:000245873000022 PM 17311260 ER PT J AU Brown, EE Lan, Q Zheng, TZ Zhang, YW Wang, SS Hoar-Zahm, S Chanock, SJ Rothman, N Baris, D AF Brown, Elizabeth E. Lan, Qing Zheng, Tongzhang Zhang, Yawei Wang, Sophia S. Hoar-Zahm, Shelia Chanock, Stephen J. Rothman, Nathaniel Baris, Dalsu TI Common variants in genes that mediate immunity and risk of multiple myeloma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE multiple myeloma; gene; polymorphism; cytokine; inflammation; immunogenetics ID NECROSIS-FACTOR-ALPHA; MARROW STROMAL CELLS; NF-KAPPA-B; IIA CD32 POLYMORPHISM; NATURAL-KILLER CELLS; GROWTH-FACTOR; INTERLEUKIN-4 RECEPTOR; THERAPEUTIC APPLICATIONS; ANTIGENIC-STIMULATION; LYMPHOKINE GENES AB Multiple myeloma (MM) is a B-cell malignancy characterized by aberrant immune function. Using genomic DNA extracted from 127 MM cases aged 21-84 years and 545 population-based controls, we examined the risks of MM associated with 82 common variants in 45 genes that mediate immunity among women of European American descent. Genotyping was determined using validated and optimized TaqMan assays. We estimated haplotype frequencies from unphased genotype data for 20 of these genes using the expectation-maximization progressive insertion algorithm. Compared with controls, MM risk was positively associated with homozygotes of single loci, IL4R (-28120T, rs2107356) and FCGR2A (-120G, rs1801274) (OR = 1.91, 95% CI 1.08-3.38 and 1-95, 95% CI 1.06-3.60, respectively). For genes in which linkage disequilibrium was observed between multiple loci, MM risk was positively associated with the haplotype block covering, part of the LTA*TNF complex (LTA -82C/-90G *TNF -1036C/-487G/ -417G, OR = 1.63, 95% CI 1.02-2.16) compared with the most frequently occurring haplotype observed among controls (LTA -82A/-90A *TNF -1036C/-487G./-417G). Our findings provide preliminary evidence that common genetic variants in specific immune-mediaied pathways could influence the risk of MM. (c) 2007 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Core Genotyping Facil, Gaithersburg, MD USA. NCI, Pediat Oncol Branch, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brown, EE (reprint author), Univ Alabama, Dept Epidemiol, RPHB 220,1530 3rd Ave S, Birmingham, AL 35294 USA. EM elbrown@uab.edu FU NCI NIH HHS [CA62006] NR 63 TC 20 Z9 20 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2007 VL 120 IS 12 BP 2715 EP 2722 DI 10.1002/ijc.22618 PG 8 WC Oncology SC Oncology GA 159NO UT WOS:000245873000025 PM 17315188 ER PT J AU Baccarelli, A Hou, LF Grillo, P Chow, WH AF Baccarelli, Andrea Hou, Lifang Grillo, Paolo Chow, Wong-Ho TI Reply to the letter to the Editor: Helicobacter pylori infection and MBL2 haplotypes: Lack of association or lack of evidence? SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter ID MANNOSE-BINDING LECTIN; RISK; DISEASE; CANCER C1 Univ Milan, EPOCA Epidemiol Res Ctr, Mol & Genet Epidemiol Ctr, Epidemiol Unit, I-20122 Milan, Italy. Univ Milan, EPOCA Epidemiol Res Ctr, Mangiagalli & Regina Elena Fdn, IRCCS Maggiore Hosp,Epidemiol Unit, I-20122 Milan, Italy. Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Baccarelli, A (reprint author), Univ Milan, EPOCA Epidemiol Res Ctr, Mol & Genet Epidemiol Ctr, Epidemiol Unit, Via San Barnaby 8, I-20122 Milan, Italy. EM andrea.baccarelli@unimi.it NR 7 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 15 PY 2007 VL 120 IS 12 BP 2750 EP 2750 DI 10.1002/ijc.22659 PG 1 WC Oncology SC Oncology GA 159NO UT WOS:000245873000031 ER PT J AU Narver, HL AF Narver, Heather Lyons TI Demographics, moral orientation, and veterinary shortages in food animal and laboratory animal medicine SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material ID GENDER DIFFERENCES; RIGHTS ACTIVISTS; STUDENTS; CAREER; JUSTICE; FUTURE; SCIENTISTS; PROFESSION; PHYSICIANS; ATTITUDES C1 NINDS, Anim Hlth & Care Sect, NIH, Bethesda, MD 20892 USA. RP Narver, HL (reprint author), NINDS, Anim Hlth & Care Sect, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. NR 64 TC 10 Z9 10 U1 2 U2 3 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JUN 15 PY 2007 VL 230 IS 12 BP 1798 EP 1804 DI 10.2460/javma.230.12.1798 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 177ZJ UT WOS:000247190700024 PM 17571978 ER PT J AU Thakurta, AG Selvanathan, SP Patterson, AD Gopal, G Dhar, R AF Thakurta, Anjan G. Selvanathan, Saravana P. Patterson, Andrew D. Gopal, Ganesh Dhar, Ravi TI The nuclear export signal of splicing factor Uap56p interacts with nuclear pore-associated protein Rae1p for mRNA export in Schizosaccharomyces pombe SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSLATION INITIATION FACTOR-4A; FISSION YEAST; SACCHAROMYCES-CEREVISIAE; COMPLEX; HOMOLOG; TRANSCRIPTION; MACHINERY; MEX67P; YRA1P; SUB2P AB Mammalian UAP56 or its homolog Sub2p in Saccharomyces cerevisiae are members of the ATP-dependent RNA helicase family and are required for splicing and nuclear export of mRNA. Previously we showed that in Schizosaccharomyces pombe Uap56p is critical for mRNA export. It links the mRNA adapter Mlo3p, a homolog of Yra1p in S. cerevisiae or Aly in mammals, to nuclear pore-associated mRNA export factor Rae1p. In this study we show that, in contrast to S. cerevisiae, Uap56p in S. pombe is not required for pre-mRNA splicing. The putative RNA helicase function of Uap56p is not required for mRNA export. However, the RNA-binding motif of Uap56p is critical for nuclear export of mRNA. Within Uap56p we identified nuclear import and export signals that may allow it to shuttle between the nucleus and the cytoplasm. Wefound that Uap56p interacts with Rae1p directly via its nuclear export signal, and this interaction is critical for the nuclear export activity