FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kalueff, AV Wheaton, M Murphy, DL AF Kalueff, A. V. Wheaton, M. Murphy, D. L. TI What's wrong with my mouse model? Advances and strategies in animal modeling of anxiety and depression SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE stress; anxiety; depression; experimental (animal) models and tests; exploration; obsessive-compulsive behaviors; stereotypies; paradigm shifts ID OBSESSIVE-COMPULSIVE DISORDER; ELEVATED PLUS-MAZE; FAWN-HOODED RATS; TAIL SUSPENSION TEST; OPEN-FIELD BEHAVIOR; DEFICIT HYPERACTIVITY DISORDER; STRESS-INDUCED HYPERTHERMIA; LA-TOURETTES-SYNDROME; FORCED SWIMMING TEST; HOLE BOARD TEST AB Stress plays a key role in pathogenesis of anxiety and depression. Animal models of these disorders are widely used in behavioral neuroscience to explore stress-evoked brain abnormalities, screen anxiolytic/antidepressant drugs and establish behavioral phenotypes of gene-targeted or transgenic animals. Here we discuss the current situation with these experimental models, and critically evaluate the state of the art in this field. Noting a deficit of fresh ideas and especially new paradigms for animal anxiety and depression models, we review existing challenges and outline important directions for further research in this field. (c) 2007 Elsevier B.V. All rights reserved. C1 NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Kalueff, AV (reprint author), NIMH, Clin Sci Lab, Bldg 10, Bethesda, MD 20892 USA. EM kalueff@inbox.ru FU Intramural NIH HHS NR 369 TC 160 Z9 168 U1 7 U2 41 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR 16 PY 2007 VL 179 IS 1 BP 1 EP 18 DI 10.1016/j.bbr.2007.01.023 PG 18 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 161RM UT WOS:000246033300001 PM 17306892 ER PT J AU Niwa, M Nitta, A Shen, LY Noda, Y Nabeshima, T AF Niwa, Minae Nitta, Atsumi Shen, Liya Noda, Yukihiro Nabeshima, Toshitaka TI Involvement of glial cell line-derived neurotrophic factor in inhibitory effects of a hydrophobic dipeptide Leu-Ile on morphine-induced sensitization and rewarding effects SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE morphine (MOR); glial cell line-derived neurotrophic factor (GDNF); sensitization; rewarding effects; Leu-Ile; mice ID NUCLEUS-ACCUMBENS; NEURONS; GDNF; ADDICTION; COCAINE; RATS; AMPHETAMINE; ACQUISITION; BRAIN; DEATH AB There are few efficacious medications for drug dependence at present. We have previously demonstrated that Leu-Ile, which induces the expression of not only tumor necrosis factor-alpha (TNF-alpha) but also glial cell line-derived neurotrophic factor (GDNF), inhibits methamphetamine (METH) and morphine (MOR)-induced sensitization and rewarding effects by regulating extracellular dopamine levels via the induction of TNF-alpha expression, and indicated the potential of Leu-Ile as a novel therapeutic agent for METH and MOR-induced dependence. In the present study, we investigated the involvement of GDNF in inhibitory effects of Leu-Ile on MOR-induced sensitization and rewarding effects. Repeated treatment with MOR for 9 days, which results in an enhancement of the locomotor-stimulating effects (sensitization) of MOR, increased GDNF levels in the nucleus accumbens compared with those in saline-treated mice. Repeated pre-treatment with Leu-Ile for 9 days potentiated the MOR-induced increase in GDNF levels. MOR at a low dose (3 mg/kg) produced place preference in GDNF heterozygous knockout (GDNF-(+/-)) mice, but not in littermate GDNF-(+/+) mice. No inhibitory effect of Leu-Ile on MOR-induced place preference was observed in GDNF-(+/-) mice. These results suggest that GDNF is involved in the inhibitory effects of Leu-Ile on MOR-induced sensitization and rewarding effects. (c) 2007 Elsevier B.V. All rights reserved. C1 Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Showa Ku, Nagoya, Aichi 4668560, Japan. NCI, Ctr Canc Res, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20983 USA. Meijo Univ, Fac Pharm, Div Clin Sci Clin Pharm Practice Management & Res, Nagoya, Aichi 4688503, Japan. RP Nabeshima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Showa Ku, 65 Tsuruma Cho, Nagoya, Aichi 4668560, Japan. EM tnabeshi@med.nagoya-u.ac.jp RI Niwa, Minae/G-5469-2011 OI Niwa, Minae/0000-0002-8784-7815 NR 20 TC 20 Z9 25 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR 16 PY 2007 VL 179 IS 1 BP 167 EP 171 DI 10.1016/j.bbr.2007.01.026 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 161RM UT WOS:000246033300020 PM 17331595 ER PT J AU Chan, WFN Perez-Diez, A Razavy, H Anderson, CC AF Chan, William F. N. Perez-Diez, Ainhoa Razavy, Haide Anderson, Colin C. TI The ability of natural tolerance to be applied to allogeneic tissue: determinants and limits SO BIOLOGY DIRECT LA English DT Article ID SKIN-GRAFT REJECTION; SELF-TOLERANCE; NK CELLS; T-CELLS; HEART-TRANSPLANTATION; ALLOGRAFT TOLERANCE; FETAL LAMBS; IMMUNITY; ACTIVATION; DANGER AB Background: Transplant rejection has been considered to occur primarily because donor antigens are not present during the development of the recipient's immune system to induce tolerance. Thus, transplantation prior to recipient immune system development (pre-immunocompetence transplants) should induce natural tolerance to the donor. Surprisingly, tolerance was often not the outcome in such 'natural tolerance models'. We explored the ability of natural tolerance to prevent immune responses to alloantigens, and the reasons for the disparate outcomes of pre-immunocompetence transplants. Results: We found that internal transplants mismatched for a single minor-H antigen and 'healedin' before immune system development were not ignored but instead induced natural tolerance. In contrast, multiple minor-H or MHC mismatched transplants did not consistently induce natural tolerance unless they carried chimerism generating passenger lymphocytes. To determine whether the systemic nature of passenger lymphocytes was required for their tolerizing capacity, we generated a model of localized vs. systemic donor lymphocytes. We identified the peritoneal cavity as a site that protects allogeneic lymphocytes from killing by NK cells, and found that systemic chimerism, but not chimerism restricted to the peritoneum, was capable of generating natural tolerance. Conclusion: These data provide an explanation for the variable results with pre-immunocompetence transplants and suggest that natural tolerance to transplants is governed by the systemic vs. localized nature of donor antigen, the site of transplantation, and the antigenic disparity. Furthermore, in the absence of systemic lymphocyte chimerism the capacity to establish natural tolerance to allogeneic tissue appears strikingly limited. C1 Univ Alberta, Surg Med Res Inst, Dept Surg, Edmonton, AB, Canada. Univ Alberta, Surg Med Res Inst, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Anderson, CC (reprint author), Univ Alberta, Surg Med Res Inst, Dept Surg, Edmonton, AB, Canada. EM fchan@ualberta.ca; aperezdiez@mail.nih.gov; hrazavy@ualberta.ca; colinand@ualberta.ca NR 51 TC 18 Z9 18 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1745-6150 J9 BIOL DIRECT JI Biol. Direct PD APR 16 PY 2007 VL 2 AR 10 DI 10.1186/1745-6150-2-10 PG 16 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 159JX UT WOS:000245863000001 PM 17437644 ER PT J AU Andersen, JF Hinnebusch, BJ Lucas, DA Conrads, TP Veenstra, TD Pham, VM Ribeiro, JMC AF Andersen, John F. Hinnebusch, B. Joseph Lucas, David A. Conrads, Thomas P. Veenstra, Timothy D. Pham, Van M. Ribeiro, Jose M. C. TI An insight into the sialome of the oriental rat flea, Xenopsylla cheopis (Rots) SO BMC GENOMICS LA English DT Article ID ADULT FEMALE MOSQUITO; PROSTATIC ACID-PHOSPHATASE; SALIVARY-GLAND TRANSCRIPTS; AEDES-AEGYPTI; SCORPION TOXINS; NITRIC-OXIDE; TYROSINE PHOSPHORYLATION; 3-DIMENSIONAL STRUCTURE; 5'-NUCLEOTIDASE FAMILY; CTENOCEPHALIDES-FELIS AB Background: The salivary glands of hematophagous animals contain a complex cocktail that interferes with the host hemostasis and inflammation pathways, thus increasing feeding success. Fleas represent a relatively recent group of insects that evolved hematophagy independently of other insect orders. Results: Analysis of the salivary transcriptome of the flea Xenopsylla cheopis, the vector of human plague, indicates that gene duplication events have led to a large expansion of a family of acidic phosphatases that are probably inactive, and to the expansion of the FS family of peptides that are unique to fleas. Several other unique polypeptides were also uncovered. Additionally, an apyrasecoding transcript of the CD39 family appears as the candidate for the salivary nucleotide hydrolysing activity in X. cheopis, the first time this family of proteins is found in any arthropod salivary transcriptome. Conclusion: Analysis of the salivary transcriptome of the flea X. cheopis revealed the unique pathways taken in the evolution of the salivary cocktail of fleas. Gene duplication events appear as an important driving force in the creation of salivary cocktails of blood feeding arthropods, as was observed with ticks and mosquitoes. Only five other flea salivary sequences exist at this time at NCBI, all from the cat flea C. felis. This work accordingly represents the only relatively extensive sialome description of any flea species. Sialotranscriptomes of additional flea genera will reveal the extent that these novel polypeptide families are common throughout the Siphonaptera. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Natl Canc Inst, Frederick, MD 21702 USA. RP Ribeiro, JMC (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. EM jandersen@niaid.nih.gov; JHINNEBUSCH@niaid.nih.gov; dl258t@nih.gov; conrads@upmc.edu; tv52i@nih.gov; VPHAM@niaid.nih.gov; jribeiro@nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 85 TC 30 Z9 30 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD APR 16 PY 2007 VL 8 AR 102 DI 10.1186/1471-2164-8-102 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 170ZR UT WOS:000246705200001 PM 17437641 ER PT J AU Nylen, S Maurya, R Eidsmo, L Das Manandhar, K Sundar, S Sacks, D AF Nylen, Susanne Maurya, Radheshyam Eidsmo, Liv Das Manandhar, Krishna Sundar, Shyam Sacks, David TI Splenic accumulation of IL-10 mRNA in T cells distinct from CD4(+) CD25(+) (Foxp3) regulatory T cells in human visceral leishmaniasis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; INDIAN KALA-AZAR; INTERFERON-GAMMA; INTERLEUKIN-10 RECEPTOR; TUBERCULOSIS PATIENTS; DONOVANI INFECTIONS; CYTOKINE PROFILES; IMMUNE-RESPONSES; LYMPH-NODES AB Visceral leishmaniasis ( VL) is a life-threatening disease characterized by uncontrolled parasitization of the spleen, liver, and bone marrow. Interleukin ( IL)-10 has been implicated in the suppression of host immunity in human VL based on the elevated levels of IL-10 observed in plasma and lesional tissue, and its role in preventing clearance of Leishmania donovani in murine models of VL. The aim of this study was to identify the cellular source of IL-10 in human VL and determine if CD4(+)CD25(+) ( Foxp3(high)) regulatory T ( T reg) cells are associated with active disease. We analyzed surface marker and gene expression in peripheral blood mononuclear cells and splenic aspirates from Indian VL patients before and 3-4 wk after treatment with Amphotericin B. The results did not point to an important role for natural CD4(+)CD25(+) ( Foxp3(high)) T reg cells in human VL. They did not accumulate in and were not a major source of IL-10 in the spleen, and their removal did not rescue antigen-specific interferon.. responses. In contrast, splenic T cells depleted of CD25(+) cells expressed the highest levels of IL-10 mRNA and were the predominant lymphocyte population in the VL spleen. The elevated levels of IL-10 in VL plasma significantly enhanced the growth of L. donovani amastigotes in human macrophages. The data implicate IL-10-producing CD25(-)Foxp3(-)T cells in the pathogenesis of human VL. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India. Karolinska Inst, MTC, S-17177 Stockholm, Sweden. RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM dsacks@nih.gov FU Intramural NIH HHS NR 56 TC 170 Z9 173 U1 1 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 16 PY 2007 VL 204 IS 4 BP 805 EP 817 DI 10.1084/jem.20061141 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 160DP UT WOS:000245920600012 PM 17389235 ER PT J AU Kuo, TC Shaffer, AL Haddad, J Choi, YS Staudt, LM Calame, K AF Kuo, Tracy C. Shaffer, Arthur L. Haddad, Joseph, Jr. Choi, Yong Sung Staudt, Louis M. Calame, Kathryn TI Repression of BCL-6 is required for the formation of human memory B cells in vitro SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID GERMINAL-CENTER FORMATION; TRANSCRIPTION FACTOR; PLASMA-CELLS; GENE-EXPRESSION; ANTIGEN RECEPTOR; SELF-RENEWAL; STEM-CELLS; MATURE B; T-CELLS; DIFFERENTIATION AB Memory B cells provide rapid protection to previously encountered antigens; however, how these cells develop from germinal center B cells is not well understood. A previously described in vitro culture system using human tonsillar germinal center B cells was used to study the transcriptional changes that occur during differentiation of human memory B cells. Kinetic studies monitoring the expression levels of several known late B cell transcription factors revealed that BCL-6 is not expressed in memory B cells generated in vitro, and gene expression profiling studies confirmed that BCL-6 is not expressed in these memory B cells. Furthermore, ectopic expression of BCL-6 in human B cell cultures resulted in formation of fewer memory B cells. In addition, the expression profile of in vitro memory B cells showed a unique pattern that includes expression of genes encoding multiple costimulatory molecules and cytokine receptors, antiapoptotic proteins, T cell chemokines, and transcription factors. These studies establish new molecular criteria for defining the memory B cell stage in human B cells. C1 Columbia Univ, Med Ctr, Dept Microbiol, New York, NY 10032 USA. NCI, Canc Res Ctr, Metab Branch, Bethesda, MD 20892 USA. Columbia Univ, Med Ctr, Div Pediat Otolaryngol, New York, NY 10032 USA. Alton Ochsner Med Fdn & Ochsner Clin, Cellular Immunol Lab, New Orleans, LA 70121 USA. Columbia Univ, Med Ctr, Dept Biochem & Mol Biophys, New York, NY 10032 USA. RP Calame, K (reprint author), Columbia Univ, Med Ctr, Dept Microbiol, New York, NY 10032 USA. EM klc1@columbia.edu FU Intramural NIH HHS; NIAID NIH HHS [R01AI50659, R01 AI043576, R01 AI050659, R01AI43576] NR 77 TC 53 Z9 53 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 16 PY 2007 VL 204 IS 4 BP 819 EP 830 DI 10.1084/jem.20062104 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 160DP UT WOS:000245920600013 PM 17403935 ER PT J AU Pinsky, PF Miller, A Kramer, BS Church, T Reding, D Prorok, P Gelmann, E Schoen, RE Buys, S Hayes, RB Berg, CD AF Pinsky, P. F. Miller, A. Kramer, B. S. Church, T. Reding, D. Prorok, P. Gelmann, E. Schoen, R. E. Buys, S. Hayes, R. B. Berg, C. D. TI Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE demography; mass screening; mortality; neoplasms; randomized controlled trials; standardized mortality ratio; survival rate ID SOCIOECONOMIC-STATUS; PREVENTION TRIALS; MORTALITY AB Volunteers for prevention or screening trials are generally healthier and have lower mortality than the general population. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) is an ongoing, multicenter, randomized trial that randomized 155,000 men and women aged 55-74 years to a screening or control arm between 1993 and 2001. The authors compared demographics, mortality rates, and cancer incidence and survival rates of PLCO subjects during the early phase of the trial with those of the US population. Incidence and mortality from PLCO cancers (prostate, lung, colorectal, and ovarian) were excluded because they are the subject of the ongoing trial. Standardized mortality ratios for all-cause mortality were 46 for men, 38 for women, and 43 overall (100 standard). Cause-specific standardized mortality ratios were 56 for cancer, 37 for cardiovascular disease, and 34 for both respiratory and digestive diseases. Standardized mortality ratios for all-cause mortality increased with time on study from 31 at year 1 to 48 at year 7. Adjusting the PLCO population to a standardized demographic distribution would increase the standardized mortality ratio only modestly to 54 for women and 55 for men. Standardized incidence ratios for all cancer were 84 in women and 73 in men, with a large range of standardized incidence ratios observed for specific cancers. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol, Marshfield, WI 54449 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X; Church, Timothy R./0000-0003-3292-5035 NR 15 TC 84 Z9 86 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 2007 VL 165 IS 8 BP 874 EP 881 DI 10.1093/aje/kwk075 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 152GI UT WOS:000245349100005 PM 17244633 ER PT J AU Lazarus, SC Chinchilli, VM Rollings, NJ Boushey, HA Cherniack, R Craig, TJ Deykin, A DiMango, E Fish, JE Ford, LG Israel, E Kiley, J Kraft, M Lemanske, RF Leone, FT Martin, RJ Pesola, GR Peters, SP Sorkness, CA Szefler, SJ Wechsler, ME Fahy, JV AF Lazarus, Stephen C. Chinchilli, Vernon M. Rollings, Nancy J. Boushey, Homer A. Cherniack, Reuben Craig, Timothy J. Deykin, Aaron DiMango, Emily Fish, James E. Ford, Lean G. Israel, Elliot Kiley, James Kraft, Monica Lemanske, Robert F., Jr. Leone, Frank T. Martin, Richard J. Pesola, Gene R. Peters, Stephen P. Sorkness, Christine A. Szefler, Stanley J. Wechsler, Michael E. Fahy, John V. CA Natl Heart Lung Blood Instit As TI Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE antiasthmatic agents; smoking adverse effects; corticosteroids; leukotrienes ID ENVIRONMENTAL TOBACCO-SMOKE; CIGARETTE-SMOKING; MILD ASTHMA; AIRWAY INFLAMMATION; PERSISTENT ASTHMA; EPITHELIAL-CELLS; CONTROLLED-TRIAL; INDUCED SPUTUM; BETA-ISOFORM; ADULTS AB Rationale One-quarter to one-third of individuals with asthma smoke, which may affect response to therapy and contribute to poor asthma control. Objectives: To determine if the response to an inhaled corticosteroid or a leukotriene receptor antagonist is attenuated in individuals with asthma who smoke. Methods: In a multicenter, placebo-controlled, double-blind, double-dummy, crossover trial, 44 nonsmokers and 39 light smokers with mild asthma were assigned randomly to treatment twice daily with inhaled beclomethasone and once daily with oral montelukast. Measurements and Main Results: Primary outcome was change in prebronchodilator FEV1 in smokers versus nonsmokers. Secondary outcomes included peak flow, PC20 methacholine, symptoms, quality of life, and markers of airway inflammation. Despite similar FEV1, bronchodilator response, and sensitivity to methacholine at baseline, subjects with asthma who smoked had significantly more symptoms, worse quality of life, and lower daily peak flow than nonsmokers. Adherence to therapy did not differ significantly between smokers and nonsmokers, or between treatment arms. Beclomethasone significantly reduced sputum eosinophils and eosinophil cationic protein (ECP) in both smokers and nonsmokers, but increased FEV1 (1170 ml, p = 0.0003) only in nonsmokers. Montelukast significantly increased A.M. peak flow in smokers (12.6 L/min, p 0.002), but not in nonsmokers. Conclusions: In subjects with mild asthma who smoke, the response to inhaled corticosteroids is attenuated, suggesting that adjustments to standard therapy may be required to attain asthma control. The greater improvement seen in some outcomes in smokers treated with montelukast suggests that leukotrienes may be important in this setting. Larger prospective studies are required to determine whether leukotriene modifiers can be recommended for managing asthma in patients who smoke. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Penn State Univ, Coll Med, Hershey, PA 17033 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harlem Hosp Med Ctr, New York, NY USA. Columbia Univ, New York, NY USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NHLBI, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. RP Lazarus, SC (reprint author), Univ Calif San Francisco, 505 Parnassus Ave,M-1083, San Francisco, CA 94143 USA. EM lazma@ucsf.edu RI Wechsler, Michael /B-3979-2013 OI Wechsler, Michael /0000-0003-3505-2946 FU NHLBI NIH HHS [5 U10 HL051823, 5 U10 HL051810, 5 U10 HL051831, 5 U10 HL051834, 5 U10 HL051843, 5 U10 HL051845, 5 U10 HL056443] NR 53 TC 211 Z9 218 U1 1 U2 12 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 15 PY 2007 VL 175 IS 8 BP 783 EP 790 DI 10.1164/rccm.200511-17460C PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 157MR UT WOS:000245724700009 PM 17204725 ER PT J AU Cho, HY Morgan, DL Bauer, AK Kleeberger, SR AF Cho, Hye-Youn Morgan, Daniel L. Bauer, Alison K. Kleeberger, Steven R. TI Signal transduction pathways of tumor necrosis factor-mediated lung injury induced by ozone in mice SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE tumor necrosis factor receptor; knockout; nuclear factor-kappa B; mitogen-activated protein kinase; activator protein-1 ID NF-KAPPA-B; TOLL-LIKE RECEPTOR-4; FACTOR-ALPHA; AIRWAY HYPERRESPONSIVENESS; INFLAMMATORY RESPONSES; PULMONARY INFLAMMATION; GENETIC SUSCEPTIBILITY; ALVEOLAR MACROPHAGES; INDUCED ACTIVATION; EPITHELIAL-CELLS AB Rationale Increasing evidence suggests that tumor necrosis factor (TNF)-alpha plays a key role in pulmonary injury caused by environmental ozone (01) in animal models and human subjects. We previously determined that mice genetically deficient in TNF response are protected from lung inflammation and epithelial injury after 03 exposure. Objectives: The present study was designed to determine the molecular mechanisms of TNF receptor (TNF-R)-mediated lung injury induced by O-3. Methods: TNF-R knockout (Tnfr(-/-)) and wild-type (Tnfr(+/+)) mice were exposed to 0.3 ppm 03 or air (for 6, 24, or 48 h), and lung RNA and proteins were prepared. Mice deficient in p50 nuclear factor (NF)-kappa B (Nfkb1(-/-)) or c-Jun-NH2 terminal kinase 1 (Jnk1(-/-)) and wild-type controls (Nfkb1(+/+), Jnk(+/+)) were exposed to 03 (48 h), and the role of NF-kappa B and mitogen-activated protein kinase (MAPK) as downstream effectors of lung injury was analyzed by bronchoalveolar lavage analyses. Results: O-3-induced early activation of TNF-R adaptor complex formation was attenuated in Tnfr(-/-) mice compared with Tnfr(+/+) mice. 03 significantly activated lung NF-kappa B in Tnfr(+/+) mice before the development of lung injury. Basal and O-3-induced NF-kappa B activity was suppressed in Tnfr(-/-) mice. Compared with Tnfr(+/+) mice, MAPKs and activator protein (AP)-1 were lower in Tnfr(-/-) mice basally and after O-3. Furthermore, inflammatory cytokines, including macrophage inflammatory protein-2, were differentially expressed in Trifir(-/-) and Tnfr(+/+). mice after O-3. O-3-induced lung injury was significantly reduced in Nfkb1(-/-) and Jnk1(-/-) mice relative to respective control animals. Conclusions: Results suggest that NF-kappa B and MAPK/AP-1 signaling pathways are essential in TNF-R-mediated pulmonary toxicity induced by O-3. C1 NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Cho, HY (reprint author), NIEHS, Lab Resp Biol, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov FU Intramural NIH HHS NR 60 TC 53 Z9 55 U1 2 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR 15 PY 2007 VL 175 IS 8 BP 829 EP 839 DI 10.1164/rccm.200509-1527OC PG 11 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 157MR UT WOS:000245724700015 PM 17255564 ER PT J AU Kipper, MJ Kleinman, HK Wang, FW AF Kipper, Matt J. Kleinman, Hynda K. Wang, Francis W. TI Covalent surface chemistry gradients for presenting bioactive peptides SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE peptide gradients; cell migration; epifluorescence microscopy ID LAMININ ALPHA-1 CHAIN; CELL-ADHESION; HUMAN-NEUTROPHILS; MIGRATION; IDENTIFICATION; FIBRONECTIN; COEFFICIENT; CHEMOTAXIS; FIBRINOGEN; SEQUENCES AB The activation of surfaces by covalent attachment of bioactive moieties is an important strategy for improving the performance of biomedical materials. Such techniques have also been used as tools to study cellular responses to particular chemistries of interest. The creation of gradients of covalently bound chemistries is a logical extension of this technique. Gradient surfaces may permit the rapid screening of a large range of concentrations in a single experiment. In addition, the biological response to the gradient itself may provide new information on receptor requirements and cell signaling. The current work describes a rapid and flexible technique for the covalent addition of bioactive peptide gradients to a surface or gel and a simple fluorescence technique for assaying the gradient. In this technique, bioactive peptides with a terminal cysteine are bound via a heterobifunctional coupling agent to primary amine-containing surfaces and gels. A gradient in the coupling agent is created on the surfaces or gels by varying the residence time of the coupling agent across the surface or gel, thereby controlling the extent of reaction. We demonstrate this technique using poly(L-lysine)-coated glass surfaces and fibrin gels. Once the surface or gel has been activated by the addition of the coupling agent gradient, the bioactive peptide is added. Quantitation of the gradient is achieved by measuring the reaction kinetics of the coupling agent with the surface or gel of interest. This can be done either by fluorescently labeling the coupling agent (in the case of surfaces) or by spectrophotometrically detecting the release of pyridine-2-thione, which is produced when the thiol-reactive portion of the coupling agent reacts. By these methods, we can obtain reasonably precise estimates for the peptide gradients without using expensive spectroscopic or radiolabeling techniques. Validation with changes in fibroblast cell migration behavior across a bioactive peptide gradient illustrates preservation of peptide function as well as the usefulness of this technique. Published by Elsevier Inc. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. 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Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 238 BP 74S EP 75S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100239 ER PT J AU Savostyanova, AA van der Veen, JW Stern, A Barnett, AS Shen, J Apud, J Weinberger, DR Marenco, S AF Savostyanova, Antonina A. van der Veen, Jan Willem Stern, Alexa Barnett, Alan S. Shen, Jun Apud, Jose Weinberger, Daniel R. Marenco, Stefano TI GABA levels in medial prefrontal cortex of patients with schizophrenia: A proton magnetic resonance spectroscopy (1H-MRS) study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. 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Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 291 BP 91S EP 91S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100292 ER PT J AU Enoch, MA Goldman, D Buzas, B Barr, CS AF Enoch, Mary-Anne Goldman, David Buzas, Beata Barr, Christina S. TI Detection of genetic vulnerability to psychiatric disorders: Getting warmer? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIH, NIAAA, LNG, Bethesda, MD 20892 USA. NIH, NIAAA, LNG, Rockville, MD USA. NIH, NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. NIH, NIAAA, LCTS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 294 BP 92S EP 92S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100295 ER PT J AU Freedman, R Manji, HK Coyle, J AF Freedman, Robert Manji, Husseini K. Coyle, Joseph TI Ask the editors: A workshop on publishing in psychiatry SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Colorado, Sch Med, Denver, CO USA. Univ Colorado, Denver, CO 80202 USA. NIMH IRP, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 293 BP 92S EP 92S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100294 ER PT J AU Marsh, AA Finger, EC Mitche, DGV Kosson, D Sims, C Reid, M Pine, DS Blair, RJR AF Marsh, Abigail A. Finger, Elizabeth C. Mitche, Derek G. V. Kosson, David Sims, Courtney Reid, Maggie Pine, Daniel S. Blair, R. J. R. TI Comparing neural activation to emotional expressions in children with psychopathy and ADHD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. Univ Western Ontario, Dept Psychiat, London, ON N6A 3K7, Canada. Rosalind Franklin Univ Med & Sci, Dept Psychol, Chicago, IL USA. RI Finger, Elizabeth/B-6453-2015 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 298 BP 93S EP 93S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100299 ER PT J AU Cadenhead, KS Addington, J Cornblatt, B Heinssen, R McGlashan, TH Perkins, DO Seidman, LJ Tsuang, M Walker, EF Woods, SW Cannon, TD AF Cadenhead, Kristin S. Addington, Jean Cornblatt, Barbara Heinssen, Robert McGlashan, Thomas H. Perkins, Diana O. Seidman, Larry J. Tsuang, Ming Walker, Elaine F. Woods, Scott W. Cannon, Tyrone D. TI Prediction of psychosis in ultra high risk youth: The north American longitudinal studies (NAPLS) consortium SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Calif San Diego, La Jolla, CA 92093 USA. Univ Toronto, Toronto, ON, Canada. Zucker Hillside Hosp, Glen Oaks, NY USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. Univ N Carolina, Chapel Hill, NC USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Emory Univ, Atlanta, GA 30322 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 321 BP 101S EP 102S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100322 ER PT J AU Ernst, M AF Ernst, Monique TI Variation in the neuropeptide Y gene predicts amygdala function during the passive viewing of facial expressions in children SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, DHHS, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 356 BP 110S EP 111S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100351 ER PT J AU Thorsell, A AF Thorsell, Annika TI Neuropeptide Y in anxiety-related behaviors and regulation of ethanol intake: Animal models SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 359 BP 111S EP 111S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100354 ER PT J AU Zhou, ZF Zhou, GS Lipsky, R Hu, XZ Buzas, B Hodgkinson, C Xu, K Mash, DC Virkkunen, M Goldman, D AF Zhou, Zhifeng Zhou, Guanshan Lipsky, Robert Hu, Xian-Zhang Buzas, Beata Hodgkinson, Colin Xu, Ke Mash, Deborah C. Virkkunen, Matti Goldman, David TI Haplotype-driven NPY expression and linkage to anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIAAA, NIH, Neurogenet Lab, Rockville, MD 20852 USA. Univ Miami, Dept Neurol, Miami, FL 33152 USA. Univ Helsinki, Helsinki, Finland. RI Hodgkinson, Colin/F-9899-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 357 BP 111S EP 111S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100352 ER PT J AU Richards, AB Ward, S Rothmond, D Lenroot, R Giedd, J Noble, P Winslow, J Woodward, R Weickert, CS AF Richards, A. Brent Ward, Sarah Rothmond, Debora Lenroot, Rhoshel Giedd, Jay Noble, Pam Winslow, James Woodward, Ruth Weickert, Cynthia Shannon TI Effects of pubertal testosterone on amygdala growth in the rhesus macaque SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, MiNDS Unit, Bethesda, MD 20892 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Nonhuman Primate Core Facility, Poolesville, MD USA. NICHHD, Res Anim Management Branch, Poolesville, MD USA. Univ New S Wales, Neurosci Inst Schizophrenia & Allied Disorders, Randwick, NSW, Australia. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 393 BP 121S EP 122S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100388 ER PT J AU Ward, SE Richards, AB Rothmond, D Noble, P Woodward, R Weickert, CS Winslow, J AF Ward, Sarah E. Richards, A. Brent Rothmond, Debora Noble, Pam Woodward, Ruth Weickert, Cynthia Shannon Winslow, Jim TI Removing pubertal testosterone impacts both the cognitive performance and emotional response of adolescent rhesus macaques SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIH, NIMH, Bethesda, MD 20892 USA. NIH, NICHD, Bethesda, MD 20892 USA. Univ New S Wales, Prince Wales Med Res Inst, Neurosci Inst Schizophrenia & Allied Disorders, Sydney, NSW, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 396 BP 122S EP 122S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100391 ER PT J AU Richtand, NM Liu, YH Ahlbrand, R Sullivan, JR Newman, AH McNamara, RK AF Richtand, Neil M. Liu, Yanhong Ahlbrand, Rebecca Sullivan, Juliana R. Newman, Amy Hauck McNamara, Robert K. TI Dopaminergic regulation of dopamine D3 and D3nf receptor mRNA expression SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH USA. Vet Affairs Med Ctr, Psychiat Serv, Cincinnati, OH 45267 USA. NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 413 BP 127S EP 127S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100408 ER PT J AU Song, J Chen, J Wu, A Liu, G Du, J Ji, Y Lu, B Sei, Y Lipska, BK Weinberger, DR AF Song, J. Chen, J. Wu, A. Liu, G. Du, J. Ji, Y. Lu, B. Sei, Y. Lipska, B. K. Weinberger, D. R. TI Brain-derived neurotrophic factor Val66met polymorphism and morphometric abnormality in bipolar disorder patients SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, NIH, CBDB, Bethesda, MD 20892 USA. NIMH, NIH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012; Du, Jing/A-9023-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 441 BP 135S EP 136S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100436 ER PT J AU Khanna, A Drevets, WC Furey, ML AF Khanna, Ashish Drevets, Wayne C. Furey, Maura L. TI Gender differences in the antidepressant response to scopolamine SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 479 BP 147S EP 147S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100474 ER PT J AU Lau, JYF Nelson, E Buzas, B Fromm, SJ Goldman, D Leibenluft, E Pine, DS Ernst, M AF Lau, Jennifer Y. F. Nelson, Eric Buzas, Beata Fromm, Stephen J. Goldman, David Leibenluft, Ellen Pine, Danny S. Ernst, Monique TI Developmental moderation of 5HTT-LPR genotypic effects on amygdala function during processing of fearful faces SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mood Anxiety Program, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 484 BP 149S EP 149S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100479 ER PT J AU Marques, AH Christie, IC Sternberg, EM Eskandari, F Torvik, S Cizza, G Phillips, TM AF Marques, Andrea H. Christie, Israel C. Sternberg, Esther M. Eskandari, Farideh Torvik, Sara Cizza, Giovanni Phillips, Terry M. TI Measurement of cytokines and neuropeptides in sweat in women with major depressive disorder and healthy controls: A novel methodological approach SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, NIH, Rockville, MD 20857 USA. Univ Pittsburgh, Dept Psychiat, Cardiovasc Behav Med Program, Pittsburgh, PA USA. NIDDK, NIH, Bethesda, MD USA. NIH, Div Bioengineering & Phys Sci, Ultramicro Analyt Immunochem Resource, Bethesda, MD 20892 USA. RI marques, andrea/H-5297-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 486 BP 149S EP 149S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100481 ER PT J AU Sarpal, D Kohn, PD Meyer-Lindenberg, A Apud, JA Wint, DP Kolachana, BS Weinberger, DR Berman, KF AF Sarpal, Deepak Kohn, Philip D. Meyer-Lindenberg, Andreas Apud, Jose A. Wint, Dylan P. Kolachana, Bhaskar S. Weinberger, Daniel R. Berman, Karen F. TI Associations between COMT val158met genotype and resting regional cerebral blood flow in medication-free patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, NIH, DHHS, IRP,Sect Integrat Neuroimaging Genes Cognit & Psy, Bethesda, MD 20892 USA. NIMH, NIH, DHHS, IRP,Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RI Sarpal, Deepak/O-5630-2014; Meyer-Lindenberg, Andreas/H-1076-2011 OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 512 BP 157S EP 157S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100507 ER PT J AU Stern, AJ Marenco, S van der Veen, JW Savostyanova, A Callicott, JH Mattay, VS Weinberger, DR AF Stern, Alexa J. Marenco, Stefano van der Veen, Jan Willem Savostyanova, Antonina Callicott, Joseph H. Mattay, Venkata S. Weinberger, Daniel R. TI Impact of the BDNF va166met polymorphism on levels of hippocampal N-acetyl aspartate: A magnetic resonance spectroscopic imaging study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 514 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100509 ER PT J AU Sutaria, S Kolachana, L Nicodemus, K Weinberger, DR AF Sutaria, Surili Kolachana, Lhaskar Nicodemus, Kristin Weinberger, Daniel R. TI Monoamine oxidase-A (MAO-A) promoter polymorphism and schizophrenia: Association study in family-based trios and case-control SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 515 BP 158S EP 158S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100510 ER PT J AU McMahon, FJ AF McMahon, Francis J. TI Genetic predictors of treatment outcome in the STAR*D cohort SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 580 BP 179S EP 179S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100575 ER PT J AU Malhotra, AK Laje, G Baca-Garcia, E AF Malhotra, Anil K. Laje, Gonzalo Baca-Garcia, Enrique TI Are pharmacodynamic genes ready for psychiatric clinical practice or not? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Zucker Hillside Hosp, Glen Oaks, NY USA. NIMH, Bethesda, MD 20892 USA. Fdn Jimez Diaz, Madrid, Spain. Columbia Univ, Dept Neurosci, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 583 BP 180S EP 180S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100578 ER PT J AU Birmaher, B Leibenluft, E Brotman, MA Guyer, AE Rich, BA Dickstein, DP Axelson, DA Birmaher, B Pine, DS Delbello, M Ladouceur, CD Phillips, ML AF Birmaher, Boris Leibenluft, Ellen Brotman, Melissa A. Guyer, Amanda E. Rich, Brendan A. Dickstein, Daniel P. Axelson, David A. Birmaher, Boris Pine, Daniel S. Delbello, Melissa Ladouceur, Cecile D. Phillips, Mary L. TI Altered processing of emotional stimuli: Endophenotype for bipolar disorder? SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Pittsburgh, Pittsburgh, PA USA. NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Psychiat, Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Cincinnati, Cincinnati, OH USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 586 BP 181S EP 181S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100581 ER PT J AU Baas, JMP Klumpers, F Grillon, C Olivier, B Kenemans, L Denys, D AF Baas, Johanna M. P. Klumpers, Floris Grillon, Christian Olivier, Berend Kenemans, Leon Denys, Damiaan TI The CB1 receptor agonist Delta 9-tetrahydrocannabinol facilitates extinction of fear conditioning in humans SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Utrecht, Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Univ Med Ctr, Utrecht, Netherlands. RI Klumpers, Floris/J-2857-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 587 BP 182S EP 182S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100582 ER PT J AU Blair, K Shaywitz, J Morton, J Smith, BW Rhodes, R Geraci, M Jones, M McCaffrey, D Vythilingam, M Finger, E Mondillo, K Charney, DS Blair, JR Drevets, WC Pine, DS AF Blair, Karina Shaywitz, John Morton, John Smith, Bruce W. Rhodes, Rebecca Geraci, Marilla Jones, Matthew McCaffrey, Daniel Vythilingam, Meena Finger, Elizabeth Mondillo, Krystal Charney, Dennis S. Blair, James R. Drevets, Wayne C. Pine, Daniel S. TI The neural response to emotional expressions in generalized social phobia (GSP) and generalized anxiety disorder (GAD): Evidence for separate disorders SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London, England. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Univ London Imperial Coll Sci & Technol, MRC Clin Sci Ctr, London, England. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 592 BP 183S EP 184S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100587 ER PT J AU Burdick, KE Hodgkinson, CA Lencz, T DeRosse, P Kane, JM Goldman, D Malhotra, AK AF Burdick, Katherine E. Hodgkinson, Colin A. Lencz, Todd DeRosse, Pamela Kane, John M. Goldman, David Malhotra, Anil K. TI NDEL1 in schizophrenia: Effect on disease susceptibility, neurocognitive function, and preliminary evidence for epistasis with DISC1 SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Zucker Hillside Hosp, Long Island Jewish Med Ctr, Glen Oaks, NY USA. NIAAA, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 608 BP 189S EP 189S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100603 ER PT J AU Leibenluft, E Rich, BA Guyer, AE Brotman, MA McClure, EB Dickstein, DR Ernst, M Pine, DS AF Leibenluft, Ellen Rich, Brendan A. Guyer, Amanda E. Brotman, Melissa A. McClure, Erin B. Dickstein, Daniel R. Ernst, Monique Pine, Daniel S. TI Facial emotional processsing deficits specific to youth with bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. RI Brotman, Melissa/H-7409-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 625 BP 195S EP 195S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100620 ER PT J AU Grillon, C AF Grillon, Christian TI Integration of basic and clinical studies of fear and anxiety SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 635 BP 198S EP 198S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100630 ER PT J AU McMahon, FJ Paddock, S Wilson, A Charney, D Manji, H Laje, G Lipsky, RJ Rush, AJ AF McMahon, Francis J. Paddock, Silvia Wilson, Alexander Charney, Dennis Manji, Husseini Laje, Gonzalo Lipsky, Robert J. Rush, A. John TI Pharmacogenetics of treatment outcome and side effects in the STAR*D cohort SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, NIH, Mood & Anxiety Program, Intramural Res Program,DHHS, Bethesda, MD 20892 USA. NHGRI, Inherited Dis Res Branch, Baltimore, MD USA. Mt Sinai Sch Med, New York, NY USA. NIMH, NIH, DHHS, Intramural Res Program, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 640 BP 199S EP 199S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100635 ER PT J AU Nakata, K Lipska, BK Hyde, TM Weinberger, DR Kleinman, JE AF Nakata, Kenji Lipska, Barbara K. Hyde, Thomas M. Weinberger, Daniel R. Kleinman, Joel E. TI Analysis of novel DISC1 transcripts in human brain SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 680 BP 211S EP 211S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100675 ER PT J AU Mueller, SC Cornwell, BR Grillon, C Temple, V Berk, M Pine, D Merke, DP Ernst, M AF Mueller, Sven C. Cornwell, Brian R. Grillon, Christian Temple, Veronica Berk, Matthew Pine, Daniel Merke, Deborah P. Ernst, Monique TI Increased spatial navigation performance in congenital adrenal hyperplasia (CAH) SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 692 BP 214S EP 214S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100687 ER PT J AU Klaver, JM Drevets, WC Cannon, DM AF Klaver, Jacqueline M. Drevets, Wayne C. Cannon, Dara M. TI Serotonin transporter binding and personality in healthy subjects assessed using PET and [C-11]DASB SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, NIH, DHHS, MAP, Bethesda, MD 20892 USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 703 BP 217S EP 217S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100698 ER PT J AU Marsh, AA Blair, KS Geraci, MF McCaffrey, D Ng, PS DeVido, J Pine, DS Blair, RJR AF Marsh, Abigail A. Blair, Karina S. Geraci, Marilla F. McCaffrey, Daniel Ng, Pamela S. DeVido, Jeffrey Pine, Daniel S. Blair, R. J. R. TI Social anxiety disorder is associated with atypical neural responses to nonverbal hierarchy cues SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Mood & Anxiety Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 705 BP 218S EP 218S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100700 ER PT J AU Nery, FG Chen, HH Hatch, JP Nicoletti, MA Mallinger, AG Soares, JC AF Nery, Fabiano G. Chen, Hua-Hsuan Hatch, John P. Nicoletti, Mark A. Mallinger, Alan G. Soares, Jair C. TI Orbitofrontal cortex volumes correlate with mood state in bipolar disorder: A structural MRI study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 17-20, 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Orthodont, San Antonio, TX USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 728 BP 225S EP 226S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100723 ER PT J AU Tinsley, RK Carlson, PJ Erickson, K Bain, E Sahakian, B Drevets, WC AF Tinsley, Ruth K. Carlson, Paul J. Erickson, Kristine Bain, Earl Sahakian, Barbara Drevets, Wayne C. TI Serotonin-1A receptor binding in depressed and healthy subjects: Correlates with performance on an affective Go/No-Go task SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. Univ Cambridge, Dept Psychiat, Cambridge, England. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 760 BP 235S EP 236S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100755 ER PT J AU Iglesias, B Deep-Soboslay, A Gold, JM Weinberger, DR Hyde, TM AF Iglesias, Bianca Deep-Soboslay, Amy Gold, James M. Weinberger, Daniel R. Hyde, Thomas M. TI Enuresis in schizophrenia: More evidence of dysmaturation of the frontal cortex SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 782 BP 242S EP 243S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100777 ER PT J AU Tan, HY Nicodemus, K Chen, Q Brooke, JK Straub, R Mattay, VS Callicott, JH Weinberger, DR AF Tan, Hao-Yang Nicodemus, Kristin Chen, Qiang Brooke, Jennifer K. Straub, Richard Mattay, Venkata S. Callicott, Joseph H. Weinberger, Daniel R. TI Genetic variation in AKT1 and COMT affects prefrontal cortical neurophysiology on fMRI SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 NIMH, Cognition & Psychosis Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 813 BP 252S EP 252S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100808 ER PT J AU Wood, SJ Berger, GE Dell'Olio, M Hamer, CA Wellard, RM Pell, G Phillips, L Nelson, B Manji, H Jackson, G Pantelis, C McGorry, PD AF Wood, Stephen J. Berger, Gregor E. Dell'Olio, Margaret Hamer, Clare A. Wellard, R. Mark Pell, Gaby Phillips, Lisa Nelson, Barnaby Manji, Husseini Jackson, Graeme Pantelis, Christos McGorry, Patrick D. TI Effects of low dose lithium on hippocampal neuropathology in people at ultra-high risk for psychosis SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Melbourne, Melbourne Neuropsychiat Ctr, Melbourne, Vic, Australia. Univ Melbourne, ORYGEN Res Ctr, Melbourne, Vic, Australia. Brain Res Inst, MRI, Melbourne, Vic, Australia. NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. RI Wellard, Robert/E-9633-2012; Jackson, Graeme/A-9064-2013; Pantelis, Christos/H-7722-2014 OI Wellard, Robert/0000-0002-7364-7708; Jackson, Graeme/0000-0002-7917-5326; Pantelis, Christos/0000-0002-9565-0238 NR 0 TC 6 Z9 6 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 838 BP 259S EP 260S PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100833 ER PT J AU Blasi, G Taurisano, P Romano, R Di Giorgio, A Sambataro, F Caforio, G Latorre, V Lo Bianco, L Fazio, L Rubino, V Nardini, M Bertolino, A AF Blasi, Giuseppe Taurisano, Paolo Romano, Raffaella Di Giorgio, Annabella Sambataro, Fabio Caforio, Grazia Latorre, Valeria Lo Bianco, Luciana Fazio, Leonardo Rubino, Valeria Nardini, Marcello Bertolino, Alessandro TI Effect of olanzapine treatment on emotional processing in patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract CT 62nd Annual Scientific Meeting of the Society-of-Biological-Psychiatry CY 2007 CL San Diego, CA SP Soc Biol Psychiat C1 Univ Bari, Dept Neurol & Psychiat Sci, Bari, Italy. NIMH, NIH, CBDB, GCAP, Bethesda, MD 20892 USA. RI Fazio, Leonardo/J-4570-2012; Sambataro, Fabio/E-3426-2010 OI Fazio, Leonardo/0000-0003-4000-974X; Sambataro, Fabio/0000-0003-2102-416X NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 SU S MA 843 BP 261S EP 261S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 157DF UT WOS:000245698100838 ER PT J AU Moss, HB Hardie, TL Dahl, JP Berrettini, W Xu, K AF Moss, Howard B. Hardie, Thomas L. Dahl, John P. Berrettini, Wade Xu, Ke TI Diplotypes of the human serotonin 1B receptor promoter predict growth hormone responses to sumatriptan in abstinent alcohol-dependent men SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcohol dependence; genetics; growth hormone; serotonin; sumatriptan ID MAJOR DEPRESSION; KNOCKOUT MICE; HTR1B GENE; POLYMORPHISM; ASSOCIATION; CHALLENGE; ETHANOL; ABUSE; NEUROENDOCRINE; DISORDER AB Background: Some studies have associated alcohol dependence (AD) with the human serotonin (5-HT)(1B) receptor (HTR1B). This investigation explored the functional responsivity of HTR1B in abstinent AD men using a sumatriptan challenge, while measuring genetic heterogeneity in the HTR1B promoter. Methods: Abstinent AD men (n = 27) and abstinent men without any alcohol use disorder (n = 19) were administered 6 mg of sumatriptan succinate, subcutaneously. Plasma samples collected over the following 2 hours were assayed for growth hormone (GH) concentrations. His DNA was genotyped for the A-161T and T-261G polymorphisms of the HTR1B promoter and diplotypes determined. Results: Integrated GH responses were predicted by interactions of AD and promoter diplotypes, as well as subject ethnicity. The final model accounted for nearly 35% of the variance in GH responses. Post hoc evaluation revealed that AD was associated with a blunting of GH secretion only among individuals with the most common HTR1B diplotype (TT/TT). Conclusions: A blunting of GH responses in abstinent AD men was observed only among those with the most common HTR1B promoter diplotype. Less common promoter diplotypes appeared protective. Controlling for genetic background is a useful augmentation of case-control pharmacological challenge strategies designed to elucidate the psychobiology of AD and other complex disorders. C1 Univ Penn, Sch Med, Ctr Studies Addict, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Univ Delaware, Dept Nursing, Newark, DE USA. NIAAA, Bethesda, MD USA. RP Moss, HB (reprint author), NIAAA, NIH, 5635 Fishers Lane,3097, Bethesda, MD 20892 USA. EM mossh@mail.nih.gov RI Hardie, Thomas/J-7776-2012; OI Hardie, Thomas/0000-0002-4547-7991 FU NCRR NIH HHS [M01 RR00040]; NIAAA NIH HHS [AA13454]; NIDA NIH HHS [T32 DA07241-12] NR 42 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 BP 974 EP 978 DI 10.1016/j.biopsych.2006.08.029 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156GP UT WOS:000245636400008 PM 17217931 ER PT J AU Heinz, A Smolka, MN Braus, DF Wrase, J Beck, A Flor, H Mann, K Schumann, G Buchel, C Hariri, AR Weinberger, DR AF Heinz, Andreas Smolka, Michael N. Braus, Dieter F. Wrase, Jana Beck, Anne Flor, Herta Mann, Karl Schumann, Gunter Buechel, Christian Hariri, Ahmad R. Weinberger, Daniel R. TI Serotonin transporter genotype (5-HTTLPR): Effects of neutral and undefined conditions on amygdala activation SO BIOLOGICAL PSYCHIATRY LA English DT Article DE 5-HTT genotype; amygdala; baseline; emotion; fixation cross; functional MRI ID ANXIETY-RELATED TRAITS; GENETIC-VARIATION; PROMOTER POLYMORPHISM; PERSONALITY-TRAITS; SURPRISED FACES; BASE-LINE; ASSOCIATION; DEPRESSION; METAANALYSIS; MODERATE AB Background: A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. Functional imaging studies show that during the presentation of aversive versus neutral cues, healthy carriers of the short (s) allele showed stronger amygdala activation than long (1) carriers. However,a recent report suggested that this interaction is driven by amygdala deactivation during presentation of neutral stimuli in s carriers. Methods: Functional MRI was used to assess amygdala activation during the presentation of a fixation cross or affectively aversive or neutral visual stimuli in 29 healthy men. Results: Amygdala activation was increased ins carriers during undefined states such as the presentation of a fixation cross compared with emotionally neutral conditions. Conclusions: This finding suggests that s carriers show stronger amygdala reactivity to stimuli and contexts that are relatively uncertain, which we propose are stressful. C1 NIMH, Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Charite Univ Med Berlin, Dept Psychiat, Berlin, Germany. Cent Inst Mental Hlth, D-6800 Mannheim, Germany. Univ Clin Hamburg Eppendorf, Dept Psychiat, Hamburg, Germany. Univ Clin Hamburg Eppendorf, Dept System Neurosci, Hamburg, Germany. Inst Psychiat, London, England. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA. RP Weinberger, DR (reprint author), NIMH, Cognit & Psychosis Program, NIH, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Smolka, Michael/B-4865-2011; Hariri, Ahmad/D-5761-2011; OI Smolka, Michael/0000-0001-5398-5569; Flor, Herta/0000-0003-4809-5398 NR 25 TC 90 Z9 94 U1 3 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2007 VL 61 IS 8 BP 1011 EP 1014 DI 10.1016/j.biopsych.2006.08.019 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 156GP UT WOS:000245636400014 PM 17157270 ER PT J AU Blkbulatov, RV Yan, F Roth, BL Zjawiony, JK AF Blkbulatov, Ruslan V. Yan, Feng Roth, Bryan L. Zjawiony, Jordan K. TI Convenient synthesis and in vitro pharmacological activity of 2-thioanalogs of salvinorins A and B SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE kappa-opioid receptors agonists; semi-synthesis; salvinorin A and B thioderivatives ID OPIOID RECEPTOR AGONIST; MINT SALVIA-DIVINORUM; NEOCLERODANE DITERPENES; ANALOGS; POTENT; C(2); THIOACETATES; DEPROTECTION; THIOLS AB To study drug-receptor interactions, new thio-derivatives of salvinorin A, an extremely potent natural kappa-opioid receptor (KOR) agonist, were synthesized. Obtained compounds were examined for receptor binding affinity. Analogs with the same configuration at carbon atom C-2 as in natural salvinorin A showed higher affinity to KOR than their corresponding epimers. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Div Med Chem & Nat Prod, Sch Pharm, NIMH Psychoact Drug Screening Program, Chapel Hill, NC 27599 USA. Univ Mississippi, Sch Pharm, Pharmaceut Sci Res Inst, Natl Ctr Nat Prod Res, University, MS 38677 USA. RP Zjawiony, JK (reprint author), Univ Mississippi, Sch Pharm, Dept Pharmacognosy, University, MS 38677 USA. EM jordan@olemiss.edu RI Roth, Bryan/F-3928-2010 NR 27 TC 0 Z9 0 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 15 PY 2007 VL 17 IS 8 BP 2229 EP 2232 DI 10.1016/j.bmcl.2007.01.100 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 161VZ UT WOS:000246045900022 ER PT J AU Moody, DL Dyba, M Kosakowska-Cholody, T Tarasova, NI Michejda, CI AF Moody, Deborah L. Dyba, Marcin Kosakowska-Cholody, Teresa Tarasova, Nadya I. Michejda, Christopher I. TI Synthesis and biological activity of 5-aza-ellipticine derivatives SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE 5-aza-ellipticine; anti-tumor agents; topoisomerase II; ellipticine ID ELLIPTICINE DERIVATIVES; BISIMIDAZOACRIDONES; ALKALOIDS; POTENT; SERIES; AGENTS; DRUG AB Novel 5-aza-ellipticine derivatives were synthesized and tested as antitumor agents. The new compounds were prepared more readily than the analogous ellipticine derivatives, which are known to be potent anti-tumor agents Although the novel 5-aza-ellipticine derivatives are not as biologically active as their corresponding ellipticine analogues, the new compounds represent a new, readily accessible class of heteroaromatic catalytic inhibitors of topoisomerase 11 and possible anti-tumor agents. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, Struct Biophys Lab, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. RP Tarasova, NI (reprint author), NCI, Struct Biophys Lab, Mol Aspects Drug Design Sect, Struct Biophys Lab, POB B, Frederick, MD 21702 USA. EM tarasova@ncifcrf.gov OI Dyba, Marcin/0000-0001-6311-6877 FU Intramural NIH HHS [Z01 BC010347-07] NR 13 TC 14 Z9 14 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 15 PY 2007 VL 17 IS 8 BP 2380 EP 2384 DI 10.1016/j.bmcl.2006.09.093 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 161VZ UT WOS:000246045900054 PM 17376678 ER PT J AU Scheinberg, P Fischer, SH Li, L Nunez, O Wu, CO Sloand, EM Cohen, JI Young, NS Barrett, AJ AF Scheinberg, Phillip Fischer, Steven H. Li, Li Nunez, Olga Wu, Colin O. Sloand, Elaine M. Cohen, Jeffrey I. Young, Neal S. Barrett, A. John TI Distinct EBV and CMV reactivation patterns following antibody-based immunosuppressive regimens in patients with severe aplastic anemia SO BLOOD LA English DT Article ID EPSTEIN-BARR-VIRUS; STEM-CELL TRANSPLANTATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; LYMPHOPROLIFERATIVE DISORDER; CYTOMEGALOVIRUS-INFECTION; ANTITHYMOCYTE GLOBULIN; SUBCUTANEOUS ALEMTUZUMAB; IMMUNE RECONSTITUTION; CLINICAL-TRIAL; T-LYMPHOCYTES AB The natural history of EBV and CMV reactivation and the potential for serious complications following antibody-based immunosuppressive treatment for bone marrow failure syndromes in the absence of transplantation is not known. We monitored blood for EBV and CMV reactivation by polymerase chain reaction (PCR) weekly in 78 consecutive patients (total of 99 immunosuppressive courses) with aplastic anemia. Four regimens were studied: (1) HC, horse ATG/cyclosporine; (2) HCS, horse ATG/CsA/sirolimus; (3) RC, rabbit ATG/CsA; and (4) CP, alemtuzumab. There were no cases of EBV or CMV disease, but EBV reactivation occurred in 82 (87%) of 94 and CMV reactivation in 19 (33%) of 57 seropositive patients after starting immunosuppression. The median peak EBV copies were higher in the IRC group when compared with HC, HCS, and alemtuzumab (P < .001). The median duration of PCR positivity for EBV was higher in the RC group compared with HC, HCS, and alemtuzumab (P = .001). Subclinical reactivation of both EBV and CMV is common and nearly always self-limited in patients with bone marrow failure receiving immunosuppression; different regimens are associated with different intensity of immunosuppression as measured by viral load and lymphocyte count; and viral reactivation patterns differ according to immunosuppressive regimens. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Scheinberg, P (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10 CRC,Rm 3-5140,MSC 1202, Bethesda, MD 20892 USA. EM scheinbp@nhlbi.nih.gov OI Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS NR 37 TC 59 Z9 63 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3219 EP 3224 DI 10.1182/blood-2006-09-045625 PG 6 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500024 PM 17148582 ER PT J AU Boasso, A Herbeuval, JP Hardy, AW Anderson, SA Dolan, MJ Fuchs, D Shearer, GM AF Boasso, Adriano Herbeuval, Jean-Philippe Hardy, Andrew W. Anderson, Stephanie A. Dolan, Matthew J. Fuchs, Dietmar Shearer, Gene M. TI HIV inhibits CD4(+) T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIGEN-PRESENTING CELLS; TRANSFER-RNA-SYNTHETASE; TRYPTOPHAN CATABOLISM; INFECTED PATIENTS; LYMPHOID-TISSUE; HIV-1-INFECTED PATIENTS; ANTIRETROVIRAL THERAPY; DISEASE PROGRESSION; FETAL REJECTION AB Infection with the human immunodeficiency virus type-1 (HIV) results in acute and progressive numeric loss of CD4(+) T-helper cells and functional impairment of T-cell responses. The mechanistic basis of the functional impairment of the surviving cells is not clear. Indoleamine 2,3-dioxygenase (IDO) is an immumosuppressive enzyme that inhibits T-cell proliferation by catabolizing the essential amino acid tryptophan (Trp) into the kynurenine (kyn) pathway. Here, we show that IDO mRNA expression is elevated in peripheral blood mononuclear cells (PBMCs) from HIV(+) patients compared with uninfected healthy controls (HCs), and that in vitro inhibition of IDO with the competitive blocker 1-methyl tryptophan (1-mT) results in increased CD4(+) T-cell proliferative response in PBMCs from HIV-infected patients. We developed an in vitro model in which exposure of PBMCs from HCs to either infectious or noninfectious, R5- or X4-tropic HIV induced IDO in plasmacytoid dendritic cells (pDCs). HIV-induced IDO was not inhibited by blocking antibodies against interferon type I or type II, which, however, induced IDO in pDCs when added to PBMC cultures. Blockade of gp120/CD4 interactions with anti-CD4 Ab inhibited HIV-mediated IDO induction. Thus, induction of IDO in pDCs by HIV may contribute to the T-cell functional impairment observed in HIV/AIDS by a non-interferon-dependent mechanism. C1 NCI, NIH, Expt Immunol Branch, Bethesda, MD 20815 USA. Univ Paris 05, Hop Necker, CNRS, UMR 8147, Paris, France. Wilford Hall USAF Med Ctr, Henry M Jackson Fdn, Lackland AFB, TX 78236 USA. Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. Innsbruck Med Univ, Div Biol Chem, Innsbruck, Austria. Ludwig Boltzmann Inst AIDS Res, Innsbruck, Austria. RP Boasso, A (reprint author), NCI, NIH, Expt Immunol Branch, 10 Ctr Dr,Bldg 10,Rm 4B36, Bethesda, MD 20815 USA. EM boassoa@mail.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS NR 64 TC 178 Z9 186 U1 2 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3351 EP 3359 DI 10.1182/blood-2006-07-034785 PG 9 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500042 PM 17158233 ER PT J AU Zhao, L Cannons, JL Anderson, S Kirby, M Xu, LP Castilla, LH Schwartzberg, PL Bosselut, R Liu, PP AF Zhao, Ling Cannons, Jennifer L. Anderson, Stacie Kirby, Martha Xu, Liping Castilla, Lucio H. Schwartzberg, Pamela L. Bosselut, Rmy Liu, P. Paul TI CBFB-MYH11 hinders early T-cell development and induces massive cell death in the thymus SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; CORE-BINDING-FACTOR; FUSION GENE CBFB-MYH11; RECEPTOR-ALPHA-CHAIN; MYOSIN HEAVY-CHAIN; CBF-BETA; TRANSCRIPTION FACTOR; LYMPHOCYTE DEVELOPMENT; CYCLIN D3; CD4 REPRESSION AB Recent studies suggest that the chromosome 16 inversion, associated with acute myeloid leukemia M4Eo, takes place in hematopoietic stem cells. If this is the case, it is of interest to know the effects of the resulting fusion gene, CBFB-MYH11, on other lineages. Here we studied T-cell development in mice expressing Cbfb-MYH11 and compared them with mice compound-heterozygous for a Cbfb null and a hypomorphic GFP knock-in allele (Cbfb(-/GFP)), which had severe Cbfb deficiency. We found a differentiation block at the DN1 stage of thymocyte development in Cbfb-MYH11 knock-in chimeras. In a conditional knock-in model in which Cbfb-MYH11 expression was activated by Lck-Cre, there was a 10-fold reduction in thymocyte numbers in adult thymus, resulting mainly from impaired survival of CD4(+)CD8(+) thymocytes. Although Cbfb-MYH11 derepressed CD4 expression efficiently in reporter assays, such derepression was less pronounced in vivo. On the other hand, CD4 expression was derepressed and thymocyte development was blocked at DN1 and DN2 stages in E17.5 Cbfb(-/GFP) thymus, with a 20-fold reduction of total thymocyte numbers. Our data suggest that Cbfb-MYH11 suppressed Cbfb in several stages of T-cell development and provide a mechanism for CBFB-MYH11 association with myeloid but not lymphoid leukemia. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. NCI, Lab Immune Cell Biol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Rm 3A26, Bethesda, MD 20892 USA. EM pliu@mail.nih.gov RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU Intramural NIH HHS; NCI NIH HHS [R01 CA096983] NR 50 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3432 EP 3440 DI 10.1182/blood-2006-10-051508 PG 9 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500052 PM 17185462 ER PT J AU Wang, SS Slager, SL Brennan, P Holly, EA De Sanjose, S Bernstein, L Boffetta, P Cerhan, JR Maynadie, M Spinelli, JJ Chiu, BCH Cocco, PL Mensah, F Zhang, YW Nieters, A Dal Maso, L Bracci, PM Costantini, AS Vineis, P Severson, RK Roman, E Cozen, W Weisenburger, D Davis, S Franceschi, S La Vecchia, C Foretova, L Becker, N Staines, A Vornanen, M Zheng, TZ Hartge, P AF Wang, Sophia S. Slager, Susan L. Brennan, Paul Holly, Elizabeth A. De Sanjose, Silvia Bernstein, Leslie Boffetta, Paolo Cerhan, James R. Maynadie, Marc Spinelli, John J. Chiu, Brian C. H. Cocco, Pier Luigi Mensah, Fiona Zhang, Yawei Nieters, Alexandra Dal Maso, Luigino Bracci, Paige M. Costantini, Adele Seniori Vineis, Paolo Severson, Richard K. Roman, Eve Cozen, Wendy Weisenburger, Dennis Davis, Scott Franceschi, Silvia La Vecchia, Carlo Foretova, Lenka Becker, Nikolaus Staines, Anthony Vornanen, Martine Zheng, Tongzhang Hartge, Patricia TI Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) SO BLOOD LA English DT Article ID FRANCISCO BAY AREA; SAN-FRANCISCO; UNITED-STATES; ALCOHOL-CONSUMPTION; CONNECTICUT WOMEN; CANCER; MIGRANTS; POLYMORPHISMS; AGGREGATION; NEOPLASMS AB A role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% Cl = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Int Agcy Res Canc, Genet Epidemiol Grp, F-69372 Lyon, France. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Catalan Inst Oncol, Epidemiol & Canc Registry Unit, Barcelona, Spain. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Fac Med Dijon, Registre Hemopathies Malignes Cote Or, Dijon, France. British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Cagliari, Italy. Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. German Canc Res Ctr, Div Clin Epidemiol, D-6900 Heidelberg, Germany. Aviano Canc Ctr, Epidemiol & Biostat Unit, I-33081 Aviano, Italy. Ctr Study & Prevent Canc, Unit Occupat & Environm Epidemiol, Florence, Italy. Univ London Imperial Coll Sci Technol & Med, London, England. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Lincoln, NE USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Program Epidemiol, Fred Hutchinson Canc Res Ctr,Div Publ Hlth Sci, Seattle, WA 98195 USA. Univ Milan, Ist Stat Med & Biometria, I-20122 Milan, Italy. Univ Milan, Ist Ric Farmacol Mario Negri, Milan, Italy. Masaryk Mem Canc Inst, Brno, Czech Republic. Tampere Univ Hosp, Tampere, Finland. Univ Coll Dublin, Dept Publ Hlth, Dublin 2, Ireland. RP Wang, SS (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov RI Slager, Susan/B-6756-2009; Spinelli, John/B-6210-2013; de Sanjose Llongueras, Silvia/H-6339-2014; OI Cerhan, James/0000-0002-7482-178X; Staines, Anthony/0000-0001-9161-1357; dal maso, luigino/0000-0001-6163-200X; La Vecchia, Carlo/0000-0003-1441-897X; Mensah, Fiona/0000-0002-6951-9949 FU NCI NIH HHS [PC 65064, CA 104682, CA 45614, CA 50850, CA 51086, CA 62006, CA 87014, CA 89745, CA 92153, CA 94919, K07 CA094919, N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010, PC 67008, PC 67009, PC 67010, PC 71105, R01 CA045614, R01 CA051086, R01 CA062006, R01 CA087014, R01 CA092153, R01 CA104682, R03 CA089745] NR 46 TC 97 Z9 106 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3479 EP 3488 DI 10.1182/blood-2006-06-031948 PG 10 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500057 PM 17185468 ER PT J AU Lundqvist, A McCoy, JP Samsel, L Childs, R AF Lundqvist, Andreas McCoy, J. Philip Samsel, Leigh Childs, Richard TI Reduction of GVHD and enhanced antitumor effects after adoptive infusion of alloreactive Ly49-mismatched NK cells from MHC-matched donors SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; NATURAL-KILLER-CELLS; KIR LIGAND INCOMPATIBILITY; HEMATOPOIETIC TRANSPLANTS; MYELOGENOUS LEUKEMIA; GENE FAMILY; IN-VITRO; EXPRESSION; RECEPTORS; REJECTION AB We investigated if an infusion of alloreactive natural killer (NK) cells would reduce GVHD and mediate antitumor effects in mice undergoing MHC-matched allogeneic stem cell transplantation (SCT). Balb/c mice bearing RENCA tumors underwent an allogeneic SCT from MHC-matched B10.d2 donors and were given a single infusion of either Ly49 ligand-matched, ligand-mismatched, or no donor NK cells. Recipients of Ly49 ligand mismatched NK cells had a reduced incidence of graft-versus-host disease (GVHD; 39% vs 100%; P < .01), and prolonged survival (median 84 days vs 39 days; P < .01) compared with SCT recipients not receiving NK cells. Recipients of Ly49 ligand-matched NK cells had the same incidence of GVHD and similar survival compared with controls not receiving NK cells. Pulmonary tumor burden was significantly (P < .01) lower in recipients that received Ly49-mismatched or Ly49-matched NK cells compared with recipients not receiving NK cells. These data provide in vivo evidence that a single infusion of alloreactive donor NK cells reduces GVHD and mediates antitumor effects following MHC-matched allogeneic transplantation. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Rm 3-5140,Bldg 10-CRC,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM childsr@nih.nhlbi.gov OI Lundqvist, Andreas/0000-0002-9709-2970 FU Intramural NIH HHS NR 18 TC 57 Z9 63 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2007 VL 109 IS 8 BP 3603 EP 3606 DI 10.1182/blood-2006-05-024315 PG 4 WC Hematology SC Hematology GA 156OJ UT WOS:000245658500075 PM 17179231 ER PT J AU Pinsky, PF Andriole, G Crawford, ED Chia, D Kramer, BS Grubb, R Greenlee, R Gohagan, JK AF Pinsky, Paul F. Andriole, Gerald Crawford, E. David Chia, David Kramer, Barnett S. Grubb, Robert Greenlee, Robert Gohagan, John K. TI Prostate-specific antigen velocity and prostate cancer Gleason grade and stage SO CANCER LA English DT Article DE prostate-specific antigen; prostate-specific antigen velocity; Gleason score; pathologic stage; prostate cancer ID PREOPERATIVE PSA VELOCITY; RADICAL PROSTATECTOMY; RISK; MEN; TRIAL AB BACKGROUND. increased preoperative prostate-specific antigen (PSA) velocity (PSAV) has been associated with increased prostate cancer mortality and higher Gleason scores. The authors evaluated the relation between PSAV, biopsy Gleason score, and pathologic stage in men who were enrolled in a prostate cancer screening trial. METHODS. Data were analyzed from 1441 men who were enrolled in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who received >= 2 PSA screens and were diagnosed with prostate cancer within I year of the last screen. PSAV was estimated by using all screening PSA values within 6 years prediagnosis. RESULTS. Both PSA and PSAV were related to biopsy Gleason score. The multivariable odds ratios (OR), controlling for PSA and demographics, for having a Gleason score of 7 to 10 were 1.3 (95% confidence interval (95% CI), 0.9-1.9), 2.2 (95% Cl, 1.5-3.3), and 2.3 (95% CL 1.4-3.9) for men with PSAV values from 0.5 to 1 ng/mL per year, from 1 to 2 ng/mL per year, and > 2 ng/mL per year, respectively, compared with men who had PSAV values < 0.5 ng/mL per year. The median PSAV was 0.60 ng/mL per year for men with Gleason scores from 2 to 6 versus 0.84 ng/mL per year for men with Gleason scores from 7 to 10 (P < .0001). 658 men who underwent prostatectomy, both PSA and PSAV were associated with advanced pathologic stage in univariate analyses; however, when the analysis controlled for clinical stage and biopsy Gleason score, the associations of PSA and PSAV were no longer statistically significant. CONCLUSIONS. PSAV and PSA levels were associated independently with biopsy Gleason score. Among men who under-went prostatectomy, PSAV and PSA were not predictive of advanced pathologic stage when the analysis was controlled for biopsy Gleason score and clinical stage. It cannot be determined yet whether PSAV is predictive of long-term prostate cancer outcome in this cohort. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Div Urol, St Louis, MO 63130 USA. Univ Colorado, Hlth Sci Ctr, Dept Urol Oncol, Denver, CO 80202 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90024 USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 14 TC 40 Z9 41 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2007 VL 109 IS 8 BP 1689 EP 1695 DI 10.1002/cncr.22558 PG 7 WC Oncology SC Oncology GA 155IK UT WOS:000245570900031 PM 17330856 ER PT J AU Swoboda, RK Somasundaram, R Caputo, L Ochoa, EM Gimotty, PA Marincola, FM Van Belle, P Barth, S Elder, D Guerry, D Czerniecki, B Schuchter, L Vonderheide, RH Herlyn, D AF Swoboda, Rolf K. Somasundaram, Rajasekharan Caputo, Laura Ochoa, Elizabeth M. Gimotty, Phyllis A. Marincola, Francesco M. Van Belle, Patricia Barth, Stephen Elder, David Guerry, DuPont Czerniecki, Brian Schuchter, Lynn Vonderheide, Robert H. Herlyn, Dorothee TI Shared MHC class II-dependent melanoma ribosomal protein L8 identified by phage display SO CANCER RESEARCH LA English DT Article ID CD4(+) T-LYMPHOCYTES; TUMOR-ANTIGEN; CELLS; VACCINES; IMMUNITY; CLONING; CANCER AB Antigens recognized by T helper (Th) cells in the context of MHC class II molecules have vaccine potential against cancer and infectious agents. We have described previously a melanoma patient's HLA-DR7-restricted Th cell clone recognizing an antigen, which is shared among melanoma and glioma cells derived from various patients. Here, this antigen was cloned using a novel antigen phage display approach. The antigen was identified as the ribosomal protein L8 (RPL8). A peptide of RPL8 significantly stimulated proliferation and/or cytokine expression of the Th cell clone and lymphocytes in four of nine HLA-DR7(+) melanoma patients but not in healthy volunteers. The RPL8 antigen may represent a relevant vaccine target for patients with melanoma, glioma, and breast carcinoma whose tumors express this protein. C1 Univ Penn, Program Immunol, Wistar Inst, Philadelphia, PA 19104 USA. Univ Penn, Ctr Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Herlyn, D (reprint author), Univ Penn, Program Immunol, Wistar Inst, 3601 Spruce St, Philadelphia, PA 19104 USA. EM dherlyn@wistar.org FU NCI NIH HHS [CA 60975, CA 10815, CA 25874, CA 88193] NR 20 TC 5 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2007 VL 67 IS 8 BP 3555 EP 3559 DI 10.1158/0008-5472.CAN-06-2763 PG 5 WC Oncology SC Oncology GA 158GL UT WOS:000245779600013 PM 17440064 ER PT J AU Hama, Y Urano, Y Koyama, Y Choyke, PL Kobayashi, H AF Hama, Yukihiro Urano, Yasuteru Koyama, Yoshinori Choyke, Peter L. Kobayashi, Hisataka TI Activatable fluorescent molecular imaging of peritoneal metastases following pretargeting with a biotinylated monoclonal antibody SO CANCER RESEARCH LA English DT Article ID IN-VIVO; ENDOSOME FUSION; BINDING ASSAY; AVIDIN; AGENT AB Optical probes that yield high target-to-background ratios are necessary to detect microfoci of cancer that would otherwise escape detection with white light imaging. Target-specific activation of the optical signal at tumor foci is one mechanism by which high target and low background signal can be achieved. Here, we describe a two-step activation process in which the tumors are first pretargeted with a nonfluorescent biotinylated monoclonal antibody [cetuximab (Erbitux) targeting human epidermal growth factor receptor type 1 (HERI)]. Following this, a second agent, neutravidin-BODIPY-FL fluorescent conjugate, is given and binds to the previously targeted antibody, resulting in an similar to 10-fold amplification of the optical fluorescence signal, leading to high tumor-to-background ratios. Spectral fluorescence imaging was done in a mouse model of peritoneal metastasis using a HER1-overexpressing cell line (A431) after pretargeting with biotinylated cetuximab and 3 h after administration of neutravidin-conjugated BODIPY-FL. Both aggregated tumors as well as small cancer implants were clearly visualized in vivo. For lesions similar to 0.8 mm or greater in diameter, the spectral fluorescence imaging had a sensitivity of 96% (178 of 185) and a specificity of 98% (188 of 191). This two-step activation paradigm (pretargeting followed by neutravidinbiotin binding with an attached activatable fluorophore) could be useful in tumor-specific molecular imaging of various targets to guide surgical resections. C1 NCI, Mol Imaging Program, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Grad Sch Pharmaceut Sci, Tokyo, Japan. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Canc Res Ctr, NIH, Bldg 10,Room 1B40,MSC 1088, Bethesda, MD 20892 USA. EM Kobayash@mail.nih.gov RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS NR 14 TC 45 Z9 45 U1 1 U2 16 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2007 VL 67 IS 8 BP 3809 EP 3817 DI 10.1158/0008-5472.CAN-06-3794 PG 9 WC Oncology SC Oncology GA 158GL UT WOS:000245779600044 PM 17440095 ER PT J AU Tsai, MH Cook, JA Chandramouli, GVR DeGraff, W Yan, HL Zhao, SP Coleman, CN Mitchell, JB Chuang, EY AF Tsai, Mong-Hsun Cook, John A. Chandramouli, Gadisetti V. R. DeGraff, William Yan, Hailing Zhao, Shuping Coleman, C. Norman Mitchell, James B. Chuang, Eric Y. TI Gene expression profiling of breast, prostate, and glioma cells following single versus fractionated doses of radiation SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR-BETA; IONIZING-RADIATION; CANCER-CELLS; WILD-TYPE; P53; STAT1; RADIOTHERAPY; SENSITIVITY; IRRADIATION; CARCINOMA AB Studies were conducted to determine whether gene expression profiles following a single dose of radiation would yield equivalent profiles following fractionated radiation in different tumor cell lines. MCF7 (breast), DU145 (prostate), and SF539 (gliosarcoma) cells were exposed to a total radiation dose of 10 Gy administered as a single dose (SD) or by daily multifractions (MF) of 5 X 2 Gy. Following radiation treatment, mRNA was isolated at 1, 4, 10, and 24 h and processed for cDNA microarray analysis. To determine the influence of the tumor microenvironment on gene expression, one cell type (DU145) was evaluated growing as a solid tumor in athymic nude mice for both radiation protocols. Unsupervised hierarchical cluster map analysis showed significant differences in gene expression profiles between SD and MF treatments for cells treated in vitro, with MF yielding a more robust induction compared with SD. Several genes were uniquely up-regulated by MF treatment, including multiple IFN-related genes (STAT1, GIP2. OAS1, OAS3, GIP3, IFITM-1) and TGF-beta-associated genes (EGR1, VEGF, THBS1, and TGFB2). DU145 cells grown in vivo exhibited a completely different set of genes induced by both SD and MF compared with the same cells exposed in vitro. The results of the study clearly show distinct differences in the molecular response of cells between SD and MF radiation exposures and show that the tumor microenvironment can significantly influence the pattern of gene expression after radiation exposures. C1 Natl Taiwan Univ, Dept Elect Engn, Grad Inst Biomed Elect & Bioinformat, Taipei 106, Taiwan. Natl Taiwan Univ, Inst Biotechnol, Taipei 106, Taiwan. NCI, Radiat Biol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Ctr Adv Technol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Chuang, EY (reprint author), Natl Taiwan Univ, Dept Elect Engn, Grad Inst Biomed Elect & Bioinformat, Taipei 106, Taiwan. EM chuangey@ntu.edu.tw FU Intramural NIH HHS NR 29 TC 91 Z9 95 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2007 VL 67 IS 8 BP 3845 EP 3852 DI 10.1158/0008-5472.CAN-06-4250 PG 8 WC Oncology SC Oncology GA 158GL UT WOS:000245779600048 PM 17440099 ER PT J AU Cohen, CJ Li, YF El-Gamil, M Robbins, PF Rosenberg, SA Morgan, RA AF Cohen, Cyrille J. Li, Yong F. El-Gamil, Mona Robbins, Paul F. Rosenberg, Steven A. Morgan, Richard A. TI Enhanced antitumor activity of T cells engineered to express T-cell receptors with a second disulfide bond SO CANCER RESEARCH LA English DT Article ID CANCER REGRESSION; TCR-ALPHA; LYMPHOCYTES; TUMOR; ANTIGEN; HETERODIMERS; ACTIVATION; EFFICIENCY; CHAINS; CD8(+) AB Adoptive transfer of genetically T-cell receptor (TCR)-modified lymphocytes has been recently reported to cause objective cancer regression. However, a major limitation to this approach is the mispairing of the introduced chains with the endogenous TCR subunits, which leads to reduced TCR surface expression and, subsequently, to their lower biological activity. We here show that it is possible to improve TCR gene transfer by adding a single cysteine on each receptor chain to promote the formation of an additional interchain disulfide bond. We show that cysteine-modified receptors were more highly expressed on the surface of human lymphocytes compared with their wild-type counterparts and able to mediate higher levels of cytokine secretion and specific lysis when cocultured with specific tumor cell lines. Furthermore, cysteine-modified receptors retained their enhanced function in CD4(+) lymphocytes. We also show that this approach can be employed to enhance the function of humanized and native murine receptors in human cells. Preferential pairing of cysteine-modified receptor chains accounts for these observations, which could have significant implications for the improvement of TCR gene therapy. C1 NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, Canc Res Ctr, NIH, Room 3W5940,Bldg 10,MSC 1201,10 Ctr Dr, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU Intramural NIH HHS [Z01 SC003811-31, Z01 SC003811-32] NR 18 TC 158 Z9 165 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2007 VL 67 IS 8 BP 3898 EP 3903 DI 10.1158/0008-5472.CAN-06-3986 PG 6 WC Oncology SC Oncology GA 158GL UT WOS:000245779600054 PM 17440104 ER PT J AU Zhou, T Chou, J Mullen, TE Elkon, R Zhou, YC Simpson, DA Bushel, PR Paules, RS Lobenhofer, EK Hurban, P Kaufmann, WK AF Zhou, Tong Chou, Jeff Mullen, Thomas E. Elkon, Rani Zhou, Yingchun Simpson, Dennis A. Bushel, Pierre R. Paules, Richard S. Lobenhofer, Edward K. Hurban, Patrick Kaufmann, William K. TI Identification of primary transcriptional regulation of cell cycle-regulated genes upon DNA damage SO CELL CYCLE LA English DT Article DE microarray; cell cycle; ionizing radiation; human fibroblasts; EPIG ID HUMAN-DIPLOID FIBROBLASTS; G(2) CHECKPOINT FUNCTION; IONIZING-RADIATION; MICROARRAY ANALYSIS; G-2/M CHECKPOINTS; P53; EXPRESSION; PROGRESSION; ARREST; REPLICATION AB The changes in global gene expression in response to DNA damage may derive from either direct induction or repression by transcriptional regulation or indirectly by synchronization of cells to specific cell cycle phases, such as G1 or G2. We developed a model that successfully estimated the expression levels of > 400 cell cycle- regulated genes in normal human fibroblasts based on the proportions of cells in each phase of the cell cycle. By isolating effects on the gene expression associated with the cell cycle phase redistribution after genotoxin treatment, the direct transcriptional target genes were distinguished from genes for which expression changed secondary to cell synchronization. Application of this model to ionizing radiation ( IR)- treated normal human fibroblasts identified 150 of 406 cycle- regulated genes as putative direct transcriptional targets of IR-induced DNA damage. Changes in expression of these genes after IR treatment derived from both direct transcriptional regulation and cell cycle synchronization. C1 Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Ctr Environm Hlth & Susceptibil, Chapel Hill, NC 27599 USA. NIEHS, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. Cogenics, Morrisville, NC USA. RP Kaufmann, WK (reprint author), Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. EM wkarlk@med.unc.edu FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [N01ES25497, U19 ES011391, ES11391, P30 ES010126, ES10126] NR 46 TC 14 Z9 15 U1 0 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 15 PY 2007 VL 6 IS 8 BP 972 EP 981 DI 10.4161/cc.6.8.4106 PG 10 WC Cell Biology SC Cell Biology GA 160NC UT WOS:000245948300016 PM 17404513 ER PT J AU Palena, C Polev, DE Tsang, KY Fernando, RI Litzinger, M Krukovskaya, LL Baranova, AV Kozlov, AP Schlom, J AF Palena, Claudia Polev, Dmitry E. Tsang, Kwong Y. Fernando, Romaine I. Litzinger, Mary Krukovskaya, Larisa L. Baranova, Ancha V. Kozlov, Andrei P. Schlom, Jeffrey TI The human T-box mesodermal transcription factor Brachyury is a candidate target for T-cell-mediated cancer immunotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITIONS; COSTIMULATORY MOLECULES; EXPRESSED SEQUENCES; TUMOR PROGRESSION; IN-SILICO; GENE; MOUSE; BINDING; METASTASIS; REGULATOR AB Purpose: Identification of tumor antigens is essential in advancing immune-based therapeutic interventions in cancer. Particularly attractive targets are those molecules that are selectively expressed by malignant cells and that are also essential for tumor progression. Experimental Design and Results: We have used a computer-based differential display analysis tool for mining of expressed sequence tag clusters in the human Unigene database and identified Brachyury as a novel tumor antigen. Brachyury, a member of the T-box transcription factor family, is a key player in mesoderm specification during embryonic development. Moreover, transcription factors that control mesoderm have been implicated in the epithelial-mesenchymal transition (EMT), which has been postulated to be a key step during tumor progression to metastasis. Reverse transcription-PCR analysis validated the in silico predictions and showed Brachyury expression in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testis, as well as in cell lines derived from lung, colon, and prostate carcinomas, but not in the vast majority of the normal tissues tested. An HLA-A0201 epitope of human Brachyury was identified that was able to expand T lymphocytes from blood of cancer patients and normal donors with the ability to lyse Brachyury-expressing tumor cells. Conclusions: To our knowledge, this is the first demonstration that (a) a T-box transcription factor and (b) a molecule implicated in mesodermal development, i.e., EMT, can be a potential target for human T-cell - mediated cancer immunotherapy. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Biomed Ctr, St Petersburg, Russia. George Mason Univ, Mol & Microbiol Dept, Fairfax, VA 22030 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Baranova, Ancha/B-4608-2012; Polev, Dmitrii/D-1386-2012; Polev, Dmitrii/J-7477-2012; Kozlov, Andrei/H-2117-2016 OI Baranova, Ancha/0000-0001-6810-5982; Polev, Dmitrii/0000-0001-9679-2791; Kozlov, Andrei/0000-0003-4611-1534 FU Intramural NIH HHS NR 35 TC 85 Z9 91 U1 1 U2 5 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 APR 15 PY 2007 VL 13 IS 8 BP 2471 EP 2478 DI 10.1158/1078-0432.CCR-06-2353 PG 8 WC Oncology SC Oncology GA 159RK UT WOS:000245883800024 PM 17438107 ER PT J AU Hjuler, T Wohlfahrt, J Simonsen, J Kaltoft, MS Koch, A Kamper-Jorgensen, M Biggar, RJ Melbye, M AF Hjuler, Thomas Wohlfahrt, Jan Simonsen, Jacob Kaltoft, Margit S. Koch, Anders Kamper-Jorgensen, Mads Biggar, Robert J. Melbye, Mads TI Perinatal and crowding-related risk factors for invasive pneumococcal disease in infants and young children: A population-based case-control study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE INFECTIONS; LOW-BIRTH-WEIGHT; UNITED-STATES; CONJUGATE VACCINE; BREAST-MILK; EPIDEMIOLOGY; CARRIAGE; ANTIBODIES; BACTERIAL; DENMARK AB Background. Denmark's systems of registry-based data offer a unique opportunity to examine, on a population basis, risk factors for invasive pneumococcal disease (IPD) relating to perinatal and crowding exposures among children. The main objective of this study was to identify the role of familial and day care factors in the risk of IPD among unvaccinated infants and children. Methods. A total of 1381 children aged 0-5 years old who experienced IPD were identified from a national surveillance program of IPD in Denmark. Risk factors were assessed in a matched, nested, case-control study that assigned 10 population control subjects to every case patient. Exposure information was obtained from several population-based, person-identifiable Danish registries. Results. Preterm birth and low birth weight significantly increased the risk of IPD among infants. In infants 0-5 months of age, the risk of IPD was high among infants who had older siblings, compared with infants of the same age who had no older siblings (adjusted rate ratio [aRR], 3.38; 95% confidence interval, 2.11-5.42), whereas the aRR was low (aRR, 0.56; 95% confidence interval, 0.47-0.65) in children aged 6-23 months. Day care attendance, compared with home care, increased the aRR of IPD 0-2 months after enrollment in a day care program (aRR, 2.28; 95% confidence interval, 1.73-3.00), whereas the aRR was 0.70; (95% confidence interval, 0.46-1.06) >= 6 months after enrollment in children aged 6-23 months. Conclusions. During infancy (age, 0-6 months), risk of IPD is associated with low birth weight, presumably because of lower levels of passively acquired maternal antibody. During early childhood, exposure to other young children (either siblings or through day care attendance) is clearly associated with IPD, but natural exposure appears to occur rapidly and confer durable immunity. C1 Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. Statens Serum Inst, Dept Bacteriol Mycol & Parasitol, DK-2300 Copenhagen, Denmark. Natl Canc Inst, Viral Epidemiol Branch, Bethesda, MD USA. RP Hjuler, T (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillerivej 5, DK-2300 Copenhagen, Denmark. EM tta@ssi.dk OI Koch, Anders/0000-0001-9205-1048 NR 32 TC 22 Z9 22 U1 0 U2 1 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 APR 15 PY 2007 VL 44 IS 8 BP 1051 EP 1056 DI 10.1086/512814 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 146IR UT WOS:000244928200006 PM 17366448 ER PT J AU Suleiman, H Heudobler, D Raschta, AS Zhao, Y Zhao, Q Hertting, I Vitzthum, H Moeller, MJ Holzman, LB Rachel, R Johnson, R Westphal, H Rascle, A Witzgall, R AF Suleiman, Ham Heudobler, Daniel Raschta, Anne-Sarah Zhao, Yangu Zhao, Qi Hertting, Irmgard Vitzthum, Helga Moeller, Marcus J. Holzman, Lawrence B. Rachel, Reinhard Johnson, Randy Westphal, Heiner Rascle, Anne Witzgall, Ralph TI The podocyte-specific inactivation of Lmx1b, Ldb1 and E2a yields new insight into a transcriptional network in podocytes SO DEVELOPMENTAL BIOLOGY LA English DT Article DE LMX1B; LDB1; E2A; podocyte; slit diaphragm; foot processes; nail-patella syndrome ID NAIL-PATELLA SYNDROME; FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; GLOMERULAR-BASEMENT-MEMBRANE; SLIT DIAPHRAGM; CD2-ASSOCIATED PROTEIN; HOMEODOMAIN PROTEINS; NEPHRIN LOCALIZES; GENE; LIM AB Patients with nail-patella syndrome, which among other symptoms also includes podocyte-associated renal failure, suffer from mutations in the LMX1B gene. The disease severity among patients is quite variable and has given rise to speculations on the presence of modifier genes. Promising candidates for modifier proteins are the proteins interacting with LMX1B, such as LDB1 and E47. Since human kidney samples from patients are difficult to obtain, conventional Lmx1b knock-out mice have been extremely valuable to study the role of Lmx1b in podocyte differentiation. In contrast to findings in these mice, however, in which a downregulation of the Col4a3, Col4a4 and Nphs2 genes has been described, no such changes have been detected in kidney biopsies from patients. We now report on our results on the characterization of constitutive podocyte-specific Lmx1b, Ldb1 and E2a knock-out mice. Constitutive podocyte-specific Lmx1b knock-out mice survive for approximately 2 weeks after birth and do not present with a downregulation of the Col4a3, Col4a4 and Nphs2 genes, therefore they mimic the human disease more closely. The podocyte-specific Ldb1 knock-out mice survive longer, but then also succumb to renal failure, whereas the E2a knock-out mice show no renal symptoms for at least 6 months after birth. We conclude that LDB1, but not E2A is a promising candidate as a modifier gene in patients with nail-patella syndrome. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Regensburg, Inst Mol & Cellular Anat, D-93053 Regensburg, Germany. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Univ Hamburg, Inst Vegetat Physiol & Pathophysiol, Hamburg, Germany. Univ Hosp, RWTH, Div Nephrol & Immunol, D-5100 Aachen, Germany. Univ Michigan, Sch Med, Div Nephrol, Ann Arbor, MI 48109 USA. Univ Regensburg, Ctr Electron Microscopy, D-8400 Regensburg, Germany. Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Witzgall, R (reprint author), Univ Regensburg, Inst Mol & Cellular Anat, Univ Str 31, D-93053 Regensburg, Germany. EM ralph.witzgall@vkl.uni-regensburg.de RI Moeller, Marcus/L-1836-2015 FU Intramural NIH HHS NR 48 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2007 VL 304 IS 2 BP 701 EP 712 DI 10.1016/vkl.uni-regensburg.de PG 12 WC Developmental Biology SC Developmental Biology GA 158UE UT WOS:000245819600020 PM 17316599 ER PT J AU Yonekura, S Xu, L Ting, CY Lee, CH AF Yonekura, Shinichi Xu, Lei Ting, Chun-Yuan Lee, Chi-Hon TI Adhesive but not signaling activity of Drosophila N-cadherin is essential for target selection of photoreceptor afferents SO DEVELOPMENTAL BIOLOGY LA English DT Article DE N-cadherin; neural target selection; layer-specific targeting; visual system development; adhesion molecule ID CELL-ADHESION; VISUAL-SYSTEM; IN-VIVO; LIPRIN-ALPHA; DN-CADHERIN; MOLECULES; CONTACTS; COMPLEX; DOMAIN; ACTIN AB Drosophila N-cadherin (CadN) is an evolutionarily conserved, atypical classical cadherm, which has a large complex extracellular domain and a catenin-binding cytoplasmic domain. We have previously shown that CadN regulates target selection of R7 photoreceptor axons. To determine the functional domains of CadN, we conducted a structure-function analysis focusing on its in vitro adhesive activity and in vivo function in R7 growth cones. We found that the cytoplasmic domain of CadN is largely dispensable for the targeting of R7 growth cones, and it is not essential for mediating homophilic interaction in cultured cells. Instead, the cytoplasmic domain of CadN is required for maintaining proper growth cone morphology. Domain swapping with the extracellular domain of CadN2, a related but non-adhesive cadherim, revealed that the CadN extracellular domain is required for both adhesive activity and R7 targeting. Using a target-mosaic system, we generated CadN mutant clones in the optic lobe and examined the target-selection of genetically wild-type R7 growth cones to CadN mutant target neurons. We found that CadN, but neither LAR nor Liprim-a, is required in the medulla neurons for R7 growth cones to select the correct medulla layer. Together, these data suggest that CadN mediates homophilic adhesive interactions between R7 growth cones and medulla neurons to regulate layer-specific target selection. (c) 2007 Elsevier Inc. All rights reserved. C1 NICHHD, Unit Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Lee, CH (reprint author), NICHHD, Unit Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bldg 18T,Room 106,MSC 5431, Bethesda, MD 20892 USA. EM leechih@mail.nih.gov RI Lee, Chi-Hon/G-9190-2012; Ting, chun-yuan/F-6448-2013 FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD008748, Z01 HD008748-04] NR 42 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 15 PY 2007 VL 304 IS 2 BP 759 EP 770 DI 10.1016/j.ydbio.2007.01.030 PG 12 WC Developmental Biology SC Developmental Biology GA 158UE UT WOS:000245819600025 PM 17320070 ER PT J AU Nagababu, E Rifkind, JM AF Nagababu, Enika Rifkind, Joseph M. TI Measurement of plasma nitrite by chemiluminescence without interference of S-, N-nitroso and nitrated species SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE plasma; nitrite; nitric oxide; chemiluminescence method; ascorbic acid; endothelial nitric oxide synthase ID OXIDE SYNTHASE ACTIVITY; CHEMI-LUMINESCENCE; HYPOXIC CONDITIONS; REDUCTION; BLOOD; DEOXYHEMOGLOBIN; NITROSOHEMOGLOBIN; ERYTHROCYTES; CIRCULATION; PATHWAY AB Recent studies have demonstrated that plasma nitrite (NO2-) reflects endothelial nitric oxide synthase activity and it has been proposed as a prognostic marker for cardiovascular disease. In addition, NO2- itself has been shown to have biological activities thought to be triggered by reduction back to NO in blood and tissues. The development of sensitive and reproducible methods for the quantitative determination of plasma NO2- is, therefore, of great importance. Ozone-based chemiluminescence assays have been shown to be highly sensitive for the determination of nanomolar quantities of NO and NO-related species in biological fluids. We report here an improved direct chemiluminescence method for the determination of plasma NO2- without interference of other nitric oxide-related species such as nitrate, S-nitrosothiols, N-nitrosamines, nitrated proteins, and nitrated lipids. The method involves a reaction system consisting of glacial acetic acid and ascorbic acid in the purge vessel of the NO analyzer. Under these acidic conditions NO2- is stoichiometrically reduced to NO by ascorbic acid. Fasting human plasma NO2- values were found in the range of 56-210 nM (mean = 110 +/- 36 W). This method has high sensitivity with an accuracy of 97% and high precision (CV < 10%) for determination of plasma nitrite. The present triethod is simple and highly specific for plasma NO2-. It is particularly suited for evaluating vasculature endothelial NO production that predicts the risks for cardiovascular disease. Published by Elsevier Inc. C1 NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Nagababu, E (reprint author), NIA, Mol Dynam Sect, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM enikan@mail.nih.gov FU Intramural NIH HHS [Z99 AG999999, Z01 AG000433-01] NR 37 TC 34 Z9 36 U1 1 U2 7 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 APR 15 PY 2007 VL 42 IS 8 BP 1146 EP 1154 DI 10.1016/j.freeradbiomed.2006.12.029 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 154NJ UT WOS:000245514000003 PM 17382196 ER PT J AU Kaczmarek, M Timofeeva, OA Karaczyn, A Malyguine, A Kasprzak, KS Salnikow, K AF Kaczmarek, Monika Timofeeva, Olga A. Karaczyn, Aldona Malyguine, Anatoli Kasprzak, Kazimierz S. Salnikow, Konstantin TI The role of ascorbate in the modulation of HIF-1 alpha protein and HIF-dependent transcription by chromium(VI) and nickel(II) SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ascorbate; chromium(VI); nickel(II); HIF-1 alpha; HIF-dependent transcription; free radicals ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; PROSTATE CARCINOMA-CELLS; GENE-EXPRESSION; PROLINE HYDROXYLATION; PROLYL 4-HYDROXYLASE; PRINCIPAL REDUCTANT; UP-REGULATION; BOUND IRON; VITAMIN-C; RAT-LIVER AB Molecular oxygen is involved in hydroxylation and subsequent degradation of HIF-1 alpha, a subunit of HIF-1 transcription factor; therefore oxygen shortage (hypoxia) stabilizes this protein. However, HIF-1 alpha can also be stabilized by transition metal ions in the presence of oxygen, suggesting that a different mechanism is involved in metal-induced hypoxic stress. Recently, we showed that the depletion of intracellular ascorbate by metals may lead to the inhibition of hydroxylases. Because nickel(II) has similarity to iron(II), an alternative hypothesis suggests that iron substitution for nickel in the enzyme inhibits hydroxylase activity. Here we investigated the induction of HIF-1 by another metal, chromium, which cannot replace iron in the enzyme. We show that chromium(VI), but not chromium(III), can oxidize ascorbate both in cells and in a cell-free system. In agreement with these data chromium(VI) stabilizes HIF-1 alpha protein in cells only until it is reduced to chromium(III). In contrast, nickel (II) was found to be a catalyst, which facilitated continuous oxidation of ascorbate by ambient oxygen. These data correlate with extended stabilization of HIF-1 alpha after acute exposur to nickel(II). The HIF-1-dependent reporter assays revealed that 20-24 h was required to fully develop the HIF-1 transcriptional response, and the acute exposure to nickel(II), but not chromium(VI), meets this requirement. However, repeated (chronic) exposure to chromium(VI) can also lead to extended stabilization of HIF-1 alpha. Thus, the obtained data emphasize the important role of ascorbate in regulation of HIF-1 transcriptional activity in metal-exposed human lung cells. Published by Elsevier Inc. C1 NCI, Frederick, MD 21701 USA. SAIC Frederick Inc, Frederick, MD 21702 USA. RP Salnikow, K (reprint author), NCI, Bldg 538,Room 205 E, Frederick, MD 21701 USA. EM salnikow@ncifcrf.gov FU Intramural NIH HHS [Z01 BC004582-32]; NCI NIH HHS [N01-CO-12400] NR 47 TC 26 Z9 29 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 15 PY 2007 VL 42 IS 8 BP 1246 EP 1257 DI 10.1016/j.freeradbiomed.2007.01.026 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 154NJ UT WOS:000245514000012 PM 17382205 ER PT J AU Burks, LM Yin, JH Plon, SE AF Burks, Lynnette M. Yin, Jinhu Plon, Sharon E. TI Nuclear import and retention domains in the amino terminus of RECQL4 SO GENE LA English DT Article DE nuclear localization signal; Rothmund-Thomson syndrome; Baller-Gerold syndrome; RAPADILINO syndrome; osteosarcoma; RecQ ID ROTHMUND-THOMSON-SYNDROME; SISTER-CHROMATID COHESION; BLOOM-SYNDROME PROTEIN; LOCALIZATION SIGNAL; DNA HELICASE; WERNERS-SYNDROME; RAPADILINO SYNDROME; GENE-PRODUCT; LEPTOMYCIN B; MUTATIONS AB Mutations in a human RecQ helicase homologue, RECQL4, have been identified in patients with Type 11 Rothmund-Thomson syndrome (RTS) with osteosarcoma predisposition, RAPADILINO syndrome, and Baller-Gerold syndrome. A role in DNA replication initiation has been demonstrated and mapped to the amino terminus upstream of the helicase domain; however, no nuclear localization signal (NLS) has been identified by sequence analysis. Here, we show both endogenous and green fluorescent protein (GFP)-tagged RECQL4 are nuclear and cytoplasmic in transformed cell lines. Using GFP-tagged constructs we identified a major nuclear localization domain within amino acids (aa) 363-492 (exons 5-8) sufficient for nuclear localization of GFP and necessary for nuclear localization of RECQL4 as GFP-RECQL4 deleted for aa 363-492 is entirely cytoplasmic. Additional mapping within this domain revealed that a conserved block of 22 basic amino acids (aa 365-386; exons 5-6) is sufficient for nuclear localization of GFP, but not required for nuclear import of RECQL4. Conversely, even though the region encoded by exon 7-8 is not sufficient for nuclear import of GFP, GFP-RECQL4 deleted for exon 7 (aa 420-463), a mutation found in all reported patients with RAPADILINO syndrome, is cytoplasmic. Nuclear localization of the exon 7 deletion construct is increased in cells treated with leptomycin B suggesting that exon 7 encodes a domain required for nuclear retention of RECQL4. This retention activity is partially conveyed by a conserved VLPLY motif (aa 450-454) in exon 7 of the human sequence. In summary, unlike other RecQ proteins with carboxyl terminal NLS, RECQL4 nuclear localization and retention activities are amino terminal. This location would provide nuclear transport of putative truncated proteins encoded by RTS mutant alleles consistent with the proposed essential replication function in the amino terminus of RECQL4. (c) 2006 Elsevier B.V. All rights reserved. C1 Baylor Coll Med, Dept Pediat Hematol & Oncol, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Plon, SE (reprint author), Baylor Coll Med, Dept Pediat Hematol & Oncol, 6621 Fannin St,MC 3-3320, Houston, TX 77030 USA. EM splon@bcm.edu FU NIGMS NIH HHS [T32 GM07330] NR 47 TC 23 Z9 24 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 APR 15 PY 2007 VL 391 IS 1-2 BP 26 EP 38 DI 10.1016/j.gene.2006.11.019 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 157YP UT WOS:000245757800003 PM 17250975 ER PT J AU Boikos, SA Stratakis, CA AF Boikos, Sosipatros A. Stratakis, Constantine A. TI Molecular genetics of the cAMP-dependent protein kinase pathway and of sporadic pituitary tumorigenesis SO HUMAN MOLECULAR GENETICS LA English DT Review ID MCCUNE-ALBRIGHT-SYNDROME; TUMOR TRANSFORMING GENE; SCHWANNOMAS CARNEY COMPLEX; ENDOCRINE NEOPLASIA TYPE-1; SPOTTY SKIN PIGMENTATION; GROWTH-FACTOR RECEPTOR-4; REGULATORY SUBUNIT; ACTIVATING MUTATIONS; FIBROUS DYSPLASIA; SEQUENCE-ANALYSIS AB Pituitary tumors are among the most common human neoplasms. Although these common lesions rarely become clinically manifest and they are almost never malignant, they are the cause of significant morbidity in affected patients. The genetic causes of common pituitary tumors remain for the most part unknown; progress has been limited to the elucidation of the molecular etiology of four genetic syndromes predisposing to pituitary neoplasias: McCune-Albright syndrome, multiple endocrine neoplasia type 1, Carney complex and, most recently, familial acromegaly and prolactinomas and other tumors caused by mutations in the GNAS, menin, PRKAR1A, AIP, and p27 (CDKN1B) genes, respectively. Intense molecular studies of sporadic pituitary tumors from patients with negative family histories and no other neoplasms have yielded interesting findings with abnormalities in growth factor expression and cell cycle control dysregulation. To add to the difficulties in understanding pituitary turnorigenesis in man, good murine models of these neoplasms simply do not exist: pituitary tumors are common in rodents, but their histologic origin (mostly from the intermediate lobe), age of presentation (late in murine life) and clinical course make them hardly models of their human counterparts. The present report reviews the clinical and molecular genetics of the cAMP-dependent protein kinase pathway in human pituitary tumors; it also reviews briefly other pathways that have been involved in sporadic pituitary neoplasms. At the end, we attempt a unifying hypothesis for pituitary tumorigenesis, taking into account data that are also discussed elsewhere in this issue. C1 NICHHD, SEGEN, DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, SEGEN, DEB, NIH, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 92 TC 36 Z9 36 U1 0 U2 6 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 APR 15 PY 2007 VL 16 SI 1 BP R80 EP R87 DI 10.1093/hmg/ddm019 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 211VY UT WOS:000249552600010 PM 17613552 ER PT J AU Hirose, Y Tsutsui, TW Ohno, M Barrett, JC Tsutsui, T AF Hirose, Yutaka Tsutsui, Takeo W. Ohno, Maki Barrett, J. Carl Tsutsui, Takeki TI Effects of a catechol-O-methyltransferase inhibitor on catechol estrogen-induced cellular transformation, chromosome aberrations and apoptosis in Syrian hamster embryo cells SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE catechol estrogen; cellular transformation; chromosome aberrations; apoptosis; catechol-O-methyltransferase ID CULTURED-MAMMALIAN-CELLS; OXIDATIVE DNA-DAMAGE; NEOPLASTIC TRANSFORMATION; EPITHELIAL-CELLS; BREAST-CANCER; CYTOCHROME-C; CARCINOGENESIS; 2-HYDROXYESTRADIOL; 4-HYDROXYESTRADIOL; 17-BETA-ESTRADIOL AB To examine a possible mechanism of endogenous estrogen-induced carcinogenesis, we studied the effect of the catechol-O-methyltransferase (COMT) inhibitor Ro 41-0960 on cell transforming and clastogenic activities of 2 catechol estrogens 2- and 4-hydroxyestrone (2- or 4-OHE1) using Syrian hamster embryo (SHE) cells. COMT activity was assayed by determining the methylation of 2- or 4-OHE1 using gas chromatography. The production of 2-methoxyestrone in cultures treated with 2-OHE1 was approximately 2-fold that of 4-methoxyestrone in cultures treated with 4-OHE1. 4-OHE1 induced morphological transformation at a higher frequency than 2-OHE1 did and the frequencies of cell transformation and chromosome aberrations were not significantly changed in cells treated with 4-OHE1 in the presence of Ro 41-0960. In contrast, the frequencies of cell transformation and chromosome aberrations were markedly increased in cells treated with 2-OHE1 along with Ro 41-0960 when compared to cells treated with 2-OHE1 alone. In addition, both catechol estrogens induced P53 protein expression and apoptosis. The frequencies of apoptotic cells induced by the catechol estrogens were modified by the COMT inhibition in a manner similar to those observed with the chromosome aberrations assay and the cell transformation assay, indicating that each effect by the catechol estrogens at the three measured endpoints might be caused by a mechanism similar to the others. Our findings indicate that COMT activity has an influence on cell transforming activity and its related genetic effects of catechol estrogens in SHE cells, which implies that an individual activity of COMT may be one of the etiological factors in endogenous estrogen-induced carcinogenesis. (c) 2007 Wiley-Liss, Inc. C1 Nippon Dent Univ Tokyo, Sch Life Dent, Dept Pharmacol, Chiyoda Ku, Tokyo 1028159, Japan. NCI, Canc Res Ctr, Lab Biosyst & Canc, Bethesda, MD 20892 USA. RP Tsutsui, T (reprint author), Nippon Dent Univ Tokyo, Sch Life Dent, Dept Pharmacol, Chiyoda Ku, 1-9-20 Fujimi, Tokyo 1028159, Japan. EM takeki@tokyo.ndu.ac.jp NR 36 TC 8 Z9 8 U1 1 U2 2 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 APR 15 PY 2007 VL 120 IS 8 BP 1627 EP 1633 DI 10.1002/ijc.22398 PG 7 WC Oncology SC Oncology GA 143DM UT WOS:000244700200004 PM 17230533 ER PT J AU Massad, LS Evans, C Weber, K Cejtin, HE Golub, ET DiGilio, K Alpern, A Watts, DH AF Massad, L. Stewart Evans, Charlesnika Weber, Kathleen Cejtin, Helen E. Golub, Elizabeth T. DiGilio, Kathy Alpern, Amy Watts, D. Heather TI Hysterectomy among women with HIV - Indications and incidence SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV in women; hysterectomy ID INTERAGENCY HIV; CYTOLOGY AB Objective: To describe hysterectomy rates and indications among women with HIV and to compare them with at-risk HIV-seronegative women. Methods: Reports of hysterectomy were collected from 3752 participants in a prospective cohort study of women with HIV and comparison uninfected women. Available operative notes were retrieved and abstracted. Comparisons were made using the Fisher exact, chi(2), Wilcoxon 2-sample, and Student's t tests. Results: Incident hysterectomy was performed for 106 (4.5%) of 2361 HIV -seropositive women, most often for cervical neoplasia, and for 24 (2.9%) of 837 HIV-seronegative women (P = 0.04). The incidence of hysterectomy was 7.7 per 1000 person-years for HIV-seropositive women and 5.3 per 1000 person-years for HIV-seronegative women (P = 0.09). HIV-seropositive and HIV-seronegative women undergoing incident hysterectomy were similar, except for a higher likelihood of an abnormal preoperative Papanicolaou test result in the former (P = 0.001). Surgical indications did not differ by serostatus. Conclusion: Women with HIV are more likely than uninfected women to require a hysterectomy, most often for cervical neoplasia. C1 So Illinois Univ, Dept Obstet & Gynaecol, Sch Med, Springfield, IL 62794 USA. Univ Illinois, Dept Epidemiol & Biostat, Chicago, IL USA. John H Stroger Hosp Cook Cty, Chicago Consortium Womens Interagcy HIV Study, Chicago, IL USA. John H Stroger Hosp, Dept Obstet & Gynecol, Chicago, IL USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Georgetown Univ, Dept Med, Washington, DC USA. Suny Downstate Med Ctr, Dept Obstet & Gynecol, Brooklyn, NY 11203 USA. NICHHD, Pediat Adolescent & Mat AIDS Branch, Bethesda, MD 20892 USA. RP Massad, LS (reprint author), So Illinois Univ, Dept Obstet & Gynaecol, Sch Med, POB 19640, Springfield, IL 62794 USA. EM lsmassad@ameritech.net FU NCRR NIH HHS [M01 RR 00071, M01 RR 00083, M01 RR 00079]; NIAID NIH HHS [U01 AI 34994, U01 AI 34993, U01 AI 23632, U01 AI 34989, U01 AI 31834, U01 AI 42590, U01 AI 35004] NR 8 TC 7 Z9 7 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 APR 15 PY 2007 VL 44 IS 5 BP 566 EP 568 DI 10.1097/QAI.0b013e318032387a PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 152YZ UT WOS:000245399700011 PM 17259909 ER PT J AU Tavel, JA Martin, JE Kelly, GG Enama, ME Shen, JM Gomez, PL Andrews, CA Koup, RA Bailer, RT Stein, JA Roederer, M Nabel, GJ Graham, BS AF Tavel, Jorge A. Martin, Julie E. Kelly, Grace G. Enama, Mary E. Shen, Jean M. Gomez, Phillip L. Andrews, Charla A. Koup, Richard A. Bailer, Robert T. Stein, Judy A. Roederer, Mario Nabel, Gary J. Graham, Barney S. CA Vaccine Res Ctr 001 Study Team TI Safety and immunogenicity of a Gag-Pol candidate HIV-1 DNA vaccine administered by a needle-free device in HIV-1-seronegative subjects SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE CD4(+) T-cell immune response; gene delivery; immunization; needle-free device; plasmid vaccine; safety ID RHESUS-MONKEYS; VIRUS; HUMANS; IMMUNIZATION; ANTIBODIES; INDUCTION; TRIAL; AIDS AB Objective: To evaluate the safety and immunogenicity of a candidate HIV DNA vaccine administered using a needle-free device. Design: In this phase 1, dose escalation, double-blind, placebo-controlled clinical trial, 21 healthy adults were randomized to receive placebo or 0.5, 1.5, or 4 mg of a single plasmid expressing a Gag/Pol fusion protein. Each participant received repeat immunizations at days 28 and 56 after the first inoculation. Safety and immunogenicity data were collected. Results: The vaccine was well tolerated, with most adverse events being mild injection site reactions, including pain, tenderness, and erythema. No dose-limiting toxicities occurred. HIV specific antibody response was not detected in any vaccinee by enzyme-linked immunosorbent assay. HIV specific T-cell responses to Gag or Pol as measured by enzyme-linked immunospot assay and intracellular cytokine staining were of low frequency and magnitude. Conclusions: This candidate HIV DNA vaccine was safe and well tolerated. No HIV specific antibody responses were detected, and only low-magnitude HIV specific T-cell responses were detected in 8 (53%) of 15 vaccinees. This initial product led to the development of a 4-plasmid multiclade HIV DNA Vaccine Research Center vaccine candidate in which envelope genes expressing Env from clades A, B, and C and a Nef gene from clade B have been added. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA. NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD USA. RP Martin, JE (reprint author), NIAID, Vaccine Res Ctr, NIH, 10 Ctr Dr,Bldg 10,Room 12s260, Bethesda, MD 20892 USA. EM jumartin@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999] NR 16 TC 38 Z9 39 U1 0 U2 3 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 APR 15 PY 2007 VL 44 IS 5 BP 601 EP 605 DI 10.1097/QAI.0b013e3180417cb6 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 152YZ UT WOS:000245399700016 PM 17325604 ER PT J AU Roux, C Gresh, N Perera, LE Piquemal, JP Salmon, L AF Roux, Celine Gresh, Nohad Perera, Lalith E. Piquemal, Jean-Philip Salmon, Laurent TI Binding of 5-phospho-D-arabinonohydroxamate and 5-phospho-D-arabinonate inhibitors to zinc phosphomannose isomerase from Candida albicans studied by polarizable molecular mechanics and quantum mechanics SO JOURNAL OF COMPUTATIONAL CHEMISTRY LA English DT Article DE phosphomannose isomerase; Zn(II) cation; polarizable molecular mechanics; ab initio computations; enzyme inhibitors; hydroxamates ID PARALLEL AB-INITIO; D-MANNOSE PYROPHOSPHORYLASE; INTRAMOLECULAR INTERACTION ENERGIES; METALLO-BETA-LACTAMASE; PHOSPHOGLUCOSE ISOMERASE; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; PYROBACULUM-AEROPHILUM; HETEROLOGOUS EXPRESSION; PYROCOCCUS-FURIOSUS AB Type I phosphomannose isomerase (PMI) is a Zn-dependent metalloenzyme involved in the isomerization Of D-fructose 6-phosphate to D-mannose 6-phosphate. One of our laboratories has recently designed and synthesized 5-phospho-D-arabinonohydroxamate (5PAH), tin inhibitor endowed with a nanomolar affinity for PMI (Roux et al., Biochemistry 2004, 43, 2926). By contrast, the 5-phospho-D-arabinonate (5PAA), in which the hydroxamate moiety is replaced by a carboxylate one, is devoid of inhibitory potency. Subsequent biochemical studies showed that in its PMI complex, 5PAH binds Zn(II) through its hydroxamate moiety rather than through its phosphate. These results have stimulated the present theoretical investigation in which we resort to the SIBFA polarizable molecular mechanics procedure to unravel the structural and energetical aspects of 5PAH and 5PAA binding to a 164-residue model of PMI. Consistent with the experimental results, our theoretical studies indicate that the complexation of PMI by 5PAH is much more favorable than by 5PAA, and that in the 5PAH complex, Zn(II) ligation by hydroxamate is much more favorable than by phosphate. Validations by parallel quantum-chemical computations on model of the recognition site extracted from the PMI-inhibitor complexes, and totaling up to 140 atoms, showed the values of the SIBFA intermolecular interaction energies in such models to be able to reproduce the quantum-chemistry ones with relative errors <3%. On the basis of the PMI-5PAH SIBFA energy-minimized structure, we report the first hypothesis of a detailed view of the active site of the zinc PMI complexed to the high-energy intermediate analogue inhibitor, which allows us to identify active site residues likely involved in the proton transfer between the two adjacent carbons of the substrates. (C) 2007 Wiley Periodicals, Inc. C1 Univ Paris 11, Inst Chim Mol & Mat Orsay, CNRS, UMR 8182,Lab Chim Bioorgan & Bioinorgan, F-91405 Orsay, France. Univ Paris 05, INSERM, U648,IFR Biomed, Lab Pharmacochim Mol & Cellulaire, F-75006 Paris, France. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27700 USA. Univ Paris 06, CNRS, UMR 7616, Chim Theor Lab, F-75252 Paris 05, France. RP Gresh, N (reprint author), Univ Paris 11, Inst Chim Mol & Mat Orsay, CNRS, UMR 8182,Lab Chim Bioorgan & Bioinorgan, Batiment 420,15 Rue Georges Clemenceau, F-91405 Orsay, France. EM lasalmon@icmo.u-psud.fr RI Piquemal, Jean-Philip/B-9901-2009; perera, Lalith/B-6879-2012 OI Piquemal, Jean-Philip/0000-0001-6615-9426; perera, Lalith/0000-0003-0823-1631 NR 85 TC 31 Z9 32 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0192-8651 J9 J COMPUT CHEM JI J. Comput. Chem. PD APR 15 PY 2007 VL 28 IS 5 BP 938 EP 957 DI 10.1002/jcc.20586 PG 20 WC Chemistry, Multidisciplinary SC Chemistry GA 144DA UT WOS:000244774500010 PM 17253648 ER PT J AU Baatar, D Olkhanud, P Sumitomo, K Taub, D Gress, R Biragyn, A AF Baatar, Dolgor Olkhanud, Purevdorj Sumitomo, Kenya Taub, Dennis Gress, Ronald Biragyn, Arya TI Human peripheral blood T regulatory cells (Tregs), functionally primed CCR4(+) Tregs and unprimed CCR4(-) Tregs, regulate effector T cells using FasL SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR EXPRESSION; IMMUNOLOGICAL SELF-TOLERANCE; CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-VITRO; DENDRITIC CELLS; SUPPRESSIVE FUNCTION; AUTOIMMUNE-DISEASES; ANTITUMOR IMMUNITY; CUTTING EDGE; TH2 CELLS AB Regulatory CD25(+)CD4(+) T cells (Tregs) play an important role in the control of peripheral tolerance. In this study we demonstrate that human peripheral blood Tregs can be divided into two distinct populations based on the expression of CCR4. The majority (similar to 75%) of freshly isolated Tregs express CCR4 and presumably represent memory-type Tregs. Interestingly, CCR4(-) Tregs require anti-CD3 Ab-mediated activation to acquire a regulatory activity, while CCR4(+) Tregs appear to be already primed to suppress the proliferation of CD8(+) T cells. CCR4 is also expressed on CD25(low)CD4(+) T cells (CCR4(+) non-Tregs) that mostly suppress Th1-type polarization without affecting T cell proliferation, presumably via the production of immunomodulatory cytokines like IL-10. In contrast, CCR4(+) Tregs express FasL to primarily regulate T cell proliferation via a contact-mediated process involving FasL/Fas signaling, a major regulatory pathway of T cell homeostasis. Finally, we also demonstrate that the depletion of CCR4(+) T cells leads to Th1-type polarization of CD4(+) T cells and augmentation of CD8(+) T cell responses to tumor Ags. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Biragyn, A (reprint author), NIA, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM biragyna@mail.nih.gov FU Intramural NIH HHS [Z01 AG000770-04] NR 51 TC 54 Z9 55 U1 1 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 APR 15 PY 2007 VL 178 IS 8 BP 4891 EP 4900 PG 10 WC Immunology SC Immunology GA 155VA UT WOS:000245605300030 PM 17404270 ER PT J AU Yu, Q Sen, JM AF Yu, Qing Sen, Jyoti Misra TI beta-catenin regulates positive lineage commitment SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; THYMOCYTE DEVELOPMENT; SELECTION; SIGNALS; ACTIVATION; EXPRESSION; RECEPTOR; MICE; WNT; DIFFERENTIATION AB Positive selection and lineage commitment to the cytolytic or helper lineage of T cells result in coordinated expression of MHC class I-restricted TCR and CD8 coreceptor or MHC class II-restricted TCR and CD4 molecule. Positive selection signals also regulate the survival and generation of requisite numbers of cytolytic or Th cells. beta-Catenin is the major transcriptional cofactor of T cell factor and plays a role in thymocyte development. In this study, using mice expressing stabilized beta-catenin and mice with T cell-specific deletion of beta-catenin, we show that beta-catenin regulates positive selection, but not lineage commitment of thymocytes. Furthermore, beta-catenin expression accelerates the timing of mature CD8 thymocyte generation such that CD4 and CD8 single-positive thymocytes mature with the same kinetics during development. C1 NIA, Immunol Lab, Lymphocyte Dev Unit, NIH, Baltimore, MD 21224 USA. RP Sen, JM (reprint author), NIA, Immunol Lab, Lymphocyte Dev Unit, NIH, Baltimore, MD 21224 USA. EM Jyoti-Sen@NIH.GOV FU Intramural NIH HHS [Z01 AG000768-04] NR 29 TC 22 Z9 22 U1 1 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 APR 15 PY 2007 VL 178 IS 8 BP 5028 EP 5034 PG 7 WC Immunology SC Immunology GA 155VA UT WOS:000245605300045 PM 17404285 ER PT J AU Woszczek, G Chen, LY Nagineni, S Alsaaty, S Harry, A Logun, C Pawliczak, R Shelhamer, JH AF Woszczek, Grzegorz Chen, Li-Yuan Nagineni, Sahrudaya Alsaaty, Sara Harry, Anya Logun, Carolea Pawliczak, Rafal Shelhamer, James H. TI IFN-gamma induces cysteinyl leukotriene receptor 2 expression and enhances the responsiveness of human endothelial cells to cysteinyl leukotrienes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYSLT(2) RECEPTOR; INTERFERON-GAMMA; 5-LIPOXYGENASE PATHWAY; MOLECULAR-CLONING; IMMUNE-RESPONSES; GENE; ATHEROSCLEROSIS; PATHOGENESIS; ADHESION AB Cysteinyl leukotrienes (cysLTs) are important mediators of cell trafficking and innate immune responses, involved in the pathogenesis of inflammatory processes, i.e., atherosclerosis, pulmonary fibrosis, and bronchial asthma. The aim of this study was to examine the regulation of cysLT signaling by IFN-gamma in human primary endothelial cells. IFN-gamma increased cysLT receptor 2 (CysLTR2) mRNA expression and CysLTR2-specific calcium signaling in endothelial cells. IFN-gamma signaled through Jak/STAT1, as both AG490, a Jak2 inhibitor, and expression of a STAT1 dominant-negative construct, significantly inhibited CysLTR2 mRNA expression in response to IFN-gamma. To determine mechanisms of IFN-gamma-induced CysLTR2 expression, the human CysLTR2-gene structure was characterized. The CysLTR2 gene has a TATA-less promoter, with multiple transcription start sites. It consists of six variably spliced exons. Eight different CysLTR2 transcripts were identified in endothelial and monocytic cells. Gene reporter assay showed potent basal promoter activity of a putative CysLTR2 promoter region. However, there were no significant changes in gene reporter and mRNA t(1/2) assays in response to IFN-gamma, suggesting transcriptional control of CysLTR2 mRNA up-regulation by ILFN-gamma response motifs localized outside of the cloned CysLTR2 promoter region. Stimulation of endothelial cells by cysLTs induced mRNA and protein expression of early growth response genes 1, 2, and 3 and cycloxygenase-2. This response was mediated by CysLTR2 coupled to G(q/11), activation of phospholipase C, and inositol-1,4,5-triphosphate, and was enhanced further 2- to 5-fold by IFN-gamma stimulation. Thus, IFN-gamma induces CysLTR2 expression and enhances cysLT-induced inflammatory responses. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Immunopathol, PL-90131 Lodz, Poland. RP Shelhamer, JH (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10,Room 2C145,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jshelhamer@cc.nih.gov RI Woszczek, Grzegorz/H-5792-2012; Pawliczak, Rafal/S-9649-2016 NR 32 TC 25 Z9 28 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 APR 15 PY 2007 VL 178 IS 8 BP 5262 EP 5270 PG 9 WC Immunology SC Immunology GA 155VA UT WOS:000245605300070 PM 17404310 ER PT J AU Fluur, C De Milito, A Fry, TJ Vivar, N Eidsmo, L Atlas, A Federici, C Matarrese, P Logozzi, M Rajnavolgyi, E Mackall, CL Fais, S Chiodi, F Rethi, B AF Fluur, Caroline De Milito, Angelo Fry, Terry J. Vivar, Nancy Eidsmo, Liv Atlas, Ann Federici, Cristina Matarrese, Paola Logozzi, Mariantonia Rajnavolgyi, Eva Mackall, Crystal L. Fais, Stefano Chiodi, Francesca Rethi, Bence TI Potential role for IL-7 in Fas-mediated T cell apoptosis during HIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIGAND EXPRESSION; EZRIN ASSOCIATION; DOWN-REGULATION; MEMORY CELLS; CD4 CELLS; IN-VITRO; INTERLEUKIN-7; HOMEOSTASIS; LYMPHOCYTES; CD95 AB IL-7 promotes survival of resting T lymphocytes and induces T cell proliferation in lymphopenic conditions. As elevated IL-7 levels occur in HIV-infected individuals in addition to high Fas expression on T cells and increased sensitivity to Fas-induced apoptosis, we analyzed whether IL-7 has a regulatory role in Fas-mediated T cell apoptosis. We show that IL-7 up-regulates Fas expression on naive and memory T cells through a mechanism that involves translocation of Fas molecules from intracellular compartments to the cell membrane. IL-7 induced the association of Fas with the cytoskeletal component ezrin and a polarized Fas expression on the cell surface. The potential role of IL-7 in Fas up-regulation in vivo was verified in IL-7-treated macaques and in HIV-infected or chemotherapy treated patients by the correlation between serum IL-7 levels and Fas expression on T cells. IL-7 treatment primed T cells for Fas-induced apoptosis in vitro and serum IL-7 levels correlated with the sensitivity of T cells to Fas-induced apoptosis in HIV-infected individuals. Our data suggest an important role for IL-7 in Fas-mediated regulation of T cell homeostasis. Elevated IL-7 levels associated with lymphopenic conditions, including HIV-infection, might participate in the increased sensitivity of T cells for activation-induced apoptosis. C1 Karolinska Inst, Microbiol & Tumor Biol Ctr, S-17177 Stockholm, Sweden. Ist Super Sanita, Dept Drug Resistance & Evaluat, I-00161 Rome, Italy. NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Karolinska Univ Hosp, Dept Med, Infect Dis Unit, Solna, Sweden. Univ Debrecen, Fac Med, Inst Immunol, Med & Hlth Sci Ctr, H-4012 Debrecen, Hungary. RP Rethi, B (reprint author), Karolinska Inst, Microbiol & Tumor Biol Ctr, Nobels Vag 16, S-17177 Stockholm, Sweden. EM Bence.Rethi@ki.se RI Rethi, Bence/C-5770-2013; Rajnavolgyi, Eva/D-4384-2013; Fais, Stefano/J-8638-2016 OI Rethi, Bence/0000-0001-8220-5015; Fais, Stefano/0000-0001-9060-2766 NR 53 TC 38 Z9 39 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2007 VL 178 IS 8 BP 5340 EP 5350 PG 11 WC Immunology SC Immunology GA 155VA UT WOS:000245605300079 PM 17404319 ER PT J AU Fischer, TK Viboud, C Parashar, U Malek, M Steiner, C Glass, R Simonsen, L AF Fischer, Thea Kolsen Viboud, Cecile Parashar, Umesh Malek, Mark Steiner, Claudia Glass, Roger Simonsen, Lone TI Hospitalizations and deaths from diarrhea and rotavirus among children < 5 years of age in the United States, 1993-2003 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MORBIDITY; GASTROENTERITIS; SURVEILLANCE; INFECTION; MORTALITY; DISEASE; TRENDS; IMPACT; CODE AB Recently a new rotavirus vaccine was licensed in the United States and recommended for universal immunization of American children. The impact of the vaccine on a decrease in hospitalizations will take several years to assess and will be based on the availability of good baseline data on the disease. We used the largest US hospital discharge database available, the Healthcare Cost and Utilization Project (HCUP), to study national rates, trends, and risk factors for diarrhea- and rotavirus-associated hospitalizations and deaths among children < 5 years of age, to establish a baseline against which vaccine implementation can be measured. Rotavirus remained the most important cause of pediatric diarrhea throughout the study period (1993-2003). When the data were extrapolated to the US population, rotavirus was estimated to be the cause of similar to 60,000 hospitalizations and 37 deaths annually. Black infants had a significantly higher risk of being hospitalized with and dying from rotavirus disease early in life, compared with white infants (risk ratio [RR] for hospitalization by 12 months of age was 2.4, with a 95% confidence interval [CI] of 1.2-4.7; RR for death was 2.0, with a 95% CI of 1.7-2.5). Such racial differences in age and risk of rotavirus-associated hospitalization and death highlight the importance of timely and early rotavirus immunization of minority children. The HCUP database serves as a sensitive and robust data source for monitoring the impact of a rotavirus-immunization program in the United States. C1 Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark. Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, Epidemiol Intelligence Serv, Atlanta, GA USA. NIH, Fogarty Int Ctr, Bethesda, MD USA. NIH, NIAID, Bethesda, MD USA. Agcy Hlth Care Res & Qual, Ctr Delivery Org & Markets, Bethesda, MD USA. RP Fischer, TK (reprint author), Statens Serum Inst, Dept Epidemiol Res, Artillivej 5, DK-2300 Copenhagen, Denmark. EM thf@ssi.dk; LSimonsen@niaid.nih.gov OI Fischer, Thea Kolsen/0000-0003-4812-980X; Simonsen, Lone/0000-0003-1535-8526 NR 27 TC 100 Z9 110 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 15 PY 2007 VL 195 IS 8 BP 1117 EP 1125 DI 10.1086/512863 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 153AW UT WOS:000245405100007 PM 17357047 ER PT J AU Kuritzkes, DR Ribaudo, HJ Squires, KE Koletar, SL Santana, J Riddler, SA Reichman, R Shikuma, C Meyer, WA Klingman, KL Gulick, RM AF Kuritzkes, Daniel R. Ribaudo, Heather J. Squires, Kathleen E. Koletar, Susan L. Santana, Jorge Riddler, Sharon A. Reichman, Richard Shikuma, Cecilia Meyer, William A., III Klingman, Karin L. Gulick, Roy M. CA ACTG Protocol Team TI Plasma HIV-1 RNA dynamics in antiretroviral-naive subjects receiving either triple-nucleoside or efavirenz-containing regimens: ACTG A5166s SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BASE-LINE FACTORS; IN-VIVO; VIRAL DYNAMICS; VIROLOGICAL RESPONSES; COMBINATION THERAPY; INITIAL TREATMENT; SEX-DIFFERENCES; INFECTION; PROGRESSION; DECAY AB Objective. We sought to compare clearance rates of plasma human immunodeficiency virus type 1 (HIV-1) RNA in men and women starting triple-nucleoside-based versus efavirenz (EFV)-based regimens. Methods. First- and second-phase decay rates of plasma HIV-1 were compared in men and women initiating a triple nucleoside reverse-transcriptase inhibitor (NRTI) regimen versus regimens that included EFV plus an NRTI. Subjects (n=64) were randomized to receive zidovudine/lamivudine/abacavir (triple-nucleoside regimen), zidovudine/ lamivudine plus EFV (3-drug EFV regimen) or zidovudine/lamivudine/abacavir plus EFV (4-drug EFV regimen). Plasma HIV-1 RNA levels were fitted to a biexponential viral-dynamics model using a nonlinear mixedeffects model. Nonparametric Wilcoxon tests compared empirical Bayes estimates of first- and second-phase viral decay rates between treatment arms and sex. Results. Median first- phase viral decay rates were significantly faster in subjects receiving the 3-drug EFV regimen (0.67/day), compared with those receiving the triple-nucleoside regimen (0.56/day; P=.02). The second-phase viral decay rate was also faster in the 3-drug EFV group than in the triple-nucleoside group (P=.09). Decay rates in the 4-drug EFV group were intermediate. Viral decay rates were not significantly different in men and women. Conclusions. Faster initial viral decay in subjects randomized to a 3-drug EFV-based regimen corresponded to the overall superior efficacy of that regimen. Viral decay rates did not differ by sex. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Retroviral Therapeut, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Div Aids, Cambridge, MA 02139 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat & AIDS Res, Cambridge, MA 02138 USA. Univ So Calif, Div Infect Dis, Los Angeles, CA 90089 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Puerto Rico, San Juan, PR 00936 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Univ Hawaii, Honolulu, HI 96822 USA. Quest Diagnost, Baltimore, MD USA. NIAID, Treatment Res Program, Div Aids, Bethesda, MD 20892 USA. RP Kuritzkes, DR (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Sect Retroviral Therapeut, 65 Landsdowne St,Rm 449, Cambridge, MA 02139 USA. EM dkuritzkes@partners.org FU NCATS NIH HHS [UL1 TR000005] NR 29 TC 32 Z9 32 U1 0 U2 1 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 APR 15 PY 2007 VL 195 IS 8 BP 1169 EP 1176 DI 10.1086/512619 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 153AW UT WOS:000245405100013 PM 17357053 ER PT J AU Ziska, LH Palowsky, R Reed, DR AF Ziska, Lewis H. Palowsky, Robert Reed, Danielle R. TI A quantitative and qualitative assessment of mung bean (Vigna mungo (L.) Wilczek) seed in response to elevated atmospheric carbon dioxide: potential changes in fatty acid composition SO JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE LA English DT Article DE CO2; fatty acids; mung bean; omega-3; omega-6 ID FIELD-GROWN STRAWBERRIES; CO2; OMEGA-3-FATTY-ACIDS AB The effect of rising atmospheric carbon dioxide concentration ([CO2]) on seed production and the fatty acid profiles of mung bean (Vigna mungo L. Wilczek) were studied under field conditions. Increased [CO2] (ca 250 ppm above ambient) resulted in significant increases in pod number, pod weight and total seed weight, but also significantly increased the percentage of immature pods at harvest. Qualitatively, increased [CO2] significantly decreased the percentages of palmitic and omega-6 fatty acids, but increased the percentage of omega-3 fatty acids and the relative proportion of omega-3 to omega-6 fatty acids in mature seed. Overall, increased carbon dioxide may significantly increase quantity and alter quality in mung bean seed, a recognized alternative source of fatty acids in the human diet. (c) 2007 Society of Chemical Industry. C1 USDA ARS, Crop Syst & Global Change Lab, Beltsville, MD 20705 USA. NIH, Lab Metab Control, Bethesda, MD 20892 USA. RP Ziska, LH (reprint author), USDA ARS, Crop Syst & Global Change Lab, Bldg 1,Room 323,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM lziska@asrr.arsusda.gov NR 22 TC 6 Z9 8 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-5142 J9 J SCI FOOD AGR JI J. Sci. Food Agric. PD APR 15 PY 2007 VL 87 IS 5 BP 920 EP 923 DI 10.1002/jsfa.2818 PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 154VT UT WOS:000245536600023 ER PT J AU Caria, A Veit, R Sitaram, R Lotze, M Weiskopf, N Grodd, W Birbaumer, N AF Caria, Andrea Veit, Ralf Sitaram, Ranganatha Lotze, Martin Weiskopf, Nikolaus Grodd, Wolfgang Birbaumer, Niels TI Regulation of anterior insular cortex activity using real-time fMRI SO NEUROIMAGE LA English DT Article DE self-regulation; physiological regulation; real-time fMRI; brain-computer interface; neurofeedback; blood oxygen level-dependent; insula ID BRAIN-COMPUTER INTERFACE; RESONANCE-IMAGING FMRI; AUTONOMIC NERVOUS-SYSTEM; ANXIETY-PRONE SUBJECTS; FUNCTIONAL MRI; PHYSIOLOGICAL CONDITION; ORBITOFRONTAL CORTEX; AMYGDALA ACTIVATION; SELF-REGULATION; EMOTION AB Recent advances in functional magnetic resonance imaging (fMRI) data acquisition and processing techniques have made real-time fMRI (rtfMRI) of localized brain areas feasible, reliable and less susceptible to artefacts. Previous studies have shown that healthy subjects learn to control local brain activity with operant training by using rtfMRI-based neurofeedback. In the present study, we investigated whether healthy subjects could voluntarily gain control over right anterior insular activity. Subjects were provided with continuously updated information of the target ROI's level of activation by visual feedback. All participants were able to successfully regulate BOLD-magnitude in the right anterior insular cortex within three sessions of 4 min each. Training resulted in a significantly increased activation cluster in the anterior portion of the right insula across sessions. An increased activity was also found in the left anterior insula but the percent signal change was lower than in the target ROI. Two different control conditions intended to assess the effects of non-specific feedback and mental imagery demonstrated that the training effect was not due to unspecific activations or non feedback-related cognitive strategies. Both control groups showed no enhanced activation across the sessions' which confirmed our main hypothesis that rtfMRI feedback is area-specific. The increased activity in the right anterior insula during training demonstrates that the effects observed are anatomically specific and self-regulation of right anterior insula only is achievable. This is the first group study investigating the volitional control of emotionally relevant brain region by using rtfMRI training and confirms that self-regulation of local brain activity with rtfMRI is possible. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, D-72074 Tubingen, Germany. Univ Trent, Dept Cognit Sci & Educ, I-38100 Trento, Italy. UCL, Inst Neurol, Wellcome Dept Imaging Neurosci, London WC1E 6BT, England. Univ Tubingen, CNS, Dept Neuroradiol, Sect Expt MR, D-72074 Tubingen, Germany. Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Caria, A (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Gartenstr 29, D-72074 Tubingen, Germany. EM andrea.caria@uni-tuebingen.de RI Weiskopf, Nikolaus/B-9357-2008; Veit, Ralf/F-8907-2012; OI Weiskopf, Nikolaus/0000-0001-5239-1881; Veit, Ralf/0000-0001-9860-642X; Sitaram, Ranganatha/0000-0002-8577-8035 NR 50 TC 178 Z9 183 U1 6 U2 25 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 APR 15 PY 2007 VL 35 IS 3 BP 1238 EP 1246 DI 10.1016/j.neuroimage.2007.01.018 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 160PZ UT WOS:000245956100024 PM 17336094 ER PT J AU Virkkunen, M Rissanen, A Naukkarinen, H Franssila-Kallunki, A Linnoila, M Tiihonen, J AF Virkkunen, Matti Rissanen, Aila Naukkarinen, Hannu Franssila-Kallunki, Anja Linnoila, Markku Tiihonen, Jari TI Energy substrate: metabolism among habitually violent alcoholic offenders having antisocial personality disorder SO PSYCHIATRY RESEARCH LA English DT Article DE antisocial personality disorder; violence; recidivism; metabolism; non-oxidative; lipid; glucose; respiratory quotient; serotonin ID CROSS-FOSTERING ANALYSIS; GROWTH-HORMONE; SERUM-CHOLESTEROL; FIRE SETTERS; HOMICIDE RECIDIVISM; INSULIN-RESISTANCE; HEALTHY-VOLUNTEERS; SLEEP; MEN; AGGRESSION AB A large proportion of violent offences in Western countries are attributable to antisocial personality disorder (APD). Several studies have shown abnormal lipid, carbohydrate and low cerebrospinal fluid (CSF) monoamine metabolite levels in habitually violent alcoholic offenders with APD, but it is not clear how these biochemical abnormalities are related to each other in this disorder. We aimed to study energy substrate metabolism among habitually violent offenders with APD. Insulin sensitivity (euglycemic insulin clamp), basal energy expenditure (indirect calorimetry), and CSF 5-hydroxyindoleacetic acid (5-HIAA) measurements were performed on 96 habitually violent antisocial male alcoholic offenders and on 40 normal male controls. Habitually violent, incarcerated offenders with APD had significantly lower non-oxidative glucose metabolism, basal glucagon, and free fatty acids when compared with normal controls, but glucose oxidation and CSF 5-HIAA did not differ markedly between these groups. The effect sizes for lower non-oxidative glucose metabolism among incarcerated and non-incarcerated APD subjects were 0.73 and 0.51, respectively, when compared with controls, indicating that this finding was not explained by incarceration. Habitually violent offenders with APD have markedly lower glucagon and non-oxidative glucose metabolism when compared with healthy controls, and these findings were more strongly associated with habitual violent offending than low CSF 5-HIAA levels, a well-established marker for impulsive violent behavior. Follow-up studies are needed to confirm if abnormal glucose and lipid metabolism can be used to predict violent offending over the course of the APD offender's life span. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Kuopio, Niuvanniemi hosp, Dept Forens Psychiat, FI-70240 Kuopio, Finland. Univ Helsinki, Cent Hosp, Dept Psychiat, Helsinki, Finland. Vanha Vaasa Hosp, Vaasa, Finland. Huutoniemi Hosp, Vaasa, Finland. NIAAA, NIH, Bethesda, MD USA. Kuopio Univ Hosp, Dept Clin Physiol, Kuopio, Finland. RP Tiihonen, J (reprint author), Univ Kuopio, Niuvanniemi hosp, Dept Forens Psychiat, FI-70240 Kuopio, Finland. EM jari.tiihonen@niuva.fi RI Tiihonen, Jari/G-3078-2012 OI Tiihonen, Jari/0000-0002-0400-6798 FU NIAAA NIH HHS [N01AA53003] NR 44 TC 14 Z9 14 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD APR 15 PY 2007 VL 150 IS 3 BP 287 EP 295 DI 10.1016/j.psychres.2006.01.013 PG 9 WC Psychiatry SC Psychiatry GA 159ZQ UT WOS:000245906900008 PM 17316826 ER PT J AU Bohr, VA Ottersen, OP Tonjum, T AF Bohr, V. A. Ottersen, O. P. Tonjum, T. TI Genome instability and DNA repair in brain, ageing and neurological disease SO NEUROSCIENCE LA English DT Editorial Material DE DNA repair; genome instability; base excision repair; nucleotide excision repair; mismatch repair; recombinational repair ID DAMAGE; MAINTENANCE; PATHWAYS; RNA; WRN C1 Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Inst Microbiol,Ctr Mol Biol & Neurosci, NO-0027 Oslo, Norway. Univ Oslo, Inst Microbiol, Ctr Mol Biol & Neurosci, NO-0027 Oslo, Norway. Univ Oslo, Inst Basic Med Sci, Ctr Mol Biol & Neurosci, NO-0317 Oslo, Norway. NIA, Lab Mol Gerontol, IRP, NIH, Baltimore, MD 21224 USA. RP Tonjum, T (reprint author), Univ Oslo, Rikshosp, Radiumhosp Med Ctr, Inst Microbiol,Ctr Mol Biol & Neurosci, NO-0027 Oslo, Norway. EM tone.tonjum@medisin.uio.no OI Tonjum, Tone/0000-0002-1709-6921 NR 41 TC 38 Z9 39 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1183 EP 1186 DI 10.1016/j.neuroscience.2007.03.015 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700001 PM 17400394 ER PT J AU Wilson, DM McNeill, DR AF Wilson, D. M., III McNeill, D. R. TI Base excision repair and the central nervous system SO NEUROSCIENCE LA English DT Article DE oxidative damage; DNA repair; brain; neurodegeneration ID DNA-POLYMERASE-BETA; AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE BRAIN; FOCAL CEREBRAL-ISCHEMIA; STRAND BREAK REPAIR; ADULT-RAT BRAIN; MITOCHONDRIAL-DNA; ENDONUCLEASE EXPRESSION; NEURONAL APOPTOSIS; OXIDATIVE LESIONS AB Reactive oxygen species generated during normal cellular metabolism react with lipids, proteins, and nucleic acid. Evidence indicates that the accumulation of oxidative damage results in cellular dysfunction or deterioration. In particular, oxidative DNA damage can induce mutagenic replicative outcomes, leading to altered cellular function and/or cellular transformation. Additionally, oxidative DNA modifications can block essential biological processes, namely replication and transcription, triggering cell death responses. The major pathway responsible for removing oxidative DNA damage and restoring the integrity of the genome is base excision repair (BER). We highlight herein what is known about BER protein function(s) in the CNS, which in cooperation with the peripheral nervous system operates to control physical responses, motor coordination, and brain operation. Moreover, we describe evidence indicating that defective BER processing can promote post-mitotic (i.e. non-dividing) neuronal cell death and neurodegenerative disease. The focus of the review is on the core mammalian BER participants, i.e. the DNA glycosylases, AP endonuclease 1, DNA polymerase beta, X-ray cross-complementing 1, and the DNA ligases. Published by Elsevier Ltd on behalf of IBRO. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov FU Intramural NIH HHS NR 89 TC 47 Z9 47 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1187 EP 1200 DI 10.1016/j.neuroscience.2006.07.011 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700002 PM 16934943 ER PT J AU Weissman, L De Souza-Pinto, NC Stevnsner, T Bohr, VA AF Weissman, L. De Souza-Pinto, N. C. Stevnsner, T. Bohr, V. A. TI DNA repair, mitochondria, and neurodegeneration SO NEUROSCIENCE LA English DT Review DE DNA damage; ROS; base excision repair; aging; brain; neurons ID BASE-EXCISION-REPAIR; AMYOTROPHIC-LATERAL-SCLEROSIS; INCREASED OXIDATIVE DAMAGE; SYNDROME GROUP-B; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE BRAIN; NITRIC-OXIDE PRODUCTION; APOPTOTIC CELL-DEATH; SPINAL MOTOR-NEURONS; CSB GENE-PRODUCT AB Accumulation of nuclear and mitochondrial DNA damage is thought to be particularly deleterious in postmitotic cells, which cannot be replaced through cell division. Recent experimental evidence demonstrates the importance of DNA damage responses for neuronal survival. Here, we summarize current literature on DNA damage responses in the mammalian CNS in aging and neurodegeneration. Base excision repair (BER) is the main pathway for the removal of small DNA base modifications, such as alkylation, deamination and oxidation, which are generated as by-products of normal metabolism and accumulate with age in various experimental models. Using neuronal cell cultures, human brain tissue and animal models, we and others have shown an active BER pathway functioning in the brain, both in the mitochondrial and nuclear compartments. Mitochondrial DNA repair may play a more essential role in neuronal cells because these cells depend largely on intact mitochondrial function for energy metabolism. We have characterized several BER enzymes in mammalian mitochondria and have shown that BER activities change with age in mitochondria from different brain regions. Together, the results reviewed here advocate that mitochondrial DNA damage response plays an important role in aging and in the pathogenesis of neurodegenerative diseases. (C) 2006 Published by Elsevier Ltd on behalf of IBRO. C1 NIA, Lab Mol Gerontol, NIH, IRP, Baltimore, MD 21224 USA. Univ Aarhus, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, IRP, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X FU Intramural NIH HHS NR 159 TC 95 Z9 96 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1318 EP 1329 DI 10.1016/j.neuroscience.2006.08.061 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700014 PM 17092652 ER PT J AU Ingram, DK Young, J Mattison, JA AF Ingram, D. K. Young, J. Mattison, J. A. TI Calorie restriction in nonhuman primates: Assessing effects on brain and behavioral aging SO NEUROSCIENCE LA English DT Article DE locomotor activity; MRI; PET; basal ganglia; neuroprotection; DNA ID AGE-RELATED DECLINE; TERM DIETARY RESTRICTION; RHESUS-MONKEYS; DOPAMINE-RECEPTORS; C-11 RACLOPRIDE; NEURODEGENERATIVE DISORDERS; ENERGY-METABOLISM; FISCHER-344 RATS; OXIDATIVE DAMAGE; STRIATAL VOLUME AB Dietary caloric restriction (CR) is the only intervention repeatedly demonstrated to retard the onset and incidence of age-related diseases, maintain function, and extend both lifespan and health span in mammals, including brain and behavioral function. In 70 years of study, such beneficial effects have been demonstrated in rodents and lower animals. Recent results emerging from ongoing studies of CR in humans and nonhuman primates suggest that many of the same anti-disease and anti-aging benefits observed in rodent studies may be applicable to long-lived species. Results of studies in rhesus monkeys indicate that CR animals (30% less than controls) are healthier than fully-fed counterparts based on reduced incidence of various diseases, exhibit significantly better indices of predisposition to disease and may be aging at a slower rate based on analysis of selected indices of aging. The current review discusses approaches taken in studies of rhesus monkeys to analyze age-related changes in brain and behavioral function and the impact of CR on these changes. Approaches include analyses of gross and fine locomotor performance as well as brain imaging. In a related study it was observed that short-term CR (6 months) in adult rhesus monkeys can provide protection against a neurotoxic insult. Increasing interest in the CR paradigm will expand its role in demonstrating how nutrition can modulate the rate of aging and the mechanisms responsible for this modulation. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA 70808 USA. Sobran, Baltimore, MD 20866 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov NR 78 TC 43 Z9 43 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1359 EP 1364 DI 10.1016/j.neuroscience.2006.10.031 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700018 PM 17223278 ER PT J AU Kraemer, KH Patronas, NJ Schiffmann, R Brooks, BP Tamura, D Digiovanna, JJ AF Kraemer, K. H. Patronas, N. J. Schiffmann, R. Brooks, B. P. Tamura, D. Digiovanna, J. J. TI Xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome: A complex genotype-phenotype relationship SO NEUROSCIENCE LA English DT Article DE cancer; neurodegeneration; DNA repair; genetic disease; neurocutaneous diseases ID DEFICIENT BRITTLE HAIR; DNA-REPAIR DISORDERS; NEUROLOGICAL DISEASE; SKIN-CANCER; ABNORMALITIES; MUTATIONS; CELLS AB Patients with the rare genetic disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) have defects in DNA nucleotide excision repair (NER). The NER pathway involves at least 28 genes. Three NER genes are also part of the basal transcription factor, TFIIH. Mutations in 11 NER genes have been associated with clinical diseases with at least eight overlapping phenotypes. The clinical features of these patients have some similarities but also have marked differences. NER is involved in protection against sunlight-induced DNA damage. While XP patients have 1000-fold increase in susceptibility to skin cancer, TTD and CS patients have normal skin cancer risk. Several of the genes involved in NER also affect somatic growth and development. Some patients have short stature and immature sexual development. TTD patients have sulfur deficient brittle hair. Progressive sensorineural deafness is an early feature of XP and CS. Many of these clinical diseases are associated with developmental delay and progressive neurological degeneration. The main neuropathology of XP is a primary neuronal degeneration. In contrast, CS and TTD patients have reduced myelination of the brain. These complex neurological abnormalities are not related to sunlight exposure but may be caused by developmental defects as well as faulty repair of DNA damage to neuronal cells induced by oxidative metabolism or other endogenous processes. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NCI, Ctr Canc Res, DNA Repair Sect, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Dept Dermatol, Div Dermatopathol, Providence, RI 02912 USA. RP Kraemer, KH (reprint author), NCI, Ctr Canc Res, DNA Repair Sect, Bldg 37 Room 4002 MSC 4258, Bethesda, MD 20892 USA. EM kraemerk@nih.gov FU Intramural NIH HHS NR 24 TC 194 Z9 198 U1 5 U2 23 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1388 EP 1396 DI 10.1016/j.neuroscience.2006.12.020 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700021 PM 17276014 ER PT J AU Brooks, PJ AF Brooks, P. J. TI The case for 8,5 '-cyclopurine-2 '-deoxynucleosides as endogenous DNA lesions that cause neurodegeneration in xeroderma pigmentosum SO NEUROSCIENCE LA English DT Article DE DNA repair; Parkinson's disease; transcription; dopamine; Cockayne syndrome; DeSanctis-Cacchione syndrome ID NUCLEOTIDE EXCISION-REPAIR; PROTEIN CROSS-LINKS; II I-COMPOUNDS; COCKAYNE-SYNDROME; GROUP-A; NEUROLOGICAL ABNORMALITIES; PARKINSONS-DISEASE; LIPID-PEROXIDATION; STRUCTURAL ORIGINS; OXIDATIVE DAMAGE AB Patients with the genetic disease xeroderma pigmentosum (XP) lack the capacity to carry out a specific type of DNA repair process called nucleotide excision repair (NER). The NER pathway plays a critical role in the repair of DNA damage resulting from ultraviolet (UV) radiation. A subset of XP patients develops a profound neurodegenerative condition known as XP neurological disease. Robbins and colleagues [Andrews A, Barrett S, Robbins J (1978) Xeroderma pigmentosum neurological abnormalities correlate with the colony forming ability after ultraviolet irradiation. Proc Natl Acad Sci U S A 75:1984-1988] hypothesized that since UV light cannot reach into the human brain, XP neurological disease results from some form of endogenous DNA damage that is normally repaired by the NER pathway. In the absence of NER, the damage accumulates, causing neuronal death by blocking transcription. In this manuscript, I consider the evidence that a particular class of oxidative DNA lesions, the 8,5 '-cyclopurine-2 '-deoxynucleosides, fulfills many of the criteria expected of neurodegenerative DNA lesions in XP. Specifically, these lesions are chemically stable, endogenous DNA lesions that are repaired by the NER pathway but not by any other known process, and strongly block transcription by RNA polymerase 11 in cells from XP patients. A similar set of criteria might be used to evaluate other candidate DNA lesions responsible for neurological diseases resulting from defects in other DNA repair mechanisms as well. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIAAA, Mol Neurobiol Sect, Neurogenet Lab, Rockville, MD 20852 USA. RP Brooks, PJ (reprint author), NIAAA, Mol Neurobiol Sect, Neurogenet Lab, 5625 Fishers Lane,Room 3S32,MSC 9412, Rockville, MD 20852 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z01 AA000083-12] NR 80 TC 76 Z9 77 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1407 EP 1417 DI 10.1016/j.neuroscience.2006.10.025 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700023 PM 17184928 ER PT J AU Zhang, P Dilley, C Mattson, MP AF Zhang, P. Dilley, C. Mattson, M. P. TI DNA damage responses in neural cells: Focus on the telomere SO NEUROSCIENCE LA English DT Review DE neurogenesis; apoptosis; trf2; gamma-H2AX; ATM; Alzheimer's disease ID INCREASED OXIDATIVE DAMAGE; AMYLOID BETA-PEPTIDE; DOUBLE-STRAND BREAKS; ALZHEIMERS-DISEASE; CATALYTIC SUBUNIT; ATAXIA-TELANGIECTASIA; HIPPOCAMPAL-NEURONS; PROTEIN TRF2; POLY(ADP-RIBOSE) POLYMERASE; DYSKERATOSIS-CONGENITA AB Postmitotic neurons must survive for the entire life of the organism and be able to respond adaptively to adverse conditions of oxidative and genotoxic stress. Unrepaired DNA damage can trigger apoptosis of neurons which is typically mediated by the ataxia telangiectasia mutated (ATM)p53 pathway. As in all mammalian cells, telomeres in neurons consist of TTAGGG DNA repeats and several associated proteins that form a nucleoprotein complex that prevents chromosome ends from being recognized as double strand breaks. Proteins that stabilize telomeres include TRF1 and TRF2, and proteins known to play important roles in DNA damage responses and DNA repair including ATM, Werner and the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). We have been performing studies of developing and adult neurons aimed at understanding the effects of global and telomere-directed DNA damage responses in neuronal plasticity and survival in the contexts of aging and neurodegenerative disorders. Deficits in specific DNA repair proteins, including DNA-PKcs and uracil DNA glycosylase (UDG), render neurons vulnerable to adverse conditions of relevance to the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and stroke. Similarly, early postmitotic neurons with reduced telomerase activity exhibit accentuated responses to DNA damage and are prone to apoptosis demonstrating a pivotal role for telomere maintenance in both mitotic cells and postmitotic neurons. Our recent findings suggest key roles for TRF2 in regulating the differentiation and survival of neurons. TRF2 affects cell survival and differentiation by modulating DNA damage pathways, and gene expression. A better understanding of the molecular mechanisms by which neurons respond to global and telomere-specific DNA damage may reveal novel strategies for prevention and treatment of neurodegenerative disorders. Indeed, work in this and other laboratories has shown that dietary folic acid can protect neurons against Alzheimer's disease by keeping homocysteine levels low and thereby minimizing the misincorporation of uracil into DNA in neurons. (C) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS; NIA NIH HHS [Z01 AG000313-05, Z01 AG000314-05] NR 104 TC 53 Z9 58 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR 14 PY 2007 VL 145 IS 4 BP 1439 EP 1448 DI 10.1016/j.neuroscience.2006.11.052 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 163KX UT WOS:000246159700026 PM 17207936 ER PT J AU Berkane, AA Nguyen, HTT Tranchida, F Waheed, AA Deyris, V Tchiakpe, L Fasano, C NiColettl, C Desseaux, V Ajandouz, EH Comeau, D Comeau, L Hiol, A AF Berkane, Amine Adda Nguyen, Hang Thi Thu Tranchida, Fabrice Waheed, Abdul A. Deyris, Valerie Tchiakpe, Leopold Fasano, Caroline NiColettl, Cendrine Desseaux, Veronique Ajandouz, El Hassan Comeau, Danielle Comeau, Louis Hiol, Abel TI Proteomic of lipid rafts in the exocrine pancreas from diet-induced obese rats SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE starch; diet; obese pancreas; rafts; proteomic; BSDL; GP2 ID SECRETION; REVEALS; MODEL; SALT AB In the present work, we induced obesity in rats with high-energy-starch diet and Studied exocrine pancreas response. The zymogen granule (ZG) or purified plasma membrane (PM) from the exocrine pancreas was used for the isolation of the detergent-resistant membranes (DRMs). Based on high content of cholesterol, GM1, the bile salt dependent lipase (BSDL), and GP2 enrichment, the low-density fractions were defined as lipid rafts. Additionally, the rafts vesicles were determined by immunogold labeling with anti BSDL. By combining MALDI-TOF/MS and nano-LC ESI Q-TOF MS/MS proteoinic identification we have selected 33 proteins from the lipid rafts which were classified into at least four functional families. Our data suggest that the acinar PM from the diet-induced obesity rats may be organized into lipid rafts, and characterization of rafts proteome can contribute to improve our understanding of food digestion under obesity. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Paul Cezanne, IMRN,FST, INRA,PNV,UMR 6153 1147, UMR 1111,LCBA, F-13397 Marseille, France. Emory Univ, Div Digest Dis, Atlanta, GA 30322 USA. NCI, HIV Drug Resistance Program, NIH, Ft Detrick, MD 21702 USA. RP Hiol, A (reprint author), Univ Paul Cezanne, IMRN,FST, INRA,PNV,UMR 6153 1147, UMR 1111,LCBA, F-13397 Marseille, France. EM a.hiol@univ-u.3mrs.fr NR 15 TC 8 Z9 8 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 2007 VL 355 IS 3 BP 813 EP 819 DI 10.1016/j.bbrc.2007.02.037 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 147KG UT WOS:000245001300035 PM 17320817 ER PT J AU Antignani, A Youle, RJ AF Antignani, Antonella Youle, Richard J. TI The cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF), can deliver Bcl-XL as an extracellular fusion protein to protect cells from apoptosis and retain differentiation induction SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEURONAL APOPTOSIS; STEM-CELLS; IN-VITRO; RECEPTOR; INHIBITION; LEUKEMIA; FAMILY; DEATH; TRANSDUCTION; ACTIVATION AB Bcl-XL, a member of the Bcl-2 protein family, is able to suppress cell death induced by diverse stimuli in many cell types, including hematopoietic cells. Human granulocyte-macrophage colony-stimulating factor ( GM-CSF) is a cytokine that promotes the proliferation and maturation of neutrophils, eosinophils, and macrophages from bone marrow progenitors. We fused GM-CSF to Bcl-XL and examined the capacity of this chimera to bind human cells through the GM-CSF receptor and prevent apoptosis. We found that the chimeric protein increased the proliferation of human monocytes in culture from 24 h until at least 72 h. In the presence of different apoptotic agents, GM-CSF-Bcl-XL protected cells from induced cell death and promoted proliferation, whereas GM-CSF alone was completely inhibited. In the presence of cytarabine, GM-CSF-Bcl-XL was able also to promote the differentiation of the CD34(+) myeloid precursor whereas Lfn-Bcl-XL, lacking the GM-CSF domain-stimulated cell proliferation and not differentiation. We conclude that recombinant GM-CSF-Bcl-XL binds the GM-CSF receptor on human monocyte/macrophage cells and bone marrow progenitors inducing differentiation and allowing Bcl-XL entry into cells where it blocks cell death and allows amplified cell proliferation. This fully human fusion protein has potential to prevent monocytopenia and represents a new strategy for engineering anti-apoptotic therapeutics. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, 35 Convent Dr MSC 3704, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov FU Intramural NIH HHS NR 37 TC 5 Z9 7 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2007 VL 282 IS 15 BP 11246 EP 11254 DI 10.1074/jbc.M609824200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LG UT WOS:000245941500047 PM 17311927 ER PT J AU Valencia, JC Rouzaud, F Julien, S Chen, KG Passeron, T Yamaguchi, Y Abu-Asab, M Tsokos, M Costin, GE Yamaguchi, H Jenkins, LMM Nagashima, K Appella, E Hearing, VJ AF Valencia, Julio C. Rouzaud, Francois Julien, Sylvain Chen, Kevin G. Passeron, Thierry Yamaguchi, Yuji Abu-Asab, Mones Tsokos, Maria Costin, Gertrude E. Yamaguchi, Hiroshi Jenkins, Lisa M. Miller Nagashima, Kunio Appella, Ettore Hearing, Vincent J. TI Sialylated core 1 O-glycans influence the sorting of Pmel17/gp100 and determine its capacity to form fibrils SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX PROTEIN PMEL17/GP100; GOLGI VESICLE MEMBRANES; SURFACE SIALIC-ACID; B16 MELANOMA-CELLS; LINKED GLYCOSYLATION; MESSENGER-RNA; DOPACHROME TAUTOMERASE; GENOMIC ORGANIZATION; MUTANT DEFICIENT; PLASMA-MEMBRANE AB Pmel17 is a melanocyte/melanoma-specific protein that is essential for the maturation of melanosomes to form mature, fibrillar, and pigmented organelles. Recently, we reported that the less glycosylated form of Pmel17 ( termed iPmel17) is sorted via the plasma membrane in a manner distinct from mature Pmel17 ( termed mPmel17), which is sorted directly to melanosomes. To clarify the mechanism( s) underlying the distinct processing and sorting of Pmel17, we generated a highly specific antibody ( termed alpha PEP25h) against an epitope within the repeat domain of Pmel17 that is sensitive to changes in O-glycosylation. alpha PEP25h recognizes only iPmel17 and allows analysis of the processing and sorting of iPmel17 when compared with alpha PEP13h, an antibody that recognizes both iPmel17 and mPmel17. Our novel findings using alpha PEP25h demonstrate that iPmel17 differs from mPmel17 not only in its sensitivity to endoglycosidase H, but also in the content of core 1 O-glycans modified with sialic acid. This evidence reveals that iPmel17 is glycosylated differently in the Golgi and that it is sorted through the secretory pathway. Analysis of Pmel17 processing in glycosylation-deficient mutant cells reveals that Pmel17 lacking the correct addition of sialic acid and galactose loses the ability to form fibrils. Furthermore, we show that addition of sialic acid affects the stability and sorting of Pmel17 and reduces pigmentation. Alterations in sialyltransferase activity and substrates differ between normal and transformed melanocytes and may represent a critical change during malignant transformation. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Guys Hosp, Canc Res UK, Breast Canc Biol Grp, London SE1 9RT, England. NCI, Image Anal Lab, NIH, Ft Detrick, MD 21702 USA. NCI, Lab Pathol, NIH, Bethesda, MD 20892 USA. RP Valencia, JC (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA. EM valencij@mail.nih.gov; hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008; Chen, Kevin/D-6769-2011; OI Chen, Kevin/0000-0003-2983-6330; Abu-Asab, Mones/0000-0002-4047-1232; Passeron, Thierry/0000-0002-0797-6570 FU Intramural NIH HHS [Z99 NS999999] NR 68 TC 27 Z9 27 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2007 VL 282 IS 15 BP 11266 EP 11280 DI 10.1074/jbc.M608449200 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LG UT WOS:000245941500049 PM 17303571 ER PT J AU Bae, E Reiter, NJ Bingman, CA Kwan, SS Lee, D Phillips, GN Butcher, SE Brow, DA AF Bae, Euiyoung Reiter, Nicholas J. Bingman, Craig A. Kwan, Sharon S. Lee, Donghan Phillips, George N., Jr. Butcher, Samuel E. Brow, David A. TI Structure and interactions of the first three RNA recognition motifs of splicing factor Prp24 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE RRM; U6 RNA; splicing; RNA chaperone; Prp24 ID TORSION ANGLE DYNAMICS; U6 SNRNP PROTEIN; SACCHAROMYCES-CEREVISIAE; MACROMOLECULAR STRUCTURES; SPLICEOSOME ACTIVATION; RECYCLING FACTOR; BINDING; U4; YEAST; PROGRAM AB The essential Saccharomyces cerevisiae pre-messenger RNA splicing protein 24 (Prp24) has four RNA recognition motifs (RRMs) and facilitates U6 RNA base-pairing with U4 RNA during spliceosome assembly. Prp24 is a component of the free U6 small nuclear ribonucleoprotein particle (snRNP) but not the U4/U6 bi-snRNP, and so is thought to be displaced from U6 by U4/U6 base-pairing. The interaction partners of each of the four RRMs of Prp24 and how these interactions direct U4/U6 pairing are not known. Here we report the crystal structure of the first three RRMs and the solution structure of the first two RRMs of Prp24. Strikingly, RRM 2 forms extensive inter-domain contacts with RRMs 1 and 3. These contacts occupy much of the canonical RNA-binding faces (beta-sheets) of RRMs 1 and 2, but leave the beta-sheet of RRM 3 exposed. Previously identified substitutions in Prp24 that suppress mutations in U4 and U6 spliceosomal RNAs cluster primarily in the beta-sheet of RRM 3, but also in a conserved loop of RRM 2. RNA binding assays and chemical shift mapping indicate that a large basic patch evident on the surface of RRMs 1 and 2 is part of a high affinity U6 RNA binding site. Our results suggest that Prp24 binds free U6 RNA primarily with RRMs I and 2, which may remodel the U6 secondary structure. The beta-sheet of RRM 3 then influences U4/U6 pairing through interaction with an unidentified ligand. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA. Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. Univ Wisconsin, Ctr Eukaryot Struct Genom, Madison, WI 53706 USA. Natl Canc Inst, Frederick, MD 21702 USA. RP Butcher, SE (reprint author), Univ Wisconsin, Dept Biomol Chem, Madison, WI 53706 USA. EM butcher@biochem.wisc.edu; dabrow@wisc.edu RI Lee, Donghan/B-6893-2011; OI Lee, Donghan/0000-0002-3971-986X; Lee, Donghan/0000-0002-6530-8060 FU NCRR NIH HHS [P41 RR002301, P41RR02301, S10 RR002781, S10 RR008438]; NIGMS NIH HHS [GM65166, GM08293, GM08349, GM54018, GM64598, GM74901, P41 GM066326, P41GM66326, P50 GM064598, R01 GM054018, R01 GM065166, T32 GM008293, T32 GM008349, U54 GM074901] NR 51 TC 27 Z9 27 U1 0 U2 7 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 13 PY 2007 VL 367 IS 5 BP 1447 EP 1458 DI 10.1016/j.jmb.2007.01.078 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 154LH UT WOS:000245508200018 PM 17320109 ER PT J AU Klauda, JB Brooks, BR AF Klauda, Jeffery B. Brooks, Bernard R. TI Sugar binding in lactose permease: Anomeric state of a disaccharide influences binding structure SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE lactose permease; sugar binding; disaccharides; molecular dynamics; membrane proteins ID MEMBRANE-TRANSPORT PROTEINS; ESCHERICHIA-COLI; MOLECULAR-DYNAMICS; CONFORMATIONAL FLEXIBILITY; LIGAND RECOGNITION; SIMULATIONS; MECHANISM; ALKANES; SYSTEMS; GALACTOPYRANOSIDES AB Lactose permease in Escherichia coli (LacY) transports both anomeric states of disaccharides but has greater affinity for a-sugars. Molecular dynamics (MD) simulations are used to probe the protein-sugar interactions, binding structures, and global protein motions in response to sugar binding by investigating LacY (the experimental mutant and wild-type) embedded in a fully hydrated lipid bilayer. A total of 12 MD simulations of 20-25 ns each with beta(alpha)-D-galactopyranosyl-(1,1)-beta-D-galactopyranoside (beta beta-(Galp)(2)) and alpha beta-(Galp)(2) result in binding conformational families that depend on the anomeric state of the sugar. Both sugars strongly interact with Glu126 and alpha beta-(Galp)(2) has a greater affinity to this residue. Binding conformations are also seen that involve protein residues not observed in the crystal structure, as well as those involved in the proton translocation (Phe118, Asn119, Asn240, His322, Glu325, and Tyr350). Common to nearly all protein-sugar structures, water acts as a hydrogen bond bridge between the disaccharide and protein. The average binding energy is more attractive for alpha beta-(Galp)(2) than beta beta-(Galp)(2), i.e. -10.7(+/- 0.7) and -3.1(+/- 1.0) kcal/mol, respectively. Of the 12 helices in LacY, helix-IV is the least stable with beta beta-(Galp)(2) binding resulting in larger distortion than alpha beta-(Galp)(2). Published by Elsevier Ltd. C1 NIH, Lab Computat Biol, Bethesda, MD 20892 USA. RP Klauda, JB (reprint author), NIH, Lab Computat Biol, Bldg 50,50 S Dr, Bethesda, MD 20892 USA. EM klauda@helix.nih.gov RI Klauda, Jeffery/A-4345-2008 FU Intramural NIH HHS [Z01 HL001051-08] NR 45 TC 24 Z9 24 U1 0 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 APR 13 PY 2007 VL 367 IS 5 BP 1523 EP 1534 DI 10.1016/j.jmb.2007.02.001 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 154LH UT WOS:000245508200024 PM 17320103 ER PT J AU Avantaggiati, ML AF Avantaggiati, Maria Laura TI NIH funding: What does the future look like? SO SCIENCE LA English DT Letter C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. NIH, Drug Discovery & Mol Pharmacol Study Sect, DMP, Bethesda, MD 20892 USA. RP Avantaggiati, ML (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. EM ma364@georgetown.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 13 PY 2007 VL 316 IS 5822 BP 199 EP 199 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MV UT WOS:000245654500015 ER PT J AU Zerhouni, EA AF Zerhouni, Elias A. TI NIH funding: What does the future look like? Response SO SCIENCE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, 1 Ctr Dr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 13 PY 2007 VL 316 IS 5822 BP 199 EP 200 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MV UT WOS:000245654500016 ER PT J AU Gibbs, RA Milosavljevic, A Cameron, J Warren, V Haase, A Li, Q Herkenham, M Leopold, D Suomi, S Lesk, AM Miller, W Raney, B Siepel, A Vinar, T AF Gibbs, Richard A. Milosavljevic, Aleksander Cameron, Judy Warren, Vince Haase, Ashley Li, Qingsheng Herkenham, Miles Leopold, David Suomi, Steve Lesk, Arthur M. Miller, Webb Raney, Brian Siepel, Adam Vinar, Thomas TI The Macaque genome SO SCIENCE LA English DT Editorial Material C1 Baylor Coll Med, Houston, TX 77030 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NIMH, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. Penn State Univ, University Pk, PA 16802 USA. Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. Cornell Univ, Ithaca, NY 14853 USA. RP Gibbs, RA (reprint author), Baylor Coll Med, Houston, TX 77030 USA. RI Cameron, Judy/J-6682-2013; Vinar, Tomas/I-3695-2014 OI Vinar, Tomas/0000-0003-3898-3447 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD APR 13 PY 2007 VL 316 IS 5822 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156MV UT WOS:000245654500042 ER PT J AU Kimura, T Ninomiya, K Futaki, S AF Kimura, Tomohiro Ninomiya, Keiko Futaki, Shiroh TI NMR investigation of the electrostatic effect in binding of a neuropeptide, achatin-I, to phosphatidylcholine bilayers SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID ANTIMICROBIAL PEPTIDES MSI-78; PHOSPHOLIPID-BILAYER; ASPARTIC-ACID; FREE-ENERGY; MEMBRANES; VESICLES; ANIONS; MODEL; DIPALMITOYLPHOSPHATIDYLCHOLINE; PHOSPHATIDYLSERINE AB Achatin-I (Gly1-D-Phe2-Ala3-Asp4), known as a neuropeptide containing a D-amino acid, binds to the surface of a zwitterionic phosphatidylcholine (PC) membrane only when the peptide N-terminal amino group is in the ionized state, NH3+ (Kimura, T.; Okamura, E.; Matubayasi, N.; Asami, K.; Nakahara, M. Biophys. J. 2004, 87, 375-385). To gain mechanistic insights into how the binding equilibrium is delicately controlled by the ionization state of the N-terminal amino group, peptide-lipid binding interactions are investigated by selectively enriched N-15 (at the N-terminus) and natural-abundance C-13 NMR spectroscopy. Upon binding to the PC membrane, the N-15 NMR of the N-terminal NH3+ shifts upfield. This observation supports a mechanism that the role of the N-terminal NH3+ in stabilizing the binding state is through electrostatic attraction with a headgroup negative charge, i.e., PO4-. Interestingly, when the side chain beta-carboxyl group in Asp4 is deionized at acidic pH, the N-15 signal of the N-terminal NH3+ exhibits no significant chemical-shift change upon membrane binding of achatin-I. The Asp4 side chain thus regulates efficiency of the electrostatic binding between the peptide N-terminal NH3+ and the lipid headgroup PO4-. C-13 chemical shifts in the hydrophobic D-Phe2 residue are largely perturbed upon membrane binding, in the case where the side chain beta-CO2- in Asp4 is deionized; the deionization of Asp4 beta-CO2- increases the net hydrophobicity of achatin-I with a reduction of both the electrostatic hydration and the electrostatic attraction with the headgroup N(CH3)(3)(+) in the most superficial region of the PC membrane, resulting in deeper anchoring of the phenyl ring. Hence, the electrostatic effect of the side chain beta-CO2- in Asp4 floats achatin-I on the PC membrane surface, and the binding equilibrium is sensitively controlled by the ionization state of the N-terminal NH3+. C1 Kyoto Univ, Inst Chem Res, Uji, Kyoto 6110011, Japan. RP Kimura, T (reprint author), NIAAA, NIH, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. EM kimurato@mail.nih.gov NR 44 TC 2 Z9 2 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD APR 12 PY 2007 VL 111 IS 14 BP 3831 EP 3838 DI 10.1021/jp067100x PG 8 WC Chemistry, Physical SC Chemistry GA 153MD UT WOS:000245438700031 PM 17388516 ER PT J AU Galburt, EA Grill, SW Wiedmann, A Lubkowska, L Choy, J Nogales, E Kashlev, M Bustamante, C AF Galburt, Eric A. Grill, Stephan W. Wiedmann, Anna Lubkowska, Lucyna Choy, Jason Nogales, Eva Kashlev, Mikhail Bustamante, Carlos TI Backtracking determines the force sensitivity of RNAP II in a factor-dependent manner SO NATURE LA English DT Article ID ELONGATION-FACTOR TFIIS; POLYMERASE-II; TRANSCRIPT-CLEAVAGE; ARREST; DNA; MECHANISM; RESOLUTION; COMPLEXES; MOLECULES; BACTERIAL AB RNA polymerase II ( RNAP II) is responsible for transcribing all messenger RNAs in eukaryotic cells during a highly regulated process that is conserved from yeast to human 1, and that serves as a central control point for cellular function. Here we investigate the transcription dynamics of single RNAP II molecules from Saccharomyces cerevisiae against force and in the presence and absence of TFIIS, a transcription elongation factor known to increase transcription through nucleosomal barriers(2\). Using a single-molecule dual-trap optical-tweezers assay combined with a novel method to enrich for active complexes, we found that the response of RNAP II to a hindering force is entirely determined by enzyme backtracking(3-6). Surprisingly, RNAP II molecules ceased to transcribe and were unable to recover from backtracks at a force of 7.5 +/- 2 pN, only one-third of the force determined for Escherichia coli RNAP(7,8). We show that backtrack pause durations follow a t(-3/2) power law, implying that during backtracking RNAP II diffuses in discrete base-pair steps, and indicating that backtracks may account for most of RNAP II pauses. Significantly, addition of TFIIS rescued backtracked enzymes and allowed transcription to proceed up to a force of 16.9 +/- 3.4 pN. Taken together, these results describe a regulatory mechanism of transcription elongation in eukaryotes by which transcription factors modify the mechanical performance of RNAP II, allowing it to operate against higher loads. C1 Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. NCI, Ctr Canc Res, Frederick, MD 21702 USA. RP Bustamante, C (reprint author), Univ Calif Berkeley, Lawrence Berkeley Lab, Phys Biosci Div, Berkeley, CA 94720 USA. EM carlos@alice.berkeley.edu RI Grill, Stephan /D-9427-2012; OI Galburt, Eric/0000-0003-4314-3215 NR 28 TC 139 Z9 145 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 APR 12 PY 2007 VL 446 IS 7137 BP 820 EP 823 DI 10.1038/nature05701 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156CX UT WOS:000245626800046 PM 17361130 ER PT J AU Wavrant-De Vrieze, F Compton, D Womick, M Arepalli, S Adighibe, O Li, L Perez-Tur, J Hardy, J AF Wavrant-De Vrieze, Fabienne Compton, Danielle Womick, Meridith Arepalli, Sampath Adighibe, Omanma Li, Ling Perez-Tur, Jordi Hardy, John TI ABCA1 polymorphisms and Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE ABCA1; Alzheimer's disease; polymorphisms ID CASSETTE TRANSPORTER A1; CORONARY-ARTERY DISEASE; TANGIER-DISEASE; COMMON POLYMORPHISMS; CHOLESTEROL LEVELS; GENETIC-VARIATION; HDL-CHOLESTEROL; GENOME SCREEN; ONSET; RISK AB In our search for genetic factors related to the development of Alzheimer's disease, we have genotyped 332 pedigrees for three coding polymorphisms in the ABCA1 gene, two of which are known to alter plasma cholesterol levels, as well as a non-coding polymorphism within the promoter. We show an apparent weak association of rs2230806 (p-value = 0.0 1) with the disease in a sibpair series of Alzheimer's disease that had shown previously evidence for linkage to the chromosome 9 locus where ABCA1 maps. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. UAB Med Ctr, Dept Med, Arteriosclerosis Res Unit, Birmingham, AL 35294 USA. CSIC, Inst Biomed Valencia, Dept Genom & Proteom, Unitat Genet Mol, E-46010 Valencia, Spain. RP Wavrant-De Vrieze, F (reprint author), NIA, Neurogenet Lab, NIH, 35 Convent Dr,Room 1A1015 MSC 3707, Bethesda, MD 20892 USA. EM wavrant@mail.nih.gov RI Perez-Tur, Jordi/A-2143-2010; Hardy, John/C-2451-2009 OI Perez-Tur, Jordi/0000-0002-9111-1712; FU Intramural NIH HHS [NIH0011356532]; Medical Research Council [G0701075]; NIA NIH HHS [U24 AG021886, U24 AG21886]; NIMH NIH HHS [U01 MH046290, U01 MH046281, U01 MH046373] NR 26 TC 10 Z9 11 U1 3 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD APR 12 PY 2007 VL 416 IS 2 BP 180 EP 183 DI 10.1016/j.neulet.2007.02.010 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 161TN UT WOS:000246039100015 PM 17324514 ER PT J AU Rother, KI AF Rother, Kristina I. TI Focus on research: Diabetes treatment - Bridging the divide SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Rother, KI (reprint author), NIDDKD, Clin Endocrinol Branch, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 DK999999] NR 4 TC 74 Z9 83 U1 1 U2 13 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2007 VL 356 IS 15 BP 1499 EP 1501 DI 10.1056/NEJMp078030 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 156CA UT WOS:000245624400003 PM 17429082 ER PT J AU Dobbin, KK AF Dobbin, Kevin K. TI Five-gene signature in non-small-cell lung cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Rockville, MD 20852 USA. RP Dobbin, KK (reprint author), NCI, Rockville, MD 20852 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2007 VL 356 IS 15 BP 1582 EP 1582 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 156CA UT WOS:000245624400021 PM 17436430 ER PT J AU Dejam, A Hunter, CJ Gladwin, MT AF Dejam, Andre Hunter, Christian J. Gladwin, Mark T. TI Effects of dietary nitrate on blood pressure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID NITRITE C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. RP Dejam, A (reprint author), Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM mgladwin@nih.gov RI Hunter, Christian/G-4344-2010 NR 5 TC 19 Z9 19 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 12 PY 2007 VL 356 IS 15 BP 1590 EP 1590 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 156CA UT WOS:000245624400035 PM 17429097 ER PT J AU Demidov, ON Kek, C Shreeram, S Timofeev, O Fornace, AJ Appella, E Bulavin, DV AF Demidov, O. N. Kek, C. Shreeram, S. Timofeev, O. Fornace, A. J. Appella, E. Bulavin, D. V. TI The role of the MKK6/p38 MAPK pathway in Wip1-dependent regulation of ErbB2-driven mammary gland tumorigenesis SO ONCOGENE LA English DT Article DE Wip1 phosphatase; p38 MAPK; MKK6; breast cancer; ErbB2; proliferation; MMTV ID TUMOR-SUPPRESSOR ACTIVITY; WIP1 PHOSPHATASE; BREAST-CANCER; PROTEIN PHOSPHATASE; IN-VIVO; PPM1D; AMPLIFICATION; KINASE; P53; ACTIVATION AB There is increasing evidence for the role of wild-type p53 induced phosphatase 1( Wip1) phosphatase in the regulation of tumorigenesis. To evaluate Wip1 as a breast cancer oncogene, we generated a mouse strain with targeted expression of Wip1 to the breast epithelium. We found that these mice are prone to cancer when intercrossed with transgenics expressing the ErbB2 oncogene but not conditional knockouts for Brca2. This tumor-prone phenotype of Wip1 is fully eliminated through attenuation of proliferation by activating the MKK6/p38 mitogen-activated protein kinases ( MAPK) cascade in mice bearing a constitutively active form of MKK6. We propose that Wip1 phosphatase operates within the MKK6/p38 MAPK signaling pathway to promote ErbB2-driven mammary gland tumorigenesis. C1 Natl Univ Singapore, Inst Mol & Cell Biol, Cell Cycle Control & Tumorigenesis Grp, Singapore 138673, Singapore. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. RP Bulavin, DV (reprint author), Natl Univ Singapore, Inst Mol & Cell Biol, Cell Cycle Control & Tumorigenesis Grp, 61 Biopolis Dr, Singapore 138673, Singapore. EM dvbulavin@imcb.a-star.edu.sg RI Fornace, Albert/A-7407-2008; ASTAR, IMCB/E-2320-2012; OI Fornace, Albert/0000-0001-9695-085X; Sathyavageeswaran, Shreeram/0000-0002-6111-1818; Demidov, Oleg/0000-0003-4323-7174 NR 20 TC 56 Z9 60 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 12 PY 2007 VL 26 IS 17 BP 2502 EP 2506 DI 10.1038/sj.onc.1210032 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 158YG UT WOS:000245831000010 PM 17016428 ER PT J AU Fogg, CN Americo, JL Lustig, S Huggins, JW Smith, SK Damon, I Resch, W Earl, PL Klinman, DM Moss, B AF Fogg, Christiana N. Americo, Jeffrey L. Lustig, Shlomo Huggins, John W. Smith, Scott K. Damon, Inger Resch, Wolfgang Earl, Patricia L. Klinman, Dennis M. Moss, Bernard TI Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges SO VACCINE LA English DT Article DE smallpox; monkeypox; vaccinia virus ID EXTRACELLULAR ENVELOPED VIRUS; T-LYMPHOCYTE RESPONSES; MONOPHOSPHORYL-LIPID-A; VACCINIA VIRUS; SMALLPOX VACCINE; IMMUNE-RESPONSES; SAPONIN ADJUVANT; POXVIRUS INFECTION; NONHUMAN-PRIMATES; CPG MOTIFS AB Recombinant proteins are being evaluated as smallpox and monkeypox vaccines because of their perceived safety compared to live vaccinia virus. Previously, we demonstrated that three or more injections of a Ribi-type adjuvant with a combination of three proteins from the outer membranes of intracellular (L1 protein) and extracellular (A33 and B5 proteins) forms of vaccinia virus protected mice against a lethal intranasal challenge with vaccinia virus. Here, we compared several adjuvants and found that QS-21 and to a lesser extent alum+CpG oligodeoxynucleotides accelerated and enhanced neutralizing antibody responses to a mixture of L1 and A33 proteins, provided the highest ratio of IgG2a to IgG1 isotype response, and protected mice against disease and death after only two immunizations 3 weeks apart. In addition, monkeys immunized with recombinant vaccinia virus proteins and QS-21 developed neutralizing antibody to monkeypox virus and had reduced virus load, skin lesions, and morbidity compared to the non-immunized group following monkeypox virus challenge. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Ctr Dis Control & Prevent, Poxvirus & Rabies Branch, Atlanta, GA 30333 USA. FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, NIH, Viral Dis Lab, 33 N Dr MSC3210,Bldg 33,Room 1E13C-1, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [U54 AI057168, RCE-U54-AI57168, Z01 AI000979-01] NR 63 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 12 PY 2007 VL 25 IS 15 BP 2787 EP 2799 DI 10.1016/j.vaccine.2006.12.037 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 158WL UT WOS:000245825800007 PM 17229505 ER PT J AU Robbins, JB Schneerson, R Keith, JA Shiloach, J Miller, M Trollors, B AF Robbins, John B. Schneerson, Rachel Keith, Jerry A. Shiloach, Joseph Miller, Mark Trollors, Birger TI The rise in pertussis cases urges replacement of chemically-inactivated with genetically-inactivated toxoid for DTP SO VACCINE LA English DT Article DE pertussis toxoid; genetically inactivated; DTP ID WHOOPING-COUGH; BORDETELLA-PERTUSSIS; UNITED-STATES; FILAMENTOUS HEMAGGLUTININ; NUCLEOTIDE-SEQUENCE; ANTIBODY-RESPONSE; VACCINE EFFICACY; CONTROLLED TRIAL; IGG ANTIBODIES; TOXIN GENES AB The number of pertussis cases reported to the CDC increased from 5158 in 1995 to 21,503 in 2005. Most of the increase was in individuals greater than 10 years of age. This increase occurred also in other developed nations despite high coverage of infants and young children with the acellular pertussis vaccine. In Goteborg Sweden, virtual elimination of pertussis occurred following immunization of 70% of the children less than 10 years old with monocomponent pertussis toxoid (PTx). Immunity following disease or vaccination with either the cellular or acellular pertussis vaccine wanes gradually so that older children and adults may again become susceptible. Currently, PTx is made from chemically-inactivated pertussis toxin (PT). The most immunogenic PTx is made from genetically-inactivated mutant PT that induces higher levels of IgG anti-PT at all ages. Because of its greater immunogenicity, the genetically-inactivated PTx can be expected to be more protective on an individual and on a community basis for a longer duration than the current product. Manufacturers have declined to produce the genetically-inactivated PTx because of the expense required to change to the improved vaccine and not because of scientific issues. (c) 2007 Elsevier Ltd. All rights reserved. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDD, NIH, Bethesda, MD 20892 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Pediat, S-41685 Gothenburg, Sweden. RP Robbins, JB (reprint author), NICHHD, NIH, 31 Ctr Dr, Bethesda, MD 20892 USA. EM robbinsjo@mail.nih.gov NR 74 TC 10 Z9 10 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 APR 12 PY 2007 VL 25 IS 15 BP 2811 EP 2816 DI 10.1016/j.vaccine.2006.12.013 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 158WL UT WOS:000245825800009 PM 17291636 ER PT J AU Liu, JY Hellerstein, M McDonnel, M Amara, RR Wyatt, LS Moss, B Robinson, HL AF Liu, Jinyan Hellerstein, Michael McDonnel, Michael Amara, Rama Rao Wyatt, Linda S. Moss, Bernard Robinson, Harriet L. TI Dose-response studies for the elicitation of CD8 T cells by a DNA vaccine, used alone or as the prime for a modified vaccinia Ankara boost SO VACCINE LA English DT Article DE DNA; MVA; CD8 T cells; dose-response; vaccine ID PLASMID DNA; DENDRITIC CELLS; HIV TYPE-1; TISSUE DISTRIBUTION; DNA/MVA VACCINE; IN-VIVO; IMMUNOGENICITY; EXPRESSION; SAFETY; CONSTRUCTION AB Here, we conduct dose-response studies in mice for the elicitation of CD8 T cells by a DNA vaccine that expresses HIV Gag. For DNA doses ranging from 1 to 100 mu g, the studies revealed greater than 10-fold increases in anti-Gag CD8 T cells following a DNA prime or a DNA prime and a constant modified vaccinia Ankara (MVA) boost. These results are in contrast to dose-response studies for MVA vectors expressing Gag, where only 2-3-fold increases in anti-Gag CD8 T cells were elicited by 100-fold increases in dose. (c) 2006 Elsevier Ltd. All rights reserved. C1 Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. GeoVax Inc, Atlanta, GA USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Robinson, HL (reprint author), 954 Gatewood Rd,Box 129, Atlanta, GA 30329 USA. EM hrobins@rmy.emory.edu FU NCRR NIH HHS [RR-00165]; NIAID NIH HHS [P01 AI49364]; NIDA NIH HHS [P30 DA 12121] NR 23 TC 17 Z9 18 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 12 PY 2007 VL 25 IS 15 BP 2951 EP 2958 DI 10.1016/j.vaccine.2006.05.081 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 158WL UT WOS:000245825800026 PM 17360078 ER PT J AU Maieron, M Iannetti, GD Bodurka, J Tracey, I Bandettini, PA Porro, CA AF Maieron, Marta Iannetti, Gian Domenico Bodurka, Jerzy Tracey, Irene Bandettini, Peter A. Porro, Carlo A. TI Functional responses in the human spinal cord during willed motor actions: Evidence for side- and rate-dependent activity SO JOURNAL OF NEUROSCIENCE LA English DT Article DE functional magnetic resonance imaging; hand; humans; cervical spinal cord; movement rate; voluntary movement ID ANTICIPATORY POSTURAL ADJUSTMENTS; VOLUNTARY MOVEMENT; HAND MOVEMENT; CORTICOSPINAL PROJECTIONS; EXCITABILITY CHANGES; CEREBRAL ACTIVATION; NEURONAL-ACTIVITY; FOREARM MUSCLES; ARM MOVEMENTS; FMRI AB Although the spinal cord is the output station of the central motor system, little is known about the relationships between its functional activity and willed movement parameters in humans. We investigated here blood oxygenation level-dependent functional magnetic resonance imaging ( fMRI) signal changes in the cervical spinal cord during a simple finger-to-thumb opposition task in 13 right-handed volunteers, using a dedicated array of 16 receive-only surface coils on a 3 Tesla MRI system. In a first experiment, we found significant fMRI signal increases on both sides of the lower cervical spinal cord while subjects performed the motor task at a comfortable pace ( similar to 0.5 Hz) using either hand. Both the spatial extent of movement-related clusters and peak signal increases were significantly higher on the side of the cord ipsilateral to the moving hand than on the contralateral side. Movement-related activity was consistently larger than signal fluctuations during rest. In a second experiment, we recorded spinal cord responses while the same motor sequence was performed using the dominant hand at two different rates ( similar to 0.5 or 1 Hz). The intensity but not the spatial extent of the response was larger during higher rates, and it was higher on the ipsilateral side of the cord. Notwithstanding the limited spatial resolving power of the adopted technique, the present results clearly indicate that the finger movement-related fMRI signals recorded from the spinal cord have a neural origin and that as a result of recent technological advances, fMRI can be used to obtain novel and quantitative physiological information on the activity of spinal circuits. C1 Univ Modena, Dept Biomed Sci, I-41100 Modena, Italy. NIMH, Funct Magnet Resonance Imaging Facil, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. Univ Udine, Dipartimento Sci Tecnol Biomed, I-33100 Udine, Italy. Univ Oxford, Dept Physiol Anat & Genet, Oxford OX1 3QX, England. RP Porro, CA (reprint author), Univ Modena, Dept Biomed Sci, Via Campi 287, I-41100 Modena, Italy. EM porro@unimore.it RI Porro, Carlo Adolfo/N-2580-2015 OI Porro, Carlo Adolfo/0000-0003-2345-5852 NR 58 TC 53 Z9 54 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 11 PY 2007 VL 27 IS 15 BP 4182 EP 4190 DI 10.1523/JNEUROSCI.3910-06.