of Uap56p as well as for exporting mRNA. RNA binding and the ability to shuttle between the nucleus and cytoplasm are important features of mRNA export carriers such as HIV-Rev. Our results suggest that Uap56p could function similarly as an export carrier of mRNA in S. pombe. C1 NCI, Basic Res Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Metab Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIGMS, Pharmacol Res Associate Program, NIH, Bethesda, MD 20892 USA. RP Dhar, R (reprint author), NCI, Basic Res Lab, Canc Res Ctr, NIH, Bldg 37,Rm 5016,37 Convent Dr,9000 Rockville Pike, Bethesda, MD 20892 USA. EM dharr@mail.nih.gov RI Patterson, Andrew/G-3852-2012 OI Patterson, Andrew/0000-0003-2073-0070 FU Intramural NIH HHS NR 33 TC 6 Z9 6 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2007 VL 282 IS 24 BP 17507 EP 17516 DI 10.1074/jbc.M609727200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176KS UT WOS:000247084500021 PM 17449473 ER PT J AU DeHaven, WI Smyth, JT Boyles, RR Putney, JW AF DeHaven, Wayne I. Smyth, Jeremy T. Boyles, Rebecca R. Putney, James W., Jr. TI Calcium inhibition and calcium potentiation of Orai1, Orai2, and Orai3 calcium release-activated calcium channels SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CURRENT I-CRAC; CA2+ CHANNELS; STORE DEPLETION; PROTEIN-KINASE; T-LYMPHOCYTES; CELLS; INFLUX; STIM1; JURKAT; INACTIVATION AB The recent discoveries of Stim1 and Orai proteins have shed light on the molecular makeup of both the endoplasmic reticulum Ca(2+) sensor and the calcium release-activated calcium ( CRAC) channel, respectively. In this study, we investigated the regulation of CRAC channel function by extracellular Ca(2+) for channels composed primarily of Orai1, Orai2, and Orai3, by coexpressing these proteins together with Stim1, as well as the endogenous channels in HEK293 cells. As reported previously, Orai1 or Orai2 resulted in a substantial increase in CRAC current ( I(crac)), but Orai3 failed to produce any detectable Ca(2+) selective currents. However, sodium currents measured in the Orai3-expressing HEK293 cells were significantly larger in current density than Stim1-expressing cells. Moreover, upon switching to divalent free external solutions, Orai3 currents were considerably more stable than Orai1 or Orai2, indicating that Orai3 channels undergo a lesser degree of depotentiation. Additionally, the difference between depotentiation from Ca(2+) and Ba(2+) or Mg(2+) solutions was significantly less for Orai3 than for Orai1 or -2. Nonetheless, the Na(+) currents through Orai1, Orai2, and Orai3, as well as the endogenous store-operated Na(+) currents in HEK293 cells, were all inhibited by extracellular Ca(2+) with a half-maximal concentration of similar to 20 mu M. We conclude that Orai1, -2, and -3 channels are similarly inhibited by extracellular Ca(2+), indicating similar affinities for Ca(2+) within the selectivity filter. Orai3 channels appeared to differ from Orai1 and -2 in being somewhat resistant to the process of Ca(2+) depotentiation. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov OI Boyles, Rebecca/0000-0003-0073-6854 FU Intramural NIH HHS NR 28 TC 142 Z9 147 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2007 VL 282 IS 24 BP 17548 EP 17556 DI 10.1074/jbc.M611374200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176KS UT WOS:000247084500025 PM 17452328 ER PT J AU Malnasi-Csizmadia, A Toth, J Pearson, DS Hetenyi, C Nyitray, L Geeves, MA Bagshaw, CR Kovacs, M AF Malnasi-Csizmadia, Andras Toth, Judit Pearson, David S. Hetenyi, Csaba Nyitray, Laszlo Geeves, Michael A. Bagshaw, Clive R. Kovacs, Mihaly TI Selective perturbation of the myosin recovery stroke by point mutations at the base of the lever arm affects ATP hydrolysis and phosphate release SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID X-RAY STRUCTURES; II MOTOR DOMAIN; KINETIC CHARACTERIZATION; TRYPTOPHAN RESIDUE; MOLECULAR MOTOR; DICTYOSTELIUM; MECHANISM; RESOLUTION; TRANSITION; DYNAMICS AB After ATP binding the myosin head undergoes a large structural rearrangement called the recovery stroke. This transition brings catalytic residues into place to enable ATP hydrolysis, and at the same time it causes a swing of the myosin lever arm into a primed state, which is a prerequisite for the power stroke. By introducing point mutations into a subdomain interface at the base of the myosin lever arm at positions Lys(84) and Arg(704), we caused modulatory changes in the equilibrium constant of the recovery stroke, which we could accurately resolve using the fluorescence signal of single tryptophan Dictyostelium myosin II constructs. Our results shed light on a novel role of the recovery stroke: fine-tuning of this reversible equilibrium influences the functional properties of myosin through controlling the effective rates of ATP hydrolysis and phosphate release. C1 Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary. Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. Univ Kent, Dept Biosci, Canterbury CT2 7NJ, Kent, England. RP Kovacs, M (reprint author), Eotvos Lorand Univ, Dept Biochem, Pazmany P Setany 1-C, H-1117 Budapest, Hungary. EM kovacsm@elte.hu RI Pearson, David/A-7892-2010; Hetenyi, Csaba/G-5249-2010; Geeves, Michael/F-7583-2011; Kovacs, Mihaly/A-6841-2011; OI Pearson, David/0000-0002-4088-8097; Hetenyi, Csaba/0000-0002-8013-971X; Bagshaw, Clive/0000-0002-5396-153X FU FIC NIH HHS [R01 TW007241-01, D43 TW006230]; Wellcome Trust [070021, 071525] NR 22 TC 15 Z9 15 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 15 PY 2007 VL 282 IS 24 BP 17658 EP 17664 DI 10.1074/jbc.M701447200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176KS UT WOS:000247084500038 PM 17449872 ER PT J AU Putney, JW AF Putney, James W., Jr. TI New molecular players in capacitative Ca2+ entry SO JOURNAL OF CELL SCIENCE LA English DT Article DE store-operated Ca2+ entry; Ca2+ channels; Stim1; Orai1; Ca2+-release; activated Ca2+ current ID ACTIVATED CALCIUM CURRENT; OPERATED CATION CHANNELS; PANCREATIC ACINAR-CELLS; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-C; CURRENT I-CRAC; PLASMA-MEMBRANE; ENDOPLASMIC-RETICULUM; STORE DEPLETION; T-LYMPHOCYTES AB Capacitative Ca2+ entry links the emptying of intracellular Ca2+ stores to the activation of store-operated Ca2+ channels in the plasma membrane. In the twenty years since the inception of the concept of capacitative Ca2+ entry, a number of activation mechanisms have been proposed, and there has been considerable interest in the possibility that TRP channels function as store- operated channels. However, in the past two years, two major players in both the signaling and permeation mechanisms for storeoperated channels have been discovered: Stim1 and the Orai proteins. Stim1 is an endoplasmic reticulum Ca2+ sensor. It appears to act by redistributing within a small component of the endoplasmic reticulum, approaching the plasma membrane, but does not seem to translocate into the plasma membrane. Stim1 signals to plasma membrane Orai proteins, which constitute pore-forming subunits of store-operated channels. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov FU Intramural NIH HHS [Z01 ES090087-11, Z99 ES999999] NR 98 TC 96 Z9 98 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN 15 PY 2007 VL 120 IS 12 BP 1959 EP 1965 DI 10.1242/jcs.03462 PG 7 WC Cell Biology SC Cell Biology GA 175PA UT WOS:000247024300002 PM 17478524 ER PT J AU Popoff, V Mardones, GA Tenza, D Rojas, R Lamaze, C Bonifacino, JS Raposo, G Johannes, L AF Popoff, Vincent Mardones, Gonzalo A. Tenza, Daniele Rojas, Raul Lamaze, Christophe Bonifacino, Juan S. Raposo, Graca Johannes, Ludger TI The retromer complex and clathrin define an early endosomal retrograde exit site SO JOURNAL OF CELL SCIENCE LA English DT Article DE retrograde transport; retromer; Shiga toxin; endosome; golgi; clathrin ID TRANS-GOLGI NETWORK; MANNOSE 6-PHOSPHATE RECEPTORS; TO-TGN TRANSPORT; TOXIN B-SUBUNIT; SHIGA-TOXIN; EARLY/RECYCLING ENDOSOMES; ENDOPLASMIC-RETICULUM; COATED VESICLES; PROTEIN TOXINS; TRAFFICKING AB Previous studies have indicated a role for clathrin, the clathrin adaptors AP1 and epsinR, and the retromer complex in retrograde sorting from early/recycling endosomes to the trans Golgi network (TGN). However, it has remained unclear whether these protein machineries function on the same or parallel pathways. We show here that clathrin and the retromer subunit Vps26 colocalize at the ultrastructural level on early/recycling endosomes containing Shiga toxin B-subunit, a well-studied retrograde transport cargo. As previously described for clathrin, we find that interfering with Vps26 expression inhibits retrograde transport of the Shiga toxin B-subunit to the TGN. Under these conditions, endosomal tubules that take the Shiga toxin B-subunit out of transferrin-containing early/recycling endosomes appear to be stabilized. This situation differs from that previously described for low-temperature incubation and clathrin-depletion conditions under which Shiga toxin B-subunit labeling was found to overlap with that of the transferrin receptor. In addition, we find that the Shiga toxin B-subunit and the transferrin receptor accumulate close to multivesicular endosomes in clathrin-depleted cells, suggesting that clathrin initiates retrograde sorting on vacuolar early endosomes, and that retromer is then required to process retrograde tubules. Our findings thus establish a role for the retromer complex in retrograde transport of the B-subunit of Shiga toxin, and strongly suggest that clathrin and retromer function in consecutive retrograde sorting steps on early endosomes. C1 Inst Curie, Lab Tafic & Signalisat, UMR144 Curie, CNRS, F-75248 Paris 05, France. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Inst Curie, Lab Struct & Compartiments Membranaires, UMR144 Curie, CNRS, F-75248 Paris 05, France. RP Johannes, L (reprint author), Inst Curie, Lab Tafic & Signalisat, UMR144 Curie, CNRS, 26 Rue Ulm, F-75248 Paris 05, France. EM ludger.johannes@curie.fr OI Bonifacino, Juan S./0000-0002-5673-6370 NR 39 TC 114 Z9 115 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN 15 PY 2007 VL 120 IS 12 BP 2022 EP 2031 DI 10.1242/jcs.003020 PG 10 WC Cell Biology SC Cell Biology GA 175PA UT WOS:000247024300008 PM 17550971 ER PT J AU Schaubert, KL Price, DA Frahm, N Li, JZ Ng, HL Joseph, A Paul, E Majumder, B Ayyavoo, V Gostick, E Adams, S Marincola, FM Sewell, AK Altfeld, M Brenchley, JM Douek, DC Yang, OO Brander, C Goldstein, H Kan-Mitchell, J AF Schaubert, Keri L. Price, David A. Frahm, Nicole Li, Jinzhu Ng, Hwee L. Joseph, Aviva Paul, Elyse Majumder, Biswanath Ayyavoo, Velpandi Gostick, Emma Adams, Sharon Marincola, Francesco M. Sewell, Andrew K. Altfeld, Marcus Brenchley, Jason M. Douek, Daniel C. Yang, Otto O. Brander, Christian Goldstein, Harris Kan-Mitchell, June TI Availability of a diversely avid CD8(+) T cell repertoire specific for the subdominant HLA-A2-restricted HIV-1 Gag p24(19-27) epitope SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MAJOR HISTOCOMPATIBILITY COMPLEX; LYMPHOCYTE RESPONSES; ESCAPE VARIANTS; IN-VIVO; HETEROLOGOUS IMMUNITY; PRIMARY INFECTION; VACCINE DESIGN; TCR REPERTOIRE; CTL RESPONSE AB HLA-A2-restricted CTL responses to immunodominant HIV-1 epitopes do not appear to be very effective in the control of viral replication in vivo. In this study, we studied human CD8(+) T cell responses to the subdominant