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 158RB UT WOS:000245810100031 PM 17428996 ER PT J AU Kempler, K Toth, J Yamashita, R Mapel, G Robinson, K Cardasis, H Stevens, S Sellers, JR Battelle, BA AF Kempler, Karen Toth, Judit Yamashita, Roxanne Mapel, Gretchen Robinson, Kimberly Cardasis, Helene Stevens, Stanley Sellers, James R. Battelle, Barbara-Anne TI Loop 2 of Limulus myosin III is phosphorylated by protein kinase A and autophosphorylation SO BIOCHEMISTRY LA English DT Article ID CIRCADIAN EFFERENT INPUT; VISUAL ARRESTIN; LATERAL EYE; VENTRAL PHOTORECEPTORS; PHORBOL ESTER; RHABDOMERE DISORGANIZATION; DROSOPHILA PHOTORECEPTORS; ADENOSINE-TRIPHOSPHATASE; MEMBRANE TURNOVER; KINETIC MECHANISM AB Little is known about the functions of class III unconventional myosins although, with an N-terminal kinase domain, they are potentially both signaling and motor proteins. Limulus myosin III is particularly interesting because it is a phosphoprotein abundant in photoreceptors that becomes more heavily phosphorylated at night by protein kinase A. This enhanced nighttime phosphorylation occurs in response to signals from an endogenous circadian clock and correlates with dramatic changes in photoreceptor structure and function. We seek to understand the role of Limulus myosin III and its phosphorylation in photoreceptors. Here we determined the sites that become phosphorylated in Limulus myosin III and investigated its kinase, actin binding, and myosin ATPase activities. We show that Limulus myosin III exhibits kinase activity and that a major site for both protein kinase A and autophosphorylation is located within loop 2 of the myosin domain, an important actin binding region. We also identify the phosphorylation of an additional protein kinase A and autophosphorylation site near loop 2, and a predicted phosphorylation site within loop 2. We show that the kinase domain of Limulus myosin III shares some pharmacological properties with protein kinase A, and that it is a potential opsin kinase. Finally, we demonstrate that Limulus myosin III binds actin but lacks ATPase activity. We conclude that Limulus myosin III is an actin-binding and signaling protein and speculate that interactions between actin and Limulus myosin III are regulated by both second messenger mediated phosphorylation and autophosphorylation of its myosin domain within and near loop 2. C1 Univ Florida, Whitney Lab Marine Biosci, St Augustine, FL 32080 USA. Univ Florida, Dept Neurosci, St Augustine, FL 32080 USA. Univ Florida, Dept Chem, Gainesville, FL 32010 USA. Univ Florida, Proteom Core ICBR, Gainesville, FL 32010 USA. Eotvos Lorand Univ, Dept Biochem, H-1117 Budapest, Hungary. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Battelle, BA (reprint author), Univ Florida, Whitney Lab Marine Biosci, 9505 Ocean Shore Blvd, St Augustine, FL 32080 USA. EM Battelle@whitney.ufl.edu RI Robinson, Kimberly/A-2821-2012 FU Intramural NIH HHS [Z01 HL004232-07] NR 74 TC 18 Z9 18 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 10 PY 2007 VL 46 IS 14 BP 4280 EP 4293 DI 10.1021/bi062112u PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 152OD UT WOS:000245370400008 PM 17367164 ER PT J AU Madej, T Panchenko, AR Chen, J Bryant, SH AF Madej, Thomas Panchenko, Anna R. Chen, Jie Bryant, Stephen H. TI Protein homologous cores and loops: important clues to evolutionary relationships between structurally similar proteins SO BMC STRUCTURAL BIOLOGY LA English DT Article ID CONSERVED DOMAIN ALIGNMENTS; HIERARCHICAL-CLASSIFICATION; INTEGRATED APPROACH; DATABASE; IDENTIFICATION; SEQUENCES; CDD AB Background: To discover remote evolutionary relationships and functional similarities between proteins, biologists rely on comparative sequence analysis, and when structures are available, on structural alignments and various measures of structural similarity. The measures/scores that have most commonly been used for this purpose include: alignment length, percent sequence identity, superposition RMSD and their different combinations. More recently, we have introduced the "Homologous core structure overlap score" (HCS) and the "Loop Hausdorff Measure" (LHM). Along with these we also consider the "gapped structural alignment score" (GSAS), which was introduced earlier by other researchers. Results: We analyze the performance of these and other conventional measures at the task of ranking structure neighbors by homology, and we show that the HCS, LHM, and GSAS scores display considerably improved performance over the conventional measures of sequence or structural similarity. Conclusion: The HCS, LHM, and GSAS scores are easily computable quantities that allow users of structure-neighbor databases to more easily identify interesting structural similarities between proteins. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Madej, T (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20894 USA. EM madej@ncbi.nlm.nih.gov; panch@ncbi.nlm.nih.gov; chenj@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 28 TC 6 Z9 6 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2237 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD APR 10 PY 2007 VL 7 AR 23 DI 10.1186/1472-6807-7-23 PG 9 WC Biophysics SC Biophysics GA 161CR UT WOS:000245992400001 PM 17425794 ER PT J AU Tao-Cheng, JH Gallant, PE Brightman, MW Dosemeci, A Reese, TS AF Tao-Cheng, Jung-Hwa Gallant, Paul E. Brightman, Milton W. Dosemeci, Ayse Reese, Thomas S. TI Structural changes at synapses after delayed perfusion fixation in different regions of the mouse brain SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE PSD thickness; PSD curvature; CaMKII; cerebellum; hippocampus; cerebral cortex ID PROTEIN-KINASE-II; CEREBELLAR PURKINJE-CELLS; POSTSYNAPTIC DENSITY; ELECTRON-MICROSCOPY; DENDRITIC SPINES; SELF-ASSOCIATION; NEURONS; CAMKII; RAT; INHIBITION AB We recently showed by electron microscopy that the postsynaptic density (PSD) from hippocampal cultures undergoes rapid structural changes after ischemia-like conditions. Here we report that similar structural changes occur after delay in transcardial perfusion fixation of the mouse brain. Delay in perfusion fixation, a condition that mimics ischemic stress, resulted in 70%, 90%, and 23% increases in the thickness of PSDs from the hippocampus (CA1), cerebral cortex (layer III), and cerebellar cortex (Purkinje spines), respectively. In step with PSD thickening, the amount of PSD-associated (alpha-calcium calmodulin-dependent protein kinase II (alpha- CaMKII) label increased more in cerebral cortical spines than in Purkinje spines. Although the Purkinje PSDs thickened only slightly after delayed fixation, they became highly curved, and many formed sub-PSD spheres similar to 80 nm in diameter that labeled for CaMKII. Delayed perfusion fixation also produced more cytoplamic CaMKII clusters (similar to 110 nm in diameter) in the somas of pyramidal cells (from hippocampus and cerebral cortex) than in Purkinje cells. Thus a short delay in perfusion fixation produces cell-specific structural changes at PSDs and neuronal somas. Purkinje cells respond somewhat differently to delayed perfusion fixation, perhaps owing to their lower levels of CaMKII, and CaMKII binding proteins at PSDs. We present here a catalogue of structural changes that signal a perfusion fixation delay, thereby providing criteria by which to assess perfusion fixation quality in experimental structural studies of brain and to shed light on the subtle changes that occur in intact brain following metabolic stress. C1 NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. NINDS, Lab Neurobiol, NIH, Bethesda, MD 20892 USA. RP Reese, TS (reprint author), NINDS, EM Facil, NIH, Bldg 49,Room 3A60, Bethesda, MD 20892 USA. EM treese@mbl.edu NR 29 TC 40 Z9 41 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 10 PY 2007 VL 501 IS 5 BP 731 EP 740 DI 10.1002/cne.21276 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 139ZN UT WOS:000244471800005 PM 17299754 ER PT J AU Scheinberg, P Melenhorst, JJ Hill, BJ Keyvanfar, K Barrett, AJ Price, DA Douek, DC AF Scheinberg, Phillip Melenhorst, Jan J. Hill, Brenna J. Keyvanfar, Keyvan Barrett, A. John Price, David A. Douek, Daniel C. TI The clonal composition of human CD4+CD25+Foxp3+ cells determined by a comprehensive DNA-based multiplex PCR for TCRB gene rearrangements SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE T cells; human; T cell receptors; repertoire development; regulatory T cells ID REGULATORY T-CELLS; POLYMERASE-CHAIN-REACTION; IMMUNOLOGICAL SELF-TOLERANCE; VERSUS-HOST-DISEASE; FOXP3; EXPRESSION; INFECTION; RESPONSES; BETA; LYMPHOPROLIFERATIONS AB The characterization of the T-cell receptor (TCR) repertoire of CD4+ regulatory T cells (T-R) has been limited due to the RNA degradation that results following permeabilization and fixation as routinely used for intracellular staining of Foxp3. In the present study the clonal composition of human umbilical cord blood (UCB) and adult peripheral blood mononuclear cell (PBMC) CD4+ TR and non-T-R was characterized by a DNA-based multiplex PCR which allowed for the consistent clonotypic characterization of cells that have undergone fixation and permeabilization. To validate this method, CD8+ T cells from two HLA A*0201 individuals were sorted and compared clonotypically based upon their ability either to secrete interferon-gamma in response to a CMV pp65 epitope or to bind to the corresponding pMHC I tetramer. Clonotypes shared between the CD4+CD25+Foxp3+ and CD4+CD25+Foxp3-subsets were observed in all 3 UCB and in one adult PBMCs, suggesting that naive and memory CD4+ TR can share the same clonotypes as CD4+ non-T-R in humans. Published by Elsevier B.V. C1 NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Weatherall Inst Mol Med, Oxford OX3 9DS, England. RP Douek, DC (reprint author), NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bldg 40,Room 3509,40 Convent Dr, Bethesda, MD 20892 USA. EM ddouek@mail.nih.gov RI Price, David/C-7876-2013; OI Price, David/0000-0001-9416-2737; Scheinberg, Phillip/0000-0002-9047-4538 FU Intramural NIH HHS [Z99 AI999999]; Medical Research Council [G0501963] NR 31 TC 15 Z9 15 U1 0 U2 0 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 APR 10 PY 2007 VL 321 IS 1-2 BP 107 EP 120 DI 10.1016/j.jim.2007.01.005 PG 14 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 158MD UT WOS:000245794700010 PM 17316678 ER PT J AU Holmes, EC AF Holmes, Edward C. TI Ancient lentiviruses leave their mark SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID INFECTION; VIRUSES; ORIGIN; HIV-1; SIV C1 Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Holmes, EC (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biol, University Pk, PA 16802 USA. EM ech15@psu.edu OI Holmes, Edward/0000-0001-9596-3552 NR 12 TC 2 Z9 2 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2007 VL 104 IS 15 BP 6095 EP 6096 DI 10.1073/pnas.0701578104 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157RG UT WOS:000245737500002 PM 17404211 ER PT J AU Vacchio, MS Olaru, A Livak, F Hodes, RJ AF Vacchio, Melanie S. Olaru, Alexandru Livak, Ferenc Hodes, Richard J. TI ATM deficiency impairs thymocyte maturation because of defective resolution of T cell receptor a locus coding end breaks SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ataxia telangiectasia mutated; recombination; T cell development ID V(D)J RECOMBINATION; ATAXIA-TELANGIECTASIA; CD4(+)CD8(+) THYMOCYTES; CD28 COSTIMULATION; IN-VIVO; MICE; AUTOPHOSPHORYLATION; TUMORIGENESIS; LYMPHOCYTES; TOLERANCE AB The ATM (ataxia telangiectasia mutated) protein plays a central role in sensing and responding to DNA double-strand breaks. Lymphoid cells are unique in undergoing physiologic double-strand breaks in the processes of Ig class switch recombination and Tor Bcell receptorV(D)J recombination, and a role for ATM in these processes has been suggested by clinical observations in ataxia telangiectasia patients as well as in engineered mice with mutations in the Atm gene. We demonstrate here a defect in thymocyte maturation in ATM-deficient mice that is associated with decreased efficiency in V-J rearrangement of the endogenous T cell receptor (TCR)alpha locus, accompanied by increased frequency of unresolved TCR J alpha coding end breaks. We also demonstrate that a functionally rearranged TCR alpha beta transgene is sufficient to restore thymocyte maturation, whereas increased thymocyte survival by bcl-2 cannot improve TCR alpha recombination and T cell development. These data indicate a direct role for ATM in TCR gene recombination in vivo that is critical for surface TCR expression in CD4(+)CD8(+) cells and for efficient thymocyte selection. We propose a unified model for the two major clinical characteristics of ATM deficiency, defective T cell maturation and increased genomic instability, frequently affecting the TCR alpha locus. In the absence of ATM, delayed TCR alpha coding joint formation results both in a reduction of alpha beta TCR-expressing immature cells, leading to inefficient thymocyte selection, and in accumulation of unstable open chromosomal DNA breaks, predisposing to TCR alpha locus-associated chromosomal abnormalities. C1 NCI, Canc Res Ctr, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Vacchio, MS (reprint author), NCI, Canc Res Ctr, Expt Immunol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 4B36, Bethesda, MD 20892 USA. EM hodesr@31.nia.nih.gov FU Intramural NIH HHS NR 32 TC 41 Z9 41 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2007 VL 104 IS 15 BP 6323 EP 6328 DI 10.1073/pnas.0611222104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157RG UT WOS:000245737500042 PM 17405860 ER PT J AU Maeda, Y Nakamura, E Nguyen, MT Suva, LJ Swain, FL Razzaque, MS Mackem, S Lanske, B AF Maeda, Yukiko Nakamura, Eiichiro Nguyen, Minh-Thanh Suva, Larry J. Swain, Frances L. Razzaque, Mohammed S. Mackem, Susan Lanske, Beate TI Indian Hedgehog produced by postnatal chondrocytes is essential for maintaining a growth plate and trablecular bone SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cre/loxP; endochondral bone; tamoxifen-inducible; cartilage; osteoblast ID HORMONE-RELATED PROTEIN; ENDOCHONDRAL SKELETON; FACTOR RECEPTOR-3; EXPRESSION; DIFFERENTIATION; CARTILAGE; PROLIFERATION; PTHRP; IHH; RAT AB Indian hedgehog (Ihh) is essential for chondrocyte and osteolblast proliferation/differentiation during prenatal enclochondral bone formation. The early lethality of various thh-ablated mutant mice, however, prevented further analysis of its role in postnatal bone growth and development. In this study, we describe the generation and characterization of a mouse model in which the lhh gene was successfully ablated from postnatal chondrocytes in a temporal/ spatial-specific manner; postnatal deletion of Ihh resulted in loss of columnar structure, premature vascular invasion, and formation of ectopic hypertrophic chondrocytes in the growth plate. Furthermore, destruction of the articular surface in long bones and premature fusion of growth plates of various enclochondral bones was evident, resulting in dwarfism in mutant mice. More importantly, these mutant mice exhibited continuous loss of trabecular bone over time, which was accompanied by reduced Wnt signaling in the osteoblastic cells. These results demonstrate, for the first time, that postnatal chond rocyte-derived Ihh is essential for maintaining the growth plate and articular surface and is required for sustaining trabecular bone and skeletal growth. C1 Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Dept Orthoped Surg, Ctr Orthoped Res, Little Rock, AR 72205 USA. RP Lanske, B (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, 188 Longwood Ave,REB 303, Boston, MA 02115 USA. EM beate_lanske@hsdm.harvard.edu FU NIAMS NIH HHS [AR050560, R01 AR050560, R01 AR050560-03] NR 26 TC 123 Z9 128 U1 4 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2007 VL 104 IS 15 BP 6382 EP 6387 DI 10.1073/pnas.0608449104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157RG UT WOS:000245737500052 PM 17409191 ER PT J AU Zahn, R Moll, J Krueger, F Huey, ED Garrido, G Grafman, J AF Zahn, Roland Moll, Jorge Krueger, Frank Huey, Edward D. Garrido, Griselda Grafman, Jordan TI Social concepts are represented in the superior anterior temporal cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE functional MRI; semantics; social cognition; temporal lobe; frontal lobe ID MEDIAL PREFRONTAL CORTEX; SEMANTIC DEMENTIA; KNOWLEDGE; SELF; LOBE; WORDS; BRAIN; PERSONALITY; IMPAIRMENT; COGNITION AB Social concepts such as "tactless" or "honorable" enable us to describe our own as well as others' social behaviors. The prevailing view is that this abstract social semantic knowledge is mainly subserved by the same medial prefrontal regions that are considered essential for mental state attribution and self-reflection. Nevertheless, neurodegeneration of the anterior temporal cortex typically leads to impairments of social behavior as well as general conceptual knowledge. By using functional MRI, we demonstrate that the anterior temporal lobe represents abstract social semantic knowledge in agreement with this patient evidence. The bilateral superior anterior temporal lobes (Brodmann's area 38) are selectively activated when participants judge the meaning relatedness of social concepts (e.g., honor-brave) as compared with concepts describing general animal functions (e.g., nutritious-useful). Remarkably, only activity in the superior anterior temporal cortex, but not the medial prefrontal cortex, correlates with the richness of detail with which social concepts describe social behavior. Furthermore, this anterior temporal lobe activation is independent of emotional valence, whereas medial prefrontal regions show enhanced activation for positive social concepts. Our results demonstrate that the superior anterior temporal cortex plays a key role in social cognition by providing abstract conceptual knowledge of social behaviors. We further speculate that these abstract conceptual representations can be associated with different contexts of social actions and emotions through integration with frontolimbic circuits to enable flexible evaluations of social behavior. C1 NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. Univ Freiburg, Dept Psychiat & Psychotherapy, D-79104 Freiburg, Germany. Hosp Albert Einstein, Inst Israelita Ensino & Pesquisa, BR-05651901 Sao Paulo, Brazil. RP Grafman, J (reprint author), NINDS, NIH, Cognit Neurosci Sect, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov RI Zahn, Roland/C-4665-2008; Moll, Jorge/B-2654-2013; OI Zahn, Roland/0000-0002-8447-1453; Grafman, Jordan H./0000-0001-8645-4457 FU Intramural NIH HHS NR 63 TC 199 Z9 204 U1 3 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 10 PY 2007 VL 104 IS 15 BP 6430 EP 6435 DI 10.1073/pnas.0607061104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 157RG UT WOS:000245737500060 PM 17404215 ER PT J AU Xu, HZ Chertova, E Chen, JB Ott, DE Roser, JD Hu, WS Pathak, VK AF Xu, Hongzhan Chertova, Elena Chen, Jianbo Ott, David E. Roser, James D. Hu, Wei-Shau Pathak, Vinay K. TI Stoichiometry of the antiviral protein APOBEC3G in HIV-1 virions SO VIROLOGY LA English DT Article DE APOBEC3G virion incorporation; peripheral mononuclear blood cells; cytidine deamination; scintillation proximity assay; Delta vif virions ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL VIF PROTEIN; CYTIDINE DEAMINATION; CELLULAR-PROTEINS; TYPE-1; DNA; HYPERMUTATION; GAG; DEGRADATION; LYMPHOCYTES AB A host cytidine deaminase, APOBEC3G (A3G), inhibits replication of human immunodeficiency virus type I (HIV-1) by incorporating into virions in the absence of the virally encoded Vif protein (Delta vif virions), at least in part by causing G-to-A hypermutation. To gain insight into the antiretroviral function of A3G, we determined the quantities of A3G molecules that are incorporated in Delta vif virions. We combined three experimental approaches-reversed-phase high-pressure liquid chromatography (HPLC), scintillation proximity assay (SPA), and quantitative immunoblotting-to determine the molar ratio of A3G to HIV-1 capsid protein in Delta vif virions. Our studies revealed that the amount of the A3G incorporated into Delta vif virions was proportional to the level of its expression in the viral producing cells, and the ratio of the A3G to Gag in the Delta vif virions produced from activated human peripheral blood mononuclear cells (PBMC) was approximately 1:439. Based on previous estimates of the stoichiometry of HIV-1 Gag in virions (1400-5000), we conclude that approximately 7 (+/- 4) molecules of A3G are incorporated into Delta vif virions produced from human PBMCs. These results indicate that virion incorporation of only a few molecules of A3G is sufficient to inhibit HIV-1 replication. Published by Elsevier Inc. C1 Natl Canc Ctr, Ctr Canc Res, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. Natl Canc Inst, SAIC Frederick Inc, AIDS Vaccine Program, Frederick, MD 21702 USA. Natl Canc Inst, Viral Recominat Sect, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Pathak, VK (reprint author), Natl Canc Ctr, Ctr Canc Res, Viral Mutat Sect, HIV Drug Resistance Program, POB B,Bldg 535,Rm 334, Frederick, MD 21702 USA. EM vpathak@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 44 TC 65 Z9 67 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2007 VL 360 IS 2 BP 247 EP 256 DI 10.1016/j.virol.2006.10.036 PG 10 WC Virology SC Virology GA 155GO UT WOS:000245566100001 PM 17126871 ER PT J AU Jones, FD Hughes, SH AF Jones, Fatima D. Hughes, Stephen H. TI In vitro analysis of the effects of mutations in the G-tract of the human immunodeficiency virus type 1 polypurine tract on RNase H cleavage specificity SO VIROLOGY LA English DT Article DE HIV-1; polypurine tract; PPT; ribonuclease J; RNase J; G-tract; G-box ID HIV-1 REVERSE-TRANSCRIPTASE; MURINE LEUKEMIA-VIRUS; SEQUENCE FEATURES IMPORTANT; STRAND DNA-SYNTHESIS; RNA/DNA HYBRIDS; RIBONUCLEASE-H; REPLICATION; PRIMER; REGION; HYDROLYSIS AB The recognition and precise cleavage of the polypurine tract (PPT) of the human immunodeficiency virus type I (HIV-1) is an essential step in HIV-1 reverse transcription. The accurate cleavage, and the subsequent removal, of the PPT by the RNase H activity of HIV-1 RT defines the left end of the double-stranded viral DNA genome, the substrate for integration into the host genome. Previous analyses have shown that mutations in the 3'-end (G-tract) of the PPT cause alterations in RNase H cleavage specificity. In particular, mutations at positions 2 and 5 in the G-tract increased the frequency of retention of PPT sequences in the 2-LTR circle junction. To better understand why these mutations affected PPT cleavage in vivo, we analyzed the cleavage of PPT substrates in vitro that contained altered sequences and unusual base substitutions. Our results, herein, confirm that mutations at positions 2 and 5 of the G-tract do significantly alter the cleavage specificity at the PPT/U3 junction, and further suggest that the miscleavages observed in vivo were due to an improper generation of the PPT primer, as opposed to its improper removal. Finally, our results point to the structure of the PPT, rather than the base-specific contacts between the PPT and HIV-1 RT, as the primary determinants of RNase H cleavage specificity at the PPT/U3 junction. (c) 2006 Elsevier Inc. All rights reserved. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Room 130A, Frederick, MD 21702 USA. EM hughes@ncifcrf.gov FU Intramural NIH HHS NR 31 TC 8 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2007 VL 360 IS 2 BP 341 EP 349 DI 10.1016/j.virol.2006.10.008 PG 9 WC Virology SC Virology GA 155GO UT WOS:000245566100010 PM 17123564 ER PT J AU Lee, SK Boyko, V Hu, WS AF Lee, Sook-Kyung Boyko, Vitaly Hu, Wei-Shau TI Capsid is an important determinant for functional complementation of murine leukemia virus and spleen necrosis virus Gag proteins SO VIROLOGY LA English DT Article DE retroviruses; capsid; infectivity; coassembly; complementation; phenotypic mixing ID ROUS-SARCOMA-VIRUS; NUCLEOCAPSID PROTEIN; EARLY EVENTS; REVERSE TRANSCRIPTION; FLUORESCENT PROTEIN; VIRAL-DNA; RETROVIRAL REPLICATION; TERMINAL DOMAIN; IN-VIVO; RNA AB In this report, we examined the abilities and requirements of heterologous Gag proteins to functionally complement each other to support viral replication. Two distantly related gammaretroviruses, murine leukemia virus (MLV) and spleen necrosis virus (SNV), were used as a model system because SNV proteins can support MLV vector replication. Using chimeric or mutant Gag proteins that could not efficiently support MLV vector replication, we determined that a homologous capsid (CA) domain was necessary for the functional complementation of MLV and SNV Gag proteins. Findings from the bimolecular fluorescence complementation assay revealed that MLV and SNV Gag proteins were capable of colocalizing and interacting in cells. Taken together, our results indicated that MLV and SNV Gag proteins can interact in cells; however, a homologous CA domain is needed for functional complementation of MLV and SNV Gag proteins to complete virus replication. This requirement of homologous Gag most likely occurs at a postassembly step(s) of the viral replication. Published by Elsevier Inc. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM whu@ncifcrf.gov FU Intramural NIH HHS [Z01 BC010506-05] NR 62 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2007 VL 360 IS 2 BP 388 EP 397 DI 10.1016/j.virol.2006.10.038 PG 10 WC Virology SC Virology GA 155GO UT WOS:000245566100014 PM 17156810 ER PT J AU Li, X Gold, B O'hUigin, C Diaz-Griffero, F Song, B Si, ZH Li, Y Yuan, W Stremlau, M Mische, C Javanbakht, H Scally, M Winkler, C Dean, M Sodroski, J AF Li, Xing Gold, Bert O'hUigin, Cohn Diaz-Griffero, Felipe Song, Byeongwoon Si, Zhihai Li, Yuan Yuan, Wen Stremlau, Matthew Mische, Claudia Javanbakht, Hassan Scally, Mark Winkler, Cheryl Dean, Michael Sodroski, Joseph TI Unique features of TRIM5 alpha among closely related human TRIM family members SO VIROLOGY LA English DT Article DE tripartite motif; restriction factor; retrovirus; nonsynonymous/synonymous; positive selection; capsid binding; B30.2(SPRY) domain; RING; RBCC ID IMMUNODEFICIENCY-VIRUS TYPE-1; RESTRICTION FACTOR TRIM5-ALPHA; COILED-COIL DOMAINS; RETROVIRAL RESTRICTION; POSTENTRY RESTRICTION; PRIMATE TRIM5-ALPHA; MONKEY TRIM5-ALPHA; CYTOPLASMIC BODIES; ADAPTIVE EVOLUTION; MOLECULAR-CLONING AB The tripartite motif (TRIM) protein, TRIM5 alpha, restricts some retroviruses, including human immunodeficiency virus (HIV-1), from infecting the cells of particular species. TRIM proteins contain RING, B-box, coiled-coil and, in some cases, B30.2(SPRY) domains. We investigated the properties of human TRIM family members closely related to TRIM5. These TRIM proteins, like TRIM5 alpha, assembled into homotrimers and colocalized in the cytoplasm with TRIM5 alpha. TRIM5 alpha turned over more rapidly than related TRIM proteins. TRIM5 alpha, TRIM34 and TRIM6 associated with HIV-1 capsid-nucleocapsid complexes assembled in vitro; the TRIM5 alpha and TRIM34 interactions with these complexes were dependent on their B30.2(SPRY) domains. Only TRIM5 alpha potently restricted infection by the retroviruses studied; overexpression of TRIM34 resulted in modest inhibition of simian immunodeficiency virus (SIVmac) infection. In contrast to the other TRIM genes examined, TRIM5 exhibited evidence of positive selection. The unique features of TRIM5 alpha among its TRIM relatives underscore its special status as an antiviral factor. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. RP Sodroski, J (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM joseph_sodroski@dfci.harvard.edu RI Li, Xing/D-3852-2009; Dean, Michael/G-8172-2012; Li, Yuan/B-4098-2013 OI Dean, Michael/0000-0003-2234-0631; FU NHLBI NIH HHS [HL54785]; NIAID NIH HHS [AI063987, AI28691, R01 AI063987] NR 61 TC 44 Z9 53 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2007 VL 360 IS 2 BP 419 EP 433 DI 10.1016/j.virol.2006.10.035 PG 15 WC Virology SC Virology GA 155GO UT WOS:000245566100017 PM 17156811 ER PT J AU Chen, ZG Schiffman, M Herrero, R DeSalle, R Burk, RD AF Chen, Zigui Schiffman, Mark Herrero, Rolando DeSalle, Rob Burk, Robert D. TI Human papillomavirus (HPV) types 101 and 103 isolated from cervicovaginal cells lack an E6 open reading frame (ORF) and are related to gamma-papillomaviruses SO VIROLOGY LA English DT Article DE human papillomavirus; novel type; complete genome; phylogeny; molecular clock ID CERVICAL-CANCER; OVERLAPPING PCR; HEALTHY SKIN; TRANSCRIPTION; SEQUENCE; CLASSIFICATION; PREVALENCE; EVOLUTION; GENES; SITES AB Complete genomes of HPV101 and HPV103 were PCR amplified and cloned from cervicovaginal cells of a 34-year-old female with cervical intraepithelial neoplasia grade 3 (CIN 3) and a 30-year-old female with a normal Pap test, respectively. HPV101 and HPV103 contain 4 early genes (E7, El, E2, and E4) and 2 late genes (L2 and L1), but both lack the canonical E6 ORE Pairwise alignment similarity of the L1 ORE nucleotide sequences of HPV101 and HPV103 indicated that they are at least 30% dissimilar to each other and all known PVs. However, similarities of the other ORFs (E7, El, E2, and L2) indicated that HPV101 and HPV103 are most related to each other. Phylogenetic analyses revealed that these two types form a rnonophyletic clade, clustering together with the gamma- and pi-PV groups. These data demonstrated that HPV genomes closely related to papillomaviruses identified from cutaneous epithelia can be isolated from the genital mucosal region. Moreover, this is the first report of HPVs lacking an E6 ORF and phylogenetic evidence suggests this occurred subsequent to their emergence from the gamma-/pi-PVs. (c) 2006 Elsevier Inc. All rights reserved. C1 Yeshiva Univ, Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, Bronx, NY 10461 USA. NCI, Div Canc Epidemiol & Genet, US Dept HHS, Bethesda, MD 20892 USA. Costa Rica Fdn Hlth Sci, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY 10024 USA. Yeshiva Univ, Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pediat Epidemiol & Populat Hlth, Bronx, NY 10461 USA. RP Burk, RD (reprint author), Yeshiva Univ, Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Microbiol & Immunol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM burk@aecom.yu.edu RI Chen, Zigui/E-8490-2017 FU NCI NIH HHS [CA78527, R01 CA078527, U01 CA078527] NR 29 TC 41 Z9 44 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2007 VL 360 IS 2 BP 447 EP 453 DI 10.1016/j.virol.2006.10.022 PG 7 WC Virology SC Virology GA 155GO UT WOS:000245566100019 PM 17125811 ER PT J AU Harris, EL McLaren, CE Reboussin, DM Gordeuk, VR Barton, JC Acton, RT McLaren, GD Vogt, TM Snively, BM Leiendecker-Foster, C Holup, JL Passmore, LV Eckfeldt, JH Lin, E Adams, PC AF Harris, Emily L. McLaren, Christine E. Reboussin, David M. Gordeuk, Victor R. Barton, James C. Acton, Ronald T. McLaren, Gordon D. Vogt, Thomas M. Snively, Beverly M. Leiendecker-Foster, Catherine Holup, Joan L. Passmore, Leah V. Eckfeldt, John H. Lin, Edward Adams, Paul C. TI Serum ferritin and transferrin saturation in Asians and pacific islanders SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID IRON-OVERLOAD; CHRONIC HEPATITIS; UNITED-STATES; HEMOCHROMATOSIS; DISEASE; POPULATION; MUTATIONS; HEALTH AB Background: Asians and Pacific Islanders in the Hemochromatosis and Iron Overload Screening (HEIRS) Study had the highest prevalence of elevated serum ferritin (SF) and transferrin saturation (TS) levels, but to our knowledge, the reasons for this have not been investigated. Methods: Using multiple linear regression, we compared TS and SF distributions for 42 720 Asian, Pacific Islander, and white HEIRS Study participants recruited through 5 field centers in North America who did not have HFE C282Y or H63D alleles. Results: Compared with their white counterparts, Asian men had a 69-ng/mL (155-pmol/L) higher adjusted mean SF level and a 3% higher TS level (P<.001); Asian women had 23-ng/mL (52-pmol/L) higher adjusted mean SF level and a 3% higher TS level (P<.001). The mean TS level of Asian women was higher than that of Pacific Islander women, and the mean SF level of Pacific Islander men was significantly higher than that of white men. These differences remained significant after adjusting for self-reported history of diabetes or liver disease. Additional information for selected participants suggested that these differences are largely unrelated to mean corpuscular volume less than 80 fL, body mass index, or self-reported alcohol intake. Available liver biopsy and phlebotomy data indicated that iron overload is probably uncommon in Asian participants. Conclusion: Higher TS and SF levels in persons of Asian or Pacific island heritage may need to be interpreted differently than for whites, although the biological basis and clinical significance of higher levels among Asians and Pacific Islanders are unclear. C1 Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Univ Calif Irvine, Irvine, CA 92717 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Howard Univ, Washington, DC 20059 USA. So Iron Disorders Ctr, Birmingham, AL USA. Univ Alabama, Birmingham, AL USA. Dept Vet Affairs, Long Beach Healthcare Syst, Long Beach, CA USA. Univ Minnesota, Med Ctr, Fairview, MN USA. Centenary Hlth Ctr, Rouge Valley Hlth Syst, Toronto, ON, Canada. London Hlth Sci Ctr, London, ON, Canada. RP Harris, EL (reprint author), NHGRI, NIH, 5635 Fisher Ln,Suite 4076,MSC 9305, Bethesda, MD 20892 USA. EM harrisel@mail.nih.gov FU NCRR NIH HHS [M01 RR 000827, M01 RR 10284, M01 RR 00032]; NHLBI NIH HHS [N01 HC 05192, N01 HC 05186, N01 HC 05189, N01 HC 05190, N01 HC 05188, N01 HC 05185, UH1 HL 03679-05, N01 HC 05191] NR 19 TC 25 Z9 25 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 9 PY 2007 VL 167 IS 7 BP 722 EP 726 DI 10.1001/archinte.167.7.722 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 156DQ UT WOS:000245628700015 PM 17420432 ER PT J AU Berezhkovskii, AM Pustovoit, MA Bezrukov, SM AF Berezhkovskii, A. M. Pustovoit, M. A. Bezrukov, S. M. TI Diffusion in a tube of varying cross section: Numerical study of reduction to effective one-dimensional description SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PERIODIC POROUS MATERIALS; RELEASE; PORES AB Brownian dynamics simulations of the particle diffusing in a long conical tube (the length of the tube is much greater than its smallest radius) are used to study reduction of the three-dimensional diffusion in tubes of varying cross section to an effective one-dimensional description. The authors find that the one-dimensional description in the form of the Fick-Jacobs equation with a position-dependent diffusion coefficient, D(x), suggested by Zwanzig [J. Phys. Chem. 96, 3926 (1992)], with D(x) given by the Reguera-Rubi formula [Phys. Rev. E 64, 061106 (2001)], D(x)=D/root 1+R-'(x)(2), where D is the particle diffusion coefficient in the absence of constraints, and R(x) is the tube radius at x, is valid when vertical bar R-'(x)vertical bar <= 1. When vertical bar R-'(x)vertical bar>1, higher spatial derivatives of the one-dimensional concentration in the effective diffusion equation cannot be neglected anymore as was indicated by Kalinay and Percus [J. Chem. Phys. 122, 204701 (2005)]. Thus the reduction to the effective one-dimensional description is a useful tool only when vertical bar R-'(x)vertical bar <= 1 since in this case one can apply the powerful standard methods to analyze the resulting diffusion equation. (c) 2007 American Institute of Physics. C1 Natl Inst Hlth, Math & Stat Comp Lab, Div Computat Biosci, Bethesda, MD 20892 USA. NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188300, Russia. RP Berezhkovskii, AM (reprint author), Natl Inst Hlth, Math & Stat Comp Lab, Div Computat Biosci, Bethesda, MD 20892 USA. RI Pustovoit, Mark/B-5249-2008 FU Intramural NIH HHS NR 22 TC 87 Z9 87 U1 1 U2 15 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD APR 7 PY 2007 VL 126 IS 13 AR 134706 DI 10.1063/1.2719193 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 154MT UT WOS:000245512400046 PM 17430055 ER PT J AU Kono, M Belyantseva, IA Skoura, A Frolenkov, GI Starost, MF Dreier, JL Lidington, D Bolz, SS Friedman, TB Hla, T Proia, RL AF Kono, Mari Belyantseva, Inna A. Skoura, Athanasia Frolenkov, Gregory I. Starost, Matthew F. Dreier, Jennifer L. Lidington, Darcy Bolz, Steffen-Sebastian Friedman, Thomas B. Hla, Timothy Proia, Richard L. TI Deafness and stria Vascularis defects in S1P(2) receptor-null mice SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR; INNER-EAR; TIGHT JUNCTIONS; ENDOTHELIAL-CELLS; MOUSE; SPHINGOSINE-1-PHOSPHATE; DYSFUNCTION; MATURATION; HEARING AB The S1P(2) receptor is a member of a family of G protein-coupled receptors that bind the extracellular sphingolipid metabolite sphingosine 1-phosphate with high affinity. The receptor is widely expressed and linked to multiple G protein signaling pathways, but its physiological function has remained elusive. Here we have demonstrated that S1P(2) receptor expression is essential for proper functioning of the auditory and vestibular systems. Auditory brainstem response analysis revealed that S1P(2) receptor-null mice were deaf by one month of age. These null mice exhibited multiple inner ear pathologies. However, some of the earliest cellular lesions in the cochlea were found within the stria vascularis, a barrier epithelium containing the primary vasculature of the inner ear. Between 2 and 4 weeks after birth, the basal and marginal epithelial cell barriers and the capillary bed within the stria vascularis of the S1P(2) receptor-null mice showed markedly disturbed structures. JTE013, an S1P(2) receptor-specific antagonist, blocked the S1P-induced vasoconstriction of the spiral modiolar artery, which supplies blood directly to the stria vascularis and protects its capillary bed from high perfusion pressure. Vascular disturbance within the stria vascularis is a potential mechanism that leads to deafness in the S1P(2) receptor-null mice. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. NIDCD, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Univ Connecticut, Ctr Hlth, Ctr Vasc Biol, Dept Cell Biol, Farmington, CT 06030 USA. NIH, Div Vet Resources, Bethesda, MD 20892 USA. Univ Toronto, Dept Physiol & Heart & Stroke, Richard Lewar Ctr Excellence, Toronto, ON M5S 1A8, Canada. NIDCD, Otolaryngol Branch, NIH, Rockville, MD 20850 USA. RP Proia, RL (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. EM proia@nih.gov RI Proia, Richard/A-7908-2012; Hla, Timothy/G-5873-2012; OI Hla, Timothy/0000-0001-8355-4065; Frolenkov, Gregory/0000-0002-9810-5024 FU Intramural NIH HHS; NHLBI NIH HHS [R37-HL-67330, P01-HL-70694] NR 30 TC 101 Z9 104 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2007 VL 282 IS 14 BP 10690 EP 10696 DI 10.1074/jbc.M700370200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LB UT WOS:000245941000063 PM 17284444 ER PT J AU Zhu, WZ Woo, AYH Yang, DM Cheng, HP Crow, MT Xiao, RP AF Zhu, Weizhong Woo, Anthony Yiu-Ho Yang, Dongmei Cheng, Heping Crow, Michael T. Xiao, Rui-Ping TI Activation of CaMKII delta C is a common intermediate of diverse death stimuli- induced heart muscle cell apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE; CALMODULIN KINASE; CARDIAC MYOCYTES; BETA(1)-ADRENERGIC STIMULATION; PHOSPHOLAMBAN PHOSPHORYLATION; DILATED CARDIOMYOPATHY; DEPENDENT FACILITATION; VENTRICULAR MYOCYTES; CALCIUM-CHANNELS; HYPERTROPHY AB Ca2+-calmodulin-dependent protein kinase II ( CaMKII) is expressed in many mammalian cells, with the delta isoform predominantly expressed in cardiomyocytes. Previous studies have shown that inhibition of CaMKII protects cardiomyocytes against beta(1)-adrenergic receptor-mediated apoptosis. However, it is unclear whether activation of CaMKII is sufficient to cause cardiomyocyte apoptosis and whether CaMKII signaling is important in heart muscle cell apoptosis mediated by other stimuli. Here, we specifically enhanced or suppressed CaMKII activity using adenoviral gene transfer of constitutively active ( CA-CaMKII delta C) or dominant negative ( DN-CaMKII delta C) mutants of CaMKII delta C in cultured adult rat cardiomyocytes. Expression of CA-CaMKII delta C promoted cardiomyocyte apoptosis that was associated with increased mitochondrial cytochrome c release and attenuated by co-expression of Bcl-XL. Importantly, isoform-specific suppression of CaMKII delta C with the DN-CaMKII delta C mutant similar to nonselective CaMKII inhibition by the pharmacological inhibitors ( KN-93 or AIP) not only prevented CA-CaMKII delta C-mediated apoptosis but also protected cells from multiple death-inducing stimuli. Thus, activation of CaMKII delta C constitutes a common intermediate by which various death-inducing stimuli trigger cardiomyocyte apoptosis via the primary mitochondrial death pathway. C1 NIA, Cardiovasc Sci Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. Johns Hopkins Univ, Dept Med, Baltimore, MD 21224 USA. RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM XiaoR@GRC.NIA.NIH.GOV RI Woo, Anthony/D-4305-2014 OI Woo, Anthony/0000-0003-0662-698X FU Intramural NIH HHS; NHLBI NIH HHS [HL073935] NR 38 TC 72 Z9 79 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 6 PY 2007 VL 282 IS 14 BP 10833 EP 10839 DI 10.1074/jbc.M611507200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 160LB UT WOS:000245941000077 PM 17296607 ER PT J AU Lee, D Walsh, JD Yu, P Markus, MA Choli-Papadopoulou, T Schwieters, CD Krueger, S Draper, DE Wang, YX AF Lee, Donghan Walsh, Joseph D. Yu, Ping Markus, Michelle A. Choli-Papadopoulou, Theodora Schwieters, Charles D. Krueger, Susan Draper, David E. Wang, Yun-Xing TI The structure of free L11 and functional dynamics of L11 in free, L11-rRNA(58 nt) binary and L11-rRNA(58 nt)-thiostrepton ternary complexes SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE ribosome protein; thiostrepton inhibition; dynamics; NMR; L11 ID SMALL-ANGLE SCATTERING; RIBOSOMAL-PROTEIN L11; X-RAY-SCATTERING; ROTATIONAL DIFFUSION ANISOTROPY; RNA TERTIARY STRUCTURE; N-TERMINAL-DOMAIN; CRYSTAL-STRUCTURE; BIOLOGICAL MACROMOLECULES; NEUTRON-SCATTERING; CHEMICAL-EXCHANGE AB The L11 binding site is one of the most important functional sites in the ribosome. The N-terminal domain of L11 has been implicated as a "reversible switch" in facilitating the coordinated movements associated with EF-G-driven GTP hydrolysis. The reversible switch mechanism has been hypothesized to require conformational flexibility involving reorientation and re-positioning of the two L11 domains, and warrants a close examination of the structure and dynamics of L11. Here we report the solution structure of free 1,11, and relaxation studies of free L11, L11 complexed to its 58 nt RNA recognition site, and L11 in a ternary complex with the RNA and thiostrepton antibiotic. The binding site of thiostrepton on L11 was also defined by analysis of structural and dynamics data and chemical shift mapping. The conclusions of this work are as follows: first, the binding of L11 to RNA leads to sizable conformation changes in the regions flanking the linker and in the hinge area that links a beta-sheet and a 3(10)-helix-turn-helix element in the N terminus. Concurrently, the change in the relative orientation may lead to re-positioning of the N terminus, as implied by a decrease of radius of gyration from 18.5 angstrom to 16.2 angstrom. Second, the regions, which undergo large conformation changes, exhibit motions on milliseconds-microseconds or nanoseconds-picoseconds time scales. Third, binding of thiostrepton results in more rigid conformations near the linker (Thr71) and near its putative binding site (Leu12). Lastly, conformational changes in the putative thiostrepton binding site are implicated by the re-emergence of cross-correlation peaks in the spectrum of the ternary complex, which were missing in that of the binary complex. Our combined analysis of both the chemical shift perturbation and dynamics data clearly indicates that thiostrepton binds to a pocket involving residues in the 3(10)-helix in L11. (c) 2007 Elsevier Ltd. All rights reserved. C1 NCI, Prot Nucl Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Wyeth Ayerst Res, Struct Biol & Computat Chem, Cambridge, MA 02140 USA. Aristotle Univ Thessaloniki, Biochem Lab, Sch Chem, GR-54006 Thessaloniki, Greece. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. Johns Hopkins Univ, Dept Chem, Baltimore, MD 21218 USA. RP Wang, YX (reprint author), NCI, Prot Nucl Acid Interact Sect, Struct Biophys Lab, NIH, Frederick, MD 21702 USA. EM wangyu@ncifcrf.gov RI Lee, Donghan/B-6893-2011; OI Lee, Donghan/0000-0002-3971-986X; Lee, Donghan/0000-0002-6530-8060 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 67 TC 23 Z9 25 U1 1 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 6 PY 2007 VL 367 IS 4 BP 1007 EP 1022 DI 10.1016/j.jmb.2007.01.013 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 154LG UT WOS:000245508000008 PM 17292917 ER PT J AU Malkin, E Long, CA Stowers, AW Zou, LL Singh, S MacDonald, NJ Narum, DL Miles, AP Orcutt, AC Muratova, O Moretz, SE Zhou, H Diouf, A Fay, M Tierney, E Leese, P Mahanty, S Miller, LH Saul, A Martin, LB AF Malkin, Elissa Long, Carole A. Stowers, Anthony W. Zou, Lanling Singh, Sanjay MacDonald, Nicholas J. Narum, David L. Miles, Aaron P. Orcutt, Andrew C. Muratova, Olga Moretz, Samuel E. Zhou, Hong Diouf, Ababacar Fay, Michael Tierney, Eveline Leese, Philip Mahanty, Siddhartha Miller, Louis H. Saul, Allan Martin, Laura B. TI Phase 1 study of two merozoite surface protein 1 (MSP142) vaccines for Plasmodium falciparum malaria SO PLOS CLINICAL TRIALS LA English DT Article ID BLOOD-STAGE VACCINE; C-TERMINAL FRAGMENT; B-CELL EPITOPES; SEQUENCE DIVERSITY; CLINICAL IMMUNITY; SERUM ANTIBODIES; GAMMA-GLOBULIN; IN-VITRO; T-CELL; TRIAL AB Objectives: To assess the safety and immunogenicity of two vaccines, MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel, targeting blood-stage Plasmodium falciparum parasites. Design: A Phase 1 open-label, dose-escalating study. Setting: Quintiles Phase 1 Services, Lenexa, Kansas between July 2004 and November 2005. Participants: Sixty healthy malaria-naive volunteers 18-48 y of age. Interventions: The C-terminal 42-kDa region of merozoite surface protein 1 (MSP1(42)) corresponding to the two allelic forms present in FVO and 3D7 P. falciparum lines were expressed in Escherichia coli, refolded, purified, and formulated on Alhydrogel (aluminum hydroxide). For each vaccine, volunteers in each of three dose cohorts (5, 20, and 80 mu g) were vaccinated at 0, 28, and 180 d. Volunteers were followed for 1 y. Outcome Measures: The safety of MSP1(42)-FVO/Alhydrogel and MSP1(42)-3D7/Alhydrogel was assessed. The antibody response to each vaccine was measured by reactivity to homologous and heterologous MSP1(42), MSP1(19), and MSP1(33) recombinant proteins and recognition of FVO and 3D7 parasites. Results: Anti-MSP1(42) antibodies were detected by ELISA in 20/27 (74%) and 22/27 (81%) volunteers receiving three vaccinations of MSP1(42)-FVO/Alhydrogel or MSP1(42)-3D7/Alhydrogel, respectively. Regardless of the vaccine, the antibodies were cross-reactive to both MSP1(42)- FVO and MSP1(42)-3D7 proteins. The majority of the antibody response targeted the C-terminal 19-kDa domain of MSP1(42), although low-level antibodies to the N-terminal 33-kDa domain of MSP1(42) were also detected. Immunofluorescence microscopy of sera from the volunteers demonstrated reactivity with both FVO and 3D7 P. falciparum schizonts and free merozoites. Minimal in vitro growth inhibition of FVO or 3D7 parasites by purified IgG from the sera of the vaccinees was observed. Conclusions: The MSP1(42)/Alhydrogel vaccines were safe and well tolerated but not sufficiently immunogenic to generate a biologic effect in vitro. Addition of immunostimulants to the Alhydrogel formulation to elicit higher vaccine-induced responses in humans may be required for an effective vaccine. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. Quintiles Phase 1 Serv, Lenexa, KS USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. PATH Malaria Vaccine Initiat, Bethesda, MD USA. RP Martin, LB (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD USA. EM LMartin@niaid.nih.gov RI Saul, Allan/I-6968-2013; Martin, Laura/N-1789-2013; OI Saul, Allan/0000-0003-0665-4091; Martin, Laura/0000-0002-4431-4381; Fay, Michael P./0000-0002-8643-9625 NR 40 TC 50 Z9 53 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1555-5887 J9 PLOS CLIN TRIALS JI PLos Clin. Trials PD APR 6 PY 2007 VL 2 IS 4 AR e12 DI 10.1371/journal.pctr.0020012 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 171LC UT WOS:000246736500001 PM 17415408 ER PT J AU Sutter, NB Bustamante, CD Chase, K Gray, MM Zhao, KY Zhu, L Padhukasahasram, B Karlins, E Davis, S Jones, PG Quignon, P Johnson, GS Parker, HG Fretwell, N Mosher, DS Lawler, DF Satyaraj, E Nordborg, M Lark, KG Wayne, RK Ostrander, EA AF Sutter, Nathan B. Bustamante, Carlos D. Chase, Kevin Gray, Melissa M. Zhao, Keyan Zhu, Lan Padhukasahasram, Badri Karlins, Eric Davis, Sean Jones, Paul G. Quignon, Pascale Johnson, Gary S. Parker, Heidi G. Fretwell, Neale Mosher, Dana S. Lawler, Dennis F. Satyaraj, Ebenezer Nordborg, Magnus Lark, K. Gordon Wayne, Robert K. Ostrander, Elaine A. TI A single IGF1 allele is a major determinant of small size in dogs SO SCIENCE LA English DT Article ID DOMESTIC DOG; WILD CANIDS; BODY-SIZE; MORPHOLOGICAL CHANGE; POSTNATAL-GROWTH; ORIGINS; GENE AB The domestic dog exhibits greater diversity in body size than any other terrestrial vertebrate. We used a strategy that exploits the breed structure of dogs to investigate the genetic basis of size. First, through a genome-wide scan, we identified a major quantitative trait locus (QTL) on chromosome 15 influencing size variation within a single breed. Second, we examined genetic variation in the 15-megabase interval surrounding the QTL in small and giant breeds and found marked evidence for a selective sweep spanning a single gene (IGF1), encoding insulin-like growth factor 1. A single IGF1 single-nucleotide polymorphism haplotype is common to all small breeds and nearly absent from giant breeds, suggesting that the same causal sequence variant is a major contributor to body size in all small dogs. C1 NHGRI, Bethesda, MD 20892 USA. Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY 14850 USA. Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. Univ Calif Los Angeles, Dept Ecol & Environm Biol, Los Angeles, CA 90095 USA. Univ So Calif, Dept Mol & Computat Biol, Los Angeles, CA 90089 USA. WALTHAM Ctr Pet Nutr, Melton Mowbray LE14 4RT, Leics, England. Univ Missouri, Dept Vet Pathobiol, Columbia, MO 65211 USA. Nestle Res Ctr NRC STL, St Louis, MO 63164 USA. RP Ostrander, EA (reprint author), NHGRI, Bldg 50,Room 5349,50 S Dr MSC 8000, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov RI Gray, Melissa/B-5025-2008; Parker, Heidi/C-6954-2008; OI Gray, Melissa/0000-0002-1756-5468; Davis, Sean/0000-0002-8991-6458; Ostrander, Elaine/0000-0001-6075-9738 FU NHGRI NIH HHS [5T32 HG002536, P50 HG002790]; NIGMS NIH HHS [R01 GM063056, R01 GM063056-06]; PHS HHS [063056] NR 28 TC 327 Z9 339 U1 4 U2 92 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD APR 6 PY 2007 VL 316 IS 5821 BP 112 EP 115 DI 10.1126/science.1137045 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 153XD UT WOS:000245470500044 PM 17412960 ER PT J AU Gornick, MC Addington, A Shaw, P Bobb, AJ Sharp, W Greenstein, D Arepalli, S Castellanos, FX Rapoport, JL AF Gornick, M. C. Addington, Anjene Shaw, P. Bobb, A. J. Sharp, W. Greenstein, D. Arepalli, S. Castellanos, F. X. Rapoport, J. L. TI Association of the dopamine receptor D4 (DRD4) gene 7-repeat allele with children with attention-deficit/hyperactivity disorder (ADHD): An update SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE genetic association; transmission disequilibrium test; quantitative TDT ID DEFICIT HYPERACTIVITY DISORDER; TRANSPORTER GENE; REPEAT POLYMORPHISM; GENOMEWIDE SCAN; RATING-SCALE; LINKAGE; SAMPLE; DISEQUILIBRIUM; ADOLESCENTS; PERFORMANCE AB d Polymorphisms of the dopamine receptor D4 gene DRD4, 11p15.5, have previously been associated with attention-deficit/hyperactivity disorder (ADHD) [Bobb et al., 2005; Am J Med Genet B Neuropsychiatr Genet 132:109-125; Faraone et al., 2005; Biol Psychiatry 57:1313-1323; Thapar et al., 2005; Hum Mol Genet 14 Spec No. 2:R275-R282]. As a follow up to a pilot study [see Castellanos et al., 1998; Mol Psychiatry 3:431434] consisting of 41 probands and 56 controls which found no significant association between the DRD4 7-repeat allele in exon 3 and ADHD, a greatly expanded study sample (cases n = 166 and controls n = 282) and long term follow-up (n = 107, baseline mean age n = 9, follow-up mean age of n = 15) prompted reexamination of this gene. The DRD4 7-repeat allele was significantly more frequent in ADHD cases than controls (OR = 1.2; P = 0.028). Further, within the ADHD group, the 7-repeat allele was associated with better cognitive performance (measured by the WISC-III) (P = 0.013-0.07) as well as a trend for association with better long-term outcome. This provides further evidence of the role of the DRD4 7-repeat allele in the etiology of ADHD and suggests that this allele may be associated with a more benign form of the disorder. (c) 2006 Wiley-Liss, Inc. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NYU, Ctr Child Study, New York, NY USA. RP Addington, A (reprint author), NIMH, Child Psychiat Branch, NIH, 10 Ctr Dr,Bldg 10,Room 3N-202, Bethesda, MD 20892 USA. EM AddingtA@mail.nih.gov RI Shaw, Philip/A-1129-2008; OI Castellanos, Francisco/0000-0001-9192-9437 NR 43 TC 39 Z9 43 U1 1 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD APR 5 PY 2007 VL 144B IS 3 BP 379 EP 382 DI 10.1002/ajmg.b.30460 PG 4 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 156YU UT WOS:000245686600023 PM 17171657 ER PT J AU Saroff, HA AF Saroff, Harry A. TI The Nernst equation applied to oxidation-reduction reactions in myoglobin and hemoglobin. Evaluation of the parameters SO BIOPOLYMERS LA English DT Article DE mathematical model; myoglobin; hemoglobin; oxidation-reduction; Nernst equation AB Analyses of the binding of oxygen to monomers such as myoglobin employ the Mass Action equation. The Mass Action equation, as such, is not directly applicable for the analysis of the binding of oxygen to oligomers such as hemoglobin. When the binding of oxygen to hemoglobin is analyzed, models incorporating extensions of mass action are employed. Oxidation-reduction reactions of the heme group in myoglobin and hemoglobin involve the binding and dissociation of electrons. This reaction is described with the Nernst equation. The Nernst equation is applicable only to a monomeric species even if the number of electrons involved is greater than unity. To analyze the oxidation-reduction reaction in a molecule such as hemoglobin a model is required which incorporates extensions of the Nernst equation. This communication develops models employing the Nernst equation for oxidation-reduction reactions analogous to those employed for hemoglobin in the analysis of the oxygenation (binding of oxygen) reaction. (c) 2006 Wiley Periodicals, Inc. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Saroff, HA (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM saroff@helix.nih.gov NR 8 TC 2 Z9 2 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD APR 5 PY 2007 VL 85 IS 5-6 BP 450 EP 455 DI 10.1002/bip.20652 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 151OB UT WOS:000245298900008 PM 17154397 ER PT J AU Garcia-Closas, M Brinton, LA Lissowska, J Richesson, D Sherman, ME Szeszenia-Dabrowska, N Peplonska, B Welch, R Yeager, M Zatonski, W Chanock, SJ AF Garcia-Closas, Montserrat Brinton, Louise A. Lissowska, Jolanta Richesson, Douglas Sherman, Mark E. Szeszenia-Dabrowska, Neonila Peplonska, Beata Welch, Robert Yeager, Meredith Zatonski, Witold Chanock, Stephen J. TI Ovarian cancer risk and common variation in the sex hormone-binding globulin gene: a population-based case-control study SO BMC CANCER LA English DT Article ID POSTMENOPAUSAL WOMEN; STEROID-HORMONES; SHBG GENE AB Background: The sex hormone-binding globulin ( SHBG) is a carrier protein that modulates the bio-availability of serum sex steroid hormones, which may be involved in ovarian cancer. We evaluated whether common genetic variation in SHBG and its 3' neighbor ATP1B2, in linkage disequilibrium, is associated with the risk of epithelial ovarian cancer. Methods: The study population included 264 women with ovarian carcinoma and 625 controls participating in a population-based case-control study in Poland. Five common single nucleotide polymorphisms ( SNPs) in SHGB and five in ATP1B2 were selected to capture most common variation in this region. Results: None of the SNPs evaluated was significantly associated with ovarian cancer risk, including the putative functional SNPs SHBG D356N (rs6259) and - 67G > A 5' UTR (rs1799941). However, our data were consistent with a decreased ovarian cancer risk associated with the variant alleles for these two SNPs, which have been previously associated with increased circulating levels of SHBG. Conclusion: These data do not support a substantial association between common genetic variation in SHBG and ovarian cancer risk. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20952 USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20952 USA. M Sklodowska Curie Inst Oncol & Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland. Nofer Inst Occupat Med, Dept Occupat & Environm Epidemiol, Lodz, Poland. RP Garcia-Closas, M (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Suite 550, Rockville, MD 20952 USA. EM montse@nih.gov; brintonl@exchange.nih.gov; lissowsj@coi.waw.pl; richessond@mail.nih.gov; shermanm@exchange.nih.gov; wies@porta.imp.lodz.pl; beatap@imp.lodz.pl; welchr@mail.nih.gov; yeagerm@mail.nih.gov; zatonskiw@coi.waw.pl; chanocks@exchange.nih.gov RI Peplonska, Beata/F-6004-2010; Perez , Claudio Alejandro/F-8310-2010; Szeszenia-Dabrowska, Neonila/F-7190-2010; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 12 TC 24 Z9 24 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD APR 5 PY 2007 VL 7 AR 60 DI 10.1186/1471-2407-7-60 PG 7 WC Oncology SC Oncology GA 166CK UT WOS:000246354600001 PM 17411440 ER PT J AU Dolman, NP More, JCA Alt, A Knauss, JL Pentikainen, OT Glasser, CR Bleakman, D Mayer, ML Collingridge, GL Jane, DE AF Dolman, Nigel P. More, Julia C. A. Alt, Andrew Knauss, Jody L. Pentikainen, Olli T. Glasser, Carla R. Bleakman, David Mayer, Mark L. Collingridge, Graham L. Jane, David E. TI Synthesis and pharmacological characterization of N-3-substituted willardiine derivatives: Role of the substituent at the 5-position of the uracil ring in the development of highly potent and selective GLU(K5) kainate receptor antagonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID SERINE BETA-LACTONES; LIGAND-BINDING CORE; ALPHA-AMINO-ACIDS; GLUTAMATE-RECEPTOR; CEREBRAL-ISCHEMIA; IN-VITRO; SYNAPTIC-TRANSMISSION; HIPPOCAMPAL-NEURONS; GENETIC ALGORITHM; ANIMAL-MODELS AB Some N-3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLU(K5) revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5-dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLU(K5)-containing kainate receptors (K-B values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLU(K5) and GLU(K5)/GLU(K2), respectively) but displayed IC50 values > 100 mu M for antagonism of GLU(A2), GLU(K6), or GLU(K6)/GLU(K2). C1 Univ Bristol, Sch Med Sci, Dept Pharmacol, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. Univ Bristol, Sch Med Sci, Dept Anat, MRC Ctr Synapt Plast, Bristol BS8 1TD, Avon, England. Eli Lilly & Co, Lilly Corp Ctr, Neurosci Res, Indianapolis, IN 46285 USA. NICHHD, Lab Cellular & Mol Neurophysiol, Porter Neurosci Res Ctr, US Dept HHS,NIH, Bethesda, MD 20892 USA. RP Jane, DE (reprint author), Univ Bristol, Sch Med Sci, Dept Pharmacol, MRC Ctr Synapt Plast, Univ Walk, Bristol BS8 1TD, Avon, England. EM david.jane@bristol.ac.uk RI Pentikainen, Olli/E-1980-2012; Mayer, Mark/H-5500-2013; Collingridge, Graham/C-4605-2015 OI Pentikainen, Olli/0000-0001-7188-4016; Collingridge, Graham/0000-0002-9572-5359 FU Biotechnology and Biological Sciences Research Council [BB/C507045/1]; Intramural NIH HHS NR 69 TC 43 Z9 43 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 5 PY 2007 VL 50 IS 7 BP 1558 EP 1570 DI 10.1021/jm061041u PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 150ZV UT WOS:000245259000015 PM 17348638 ER PT J AU Fenton, JJ Taplin, SH Carney, PA Abraham, L Sickles, EA D'Orsi, C Berns, EA Cutter, G Hendrick, RE Barlow, WE Elmore, JG AF Fenton, Joshua J. Taplin, Stephen H. Carney, Patricia A. Abraham, Linn Sickles, Edward A. D'Orsi, Carl Berns, Eric A. Cutter, Gary Hendrick, R. Edward Barlow, William E. Elmore, Joann G. TI Influence of computer-aided detection on performance of screening mammography SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Breast Cancer Surveillance Consoritium CY APR 24, 2006 CL Chapel Hill, NC ID CARCINOMA IN-SITU; DETECTION SYSTEM; ROC CURVE; BREAST; COMMUNITY; WOMEN; ACCURACY; MICROCALCIFICATIONS; RADIOLOGISTS; SENSITIVITY AB BACKGROUND Computer-aided detection identifies suspicious findings on mammograms to assist radiologists. Since the Food and Drug Administration approved the technology in 1998, it has been disseminated into practice, but its effect on the accuracy of interpretation is unclear. METHODS We determined the association between the use of computer-aided detection at mammography facilities and the performance of screening mammography from 1998 through 2002 at 43 facilities in three states. We had complete data for 222,135 women (a total of 429,345 mammograms), including 2351 women who received a diagnosis of breast cancer within 1 year after screening. We calculated the specificity, sensitivity, and positive predictive value of screening mammography with and without computer-aided detection, as well as the rates of biopsy and breast-cancer detection and the overall accuracy, measured as the area under the receiver-operating-characteristic (ROC) curve. RESULTS Seven facilities (16%) implemented computer-aided detection during the study period. Diagnostic specificity decreased from 90.2% before implementation to 87.2% after implementation (P<0.001), the positive predictive value decreased from 4.1% to 3.2% (P=0.01), and the rate of biopsy increased by 19.7% (P<0.001). The increase in sensitivity from 80.4% before implementation of computer-aided detection to 84.0% after implementation was not significant (P=0.32). The change in the cancer-detection rate (including invasive breast cancers and ductal carcinomas in situ) was not significant (4.15 cases per 1000 screening mammograms before implementation and 4.20 cases after implementation, P=0.90). Analyses of data from all 43 facilities showed that the use of computer-aided detection was associated with significantly lower overall accuracy than was nonuse (area under the ROC curve, 0.871 vs. 0.919; P=0.005). CONCLUSIONS The use of computer-aided detection is associated with reduced accuracy of interpretation of screening mammograms. The increased rate of biopsy with the use of computer-aided detection is not clearly associated with improved detection of invasive breast cancer. C1 Univ Calif Davis, Sacramento, CA 95817 USA. NCI, Bethesda, MD 20892 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Grp Hlth Cooperat Puget Sound, Seattle, WA 98121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Emory Clin, Atlanta, GA 30322 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Alabama, Birmingham, AL USA. Canc Res & Biostat, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. RP Fenton, JJ (reprint author), UC Davis Hlth Syst, Dept Family & Community Med, 4860 Y St,Ste 2300, Sacramento, CA 95817 USA. EM joshua.fenton@ucdmc.ucdavis.edu FU NCI NIH HHS [U01 CA063736, U01 CA69976, U01 CA069976, U01CA63736, R01 CA107623, R01 CA 107623, U01 CA086082, K05 CA104699, U01CA86082] NR 39 TC 213 Z9 218 U1 0 U2 10 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 5 PY 2007 VL 356 IS 14 BP 1399 EP 1409 DI 10.1056/NEJMoa066099 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 153GG UT WOS:000245419600003 PM 17409321 ER PT J AU Brauweiler, A Lorick, KL Lee, JP Tsai, YC Chan, D Weissman, AM Drabkin, HA Gemmill, RM AF Brauweiler, A. Lorick, K. L. Lee, J. P. Tsai, Y. C. Chan, D. Weissman, A. M. Drabkin, H. A. Gemmill, R. M. TI RING-dependent tumor suppression and G2/M arrest induced by the TRC8 hereditary kidney cancer gene SO ONCOGENE LA English DT Article DE ubiquitin ligase; SREBP; clear-cell renal carcinoma; RING-H2 ID RENAL-CELL CARCINOMA; ELEMENT-BINDING PROTEIN; FISSION YEAST; GROWTH; TRANSLOCATION; CHOLESTEROL; EXPRESSION; PATHWAY; ACTIVATION; MECHANISMS AB TRC8/RNF139 and von Hippel-Lindau (VHL) both encode E3 ubiquitin (Ub) ligases mutated in clear-cell renal carcinomas (ccRCC). VHL, inactivated in nearly 70% of ccRCCs, is a tumor suppressor encoding the targeting subunit for a Ub ligase complex that down-regulates hypoxia-inducible factor-alpha. TRC8/RNF139 is a putative tumor suppressor containing a sterol-sensing domain and a RING-H2 motif essential for Ub ligase activity. Here we report that human kidney cells are growth inhibited by TRC8. Inhibition is manifested by G2/M arrest, decreased DNA synthesis and increased apoptosis and is dependent upon the Ub ligase activity of the RING domain. Tumor formation in a nude mouse model is inhibited by TRC8 in a RING-dependent manner. Expression of TRC8 represses genes involved in cholesterol and fatty acid biosynthesis that are transcriptionally regulated by the sterol response element binding proteins (SREBPs). Expression of activated SREBP-1a partially restores the growth of TRC8-inhibited cells. These data suggest that TRC8 modulation of SREBP activity comprises a novel regulatory link between growth control and the cholesterol/lipid homeostasis pathway. C1 Univ Colorado Denver & Hlth Sci Ctr, Div Med Oncol, Dept Med, Aurora, CO 80045 USA. Univ Colorado, Ctr Canc, Aurora, CO 80045 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Gemmill, RM (reprint author), Univ Colorado Denver & Hlth Sci Ctr, Div Med Oncol, Dept Med, 12801 E 17th Ave,Mail Stop 8117,POB 6511, Aurora, CO 80045 USA. EM robert.gemmill@uchsc.edu OI Tsai, Yien Che/0000-0001-9624-1092 FU Intramural NIH HHS; NCI NIH HHS [R01 CA076035] NR 28 TC 23 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 5 PY 2007 VL 26 IS 16 BP 2263 EP 2271 DI 10.1038/sj.onc.1210017 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 153WC UT WOS:000245466000002 PM 17016439 ER PT J AU Dautin, N Barnard, TJ Anderson, DE Bernstein, HD AF Dautin, Nathalie Barnard, Travis J. Anderson, D. Eric Bernstein, Harris D. TI Cleavage of a bacterial autotransporter by an evolutionarily convergent autocatalytic mechanism SO EMBO JOURNAL LA English DT Article DE autotransporters; enzyme mechanism; E. coli; protease; secretion ID ENTEROAGGREGATIVE ESCHERICHIA-COLI; OUTER-MEMBRANE; NEISSERIA-MENINGITIDIS; SHIGELLA-FLEXNERI; PROTEASE; SECRETION; DOMAIN; PROTEINS; RESIDUES; FAMILY AB Bacterial autotransporters are comprised of an N-terminal 'passenger domain' and a C-terminal beta barrel ('beta domain') that facilitates transport of the passenger domain across the outer membrane. Following translocation, the passenger domains of some autotransporters are cleaved by an unknown mechanism. Here we show that the passenger domain of the Escherichia coli O157:H7 autotransporter EspP is released in a novel autoproteolytic reaction. After purification, the uncleaved EspP precursor underwent proteolytic processing in vitro. An analysis of protein topology together with mutational studies strongly suggested that the reaction occurs inside the b barrel and revealed that two conserved residues, an aspartate within the b domain (Asp(1120)) and an asparagine (Asn(1023)) at the P1 position of the cleavage junction, are essential for passenger domain cleavage. Interestingly, these residues were also essential for the proteolytic processing of two distantly related autotransporters. The data strongly suggest that Asp(1120) and Asn(1023) form an unusual catalytic dyad that mediates self-cleavage through the cyclization of the asparagine. Remarkably, a very similar mechanism has been proposed for the maturation of eukaryotic viral capsids. C1 NIH, Genet & Biochem Branch, Bethesda, MD 20892 USA. NIH, NIDDKD, Proteom & Mass Spect Facil, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIH, Genet & Biochem Branch, Bldg 5,Room 201, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov FU Intramural NIH HHS NR 35 TC 75 Z9 79 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD APR 4 PY 2007 VL 26 IS 7 BP 1942 EP 1952 DI 10.1038/sj.emboj.7601638 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 153WB UT WOS:000245465800018 PM 17347646 ER PT J AU Rossouw, JE Prentice, RL Manson, JE Wu, LL Barad, D Barnabei, VM Ko, M LaCroix, AZ Margolis, KL Stefanick, ML AF Rossouw, Jacques E. Prentice, Ross L. Manson, Joann E. Wu, LieLing Barad, David Barnabei, Vanessa M. Ko, Marcia LaCroix, Andrea Z. Margolis, Karen L. Stefanick, Marcia L. TI Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; REPLACEMENT THERAPY; SECONDARY PREVENTION; MYOCARDIAL-INFARCTION; EQUINE ESTROGEN; WOMEN; HEALTH; ATHEROSCLEROSIS AB Context The timing of initiation of hormone therapy may influence its effect on cardiovascular disease. Objective To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began. Design, Setting, and Participants Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10 739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16 608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate ( CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998. Main Outcome Measures Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials. Results In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 379 cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 ( 95% CI, 0.84-1.45); and 20 or more years, 1.28 ( 95% CI, 1.03-1.58) ( P for trend=. 02). The estimated absolute excess risk for CHD for women within 10 years of menopause was - 6 per 10 000 person-years; for women 10 to 19 years since menopause began, 4 per 10 000 person-years; and for women 20 or more years from menopause onset, 17 per 10 000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 ( 95% CI, 0.65-1.33) and the absolute excess risk was - 2 per 10 000 person-years; 60 to 69 years, 0.98 ( 95% CI, 0.79-1.21) and - 1 per 10 000 person-years; and 70 to 79 years, 1.26 ( 95% CI, 1.00-1.59) and 19 per 10 000 person-years (P for trend=. 16). Hormone therapy increased the risk of stroke ( HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women ( HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend=. 06). Conclusions Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms. C1 NHLBI, Womens Hlth Initiat Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Prevent Med, Boston, MA 02115 USA. Albert Einstein Coll Med, Dept Obstet & Gynecol, New York, NY USA. Albert Einstein Coll Med, Dept Womens Hlth, New York, NY USA. Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA. Mayo Clin, Div Womens Hlth Internal Med, Scottsdale, AZ USA. Univ Minnesota, Berman Ctr Clin Res, Minneapolis, MN USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat Branch, 6701 Rockledge Dr,Bldg 2,Suite 10018, Bethesda, MD 20892 USA. EM rossouwj@nih.gov NR 28 TC 846 Z9 893 U1 2 U2 30 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 APR 4 PY 2007 VL 297 IS 13 BP 1465 EP 1477 DI 10.1001/jama.297.13.1465 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 153AM UT WOS:000245404100023 PM 17405972 ER PT J AU Cheng, AW Shin-ya, K Wan, RQ Tang, SC Miura, T Tang, HY Khatri, R Gleichman, M Ouyang, X Liu, D Park, HR Chiang, JY Mattson, MP AF Cheng, Aiwu Shin-ya, Kazuo Wan, Ruiqian Tang, Sung-chun Miura, Takumi Tang, Hongyang Khatri, Rina Gleichman, Marc Ouyang, Xin Liu, Dong Park, Hae-Rong Chiang, Jeffrey Y. Mattson, Mark P. TI Telomere protection mechanisms change during neurogenesis and neuronal maturation: Newly generated neurons are hypersensitive to telomere and DNA damage SO JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; DNA; histone modification; neurogenesis; neuronal death; neuronal progenitor cell ID DOUBLE-STRAND BREAKS; APOPTOSIS-INDUCING FACTOR; CYCLIN-DEPENDENT KINASES; LIGASE IV DEFICIENCY; CELL-DEATH; PROGENITOR CELLS; HISTONE H2AX; G-QUADRUPLEX; POLY(ADP-RIBOSE) POLYMERASE-1; DEFECTIVE NEUROGENESIS AB Telomeres are DNA-protein complexes at the ends of eukaryotic chromosomes that play an important role in maintaining the integrity of the genome. In proliferative stem cells and cancer cells, telomere length is maintained by telomerase, and telomere structure and functions are regulated by telomere-associated proteins. We find that telomerase levels are high in embryonic cortical neural progenitor cells (NPCs) and low in newly generated neurons (NGNs) and mature neurons (MNs). In contrast, telomere repeat-binding factor 2 (TRF2) expression is undetectable in early brain development in vivo and in cultured NPCs and is expressed at progressively higher levels as NPCs cease proliferation and differentiate into postmitotic neurons. The telomere-disrupting agent telomestatin induces a DNA damage response and apoptosis in NGNs (which have low levels of TRF2 and telomerase), whereas NPCs (which have high levels of telomerase) and MNs (which have high levels of TRF2) are resistant to telomere damage. Overexpression of TRF2 in NGNs protects them against death induced by telomestatin and other DNA-damaging agents. Knockdown of TRF2 expression in MNs and knock-out of telomerase reverse transcriptase in NPCs increased their sensitivity to telomere-and DNA-damaging agents but did not affect the vulnerability of NGNs. These findings suggest that TRF2 and telomerase function as distinct telomere protection mechanisms during the processes of neurogenesis and neuronal maturation and that hypersensitivity of NGNs to telomere damage results from relative deficiencies of both telomerase and TRF2. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Univ Tokyo, Inst Mol & Cellular Biosci, Tokyo 1138656, Japan. Natl Taiwan Univ Hosp, Dept Neurol, Stroke Ctr, Taipei 100, Taiwan. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Cheng, AW (reprint author), NIA, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM chengai@grc.nia.nih.gov; mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI Tang, Sung-Chun/0000-0003-3731-5973 FU Intramural NIH HHS NR 84 TC 44 Z9 48 U1 0 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 APR 4 PY 2007 VL 27 IS 14 BP 3722 EP 3733 DI 10.1523/JNEUROSCI.0590-07.2007 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 153WU UT WOS:000245468300013 PM 17409236 ER PT J AU DeRosa, F Kibbe, MR Najjar, SF Citro, ML Keefer, LK Hrabie, JA AF DeRosa, Frank Kibbe, Melina R. Najjar, Samer F. Citro, Michael L. Keefer, Larry K. Hrabie, Joseph A. TI Nitric oxide-releasing fabrics and other acrylonitrile-based diazeniumdiolates SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID POLYMERS; BIOCOMPATIBILITY AB Attachment of the diazeniumdiolate [-N(O)N-O-] functional group to polymers is of increasing interest pharmacologically for their ability to generate up to two molar equivalents of bioactive nitric oxide (NO) spontaneously on exposure to aqueous environments and yet limit physiological effects to sites in close physical proximity. Carbon-bound diazeniumdiolated polymers formed by reaction of NO with the enediamine tautomer of amidines generated on treatment of acrylonitrile-based polymers containing 1,3-dicyano groups are shown to be long lasting NO-releasing materials which may be stored for months at room temperature. NO-releasing derivatives of poly(acrylonitrile) (PAN) powder and fabrics have been prepared and shown to release NO for more than 80 d when exposed to pH 7.4 phosphate buffer at 37 degrees C. PAN/NO powder has been shown to inhibit the formation of neointimal hyperplasia in injured rat carotid arteries. NO-releasing (> 7 d) diazeniumdiolates have also been prepared from poly(styrene-co-acrylonitrile) (SAN resin) and poly(butadiene-co-acrylonitrile) (nitrile rubber). 2,4-Bisdiazeniumdiolated-2,4,6-tricyanoheptane is a carbon-bound diazeniumdiolate that releases NO for more than 200 d in solution in pH 7.4 phosphate buffer at 37 degrees C. C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Chem Sect, Lab Comparat Carcinogenesis, SAIC Frederick Inc, Frederick, MD 21702 USA. Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. RP Hrabie, JA (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM hrabie@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Intramural NIH HHS; NCI NIH HHS [N01 CO 12400] NR 14 TC 29 Z9 30 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 4 PY 2007 VL 129 IS 13 BP 3786 EP + DI 10.1021/ja0686864 PG 3 WC Chemistry, Multidisciplinary SC Chemistry GA 150TM UT WOS:000245241600006 PM 17343382 ER PT J AU Kamiya, M Kobayashi, H Hama, Y Koyama, Y Bernardo, M Nagano, T Choyke, PL Urano, Y AF Kamiya, Mako Kobayashi, Hisataka Hama, Yukihiro Koyama, Yoshinori Bernardo, Marcelino Nagano, Tetsuo Choyke, Peter L. Urano, Yasuteru TI An enzymatically activated fluorescence probe for targeted tumor imaging SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID BETA-GALACTOSIDASE ACTIVITY; PROTEIN-PROTEIN INTERACTIONS; ENZYME-IMMUNOASSAY; RATIONAL DESIGN; REPORTER-ENZYME; EXPRESSION; SUBSTRATE; CELLS; SYSTEM; AVIDIN AB beta-Galactosidase is a widely used reporter enzyme, but although several substrates are available for in vitro detection, its application for in vivo optical imaging remains a challenge. To obtain a probe suitable for in vivo use, we modified our previously developed activatable fluorescence probe, TG-beta Gal (J. Am. Chem. Soc. 2005, 127, 4888-4894), on the basis of photochemical and photophysical experiments. The new probe, AM-TG-beta Gal, provides a dramatic fluorescence enhancement upon reaction with beta-galactosidase, and further hydrolysis of the ester moiety by ubiquitous intracellular esterases affords a hydrophilic product that is well retained within the cells without loss of fluorescence. We used a mouse tumor model to assess the practical utility of AM-TG-beta Gal, after confirming that tumors in the model could be labeled with an avidin-beta-galactosidase conjugate. This conjugate was administered to the mice in vivo, followed by AM-TG-beta Gal, and subsequent ex vivo fluorescence imaging clearly visualized intraperitoneal tumors as small as 200 mu m. This strategy has potential clinical application, for example, in video-assisted laparoscopic tumor resection. C1 NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. SAIC, Res Technol Program, Frederick, MD 21702 USA. Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama 3320012, Japan. Univ Tokyo, Grad Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Rm 1B40,10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov; urano@mol.f.u-tokyo.ac.jp RI Urano, Yasuteru/H-1380-2012 FU Intramural NIH HHS [Z01 BC010657-03] NR 39 TC 94 Z9 95 U1 7 U2 56 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD APR 4 PY 2007 VL 129 IS 13 BP 3918 EP 3929 DI 10.1021/ja067710a PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA 150TM UT WOS:000245241600044 PM 17352471 ER PT J AU Fossa, SD Gilbert, E Dores, GM Chen, JB McGlynn, KA Schonfeld, S Storm, H Hall, P Holowaty, E Andersen, A Joensuu, H Andersson, M Kaijser, M Gospodarowicz, M Cohen, R Pukkala, E Travis, LB AF Fossa, Sophie D. Gilbert, Ethel Dores, Graca M. Chen, Jinbo McGlynn, Katherine A. Schonfeld, Sara Storm, Hans Hall, Per Holowaty, Eric Andersen, Aage Joensuu, Heikki Andersson, Michael Kaijser, Magnus Gospodarowicz, Mary Cohen, Randi Pukkala, Eero Travis, Lois B. TI Noncancer causes of death in survivors of testicular cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GERM-CELL TUMORS; LONG-TERM SURVIVORS; STAGE-I; CARDIOVASCULAR-DISEASE; ADJUVANT RADIOTHERAPY; RADIATION-THERAPY; RANDOMIZED-TRIAL; SEMINOMA; MORTALITY; CHEMOTHERAPY AB Background Although modern treatments for testicular cancer are associated with increased survival, the long-term health effects of these treatments are unclear. We conducted a population-based study to quantify the long-term risks of mortality from noncancer causes among men with testicular cancer. Methods We identified 38907 one-year survivors of testicular cancer within 14 population-based cancer registries in North America and Europe (from 1943 through 2002). We used data from these registries to calculate standardized mortality ratios (SMRs) for noncancer deaths and to evaluate associations between histology, age at testicular cancer diagnosis, calendar year of diagnosis, and initial treatment and the risk of noncancer mortality. All statistical tests were two-sided. Results A total of 2942 deaths from all noncancer causes were reported after a median follow-up of 10 years, exceeding the expected number of deaths from all noncancer causes in the general population by 6% (SMR = 1.06, 95% confidence interval [Cl] = 1.02 to 1.10); the noncancer standardized mortality ratios did not differ statistically significantly between patients diagnosed before and after 1975, when cisplatin-based chemotherapy came into widespread use. Compared with the general population, testicular cancer survivors had higher mortality from infections (SMR = 1.28, 95% Cl = 1.12 to 1.47) and from digestive diseases (SMR = 1.44, 95% Cl = 1.26 to 1.64). Mortality from all circulatory diseases was statistically significantly elevated in men diagnosed with testicular cancer before age 35 years (1.23, 95% C1 = 1.09 to 1.39) but not in men diagnosed at older ages (SMR = 0.94; 95% Cl = 0.89 to 1.00). Men treated with chemotherapy (with or without radiotherapy) in 1975 or later had higher mortality from all noncancer causes (SMR = 1.34, 95% Cl = 1.15 to 1.55), all circulatory diseases (SMR = 1.58, 95% Cl = 1.25 to 2.01), all infections (SMR = 2.48, 95% Cl = 1.70 to 3.50), and all respiratory diseases (SMR = 2.53, 95% C1 = 1.26 to 4.53). Testicular cancer patients who were younger than 35 years at diagnosis and were treated with radiotherapy alone in 1975 or later had higher mortality from all circulatory diseases (SMR = 1.70, 95% Cl = 1.21 to 2.31) compared with the general population. Conclusion Men who have survived for at least 1 year after being diagnosed with testicular cancer have a slightly higher risk of dying from noncancer causes, including infections, digestive diseases, and circulatory diseases, than the general population. Men treated with chemotherapy in 1975 or later may be at particularly high risk. C1 Univ Oslo, Rikshosp, Radiumhosp, Dept Clin Canc Res,Fac Med, Oslo, Norway. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. Natl Canc Inst, Div Canc Prevent, NIH, Bethesda, MD USA. Danish Canc Soc, Dept Med Epidemiol & Biostat, Copenhagen, Denmark. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Canc Care Ontario, Toronto, ON, Canada. Canc Reg Norway, Oslo, Norway. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Inst Stat & Epidemiol Canc Res, Finnish Canc Reg, Helsinki, Finland. RP Fossa, SD (reprint author), Univ Oslo, Rikshosp, Radiumhosp, Dept Clin Canc Res,Fac Med, Oslo, Norway. OI Storm, Hans/0000-0001-7223-8198; Joensuu, Heikki/0000-0003-0281-2507 FU Intramural NIH HHS NR 66 TC 70 Z9 70 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2007 VL 99 IS 7 BP 533 EP 544 DI 10.1093/jnci/djk111 PG 12 WC Oncology SC Oncology GA 158GV UT WOS:000245780700010 PM 17405998 ER PT J AU Heath, EI Canto, MI Piantadosi, S Montgomery, E Weinstein, WM Herman, JG Dannenberg, AJ Yang, VW Shar, AO Hawk, E Forastiere, AA AF Heath, Elisabeth I. Canto, Marcia Irene Piantadosi, Steven Montgomery, Elizabeth Weinstein, Wilfred M. Herman, James G. Dannenberg, Andrew J. Yang, Vincent W. Shar, Albert O. Hawk, Ernest Forastiere, Arlene A. CA Chemoprevention Barretts Esophagus TI Secondary chemoprevention of Barrett's esophagus with celecoxib: Results of a randomized trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HIGH-GRADE DYSPLASIA; FAMILIAL ADENOMATOUS POLYPOSIS; SQUAMOUS-CELL CARCINOMA; PUMP INHIBITOR THERAPY; UNITED-STATES; ADENOCARCINOMA; RISK; CYCLOOXYGENASE-2; DIAGNOSIS; EXPRESSION AB Background Barrett's esophagus is a premalignant condition that is a risk factor for the development of esophageal adenocarcinoma, a disease whose incidence is rapidly increasing. Because aspirin and other nonsteroidal anti-inflammatory drugs, such as celecoxib, may decrease the risk of developing esophageal cancer, we investigated the effect of long-term administration of celecoxib in patients with Barrett's esophagus with dysplasia. Methods Chemoprevention for Barrett's Esophagus Trial (CBET) is a phase Ilb multicenter randomized placebo-controlled trial of celecoxib in patients with Barrett's esophagus and low- or high-grade dysplasia. Patients were randomly assigned to treatment with 200 mg of celecoxib or placebo, both administered orally twice daily, and then stratified by grade of dysplasia. The primary outcome was the change from baseline to 48 weeks of treatment in the proportion of biopsy samples with dysplasia between the celecoxib and placebo arms. Secondary and tertiary outcomes included evaluation of changes in histology and expression levels of relevant biomarkers. All statistical tests were two-sided. Results From April 1, 2000, through June 30, 2003, 222 patients were registered into CBET, and 100 of them with low or high-grade Barrett's dysplasia were randomly assigned to treatment (49 to celecoxib and 51 to placebo). After 48 weeks of treatment, no difference was observed in the median change in the proportion of biopsy samples with dysplasia or cancer between treatment groups in either the low-grade (median change with celecoxib = -0.09, interquartile range [IQR] = -0.32 to 0.14 and with placebo = -0.07, IQR = -0.26 to 0,12; P=.64) or high-grade (median change with celecoxib = 0.12, IQR = -0.31 to 0.55, and with placebo = 0.02, IQR = -0.24 to 0.28; P=.88) stratum. No statistically significant differences in total surface area of the Barrett's esophagus; in prostaglandin levels; in cyclooxygenase-1/2 mRNA levels; or in methylation of tumor suppressor genes p16, adenomatous polyposis coli, and E-cadherin were found with celecoxib compared with placebo. Conclusions Administration of 200 mg of celecoxib twice daily for 48 weeks of treatment does not appear to prevent progression of Barrett's dysplasia to cancer. C1 Johns Hopkins Ctr Clin Trials, CBET Coordinating Ctr, Baltimore, MD 21205 USA. Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Univ Calif Los Angeles, Ctr Hlth Sci, Dept Gastroenterol, Los Angeles, CA USA. Cornell Univ, Weill Med Coll, Dept Gastroenterol, New York, NY USA. Emory Univ, Sch Med, Atlanta, GA USA. Emory Univ, Robert Wood Johnson Fdn, Sch Med, Princeton, NJ USA. NCI, Div Canc Prevent, Rockville, MD USA. RP Heath, EI (reprint author), Johns Hopkins Ctr Clin Trials, CBET Coordinating Ctr, 615 N Wolfe St,Rm 5010, Baltimore, MD 21205 USA. EM heathe@karmanos.org FU NCI NIH HHS [R01 CA084197, N01-CN-85185]; NIDDK NIH HHS [R01 DK052230] NR 37 TC 101 Z9 103 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2007 VL 99 IS 7 BP 545 EP 557 DI 10.1093/jnci/djk112 PG 13 WC Oncology SC Oncology GA 158GV UT WOS:000245780700011 PM 17405999 ER PT J AU Chow, WH Linehan, WM Devesa, SS AF Chow, Wong-Ho Linehan, W. Marston Devesa, Susan S. TI Re: Rising incidence of small renal masses: A need to reassess treatment effect SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Chow, WH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8100, Bethesda, MD 20892 USA. EM choww@mail.nih.gov NR 3 TC 12 Z9 12 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD APR 4 PY 2007 VL 99 IS 7 BP 569 EP 570 DI 10.1093/jnci/djk114 PG 2 WC Oncology SC Oncology GA 158GV UT WOS:000245780700013 PM 17406001 ER PT J AU Yaung, J Jin, ML Barron, E Spee, C Wawrousek, EF Kannan, R Hinton, DR AF Yaung, Jennifer Jin, Manlin Barron, Ernesto Spee, Christine Wawrousek, Eric F. Kannan, Ram Hinton, David R. TI alpha-Crystallin distribution in retinal pigment epithelium and effect of gene knockouts on sensitivity to oxidative stress SO MOLECULAR VISION LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; B-CRYSTALLIN; A-CRYSTALLIN; MOLECULAR CHAPERONE; INDUCED APOPTOSIS; CYTOCHROME-C; MACULAR DEGENERATION; PROTECTIVE ACTIVITY; PROTEIN; CELLS AB Purpose: To investigate the susceptibility of retinal pigment epithelium (RPE) from alpha A (-/-) and alpha B (-/-) mice to oxidative stress, and the subcellular changes of alpha A and alpha B-crystallins under oxidative stress. Methods: The effect of hydrogen peroxide (H2O2) on apoptosis in RPE from alpha A (-/-), alpha B (-/-), and wild type (wt) mice was assessed by TUNEL and AnnexinV/Propidium Iodide assays. H2O2-induced changes in caspase-3 activity and mitochondrial permeability transition (MPT) were determined. Human RPE in early passages (2-4) were starved in 1% FBS-containing Dulbecco's modified Eagle medium (DMEM) and treated with H2O2 for 24 h. Gene expression was quantitated by real time PCR. Confocal microscopy was used to examine alpha-crystallin compartmentalization. Whole cell and mitochondrial alpha-crystallin protein amounts were examined by transmission electron microscopy (TEM) and Western blot analysis. Results: RPE from alpha A (-/-), alpha B (-/-) mice exhibited increased susceptibility to apoptosis induced by H2O2, increased caspase-3 activation, and increased MPT. Treatment of human RPE with H2O2 resulted in a dose-dependent decrease in alpha B-crystallin mRNA expression. Confocal microscopy and subcellular fractionation of RPE showed that H2O2 treatment decreased cytosolic and mitochondrial pools of alpha B-crystallin but caused no change in alpha A-crystallin content. TEM confirmed changes in expression of alpha A and alpha B-crystallins with oxidative stress. Conclusions: Lack of alpha-crystallins renders RPE cells more susceptible to apoptosis from oxidative stress. Mitochondrial alpha-crystallins may play an important role in the protection from increased susceptibility of RPE in oxidative stress. C1 Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. Arnold & Mabel Beckman Macular Res Ctr, Los Angeles, CA USA. Doheny Eye Inst, Los Angeles, CA 90033 USA. NEI, US Dept HHS, Bethesda, MD 20892 USA. RP Hinton, DR (reprint author), Univ So Calif, Keck Sch Med, Dept Pathol, 2011 Zonal Ave,HMR 209, Los Angeles, CA 90033 USA. EM dhinton@usc.edu RI Wawrousek, Eric/A-4547-2008 FU NEI NIH HHS [EY02061, EY03040, P30 EY003040, R01 EY002061] NR 48 TC 59 Z9 64 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD APR 4 PY 2007 VL 13 IS 57-61 BP 566 EP 577 PG 12 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 157KT UT WOS:000245719300005 PM 17438522 ER PT J AU Kouprina, N Noskov, VN Pavlicek, A Collins, NK Bortz, PDS Ottolenghi, C Loukinov, D Goldsmith, P Risinger, JI Kim, JH Westbrook, VA Solomon, G Sounders, H Herr, JC Jurka, J Lobanenkov, V Schlessinger, D Larionov, V AF Kouprina, Natalay Noskov, Vladimir N. Pavlicek, Adam Collins, N. Keith Bortz, Pamela D. Schoppee Ottolenghi, Chris Loukinov, Dmitri Goldsmith, Paul Risinger, John I. Kim, Jung-Hyun Westbrook, V. Anne Solomon, Gregory Sounders, Hanna Herr, John C. Jurka, Jerzy Lobanenkov, Victor Schlessinger, David Larionov, Vladimir TI Evolutionary Diversification of SPANX-N Sperm Protein Gene Structure and Expression SO PLOS ONE LA English DT Article AB The sperm protein associated with nucleus in the X chromosome (SPANX) genes cluster at Xq27 in two subfamilies, SPANX-A/D and SPANX-N. SPANX-A/D is specific for hominoids and is fairly well characterized. The SPANX-N gave rise to SPANX-A/D in the hominoid lineage similar to 7 MYA. Given the proposed role of SPANX genes in spermatogenesis, we have extended studies to SPANX-N gene evolution, variation, regulation of expression, and intra-sperm localization. By immunofluorescence analysis, SPANX-N proteins are localized in post-meiotic spermatids exclusively, like SPANX-A/D. But in contrast to SPANX-A/D, SPANX-N are found in all ejaculated spermatozoa rather than only in a subpopulation, are localized in the acrosome rather than in the nuclear envelope, and are expressed at a low level in several nongametogenic adult tissues as well as many cancers. Presence of a binding site for CTCF and its testis-specific paralogue BORIS in the SPANX promoters suggests, by analogy to MAGE-A1 and NY-ESO-1, that their activation in spermatogenesis is mediated by the programmed replacement of CTCF by BORIS. Based on the relative density of CpG, the more extended expression of SPANX-N compared to SPANX-A/D in nongametogenic tissues is likely attributed to differences in promoter methylation. Our findings suggest that the recent duplication of SPANX genes in hominoids was accompanied by different localization of SPANX-N proteins in post-meiotic sperm and additional expression in several nongonadal tissues. This suggests a corresponding functional diversification of SPANX gene families in hominoids. SPANX proteins thus provide unique targets to investigate their roles in the function of spermatozoa, selected malignancies, and for SPANX-N, in other tissues as well. C1 [Kouprina, Natalay; Noskov, Vladimir N.; Collins, N. Keith; Goldsmith, Paul; Risinger, John I.; Kim, Jung-Hyun; Larionov, Vladimir] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Pavlicek, Adam; Jurka, Jerzy] Genet Informat Res Inst, Mountain View, CA USA. [Bortz, Pamela D. Schoppee; Herr, John C.] Univ Virginia Hlth Syst, Dept Cell Biol, Charlottesville, VA USA. [Ottolenghi, Chris; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. [Loukinov, Dmitri; Lobanenkov, Victor] NIAID, Immunol Lab, Bethesda, MD 20892 USA. [Westbrook, V. Anne] Univ Virginia, Dept Biochem & Mol Genet, Charlottesville, VA USA. [Solomon, Gregory; Sounders, Hanna] NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kouprina, N (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM kouprinn@mail.nih.gov OI Lobanenkov, Victor/0000-0001-6665-3635 FU NIH; National Cancer Institute; Center for Cancer Research; National Institute on Aging, NIA FX This research was supported by the intramural research program of the NIH, National Cancer Institute, Center for Cancer Research and National Institute on Aging, NIA. NR 57 TC 17 Z9 18 U1 0 U2 1 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 APR 4 PY 2007 VL 2 IS 4 AR e359 DI 10.1371/journal.pone.0000359 PG 15 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DS UT WOS:000207445300021 PM 17406683 ER PT J AU Hsieh, MM Everhart, JE Byrd-Holt, DD Tisdale, JF Rodgers, GP AF Hsieh, Matthew M. Everhart, James E. Byrd-Holt, Danita D. Tisdale, John F. Rodgers, Griffin P. TI Prevalence of neutropenia in the US population: Age, sex, smoking status, and ethnic differences SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BENIGN IDIOPATHIC NEUTROPENIA; FAMILIAL LEUKOPENIA; LEUKOCYTE COUNTS; GENETIC NEUTROPENIA; INFECTION; MARROW; WHITE; BLACK; NEGROES; CELL AB Background: Benign reductions in neutrophil counts may be more common at certain ages and in certain ethnic groups and may be affected by sex and smoking status. Objective: To determine differences in neutrophil counts in the U.S. population according to ethnicity, age, sex, and smoking status. Design: Population-based, cross-sectional study. Setting: Various locations in the United States. Participants: 25 222 participants in the 1999 to 2004 National Health and Nutrition Examination Survey who were 1 year of age or older. Measurements: Complete blood counts and comparison of means and the proportion of participants with neutropenia. Results: Relative to white participants, black participants had lower leukocyte counts (mean difference, 0.89 x 10(9) cells/L; P < 0.001), lower neutrophil counts (0.83 x 10(9) cells/L; P < 0.001), and similar lymphocyte counts (0.022 x 10(9) cells/L; P = 0.36), whereas Mexican-American participants had slightly higher mean leukocyte counts (0.16 x 10(9) cells/L; P = 0.014), higher neutrophil counts (0.11 x 10(9) cells/L; P = 0.026), and higher lymphocyte counts (0.095 x 10(9) cells/L; P < 0.001). The prevalence of neutropenia (neutrophil count < 1.5 x 10(9) cells/L) was 4.5% among black participants, 0.79% among white participants, and 0.38% among Mexican-American participants. The prevalence of neutropenia was higher among males and children younger than 5 years of age. Neutrophil counts less than 1.0 x 10(9) cells/L were observed in fewer than 1% of the overall sample (0.57% in black participants, 0.11% in white participants, and 0.08% in Mexican-American participants). Smoking was associated with higher leukocyte and neutrophil counts but had a smaller effect among black and Mexican-American participants than among white participants. Limitation: Because estimates are based on single measures, fluctuations over time could not be determined. Conclusions: In the United States, neutrophil counts are lower in black persons than in white persons and neutropenia is more prevalent in black persons. Neutrophil counts are slightly higher in Mexican -American persons than in white persons, and neutropenia is uncommon in both groups. The clinical implications of these findings are unclear, but they suggest that when determining the need for a diagnostic evaluation for neutropenia, clinicians should consider the patient's age, sex, ethnicity, and smoking status. C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, 9000 Rockville Pike,Bldg 10,9N 119, Bethesda, MD 20892 USA. EM gr5n@nih.gov FU Intramural NIH HHS NR 35 TC 111 Z9 114 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 3 PY 2007 VL 146 IS 7 BP 486 EP 492 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 153VB UT WOS:000245463200002 PM 17404350 ER PT J AU Malozowski, S AF Malozowski, Saul TI Exenatide in combination therapy: Small study, big market, and many unanswered questions SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID MANAGEMENT C1 NIDDKD, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. RP Malozowski, S (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, Democracy 2,6707 Democracy Blvd,Room 607, Bethesda, MD 20892 USA. EM sm87j@nih.gov NR 10 TC 5 Z9 5 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 3 PY 2007 VL 146 IS 7 BP 527 EP 528 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 153VB UT WOS:000245463200007 PM 17404355 ER PT J AU Kasai, S Urushibata, S Hozumi, K Yokoyama, F Ichikawa, N Kadoya, Y Nishi, N Watanabe, N Yamada, Y Nomizu, M AF Kasai, Shingo Urushibata, Shunsuke Hozumi, Kentaro Yokoyama, Fumiharu Ichikawa, Naoki Kadoya, Yuichi Nishi, Norio Watanabe, Nobuhisa Yamada, Yoshihiko Nomizu, Motoyoshi TI Identification of multiple amyloidogenic sequences in laminin-1 SO BIOCHEMISTRY LA English DT Article ID TERMINAL GLOBULAR DOMAIN; CELL-BINDING SEQUENCES; ALZHEIMERS-DISEASE; ALPHA-1 CHAIN; NEURITE OUTGROWTH; FIBRIL FORMATION; SYNTHETIC PEPTIDES; BETA-PEPTIDE; CONGO RED; A-CHAIN AB Amyloid fibril formation is associated with several pathologies, including Alzheimer's disease, Parkinson's disease, type II diabetes, and prion diseases. Recently, a relationship between basement membrane components and amyloid deposits has been reported. The basement membrane protein, laminin, may be involved in amyloid-related diseases, since laminin is present in amyloid plaques in Alzheimer's disease and binds to amyloid precursor protein. Recently, we showed that peptide A208 (AASIKVAVSADR), the IKVAV-containing peptide, formed amyloid-like fibrils. We previously identified 60 cell adhesive sequences in laminin-1 using a total of 673 12-mer synthetic peptides. Here, we screened for additional amyloidogenic sequences among 60 cell adhesive peptides derived from laminin-1. We first examined amyloid-like fibril formation by the 60 active peptides with Congo red, a histological dye binding to many amyloid-like proteins. Thirteen peptides were stained with Congo red. Four of the 13 peptides promoted cell attachment and neurite outgrowth like the IKVAV-containing peptide. The four peptides also showed amyloid-like fibril formation in both X-ray diffraction and electron microscopic analyses. The amyloidogenic peptides contain consensus amino acid components, including both basic and acidic amino acids and Ser and Ile residues. These results indicate that at least five laminin-derived peptides can form amyloid-like fibrils. We conclude that the laminin-derived amyloidogenic peptides have the potential to form amyloid-like fibrils in vivo, possibly when laminin-1 is degraded. C1 Tokyo Univ Pharm & Life Sci, Hachioji, Tokyo 1920392, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Div Biosci, Sapporo, Hokkaido 0600810, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 2288555, Japan. Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido 0600810, Japan. RP Nomizu, M (reprint author), Tokyo Univ Pharm & Life Sci, Hachioji, Tokyo 1920392, Japan. EM nomizu@ps.toyaku.ac.jp NR 51 TC 20 Z9 20 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 3 PY 2007 VL 46 IS 13 BP 3966 EP 3974 DI 10.1021/bi062097t PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 150HY UT WOS:000245207800004 PM 17348688 ER PT J AU Uhl, GR Liu, QR Drgon, T Johnson, C Walther, D Rose, JE AF Uhl, George R. Liu, Qing-Rong Drgon, Tomas Johnson, Catherine Walther, Donna Rose, Jed E. TI Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs SO BMC GENETICS LA English DT Article ID MILD MENTAL IMPAIRMENT; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-I; T-CADHERIN; SMOKING-BEHAVIOR; POOLED DNA; ENVIRONMENTAL-INFLUENCES; POLYSUBSTANCE ABUSERS; SUSCEPTIBILITY LOCI; VULNERABILITY LOCI AB Background: Classical genetic studies indicate that nicotine dependence is a substantially heritable complex disorder. Genetic vulnerabilities to nicotine dependence largely overlap with genetic vulnerabilities to dependence on other addictive substances. Successful abstinence from nicotine displays substantial heritable components as well. Some of the heritability for the ability to quit smoking appears to overlap with the genetics of nicotine dependence and some does not. We now report genome wide association studies of nicotine dependent individuals who were successful in abstaining from cigarette smoking, nicotine dependent individuals who were not successful in abstaining and ethnically-matched control subjects free from substantial lifetime use of any addictive substance. Results: These data, and their comparison with data that we have previously obtained from comparisons of four other substance dependent vs control samples support two main ideas: 1) Single nucleotide polymorphisms ( SNPs) whose allele frequencies distinguish nicotine-dependent from control individuals identify a set of genes that overlaps significantly with the set of genes that contain markers whose allelic frequencies distinguish the four other substance dependent vs control groups ( p < 0.018). 2) SNPs whose allelic frequencies distinguish successful vs unsuccessful abstainers cluster in small genomic regions in ways that are highly unlikely to be due to chance ( Monte Carlo p < 0.00001). Conclusion: These clustered SNPs nominate candidate genes for successful abstinence from smoking that are implicated in interesting functions: cell adhesion, enzymes, transcriptional regulators, neurotransmitters and receptors and regulation of DNA, RNA and proteins. As these observations are replicated, they will provide an increasingly- strong basis for understanding mechanisms of successful abstinence, for identifying individuals more or less likely to succeed in smoking cessation efforts and for tailoring therapies so that genotypes can help match smokers with the treatments that are most likely to benefit them. C1 NIDA, IRP, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Duke Univ, Dept Psychiat, Durham, NC 27708 USA. Duke Univ, Ctr Nicotine & Smoking Cessat Res, Durham, NC 27708 USA. RP Uhl, GR (reprint author), NIDA, IRP, Mol Neurobiol Branch, NIH, Suite 3510,333 Cassell Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov; liu@intra.nida.nih.gov; tdrgon@intra.nigs.nih.gov; johnsoncat@intra.nida.nih.gov; dwalther@intra.nida.nih.gov; jerose@duke.edu RI Liu, Qing-Rong/A-3059-2012 OI Liu, Qing-Rong/0000-0001-8477-6452 FU Intramural NIH HHS NR 57 TC 88 Z9 92 U1 0 U2 6 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 APR 3 PY 2007 VL 8 AR 10 DI 10.1186/1471-2156-8-10 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 158OL UT WOS:000245800700001 PM 17407593 ER PT J AU Humphrey, JA Hamming, KS Thacker, CM Scott, RL Sedensky, MM Snutch, TP Morgan, PG Nash, HA AF Humphrey, John A. Hamming, Kevin S. Thacker, Colin M. Scott, Robert L. Sedensky, Margaret M. Snutch, Terrance P. Morgan, Phil G. Nash, Howard A. TI A putative cation channel and its novel regulator: Cross-species conservation of effects on general anesthesia SO CURRENT BIOLOGY LA English DT Article ID CAENORHABDITIS-ELEGANS; DROSOPHILA-MELANOGASTER; ION-CHANNEL; SENSITIVITY; HALOTHANE; INTERACT; STOMATIN; MUTANTS AB Volatile anesthetics like halothane and enflurane are of interest to clinicians and neuroscientists because of their ability to preferentially disrupt higher functions that make up the conscious state. All. volatiles were once thought to act identically; if so, they should be affected equally by genetic variants. However, mutations in two distinct genes, one in Caenorhabditis and one in Drosophila, have been reported to produce much larger effects on the response to halothane than enflurane [1, 2]. To see whether this anesthesia signature is adventitious or fundamental, we have identified orthologs of each gene and determined the mutant phenotype within each species. The fly gene, narrow abdomen (na), encodes a putative ion channel whose sequence places it in a unique family; the nematode gene, unc-79, is identified here as encoding a large cytosolic protein that lacks obvious motifs. In Caenorhabditis, mutations that inactivate both of the na orthologs produce an Unc-79 phenotype; in Drosophila, mutations that inactivate the unc-79 orthologs produce an na phenotype. In each organism, studies of double mutants place the genes in the same pathway, and biochemical studies show that proteins of the UNC-79 family control NA protein levels by a posttranscriptional mechanism. Thus, the anesthetic signature reflects an evolutionarily conserved role for the na orthologs, implying its intimate involvement in drug action. C1 Univ Hosp, Dept Anesthesiol, Cleveland, OH 44106 USA. Univ Hosp, Dept Genet, Cleveland, OH 44106 USA. Case Med Ctr, Dept Genet, Cleveland, OH 44106 USA. Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada. NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Morgan, PG (reprint author), Univ Hosp, Dept Anesthesiol, Cleveland, OH 44106 USA. EM philip.morgan@case.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM45402, T32 GM008613] NR 24 TC 59 Z9 69 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD APR 3 PY 2007 VL 17 IS 7 BP 624 EP 629 DI 10.1016/j.cub.2007.02.037 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 155IX UT WOS:000245572200024 PM 17350263 ER PT J AU Yeo, SY Chitnis, AB AF Yeo, Sang-Yeob Chitnis, Ajay B. TI Jagged-mediated Notch signaling maintains proliferating neural progenitors and regulates cell diversity in the ventral spinal cord SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neurogenesis; p3; progenitor; zebrafish; Jagged2 ID NERVOUS-SYSTEM; MOTOR-NEURON; ZEBRAFISH; SPECIFICATION; DELTA; FATE; INHIBITION; ACTIVATION; IDENTITY; HOMOLOG AB Previous studies have shown that Delta-mediated Notch signaling regulates the number of early differentiating neurons. However, the role of Notch activation and Jagged-mediated signaling during late neurogenesis remains poorly defined. In the developing spinal cord of zebrafish, GABAergic Kolmer-Agduhr (KA") cells and motor neurons (MN) emerge sequentially from their progenitors in the p3 domain. Jagged2 is expressed uniformly in the pMN domain during late neurogenesis where Olig2 is required for its expression. We suggest that Jagged2 interacts ventrally with progenitors in the adjacent p3 domain, where it has a critical role in the maintenance of proliferating neural progenitors and in preventing differentiation of these progenitors as GABAergic KA" cells or secondary MN. This study identifies a critical role for Jagged-Notch signaling in the maintenance of proliferating neural precursors in a discrete compartment of the neural tube during the continuing growth and development of the vertebrate nervous system. C1 Kyungpook Natl Univ, Dept Genet Engn, Taegu 702701, South Korea. NICHHD, Sect Neural Dev Dynam, Mol Genet Lab, NIH, Rockville, MD 20852 USA. RP Yeo, SY (reprint author), Kyungpook Natl Univ, Dept Genet Engn, 1370 San Kyuk Dong, Taegu 702701, South Korea. EM sangyeobyeo@knu.ac.kr; chitnisa@mail.nih.gov FU Intramural NIH HHS NR 28 TC 30 Z9 31 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 3 PY 2007 VL 104 IS 14 BP 5913 EP 5918 DI 10.1073/pnas.0607062104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 156OA UT WOS:000245657600039 PM 17389390 ER PT J AU Jang, H Ma, BY Nussinov, R AF Jang, Hyunbum Ma, Buyong Nussinov, Ruth TI Conformational study of the protegrin-I (PG-I) dimer interaction with lipid bilayers and its effect SO BMC STRUCTURAL BIOLOGY LA English DT Article ID SOLID-STATE NMR; HAIRPIN ANTIMICROBIAL PEPTIDE; MOLECULAR-DYNAMICS SIMULATIONS; PORE FORMATION; MEMBRANE; OLIGOMERIZATION; MICELLES; MELITTIN; PROTEINS AB Background: Protegrin-I (PG-I) is known as a potent antibiotic peptide; it prevents infection via an attack on the membrane surface of invading microorganisms. In the membrane, the peptide forms a pore/ channel through oligomerization of multiple subunits. Recent experimental and computational studies have increasingly unraveled the molecular-level mechanisms underlying the interactions of the PG-I beta-sheet motifs with the membrane. The PG-I dimer is important for the formation of oligomers, ordered aggregates, and for membrane damaging effects. Yet, experimentally, different dimeric behavior has been observed depending on the environment: antiparallel in the micelle environment, and parallel in the POPC bilayer. The experimental structure of the PG-I dimer is currently unavailable. Results: Although the beta-sheet structures of the PG-I dimer are less stable in the bulk water environment, the dimer interface is retained by two intermolecular hydrogen bonds. The formation of the dimer in the water environment implies that the pathway of the dimer invasion into the membrane can originate from the bulk region. In the initial contact with the membrane, both the antiparallel and parallel beta-sheet conformations of the PG-I dimer are well preserved at the amphipathic interface of the lipid bilayer. These beta-sheet structures illustrate the conformations of PG-I dimer in the early stage of the membrane attack. Here we observed that the activity of PG-1 beta-sheets on the bilayer surface is strongly correlated with the dimer conformation. Our long- term goal is to provide a detailed mechanism of the membranedisrupting effects by PG-1 beta-sheets which are able to attack the membrane and eventually assemble into the ordered aggregates. Conclusion: In order to understand the dimeric effects leading to membrane damage, extensive molecular dynamics ( MD) simulations were performed for the beta-sheets of the PG-I dimer in explicit water, salt, and lipid bilayers composed of POPC lipids. Here, we studied PG-I dimers when organized into a beta-sheet motif with antiparallel and parallel beta-sheet arrangements in an NCCN packing mode. We focus on the conformations of PG-I dimers in the lipid bilayer, and on the correlation between the conformations and the membrane disruption effects by PG-I dimers. We investigate equilibrium structures of the PG-I dimers in different environments in the early stage of the dimer invasion. The dimer interface of the antiparallel alpha- sheets is more stable than the parallel beta-sheets, similar to the experimental observation in micelle environments. However, we only observe membrane disruption effects by the parallel beta-sheets of the PG-I dimer. This indicates that the parallel beta-sheets interact with the lipids with the beta-sheet plane lying obliquely to the bilayer surface, increasing the surface pressure in the initial insertion into the lipid bilayer. Recent experimental observation verified that parallel PG-I dimer is biologically more active to insert into the POPC lipid bilayer. C1 SAIC Frederick Inc, NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Inst Mol Med, Dept Human Genet & Mol Med, Sackler Sch Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), SAIC Frederick Inc, NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. EM jangh@ncifcrf.gov; mab@ncifcrf.gov; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 39 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 1471-2237 J9 BMC STRUCT BIOL JI BMC Struct. Biol. PD APR 2 PY 2007 VL 7 AR 21 DI 10.1186/1472-6807-7-21 PG 15 WC Biophysics SC Biophysics GA 166NX UT WOS:000246386800001 PM 17407565 ER PT J AU Hussain, SP Schwank, J Staib, F Wang, XW Harris, CC AF Hussain, S. P. Schwank, J. Staib, F. Wang, X. W. Harris, C. C. TI TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer SO ONCOGENE LA English DT Review DE hepatocellular carcinoma; p53; aflatoxin B-1; HBV; HCV; oxidative/nitrosative stress ID HEPATITIS-B-VIRUS; NITRIC-OXIDE SYNTHASE; P53 TUMOR-SUPPRESSOR; DIFFERENTIAL GENE-EXPRESSION; NUCLEOTIDE EXCISION-REPAIR; CHRONIC VIRAL-HEPATITIS; X-PROTEIN; DNA-REPAIR; TRANSCRIPTION FACTOR; AFLATOXIN EXPOSURE AB Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and the major risk factors include chronic infections with the hepatitis B (HBV) or C (HCV) virus, and exposure to dietary aflatoxin B-1 (AFB(1)) or alcohol consumption. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC, for example, somatic mutations in the p53 tumor suppressor gene (TP53) and the activation of the WNT signal transduction pathway. AFB1 frequently induces G: C to T: A transversions at the third base in codon 249 of TP53 and cooperates with HBV in causing p53 mutations in HCC. The detection of TP53 mutant DNA in plasma is a biomarker of both AFB1 exposure and HCC risk. Chronic infection with HBV and HCV viruses, and oxyradical disorders including hemochromatosis, also generate reactive oxygen/nitrogen species that can both damage DNA and mutate cancer-related genes such as TP53. Certain mutant p53 proteins may exhibit a 'gain of oncogenic function'. The p53 biological network is a key responder to this oxidative and nitrosative stress. Depending on the extent of the DNA damage, p53 regulates the transcription of protective antioxidant genes and with extensive DNA damage, transactivates pro-oxidant genes that contribute to apoptosis. The X gene of HBV (HBx) is the most common open reading frame integrated into the host genome in HCC and the integrated HBx is frequently mutated. Mutant HBx proteins still retain their ability to bind to p53, and attenuate DNA repair and p53-mediated apoptosis. In summary, both viruses and chemicals are implicated in the etiology of TP53 mutations during the molecular pathogenesis of HCC. C1 NCI, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, Lab Human Carcinogenesis, NIH, Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov RI Wang, Xin/B-6162-2009 NR 128 TC 251 Z9 268 U1 7 U2 37 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 2 PY 2007 VL 26 IS 15 BP 2166 EP 2176 DI 10.1038/sj.onc.1210279 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 152XE UT WOS:000245394800005 PM 17401425 ER PT J AU Menendez, D Inga, A Jordan, JJ Resnick, MA AF Menendez, D. Inga, A. Jordan, J. J. Resnick, M. A. TI Changing the p53 master regulatory network: ELEMENTary, my dear Mr Watson SO ONCOGENE LA English DT Review DE p53; response element; mutants; transactivation; SNP; evolution ID WILD-TYPE P53; TUMOR-SUPPRESSOR PROTEIN; DNA-BINDING SITE; RNA-POLYMERASE-II; TRANSCRIPTIONAL REPRESSION; IN-VIVO; FUNCTIONAL ASSAY; HUMAN GENOME; MUTANT P53; DIRECTED MUTAGENESIS AB The p53 master regulatory network provides for the stress-responsive direct control of a vast number of genes in humans that can be grouped into several biological categories including cell-cycle control, apoptosis and DNA repair. Similar to other sequence-specific master regulators, there is a matrix of key components, which provide for variation within the p53 master regulatory network that include p53 itself, target response element sequences (REs) that provide for p53 regulation of target genes, chromatin, accessory proteins and transcription machinery. Changes in any of these can impact the expression of individual genes, groups of genes and the eventual biological responses. The many REs represent the core of the master regulatory network. Since defects or altered expression of p53 are associated with over 50% of all cancers and greater than 90% of p53 mutations are in the sequence-specific DNA-binding domain, it is important to understand the relationship between wildtype or mutant p53 proteins and the target response elements. In the words of the legendary detective Sherlock Holmes, it is 'Elementary, my dear Mr. Watson.' C1 Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, Lab Mol Genet, NIH, Res Triangle Pk, NC 27709 USA. IST, Natl Inst Canc Res, Mol Mutageneis Unit, Dept Translat Oncol, Genoa, Italy. RP Resnick, MA (reprint author), Natl Inst Environm Hlth Sci, Chromosome Stabil Sect, Lab Mol Genet, NIH, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM resnick@niehs.nih.gov FU Intramural NIH HHS NR 98 TC 22 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 2 PY 2007 VL 26 IS 15 BP 2191 EP 2201 DI 10.1038/sj.onc.1210277 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 152XE UT WOS:000245394800008 PM 17401428 ER PT J AU Tintle, NL Gordon, D McMahon, FJ Finch, SJ AF Tintle, Nathan L. Gordon, Derek McMahon, Francis J. Finch, Stephen J. TI Using duplicate genotyped data in genetic analyses: Testing association and estimating error rates SO STATISTICAL APPLICATIONS IN GENETICS AND MOLECULAR BIOLOGY LA English DT Article DE genotype error; misclassification; test of association; case-control; re-genotype; inconsistency rate; duplicate genotype; whole genome association; genome wide association ID SAMPLE-SIZE CALCULATIONS; PROBABILITY MODEL; POWER; MISCLASSIFICATION; CLASSIFICATION; SCHEME AB Although researchers use duplicate genotyped data to calculate an inconsistency rate, there is no power analysis to assess the value of the duplicate data. In this paper, we present a model in which the genotyping error rate is related to the inconsistency rate. We extend the g genotype by h phenotype chi-squared test to incorporate the duplicate genotyped data. When a subject is inconsistently genotyped (that is, has two observed genotypes), our procedure is to allocate 0.5 units to each of the two genotypes. We specify the multivariate analysis of variance (MANOVA) test comparing these extended counts. We provide freely available software for this test and also for a permutation test used on small samples. A simulation study shows that the asymptotic null distribution of the MANOVA test holds when the total number of subjects, N, is at least 300. We also document with a simulation study that the asymptotic distribution of this test under various alternative hypotheses is a satisfactory approximation to the simulated power. In all cases, the power of the MANOVA test using the duplicate genotyped data is greater than the power of the chi-squared test ignoring the duplicate data. Power increases ranged from 0.776% to 4.652% for 80% powered tests and 0.292% to 2.028% for 95% powered tests. Researchers now can compute the value of the duplicate genotyped data as part of the design of the study. C1 Hope Coll, Holland, MI 49422 USA. Rutgers State Univ, Piscataway, NJ 08855 USA. NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. RP Tintle, NL (reprint author), Hope Coll, Holland, MI 49422 USA. EM tintle@hope.edu; gordon@biology.rutgers.edu; mcmahonf@mail.nih.gov; sjfinch@optonline.net RI McMahon, Francis/A-7290-2009 NR 40 TC 16 Z9 16 U1 0 U2 1 PU BERKELEY ELECTRONIC PRESS PI BERKELEY PA 2809 TELEGRAPH AVENUE, STE 202, BERKELEY, CA 94705 USA SN 1544-6115 J9 STAT APPL GENET MOL JI Stat. Appl. Genet. Mol. Biol. PD APR 2 PY 2007 VL 6 AR 4 PG 29 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Mathematical & Computational Biology; Mathematics GA 152BN UT WOS:000245335600006 ER PT J AU Chruszcz, M Kong, Y Dauter, Z Brown, ML Minor, W AF Chruszcz, Maksymilian Kong, Yali Dauter, Zbigniew Brown, Milton L. Minor, Wladek TI 2-amino-4-(4-chloro-3-methylphenyl)-5-propyl-1,3-thiazolium iodide SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE LA English DT Article ID 2-AMINO-4-PHENYLTHIAZOLE; DERIVATIVES; THIAZOLES; CRYSTAL AB In the crystal structure of the title compound, C13H16ClN2S+ center dot I-, the molecule of 2-amino-4-(4-chloro-3-methylphenyl)-5-propyl-1,3-thiazole is protonated on the ring N atom. The angle between the planes formed by the 1,3-thiazole and benzene rings is 39.3 (1)degrees, and this conformation is caused by the presence of the propyl group in position 5 of the heterocyclic ring. The packing in the crystal structure is mainly stabilized by +NH center dot center dot center dot I-and NH center dot center dot center dot I-hydrogen bonds and stacking of 2-amino-4-(4-chloro-3-methylphenyl)-5-propyl-1,3-thiazolium cations. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Georgetown Univ, Med Ctr, Drug Discovery Program, Dept Oncol, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Drug Discovery Program, Dept Neurosci, Washington, DC 20057 USA. Argonne Natl Lab, Natl Canc Inst, Synchrotron Radiat Res Sect, MCL, Argonne, IL 60439 USA. RP Minor, W (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, 1340 Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM wladek@iwonka.med.virginia.edu RI Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014; OI Chruszcz, Maksymilian/0000-0001-7521-5485; Minor, Wladek/0000-0001-7075-7090 NR 21 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-5368 J9 ACTA CRYSTALLOGR E JI Acta Crystallogr. Sect. E.-Struct Rep. Online PD APR PY 2007 VL 63 BP O1598 EP O1600 DI 10.1107/S1600536807009427 PN 4 PG 3 WC Crystallography SC Crystallography GA 153LL UT WOS:000245436300142 ER PT J AU Cymborowski, M Chruszcz, M Dauter, Z Minor, W AF Cymborowski, Marcin Chruszcz, Maksymilian Dauter, Zbigniew Minor, Wladek TI 3-Iodo-L-tyrosine hemihydrate SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE LA English DT Article ID TYROSINE-HYDROXYLASE AB The crystal structure of the title compound [systematic name: (S)-2-ammonio-3-(3-iodo-4-hydroxyphenyl) propanoate hemihydrate], C9H10INO3.0.5H(2)O, is stabilized by ionic interactions and a hydrogen-bond network. The hydrogen bonds, involving a water molecule located on a twofold axis, form bridged layers of 3-iodo-L-tyrosine molecules. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Argonne Natl Lab, Natl Canc Inst, Synchrotron Radiat Res Sect, MCL, Argonne, IL 60439 USA. RP Minor, W (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, 1340 Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM wladek@iwonka.med.virginia.edu RI Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014; OI Chruszcz, Maksymilian/0000-0001-7521-5485; Minor, Wladek/0000-0001-7075-7090 NR 18 TC 1 Z9 1 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-5368 J9 ACTA CRYSTALLOGR E JI Acta Crystallogr. Sect. E.