HEA-A2-restricted epitope TV9 (Gag p24(19-27), TLNAWVKVV) to explore the possibility of increasing its immune recognition. We confirmed in a cohort of 313 patients, infected by clade B or clade C viruses, that TV9 is rarely recognized. Of interest, the functional sensitivity of the TV9 response can be relatively high. The potential T cell repertoires for TV9 and the characteristics of constituent clonotypes were assessed by ex vivo priming of circulating CD8(+) T cells from healthy seronegative donors. TV9-specific CTLs capable of suppressing viral replication in vitro were readily generated, suggesting that the cognate T cell repertoire is not limiting. However, these cultures contained multiple discrete populations with a range of binding avidities for the TV9 tetramer and correspondingly distinct functional dependencies on the CD8 coreceptor. The lack of dominant clonotypes was not affected by the stage of maturation of the priming dendritic cells. Cultures primed by dendritic cells transduced to present endogenous TV9 were also incapable of clonal maturation. Thus, a diffuse TCR repertoire appeared to be an intrinsic characteristic of TV9-specific responses. These data indicate that subdominance is not a function of poor immunogenicity, cognate TCR repertoire availability, or the potential avidity properties thereof, but rather suggest that useful responses to this epitope are suppressed by competing CD8(+) T cell populations during HIV-1 infection. C1 Univ Texas, Dept Biol Sci, El Paso, TX 79968 USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI 48201 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Nuffield Dept Med, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Charlestown, MA 02192 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, AIDS Inst, Ctr Hlth Sci, Los Angeles, CA 90095 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Infect Dis & Microbiol, Pittsburgh, PA 15261 USA. NIH, Sect Immunogenet, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Cardiff Wales, Dept Med Biochem & Immunol, Cardiff, Wales. RP Kan-Mitchell, J (reprint author), Univ Texas, Dept Biol Sci, Biol Sci Bldg,500 W Univ Ave, El Paso, TX 79968 USA. EM jkanmitchell@utep.edu RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Ayyavoo, Velpandi/0000-0002-9043-0885 FU Intramural NIH HHS [Z01 AI001029-01, Z99 AI999999, ZIA AI001029-02]; Medical Research Council [G0501963]; NCRR NIH HHS [5G12 RR 008124, G12 RR008124]; NIAID NIH HHS [R01 AI 064069, R01 AI064069] NR 93 TC 19 Z9 19 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 JUN 15 PY 2007 VL 178 IS 12 BP 7756 EP 7766 PG 11 WC Immunology SC Immunology GA 177YX UT WOS:000247189500034 PM 17548613 ER PT J AU Ma, JSY Monu, N Shen, DT Mecklenbrauker, I Radoja, N Haydar, TF Leitges, M Frey, AB Vukmanovic, S Radoja, S AF Ma, Jennifer S. Y. Monu, Ngozi Shen, David T. Mecklenbrauker, Ingrid Radoja, Nadezda Haydar, Tarik F. Leitges, Michael Frey, Alan B. Vukmanovic, Stanislav Radoja, Sasa TI Protein kinase C delta regulates antigen receptor-induced lytic granule polarization in mouse CD8(+) CTL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; MEDIATED CYTOTOXICITY; EFFECTOR FUNCTIONS; CYTOLYTIC ACTIVITY; CELL; ACTIVATION; EXOCYTOSIS; DEGRANULATION; EXPRESSION AB Lytic granule exocytosis is the major pathway used by CD8(+) CTL to kill virally infected and tumor cells. Despite the obvious importance, of this pathway in adaptive T cell immunity, the molecular identity of enzymes involved in the regulation of this process is poorly characterized. One signal known to be critical for the regulation of granule exocytosis-mediated cytotoxicity in CD8+ T cells is Ag receptor-induced activation of protein kinase C (PKC). However, it is not known which step of the process is regulated by PKC. In addition, it has not been determined to date which of the PKC family members is required for the regulation of lytic granule exocytosis. By combination of pharmacological inhibitors and use of mice with targeted gene deletions, we show that PKC delta is required for granule exocytosis-mediated lytic function in mouse CD8(+) T cells. Our studies demonstrate that PKC delta is required for lytic granule exocytosis, but is dispensable for activation, cytokine production, and expression of cytolytic molecules in response to TCR stimulation. Importantly, defective lytic function in PKC delta-deficient cytotoxic lymphocytes is reversed by ectopic expression of PKC delta. Finally, we show that PKC delta is not involved in target cell-induced reorientation of the microtubule-organizing center, but is required for the subsequent exocytosis step, i.e., lytic granule polarization. Thus, our studies identify PKC delta as a novel and selective regulator of Ag receptor-induced lytic granule polarization in mouse CD8+ T cells. C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol, Washington, DC 20010 USA. Childrens Natl Med Ctr, Childrens Res Inst, Ctr Neurosci, Washington, DC 20010 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Canc Ctr, New York, NY 10016 USA. Rockefeller Univ, Lab Lymphocyte Signaling, New York, NY 10021 USA. NIAMSD, Dev Skin Biol Unit, NIH, Bethesda, MD 20892 USA. Max Planck Inst Expt Endocrinol, Hannover, Germany. RP Radoja, S (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Canc & Immunol, 111 Michigan Ave,NW, Washington, DC 20010 USA. EM michael.leitges@biotek.uio.no; sradoja@cnmc.org FU NCI NIH HHS [F32 CA 101449-02, F32 CA101449, R01 CA 108573, R01 CA108573]; NIAID NIH HHS [R01 AI 41573, R01 AI 48837, R01 AI041573, R01 AI048837] NR 45 TC 19 Z9 21 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 JUN 15 PY 2007 VL 178 IS 12 BP 7814 EP 7821 PG 8 WC Immunology SC Immunology GA 177YX UT