-Struct Rep. Online PD APR PY 2007 VL 63 BP O1557 EP O1559 DI 10.1107/S1600536807009129 PN 4 PG 3 WC Crystallography SC Crystallography GA 153LL UT WOS:000245436300125 ER PT J AU Milstien, S Gude, D Spiegel, S AF Milstien, Sheldon Gude, David Spiegel, Sarah TI Sphingosine 1-phosphate in neural signalling and function SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT 6th International Symposium on Lysosmal Storage Diseases CY APR, 2006 CL Stockholm, SWEDEN DE differentiation; neural degenerative disorders; neurons; sphingosine 1-phosphate; sphingolipids; sphingosine ID PROTEIN-COUPLED RECEPTOR; NERVE GROWTH-FACTOR; CERAMIDE INDUCES APOPTOSIS; CULTURED MESENCEPHALIC NEURONS; CEREBELLAR GRANULE CELLS; SPHINGOSINE-1-PHOSPHATE RECEPTORS; PC12 CELLS; CASPASE ACTIVATION; KINASE TYPE-2; EXPRESSION AB Complex sphingolipids are particularly enriched in the central nervous system. Although they were long considered to be structural components of membranes, in the last decades it has become apparent that they have other important functions. More recently, attention has been given to the sphingolipid metabolites ceramide, sphingosine and sphingosine 1-phosphate (S1P), which have been implicated in the regulation of many aspects of neuronal proliferation, differentiation, survival and apoptosis. Dysregulation of the relative levels of these bioactive sphingolipid metabolites may have implications for a wide array of neurodegenerative disorders and neural malformations. In this paper, we will focus on studies from our laboratory over the past few years using cultured neurons to examine the roles of the sphingolipid metabolite S1P in neuronal survival and differentiation. Conclusion: Identification of potential intracellular targets of S1P remains a crucial objective for attaining a better understanding of the potent role this molecule plays in regulating cell fate. C1 Virginia Commonwealth Univ, Dept Biochem, Sch Med, Richmond, VA 23892 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Dept Biochem, Sch Med, 1101 E Marshall St,Sanger Hall Room 2011, Richmond, VA 23892 USA. EM sspiegel@vcu.edu FU Intramural NIH HHS; NIGMS NIH HHS [R37 GM43880] NR 41 TC 26 Z9 28 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD APR PY 2007 VL 96 SU 455 BP 40 EP 43 DI 10.1111/j.1651-2227.2007.00206.x PG 4 WC Pediatrics SC Pediatrics GA 149WP UT WOS:000245177900009 PM 17391440 ER PT J AU Chen, SQ Zhai, HF Cui, YY Shi, J Le Foll, B Lu, L AF Chen, Su-Qing Zhai, Hai-Feng Cui, Yan-Ying Shi, Jie Le Foll, Bernard Lu, Lin TI Clonidine attenuates morphine withdrawal and subsequent drug sensitization in rhesus monkeys SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE cocaine; withdrawal; drug challenge; cross-sensitization; recurrence; monkeys ID CONDITIONED PLACE PREFERENCE; STRESS-INDUCED REINSTATEMENT; COCAINE-SEEKING BEHAVIOR; LONG-TERM SENSITIZATION; IN-VIVO MICRODIALYSIS; OPIATE WITHDRAWAL; OPIOID WITHDRAWAL; LOCUS-COERULEUS; DEPENDENT RATS; NORADRENERGIC NEURONS AB Aim: Clonidine is an alpha(2) adrenoceptor agonist that is frequently used to reduce withdrawal symptoms during opioid detoxification in humans. The long-term effects of clonidine on withdrawal symptoms and its effects on subsequent drug exposure have not been thoroughly documented. The aim of the study was to determine if clonidine administered during morphine withdrawal in rhesus monkeys produces long-lasting effects on withdrawal symptoms and alters the effects of subsequently taken drugs of abuse. Methods: Adult male rhesus monkeys were treated with increasing doses of morphine for 90 d to induce opiate (narcotic) dependence. The immediate and long-lasting effects of 1 week's administration of clonidine were measured via the recording of morphine withdrawal signs and the subsequent effects of challenge injections of morphine or cocaine. Results: Monkeys chronically treated with morphine displayed withdrawal signs that lasted 2 weeks after cessation of morphine administration and displayed sensitized responses to subsequent morphine and cocaine injections. Clonidine significantly reduced certain morphine withdrawal signs and overall withdrawal score, but these effects did not persist upon cessation of clonidine treatment. Sensitization to the effects of morphine and cocaine were significantly reduced in monkeys previously treated with clonidine. Conclusion: Our results suggest that in addition to its short-term alleviating effect on morphine withdrawal signs, clonidine may reduce subsequent effects of drugs of abuse after prolonged abstinence. C1 Peking Univ, Natl Inst Drug Dependence, Dept Neuropharmacol, Beijing 100083, Peoples R China. Peking Univ, Natl Inst Drug Dependence, Dept Clin Pharmacol, Beijing 100083, Peoples R China. NIDA, Behav Neurosci Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Lu, L (reprint author), Peking Univ, Natl Inst Drug Dependence, Dept Neuropharmacol, Beijing 100083, Peoples R China. EM linlu@bjmu.edu.cn RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 FU Intramural NIH HHS NR 79 TC 7 Z9 10 U1 0 U2 0 PU ACTA PHARMACOLOGICA SINICA PI SHANGHAI PA 294 TAI-YUAN RD, SHANGHAI, 200031, PEOPLES R CHINA SN 1671-4083 EI 1745-7254 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD APR PY 2007 VL 28 IS 4 BP 473 EP 483 DI 10.1111/j.1745-7254.2007.00526.x PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 150NY UT WOS:000245224700002 PM 17376286 ER PT J AU Taube, W Gruber, M Beck, S Faist, M Gollhofer, A Schubert, M AF Taube, W. Gruber, M. Beck, S. Faist, M. Gollhofer, A. Schubert, M. TI Cortical and spinal adaptations induced by balance training: correlation between stance stability and corticospinal activation SO ACTA PHYSIOLOGICA LA English DT Article DE H-reflex; neuroplasticity; posture; sensorimotor training; transcranial magnetic stimulation ID TRANSCRANIAL MAGNETIC STIMULATION; SOLEUS H-REFLEX; LATENCY STRETCH REFLEXES; MOTOR CORTEX STIMULATION; TIBIALIS ANTERIOR MUSCLE; PRESYNAPTIC INHIBITION; VOLUNTARY CONTRACTION; POSTURAL RESPONSES; PROSPECTIVE COHORT; NEURAL ADAPTATION AB Aim: To determine the sites of adaptation responsible for improved stance stability after balance (=sensorimotor) training, changes in corticospinal and spinal excitability were investigated in 23 healthy subjects. Methods: Neural adaptations were assessed by means of H-reflex stimulation, transcranial magnetic stimulation (TMS) and conditioning of the H-reflex by TMS (H-cond) before and after 4 weeks of balance training. All measurements were performed during stance perturbation on a treadmill. Fast posterior translations induced short- (SLR), medium- and long-latency responses (LLR) in the soleus muscle. Motor-evoked potential- (MEP) and H-cond-amplitudes as well as H-max/M-max ratios were determined at SLR and LLR. Postural stability was measured during perturbation on the treadmill. Results: Balance training improved postural stability. H-max/M-max ratios were significantly decreased at LLR. MEPs and H-cond revealed significantly reduced facilitation at LLR following training. A negative correlation between adaptations of H-cond and changes in stance stability was observed (r = -0.87; P < 0.01) while no correlation was found between stance stability and changes in H-max/M-max ratio. No changes in any parameter occurred at the spinally organized SLR and in the control group. Conclusion: The decrease in MEP- and H-cond-facilitation implies reduced corticospinal and cortical excitability at the transcortically mediated LLR. Changes in cortical excitability were directly related to improvements in stance stability as shown by correlation of these parameters. The absence of such a correlation between H-max/M-max ratios and stance stability suggests that mainly supraspinal adaptations contributed to improved balance performance following training. C1 Univ Freiburg, Dept Sport Sci, D-79117 Freiburg, Germany. Dept Neurol & Clin Neurophysiol, Freiburg, Germany. Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, NIH, Bethesda, MD USA. RP Taube, W (reprint author), Univ Freiburg, Dept Sport Sci, Schwarzwaldstr 175, D-79117 Freiburg, Germany. EM wolfgang.taube@sport.uni-freiburg.de RI Taube, Wolfgang/E-4018-2012 OI Taube, Wolfgang/0000-0002-8802-2065 NR 59 TC 81 Z9 81 U1 5 U2 23 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1748-1708 J9 ACTA PHYSIOL JI Acta Physiol. PD APR PY 2007 VL 189 IS 4 BP 347 EP 358 DI 10.1111/j.1748-1716.2007.01665.x PG 12 WC Physiology SC Physiology GA 145TI UT WOS:000244887000005 PM 17263693 ER PT J AU Rawson, RA Condon, TP AF Rawson, Richard A. Condon, Timothy P. TI Why do we need an Addiction supplement focused on methamphetamine? SO ADDICTION LA English DT Editorial Material DE epidemiology; methamphetamine; policy ID HIV RISK; CALIFORNIA; GAY AB Methamphetamine is a substantial public health problem in many communities in the United States and in other parts of the world. In order to bring new knowledge about methamphetamine to policy makers, clinicians and researchers, this volume has compiled a set of articles containing new information about the drug and its effects. The articles contain information presented by researchers at two special methamphetamine meetings sponsored by the National Institute on Drug Abuse in 2005. C1 Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90025 USA. NIDA, NIH, Bethesda, MD 20892 USA. RP Rawson, RA (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst Neurosci & Human Behav, 1640 S Sepulveda Blvd,Suite 200, Los Angeles, CA 90025 USA. EM rrawson@mednet.ucla.edu FU NIDA NIH HHS [N01DA-3-8824, N01DA-0-8804] NR 19 TC 36 Z9 37 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2007 VL 102 SU 1 BP 1 EP 4 DI 10.1111/j.1360-0443.2006.01781.x PG 4 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 140QR UT WOS:000244521200001 PM 17493048 ER PT J AU Chang, L Alicata, D Ernst, T Volkow, N AF Chang, Linda Alicata, Daniel Ernst, Thomas Volkow, Nora TI Structural and metabolic brain changes in the striatum associated with methamphetamine abuse SO ADDICTION LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat DE basal ganglia; dopamine; methamphetamine; MRI; PET ID ACETYL-L-CYSTEINE; ABSTINENT METHAMPHETAMINE; DOPAMINE TRANSPORTERS; INDUCED NEUROTOXICITY; PSYCHIATRIC-SYMPTOMS; DEPENDENT SUBJECTS; RESONANCE SPECTROSCOPY; MICROGLIAL ACTIVATION; PROTRACTED ABSTINENCE; DORSAL STRIATUM AB Aims To review structural, chemical and metabolic brain changes, particularly those in the basal ganglia, in individuals who used methamphetamine, as well as in children with prenatal methamphetamine exposure. Methods Magnetic resonance imaging (MRI) and positron emission tomography (PET) studies that evaluated brain structural, chemical and metabolite changes in methamphetamine subjects, or children with prenatal methamphetamine exposure, were reviewed and summarized. Relevant pre-clinical studies that provided insights to the interpretations of these imaging studies were also reviewed. Results In adults who used methamphetamine, MRI demonstrates enlarged striatal volumes, while MR spectroscopy shows reduced concentrations of the neuronal marker N-acetylasparate and total creatine in the basal ganglia. In contrast, children with prenatal methamphetamine exposure show smaller striatal structures and elevated total creatine. Furthermore, PET studies consistently showed reduced dopamine transporter (DAT) density and reduced dopamine D-2 receptors in the striatum of methamphetamine subjects. PET studies also found lower levels of serotonergic transporter density and vesicular monoamine transporter (VMAT2) across striatal subregions, as well as altered brain glucose metabolism that correlated with severity of psychiatric symptoms in the limbic and orbitofrontal regions. Conclusion Neuroimaging studies demonstrate abnormalities in brain structure and chemistry convincingly in individuals who used methamphetamine and in children with prenatal methamphetamine exposure, especially in the striatum. However, many important questions remain and larger sample sizes are needed to validate these preliminary observations. Furthermore, longitudinal studies are needed to evaluate the effects of treatment and abstinence on these brain changes and to determine whether imaging, and possibly genetic, markers can be used to predict treatment outcome or relapse. C1 Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96813 USA. NIDA, NIH, Rockville, MD USA. NIAAA, NIH, Rockville, MD 20852 USA. RP Chang, L (reprint author), Univ Hawaii, John A Burns Sch Med, Dept Med, 1356 Lusitana St,7th Floor,UH Tower, Honolulu, HI 96813 USA. EM LChang@hawaii.edu FU NIDA NIH HHS [K02-DA16991, K24-DA16170]; NINDS NIH HHS [2U54 NS3906-06] NR 64 TC 175 Z9 180 U1 8 U2 23 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2007 VL 102 SU 1 BP 16 EP 32 DI 10.1111/j.1360-0443.2006.01782.x PG 17 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 140QR UT WOS:000244521200003 PM 17493050 ER PT J AU Vocci, FJ Appel, NM AF Vocci, Frank J. Appel, Nathan M. TI Approaches to the development of medications for the treatment of methamphetamine dependence SO ADDICTION LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat DE immunotherapy; methamphetamine; pharmacotherapy; stimulants ID ANGIOTENSIN-CONVERTING ENZYME; VESICULAR MONOAMINE TRANSPORTER; GAMMA-VINYL GABA; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; INDUCED DOPAMINERGIC NEUROTOXICITY; RANDOMIZED CONTROLLED-TRIAL; NUCLEUS-ACCUMBENS DOPAMINE; VENTRAL TEGMENTAL AREA; RAT-BRAIN SYNAPTOSOMES; IN-VIVO MICRODIALYSIS AB Background Methamphetamine abuse has become an increasing problem in both the United States and globally with concomitant increases in adverse medical, social and environmental sequelae. Behavioral therapies have been used with some success to treat methamphetamine abusers and dependent individuals, but are not universally efficacious. Methamphetamine has a rich pharmacology that theoretically provides many opportunities for potential pharmacotherapeutic intervention. Nevertheless, there are no approved medications with an indication for treating methamphetamine abusers or addicts at this time. Aim To describe briefly how methamphetamine functions and affects function in brain and report how basic researchers and clinicians are attempting to exploit and exploiting this knowledge to discover and develop effective pharmacotherapies. Results Scientifically based approaches to medications development by evaluating medications that limit brain exposure to methamphetamine; modulate methamphetamine effects at vesicular monoamine transporter-2 (VMAT-2); or affect dopaminergic, serotonergic, GABAergic, and/ orglutamatergic brain pathways that participate in methamphetamine's reinforcing effects are presented. Conclusion The evidence supports the rationale that pharmacotherapies to decrease methamphetamine use, or reduce craving during abstinence may be developed from altering the pharmacokinetics and pharmacodynamics of methamphetamine or its effects on appetitive systems in the brain. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Vocci, FJ (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, US Dept HHS, 6001 Execut Blvd,MSC 9551,Room 4133, Bethesda, MD 20892 USA. EM fv6k@nih.gov NR 150 TC 64 Z9 65 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2007 VL 102 SU 1 BP 96 EP 106 DI 10.1111/j.1360-0443.2007.01772.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 140QR UT WOS:000244521200011 PM 17493058 ER PT J AU Elkashef, A Rawson, RA Smith, E Pearce, V Flammino, F Campbell, J Donovick, R Gorodetzky, C Haning, W Mawhinney, J McCann, M Weis, D Williams, L Ling, W Vocci, F AF Elkashef, Ahmed Rawson, Richard A. Smith, Edwina Pearce, Valerie Flammino, Frank Campbell, Jan Donovick, Roger Gorodetzky, Charles Haning, William Mawhinney, Joseph McCann, Michael Weis, Dennis Williams, Lorie Ling, Walter Vocci, Frank TI The NIDA Methamphetamine Clinical Trials Group: A strategy to increase clinical trials research capacity SO ADDICTION LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat DE medication; methamphetamine; multi-site; pharmacotherapy ID 5-HT3 RECEPTOR ANTAGONIST; CONTINUOUS COCAINE; ONDANSETRON; WITHDRAWAL; SENSITIZATION; EXPRESSION; TOLERANCE; BLOCKADE; DRUGS; ABUSE AB Aims In order to increase the number of investigative teams and sites conducting research on pharmacological treatments for methamphetamine use disorders, the National Institute on Drug Abuse ( NIDA) established an infrastructure of clinical sites in areas where methamphetamine addiction is prevalent. This multi-site infrastructure would serve to run multiple Phases II and III protocols effectively and expeditiously. Methods NIDA collaborated with investigators from the University of California at Los Angeles (UCLA) to set up the Methamphetamine Clinical Trials Group (MCTG). This paper describes the development process, as well as data from a test trial to assess the capability of research-naive sites to recruit research participants and conduct study procedures according to research protocol. Subsequent trials are also described. Results A total of 151 candidates signed consent; 65 individuals were enrolled and 35 (53.8%) completed the 12 weeks' behavioral trial. Self-reported substance use report (SUR) showed comparable use of methamphetamine across sites with the individual site means ranging from 59% (site 5) to 80% (site 3). Drug use as measured by urinalysis was greatly reduced at week 13 compared to the baseline measure; the average rate of methamphetamine-free urine samples across all participants in sites at week 13 was 53%. The highest percentage of methamphetamine-free samples was 85% at site 5; the lowest was at site 1 (40%). Addiction severity index (ASI) composite scores at baseline and protocol completion for all participants demonstrated improvement in all categories over time, except for the medical composite score. The largest composite score reduction in baseline-protocol completion was in the drug domain (0.23 versus 0.15). The changes in the ASI scores from baseline to week 13 were consistent across all five sites. Conclusions Outcomes of the behavioral trial indicated that the MCTG recruited well; collected study data accurately and reliably; and created a vehicle that can assess promising pharmacotherapies for methamphetamine addiction treatment medications. The MCTG strategy appears to be a feasible approach to increase NIDA's capacity to conduct clinical trials to evaluate potential pharmacotherapies for methamphetamine addiction. C1 NIDA, Div Treatment Res & Dev, NIH, US Dept HHS, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Neuropsychiat Inst & Hosp, Integrated Subst Abuse Program, Los Angeles, CA 90024 USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. Univ Missouri, Dept Psychiat, Kansas City, MO 64110 USA. Matrix Inst Addict, Costa Mesa, CA USA. Quintiles Inc, Kansas City, MO USA. Univ Hawaii, John A Burns Sch Med, Dept Psychiat, Honolulu, HI 96822 USA. S Bay Treatment Ctr, San Diego, CA USA. Matrix Inst Addict, Los Angeles, CA USA. Lutheran Gen Hosp, Res Off, Des Moines, IA USA. SW Kidney Inst PLC, Mesa, AZ USA. RP Elkashef, A (reprint author), NIDA, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH,Dept Hlth & Human Serv, 6001 Execut Blvd,Room 4151, Bethesda, MD 20892 USA. EM ae8a@nih.gov NR 16 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 2007 VL 102 SU 1 BP 107 EP 113 DI 10.1111/j.1360-0443.2007.01779.x PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 140QR UT WOS:000244521200012 PM 17493059 ER PT J AU Caceres, CF Celentano, DD Coates, TJ Hartwell, TD Kasprzyk, D Kelly, JA Kozlov, AP Pequegnat, W Rotheram-Borus, MJ Solomon, S Woelk, G Wu, ZY AF Caceres, Carlos F. Celentano, David D. Coates, Thomas J. Hartwell, Tyler D. Kasprzyk, Danuta Kelly, Jeffrey A. Kozlov, Andrei P. Pequegnat, Willo Rotheram-Borus, Mary Jane Solomon, Suniti Woelk, Godfrey Wu, Zunyou CA NIMH Collaborative HIV STD Prev TI Ethical issues in the NIMH Collaborative HIV/STD Prevention Trial SO AIDS LA English DT Article DE aIDS; behavioral intervention; HIV; international ethics ID SEXUALLY-TRANSMITTED-DISEASES; HUMAN-IMMUNODEFICIENCY-VIRUS; COMMERCIAL PLASMA DONORS; HIV-INFECTION; PARTNER NOTIFICATION; DEVELOPING-COUNTRIES; SEX; TRANSMISSION; SYPHILIS; AFRICA AB Objective: To develop decision rules regarding key ethical dimensions in scientific protocols for the National Institute for Mental Health (NIMH) Collaborative HIV/STD Prevention Trial taking place in five countries (China, India, Peru, Russia, and Zimbabwe). Design: Countries had HIV rates from 27 to 0.1%, the standard of care varied from access to anti retrovi ral drugs to no availability, and the reporting of sexually transmitted diseases (STD) to government agencies was mandatory in some countries and not in others. These variations presented challenges when developing decision rules that could be uniformly adopted across countries and simultaneously follow the ethical principles of beneficence, respect, and justice. Methods: We used several strategies to identify and resolve ethical dilemmas for this international HIV prevention trial. First, we identified key principles, especially those derived for clinical therapeutic, biomedical preventive, or device trials. We convened a 'workgroup on protecting human participants' and charged them with identifying and implementing optimal procedures for ensuring the ethical and equitable treatment of participants and making recommendations to minimize physical, psychological, and social harm to the participants. Each site had a community advisory board, essential in identifying local ethical issues and possible resolutions to them. The NIMH established a data safety and monitoring board with ultimate responsibility for adjudicating ethical dilemmas and decisions. The protocols were deliberated thoroughly by the Trial steering committee, and approved by nine United States and five in-country institutional review boards. Results: We summarize the decision rules adopted to resolve the ethical dilemmas identified. Especially important were the translation of clinical trials principles for a behavioral intervention trial, strategies for ensuring confidentiality and informed consent, dilemmas relating to partner notification of sexually transmitted infections including HIV, minimizing the risks of social harm, establishing community partnerships, ensuring equity among United States and in-country principal investigators, and building capacity for additional research. Conclusion: We document our processes and decisions, and their underlying rationales, and hope they contribute to the development of further thinking and practice regarding the ethics of social and behavioral HIV and STD prevention trials in resource-poor settings. (C) 2007 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Ctr Biomed, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Yale Univ, New Haven, CT 06520 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. SAHAI Trust, Madras, Tamil Nadu, India. Natl Ctr STD Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016 OI Kozlov, Andrei/0000-0003-4611-1534 NR 62 TC 0 Z9 0 U1 4 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S69 EP S80 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700008 ER PT J AU Caceres, CF Coates, TJ Hartwell, TD Kasprzyk, D Kelly, JA Kozlov, AP Pequegnat, W Rotheram-Borus, MJ Solomon, S Woelk, G Wu, ZY AF Caceres, Carlos F. Coates, Thomas J. Hartwell, Tyler D. Kasprzyk, Danuta Kelly, Jeffrey A. Kozlov, Andrei P. Pequegnat, Willo Rotheram-Borus, Mary Jane Solomon, Suniti Woelk, Godfrey Wu, Zunyou CA NIMH Collaborative HIV STD Prev TI Role of the data safety and monitoring board in an international trial SO AIDS LA English DT Article DE community popular opinion leader; data safety and monitoring board; sexually transmitted diseases; HIV AB Objective: To describe the composition and role of the data safety and monitoring board (DSMB) for the National Institute of Mental Health (NIMH) Collaborative HIV/STD Prevention Trial. Design: NIMH appointed to the DSMB nine members representing the following areas of expertise: prevention science, ethnography, infectious diseases (especially HIV and sexually transmitted diseases), laboratory diagnostics, clinical practice, methodology, international trial experience, statistics, and ethics. Methods: The DSMB assessed the overall study for any concern about plans or implementation and reviewed cumulative study data to evaluate the safety of study participants, the ongoing conduct of the study, and the scientific validity and integrity of the Trial. Because of the Trial's international scope, the DSMB examined the effects of cultural differences on study implementation and fidelity. Results: Among the DSMB recommendations that strengthened the Trial was one to conduct initial epidemiological studies of the venues selected for the intervention to verify risk and to establish intraclass correlation coefficients that could be used to calculate appropriate sample sizes. Conclusions: The DSMB played a critical role in this Trial. Because members have the expertise required to monitor the Trial, are not involved in the daily management of the Trial, and can review interim analyses and adverse event reports, they are in an excellent position to provide expert advice to ensure that the Trial's goals are achieved and that NIH funds are well invested. (C) 2007 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Biomed Ctr, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Yale Univ, New Haven, CT 06520 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. SAHAI Trust, Madras, Tamil Nadu, India. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016 OI Kozlov, Andrei/0000-0003-4611-1534 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S99 EP S102 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700011 ER PT J AU Caceres, CF Celentano, DD Coates, TJ Hartwell, TD Kelly, JA Kozlov, AP Pequegnat, W Rotheram-Borus, MJ Solomon, S Woelk, G Wu, ZY AF Caceres, Carlos F. Celentano, David D. Coates, Thomas J. Hartwell, Tyler D. Kelly, Jeffrey A. Kozlov, Andrei P. Pequegnat, Willo Rotheram-Borus, Mary Jane Solomon, Suniti Woelk, Godfrey Wu, Zunyou CA NIMH Collaborative HIV STD Prev TI Formative study conducted in five countries to adapt the community popular opinion leader intervention SO AIDS LA English DT Article DE behavioral interventions; culture; ethnography; low-resource countries; qualitative data; risk factors; sexual behavior ID DOMESTIC VIOLENCE; CHENNAI; INDIA; RISK AB Objective: To obtain information about the social and cultural factors related to health behaviors influencing HIV/sexually transmitted disease (STD) transmission in study communities in China, India, Peru, Russia, and Zimbabwe so that the assessment and intervention of the National Institute for Mental Health (NIMH) Collaborative HIV/STD Prevention Trial could be adapted appropriately. Methods: Field observations, focus groups, in-depth interviews with key informants, and an observation of community social dynamics were conducted as part of a rapid ethnographic assessment. Results: All five sites reported a power dynamic tilted towards men, which rendered women particularly vulnerable to HIV and other STDs. Women's relative lack of power was exemplified by a double standard for extramarital sex, women's limited ability to negotiate sex or condom use, and sexual and physical violence against women. In all sites except Russia, extramarital sex is tolerated for men but proscribed for women. In Peru, power dynamics between men who have sex with men were tilted towards men who self-identified as heterosexual. Condom use (reported to be low across all sites) was often linked to having sex with only those perceived as high-risk partners. Regardless of site or study population, participants agreed on the following characteristics of an ideal community popular opinion leader (C-POL): respectable, credible, experienced (life and sexual), trustworthy, empathetic, well-spoken, and self-confident. Conclusion: The ethnographic studies provided critical information that enabled the study teams to adapt elements of the Trial in culturally appropriate ways in diverse international settings. (C) 2007 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Ctr Biomed, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Yale Univ, New Haven, CT 06520 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. SAHAI Trust, Madras, Tamil Nadu, India. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016 OI Kozlov, Andrei/0000-0003-4611-1534 NR 21 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S91 EP S98 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700010 ER PT J AU Caceres, CF Celentano, DD Coates, TJ Hartwell, TD Kelly, JA Kozlov, AP Pequegnat, W Rotheram-Borus, MJ Solomon, S Woelk, G Wu, ZY AF Caceres, Carlos F. Celentano, David D. Coates, Thomas J. Hartwell, Tyler D. Kelly, Jeffrey A. Kozlov, Andrei P. Pequegnat, Willo Rotheram-Borus, Mary Jane Solomon, Suniti Woelk, Godfrey Wu, Zunyou CA NIMH Collaborative HIV STD Prev TI Sexually transmitted disease and HIV prevalence and risk factors in concentrated and generalized HIV epidemic settings SO AIDS LA English DT Article DE developing nations; epidemiology; HIV; risk behaviors; risk factors; sexual behavior; sexually transmitted disease prevalence ID IMMUNODEFICIENCY-VIRUS-INFECTION; PREVENTION INTERVENTION; REDUCTION INTERVENTION; COST-EFFECTIVENESS; AIDS-PREVENTION; MENTAL-ILLNESS; VAGINAL SWABS; RURAL UGANDA; TRIAL; BEHAVIOR AB Background: in many developing countries, the threat of nascent HIV epidemics expanding rapidly requires immediate and appropriate HIV prevention activities. Inexpensive and sustainable interventions are especially relevant in resource-constrained environments. In 2001, we assessed the prevalence and behavioral risk of sexually transmitted disease (STD) and HIV among at-risk populations in five developing countries in preparation for a community-randomized controlled trial, the NIMH Collaborative HIV/STD Prevention Trial. Methods: Using a standardized protocol, more than 1000 participants in each country (China, India, Peru, Russia, and Zimbabwe) were selected by random sampling methods, completed a behavioral risk assessment, and provided biological specimens using a common laboratory protocol. Sample characteristics were studied within each country, and risk factors for HIV/STD acquisition were evaluated using logistic regression models. Results: HIV rates were low (<1%) in China, India, Peru, and Russia but were high (26%) in rural Zimbabwe. STDs were generally twice as common in women as men, and serological evidence of herpes simplex virus type 2 infection was the most frequently detected STD. Behavioral data showed high rates of multiple partners in the Russian sample, and very low condom use rates in India and China. Among participants who reported ever having sex, female sex and having two or more sex partners were the factors most frequently associated with an increased risk of prevalent STD. Conclusion: Behavioral or biological risks were of sufficient magnitude in the locations selected in China, Russia, and Zimbabwe to implement the community-based randomized trial. Higher-risk subsets of community residents in India and Peru were identified before beginning the Trial. (C) 2007 Lippincott Williams & Wilkins. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90024 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Biomed Ctr, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Yale Univ, New Haven, CT 06520 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. SAHAI Trust, Madras, Tamil Nadu, India. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016 OI Kozlov, Andrei/0000-0003-4611-1534 NR 38 TC 2 Z9 2 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S81 EP S90 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700009 ER PT J AU Caceres, CF Celentano, DD Coates, TJ Hartwell, TD Kasprzyk, D Kelly, JA Kozlov, AP Pequegnat, W Rotheram-Borus, MJ Solomon, S Woelk, G AF Caceres, Carlos F. Celentano, David D. Coates, Thomas J. Hartwell, Tyler D. Kasprzyk, Danuta Kelly, Jeffrey A. Kozlov, Andrei P. Pequegnat, Willo Rotheram-Borus, Mary Jane Solomon, Suniti Woelk, Godfrey CA NIMH Collaborative HIV STD Prev TI The community popular opinion leader HIV prevention programme: conceptual basis and intervention procedures SO AIDS LA English DT Article DE behavioral intervention; developing nations; HIV; sexual behavior; sexually transmitted disease ID PEER EDUCATION; RISK REDUCTION; GAY MEN; BEHAVIOR; CITIES; LONDON AB Objective: To describe the community popular opinion leader (C-POL) intervention employed in the NIMH Collaborative HIV/STD Prevention Trial, including its theoretical, conceptual, and empirical basis, intervention procedures and methods, core elements, and how its content was culturally tailored to address the needs of varied populations. Design: The programme is designed to identify, recruit, train, and intensively engage C-POLs of a target population to convey HIV risk reduction messages to people in their communities, with the intention of reducing high-risk behavior at a population level. Methods: Based on the diffusion of innovation theory, the intervention identified, trained, and engaged C-POL within a high-risk community population to advocate, recommend, and endorse the importance of safer behavior to other members of the same population. Nine core elements of the intervention are discussed. Data collected during rapid ethnography were used to adapt the content of the intervention for food market owners and workers in China, male patrons of wine shops and at-risk women congregating nearby in India, young people in social gathering venues in Peruvian barrios, dormitory students in Russia, and people congregating in commercial areas of growth points in Zimbabwe. Results: The C-POL intervention model taps into community strengths, altruism, and people's desire to do something to help fight against AIDS. With few exceptions, C-POLs participated enthusiastically in the training sessions and reported having conversations in the community. Conclusion: Rapid ethnography can be used to tailor an intervention to diverse settings while maintaining fidelity to the core elements of the intervention. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Biomed Ctr, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Fujian Ctr Dis Control & Prevent, Fujian, Peoples R China. Yale Univ, New Haven, CT 06520 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ Arizona, Tucson, AZ 85721 USA. SAHAI Trust, Madras, Tamil Nadu, India. CDC, Atlanta, GA 30333 USA. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ N Carolina, Chapel Hill, NC USA. RP Caceres, CF (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru. RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016 OI Kozlov, Andrei/0000-0003-4611-1534 NR 24 TC 0 Z9 0 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S59 EP S68 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700007 ER PT J AU Caceres, CF Celentano, DD Coates, TJ Hartwell, TD Kasprzyk, D Kelly, JA Kozlov, AP Pequegnat, W Rotheram-Borus, MJ Solomon, S Woelk, G Wu, Z AF Caceres, Carlos F. Celentano, David D. Coates, Thomas J. Hartwell, Tyler D. Kasprzyk, Danuta Kelly, Jeffrey A. Kozlov, Andrei P. Pequegnat, Willo Rotheram-Borus, Mary Jane Solomon, Suniti Woelk, Godfrey Wu, Zunyou CA NIMH Collaborative HIV STD Prev TI The feasibility of audio computer-assisted self-interviewing in international settings SO AIDS LA English DT Article DE developing nations; knowledge/attitude/practice studies; sexual behavior; survey methods ID FACE-TO-FACE; REPORTED DRUG-USE; RISK BEHAVIORS; METHODOLOGICAL EXPERIMENT; DATA-COLLECTION; QUESTIONNAIRES; COMPARABILITY; ADOLESCENTS; RELIABILITY; SAMPLE AB Objective: To determine the feasibility interviewing (ACASI) for data collection responses to questions eliciting sensitive ACASI versus computer-assisted persona countries. of using audio computer-assisted self-in developing countries, and to compare information about sexual behavior using I interviewing (CAPI) in five developing Design: A feasibility study determined whether ACASI could be used in populations in developing countries. A follow-up, randomized crossover study compared responses to questions eliciting sensitive information about sexual behavior using ACASI versus CAP[. Methods: The NIMH Collaborative HIV/STD Prevention Trial conducted a feasibility study of ACASI in convenience samples in China, India, Peru, and Russia, then a randomized crossover ACASI versus CAN study among volunteers in these countries plus Zimbabwe. Results: Approximately equal numbers of men and women completed the feasibility study; the results suggested a high comfort level among participants. Married respondents in China and India appeared to give unreliable responses on sexual activity. In the crossover study, the pattern of responses to sensitive questions showed few differences. In China, higher rates of sexual risk were reported on CAPI. In Peru and Russia, differences by mode were found in the number of partners in the past year. Conclusion: Despite variable computer experience and literacy, feasibility study participants reported ease in completing ACASI, and preferred a computer to an interviewer for answering sensitive questions, or had no preference. In the crossover study, most participants gave similar responses on both modes of survey administration. ACASI appears to be feasible in these settings, although low literacy may pose problems if participants cannot clarify questions. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Biomed Ctr, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Fujian Ctr Dis Control & Prevent, Fujian, Peoples R China. Yale Univ, New Haven, CT 06520 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC USA. SAHAI Trust, Madras, Tamil Nadu, India. CDC, Atlanta, GA 30333 USA. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RP Caceres, CF (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru. RI Strader, Lisa/H-3083-2013; Kozlov, Andrei/H-2117-2016 OI Kozlov, Andrei/0000-0003-4611-1534 NR 32 TC 1 Z9 1 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S49 EP S58 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700006 ER PT J AU Caceres, CF AF Caceres, Carlos F. TI Design and integration of ethnography within an international behavior change HIV/sexually transmitted disease prevention trial - NIMH Collaborative HIV/STD Prevention Trial Group SO AIDS LA English DT Article DE behavioral interventions; culture; developing nations; ethnography; qualitative data ID OPINION LEADERS; RISK BEHAVIOR; COMMUNITY; INTERVENTION; AIDS; ISSUES AB Objective: To use a common ethnographic study protocol across five countries to provide data to confirm social and risk settings and risk behaviors, develop the assessment instruments, tailor the intervention, design a process evaluation of the intervention, and design an understandable informed consent process. Design: Methods determined best for capturing the core data elements were selected. Standards for data collection methods were established to enable comparable implementation of the ethnographic study across the five countries. Methods: The methods selected were participant observation, focus groups, open-ended interviews, and social mapping. Standards included adhering to core data elements, number of participants, mode of data collection, type of data collection instrument, number of data collectors at each type of activity, duration of each type of activity, and type of informed consent administered. Sites had discretion in selecting which methods to use to obtain specific data. Results: The ethnographic studies provided input to the Trial's methods for data collection, described social groups in the target communities, depicted sexual practices, and determined core opinion leader characteristics; thus providing information that drove the adaptation of the intervention and facilitated the selection of venues, behavioral outcomes, and community popular opinion leaders (C-POLs). Conclusion: The described rapid ethnographic approach worked well across the five countries, where findings allowed local adaptation of the intervention. When introducing the C-POL intervention in new areas, local non-governmental and governmental community and health workers can use this rapid ethnographic approach to identify the communities, social groups, messages, and C-POLs best suited for local implementation. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Ctr Biomed, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Yale Univ, New Haven, CT 06520 USA. Fujian Ctr Dis Control & Prevent, Fujian, Peoples R China. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC USA. SAHAI Trust, Madras, Tamil Nadu, India. CDC, Atlanta, GA 30333 USA. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RP Caceres, CF (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru. NR 35 TC 0 Z9 0 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S37 EP S48 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700005 ER PT J AU Caceres, CF AF Caceres, Carlos F. TI Challenges and processes of selecting outcome measures for the NIMH Collaborative HIV/STD Prevention Trial - NIMH Collaborative HIV/STD Prevention Trial Group SO AIDS LA English DT Article DE AIDS; behavioral endpoints; behavioral intervention; biological endpoints; community popular opinion leader; developing nations; HIV; outcome measures; risk behavior ID COMMUNITY INTERVENTION TRIAL; INCOME HOUSING DEVELOPMENTS; SMOKING CESSATION COMMIT; HIV-PREVENTION; DEMONSTRATION PROJECTS; OPINION LEADERS; SEXUAL-BEHAVIOR; EASTERN CHINA; RISK BEHAVIOR; CONDOM USE AB Objective: To review the challenges of designing behavioral and biological outcome measures for the multinational NIMH Collaborative HIV/STD Prevention Trial and provide the rationale for selecting these measures. Design: Although many different evidence-based prevention programmes have been developed, few have been evaluated in different countries, cultures, and populations. One issue in evaluating the generalized efficacy of any prevention approach is to identify a set of common outcome measures useful across diverse settings and peoples. The Trial is designed to evaluate whether the community popular opinion leader intervention can be adapted cross-nationally and cross-culturally for different populations and still retain its efficacy. Methods: Literature reviews, investigator experience, ethnographic study, pilot studies, and epidemiological studies were used to select the endpoints for the Trial. Results and conclusion: Both biological and behavioral data will be obtained at baseline and 12 and 24 months post-baseline. Communities that receive the intervention will be compared with matched control communities on two primary outcomes: (i) a change in self-reported unprotected sexual acts with non-spousal, non-live-in partners; and (ii) the incidence of sexually transmitted disease (STD), defined as a composite index of viral and bacterial STD. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Ctr Biomed, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Fujian Ctr Dis Control & Prevent, Fujian, Peoples R China. Yale Univ, New Haven, CT 06520 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Arizona, Tucson, AZ 85721 USA. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. CDC, Atlanta, GA 30333 USA. SAHAI Trust, Madras, Tamil Nadu, India. RP Caceres, CF (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru. NR 43 TC 0 Z9 0 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S29 EP S36 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700004 ER PT J AU Caceres, CF AF Caceres, Carlos F. TI Selection of populations represented in the NIMH collaborative HIV/STD prevention trial - NIMH Collaborative HIV/STD Prevention Trial Group SO AIDS LA English DT Article DE behavioral interventions; developing nations; epidemiological methods; epidemiology; intervention studies; risk factors; sexual behavior ID SEXUALLY-TRANSMITTED-DISEASES; HIV TRANSMISSION; SEX WORKERS; CHINA; PETERSBURG; EPIDEMIC; SYPHILIS; RUSSIA; TRENDS; INDIA AB Objective: To identify venues with vulnerable populations suitable for testing the community popular opinion leader intervention in each of the five countries (China, India, Peru, Russia, and Zimbabwe) participating in the National Institute of Mental Health (NIMH) Collaborative HIV/STD Prevention Trial. Design: HIV epidemiology and vulnerable populations differ considerably across the countries. Therefore, different community populations were targeted in the five countries. Methods: Venues and populations were chosen on the basis of specific selection criteria (investigated during the Trial's ethnographic research phase): the willingness of stakeholders and gatekeepers of the venues to cooperate; geographical boundaries defining each venue; population stability within venues; the independence of venues and non-overlap of population members across multiple venues; population size within each venue; social interaction opportunities; and either a high level of sexual risk behavior or a high prevalence of sexually transmitted diseases (STDs) or HIV. Results: Venues and populations selected were food market stall owners and workers in China, male patrons of wine shops and at-risk women congregating near the shops in India, young men and women in social gathering points in neighborhoods in Peru, trade and vocational school dormitory residents in Russia, and people congregating in growth points in Zimbabwe. Conclusion: Although the target populations differed across countries, they shared in common high behavioral or biological risk at baseline and suitability for a randomized trial of a community-level HIV/STD prevention behavioral intervention. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Ctr Biomed, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Fujian Ctr Dis Control & Prevent, Fujian, Peoples R China. Yale Univ, New Haven, CT 06520 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Arizona, Tucson, AZ 85721 USA. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. SAHAI Trust, Madras, Tamil Nadu, India. CDC, Atlanta, GA 30333 USA. RP Caceres, CF (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru. NR 41 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S19 EP S28 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700003 ER PT J AU Caceres, CF AF Caceres, Carlos F. TI Methodological overview of a five-country community-level HIV/sexually transmitted disease prevention trial - NIMH Collaborative HIV/STD Prevention Trial Group SO AIDS LA English DT Article DE AIDS; behavioral intervention; clinical trial; HIV; international settings; sexually transmitted diseases ID OPINION LEADERS; RISK BEHAVIOR; INTERVENTION; REDUCTION; CITIES; MODELS AB Objective: To provide an overview of the National Institute of Mental Health (NIMH) Collaborative HIV/STD Prevention Trial taking place in five populations at risk of HIV and sexually transmitted diseases in China, India, Peru, Russia, and Zimbabwe, including the rationale, study management, methods, and proposed data analyses. Design: The Trial will scientifically evaluate the effectiveness of the community popular opinion leader (C-POL) community-level HIV prevention intervention that was adapted for use in the various cultures within the resource limitations faced by service providers in world regions threatened by high rates of HIV infection. Methods: The study phases consist of an ethnographic study, pilot studies, an epidemiological study, and a community-randomized trial. The Trial uses the C-POL intervention, which researchers selected on the basis of research that shows the intervention's success in populations vulnerable to HIV risk behavior in the United States, and has the potential to be applied in a variety of international settings. Results: Trial results will be tabulated by and across country by randomization assignment. Results will include a careful review of data to substantiate original assumptions used in the study design. Data collection will not conclude until August 2007. Conclusion: Although data collection is incomplete, researchers have learned lessons throughout the development of the study. These include the importance of preliminary epidemiological studies; the close monitoring of biological testing, follow-up rates and process measures at international sites; the tailoring of assessments and interventions to various cultures; regular communication; and a review of the timeline to accommodate Institutional Review Board clearances. (C) 2007 Lippincott Williams & Wilkins. C1 Univ Peruana Cayetano Heredia, Lima, Peru. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. St Petersburg State Univ, Biomed Ctr, St Petersburg, Russia. NIMH, Bethesda, MD 20892 USA. Univ Zimbabwe, Sch Med, Harare, Zimbabwe. Fujian Ctr Dis Control & Prevent, Fujian, Peoples R China. Yale Univ, New Haven, CT 06520 USA. Univ Calif San Francisco, San Francisco Dept Publ Hlth, San Francisco, CA 94143 USA. Miriam Hosp, Providence, RI 02906 USA. Univ N Carolina, Chapel Hill, NC USA. SAHAI Trust, Madras, Tamil Nadu, India. CDC, Atlanta, GA 30333 USA. Natl Ctr STD & Leprosy Control, Nanjing, Peoples R China. Univ Arizona, Tucson, AZ 85721 USA. RP Caceres, CF (reprint author), Univ Peruana Cayetano Heredia, Lima, Peru. NR 28 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD APR PY 2007 VL 21 SU 2 BP S3 EP S18 PG 16 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 164II UT WOS:000246226700002 ER PT J AU Wilson, TE Feldman, J Vega, MY Gandhi, M Richardson, J Cohen, MH McKaig, R Ostrow, D Robison, E Gange, SJ AF Wilson, Tracey E. Feldman, Joseph Vega, Miriam Y. Gandhi, Monica Richardson, Jean Cohen, Mardge H. McKaig, Rosemary Ostrow, David Robison, Esther Gange, Stephen J. TI Acquisition of new sexual partners among women with HIV infection: Patterns of disclosure and sexual behavior within new partnerships SO AIDS EDUCATION AND PREVENTION LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; RISK BEHAVIOR; INTERAGENCY HIV; UNITED-STATES; TRANSMISSION; MEN; SEROSTATUS; PREVENTION; STRATEGIES; EPIDEMIC AB This study describes the sexual behavior of HIV-positive women within new versus more established relationships and determines whether beliefs about HIV antiretroviral therapy (ART) impact these behaviors. The Women's Interagency HIV Study is a longitudinal cohort study of HIV among women in the United States. Sexually active HIV-positive women (N = 1,090) completed interviews on beliefs and behaviors at 6-month intervals. Data were analyzed for the period between April 2002 and March 2003. Of 1,517 sexual partners reported, 32% were newly acquired within the previous 6 months. As compared with more established sexual relationships, newer partnerships were characterized by greater condom use consistency (odds ratio = 1.8, 95% confidence interval = 1.4 -2.3). Holding beliefs that ART is protective for HIV transmission impacted the relationship between partner type and condom use. In established relationships, 63% reported consistent condom use if they believed that ART is not protective, whereas 54% reported consistent condom use if they believed that ART is protective. Conclusions: These findings highlight the importance of ongoing support for sexual risk reduction among women with HIV-infection and for strategies that reduce the strength of relationships between ART beliefs and sexual risk behavior. C1 Suny Downstate Med Ctr, Dept Prevent Med & Community Hlth, Brooklyn, NY 11203 USA. Latino Commiss AIDS, New York, NY USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Sch Med, Los Angeles, CA USA. Cook Cty Hosp, Chicago, IL 60612 USA. NIAID, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Wilson, TE (reprint author), Suny Downstate Med Ctr, Dept Prevent Med & Community Hlth, Box 1240,450 Clarkson Ave, Brooklyn, NY 11203 USA. EM Tracey.Wilson@downstate.edu OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [M01-RR-00083, M01-RR-00071, M01-RR-00079]; NIAID NIH HHS [U01-AI-35004, U01-AI-34989, U01 AI042590-12, U01 AI042590, U-1-AI-34994, U01-AI-31834, U01-AI-34993, U01-AI-42590]; NICHD NIH HHS [U01-HD-32632]; PHS HHS [U50/CCU300860] NR 26 TC 15 Z9 15 U1 2 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD APR PY 2007 VL 19 IS 2 BP 151 EP 159 DI 10.1521/aeap.2007.19.2.151 PG 9 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 155LY UT WOS:000245580100005 PM 17411417 ER PT J AU Rutebemberwa, A Bess, JW Brown, B Arroyo, M Eller, M Slike, B Polonis, V McCutchan, F Currier, JR Birx, D Robb, M Marovich, M Lifson, JD Cox, JH AF Rutebemberwa, A. Bess, J. W. Brown, B. Arroyo, M. Eller, M. Slike, B. Polonis, V. McCutchan, F. Currier, J. R. Birx, D. Robb, M. Marovich, M. Lifson, J. D. Cox, J. H. TI Evaluation of aldrithiol-2-inactivated preparations of HIV type 1 subtypes A, B, and D as reagents to monitor T cell responses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID SIMIAN IMMUNODEFICIENCY VIRUS; PLASMACYTOID DENDRITIC CELLS; CYTOKINE FLOW-CYTOMETRY; VIRAL LOAD; HIV-1-POSITIVE INDIVIDUALS; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; PEPTIDE SETS; INFECTION; CD8 AB The development of HIV vaccines is an urgent priority and there is need to generate reagents representing multiple subtypes that can be used to screen HIV-1-specific responses. We used Aldrithiol-2 ( AT-2), a mild oxidizing reagent, to eliminate the infectivity of HIV while maintaining its structure and ability to be processed for presentation to T cells. Inactivated subtype A, B, and D viruses were evaluated for their ability to stimulate T cell responses in PBMC samples from 18 U. S. subjects infected with HIV-1 subtype B and 32 Ugandan subjects infected with subtypes A and D or recombinants AC and AD. Five HIV-1-negative samples were also analyzed. T cell responses to AT-2-inactivated viral isolates were monitored by interferon-gamma ( IFN-gamma) intracellular cytokine secretion ( ICS) analysis; matched microvesicle preparations served as negative controls. Among the 18 subtype B infected subjects, 39% had CD3(+) CD4(+) IFN-gamma responses and 67% had CD3(+) CD8(+) IFN-gamma responses. Of the 32 Ugandan subjects, 34% demonstrated CD3(+) CD4(+) IFN-gamma responses and 78% demonstrated CD3(+) CD8(+) IFN-gamma responses. Both subtype-specific and cross-reactive responses were observed. Responses to the AT-2 viruses tended to be lower in magnitude than those detected by a set of overlapping gag peptides. Robust lymphoproliferative responses to AT-2 viruses were seen in a subset of subjects. In conclusion, AT-2-inactivated HIV-1 virions stimulated both CD4 and CD8 HIV-1-specific responses and may provide an additional reagent for screening HIV-1-specific responses in HIV seropositives and vaccinees. C1 Henry Jackson Fdn, US Mil HIV Res Program, Rockville, MD 20850 USA. Natl Canc Inst Frederick, SAIC Frederick, AIDS Vaccine Program, Frederick, MD 21702 USA. Makerere Univ, Walter Reed Project, Kampala, Uganda. RP Cox, JH (reprint author), Henry Jackson Fdn, US Mil HIV Res Program, 13 Taft Court, Rockville, MD 20850 USA. EM jcox@hivresearch.org OI Arroyo, Miguel/0000-0001-7416-8867 FU NCI NIH HHS [N01 CO 12400] NR 72 TC 13 Z9 13 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 532 EP 542 DI 10.1089/aid.2006.0136 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300007 PM 17506610 ER PT J AU Ratner, L Harrington, W Feng, X Grant, C Jacobson, S Noy, A Sparano, J Lee, J Ambinder, R Campbell, N Lairmore, M AF Ratner, Lee Harrington, William Feng, Xuan Grant, Christopher Jacobson, Steve Noy, Ariela Sparano, Joseph Lee, Jeannette Ambinder, Richard Campbell, Nancy Lairmore, Michael CA AIDS Malignancy Consortium TI Chemoantiretroviral therapy for adult T cell leukemia lymphoma SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Washington Univ, Div Oncol, St Louis, MO USA. Univ Miami, Sch Med, Dept Med, Miami, FL USA. NIH, NINDS, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Montefiore Med Ctr, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. Univ Alabama, AIDS Malignacy Consortium Operat Ctr, Birmingham, AL USA. Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA. Ohio State Univ, Comprehens Canc Hosp 5, Coll Vet Med, Solove Res Inst,Dept Oncol, Columbus, OH 43210 USA. EM lratner@im.wustl.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 587 EP 587 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300032 ER PT J AU Iha, H Taguchi, S Kawaguchi, A Kawashima, T Tanaka, Y Sawa, H Nishizono, A Sata, T Hall, W Jeang, KT Hasegawa, HT AF Iha, Hidekatsu Taguchi, Sin-ya Kawaguchi, Akira Kawashima, Taro Tanaka, Yuetsu Sawa, Hirofumi Nishizono, Akira Sata, Tetsutaro Hall, William Jeang, Kuan T. Hasegawa, Hideki T. TI A water-soluble hsp90 inhibitor 17-DMAG suppresses tax-mediated oncogenic signaling both in vitro and in vivo SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Oita Univ, Fac Med, Dept Infect Dis, Oita 87011, Japan. Natl Inst Infect Dis, Dept Pathol, Tokyo, Japan. Univ Ryukyus, Dept Immunol, Okinawa, Japan. Hokkaido Univ, Dept Mol Pathobiol, Sapporo, Hokkaido, Japan. Univ Coll Dublin, Dept Med Microbiol, Dublin 2, Ireland. NIAID, Mol Biol Lab, Bethesda, MD 20892 USA. EM hiha@med.oita-u.ac.jp RI Jeang, Kuan-Teh/A-2424-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 594 EP 595 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300052 ER PT J AU Harashima, N Shimizu, Y Takamori, A Kurihara, K Utsunomiya, A Tanosaki, R Masuda, M Okamura, J Kannagi, M AF Harashima, Nanae Shimizu, Yukiko Takamori, Ayako Kurihara, Kiyoshi Utsunomiya, Atae Tanosaki, Ryuji Masuda, Masato Okamura, Jun Kannagi, Mari TI Positive conversion of tax-specific CTL response in ATL patients after hematopoietic stem cell transplantation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Tokyo Med & Dent Univ, Dept Immunotherapeut, Tokyo, Japan. NIH, NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Imamura Bunin Hosp, Dept Hematol, Kagoshima, Japan. Natl Canc Ctr, Stem Cell Transplantat Unit, Tokyo, Japan. Univ Ryukyus, Dept Internal Med 2, Okinawa, Japan. Kyushu Natl Canc Ctr, Inst Clin Res, Fukuoka, Japan. EM kann.impt@tmd.ac.jp NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 595 EP 595 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300053 ER PT J AU O'Mahony, D Morris, JC Moses, L Diana, O Matthews, H Stetler-Stevenson, M Urquhart, N Kaucic, K Hammershaimb, L Warfe, G Waldmann, TA Janik, JE AF O'Mahony, Deirdre Morris, John C. Moses, Leslie Diana, O'Hagan Matthews, Helen Stetler-Stevenson, Maryalice Urquhart, Nicole Kaucic, Karen Hammershaimb, Luz Warfe, Gillian Waldmann, Thomas A. Janik, John E. TI A phase I trial of siplizumab in CD2-positive lymphoproliferative disease SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. Univ W Indies, Dept Hematol, Kingston 7, Jamaica. MedImmune Oncol Inc, Gaithersburg, MD USA. Univ W Indies, Dept Pathol, Mona, Jamaica. EM omahonyd@mail.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 598 EP 598 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300063 ER PT J AU Janik, JE Dunleavy, KE Pittaluga, SE Jaffe, ES Grant, N Shovlin, M Sharma, K Warfe, G Stetler-Stevenson, M Wilson, WH AF Janik, John E. Dunleavy, Kieron E. Pittaluga, Stefania E. Jaffe, Elaine S. Grant, Nicole Shovlin, Margaret Sharma, Kamal Warfe, Gillian Stetler-Stevenson, Maryalice Wilson, Wyndham H. TI A pilot trial of alemtuzumab (campath-1H) and dose-adjusted EPOCH (DA- EPOCH) in CD52-expressing aggressive T cell malignancies SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. Univ West Indies, Dept Pathol, Mona, Jamaica. EM janikj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 606 EP 606 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300085 ER PT J AU Grant, CW Oh, UW Yao, KW Yamano, YW Jacobson, SW AF Grant, Christian W. Oh, Unsong W. Yao, Karen W. Yamano, Yoshihisa W. Jacobson, Steven W. TI Impairment of treg-specific Foxp3 expression by HTLV-I-induced dysregulation of TGF-beta signaling SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NIH, NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. Kagoshima City Hosp, Dept Neurol, Kagoshima 890, Japan. EM jacobsons@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 614 EP 614 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300108 ER PT J AU Enose-Akahata, Y Oh, U Jacobson, S AF Enose-Akahata, Yoshimi Oh, Unsong Jacobson, Steve TI Spontaneous CD8 T cell degranulation in patients with human T lymphocyte virus type I-associated neurological disease. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NIH, NINDS, Viral Immunol Sect, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 616 EP 616 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300115 ER PT J AU Wencker, M Sausse, C Derse, D Gazzolo, L Dodon, MD AF Wencker, Melanie Sausse, Celine Derse, David Gazzolo, Louis Dodon, Madeleine Duc TI Regulation of the pre-TCRalpha gene transcription by tax in human immature thymocytes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Ecole Normale Super Lyon, INSERM, U758, IFR BioSci Lyon Gerland 128, F-69364 Lyon, France. NCI, Ctr Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM melanie.wencker@ens-lyon.fr RI Duc-Dodon, Madeleine/I-6580-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 619 EP 619 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300123 ER PT J AU Wencker, M Derse, D Gazzolo, L Dodon, MD AF Wencker, Melanie Derse, David Gazzolo, Louis Dodon, Madeleine Duc TI Effect of tax on gene expression during human T cell differentiation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Ecole Normale Super Lyon, INSERM, IFR BioSci Lyon Gerland 128, U758 Virol Human, F-69364 Lyon, France. NCI, Ctr Canc Res, HIV Drug Resistance Program, Frederick, MD 21702 USA. EM melanie.wencker@ens-lyon.fr RI Duc-Dodon, Madeleine/I-6580-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 623 EP 623 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300135 ER PT J AU Morris, J Sharma, K O'Mahony, D O'Hagan, D Leslie, M Urquhart, N Wharfe, G Cranston, B Waldmann, TA Janik, JE AF Morris, John Sharma, Kamal O'Mahony, Deirdre O'Hagan, Diana Leslie, Moses Urquhart, Nicole Wharfe, Gilian Cranston, Bev Waldmann, Thomas A. Janik, John E. TI A phase II study of the efficacy and toxicity of alemtuzumab (Campath) for treatment of human T cell lymphotrophic virus-1 (HTLV-1)-associated adult T cell leukemia/lymphoma (ATL) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NCI, Ctr Canc Res, Metab Branch, Bethesda, MD 20892 USA. Univ W Indies, Dept Haematol, Kingston 7, Jamaica. Univ W Indies, Dept Pathol, Kingston 7, Jamaica. EM jmorris@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 632 EP 633 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300163 ER PT J AU Jeong, SJ Lu, HX Cho, WK Park, HU Pise-Masison, CA Brady, JN AF Jeong, Soo-Jin Lu, Hanxin Cho, Won-Kyung Park, Hyeon Ung Pise-Masison, Cynthia A. Brady, John N. TI CARM1 enhances transcription of the HTLV-1 LTR through a direct interaction with tax protein SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NIH, NCI, Ctr Canc Res, Virus Tumor Biol Sect,Lab Cellular Oncol, Bethesda, MD 20892 USA. Natl Inst Infect Dis, Ctr AIDS Res, Tokyo, Japan. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 643 EP 643 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300193 ER PT J AU Umeki, K Hisada, M Cranston, B Maloney, E Hanchard, B Okayama, A AF Umeki, Kazumi Hisada, Michie Cranston, Beverley Maloney, Elizabeth Hanchard, Barrie Okayama, Akihiko TI Analysis of clonal expansion of HTLV-1-infected cells in the children in Jamaica SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Miyazaki Univ, Dept Rheumatol, Infect Dis & Lab Med, Miyazaki, Japan. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ W Indies, Dept Pathol, Mona, Jamaica. Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 645 EP 645 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300198 ER PT J AU Lambert, S Hermine, O Petrow-Sadowski, C Bouttier, M Ruscetti, FW Jones, KS Pique, CS AF Lambert, Sophie Hermine, Olivier Petrow-Sadowski, Cari Bouttier, Manuella Ruscetti, Francis W. Jones, Kathryn S. Pique, Claudine S. TI Roles of HSPG and NRP1 in HTLV-1 entry SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 Inst Cochin, INSERM, CNRS, Fac Med Rene Descartes,UMR 8104,Dept Biol Cellula, Paris, France. Univ Paris 05, CNRS, Inst Federat Necker, UMR 8147,Fac Med, F-75270 Paris, France. NCI, SAIC, Basic Res Program, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 649 EP 650 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300213 ER PT J AU Fukumoto, R Magruder, JT Goss, TA Ostas, JA Bialuk, IA Valeri, VW Guszcznski, T Andresen, V Nicot, C Franchini, G AF Fukumoto, Risaku Magruder, Jonathan T. Goss, Talisa A. Ostas, Joanna A. Bialuk, Izabela A. Valeri, Valerio W. Guszcznski, Tad Andresen, Vibeke Nicot, Christophe Franchini, Genoveffa TI Importance of signal peptide removal, palmitoylation, and dimerization of the HTLV-1 p12 protein complex for lipid raft localization and proximal TCR signaling downregulation SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NCI, Lab Protein Dynam & Signaling, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 654 EP 654 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300226 ER PT J AU Pise-Masison, CA Radonovich, MA Dohoney, KA Morris, JC O'Mahoney, DC Waldmann, TA Janik, JE Brady, JN AF Pise-Masison, Cynthia A. Radonovich, Michael A. Dohoney, Kathleen A. Morris, John C. O'Mahoney, Deirdre C. Waldmann, Thomas A. Janik, John E. Brady, John N. TI Gene expression profiling of ATL patients: Identification of signaling pathways that contribute to ATL SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NIH, NCI, CCR, Lab Cellular Oncol, Bethesda, MD 20892 USA. NIH, NCI, CCR, Metab Branch, Bethesda, MD 20892 USA. EM masisonc@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 655 EP 656 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300229 ER PT J AU Yao, K Lisinski, I Takenouchi, N Jones, K Fugo, K Cushman, SW Ruscetti, FW Jacobson, SW AF Yao, Karen Lisinski, Ivonne Takenouchi, Norihiro Jones, Kathryn Fugo, Kazunori Cushman, Samuel W. Ruscetti, Francis W. Jacobson, Steven W. TI GLUT1 is not the primary receptor, but is associated with cell cell transmission of HTLV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT 13th International Conference on Human Retrovirology - HTLV and Related Viruses CY MAY 21-25, 2007 CL Hakone, JAPAN C1 NIH, NINDS, Viral Immunol Sect, Neuroimmunol Branch, Bethesda, MD 20892 USA. NIH, NIDDK, Expt Diabet Metab & Nutr Sect, Bethesda, MD 20892 USA. SAIC, Basic Res Program, Frederick, MD USA. NCI, Ctr Canc Res, Expt Immunol Lab, Frederick, MD 21701 USA. EM jacobsons@ninds.