WOS:000247189500040 PM 17548619 ER PT J AU Wilflingseder, D Banki, Z Garcia, E Pruenster, M Pfister, G Muellauer, B Nikolic, DS Gassner, C Ammann, CG Dierich, MP Piguet, V Stoiber, H AF Wilflingseder, Doris Banki, Zoltan Garcia, Eduardo Pruenster, Monika Pfister, Gerald Muellauer, Brigitte Nikolic, Damjan S. Gassner, Christoph Ammann, Christoph G. Dierich, Manfred P. Piguet, Vincent Stoiber, Heribert TI IgG opsonization of HIV impedes provirus formation in and infection of dendritic cells and subsequent long-term transfer to T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RECEPTOR-MEDIATED PHAGOCYTOSIS; FC-GAMMA-RECEPTORS; DC-SIGN; IN-VIVO; TYPE-1; COMPLEMENT; TRANSMISSION; EXPRESSION; MOLECULES AB Already at initial phases of infection, HIV is coated with complement fragments. During the chronic phase, when HIV-specific IgGs appear, the virus circulates immune complexed with IgG and complement. Thus, we studied the interaction of dendritic cells (DCs) and DC-T cell cocultures; with complement (C)-opsonized and C-IgG-opsonized HIV. HIV infection of monocyte-derived DCs and circulating BDCA-1-positive DCs was significantly reduced upon the presence of virus-specific but non-neutralizing IgGs. DCs exposed to C-Ig-HIV or IgG-opsonized HIV showed an impaired provirus formation and p24 production and a decreased transmission rate to autologous nonstimulated T cells upon migration along a chemokine gradient. This reduced infectivity was also observed in long-term experiments, when T cells were added delayed to DCs exposed to IgG-coated HIV without migration. Similar kinetics were seen when sera from HIV-1-infected individuals before and after seroconversion were used in infection assays. Both G and C-IgG-opsonized HIV were captured and targeted to a tetraspanin-rich endosome in immature DCs, but differed with respect to MHC class II colocalization. The reduced infection by IgG-opsonized HIV is possibly due to interactions of virus-bound IgG with Fc gamma RIIb expressed on DCs. Therefore, the intracellular fate and transmission of immune-complexed HIV seems to differ depending on time and opsonization pattern. C1 Innsbruck Med Univ, Dept Hyg Microbiol & Social Med, A-6020 Innsbruck, Austria. Univ Hosp Geneva, Dept Dermatol & Venerol, Dept Microbiol & Mol Med, Geneva, Switzerland. Sch Med, Geneva, Switzerland. Novartis Inst Biomed Res, Vienna, Austria. Inst Biomed Aging Res, Innsbruck, Austria. Cent Inst Blood Transfus, Innsbruck, Austria. Dept Immunol, Innsbruck, Austria. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Wilflingseder, D (reprint author), Innsbruck Med Univ, Dept Hyg Microbiol & Social Med, Fritz Pregl Str 3, A-6020 Innsbruck, Austria. EM doris.wilflingseder@i-med.ac.at RI Gassner, Christoph/B-2171-2012; OI Ammann, Christoph/0000-0002-6267-1286 NR 55 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2007 VL 178 IS 12 BP 7840 EP 7848 PG 9 WC Immunology SC Immunology GA 177YX UT WOS:000247189500043 PM 17548622 ER PT J AU Chun, TW Justement, JS Moir, S Hallahan, CW Maenza, J Mullins, JI Collier, AC Corey, L Fauci, AS AF Chun, Tae-Wook Justement, J. Shawn Moir, Susan Hallahan, Claire W. Maenza, Janine Mullins, James I. Collier, Ann C. Corey, Lawrence Fauci, Anthony S. TI Decay of the HIV reservoir in patients receiving antiretroviral therapy for extended periods: Implications for eradication of virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CD4(+) T-CELLS; LATENT RESERVOIR; INFECTION; ESTABLISHMENT; INDIVIDUALS; REPLICATION; SUPPRESSION; POOL AB The persistence of latently infected resting CD4(+) T cells has been clearly demonstrated in human immunodeficiency virus (HIV)-infected individuals receiving effective antiviral therapy. However, estimates of the half-life of this viral reservoir have been quite divergent. We demonstrate clear evidence for decay of this HIV reservoir in patients who initiated antiviral therapy early in infection. The half-life of this latent viral reservoir was estimated to be 4.6 months. It is projected that it will take up to 7.7 years of continuous therapy to completely eliminate latently infected resting CD4(+) T cells in infected individuals who initiate antiviral therapy early in HIV infection. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A32,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twchun@nih.gov FU Intramural NIH HHS; NCRR NIH HHS [M01 RR-00037]; NIAID NIH HHS [AI41535, AI57005] NR 15 TC 124 Z9 125 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2007 VL 195 IS 12 BP 1762 EP 1764 DI 10.1086/518250 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175BK UT WOS:000246986900006 PM 17492591 ER PT J AU Ota, MO Ndhlovu, Z Oh, S Piyasirisilp, S Berzofsky, JA Moss, WJ Griffin, DE AF Ota, Martin O. Ndhlovu, Zaza Oh, SangKon Piyasirisilp, Sucheep Berzofsky, Jay A. Moss, William J. Griffin, Diane E. TI Hemagglutinin protein is a primary target of the measles virus-specific HLA-A2-restricted CD8(+) T cell response during measles and after vaccination SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PASSIVELY ACQUIRED ANTIBODIES; PROTECTIVE IMMUNITY; RHESUS MACAQUES; FUSION; LYMPHOCYTES; INFECTION; ANTIGEN; CTL; IDENTIFICATION; PEPTIDES AB To characterize the measles virus (MV)-specific T cell responses important for evaluation of measles vaccines, human leukocyte antigen (HLA)-A2-positive and -negative adults immunized with measles-mumps-rubella vaccine were studied. Both groups developed increases in antibody and in interferon (IFN)-gamma-producing cells in response to pooled hemagglutinin (H) and fusion peptides. HLA-A2-binding peptides were predicted for all MV-encoded proteins and confirmed by T2 cell stabilization. Twenty-nine peptides were tested, and 19 (6 from H) stimulated increased IFN-gamma secretion in a majority of vaccinees. Peptide-loaded HLA-A2 tetramers or immunoglobulin dimers documented MV-specific CD8(+) T cell responses after vaccination and during measles and confirmed new A2 epitopes in H (250 - 259 and 516 - 525 aa) and matrix (M; 50 - 58 aa) protein and previously described epitopes in H (30 - 38 aa), M (211 - 219 aa), and nonstructural protein C (84 - 92 aa). No single peptide dominated the response. We conclude that H is an important stimulus for CD8(+) T cell as well as for antibody responses in HLA-A2-positive individuals. C1 Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. RP Griffin, DE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, 615 N Wolfe St,Rm E5132, Baltimore, MD 21205 USA. EM dgriffin@jhsph.edu FU Intramural NIH HHS; NIAID NIH HHS [AI-23047] NR 46 TC 18 Z9 18 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUN 15 PY 2007 VL 195 IS 12 BP 1799 EP 1807 DI 10.1086/518006 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 175BK UT WOS:000246986900011 PM 17492596 ER PT J AU Lee, HJ Oh, YK Rhee, M Lim, JY Hwang, JY Park, YS Kwon, Y Choi, KH Jo, I Park, SI Gao, B AF Lee, Hyun Jung Oh, Yeo Kyoung Rhee, Marie Lim, Joong-Yeon Hwang, Ji-Young Park, Yoon Shin Kwon, Yongil Choi, Kyung-Hee Jo, Inho Park, Sang Ick Gao, Bin TI The role of STAT1/IRF-1 on synergistic ROS production and loss of mitochondrial transmembrane potential during hepatic cell death induced by LPS/D-GaIN SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE liver injury; hepatitis; STAT1; ROS; iNOS ID NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; TNF-ALPHA; INTERFERON-GAMMA; LIVER-INJURY; ACTIVATED MACROPHAGES; SIGNALING PATHWAYS; MEDIATED HEPATITIS; INDUCED APOPTOSIS; OXIDATIVE STRESS AB Previously, we demonstrated that signal transducer and activator of transcription factor 1 (STAT1) plays an essential role in liver injury induced by lipopolysaccharide (LPS)/D-galactosamine (D-GalN); however, the underlying mechanism involved remains unclear. Here, we showed that LPS/D-GalN administration induced secretion of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (lFN-gamma), which mediated apoptosis synergistically. Moreover, LPS/D-GalN-induced apoptosis was associated with increased inducible nitric oxide synthase (iNOS) and nitric oxide (NO) production, as well as elevated reactive oxygen species (ROS) production, which were all strongly inhibited by treatment with the antioxidant N-acetyl-L-cysteine (NAC) and an iNOS/NO inhibitor, L-NMMA. Although STAT1 activation and expression did not change significantly in TNF-alpha/IFN-gamma-cotreated cells compared with cells treated with IFN-gamma alone, the absence of STAT1 or interferon regulatory factor I (IRF-1) in genetic knockout mice strongly abrogated the observed effects of TNF(alpha/IFN-gamma on iNOS/NO induction, ROS production, loss of mitochondrial transmembrane potential (Delta Psi m), and apoptosis compared with STAT1 (+/+) and IRF-1(+/+) mice. Additionally, the synergistic effects of TNF(alpha/IFN-gamma on iNOS/NO induction, ROS production, and apoptosis were significantly inhibited by overexpression of dominant negative STAT1 in contrast to overexpression of wild-type STAT1. In STAT1-deficient mice, nuclear factor KB (NF-KB) activation by TNF-alpha/IFN-gamma, was attenuated and strongly inhibited by both NAC and L-NMMA. Moreover, the proteasome inhibitor, MG132, inhibited NF-KB activation and strongly inhibited iNOS/NO induction, ROS production, and loss of Delta Psi m induced by TNF-alpha-/IFN-gamma, thereby inhibiting apoptosis. Interestingly, it appears peroxynitrite, which is produced by TNF-alpha/IFN-, may interfere with STAT1 phosphorylation by inducing STAT1. nitration. Collectively, these findings demonstrate that TNF-alpha/IFN-gamma synergisti cally potentiates iNOS/NO induction, ROS production, and loss of Delta Psi m via STAT1 overexpression, Playing an important role in promoting apoptosis and liver injury induced by LPS/D-GalN. (C) 2007 Elsevier Ltd. All rights reserved. C1 Natl Inst Hlth, Div Intractable Dis, Ctr Biomed Sci, Seoul 122701, South Korea. Hallym Univ, Gynecol Oncol Kangdong Sacred Heart Hosp, Seoul, South Korea. Chung Ang Univ, Mol Biol Lab, Dept Biol, Coll Nat Sci, Seoul 156756, South Korea. NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Lee, HJ (reprint author), Natl Inst Hlth, Div Intractable Dis, Ctr Biomed Sci, 194 Tongillo Eunpyeong Gu, Seoul 122701, South Korea. EM jhkwh@nih.go.kr NR 40 TC 30 Z9 33 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 15 PY 2007 VL 369 IS 4 BP 967 EP 984 DI 10.1016/j.jmb.2007.03.072 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176OY UT WOS:000247096000008 PM 17475277 ER PT J AU Sanches, M Krauchenco, S Martins, NH Gustchina, A Wlodawer, A Polikarpov, I AF Sanches, Mario Krauchenco, Sandra Martins, Nadia H. Gustchina, Alla Wlodawer, Alexander Polikarpov, Igor TI Structural characterization of B and non-B subtypes of HIV-protease: Insights into the natural susceptibility to drug resistance development SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1 protease structures; non-B subtype; drug resistance; subtype F protease; L89M mutation ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL PROTEASES; CRYSTAL-STRUCTURE; SITE MUTATIONS; ACTIVE-SITE; INHIBITOR; MUTANT; CRYSTALLOGRAPHY; COMPLEX; FIV AB Although a majority of HIV-1 infections in Brazil are caused by the subtype B virus (also prevalent in the United States and Western Europe), viral subtypes F and C are also found very frequently. Genomic differences between the subtypes give rise to sequence variations in the encoded proteins, including the HIV-1 protease. The current anti-HIV drugs have been developed primarily against subtype B and the effects arising from the combination of drug-resistance mutations with the naturally existing polymorphisms in non-B HIV-1 subtypes are only beginning to be elucidated. To gain more insights into the structure and function of different variants of HIV proteases, we have determined a 2.1 angstrom structure of the native subtype F HIV-1 protease (PR) in complex with the protease inhibitor TL-3. We have also solved crystal structures of two multi-drug resistant mutant HlV PRs in complex with TL-3, from subtype B (Bmut) carrying the primary mutations V82A and L90M, and from subtype F (Fmut) carrying the primary mutation V82A plus the secondary mutation M361, at 1.75 A and 2.8 angstrom resolution, respectively. The proteases Bmut, Fwt and Fmut exhibit sevenfold, threefold, and 54-fold resistance to TL-3, respectively. In addition, the structure of subtype B wild type HIV-PR in complex with TL-3 has been redetermined in space group P6(1), consistent with the other three structures. Our results show that the primary mutation V82A causes the known effect of collapsing the S1/S1' pockets that ultimately lead to the reduced inhibitory effect of TL-3. Our results further indicate that two naturally occurring polymorphic substitutions in subtype F and other non-B HIV proteases, M361 and L89M, may lead to early development of drug resistance in patients infected with non-B HIV subtypes. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ Sao Paulo, Grp Cristalog, Inst Fis & Quim Sao Carlos, BR-13560970 Sao Carlos, SP, Brazil. NCI, Prot Struct Sect, Mol Crystallog Lab, Frederick, MD 21702 USA. RP Polikarpov, I (reprint author), Univ Sao Paulo, Grp Cristalog, Inst Fis & Quim Sao Carlos, Av Trabalhador Saocarlense 400, BR-13560970 Sao Carlos, SP, Brazil. EM ipolikarpov@if.sc.usp.br RI Polikarpov, Igor/D-2575-2012; Sao Carlos Institute of Physics, IFSC/USP/M-2664-2016 FU Intramural NIH HHS NR 42 TC 29 Z9 31 U1 1 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 JUN 15 PY 2007 VL 369 IS 4 BP 1029 EP 1040 DI 10.1016/j.jmb.2007.03.049 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 176OY UT WOS:000247096000012 PM 17467738 ER PT J AU Moore, DF Kaneski, CR Askari, H Schiffmann, R AF Moore, David F. Kaneski, Christine R. Askari, Hasan Schiffmann, Raphael TI The cerebral vasculopathy of Fabry disease SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 4th International Congress on Vascular Dementia CY OCT 20-23, 2005 CL Oporto, PORTUGAL DE stroke; atherosclerosis; Fabry disease; lysosomal disease; x-linked disorder; glycolipid; vasculopathy ID ENZYME REPLACEMENT THERAPY; GALACTOSIDASE-A DEFICIENCY; ALPHA-GALACTOSIDASE; HYPERPERFUSION; SAFETY; COMPLICATIONS; PULVINAR; REVERSAL; EFFICACY; LESIONS AB Fabry disease is an X-linked disorder affecting both males and females. It is associated with an increased risk of stroke in up to 4% of patients below 55 years of age in the general population. The cerebral vasculopathy consists of ischemic strokes involving large and small vessels. The neuronal accumulation of glycosphingolipids appears to have no clinical effect on the natural history of Fabry disease with the possible exception of some reported mild cognitive abnormalities. The pathogenesis of Fabry vasculopathy remains poorly understood but is associated with abnormal functional control of the vessel secondary to endothelial dysfunction, cerebral hyper-perfusion and a prothrombotic state with likely increased production of reactive oxygen species. These abnormalities are further modified by genetic and possibly other vascular risk factors. This vasculopathy illustrates the role of glycolipids in this and possibly other types of cerebral vasculopathies. Therapy is preventive relying on standard medical care and in particular on anti-platelet agents such as clopidogrel. (c) 2007 Elsevier B.V. All rights reserved. C1 NINDS, NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. Univ Manitoba, Neurol Sect, Winnipeg, MB R3C 4J5, Canada. RP Schiffmann, R (reprint author), NINDS, NIH, Dev & Metab Neurol Branch, Bldg 10 Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM RS4e@nih.gov OI Kaneski, Christine/0000-0003-1453-2502 NR 37 TC 74 Z9 77 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2007 VL 257 IS 1-2 BP 258 EP 263 DI 10.1016/j.jns.2007.01.053 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 184MV UT WOS:000247646700041 PM 17362993 ER PT J AU Ravina, B Marder, K Fernandez, HH Friedman, JH McDonald, W Murphy, D Aarsland, D Babcock, D Cummings, J Endicott, J Factor, S Galpern, W Lees, A Marsh, L Stacy, M Gwinn-Hardy, K Voon, V Goetz, C AF Ravina, Bernard Marder, Karen Fernandez, Hubert H. Friedman, Joseph H. McDonald, William Murphy, Diane Aarsland, Dag Babcock, Debra Cummings, Jefferey Endicott, Jean Factor, Stewart Galpern, Wendy Lees, Andrew Marsh, Laura Stacy, Mark Gwinn-Hardy, Katrina Voon, Valerie Goetz, Christopher TI Diagnostic criteria for psychosis in Parkinson's disease: Report of an NINDS, NIMH work group SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's; psychosis; diagnosis ID DRUG-INDUCED PSYCHOSIS; VISUAL HALLUCINATIONS; LEWY BODIES; RISK-FACTORS; FOLLOW-UP; AUDITORY HALLUCINATIONS; DEMENTIA; SYMPTOMS; LEVODOPA; PREVALENCE AB There are no standardized diagnostic criteria for psychosis associated with Parkinson's disease (PDPsy). As part of an NIH sponsored workshop, we reviewed the existing literature on PDPsy to provide criteria that distinguish PDPsy from other causes of psychosis. Based on these data, we propose provisional criteria for PDPsy in the style of the Diagnostic and Statistical Manual of Mental Disorders IV-TR. PDPsy has a well-characterized temporal and clinical profile of hallucinations and delusions, which is different than the pattern seen in other psychotic disorders such as substance induced psychosis or schizophrenia. PDPsy is associated with a poor prognosis of chronic psychosis, nursing home placement, and death. Medications used to treat Parkinson's disease (PD) contribute to PDPsy but may not be sufficient or necessary contributors to PDPsy. PDPsy is associated with Lewy bodies pathology, imbalances of monoaminergic neurotransmitters, and visuospatial processing deficits. These findings suggest that PDPsy may result from progression of the disease process underlying PD, rather than a comorbid psychiatric disorder or drug intoxication. PDPsy is not adequately described by existing criteria for psychotic disorders. We established provisional diagnostic criteria that define a constellation of clinical features not shared by other psychotic syndromes. The criteria are inclusive and contain descriptions of the full range of characteristic symptoms, chronology of onset, duration of symptoms, exclusionary diagnoses, and associated features such as dementia. These criteria require validation and may be refined, but form a starting point for studies of the epidemiology and pathophysiology of PDPsy, and are a potential indication for therapy development. (c) 2007 Movement Disorder Society. C1 Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA. Columbia Univ, Coll Phys & Surg, Columbia Presbyterian Med Ctr, Dept Neurol, New York, NY 10032 USA. Univ Florida, McKnight Brain Inst, Dept Neurol, Gainesville, FL 32611 USA. Brown Univ, Dept Clin Neurosci, Warwick, RI USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. NINDS, NIH, Bethesda, MD 20892 USA. Stavanger Univ Hosp, Norwegian Ctr Movement Disorders, Bergen, Norway. Univ Bergen, Inst Clin Med, N-5020 Bergen, Norway. Univ Calif Los Angeles, Reed Neurol Res Ctr, Los Angeles, CA 90024 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. UCL, Reta Lila Weston Inst Neurol Studies, London, England. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Duke Univ, Dept Neurol, Durham, NC USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. RP Ravina, B (reprint author), 1351 Mt Hope Ave,Suite 223, Rochester, NY 14620 USA. EM Bemard.ravina@ctcc.rochester.edu RI Gwinn, Katrina/C-2508-2009; Lees, Andrew/A-6605-2009; OI Gwinn, Katrina/0000-0002-8277-651X; Aarsland, Dag/0000-0001-6314-216X NR 61 TC 136 Z9 142 U1 4 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN 15 PY 2007 VL 22 IS 8 BP 1061 EP 1068 DI 10.1002/mds.21382 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 184GF UT WOS:000247628400001 PM 17266092 ER PT J AU Zenner, KE Peller, M Knutzen, A Holler, I Munchau, A Hallett, M Deuschl, G Siebner, HR AF Zenner, Kirsten E. Peller, Martin Knutzen, Arne Holler, Iris Muenchau, Alexander Hallett, Mark Deuschl, Guenther Siebner, Hartwig R. TI How to assess motor impairment in writer's cramp SO MOVEMENT DISORDERS LA English DT Article DE Arm Dystonia Disability Scale; focal hand dystonia; writer's cramp; Writer's Cramp Rating Scale; kinematic handwriting analysis ID PARKINSONS-DISEASE PATIENTS; FOCAL HAND DYSTONIA; HANDWRITING MOVEMENTS; FUNCTIONAL MRI; YOUNG CONTROLS; STIMULATION; PERFORMANCE; INTEGRATION; ADAPTATION; SIZE AB Writer's cramp is a task-specific hand dystonia affecting handwriting. Clinical scores such as the Arm Dystonia Disability Scale (ADDS) or Writer's Cramp Rating Scale (WCRS) as well as kinematic analysis of handwriting movements have been used to assess functional impairment in affected patients. In 21 patients with writer's cramp and healthy controls, we analyzed the kinematics of writing and cyclic drawing movements. We rated the severity of dystonia using the ADDS and WCRS and correlated the clinical scores with movement kinematics. Mean stroke frequency was significantly reduced in dystonic patients. Drawing movements showed more frequently a decrease in stroke frequency than handwriting movements. During circle drawing, mean vertical peak velocity was more variable in patients relative to controls, indicating an impaired ability to reproduce the same kinematic pattern over time. An increase in vertical writing pressure was only observed during handwriting but not during circle drawing and may reflect a compensatory effort to stabilize the pencil. Kinematic measures and individual ADDS and WCRS scores did not correlate with each other. The lack of correlation is not surprising as ADDS, WCRS, and kinematic analysis probe different aspects of motor impairment. The ADDS characterizes how dystonia affects a set of fine manual tasks, whereas the WCRS scores the manifestation of dystonia during handwriting. Therefore, the clinical scores and kinematic analysis of handwriting provide complementary insights into motor impairment. Future studies need to address which combination of clinical scores and kinematic measures are most appropriate to quantify impairment in writer's cramp. (c) 2007 Movement Disorder Society. C1 Univ Kiel, Dept Neurol, Neurozentrum, D-24105 Kiel, Germany. Univ Hamburg Hosp, Dept Neurol, D-2000 Hamburg, Germany. NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NeuroImageNord Kiel Hamburg Lubeck, Lubeck, Germany. RP Zenner, KE (reprint author), Univ Kiel, Dept Neurol, Neurozentrum, Schittenhelmstr 10, D-24105 Kiel, Germany. EM k.zeuner@neurologie.uni-kiel.de RI Deuschl, Gunther/A-7986-2010; Siebner, Hartwig/G-4052-2016 NR 29 TC 10 Z9 11 U1 0 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUN 15 PY 2007 VL 22 IS 8 BP 1102 EP 1109 DI 10.1002/mds.21294 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 184GF UT WOS:000247628400007 PM 17230462 ER EF