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 2007 VL 23 IS 4 BP 657 EP 657 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 160AN UT WOS:000245909300234 ER PT J AU Soriano, V Heneine, W Vandamme, A Franchini, G AF Soriano, Vincent Heneine, Walid Vandamme, Annemieke Franchini, Genoveffa TI Foreword SO AIDS REVIEWS LA English DT Editorial Material C1 Hosp Carlos III, Madrid, Spain. CDC, Atlanta, GA 30333 USA. Rega Inst, Louvain, Belgium. NIH, Bethesda, MD 20892 USA. RP Soriano, V (reprint author), Hosp Carlos III, Madrid, Spain. RI Vandamme, Anne Mieke/I-4127-2012; santos, sofia/I-1637-2012 OI Vandamme, Anne Mieke/0000-0002-6594-2766; NR 0 TC 0 Z9 0 U1 0 U2 2 PU PERMANYER PUBLICATIONS PI BARCELONA PA MALLORCA, 310, BARCELONA, SPAIN SN 1139-6121 J9 AIDS REV JI Aids Rev. PD APR-JUN PY 2007 VL 9 IS 2 BP 67 EP 67 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 193PK UT WOS:000248286300001 ER PT J AU Clarimon, J Gray, RR Williams, LN Enoch, MA Robin, RW Albaugh, B Singleton, A Goldman, D Mulligan, CJ AF Clarimon, Jordi Gray, Rebecca R. Williams, Lindsey N. Enoch, Mary-Anne Robin, Robert W. Albaugh, Bernard Singleton, Andrew Goldman, David Mulligan, Connie J. TI Linkage disequilibrium and association analysis of alpha-synuclein and alcohol and drug dependence in two American Indian populations SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dependence; drug dependence; alpha-synuclein; NACP-REP1; association analysis ID MESSENGER-RNA LEVELS; AFFECTIVE-DISORDERS; PARKINSONS-DISEASE; ALLELIC VARIATION; MISSION INDIANS; GENE; HAPLOTYPES; GENOME; ASSIGNMENT; NACP-REP1 AB Background: alpha-Synuclein is involved in dopaminergic neurotransmission and has been implicated in a number of neurodegenerative disorders, such as Parkinson's disease. Recent studies, in humans and in rat and monkey models, have suggested that alpha-synuclein may play a role in the development and maintenance of certain addictive disorders. Methods: Fifteen single-nucleotide polymorphisms (SNPs) in the alpha-synuclein gene (SNCA) and 1 upstream microsatellite repeat (NACP-REP1) were assayed in Southwest (SW; n=514) and Plains (n=420) American Indian populations. Patterns of linkage disequilibrium (LD) at SNCA were determined for the 2 populations and compared with Caucasian, African, and Asian populations in the HapMap database (http://www.hapmap.org). Assayed alleles and constructed haplotypes in the study populations were tested for association with 4 clinical phenotypes [alcohol dependence, alcohol use disorders, drug dependence, and drug use disorders (lifetime diagnoses)] as well as with 2 symptom count phenotypes (all 18 questions and the 8 questions diagnostic for alcohol dependence). Results: Patterns of LD at SNCA were similar in both Indian populations and were consistent with the LD structure in other populations as reflected in the HapMap database. Single allele tests revealed significant associations between 4 SNPs and drug dependence in the SW population and between 2 of those SNPs plus 2 other SNPs and drug dependence in SW males only. In the Plains population, a significant association was detected only in males between 2 SNPs and alcohol use disorders and between 1 SNP and alcohol dependence. In the SW population, 1 SNP was marginally significant with the total symptom count. However, in all cases, the support was modest and disappeared with correction for multiple comparisons. No association was found between constructed haplotypes and any of the phenotypes in either population. Conclusions: Despite modest support for association between multiple SNCA SNPs and several of the addictive disorders tested in this study, statistical significance disappeared after correction for multiple testing. Thus, our data do not support a role for a variant in the SNCA gene that contributes to alcohol or drug addiction in the 2 studied American Indian populations. Future research may focus on variants in the promoter region that could cause the changes in mRNA and protein levels observed in previous studies. C1 Univ Florida, Dept Anthropol, Gainesville, FL 32610 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Neurogenet Lab, Rockville, MD USA. Yale Univ, Sch Med, Juneau, AK USA. Ctr Human Behav Studies Inc, Weatherford, OK USA. RP Mulligan, CJ (reprint author), Univ Florida, Dept Anthropol, 1376 Mowry Rd, Gainesville, FL 32610 USA. EM mulligan@anthro.ufl.edu RI Singleton, Andrew/C-3010-2009; Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Clarimon, Jordi/0000-0002-6824-6942 FU NIAAA NIH HHS [R03 AA 12906] NR 43 TC 18 Z9 19 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2007 VL 31 IS 4 BP 546 EP 554 DI 10.1111/j.1530-0277.2007.00338.x PG 9 WC Substance Abuse SC Substance Abuse GA 147AQ UT WOS:000244976200003 PM 17374033 ER PT J AU Krupitsky, EM Rudenko, AA Burakov, AM Slavina, TY Grinenko, AA Pittman, B Gueorguieva, R Petrakis, IL Zvartau, EE Krystal, JH AF Krupitsky, Evgeny M. Rudenko, Anatoly A. Burakov, Andrey M. Slavina, Tatyana Y. Grinenko, Alexander A. Pittman, Brian Gueorguieva, Ralitza Petrakis, Ismene L. Zvartau, Edwin E. Krystal, John H. TI Antiglutamatergic strategies for ethanol detoxification: Comparison with placebo and diazepam SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE ethanol; alcoholism; dependence; withdrawal; glutamate; glutamate receptors (NMDA, AMPA, kainate); anticonvulsant; lamotrigine; memantine; topiramate ID CEREBELLAR GRANULE CELLS; RAT HIPPOCAMPAL-NEURONS; ALCOHOL-WITHDRAWAL; NMDA RECEPTOR; GABA(A) RECEPTORS; GLUTAMATE RECEPTORS; AMYGDALAR NEURONS; CALCIUM CURRENTS; A RECEPTORS; IN-VITRO AB Background: Benzodiazepines are the standard pharmacotherapies for ethanol detoxification, but concerns about their abuse potential and negative effects upon the transition to alcohol abstinence drive the search for new treatments. Glutamatergic activation and glutamate receptor up-regulation contribute to ethanol dependence and withdrawal. This study compared 3 antiglutamatergic strategies for ethanol detoxification with placebo and to the benzodiazepine, diazepam: the glutamate release inhibitor, lamotrigine; the N-methyl-D-aspartate glutamate receptor antagonist, memantine; and the AMPA/kainite receptor inhibitor, topiramate. Methods: This placebo-controlled randomized single-blinded psychopharmacology trial studied male alcohol-dependent inpatients (n=127) with clinically significant alcohol withdrawal symptoms. Subjects were assigned to 1 of 5 treatments for 7 days: placebo, diazepam 10 mg TID, lamotrigine 25 mg QID, memantine 10 mg TID, or topiramate 25 mg QID. Additional diazepam was administered when the assigned medication failed to suppress withdrawal symptoms adequately. Results: All active medications significantly reduced observer-rated and self-rated withdrawal severity, dysphoric mood, and supplementary diazepam administration compared with placebo. The active medications did not differ from diazepam. Conclusions: This study provides the first systematic clinical evidence supporting the efficacy of a number of antiglutamatergic approaches for treating alcohol withdrawal symptoms. These data support the hypothesis that glutamatergic activation contributes to human alcohol withdrawal. Definitive studies of each of these medications are now needed to further evaluate their effectiveness in treating alcohol withdrawal. C1 VA Connecticut Healthcare Syst, Alcohol Res Ctr 116 A, West Haven, CT 06516 USA. Pavlov State Med Univ, St Petersburg Reg Ctr Addict & Psychopharmacol, St Petersburg, Russia. Yale Univ, Sch Med, NIAAA,Dept Psychiat, Ctr Translat Neurosci Alcoholism, New Haven, CT 06520 USA. RP Krystal, JH (reprint author), VA Connecticut Healthcare Syst, Alcohol Res Ctr 116 A, 950 Campbell Ave, West Haven, CT 06516 USA. EM john.krystal@yale.edu OI Gueorguieva, Ralitza/0000-0003-0944-5973 FU NIAAA NIH HHS [I-P50 AA-12870-04, K05 AA 14906-01, R21-AA014543-01A1] NR 52 TC 79 Z9 80 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD APR PY 2007 VL 31 IS 4 BP 604 EP 611 DI 10.1111/j.1530-0277.2007.00344.x PG 8 WC Substance Abuse SC Substance Abuse GA 147AQ UT WOS:000244976200009 PM 17374039 ER PT J AU Albert, MS Brown, DR Buchner, D Laditka, J Launer, LJ Scherr, P Thies, W Wagster, MV AF Albert, Marilyn S. Brown, David R. Buchner, David Laditka, James Launer, Lenore J. Scherr, Paul Thies, William Wagster, Molly V. TI The healthy brain and our aging population: Translating science to public health practice - Foreword SO ALZHEIMERS & DEMENTIA LA English DT Editorial Material C1 Univ S Carolina, Columbia, SC 29208 USA. Johns Hopkins Univ, Baltimore, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIA, Natl Inst Hlth, US Dept HHS, Bethesda, MD USA. Alzhiemers Assoc, Chicago, IL USA. RP Laditka, J (reprint author), Univ S Carolina, Columbia, SC 29208 USA. EM jladitka@gwm.sc.edu NR 0 TC 25 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD APR PY 2007 VL 3 IS 2 SU 1 BP S3 EP S5 DI 10.1016/j.jalz.2007.01.016 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 214SD UT WOS:000249757500002 PM 19595971 ER PT J AU Morrison-Bogorad, M Cahan, V Wagster, MV AF Morrison-Bogorad, Marcelle Cahan, Vicky Wagster, Molly V. TI Brain health interventions: The need for further research SO ALZHEIMERS & DEMENTIA LA English DT Article; Proceedings Paper CT Research Meeting on the Healthy Brain and Our Aging Population CY MAY 01-02, 2006 CL Atlanta, GA SP Ctr Dis Contro & Prevent, Alzheimers Assoc ID CONJUGATED EQUINE ESTROGENS; MILD COGNITIVE IMPAIRMENT; JAPANESE-AMERICAN MEN; ALZHEIMER-DISEASE; OLDER-ADULTS; LIFE-STYLE; POSTMENOPAUSAL WOMEN; INITIATIVE MEMORY; INCIDENT DEMENTIA; AGING HUMANS C1 NIA, Natl Inst Hlth, US Dept HHS, Bethesda, MD 20892 USA. RP Morrison-Bogorad, M (reprint author), NIA, Natl Inst Hlth, US Dept HHS, Bethesda, MD 20892 USA. EM morrisom@mail.nih.gov NR 46 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1552-5260 J9 ALZHEIMERS DEMENT JI Alzheimers. Dement. PD APR PY 2007 VL 3 IS 2 SU 1 BP S80 EP S85 DI 10.1016/j.jalz.2007.01.015 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 214SD UT WOS:000249757500014 PM 19595981 ER PT J AU Djousse, L Karamohamed, S Herbert, AG D'Agostino, RB Cupples, LA Ellison, RC AF Djousse, Luc Karamohamed, Samer Herbert, Alan G. D'Agostino, Ralph B. Cupples, L. Adrienne Ellison, R. Curtis TI Fucosyltransferase 3 polymorphism and atherothrombotic disease in the Framingham Offspring Study SO AMERICAN HEART JOURNAL LA English DT Article ID ISCHEMIC-HEART-DISEASE; LEWIS BLOOD-GROUP; GROUP PHENOTYPE; GENETIC-MARKER; RISK; PRODUCT; SYSTEM; MEN AB Background Previous studies have suggested a positive association between phenotypes of fucosyltransferase 3 (FUT3) gene (also known as Lewis. gene) and coronary heart disease. Methods We used data on 1735 unrelated subjects in the Framingham Offspring Study to assess whether 3 functional single-nucleotide polymorphisms (SNPs) of the FUT3 gene (T59G, T1067A, and T202C) were associated with prevalent atherothrombotic disease. Results Contrary to T1067A and T202C SNPs, there was evidence for an association between T59G.SNP and atherothrombotic disease prevalence. In a multivariable model controlling for age, sex, alcohol intake, pack-years of smoking, ratio of total to high-density lipoprotein cholesterol, and diabetes mellitus, ORs (95% Cl) for prevalent atherothrombotic disease were 1.0 (reference), 0.80 (0.46-1.41), and 6.70 (1.95-23.01) for TT, TG, and GG genotypes of the T59G SNP, respectively. Minor alleles of T202C and T1067A SNPs showed a modest and nonsignificant association with atherothrombotic disease. Overall, FUT3 polymorphism that influences the enzyme activity (GG genotype for T59G or :>= 1 minor allele of T202C or T1067A) was associated with increased atherothrombotic disease prevalence (OR 1.57, 1.05-2.34), and this association was stronger among abstainers (2-fold increased odds) than among current drinkers ( P for interaction 11). Conclusions Our data suggest that functional mutations of the FUT3 gene may be associated with an increased atherothrombotic disease prevalence, especially among abstainers. Additional studies are warranted to confirm these findings. C1 Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sect Prevent Med, Boston, MA 02215 USA. RP Djousse, L (reprint author), Brigham & Womens Hosp, Div Aging, 1620 Tremont St, Boston, MA 02115 USA. EM ldjousse@rics.bwh.harvard.edu RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [5K01 HL070444, K01 HL070444, N01-HC-25195, N01HC25195] NR 20 TC 5 Z9 6 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 2007 VL 153 IS 4 BP 636 EP 639 DI 10.1076/j.ahj.2006.12.015 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 158IE UT WOS:000245784200028 PM 17383304 ER PT J AU Stote, KS Baer, DJ Spears, K Paul, DR Harris, GK Rumpler, WV Strycula, P Najjar, SS Ferrucci, L Ingram, DK Longo, DL Mattson, MP AF Stote, Kim S. Baer, David J. Spears, Karen Paul, David R. Harris, G. Keith Rumpler, William V. Strycula, Pilar Najjar, Samer S. Ferrucci, Luigi Ingram, Donald K. Longo, Dan L. Mattson, Mark P. TI A controlled trial of reduced meal frequency without caloric restriction in healthy, normal-weight, middle-aged adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE caloric restriction; meal frequency; intermittent fasting; cholesterol metabolism; blood pressure; controlled diet; normal-weight adults ID FED CONTROLLED DIETS; LIPID PROFILES; BLOOD-PRESSURE; RISK-FACTORS; HUMANS; PLASMA; BREAKFAST; RATS; GLUCONEOGENESIS; CHOLESTEROL AB Background: Although consumption of 3 meals/d is the most common pattern of eating in industrialized countries, a scientific rationale for this meal frequency with respect to optimal health is lacking. A diet with less meal frequency can improve the health and extend the lifespan of laboratory animals, but its effect on humans has never been tested. Objective: A pilot study was conducted to establish the effects of a reduced-meal-frequency diet on health indicators in healthy, normal-weight adults. Design: The study was a randomized crossover design with two 8-wk treatment periods. During the treatment periods, subjects consumed all of the calories needed for weight maintenance in either 3 meals/d or 1 meal/d. Results: Subjects who completed the study maintained their body weight within 2 kg of their initial weight throughout the 6-mo period. There were no significant effects of meal frequency on heart rate, body temperature, or most of the blood variables measured. However, when consuming I meal/d, subjects had a significant increase in hunger; a significant modification of body composition, including reductions in fat mass; significant increases in blood pressure and in total, LDL-, and HDL-cholesterol concentrations; and a significant decrease in concentrations of cortisol. Conclusions: Normal-weight subjects are able to comply with a I meal/d diet. When meal frequency is decreased without a reduction in overall calorie intake, modest changes occur in body composition, some cardiovascular disease risk factors, and hematologic variables. Diurnal variations may affect outcomes. C1 USDA, ARS, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. Natl Inst Aging Intramural Res Program, Clin Res Branch, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Lab Cardiovasc Sci, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Lab Expt Gerontol, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Lab Immunol, Baltimore, MD USA. Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD USA. RP Baer, DJ (reprint author), USDA, ARS, Beltsville Human Nutr Res Ctr, 307B Ctr Rd, Beltsville, MD 20705 USA. EM david.baer@ars.usda.gov RI Mattson, Mark/F-6038-2012; Biguzzi, Felipe/E-4724-2015 FU Intramural NIH HHS [Z99 AG999999] NR 38 TC 71 Z9 72 U1 2 U2 20 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2007 VL 85 IS 4 BP 981 EP 988 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 156PO UT WOS:000245661700010 PM 17413096 ER PT J AU Das, SK Gilhooly, CH Golden, JK Pittas, AG Fuss, PJ Cheatham, RA Tyler, S Tsay, M McCrory, MA Lichtenstein, AH Dallal, GE Dutta, C Bhapkar, MV DeLany, JP Saltzman, E Roberts, SB AF Das, Sai Krupa Gilhooly, Cheryl H. Golden, Julie K. Pittas, Anastassios G. Fuss, Paul J. Cheatham, Rachel A. Tyler, Stephanie Tsay, Michelle McCrory, Megan A. Lichtenstein, Alice H. Dallal, Gerard E. Dutta, Chhanda Bhapkar, Manjushri V. DeLany, James P. Saltzman, Edward Roberts, Susan B. TI Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE glycemic load; caloric restriction; body weight; metabolism ID DOUBLY LABELED WATER; WEIGHT-LOSS DIETS; LOW-FAT DIET; LOW-CARBOHYDRATE-DIET; HEART-DISEASE; FOOD PROVISION; RISK-FACTORS; INDEX DIET; OBESITY; EXPENDITURE AB Background: There remains no consensus about the optimal dietary composition for sustained weight loss. Objective: The objective was to examine the effects of 2 dietary macronutrient patterns with different glycemic loads on adherence to a prescribed regimen of calorie restriction (CR), weight and fat loss, and related variables. Design: A randomized controlled trial (RCT) of diets with a high glycemic load (HG) or a low glycemic load (LG) at 30% CR was conducted in 34 healthy overweight adults with a mean (+/- SD) age of 35 +/- 6 y and body mass index (kg/m(2)) of 27.6 +/- 1.4. All food was provided for 6 mo in diets controlled for confounding variables, and subjects self-administered the plans for 6 additional months. Primary and secondary outcomes included energy intake measured by doubly labeled water, body weight and fatness, hunger, satiety, and resting metabolic rate. Results: All groups consumed significantly less energy during CR than at baseline (P < 0.01), but changes in energy intake, body weight, body fat, and resting metabolic rate did not differ significantly between groups. Both groups ate more energy than provided (eg, 21% and 28% CR at 3 mo and 16% and 17% CR at 6 mo with HG and LG, respectively). Percentage weight change at 12 mo was -8.04 +/- 4.1% in the HG group and -7.81 +/- 5.0% in the LG group. There was no effect of dietary composition on changes in hunger, satiety, or satisfaction with the amount and type of provided food during CR. Conclusions: These findings provide more detailed evidence to suggest that diets differing substantially in glycemic load induce comparable long-term weight loss. C1 USDA, Human Nutr Res Ctr Aging, Energy Metab Lab, Boston, MA 02111 USA. Tufts Univ, Res Ctr Aging, Boston, MA USA. Tufts New England Med Ctr Hosp, Boston, MA USA. Natl Inst Aging, NIH, Bethesda, MD USA. Duke Clin Res Inst, Durham, NC USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Roberts, SB (reprint author), USDA, Human Nutr Res Ctr Aging, Energy Metab Lab, Room 1312,711 Washington St, Boston, MA 02111 USA. EM susan.roberts@tufts.edu RI Biguzzi, Felipe/E-4724-2015 FU NIA NIH HHS [NGA-3U01-AG20480]; NIDDK NIH HHS [K23DK61506, P30 DK040561, P30 DK040561-11, T32 DK062032]; PHS HHS [H150001] NR 51 TC 139 Z9 141 U1 1 U2 21 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2007 VL 85 IS 4 BP 1023 EP 1030 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 156PO UT WOS:000245661700015 PM 17413101 ER PT J AU Ruhl, CE Harris, TB Ding, JZ Goodpaster, BH Kanaya, AM Kritchevsky, SB Simonsick, EM Tylavsky, FA Everhart, JE AF Ruhl, Constance E. Harris, Tamara B. Ding, Jingzhong Goodpaster, Bret H. Kanaya, Alka M. Kritchevsky, Stephen B. Simonsick, Eleanor M. Tylavsky, Frances A. Everhart, James E. CA Health ABC Study TI Body mass index and serum leptin concentration independently estimate percentage body fat in older adults SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE leptin; body composition; anthropometry; dual-energy X-ray absorptiometry; race; epidemiology; health; aging; and body composition study; Health ABC ID GENDER DIFFERENCES; RELATIVE WEIGHT; VISCERAL FAT; OBESITY; ADIPOSITY; PLASMA; RESISTANCE; OVERWEIGHT; HEIGHT; HUMANS AB Background: Because serum concentrations of leptin, a hormone produced by adipocytes, can be relatively reliably and inexpensively measured, it may be considered complementary to, or even a substitute for, body mass index (BMI) as a measure of adiposity. Objective: We examined the ability of BMI and leptin concentrations, separately and together, to estimate total percentage fat in older adults. Design: Total percentage fat measured by dual-energy X-ray absorptiometry and fasting serum leptin concentrations were measured in 2911 well-functioning 70-79-y-old participants (42% black, 51% women) in the Health, Aging, and Body Composition Study. Results: Mean (+/- SD) total percentage fat was 29.2 +/- 5.0% in men and 40.5 +/- 5.7% in women, and the geometric mean (+/- SD) serum leptin concentration was 5.6 +/- 2.5 ng/mL in the men and 16.4 +/- 2.3 ng/mL in the women. Among men, total percentage fat was strongly associated with both BMI (R-2 = 0.56) and leptin (R-2 = 0.57) in separate linear regression analyses and in a combined linear regression analysis (R-2 = 0.68). Similarly, among women, total percentage fat was associated with both BMI (R-2 = 0.65)and leptin (R-2 = 0.54) separately and in combination (model R-2 = 0.71). Independent relations of BMI and leptin with total percentage fat were also found among both black and white participants. With the population divided into quintiles according to percentage fat, BMI and serum leptin correctly classified 49% of men and 50% of women in the correct quintile. Conclusions: Among older adults, total percentage fat was better estimated by using both serum leptin concentrations and BMI than by using either alone. However, their performance does not suggest that they can substitute for more accurate measures. C1 Social & Sci Syst Inc, Silver Spring, MD 20910 USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD USA. NIA, Clin Res Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Internal Med,J Paul Sticht Ctr, Div Geriatr,Sect Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Div Endocrinol & Metab, Dept Med, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. NIDDKD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Ruhl, CE (reprint author), Social & Sci Syst Inc, 8757 Georgia Ave,12th Floor, Silver Spring, MD 20910 USA. EM cruhl@s-3.com FU Intramural NIH HHS; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIDDK NIH HHS [N01-DK-1-2478] NR 25 TC 32 Z9 33 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD APR PY 2007 VL 85 IS 4 BP 1121 EP 1126 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 156PO UT WOS:000245661700028 PM 17413114 ER PT J AU Derauf, C LaGasse, LL Smith, LM Grant, P Shah, R Arria, A Huestis, M Haning, W Strauss, A Della Grotta, S Liu, J Lester, BM AF Derauf, Chris LaGasse, Linda L. Smith, Lynne M. Grant, Penny Shah, Rizwan Arria, Amelia Huestis, Marilyn Haning, William Strauss, Arthur Della Grotta, Sheri Liu, Jing Lester, Barry M. TI Demographic and psychosocial characteristics of mothers using methamphetamine during pregnancy: Preliminary results of the Infant Development, Environment, and Lifestyle Study (IDEAL) SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE LA English DT Article DE maternal behavior; methamphetamine; parenting; substance abuse ID SUBSTANCE-ABUSING WOMEN; RISK; USERS; CHILDREN AB This study describes the psychological characteristics and caretaking environments of 131 women enrolled in the first longitudinal study of prenatal methamphetamine (MA) exposure and child development. Prenatal MA use was associated with lower maternal perceptions on quality of life, greater likelihood of substance use among family and friends, increased risk for ongoing legal difficulties, and a markedly increased likelihood of developing a substance abuse disorder. Our preliminary findings suggest that MA using women are more likely to have multiple, intertwined psychosocial risks that may result in maladaptive parenting and caregiving. These factors may impact the developmental outcomes of affected children. C1 Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. Brown Univ, Women & Infants Hosp, Brown Med Sch, Providence, RI USA. Bradley Hosp, Providence, RI USA. Harbor UCLA Med Ctr, Los Angeles Biomed Inst, Torrance, CA 90509 USA. Univ Calif Los Angeles, David Geffen Sch Med, Torrance, CA USA. Univ Oklahoma, Tulsa, OK USA. Blank Childrens Hosp Iowa Hlth, Des Moines, IA USA. Univ Maryland, College Pk, MD 20742 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. Long Beach Mem Med Ctr, Long Beach, CA USA. RP Derauf, C (reprint author), Dept Pediat, 1319 Punahou St, Honolulu, HI 96826 USA. EM dderauf@hawaii.edu OI Arria, Amelia/0000-0002-6360-9265 FU Intramural NIH HHS [Z01 DA000413-10, Z01 DA000433-08]; NCRR NIH HHS [P20 RR011091, P20 RR11091]; NIDA NIH HHS [R01 DA014948, 1R01DA014918] NR 20 TC 29 Z9 29 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0095-2990 J9 AM J DRUG ALCOHOL AB JI Am. J. Drug Alcohol Abuse PD APR PY 2007 VL 33 IS 2 BP 281 EP 289 DI 10.1080/00952990601175029 PG 9 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 163RX UT WOS:000246182000010 PM 17497551 ER PT J AU Pietrzak, RH Morasco, BJ Blanco, C Grant, BF Petry, NM AF Pietrzak, Robert H. Morasco, Benjamin J. Blanco, Carlos Grant, Bridget F. Petry, Nancy M. TI Gambling level and psychiatric and medical disorders in older adults: Results from the national epidemiologic survey on alcohol and related conditions SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT Summer Training on Aging Research Topics in Mental Health Conference CY AUG 05-07, 2005 CL San Diego, CA DE older adults; problem gambling; pathological gambling; recreational gambling; health; substance abuse; epidemiology ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; QUALITY-OF-LIFE; DSM-IV ALCOHOL; UNITED-STATES; PATHOLOGICAL GAMBLERS; PERSONALITY-DISORDERS; RHEUMATOID-ARTHRITIS; SOCIAL ACTIVITY; FAMILY-HISTORY AB Objective: This study examined the association between gambling level and psychiatric and medical disorders in a nationally representative sample of older adults. Method: Data on 10,563 U. S. older adults (age 60 or older) were analyzed from the National Epidemiologic Survey on Alcohol and Related Conditions. Results: A total 28.74% of older adults were lifetime recreational gamblers and 0.85% were lifetime disordered gamblers. Compared with older adults without a history of regular gambling, recreational gamblers had significantly elevated rates of alcohol (30.1% versus 12.8%), nicotine (16.9% versus 8.0%), mood (12.6% versus 11.0%), anxiety (15.0% versus 11.6%), and personality disorders (11.3% versus 7.3%) and obesity (25.6% versus 20.8%), but were less likely to have past-year diagnoses of arteriosclerosis (4.7% versus 6.0%) or cirrhosis (0.2% versus 0.4%). Disordered gamblers were significantly more likely than older adults without a history of regular gambling to have alcohol (53.2% versus 12.8%), nicotine (43.2% versus 8.0%), drug (4.6% versus 0.7%), mood (39.5% versus 11.0%), anxiety (34.5% versus 11.6%), and personality (43.0% versus 7.3%) disorders, and to have past-year diagnoses of arthritis (60.2% versus 44.3%) or angina (22.7% versus 8.8%). These results remained significant even after controlling for demographic, psychiatric, and behavioral risk factors. Conclusions: Lifetime recreational gamblers were more likely than nonregular gamblers to have psychiatric disorders but were less likely to have some medical conditions. Lifetime disordered gamblers had a range of lifetime psychiatric disorders and were more likely than nonregular gamblers to have past-year diagnoses of angina and arthritis. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06030 USA. Portland VA Med Ctr, Div Behav Hlth & Clin Neurosci, Portland, OR USA. Columbia Univ, Dept Psychiat, New York, NY USA. NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, 263 Farmington Ave, Farmington, CT 06030 USA. EM petry@psychiatry.uchc.edu RI Blanco, Carlos/I-4906-2013 OI Blanco, Carlos/0000-0001-6187-3057 FU Intramural NIH HHS; NIAAA NIH HHS [P50-AA03510]; NIDA NIH HHS [P50-DA09241, R01-DA016855, R01-DA13444, R01-DA14618]; NIMH NIH HHS [R01-MH60417, R01-MH60417-SUPP] NR 58 TC 51 Z9 51 U1 2 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2007 VL 15 IS 4 BP 301 EP 313 DI 10.1097/01.JGP.0000239353.40880.cc PG 13 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 149NX UT WOS:000245154800005 PM 17095749 ER PT J AU Foley, DJ Vitiello, MV Bliwise, DL Ancoli-Israel, S Monjan, AA Walsh, JK AF Foley, Daniel J. Vitiello, Michael V. Bliwise, Donald L. Ancoli-Israel, Sonia Monjan, Andrew A. Walsh, James K. TI Frequent napping is associated with excessive daytime sleepiness, depression, pain, and nocturia in older adults: Findings from the National Sleep Foundation '2003 Sleep in America' Poll SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE aging; naps; sleepiness; comorbidity; depression; nocturia ID CARDIOVASCULAR HEALTH; ELDERLY PERSONS; DISTURBANCES; EPIDEMIOLOGY; POPULATION; PREVALENCE; DISORDERS; DISEASE; NEED; NAP AB Objective: The objective of this study was to describe the prevalence and correlates of regular napping among older adults. Methods: The National Sleep Foundation's "2003 Sleep in America Poll," a 20-minute telephone interview that focused on the topic of " sleep and aging" (N = 1,506 adults 55-84 years of age). Results: Overall, 15% of respondents reported regular napping, ranging in prevalence from 10% among those 55-64 years of age to 25% among those 75-84 years of age. In addition to older age and a strong association with excessive daytime sleepiness, other factors that independently increased prevalence included a diagnosis of depression, bodily pain, and nocturia. Conclusions: Regular napping is common among older adults. Longitudinal studies of napping behavior and health status are needed to establish risk factors other than excessive daytime sleepiness. C1 Subst Abuse & Mental Hlth Serv Adm, US Dept HHS, Rockville, MD 20857 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Emory Univ, Dept Neurol, Atlanta, GA 30322 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. NIA, Neurobiol Aging Branch, Bethesda, MD 20892 USA. St Lukes Hosp, Sleep Med & Res Ctr, St Louis, MO USA. RP Foley, DJ (reprint author), Subst Abuse & Mental Hlth Serv Adm, US Dept HHS, 1 Choke Cherry Rd, Rockville, MD 20857 USA. EM daniel.foley@samhsa.hhs.gov OI Vitiello, Michael/0000-0002-9776-0473 NR 22 TC 81 Z9 82 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD APR PY 2007 VL 15 IS 4 BP 344 EP 350 DI 10.1097/01.JGP.0000249385.50101.67 PG 7 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 149NX UT WOS:000245154800009 PM 17384317 ER PT J AU Graf, SA Calado, RT Young, NS AF Graf, Solomon A. Calado, Rodrigo T. Young, Neal S. TI PTPN22 620W allele is not associated with aplastic anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE aplastic anemia; PTPN22; autoimmune disease; polymorphism AB The 1858C/T variant in PTPN22 imparts a gain of function mutation dysregulating T-cell stimulation and is associated with an array of autoimmune diseases. Using a case-control design, we compared the frequency of this polymorphism in 91 patients with acquired aplastic anemia to 132 ethnically matched controls. Representation of the PTPN22 variant was not significantly different between the two populations, suggesting that this gene polymorphism does not contribute to the etiology of aplastic anemia. Aplastic anemia thus joins a list of autoimmune diseases that commonly lack a major humoral disease component and do not associate with the PTPN22 variant. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr,Bldg 10-CRC,Rm 3E-5140, Bethesda, MD 20892 USA. EM youngns@mail.nih.gov RI Calado, Rodrigo/G-2619-2011; OI Calado, Rodrigo/0000-0002-7966-6029 FU Intramural NIH HHS NR 10 TC 4 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 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD APR PY 2007 VL 82 IS 4 BP 291 EP 292 DI 10.1002/ajh.20768 PG 2 WC Hematology SC Hematology GA 153VN UT WOS:000245464400007 PM 17034023 ER PT J AU Reich, D Patterson, N Ramesh, V De Jager, PL McDonald, GJ Tandon, A Choy, E Hu, DL Tamraz, B Pawlikowska, L Wassel-Fyr, C Huntsman, S Waliszewska, A Rossin, E Li, RL Garcia, M Reiner, A Ferrell, R Cummings, S Kwok, PY Harris, T Zmuda, JM Ziv, E AF Reich, David Patterson, Nick Ramesh, Vijaya De Jager, Philip L. McDonald, Gavin J. Tandon, Arti Choy, Edwin Hu, Donglei Tamraz, Bani Pawlikowska, Ludmila Wassel-Fyr, Christina Huntsman, Scott Waliszewska, Alicja Rossin, Elizabeth Li, Rongling Garcia, Melissa Reiner, Alexander Ferrell, Robert Cummings, Steve Kwok, Pui-Yan Harris, Tamara Zmuda, Joseph M. Ziv, Elad CA Hlth ABC Study TI Admixture mapping of an allele affecting interleukin 6 soluble receptor and interleukin 6 levels SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; NECROSIS-FACTOR-ALPHA; LINKAGE-DISEQUILIBRIUM; CARDIOVASCULAR HEALTH; INFLAMMATORY MARKERS; OLDER-ADULTS; GENOME; ASSOCIATION; GENES AB Circulating levels of inflammatory markers can predict cardiovascular disease risk. To identify genes influencing the levels of these markers, we genotyped 1,343 single-nucleotide polymorphisms (SNPs) in 1,184 African Americans from the Health, Aging and Body Composition (Health ABC) Study. Using admixture mapping, we found a significant association of interleukin 6 soluble receptor (IL-6 SR) with European ancestry on chromosome 1 (LOD 4.59), in a region that includes the gene for this receptor (IL-6R). Genotyping 19 SNPs showed that the effect is largely explained by an allele at 4% frequency in West Africans and at 35% frequency in European Americans, first described as associated with IL-6 SR in a Japanese cohort. We replicate this association (P << 1.0 x 10(-12)) and also demonstrate a new association with circulating levels of a different molecule, IL-6 (P < 3.4 x 10(-5)). After replication in 1,674 European Americans from Health ABC, the combined result is even more significant: P << 1.0 x 10(-12) for IL-6 SR, and P < 2.0 x 10(-9) for IL-6. These results also serve as an important proof of principle, showing that admixture mapping can not only coarsely localize but can also fine map a phenotypically important variant. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Richard B Simches Res Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Neurol, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Grad Program Pharmaceut Sci & Pharmacogenom, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Calif Pacific Med Ctr Res Inst, San Francisco Coordinating Ctr, San Francisco, CA USA. Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Washington, Sch Publ Hlth & Community Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Pittsburgh, Dept Epidemiol & Human Genet, Pittsburgh, PA 15260 USA. RP Reich, D (reprint author), Harvard Univ, Sch Med, Dept Genet, New Res Bldg,77 Ave Louis Pasteur, Boston, MA 02115 USA. EM reich@genetics.med.harvard.edu RI Kwok, Pui-Yan/F-7725-2014; Ziv, Elad/L-5396-2014; OI Kwok, Pui-Yan/0000-0002-5087-3059; Choy, Edwin/0000-0001-9896-8084 FU NCI NIH HHS [K22 CA109351]; NCRR NIH HHS [U54 RR020278]; NIA NIH HHS [N01 AG062103, N01 AG062101, N01 AG062106, R01 AG021024]; NIGMS NIH HHS [T32 GM007753]; NINDS NIH HHS [P30 NS045776] NR 43 TC 111 Z9 114 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD APR PY 2007 VL 80 IS 4 BP 716 EP 726 DI 10.1086/513206 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 153VV UT WOS:000245465200012 PM 17357077 ER PT J AU Moran, A Roux, AVD Jackson, SA Kramer, H Manolio, TA Shrager, S Shea, S AF Moran, Andrew Roux, Ana V. Diez Jackson, Sharon A. Kramer, Holly Manolio, Teri A. Shrager, Sandi Shea, Steven TI Acculturation is associated with hypertension in a multiethnic sample SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE hypertension; acculturation; ethnicity; Chinese; hispanic; African-American ID MEXICAN-AMERICAN ADULTS; HIGH BLOOD-PRESSURE; RISK-FACTORS; UNITED-STATES; NHANES-III; PREVALENCE; HEALTH; IMMIGRANTS; BEHAVIORS; MIGRATION AB Background: Hypertension varies in prevalence among race/ethnic groups in the United States. Within-ethnic group differences associated with acculturation have been less frequently examined. We studied the association of three measures of acculturation (language spoken at home, place of birth, and years living in the US) with hypertension in a population sample of 2619 white, 1898 African American, 1,494 Hispanic, and 803 Chinese participants in the Multiethnic Study of Atherosclerosis. Methods: Multivariate Poisson regression was used to estimate the association between the acculturation variables and hypertension. Results: Birthplace outside the US and speaking a non-English language at home were each associated with a lower prevalence of hypertension after adjustment for age, gender, and socioeconomic status (prevalence ratio [95% confidence intervals] 0.82 (0.77-0.87) for non-US born versus US born and 0.80 (0.74-0.85) for those not speaking English at home versus speakers of English at home, both P<.001). For participants born outside of the US, each 10-year increment of years in the US was associated with a higher prevalence of hypertension after adjustment for age, gender, and socioeconomic status (P for trend <.01). The associations between acculturation variables and hypertension were weakened after adjustment for race/ethnic category and risk factors for hypertension. Compared to US-born Hispanics, those born in Mexico or South America had lower prevalence of hypertension, but those born in the Caribbean and Central America had higher prevalence of hypertension. Conclusions: Acculturation and place of birth are associated with hypertension in a multiethnic sample. C1 Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Dept Epidemiol, Ann Arbor, MI 48104 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Loyola Univ, Dept Prevent Med, Maguire Ctr, Maywood, IL 60153 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Washington, Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98195 USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Epidemiol, Joseph Mailman Sch Publ Hlth, New York, NY USA. RP Roux, AVD (reprint author), Univ Michigan, Ctr Social Epidemiol & Populat Hlth, Dept Epidemiol, 1214 S Univ, Ann Arbor, MI 48104 USA. EM adiezrou@umich.edu OI Kramer, Holly/0000-0002-6374-837X FU NHLBI NIH HHS [N01-HC-95159, N01-HC-95166, N01 HC095161, N01-HC-95165] NR 29 TC 53 Z9 53 U1 4 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD APR PY 2007 VL 20 IS 4 BP 354 EP 363 DI 10.1016/j.amjhyper.2006.09.025 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 156YQ UT WOS:000245686200003 PM 17386340 ER PT J AU Krstev, S Ji, BT Shu, XO Blair, A Zheng, W Lubin, J Vermeulen, R Hauptmann, M Rothman, N Gao, YT Mustafa, D Chow, WH AF Krstev, Srmena Ji, Bu-Tian Shu, Xiao-Ou Blair, Aaron Zheng, Wei Lubin, Jay Vermeulen, Roel Hauptmann, Michael Rothman, Nathaniel Gao, Yu-Tang Mustafa, Dosemeci Chow, Wong-Ho TI Occupation and adult-onset asthma among Chinese women in a population-based cohort SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE occupational asthma; women; population-based case control study; occupation; industry ID WORK-RELATED ASTHMA; PHYSICIAN-DIAGNOSED ASTHMA; RESPIRATORY SYMPTOMS; LUNG-DISEASE; RISK-FACTORS; PREVALENCE; EXPOSURES; COMMUNITY; HEALTH; INCREASE AB Background Exposure to industrial irritants is believed to have contributed to the increasing prevalence of asthma worldwide. We examined the associations between occupation and asthma among women in a case-control study nested in the population-based Shanghai Women's Health Study cohort in China. Methods Cases were 1,050 women who reported a physician-diagnosed asthma as adults. Controls were 4,200 women matched to the cases by year of birth and age at diagnosis. Lifetime occupational histories were obtained. Logistic regression was applied to estimate odds ratios (ORs) adjusting for smoking, education, family income, and concurrent chronic bronchitis. Results Asthma is more prevalent in production industries, for metal tools (OR = 2.4; 1.3-4.7), metal products for everyday use (OR = 1.6; 1.1-2.4), ships (OR = 2.6; 1.0-6.8), and clocks (OR = 1.9; 1.0-3.4), and in occupations as farm, workers (OR = 4.0; 1.2-13.0), laboratory technicians and analyzers (OR = 2.2; 1.2-3.9), and installation and maintenance workers for weaving and knitting machineries (OR = 2.4; 1.1-5.4). Other associations less commonly reported were identified for electricians (OR = 2.1; 1.1-4.1), performers (OR = 3.2; 1.4-7.4), administrative workers in organizations and enterprises (OR = 1.8; 1.1-2.8), and postal and telecommunication workers (OR = 3.5; 1.6-7.6). Conclusions Our findings suggest that occupational exposures contribute to the development of asthma in women. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Clin Ctr Serbia, Inst Occupat Hlth, Belgrade, Serbia. Vanderbilt Univ, Ctr Hlth Serv Res, Nashville, TN USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD USA. Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. Netherlands Canc Inst, Amsterdam, Netherlands. Shanghai Canc Inst, Shanghai, Peoples R China. RP Ji, BT (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 8120, Bethesda, MD 20892 USA. EM jib@exchange.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU Intramural NIH HHS; NCI NIH HHS [R01 CA70867] NR 50 TC 6 Z9 6 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 2007 VL 50 IS 4 BP 265 EP 273 DI 10.1002/ajim.20439 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 154IW UT WOS:000245501400003 PM 17311256 ER PT J CA FHN Trial Grp TI The Frequent Hemodialysis Network randomized trial of home nocturnal hemodialysis: Change of trial design SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 10-14, 2007 CL Orlando, FL SP Natl Kidney Fdn C1 NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2007 VL 49 IS 4 MA 62 BP A40 EP A40 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 155QN UT WOS:000245593100074 ER PT J CA FHN Trial Grp TI Progress of the frequent hemodialysis network randomized trial of in-center daily hemodialysis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 10-14, 2007 CL Orlando, FL SP Natl Kidney Fdn C1 NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2007 VL 49 IS 4 MA 61 BP A40 EP A40 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 155QN UT WOS:000245593100073 ER PT J AU Mansour, W Holvoet, P Shlipak, MG Kritchevsky, S Harris, T Newman, AB Fried, LF AF Mansour, Wissam Holvoet, Paul Shlipak, Michael G. Kritchevsky, Stephen Harris, Tamara Newman, Anne B. Fried, Linda F. CA Hlth Aging & Body Composit Study TI Kidney function, oxidized LDL and cardiovascular disease (CVD) SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 10-14, 2007 CL Orlando, FL SP Natl Kidney Fdn C1 Univ Pittsburgh, Pittsburgh, PA USA. Catholic Univ Louvain, B-3000 Louvain, Belgium. San Francisco VA, San Francisco, CA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIH, Bethesda, MD 20892 USA. VAPHCS, Pittsburgh, PA USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2007 VL 49 IS 4 MA 135 BP A58 EP A58 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 155QN UT WOS:000245593100147 ER PT J AU Ponda, M Siconolfi-Baez, L Kopp, JB Angeletti, RH Hostetter, TH Bitzer, M AF Ponda, M. Siconolfi-Baez, L. Kopp, J. B. Angeletti, R. H. Hostetter, T. H. Bitzer, M. TI NGAL and extracellular matrix proteins in TGF-beta induced chronic renal fibrosis SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract CT Spring Clinical Meeting of the National-Kidney-Foundation CY APR 10-14, 2007 CL Orlando, FL SP Natl Kidney Fdn C1 Albert Einstein Coll Med, Bronx, NY 10467 USA. NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2007 VL 49 IS 4 MA 166 BP A66 EP A66 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 155QN UT WOS:000245593100178 ER PT J AU Kass, NE Medley, AM Natowicz, MR Hull, SC Faden, RR Plantinga, L Gostin, LO AF Kass, Nancy E. Medley, Amy M. Natowicz, Marvin R. Hull, Sara Chandros Faden, Ruth R. Plantinga, Laura Gostin, Lawrence O. TI Access to health insurance: Experiences and attitudes of those with genetic versus non-genetic medical conditions SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE access to health insurance; genetic discrimination; hereditary disease; cross-sectional survey ID DISCRIMINATION; INFORMATION; DISCLOSURE; PRIVACY; TESTS; ACT AB While studies reveal that individuals with both genetic and other chronic medical conditions have difficulty obtaining health insurance, no large-scale studies have compared the health insurance experiences of these groups. The goal of this study was to document and compare the health insurance experience, attitudes, and beliefs of persons with genetic conditions to those of persons with or at risk for other serious medical conditions. We interviewed approximately 100 adults or parents of children with one of each of the following medical conditions; sickle cell disease (SCD), cystic fibrosis (CF), diabetes, and HIV, and 200 adults with or at risk for breast (BC) or colon cancer (CC). The interview included items related to respondents' experiences and attitudes regarding health insurance. Twenty-seven percent of 597 total respondents self-reported having been denied health insurance or offered insurance at a prohibitive rate. Respondents with single-gene disorders (CF and SCD) were twice as likely to report this as those with non-genetic conditions. Legislation that exists to limit genetic discrimination in insurance addresses genetic risks or traits only, however, rather than protecting those with actual disease. Thus, current legislation may not address the challenges faced by individuals like those in this study, who try to maintain access to health insurance when they or their children are symptomatic with a genetic or other serious health condition. More than one-third of all respondents thought there was a high chance they would be denied health insurance in the future or their insurance would become unaffordable. That individuals with all six health conditions expressed concern regarding their ability to obtain future health insurance suggests policy proposals should be broad-based, addressing the needs and concerns of individuals with diverse health conditions. (c) 2007 Wiley-Liss, Inc C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, John Hopkins Berman Inst Bioeth, Dept Hlth Policy & Management, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Georgetown Univ, Ctr Law, Washington, DC USA. Johns Hopkins Univ, Ctr Law & Publ Hlth, Baltimore, MD USA. Georgetown Univ, Kennedy Inst Eth, Washington, DC USA. RP Kass, NE (reprint author), 624 N Broadway,Hampton House 344, Baltimore, MD 21205 USA. EM nkass@jhsph.edu FU Intramural NIH HHS [Z99 HG999999]; NHGRI NIH HHS [R01 HG01086] NR 20 TC 18 Z9 18 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD APR 1 PY 2007 VL 143A IS 7 BP 707 EP 717 DI 10.1002/ajmg.a.31576 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 153QN UT WOS:000245450200010 PM 17290434 ER PT J AU Haylock, PJ Mitchell, SA Cox, T Temple, SV Curtiss, CP AF Haylock, Pamela J. Mitchell, Sandra A. Cox, Tricia Temple, Susan Vogt Curtiss, Carol P. TI The cancer survivor's prescription for living SO AMERICAN JOURNAL OF NURSING LA English DT Article ID CARE; CHALLENGE C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NCI, Bethesda, MD 20892 USA. John Randolph Med Ctr, Hopewell, VA USA. GlaxoSmithKline Inc, Oncol, Seale, AL USA. Curtiss Consulting, Greenfield, MA USA. RP Haylock, PJ (reprint author), Univ Texas, Med Branch, Galveston, TX 77550 USA. EM pjhaylock@indian-creek.net NR 36 TC 23 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD APR PY 2007 VL 107 IS 4 BP 58 EP 70 PG 13 WC Nursing SC Nursing GA 158BG UT WOS:000245765300026 PM 17413737 ER PT J AU Espinoza, J Romero, R Nien, JK Gomez, R Kusanovic, JP Goncalves, LF Medina, L Edwin, S Hassan, S Carstens, M Gonzalez, R AF Espinoza, Jimmy Romero, Roberto Nien, Jyh Kae Gomez, Ricardo Kusanovic, Juan Pedro Goncalves, Luis F. Medina, Luis Edwin, Sam Hassan, Sonia Carstens, Mario Gonzalez, Rogelio TI Identification of patients at risk for early onset and/or severe preeclampsia with the use of uterine artery Doppler velocimetry and placental growth factor SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE gestational hypertension; placental growth factor (PIGF); preeclampsia; small for gestational age; soluble vascular endothelial growth factor receptor-1 (VEGFR-1); uterine artery Doppler velocimetry; vascular endothelial growth factor (VEGF) ID VELOCITY WAVE-FORMS; CIRCULATING ANGIOGENIC FACTORS; FETAL-GROWTH; GESTATIONAL-AGE; SPIRAL ARTERIES; 2ND TRIMESTER; TROPHOBLAST DEPORTATION; PHYSIOLOGICAL TRANSFORMATION; EXPECTANT MANAGEMENT; VASCULAR DEVELOPMENT AB OBJECTIVE: Preeclampsia has been proposed to be an antiangiogenic state that may be detected by the determination of the concentrations of the soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor ( PlGF) in maternal blood even before the clinical development of the disease. The purpose of this study was to determine the role of the combined use of uterine artery Doppler velocimetry (UADV) and maternal plasma PlGF and sVEGFR-1 concentrations in the second trimester for the identification of patients at risk for severe and/or early onset preeclampsia. STUDY DESIGN: A prospective cohort study was designed to examine the relationship between abnormal UADV and plasma concentrations of PlGF and sVEGFR-1 in 3348 pregnant women. Plasma samples were obtained between 22 and 26 weeks of gestation at the time of ultrasound examination. Abnormal UADV was defined as the presence of bilateral uterine artery notches and/or a mean pulsatility index above the 95th percentile for the gestational age. Maternal plasma PlGF and sVEGFR-1 concentrations were determined with the use of sensitive and specific immunoassays. The primary outcome was the development of early onset preeclampsia (<= 34 weeks of gestation) and/ or severe preeclampsia. Secondary outcomes included preeclampsia, the delivery of a small for gestational age (SGA) neonate without preeclampsia, spontaneous preterm birth at <= 32 and <= 35 weeks of gestation, and a composite of severe neonatal morbidity. Contingency tables, chi-square test, receiver operating characteristic curve, and multivariate logistic regression were used for statistical analyses. A probability value of <.05 was considered significant. RESULTS: ( 1) The prevalence of preeclampsia, severe preeclampsia, and early onset preeclampsia were 3.4% (113/3296), 1.0% (33/3296), and 0.8% (25/3208), respectively. UADV was performed in 95.4% (3146/3296) and maternal plasma PlGF concentrations were determined in 93.5% (3081/3296) of the study population. ( 2) Abnormal UADV and a maternal plasma PlGF of <280 pg/mL were independent risk factors for the occurrence of preeclampsia, severe preeclampsia, early onset preeclampsia, and SGA without preeclampsia. ( 3) Among patients with abnormal UADV, maternal plasma PlGF concentration contributed significantly in the identification of patients destined to develop early onset preeclampsia ( area under the curve, 0.80; P <.001) and severe preeclampsia ( area under the curve, 0.77; P <.001). ( 4) In contrast, maternal plasma sVEGFR-1 concentration was of limited use in the prediction of early onset and/ or severe preeclampsia. ( 5) The combination of abnormal UADV and maternal plasma PlGF of < 280 pg/mL was associated with an odds ratio ( OR) of 43.8 ( 95% Cl, 18.48-103.89) for the development of early onset preeclampsia, an OR of 37.4 ( 95% Cl, 17.64-79.07) for the development of severe preeclampsia, an OR of 8.6 ( 95% Cl, 5.35-13.74) for the development of preeclampsia, and an OR of 2.7 ( 95% Cl, 1.73-4.26) for the delivery of a SGA neonate in the absence of preeclampsia. CONCLUSION: The combination of abnormal UADV and maternal plasma PlGF concentration of < 280 pg/mL in the second trimester is associated with a high risk for preeclampsia and early onset and/ or severe preeclampsia in a low-risk population. Among those with abnormal UADV, a maternal plasma concentration of PlGF of < 280 pg/mL identifies most patients who will experience early onset and/ or severe preeclampsia. C1 Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS,Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48202 USA. Hosp Dr Sotero del Rio, CEDIP, Dept Obstet & Gynecol, Puente Alto, Chile. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS,Dept Obstet & Gynecol, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS [Z01 HD002401-15, Z99 HD999999] NR 79 TC 11 Z9 16 U1 0 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2007 VL 196 IS 4 AR 326.e1 DI 10.1016/j.ajog.2006.11.002 PG 13 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 157UT UT WOS:000245747600013 PM 17403407 ER PT J AU Hitti, J Andersen, J McComsey, G Liu, T Melvin, A Smith, L Stek, A Aberg, J Hull, A Alston-Smith, B Watts, DH Livingston, E AF Hitti, Jane Andersen, Janet McComsey, Grace Liu, Tun Melvin, Ann Smith, Laura Stek, Alice Aberg, Judith Hull, Andrew Alston-Smith, Beverly Watts, D. Heather Livingston, Elizabeth CA AIDS Clin Trials Grp 5084 TI Protease inhibitor-based antiretroviral therapy and glucose tolerance in pregnancy: AIDS Clinical Trials Group A5084 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 13th Conference on Retroviruses and Opportunistic Infections CY FEB 05-09, 2006 CL Denver, CO DE glucose intolerance; human immunodeficiency virus-1; insulin resistance; pregnancy; protease inhibitor ID HUMAN-IMMUNODEFICIENCY-VIRUS; INSULIN-RESISTANCE; INTOLERANCE; METABOLISM; WOMEN; MODEL AB OBJECTIVE: The objective of the study was to determine whether protease inhibitors increase glucose intolerance and insulin resistance in pregnancy. STUDY DESIGN: In this multicenter, prospective, observational study, 149 human immunodeficiency virus-1-infected pregnant women had fasting insulin, glucose, and C-peptide measured followed by a 1 hour, 50 g glucose test. Glucose intolerance was defined as a 1 hour glucose greater than 130 mg/dL. Glucose intolerance, homeostasis model assessment of insulin resistance and pancreatic beta-cell function, and pregnancy outcomes were compared between those taking protease inhibitors and those not. RESULTS: Fifty-seven of 149 subjects (38%) had glucose intolerance. Body mass index, Hispanic ethnicity, and maternal age, but not protease inhibitors, were associated with glucose intolerance. There were no differences in insulin resistance, beta-cell function, or pregnancy outcome associated with protease inhibitor use. CONCLUSIONS: Protease inhibitors do not increase risk of glucose intolerance or insulin resistance among pregnant women. C1 Univ Washington, Seattle, WA 98195 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Frontier Sci Technol & Res Fdn, Amherst, NY USA. Univ So Calif, Los Angeles, CA 90089 USA. NYU, New York, NY USA. Univ Calif San Diego, San Diego, CA 92103 USA. NIH, Bethesda, MD 20892 USA. Duke Univ, Durham, NC 27706 USA. RP Hitti, J (reprint author), Univ Washington, Seattle, WA 98195 USA. FU NCRR NIH HHS [RR000080, RR00044, M01RR00096, RR00043, RR00069, RR00096]; NIAID NIH HHS [AI25883, AI25915, AI27661, AI27665, AI27670, AI277664, AI39156, U01 AI41089, UO1 AI38558, AI25859, AI25879, AI25897, AI25903, AI27563, AI27664, AI32907, AI34853, AI38855, AI42845]; NICHD NIH HHS [HD33345, N01 HD33345] NR 21 TC 6 Z9 6 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2007 VL 196 IS 4 AR 331.e1 DI 10.1016/j.ajog.2006.11.037 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 157UT UT WOS:000245747600015 PM 17403409 ER PT J AU Page, JG Tian, BH Schweikart, K Tomaszewski, J Harris, R Broadt, T Polley-Nelson, J Noker, PE Wang, MH Makhija, S Aurigemma, R Curiel, DT Alvarez, RD AF Page, John G. Tian, Baohong Schweikart, Karen Tomaszewski, Joseph Harris, Ray Broadt, Trevor Polley-Nelson, Judith Noker, Patricia E. Wang, Minghui Makhija, Sharmila Aurigemma, Rose Curiel, David T. Alvarez, Ronald D. TI Identifying the safety profile of a novel infectivity-enhanced conditionally replicative adenovirus, Ad5-Delta 24-RGD, in anticipation of a phase I trial for recurrent ovarian cancer SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the American-Gynecological-and-Obstetrical-Society CY SEP 14-16, 2006 CL Willamsburg, VA SP Amer Gynecol & Obstetr Soc DE virotherapy; vector; toxicity; biodistribution study ID GENE-THERAPY; MOLECULAR CHEMOTHERAPY; ONCOLYTIC ADENOVIRUS; ADVANCED GENERATION; TUMOR-CELLS; VECTORS; VIVO AB OBJECTIVE: The purpose of this study was to evaluate the biodistribution and toxicity of the tropism-modified infectivity-enhanced conditionally replicative adenovirus, Ad5-Delta 24-arginine-glycine-aspartate (RGD). STUDY DESIGN: Cohorts of cotton rats were treated intravenously or intraperitoneally for 3 consecutive days with 5 x 10(8) to 5 x 10(11) particles/kg of Ad5-Delta 24-RGD or controls and killed on day 8, 17, or 56. For biodistribution studies, tissue samples from 14 organ sites and serum samples were evaluated for the presence of virus with the use of quantitative polymerase chain reaction analysis. For toxicity experiments, tissue samples from more than 30 organ sites and serum samples were obtained for the assessment of vector-related tissue or laboratory effects. RESULTS: Ad5-Delta 24-RGD was noted in tested samples at days 8 and 17 in animals that were treated intravenously and intraperitoneally with clearance by day 56. There were lower copies of vector noted in the blood and liver specimens of intraperitoneally treated animals. Mild peritonitis histopathologic findings were noted in rats that were treated intraperitoneally with Ad5-Delta 24-RGD; pathologic findings did not vary significantly with dose, over time, or in comparison to that noted in animals that were treated with Ad5-Delta 24. CONCLUSION: These studies provide critical insights regarding Ad5-Delta 24-RGD dosing and anticipated toxicity for a planned clinical trial for ovarian cancer. C1 So Res Inst, Birmingham, AL 35255 USA. NCI, Bethesda, MD 20892 USA. SAIC Frederick, Frederick, MD USA. Univ Alabama, Birmingham, AL USA. RP Alvarez, RD (reprint author), Room OHB 538,619 20th St S, Birmingham, AL 35249 USA. EM rdalvarez@uab.edu FU NCI NIH HHS [P50-CA83591, N01-CO-12400]; PHS HHS [NSC 723256] NR 25 TC 6 Z9 6 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD APR PY 2007 VL 196 IS 4 AR 389.e1 DI 10.1016/j.ajog.2006.12.016 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 157UT UT WOS:000245747600038 PM 17403430 ER PT J AU Shah, YM Ma, XC Morimura, K Kim, I Gonzalez, FJ AF Shah, Yatrik M. Ma, Xiaochao Morimura, Keiichirou Kim, Insook Gonzalez, Frank J. TI Pregnane X receptor activation ameliorates DSS-induced inflammatory bowel disease via inhibition of NF-kappa B target gene expression SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE pregnane X receptor; peroxisome proliferator-activated receptor-gamma; chemokine (C-C motif) receptor 2; Crohn's disease; dextran sulfate sodium; monocyte chemoattractant protein-1 ID ANION-TRANSPORTING POLYPEPTIDE-2; GLUCOCORTICOID-RECEPTOR; SIGNALING PATHWAY; XENOBIOTIC METABOLISM; CYTOCHROME-P-450 3A4; MOLECULAR-MECHANISMS; ULCERATIVE-COLITIS; NUCLEAR RECEPTORS; INDUCTION; PREGNENOLONE-16-ALPHA-CARBONITRILE AB Pregnane X receptor ( PXR) expression was shown to be protective in inflammatory bowel disease ( IBD). However, the mechanism by which PXR provides protection remains unclear. Wild-type and Pxr-null mice were treated with the PXR agonist pregnenolone-16 alpha-carbonitrile or vehicle and administered 2.5% dextran sulfate sodium ( DSS) in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis. In vivo intestinal permeability assays and proinflammatory cytokine analysis were performed. PXR agonist-treated mice were protected from DSS-induced colitis compared with vehicle-reated mice, as defined by body weight loss, diarrhea, rectal bleeding, colon length, and histology. Pregnenolone-16 alpha-carbonitrile did not decrease the severity of IBD in Pxr-null mice. PXR agonist treatment did not increase epithelial barrier function but did decrease mRNA expression of several NF-kappa B target genes in a PXR-dependent manner. The present study clearly demonstrates a protective role for PXR agonist in DSS-induced IBD. The data suggest that PXR-mediated repression of NF-kappa B target genes in the colon is a critical mechanism by which PXR activation decreases the susceptibility of mice to DSS- induced IBD. C1 NCI, Lab Metab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Canc Res Ctr, NIH, Bldg 37,Rm 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS NR 42 TC 103 Z9 105 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD APR PY 2007 VL 292 IS 4 BP G1114 EP G1122 DI 10.1152/ajpgi.00528.2006 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 153KP UT WOS:000245433400020 PM 17170021 ER PT J AU Card, JW Voltz, JW Ferguson, CD Carey, MA DeGraff, LM Peddada, SD Morgan, DL Zeldin, DC AF Card, Jeffrey W. Voltz, James W. Ferguson, Catherine D. Carey, Michelle A. DeGraff, Laura M. Peddada, Shyamal D. Morgan, Daniel L. Zeldin, Darryl C. TI Male sex hormones promote vagally mediated reflex airway responsiveness to cholinergic stimulation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE respiratory mechanics; methacholine; androgens ID BRONCHIAL HYPERRESPONSIVENESS; MICE; METHACHOLINE; BRONCHOCONSTRICTION; INFLAMMATION; ACETYLCHOLINE; SENSITIVITY; BRADYCARDIA; POPULATION; EXPRESSION AB A sex disparity in airway responsiveness to cholinergic stimulation has been observed in laboratory mice in that males are considerably more responsive than females, but the basis for this difference is unclear. In this report, we demonstrate that male sex hormones promote murine airway responsiveness to cholinergic stimulation via vagus nerve-mediated reflex mechanisms. In tissue bath preparations, no sex- based differences were observed in the contractile responses of isolated tracheal and bronchial ring segments to carbachol, indicating that the mechanism( s) responsible for the in vivo sex difference is ( are) absent ex vivo. Bilateral cervical vagotomy was found to abolish in vivo airway responsiveness to methacholine in male mice, whereas it did not alter the responses of females, suggesting a regulatory role for male sex hormones in promoting reflex airway constriction. To test this possibility, we next studied mice with altered circulating male sex hormone levels. Castrated male mice displayed airway responsiveness equivalent to that observed in intact females, whereas administration of exogenous testosterone to castrated males restored responsiveness, albeit not to the level observed in intact males. Administration of exogenous testosterone to intact female mice similarly enhanced responsiveness. Importantly, the promotive effects of exogenous testosterone in castrated male and intact female mice were absent when bilateral vagotomy was performed. Together, these data indicate that male sex hormones promote cholinergic airway responsiveness via a vagally mediated reflex mechanism that may be important in the regulation of airway tone in the normal and diseased lung. C1 Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), Natl Inst Environm Hlth Sci, Div Intramural Res, NIH, 111 TW Alexander Dr,Bldg 101 Rm D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS [Z01 ES101885-03] NR 31 TC 19 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD APR PY 2007 VL 292 IS 4 BP L908 EP L914 DI 10.1152/ajplung.00407.2006 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 188QX UT WOS:000247935500011 PM 17158599 ER PT J AU Kant, AK Graubard, BI Kumanyika, SK AF Kant, Ashima K. Graubard, Barry I. Kumanyika, Shiriki K. TI Trends in black-white differentials in dietary intakes of US adults, 1971-2002 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; UNITED-STATES; SOCIOECONOMIC-STATUS; ENERGY DENSITY; PROSTATE-CANCER; NUTRIENT INTAKE; SECULAR TRENDS; BLOOD-PRESSURE; FOOD STORES AB Background: Disparities in the health status of blacks and whites have persisted despite considerable gains in improved health of the U.S. population. Tracking changes in black-white differentials in dietary attributes over time may help in understanding the contribution of diet to these disparities. Methods: Data were used from four National Health and Nutrition Examination Surveys conducted between 1971 and 2002 for trends in self-reported intakes of energy, macronutrients, micronutrients, fruits and vegetables, and the energy density of foods among U.S. non-Hispanic black (n=7099) and white (n=23,314) men and women aged 25 to 74 years. Logistic and linear regression methods were used to adjust for multiple covariates and survey design. Results: Energy intake, amount of food, and carbohydrate energy increased, whereas percentage of energy from protein, fat, and saturated fat decreased over time in all race and gender groups (p < 0.001). In whites and in black women, energy density increased (p < 0.001) in parallel to increases in obesity prevalence. In all surveys, black men and women reported lower intakes of vegetables, potassium, and calcium (p < 0.001) than their white counterparts. In men, the race differential in calcium intake increased across surveys (p=0.004). Conclusions: Dietary intake trends in blacks and whites from 1971 to 2002 were similar, which suggests that previously identified dietary risk factors that differentially affect black Americans have not improved in a relative sense. C1 CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306E, Flushing, NY 11367 USA. EM ashima.kant@qc.cuny.edu FU Intramural NIH HHS; NCI NIH HHS [CA108274, R03 CA108274, R03 CA108274-02]; NIMHD NIH HHS [P60 MD000209, P60MD000209] NR 52 TC 71 Z9 71 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2007 VL 32 IS 4 BP 264 EP 272 DI 10.1016/j.amepre.2006.12.011 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 155FH UT WOS:000245562800002 PM 17383557 ER PT J AU Allison, MA Ho, E Denenberg, JO Langer, RD Newman, AB Fabsitz, RR Criqui, MH AF Allison, Matthew A. Ho, Elena Denenberg, Julie O. Langer, Robert D. Newman, Anne B. Fabsitz, Richard R. Criqui, Michael H. TI Ethnic-specific prevalence of peripheral arterial disease in the United States SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID ANKLE-BRACHIAL INDEX; NUTRITION EXAMINATION SURVEY; RISK-FACTORS; SUBCLAVIAN ARTERY; CARDIOVASCULAR HEALTH; DEFINED POPULATION; NONINVASIVE TESTS; NATIONAL-HEALTH; ARM INDEX; ATHEROSCLEROSIS AB Background: Individuals diagnosed with peripheral arterial disease (PAD) are at increased risk for future functional limitations as well as cardiovascular morbidity and mortality. The aim of this study was to estimate the age-, gender-, and ethnic-specific burden of PAD in the United States for the year 2000. Methods: Data were collected from seven community-based studies that assessed subjects for the presence of PAD using the ankle-brachial index (ABI). Using standardized weighting criteria, age-, gender-, and ethnic-specific prevalence rates were computed and then multiplied by the corresponding 2000 Census population totals to estimate the burden of PAD in the United States for that year. Evidence-based adjustments for studies which did not consider possible subclavian stenosis, prior revascularization for PAD, or both were employed. Results: In 2000, it is conservatively estimated that at least 6.8 million (5.8%) individuals aged 40 years or older had PAD based on an ABI of less than 0.9 or previous revascularization for PAD, and that that there are an additional 1.7 million Americans with PAD but "normal" ABIs. Including this group gives a total of 8.5 million (7.2%) individuals with PAD. Conclusions: Roughly one in 16 individuals residing in the United States in 2000 who were aged 40 years and older had PAD. Clinicians are encouraged to screen for the presence of PAD using the ABI. C1 Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. Geisinger Hlth Syst, Danville, PA USA. Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. NHLBI, Bethesda, MD 20892 USA. RP Allison, MA (reprint author), 3385 Hlth Sci Dr, La Jolla, CA 92093 USA. EM mallison@ucsd.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Allison, Matthew/0000-0003-0777-8272 FU NHLBI NIH HHS [HL73089] NR 29 TC 136 Z9 141 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2007 VL 32 IS 4 BP 328 EP 333 DI 10.1016/j.amepre.2006.12.010 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 155FH UT WOS:000245562800010 PM 17383564 ER PT J AU Nebeling, L Yaroch, AL Seymour, JD Kimmons, J AF Nebeling, Linda Yaroch, Amy L. Seymour, Jennifer D. Kimmons, Joel TI Still not enough - Can we achieve our goals for Americans to eat more fruits and vegetables in the future? SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Editorial Material ID BLACK CHURCHES; INTERVENTION; CONSUMPTION C1 NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA USA. RP Nebeling, L (reprint author), NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4060, Bethesda, MD 20892 USA. EM NebelinL@mail.nih.gov NR 19 TC 15 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2007 VL 32 IS 4 BP 354 EP 355 DI 10.1016/j.amepre.2006.12.018 PG 2 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 155FH UT WOS:000245562800014 PM 17383568 ER PT J AU McGowan, A Hahn, R Liberman, A Crosby, A Fullilove, M Johnson, R Moscicki, E Price, L Snyder, S Tuma, F Lowy, J Briss, P Cory, S Stone, G AF McGowan, Angela Hahn, Robert Liberman, Akiva Crosby, Alex Fullilove, Mindy Johnson, Robert Moscicki, Eve Price, LeShawndra Snyder, Susan Tuma, Farris Lowy, Jessica Briss, Peter Cory, Stella Stone, Glenda CA Task Force Community Preventive S TI Effects on violence of laws and policies facilitating the transfer of juveniles system to the adult - A systematic review SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CRIMINAL COURTS; CRIME; ADOLESCENTS; OFFENDERS; JUSTICE; WAIVER; YOUTH AB The independent, nonfederal Task Force on Community Preventive Services (Task Force), which directs development of the Guide to Community Preventive Services (Community Guide), has conducted a systematic review of published scientific evidence concerning the effectiveness of laws and policies that facilitate the transfer of juveniles to the adult criminal justice system, on either preventing or reducing violence (1) among those youth who experience the adult criminal system or (2) in the juvenile population as a whole. This review focuses on interpersonal violence. Violence may lead to the juvenile's initial arrest and entry into the justice system and, for those who are arrested, may be committed subsequent to exiting the justice system. Here transfer is defined as the placement of juveniles aged less than 18 years under the jurisdiction of the adult criminal justice system, rather than the juvenile justice system, following arrest. Using the methods developed by the Community Guide to conduct a systematic review of literature and provide recommendations to public health decision makers, the review team found that transferring juveniles to the adult justice system generally increases, rather than decreases, rates of violence among transferred youth. Evidence was insufficient for the Task Force on Community Preventive Services to determine the effect of such laws and policies in reducing violent behavior in the overall juvenile population. Overall, the Task Force recommends against laws or policies facilitating the transfer of juveniles from the juvenile to the adult judicial system for the purpose of reducing violence. C1 Ctr Dis Control & Prevent, Coordinating Ctr Hlth Informat & Serv, Community Guide Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Etiol & Surveillance Branch, Atlanta, GA 30333 USA. Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10027 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pediat, Newark, NJ 07103 USA. Natl Inst Justice, Washington, DC USA. NIMH, Div Pediat Translat Res & Treatment Dev, Bethesda, MD 20892 USA. NIMH, Div Adult Translat Res & Treatment Dev, Bethesda, MD 20892 USA. RP Hahn, R (reprint author), Ctr Dis Control & Prevent, Coordinating Ctr Hlth Informat & Serv, Community Guide Branch, 1600 Clifton Rd,MS E-69, Atlanta, GA 30333 USA. EM rah1@cdc.gov NR 54 TC 26 Z9 26 U1 3 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2007 VL 32 IS 4 SU S BP S7 EP S28 DI 10.1016/j.amepre.2006.12.003 PG 22 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 156FG UT WOS:000245632900004 PM 17386331 ER PT J AU Baker, KC Weed, JL Crockett, CM Bloomsmith, MA AF Baker, Kate C. Weed, James L. Crockett, Carolyn M. Bloomsmith, Mollie A. TI Survey of environmental enhancement programs for laboratory primates SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article DE behavioral management; psychological well-being; enrichment implementation; social enrichment; feeding enrichment; object enrichment; structural enrichment ID SELF-INJURIOUS-BEHAVIOR; MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; RETROSPECTIVE ANALYSIS; HEART-RATE; MACAQUES; CHIMPANZEES; ENRICHMENT; EXPERIENCE AB Animal welfare regulations in the United States require that nonhuman primate environmental enhancement plans be made in accordance with currently accepted professional standards; however, little information is available for quantifying common practice. Here we report the results of a 2003 survey that was sent to individuals overseeing enrichment programs at a variety of primate research institutions. The surveys requested information on program administration and management, implementation standards, procedures, and constraints pertaining to major categories of environmental enrichment, as well as intervention plans for animals exhibiting behavioral pathologies. Data were obtained on the management of 35,863 primates in 22 facilities. Behavioral scientists performed program oversight at the majority of facilities. Most programs reported recent changes, most commonly due to external site visits, and least commonly resulting from internal review. Most facilities' institutional animal care and use committees (IACUCs) included of individuals with behavioral expertise, and about two-thirds reported that enrichment issues could influence research protocol design. While most primates were reported to be housed socially (73%), social housing for indoor-housed primates appears to have changed little over the past 10 years. Research protocol issues and social incompatibility were commonly cited constraints. Implementation of feeding, manipulanda, and structural enrichment was relatively unconstrained, and contributions to these aspects of behavioral management generally included individuals in a wide variety of positions within a facility. In contrast, enrichment devices were used on a less widespread basis within facilities, and positive reinforcement programs that involved dedicated trainers were rare. We suggest that altering the role of the IACUC would be a productive avenue for increasing the implementation of social housing, and that an emphasis on prevention rather than intervention against behavioral pathology is warranted. The data from this survey may be useful for anticipating future program evaluations, establishing more effective internal evaluations, and assessing program progress and resource allocation. C1 Tulane Univ, Natl Primate Res Ctr, Div Vet Med, Covington, LA 70433 USA. NIH, Div Vet Resources, Off Res Serv, DHHS, Bethesda, MD 20892 USA. Washington Natl Primate Res Ctr, Psychol Well Being Program, Seattle, WA USA. Yerkes Natl Primate Res Ctr, Div Anim Resources, Atlanta, GA USA. RP Baker, KC (reprint author), Tulane Univ, Natl Primate Res Ctr, Div Vet Med, 18703 3 Rivers Rd, Covington, LA 70433 USA. EM kbaker1@tulane.edu FU NCRR NIH HHS [RR00165, RR00166, RR00164] NR 41 TC 40 Z9 40 U1 1 U2 14 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD APR PY 2007 VL 69 IS 4 BP 377 EP 394 DI 10.1002/ajp.20347 PG 18 WC Zoology SC Zoology GA 172MF UT WOS:000246807700002 PM 17171695 ER PT J AU Mackie, S Shaw, P Lenroot, R Pierson, R Greenstein, DK Nugent, TF Sharp, WS Giedd, JN Rapoport, JL AF Mackie, Susan Shaw, Philip Lenroot, Rhoshel Pierson, Ron Greenstein, Deanna K. Nugent, Tom F., III Sharp, Wendy S. Giedd, Jay N. Rapoport, Judith L. TI Cerebellar development and clinical outcome in attention deficit hyperactivity disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID VERBAL WORKING-MEMORY; DEFICIT/HYPERACTIVITY-DISORDER; MRI DATA; CHILDREN; ADOLESCENTS; ACTIVATION; TIME; SYSTEM; ADHD; FMRI AB Objective: Anatomic magnetic resonance imaging (MRI) studies have detected smaller cerebellar volumes in children with attention deficit hyperactivity disorder (ADHD) than in comparison subjects. However, the regional specificity and longitudinal progression of these differences remain to be determined. The authors compared the volumes of each lobe of the cerebellar hemispheres and vermis in children with ADHD and comparison subjects and used a new regional cerebellar volume measurement to characterize the developmental trajectory of these differences. Method: In a longitudinal case-control study, 36 children with ADHD were divided into a group of 18 with better outcomes and a group of 18 with worse outcomes and were compared with 36 matched healthy comparison subjects. The volumes of six cerebellar hemispheric lobes, the central white matter, and three vermal subdivisions were determined from MR images acquired at baseline and two or more follow-up scans conducted at 2-year intervals. A measure of global clinical outcome and DSM-IV criteria were used to define clinical outcome. Results: In the ADHD groups, a nonprogressive loss of volume was observed in the superior cerebellar vermis; the volume loss persisted regardless of clinical outcome. ADHD subjects with a worse clinical outcome exhibited a downward trajectory in volumes of the right and left inferior-posterior cerebellar lobes, which became progressively smaller during adolescence relative to both comparison subjects and ADHD subjects with a better outcome. Conclusions: Decreased volume of the superior cerebellar vermis appears to represent an important substrate of the fixed, nonprogressive anatomical changes that underlie ADHD. The cerebellar hemispheres constitute a more plastic, statespecific marker that may prove to be a target for clinical intervention. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Columbia Univ, Sch Med, New York, NY USA. Univ Iowa, Sch Med, Dept Psychiat, Iowa City, IA USA. RP Shaw, P (reprint author), NIMH, Child Psychiat Branch, 10 Ctr Dr,Bldg 10 3N202, Bethesda, MD 20892 USA. EM shawp@mail.nih.gov RI Shaw, Philip/A-1129-2008; Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 55 TC 154 Z9 161 U1 0 U2 6 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD APR PY 2007 VL 164 IS 4 BP 647 EP 655 DI 10.1176/appi.ajp.164.4.647 PG 9 WC Psychiatry SC Psychiatry GA 152ZZ UT WOS:000245402600020 PM 17403979 ER PT J AU Kelly-Hope, LA Alonso, WJ Thiem, VD Anh, DD Canh, DG Lee, H Smith, DL Miller, MA AF Kelly-Hope, Louise A. Alonso, Wladimir J. Thiem, Vu Dinh Anh, Dang Duc Canh, Do Gia Lee, Hyejon Smith, David L. Miller, Mark A. TI Geographical distribution and risk factors associated with enteric diseases in Vietnam SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID RESISTANT SALMONELLA-TYPHI; LESS-DEVELOPED-COUNTRIES; ORAL CHOLERA VACCINE; VIBRIO-CHOLERAE; GLOBAL BURDEN; ANTIBIOTIC-RESISTANCE; DIARRHEAL DISEASE; SEROVAR TYPHI; MEKONG-DELTA; FEVER AB In Vietnam, shigellosis, typhoid fever, and cholera are important enteric diseases. To determine their magnitude and geographical distribution, and explore associated risk factors, we examined national surveillance data from 1991 to 2001 and potential ecological determinants. Average annual incidence rates were calculated and mapped for each province. Bivariate and multiple regression analyses were used to explore associations with selected environmental and human risk factors. Overall, shigellosis rates per 100,000 population (median, 41; mean, 70) were higher and more widespread than rates for typhoid fever (median, 7; mean, 23) and cholera (median, 0.3; mean, 2.7). Shigellosis was highest in the Central Highlands and was significantly associated with rainfall and urban poverty; typhoid fever prevailed in the Mekong River Delta and was most associated with vapor pressure and river/stream drinking water; and cholera predominated along the Central Coastal regions and correlated positively with rainfall and public well drinking water. The distinct geographical patterns of each disease appear to be driven by a combination of different ecological factors. C1 NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA. Natl Inst Hyg & Epidemiol, Hanoi, Vietnam. Int Vaccine Inst, Seoul, South Korea. RP Kelly-Hope, LA (reprint author), NIH, Fogarty Int Ctr, Div Int Epidemiol & Populat Studies, Bethesda, MD 20892 USA. EM kellyhopel@mail.nih.gov NR 53 TC 45 Z9 47 U1 0 U2 10 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2007 VL 76 IS 4 BP 706 EP 712 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 155UV UT WOS:000245604800020 PM 17426175 ER PT J AU Chavez, M Insel, TR AF Chavez, Mark Insel, Thomas R. TI Eating disorders - National Institute of Mental Health's perspective SO AMERICAN PSYCHOLOGIST LA English DT Article DE eating disorders; NIMH; pathophysiology; treatment ID COGNITIVE-BEHAVIORAL THERAPY; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; DOUBLE-BLIND; OUTCOME PREDICTORS; FAMILY-THERAPY; FLUOXETINE; COMORBIDITY AB The mission of the National Institute of Mental Health (NIMH) is to reduce the burden of mental and behavioral disorders through research, and eating disorders embody an important fraction of this burden. Although past and current research has provided important knowledge regarding the etiology, classification, pathophysiology, and treatment of the eating disorders, there are still significant challenges that need to be addressed. This article briefly describes some of these challenges, recent NIMH-supported research and research-related activities directed at addressing these challenges, and approaches and areas of research that hold promise for furthering the understanding and treatment of eating disorders. C1 NIMH, Bethesda, MD 20892 USA. RP Chavez, M (reprint author), NIMH, 6001 Execut Blvd,MSC 9632, Bethesda, MD 20892 USA. EM nichavez1@mail.nih.gov NR 57 TC 23 Z9 23 U1 4 U2 9 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD APR PY 2007 VL 62 IS 3 BP 159 EP 166 DI 10.1037/0003-066X.62.3.159 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 158KR UT WOS:000245790900002 PM 17469895 ER PT J AU Marini, AM Jiang, X Wu, X Pan, H Guo, Z Mattson, MP Blondeau, N Novelli, A Lipsky, RH AF Marini, A. M. Jiang, X. Wu, X. Pan, H. Guo, Z. Mattson, M. P. Blondeau, N. Novelli, A. Lipsky, R. H. TI Preconditioning and neurotrophins: a model for brain adaptation to seizures, ischemia and other stressful stimuli SO AMINO ACIDS LA English DT Article DE preconditioning; epilepsy; neuroprotection; hippocampus; BDNF; NF-kappa B ID METHYL-D-ASPARTATE; FACTOR-KAPPA-B; RECEPTOR-MEDIATED NEUROPROTECTION; NERVE GROWTH-FACTOR; HIPPOCAMPAL-NEURONS; IN-VIVO; GLUTAMATE RECEPTORS; NMDA RECEPTORS; MESSENGER-RNAS; ACTIVATION AB The amino acid glutamate, the major excitatory neurotransmitter in the central nervous system, activates receptors coupled to calcium influx. Excessive activation of glutamate receptors in conditions such as severe epileptic seizures or stroke can kill neurons in a process called excitotoxicity. However, subtoxic levels of activation of the N-methyl-D-aspartate (NMDA) type of glutamate receptor elicit adaptive responses in neurons that enhance their ability to withstand more severe stress. A variety of stimuli induce adaptive responses to protect neurons. For example, sublethal ischemic episodes or a mild epileptic insult can protect neurons in a process referred to as tolerance. The molecular mechanisms that protect neurons by these different stressful stimuli are largely unknown but they share common features such as the transcription factor, nuclear factor kappa B (NF-kappa B), which is activated by ischemic and epileptic preconditioning as well as exposure to subtoxic NMDA concentrations. In this article, we describe stress-induced neuroprotective mechanisms highlighting the role of brain-derived neurotrophic factor (BDNF), a protein that plays a crucial role in neuronal survival and maintenance, neurogenesis and learning and memory. C1 Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Program Neurosci, Bethesda, MD 20814 USA. NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA. UNSA, CNRS, Inst Pharmacol Mol & Cellulaires, Valbonne, France. Univ Oviedo, Fac Psychol, Dept Psychol, Oviedo, Spain. NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD USA. RP Marini, AM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Neurol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM amarini@usuhs.mil RI Mattson, Mark/F-6038-2012; Novelli, Antonello/P-7476-2015; Blondeau, Nicolas/M-5002-2016; OI Novelli, Antonello/0000-0002-0129-8350; Blondeau, Nicolas/0000-0001-5954-4094; Lipsky, Robert/0000-0001-7753-1473 NR 41 TC 48 Z9 59 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD APR PY 2007 VL 32 IS 3 BP 299 EP 304 DI 10.1007/s00726-006-0414-y PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 156LJ UT WOS:000245649200002 PM 16998712 ER PT J AU Kocisko, DA Bertholet, N Moore, RA Caughey, B Vaillant, A AF Kocisko, David A. Bertholet, Nadine Moore, Roger A. Caughey, Byron Vaillant, Andrew TI Identification of prion inhibitors by a fluorescence-polarization-based competitive binding assay SO ANALYTICAL BIOCHEMISTRY LA English DT Editorial Material ID PROTEIN-FORMATION; ANTIPRION DRUGS; SCRAPIE C1 REPLICor Inc, Laval, PQ H7V 5B7, Canada. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. RP Vaillant, A (reprint author), REPLICor Inc, Laval, PQ H7V 5B7, Canada. EM availlant@replicor.com FU Intramural NIH HHS NR 14 TC 7 Z9 10 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 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 1 PY 2007 VL 363 IS 1 BP 154 EP 156 DI 10.1016/j.ab.2006.11.007 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 149OE UT WOS:000245155500018 PM 17276383 ER PT J AU Roedler, R Neuhauser, MM Penzak, SR AF Roedler, Rhonda Neuhauser, Melinda M. Penzak, Scoft R. TI Does metronidazole interact with CYP3A substrates by inhibiting their metabolism through this metabolic pathway? Or should other mechanisms be considered? SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE cytochrome P450; drug interactions; metronidazole ID IN-VIVO; PHARMACOKINETICS; CARBAMAZEPINE; CYCLOSPORINE; ALPRAZOLAM; AMIODARONE; ELEVATION; WARFARIN; THERAPY; ENZYMES AB OBJECTIVE: To explore whether CYP3A inhibition by metronidazole is the primary mechanism by which metronidazole interacts with coadministered CYP3A substrates. DATA SOURCES: Literature was accessed using the MEDLINE database (1966-February 2007). Search terms included metronidazole, cytochrome P450, CYP3A4, CYP3A5, drug interactions, and P-glycoprotein. References from pertinent articles, as well as from tertiary sources, were also considered. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources that were published in English were evaluated. Case reports and pharmacokinetic evaluations were included. DATA SYNTHESIS: Elevated plasma concentrations and toxicities have been reported for a number of CYP3A substrates including amiodarone, carbamazepine quinidine, tacrolimus, and cyclosporine when administered with metronidazole. This has led to the widespread belief that metronidazole is a significant inhibitor of CYP3A4. However, 4 pharmacokinetic studies conducted in humans showed that metronidazole did not increase plasma concentrations of the CYP3A substrates midazolam, erythromycin, cyclosporine, and alprazolam, thereby refuting the suggestion that metronidazole is a CYP3A4/5 inhibitor. CONCLUSIONS: Drug interactions between metronidazole and certain CYP3A substrates do not appear to result from CYP3A4/5 inhibition by metronidazole. Until any mechanism is identified by which metronidazole alters the disposition of certain CYP3A substrates, drug interactions with this agent should be assessed on a case-by-case basis, taking into account the safety index of the coadministered drug and the availability of equally effective substitutes for either metronidazole or the drug with which it putatively interacts. C1 NIAID, Clin Pharmacokinet Res Lab, Clin Ctr, Dept Pharm,NIH, Bethesda, MD 20892 USA. Peter Lougheed Ctr, Calgary, AB, Canada. RP Penzak, SR (reprint author), NIAID, Clin Pharmacokinet Res Lab, Clin Ctr, Dept Pharm,NIH, Bldg 10 1N 257, Bethesda, MD 20892 USA. EM spenzak@mail.cc.nih.gov NR 24 TC 19 Z9 21 U1 0 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD APR PY 2007 VL 41 IS 4 BP 653 EP 658 DI 10.1345/aph.1H401 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 158BA UT WOS:000245764700015 PM 17374625 ER PT J AU McKenzie, FE AF McKenzie, F. E. TI Multiply infected vectors SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Letter ID MICROFILARIAE; TRANSMISSION; MOSQUITOS; EHRLICHIA; BORRELIA; TICKS C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 TW999999] NR 10 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2007 VL 73 IS 7 BP 2398 EP 2398 DI 10.1128/AEM.02767-06 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 155KM UT WOS:000245576300052 PM 17403941 ER PT J AU Fong, DS Strauber, SF Aiello, LP Beck, RW Callanan, DG Danis, RP Davis, MD Feman, SS Ferris, F Friedman, SM Garcia, CA Glassman, AR Han, DP le, D Kollman, C Lauer, AK Recchia, FM Solomon, SD AF Fong, Donald S. Strauber, Samara F. Aiello, Lloyd Paul Beck, Roy W. Callanan, David G. Danis, Ronald P. Davis, Matthew D. Feman, Stephen S. Ferris, Frederick Friedman, Scott M. Garcia, Charles A. Glassman, Adam R. Han, Dennis P. le, Darma Kollman, Craig Lauer, Andreas K. Recchia, Franco M. Solomon, Sharon D. CA Writing Comm Diabet Retinopathy TI Comparison of the modified early treatment diabetic retinopathy study and mild macular grid laser photocoagulation strategies for diabetic macular edema SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID GROWTH-FACTOR; RETINA; DDME AB Objective: To compare 2 laser photocoagulation techniques for treatment of diabetic macular edema: the modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid photocoagulation technique and a potentially milder (but potentially more extensive) mild macular grid (MMG) laser technique in which microaneurysms are not treated directly and small mild burns are placed throughout the macula, whether or not edema is present. Methods: Two hundred sixty-three subjects (mean age, 59 years) with previously untreated diabetic macular edema were randomly assigned to receive laser photocoagulation by either the modified ETDRS (162 eyes) or MMG (161 eyes) technique. Visual acuity, fundus photographs, and optical coherence tomography measurements were obtained at baseline and at 3.5, 8, and 12 months. Treatment was repeated if diabetic macular edema persisted. Main Outcome Measure: Change in optical coherence tomography measurements at 12-month follow-up. Results: Among eyes with a baseline central subfield thickness of 250 mu m or greater, central subfield thickening decreased by an average of 88 mu m in the modified ETDRS group and by 49 mu m in the MMG group at 12-month follow-up (adjusted mean difference, 33 mu m; 95% confidence interval, 5-61 mu m; P =. 02). Weighted inner zone thickening by optical coherence tomography decreased by 42 mu m in the modified ETDRS group and by 28 mu m in the MMG group (adjusted mean difference, 14 mu m; 95% confidence interval, 1-27 mu m; P =. 04); maximum retinal thickening ( maximum thickening of the central and 4 inner subfields) decreased by 66 and 39 mu m, respectively (adjusted mean difference, 27 mu m; 95% confidence interval, 6- 47 mu m; P =. 01), and retinal volume decreased by 0.8 and 0.4 mm(3), respectively (adjusted mean difference, 0.3 mm(3); 95% confidence interval, 0.02-0.53 mm(3); P =. 03). At 12 months, the mean change in visual acuity was 0 letters in the modified ETDRS group and 2 letters worse in the MMG group (adjusted mean difference, 2 letters; 95% confidence interval, -0.5 to 5 letters; P =. 10). Conclusions: At 12 months after treatment, the MMG technique was less effective at reducing optical coherence tomography-measured retinal thickening than the more extensively evaluated current modified ETDRS laser photocoagulation approach. However, the visual acuity outcome with both approaches is not substantially different. Given these findings, a larger long-term trial of the MMG technique is not justified. Application to Clinical Practice: Modified ETDRS focal photocoagulation should continue to be a standard approach for treating diabetic macular edema. C1 Jaeb Ctr Hlth Res, Diabet Retinopathy Clin Res Network, Tampa, FL 33647 USA. Wilmer Eye Inst, Baltimore, MD USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Palmetto Retina Ctr, Columbia, SC USA. Retina Ctr, Aiea, HI USA. Texas Retina Associates, Arlington, TX USA. Austin Retina Associates, Austin, TX USA. Elman Retina Grp PA, Baltimore, MD USA. NEI, NIH, Bethesda, MD 20892 USA. Charlotte Eye Ear Nose & Throat Associates PA, Charlotte, NC USA. Texas Retina Associates, Dallas, TX USA. Denver Hlth Med Ctr, Denver, CO USA. Henry Ford Hlth Syst, Dept Ophthalmol, Detroit, MI USA. Henry Ford Hlth Syst, Eye Care Serv, Detroit, MI USA. Retinal Consultants Inc, Dublin, OH USA. Retina Consultants SW Florida, Ft Myers, FL USA. Retina Vitreous Consultants, Ft Lauderdale, FL USA. Univ Texas, Med Branch, Dept Ophthalmol & Visual Sci, Galveston, TX USA. Associted Retinal Consultants, Grand Rapids, MI USA. Charles A Garcia PA & Associates, Houston, TX USA. Vitreoretinal Consultants, Houston, TX USA. Midw Eye Inst, Indianapolis, IN USA. Cent Florida Retina Inst, Lakeland, FL USA. Delaware Valley Retina Associates, Lawrenceville, NJ USA. Eldorado Retina Associates PC, Louisville, CO USA. Univ Wisconsin, Dept Ophthalmol, Retina Serv, Madison, WI USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Dean A McGee Eye Inst, Oklahoma City, OK USA. Paducah Retinal Ctr, Paducah, KY USA. Lahey Clin Inc, Inst Eye, Peabody, MA USA. Rocky Mt Retina Consultants, Salt Lake City, UT USA. W Coast Retina Med Grp Inc, San Francisco, CA USA. Univ Washington, Med Ctr, Seattle, WA USA. Retina Consultants PLLC, New Lions Eye Inst, Slingerlands, NY USA. St Louis Univ, Inst Eye, St Louis, MO 63103 USA. REtina Vitreous Surg Cent New York PC, Syracuse, NY USA. Int Eye Ctr, Tampa, FL USA. Wake Forest Univ, Ctr Eye, Winston Salem, NC USA. Med Coll Georgia, Augusta, GA 30912 USA. Retina Associates Cleveland Inc, Beachwood, OH USA. Univ N Carolina, Dept Ophthalmol, Chapel Hill, NC USA. Horizon Eye Care PA, Charlotte, NC USA. Vitreo Retinal Asociates, Grand Rapids, MI USA. Retina Grp Washington, Greenbelt, MD USA. Retina Associates Hawaii Inc, Honolulu, HI USA. SE Retina Associates PC, Kingsport, TN USA. Doheny Eye Inst, Los Angeles, CA 90033 USA. Univ Rochester, Rochester, NY 14627 USA. No Illinois Retina Ltd, Rockford, IL USA. So Calif Permanente Med Grp, Santa Ana, CA USA. W Texas Retina Consultants PA, Abilene, TX USA. Retina Consultants Alabama, Birmingham, AL USA. Rush Univ, Ctr Med, Chicago, IL USA. Duke Univ, Ctr Eye, Durham, NC USA. Univ Calif Irvine, Irvine, CA USA. Univ Kentucky, Lexington, KY USA. Loma Linda Univ Hlth Care, Dept Ophthalmol, Loma Linda, CA USA. Virginia Eye Inst, Richmond Retina Associates, Richmond, VA USA. Associated Retinal Consultants PC, Royal Oak, MI USA. Barnes Retina Inst, St Louis, MO USA. Retina Specialists, Towson, MD USA. Miramar Eye Specialist Med Grp, Ventura, CA USA. Northwestern Med Fac Fdn, Chicago, IL USA. Retina NW PC, Portland, OR USA. George Washington Univ, Dept Ophthalmol, Washington, DC USA. RP Fong, DS (reprint author), Jaeb Ctr Hlth Res, Diabet Retinopathy Clin Res Network, 15310 Amberly Dr,Suite 350, Tampa, FL 33647 USA. EM drcrnet@jaeb.org NR 22 TC 101 Z9 110 U1 2 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2007 VL 125 IS 4 BP 469 EP 480 PG 12 WC Ophthalmology SC Ophthalmology GA 155AC UT WOS:000245548900003 ER PT J AU Klein, R Klein, BEK Knudtson, MD Cotch, MF Wong, TY Liu, K Burke, GL Saad, MF Jacobs, DR Sharrett, AR AF Klein, Ronald Klein, Barbara E. K. Knudtson, Michael D. Cotch, Mary Frances Wong, Tien Yin Liu, Kiang Burke, Gregory L. Saad, Mohammed F. Jacobs, David R., Jr. Sharrett, A. Richey TI Subclinical atherosclerotic cardiovascular disease and early age-related macular degeneration in a multiracial cohort - The multiethnic study of atherosclerosis SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CORONARY-ARTERY-DISEASE; BEAVER DAM EYE; RISK-FACTORS; POOLED FINDINGS; BLOOD-PRESSURE; UNITED-STATES; OXIDIZED LDL; 3 CONTINENTS; MACULOPATHY; ASSOCIATION AB Objective: To investigate the relationship of subclinical atherosclerotic cardiovascular disease (CVD) and its risk factors with age-related macular degeneration (AMD) in the Multiethnic Study of Atherosclerosis. Methods: This study included 6176 white, black, Hispanic, and Chinese participants aged 44 to 84 years from 6 communities in the United States. Measurements of subclinical CVD were performed according to standardized protocols. Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System. Results: In analyses controlled for age, sex, race/ethnicity, and study location, early AMD was associated with a higher serum high-density lipoprotein cholesterol level (odds ratio per 15 mg/dL, 1.16; 95% confidence interval, 1.01-1.36) and the presence of echolucent carotid artery plaque (odds ratio for present vs no plaque, 0.37; 95% confidence interval, 0.18-0.74) in the whole cohort. Interactions of race/ethnicity and early AMD were found for carotid intima-media thickness, increasing severity of maximum carotid artery stenosis, serum triglyceride level, subclinical CVD severity, and Agatston calcium score. Conclusion: Few associations were found between subclinical CVD and CVD risk factors with early AMD. The findings of associations of early AMD with some signs of subclinical atherosclerotic CVD are different among the 4 racial/ethnic groups, which suggests that care must be taken in generalizing from one racial/ethnic group to another. C1 Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI 53726 USA. NEI, NIH, Div Epidemiol & Clin Res, Bethesda, MD 20892 USA. Univ Melbourne, Ctr Eye Res, Melbourne, Vic, Australia. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. SUNY Stony Brook, Sch Med, Dept Prevent Med, Stony Brook, NY 11794 USA. Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Klein, R (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 610 N Walnut St,450 WARF, Madison, WI 53726 USA. EM kleinr@epi.ophth.wisc.edu OI Cotch, Mary Frances/0000-0002-2046-4350 FU Intramural NIH HHS [ZIA EY000403-10, Z01 EY000403-06, ZIA EY000403-08, Z01 EY000403-07, ZIA EY000403-09, Z99 EY999999]; NCRR NIH HHS [M01-RR00645]; NHLBI NIH HHS [N01-HC-95169, HL69979-03, N01-HC-95159, N01-HC-95160, N01-HC-95165, N01-HC-95161, N01-HC-95163, N01-HC-95162, N01-HC-95166, N01-HC-95164] NR 48 TC 26 Z9 28 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2007 VL 125 IS 4 BP 534 EP 543 DI 10.1001/archopht.125.4.534 PG 10 WC Ophthalmology SC Ophthalmology GA 155AC UT WOS:000245548900011 PM 17420374 ER PT J AU Begnami, MD Quezado, M Pinto, P Linehan, WM Merino, M AF Begnami, Maria Dirlei Quezado, Martha Pinto, Peter Marston Linehan, W. Merino, Maria TI Adenoid cystic/basal cell carcinoma of the prostate - Review and update SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review ID BASAL-CELL; SALIVARY-GLAND; HYPERPLASIA; TUMOR; ADENOCARCINOMA; EXPRESSION; NEOPLASMS; LUNG AB Context.-Although most prostate carcinomas are of the conventional acinar type, unusual variants have been reported. Adenoid cystic/basal cell carcinoma of the prostate is a rare tumor with distinctive histopathologic features. There are only a few publications in the literature concerning the diagnosis, treatment, and prognosis of this neoplasm. Objective.-To review current literature together with the clinical, pathologic, and immunohistochemical features of adenoid cystic/basal cell carcinoma of the prostate and offer a practical approach to the diagnosis-including the differential diagnosis-of this neoplasm in surgical pathologic specimens. Data Sources.-Adenoid cystic/basal cell carcinoma of the prostate is composed of infiltrating basaloid cells forming dilated acinar and cribriform spaces with luminal basement-like material. Differentiation of adenoid cystic/basal cell carcinoma from basal cell hyperplasia and cribriform pattern of acinar adenocarcinoma may be difficult. The use of cytokeratin 34 beta E12 and prostate-specific antigen can help in difficult cases. Most cases are indolent, but metastasis has been documented in a few cases. Conclusions.-Various histologic and immunohistochemical features are helpful in recognizing adenoid cystic/basal cell carcinoma of the prostate. This is a rare subtype of prostate cancer and correct diagnosis is important because of the unique clinical and biological features and the implications for treatment and prognosis. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Begnami, MD (reprint author), NCI, Pathol Lab, NIH, Bldg 10 Room 2N216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM begnamim@mail.nih.gov RI Begnami, Maria/D-9663-2012 OI Begnami, Maria/0000-0003-0848-7813 NR 30 TC 16 Z9 20 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD APR PY 2007 VL 131 IS 4 BP 637 EP 640 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 155WY UT WOS:000245610500024 PM 17425398 ER PT J AU Aksentijevich, I Putnam, CD Remmers, EF Mueller, JL Le, J Kolodner, RD Moak, Z Chuang, M Austin, F Goldbach-Mansky, R Hoffman, HM Kastner, DL AF Aksentijevich, Ivona Putnam, Christopher D. Remmers, Elaine F. Mueller, James L. Le, Julie Kolodner, Richard D. Moak, Zachary Chuang, Michael Austin, Frances Goldbach-Mansky, Raphaela Hoffman, Hal M. Kastner, Daniel L. TI The clinical continuum of cryopyrinopathies - Novel CIAS1 mutations in north American patients and a new cryopyrin model SO ARTHRITIS AND RHEUMATISM LA English DT Article ID MULTISYSTEM INFLAMMATORY DISEASE; MUCKLE-WELLS-SYNDROME; INTERLEUKIN-1 RECEPTOR ANTAGONIST; COLD AUTOINFLAMMATORY SYNDROME; SECONDARY STRUCTURE PREDICTION; ARTICULAR SYNDROME; GENETIC-HETEROGENEITY; ACTIVATE CASPASE-1; CINCA SYNDROME; PROTEIN AB Objective. The cryopyrinopathies are a group of rare autoinflammatory disorders that are caused by mutations in CIAS1, encoding the cryopyrin protein. However, cryopyrin mutations are found only in 50% of patients with clinically diagnosed cryopyrinopathies. This study was undertaken to investigate the structural effect of disease-causing mutations on cryopyrin, in order to gain better understanding of the impact of disease-associated mutations on protein function. Methods. We tested for CIAS1 mutations in 22 patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome, 12 with Muckle-Wells syndrome (MWS), 18 with familial cold-induced autoinflammatory syndrome (FCAS), and 3 probands with MWS/FCAS. In a subset of mutation-negative patients, we screened for mutations in proteins that are either homologous to cryopyrin or involved in the caspase 1/interleukin-1 beta signaling pathway. CIAS1 and other candidate genes were sequenced, models of cryopyrin domains were constructed using structurally homologous proteins as templates, and disease-causing mutations were mapped. Results. Forty patients were mutation positive, and 7 novel mutations, V262A, C259W, L264F, V351L, F443L, F523C, and Y563N, were found in 9 patients. No mutations in any candidate genes were identified. Most mutations mapped to an inner surface of the hexameric ring in the cryopyrin model, consistent with the hypothesis that the mutations disrupt a closed form of cryopyrin, thus potentiating inflammasome assembly. Disease-causing mutations correlated with disease severity only for a subset of known mutations. Conclusion. Our modeling provides insight into potential molecular mechanisms by which cryopyrin mutations can inappropriately activate an inflammatory response. A significant number of patients who are clinically diagnosed as having cryopyrinopathies do not have identifiable disease-associated mutations. C1 NIAMSD, Bethesda, MD 20892 USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. RP Aksentijevich, I (reprint author), NIH, Genet & Genom Branch, Bldg 9,Room 1N132,9000 Rockville Pike, Bethesda, MD 20892 USA. EM aksentii@exchange.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [R01 AI052430, R01-AI-52430] NR 54 TC 192 Z9 195 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2007 VL 56 IS 4 BP 1273 EP 1285 DI 10.1002/art.22491 PG 13 WC Rheumatology SC Rheumatology GA 159DH UT WOS:000245845100026 PM 17393462 ER PT J AU Aletaha, D Smolen, JS Ward, MM AF Aletaha, Daniel Smolen, Josef S. Ward, Michael M. TI The irreversible component of the disability index of the Health Assessment Questionnaire: comment on the article by Aletaha et al - Reply SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID RHEUMATOID-ARTHRITIS C1 Med Univ Vienna, NIH, Vienna, Austria. NIH, Bethesda, MD 20892 USA. RP Aletaha, D (reprint author), Med Univ Vienna, NIH, Vienna, Austria. NR 3 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 2007 VL 56 IS 4 BP 1369 EP 1370 DI 10.1002/art.22518 PG 2 WC Rheumatology SC Rheumatology GA 159DH UT WOS:000245845100039 ER PT J AU Samuels, JF Bienvenu, OJ Pinto, A Fyer, AJ McCracken, JT Rauch, SL Murphy, DL Grados, MA Greenberg, BD Knowles, JA Placentini, J Cannistraro, PA Cullen, B Riddle, MA Rasmussen, SA Pauls, DL Willour, VL Shugart, YY Liang, KY Hoehn-Saric, R Nestadt, G AF Samuels, Jack F. Bienvenu, O. Joseph Pinto, Anthony Fyer, Abby J. McCracken, James T. Rauch, Scott L. Murphy, Dennis L. Grados, Marco A. Greenberg, Benjamin D. Knowles, James A. Placentini, John Cannistraro, Paul A. Cullen, Bernadette Riddle, Mark A. Rasmussen, Steven A. Pauls, David L. Willour, Virginia L. Shugart, Yin Y. Liang, Kung-yee Hoehn-Saric, Rudolf Nestadt, Gerald TI Hoarding in obsessive-compulsive disorder: results from the OCD collaborative genetics study SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE hoarding; obsessive-compulsive disorder; comorbidity; personality ID FACTOR-ANALYZED SYMPTOM; PERSONALITY-DISORDERS; DIMENSIONS; BEHAVIOR; FAMILY; SCHIZOPHRENIA; RATIONALE; MODEL; LA AB Hoarding behavior occurs frequently in obsessive-compulsive disorder (OCD). Results from previous studies suggest that individuals with OCD who have hoarding symptoms are clinically different than non-hoarders and may represent a distinct clinical group. In the present study, we compared 235 hoarding to 389 non-hoarding participants, all of whom had OCD, collected in the course of the OCD Collaborative Genetics Study. We found that, compared to non-hoarding individuals, boarders were more likely to have symmetry obsessions and repeating, counting, and ordering compulsions; poorer insight; more severe illness; difficulty initiating or completing tasks, and indecision. Hoarders had a greater prevalence of social phobia and generalized anxiety disorder. Hoarders also had a greater prevalence of obsessive-compulsive and dependent personality disorders. Five personality traits were independently associated with hoarding: miserliness, preoccupation with details, difficulty making decisions, odd behavior or appearance, and magical thinking. Hoarding and indecision were more prevalent in the relatives of hoarding than of non-hoarding probands. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. Brown Univ, Sch Med, Butler Hosp, Dept Psychiat & Human Behav, Providence, RI 02906 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Sch Med, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD 21287 USA. RP Samuels, JF (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Meyer 4-181, Baltimore, MD 21287 USA. EM jacks@jhmi.edu RI Liang, Kung-Yee/F-8299-2011; Pinto, Anthony/D-2718-2017; OI Pinto, Anthony/0000-0002-6078-7242; Samuels, Jack/0000-0002-6715-7905 FU NCRR NIH HHS [RR00052]; NIMH NIH HHS [K23-MH64543, R01 MH50214] NR 51 TC 112 Z9 114 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD APR PY 2007 VL 45 IS 4 BP 673 EP 686 DI 10.1016/j.brat.2006.05.008 PG 14 WC Psychology, Clinical SC Psychology GA 149RO UT WOS:000245164500004 PM 16824483 ER PT J AU Omvik, S Pallesen, S Bjorvatn, B Thayer, J Nordhus, IH AF Omvik, Siri Pallesen, Stale Bjorvatn, Bjorn Thayer, Julian Nordhus, Inger Hilde TI Night-time thoughts in high and low worriers: Reaction to caffeine-induced sleeplessness SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Article DE sleeplessness; insomnia; caffeine; worry ID STATE WORRY QUESTIONNAIRE; SLEEP-ONSET INSOMNIA; PERSISTENCE; VALIDITY; MODEL AB There is ample evidence for the existence of an association between sleeplessness and worry. Not much is known, however, concerning the nature of this relationship. Therefore, a study was conducted investigating the causal relationship between sleeplessness and nocturnal worry. A 2 x 2 (Worry x Induced sleeplessness) analysis of covariance design was used. The first factor consisted of a subject variable defined by scoring either high or low on a trait measure of worry (the Penn State Worry Questionnaire) and the second factor consisted of 300 mg caffeine or placebo. A total of 96 female undergraduate students participated. The dependent variables comprised measures of nocturnal worry (the Night-Time Thoughts Questionnaire) and subjective and objective sleep parameters. Overall, caffeine caused an increase in nocturnal worry and sleeplessness. A significant interaction effect occurred between Worry and Induced sleeplessness on one of the objective sleep parameters, but no other interaction effects were significant. The results suggest that worry may occur as an epiphenomenon of sleeplessness. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Bergen, Dept Clin Psychol, N-5015 Bergen, Norway. NIA, Baltimore, MD 21224 USA. RP Omvik, S (reprint author), Univ Bergen, Dept Clin Psychol, Christies Gate 12, N-5015 Bergen, Norway. EM siri.omvik@psykp.uib.no NR 34 TC 8 Z9 9 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD APR PY 2007 VL 45 IS 4 BP 715 EP 727 DI 10.1016/j.brat.2006.06.006 PG 13 WC Psychology, Clinical SC Psychology GA 149RO UT WOS:000245164500007 PM 16949554 ER PT J AU Kessl, JJ Moskalev, NV Gribble, GW Nasr, M Meshnick, SR Trumpower, BL AF Kessl, Jacques J. Moskalev, Nikolai V. Gribble, Gordon W. Nasr, Mohamed Meshnick, Steven R. Trumpower, Bernard L. TI Parameters determining the relative efficacy of hydroxy-naphthoquinone inhibitors of the cytochrome bc(1) complex SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Article DE hydroxy-naphthoquinones; cytochrome bc(1); complex; malaria; Plasmodium; Pneumocystis; atovaquone ID SACCHAROMYCES-CEREVISIAE; MOLECULAR-BASIS; ATOVAQUONE RESISTANCE; TOXOPLASMA-GONDII; BROAD-SPECTRUM; AIDS PATIENTS; IN-VITRO; 566C80; HYDROXYNAPHTHOQUINONE; BINDING AB Hydroxy-naphthoquinones are competitive inhibitors of the cytochrome bc(1) complex that bind to the ubiquinol oxidation site between cytochrome b and the iron-sulfur protein and presumably mimic a transition state in the ubiquinol oxidation reaction catalyzed by the enzyme. 19 The parameters that affect efficacy of binding of these inhibitors to the bc(1) complex are not well understood. Atovaquone (R), a hydroxynaphthoquinone, has been used therapeutically to treat Pneumocystis carinii and Plasmodium infections. As the pathogens have developed resistance to this drug, it is important to understand the molecular basis of the drug resistance and to develop new drugs that can circumvent the drug resistance. We previously developed the yeast and bovine he, complexes as surrogates to model the interaction of atovaquone with the bc(1) complexes of the target pathogens and human host. As a first step to identify new cytochrome bc(1) complex inhibitors with therapeutic potential and to better understand the determinants of inhibitor binding, we have screened a library of 2-hydroxy-naphthoquinones with aromatic, cyclic, and non-cyclic alkyl side-chain substitutions at carbon-3 on the hydroxy-quinone ring. We found a group of compounds with alkyl side-chains that effectively inhibit the yeast bc(1) complex. Molecular modeling of these into the crystal structure of the yeast cytochrome bc(1) complex provides structural and quantitative explanations for their binding efficacy to the target enzyme. In addition we also identified a 2-hydroxy-naphthoquinones with a branched side-chain that has potential for development as an anti-fungal and anti-parasitic therapeutic. (C) 2007 Elsevier B.V. All rights reserved. C1 Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH 03755 USA. Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. NIAID, Div AIDS, Drug Dev & Clin Sci, Bethesda, MD 20892 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. RP Trumpower, BL (reprint author), Dartmouth Coll Sch Med, Dept Biochem, 7200 Vail, Hanover, NH 03755 USA. EM Trumpower@Dartmouth.edu RI Kessl, Jacques/J-6073-2015 FU NIGMS NIH HHS [R01 GM020379-33] NR 25 TC 24 Z9 25 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PD APR PY 2007 VL 1767 IS 4 BP 319 EP 326 DI 10.1016/j.bbabio.2007.02.014 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 165UW UT WOS:000246332400006 PM 17383607 ER PT J AU Birnbaumer, L AF Birnbaumer, Lutz TI The discovery of signal transduction by G proteins. A personal account and an overview of the initial findings and contributions that led to our present understanding SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review ID ADENYL CYCLASE SYSTEM; CYCLIC NUCLEOTIDE PHOSPHODIESTERASE; ISLET-ACTIVATING PROTEIN; STIMULATORY REGULATORY COMPONENT; CHOLERA-TOXIN; PLASMA-MEMBRANES; RAT-LIVER; FAT CELLS; GUANYL NUCLEOTIDES; VERTEBRATE PHOTORECEPTORS AB The realization that there existed a G-protein coupled signal transduction mechanism developed gradually and was initially the result of an ill fated quest for uncovering the mechanism of action of insulin, followed by a refocused research in many laboratories, including mine, on how GTP acted to increase hormonal stimulation of adenylyl cyclase. Independent research into how light-activated rhodopsin triggers a response in photoreceptor cells of the retina and the attendant biochemical studies joined midway and, without the left hand knowing well what the right hand was doing, preceded classical G protein research in identifying the molecular players responsible for signal transduction by G proteins. (c) 2006 Elsevier B.V. All rights reserved. C1 NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, Bldg 101,Room A214,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES101684-03, Z01 ES101683-03, Z01 ES101643-03] NR 77 TC 22 Z9 22 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR PY 2007 VL 1768 IS 4 BP 756 EP 771 DI 10.1016/j.bbamem.2006.09.027 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160WG UT WOS:000245972500003 PM 17141178 ER PT J AU Birnbaumer, L AF Birnbaumer, Lutz TI Expansion of signal transduction by G proteins - The second 15 years or so: From 3 to 16 alpha subunits plus beta gamma dimers SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review ID NUCLEOTIDE-BINDING-PROTEIN; HETEROTRIMERIC G-PROTEINS; PHOSPHOLIPASE-C-BETA; AMINO-ACID-SEQUENCE; POLYMORPHONUCLEAR LEUKOCYTE MEMBRANES; GTPASE-ACTIVATING PROTEINS; ADRENERGIC-RECEPTOR KINASE; BLOOD MONONUCLEAR-CELLS; BRUTON TYROSINE KINASE; LIVER PLASMA-MEMBRANES AB The first 15 years, or so, brought the realization that there existed a G protein coupled signal transduction mechanism by which hormone receptors regulate adenylyl cyclases and the light receptor rhodopsin activates visual phosphodiesterase. Three G proteins, Gs, Gi and transducin (T) had been characterized as alpha beta-gamma heterotrimers, and Gs alpha-GTP and T alpha-GTP had been identified as the sigaling arms of Gs and T. These discoveries were made using classical biochemical approaches, and culminated in the purification of these G proteins. The second 15 years, or so, are the subject of the present review. This time coincided with the advent of powerful recombinant DNA techniques. Combined with the classical approaches, the field expanded the repertoire of G proteins from 3 to 16, discovered the superfamily of seven transmembrane G protein coupled receptors (GPCRs) - which is not addressed in this article - and uncovered an amazing repertoire of effector functions regulated not only by alpha GTP complexes but also by beta gamma dimers. Emphasis is placed in presenting how the field developed with the hope of conveying why many of the new findings were made. (c) 2006 Elsevier B.V. All rights reserved. C1 NIEHS, Lab signal Transduct, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Birnbaumer, L (reprint author), NIEHS, Lab signal Transduct, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM birnbau1@niehs.nih.gov FU Intramural NIH HHS; NIEHS NIH HHS [Z01 ES101643-03, Z01 ES101683-03, Z01 ES101684-03] NR 183 TC 90 Z9 92 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR PY 2007 VL 1768 IS 4 BP 772 EP 793 DI 10.1016/j.bbamem.2006.12.002 PG 22 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160WG UT WOS:000245972500004 PM 17258171 ER PT J AU Catapano, LA Manji, HK AF Catapano, Lisa A. Manji, Husseini K. TI G protein-coupled receptors in major psychiatric disorders SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Review DE G protein-coupled receptors (GPCRs); depression; bipolar disorder; schizophrenia; serotonin; dopamine; glutamate ID DOPAMINE D2 RECEPTOR; BIPOLAR AFFECTIVE-DISORDER; SEROTONIN 2A RECEPTOR; BETA-ADRENERGIC RECEPTORS; EUROPEAN MULTICENTER ASSOCIATION; POSITRON-EMISSION-TOMOGRAPHY; GROWTH-HORMONE RESPONSE; TRICYCLIC ANTIDEPRESSANT DESIPRAMINE; FAMILY-BASED ASSOCIATION; RAT PREFRONTAL CORTEX AB Although the molecular mechanisms underlying psychiatric illnesses such as depression, bipolar disorder and schizophrenia remain incompletely understood, there is increasing clinical, pharmacologic, and genetic evidence that G protein-coupled receptors (GPCRs) play critical roles in these disorders and their treatments. This perspectives paper reviews and synthesizes the available data. Dysfunction of multiple neurotransmitter and neuropeptide GPCRs in frontal cortex and limbic-related regions, such as the hippocampus, hypothalamus and brainstem, likely underlies the complex clinical picture that includes cognitive, perceptual, affective and motoric symptoms. The future development of novel agents targeting GPCR signaling cascades remains an exciting prospect for patients refractory to existing therapeutics. (c) 2006 Elsevier B.V. All rights reserved. C1 NIMH, Mood & Anxiety Disorders Program, Lab Mol Pathophysiol, Porter Neurosci Res Ctr,HHS, Bethesda, MD 20892 USA. RP Manji, HK (reprint author), NIMH, Mood & Anxiety Disorders Program, Lab Mol Pathophysiol, Porter Neurosci Res Ctr,HHS, Bldg 35,Room IC-917,35 Convent Dr, Bethesda, MD 20892 USA. EM catapanol@mail.nih.gov; manji@nih.gov FU Intramural NIH HHS; NIMH NIH HHS [Z01 MH002831-03, Z01 MH002847-02] NR 246 TC 43 Z9 44 U1 4 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR PY 2007 VL 1768 IS 4 BP 976 EP 993 DI 10.1016/j.bbamem.2006.09.025 PG 18 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 160WG UT WOS:000245972500018 PM 17078926 ER PT J AU Berna, MJ Hoffmann, KM Tapia, JA Thill, M Pace, A Mantey, SA Jensen, RT AF Berna, Marc J. Hoffmann, K. Martin Tapia, Jose A. Thill, Michelle Pace, Andrea Mantey, Samuel A. Jensen, Robert T. TI CCK causes PKD1 activation in pancreatic acini by signaling through PKC-delta and PKC-independent pathways SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PKD1 activation; pancreas; cholecystokinin; gastrointestinal hormone; growth factor; PKC ID PROTEIN-KINASE-D; NF-KAPPA-B; PLECKSTRIN HOMOLOGY DOMAIN; INTESTINAL EPITHELIAL-CELLS; POTENTIATES DNA-SYNTHESIS; TYROSINE PHOSPHORYLATION; GROWTH-FACTOR; PHORBOL ESTERS; IN-VIVO; C-DELTA AB Protein kinase D1 (PKD1) is involved in cellular processes including protein secretion, proliferation and apoptosis. Studies suggest PKD1 is activated by various stimulants including gastrointestinal (GI) hormones/neurotransmitters and growth factors in a protein kinase C (PKC)-dependent pathway. However, little is known about the mechanisms of PKD1 activation in physiologic GI tissues. We explored PKD1 activation by GI hormones/neurotransmitters and growth factors and the mediators involved in rat pancreatic acini. Only hormones/neurotransmitters activating phospholipase C caused PKD1 phosphorylation (S916, S744/748). CCK activated PKD1 and caused a time- and dose-dependant increase in serine phosphorylation by activation of high- and low-affinity CCKA receptor states. Inhibition of CCK-stimulated increases in phospholipase C, PKC activity or intracellular calcium decreased PKD1 S916 phosphorylation by 56%, 62% and 96%, respectively. PKC inhibitors GF109203X/Go6976/Go6983/PKC-zeta pseudosubstrate caused a 62/43/49/0% inhibition of PKD1 S916 phosphorylation and an 87/13/82/0% inhibition of PKD1S744/748 phosphorylation. Expression of dominant negative PKC-delta, but not PKC-epsilon, or treatment with PKC-delta translocation inhibitor caused marked inhibition of PKD phosphorylation. Inhibition of Src/PI3K/MAPK/tyrosine phosphorylation had no effect. In unstimulated cells, PKD1 was mostly located in the cytoplasm. CCK stimulated translocation of total and phosphorylated PKD1 to the membrane. These results demonstrate that CCKA receptor activation leads to PKD activation by signaling through PKC-dependent and PKC-independent pathways. (c) 2006 Elsevier B.V. All rights reserved. C1 NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Extremadura, Dept Fisiol, Caceres 10071, Spain. NEI, NIH, Bethesda, MD 20892 USA. Univ Hamburg, Klinikum Eppendorf, Med Klin 1, D-20246 Hamburg, Germany. RP Jensen, RT (reprint author), NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov RI Tapia, Jose/C-5181-2008 OI Tapia, Jose/0000-0002-3614-6867 FU Intramural NIH HHS [Z01 DK053101-17] NR 72 TC 38 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR PY 2007 VL 1773 IS 4 BP 483 EP 501 DI 10.1016/j.bbamcr.2006.12.008 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158II UT WOS:000245784700004 PM 17306383 ER PT J AU Lindh, R Ahmad, F Resjo, S James, P Yang, JS Fales, HM Manganiello, V Degerman, E AF Lindh, Rebecka Ahmad, Faiyaz Resjo, Svante James, Peter Yang, Jeong S. Fales, Henry M. Manganiello, Vincent Degerman, Eva TI Multisite phosphorylation of adipocyte and hepatocyte phosphodiesterase 3B SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE PDE3B; phosphorylation; adipocyte; hepatocyte; insulin; cAMP ID PROTEIN-KINASE-B; INHIBITED CAMP-PHOSPHODIESTERASE; INSULIN-INDUCED PHOSPHORYLATION; RAT ADIPOCYTES; PHOSPHATIDYLINOSITOL 3-KINASE; FAT-CELLS; PLASMA-MEMBRANE; CYCLIC-AMP; IN-VITRO; ACTIVATION AB Phosphodiesterase 3B (PDE3B) is an important component of insulin and cAMP-dependent signalling pathways. In order to study phosphorylation of PDE3B, we have used an adenoviral system to express recombinant flag-tagged PDE3B in primary rat adipocytes and H4IIE hepatoma cells. Phosphorylation of PDE3B after treatment of cells with insulin, cAMP-increasing agents, or the phosphatase inhibitor, calyculin A was analyzed by two-dimensional tryptic phosphopeptide mapping and mass spectrometry. We found that PDE3B is multisite phosphorylated in adipocytes and H4IIE hepatoma cells in response to all these stimuli. Several sites were identified; serine (S)273, S296, S421, S424/5, S474 and S536 were phosphorylated in adipocyte as well as H4IIE hepatoma cells whereas S277 and S507 were phosphorylated in hepatoma cells only. Several of the sites were phosphorylated by insulin as well as cAMP-increasing hormones indicating integration of the two signalling pathways upstream of PDE3B, maybe at the level of protein kinase B. (c) 2007 Elsevier B.V. All rights reserved. C1 Lund Univ, Dept Expt Med Sci, Div Endocrinol Diabet & Metab, S-22100 Lund, Sweden. NHLBI, Bethesda, MD 20824 USA. Lund Univ, Dept Prot Technol, S-22100 Lund, Sweden. NHLBI, Lab Appl Mass Spect, Bethesda, MD 20892 USA. RP Lindh, R (reprint author), Lund Univ, Dept Expt Med Sci, Div Endocrinol Diabet & Metab, S-22100 Lund, Sweden. EM rebecka.lindh@med.lu.se NR 31 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD APR PY 2007 VL 1773 IS 4 BP 584 EP 592 DI 10.1016/j.bbamcr.2007.01.010 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 158II UT WOS:000245784700013 PM 17320989 ER PT J AU Zhang, HL Meng, LH Pommier, Y AF Zhang, Hongliang Meng, Ling-Hua Pommier, Yves TI Mitochondrial topoisomerases and alternative splicing of the human TOP1mt gene SO BIOCHIMIE LA English DT Article DE mitochondrial DNA (mtDNA); mitochondrial topoisomerase; Top1; Top2; Top3 alpha; alternative splicing; dual localization ID II DNA TOPOISOMERASE; HEMOFLAGELLATE LEISHMANIA-DONOVANI; SINGLE-COPY GENE; SACCHAROMYCES-CEREVISIAE; CRITHIDIA-FASCICULATA; TRYPANOSOMA-BRUCEI; CAMPTOTHECIN RESISTANCE; MAMMALIAN MITOCHONDRIA; RNA INTERFERENCE; KINETOPLAST DNA AB Mitochondria are the only organelles containing metabolically active DNA besides nuclei. By analogy with the nuclear topoisomerases, mitochondrial topoisomerase activities are probably critical for maintaining the topology of mitochondrial DNA during replication, transcription, and repair. Mitochondrial diseases include a wide range of defects including neurodegeneracies, myopathies, metabolic abnormalities and premature aging. Vertebrates only have one known specific mitochondrial topoisomerase gene (TOPlmt), coding for a type IB topoisomerase. Like the mitochondrial DNA and RNA polymerase, the TOPlmt gene is encoded in the nuclear genome. The TOP1mt gene possesses the 13 exon Top1B signature motif and codes for a mitochondrial targeting signals at the N-terminus of the Top I mt polypeptide. This review summarizes our current knowledge of mitochondrial topoisomerases (type IA, IB and type 11) in eukaryotes including budding and fission yeasts (Saccharomyces cerevisiae and Schizosaccharomyces pombe) and protozoan parasites (kinetoplastidiae and plasmodium). It also includes new data showing alternative splice variants of human TOP1mt. (C) 2006 Elsevier Masson SAS. All rights reserved. C1 NCI, Ctr Canc Res, Lab Mol Pharmacol, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Ctr Canc Res, Lab Mol Pharmacol, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov FU Intramural NIH HHS NR 67 TC 27 Z9 28 U1 0 U2 5 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0300-9084 J9 BIOCHIMIE JI Biochimie PD APR PY 2007 VL 89 IS 4 BP 474 EP 481 DI 10.1016/j.biochi.2006.11.002 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 173JO UT WOS:000246869500006 PM 17161897 ER PT J AU Niwa, M Nitta, A Yamada, Y Nakajima, A Saito, K Seishima, M Shen, LY Noda, Y Furukawa, S Nabeshima, T AF Niwa, Minae Nitta, Atsumi Yamada, Yuichiro Nakajima, Akira Saito, Kuniaki Seishima, Mitsuru Shen, Liya Noda, Yukihiro Furukawa, Shoei Nabeshima, Toshitaka TI An inducer for glial cell line-derived neurotrophic factor and tumor necrosis factor-alpha protects against methamphetamine-induced rewarding effects and sensitization SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dopamine (DA); glial cell line-derived neurotrophic factor (GDNF); methamphetamine (METH); rewarding effects; sensitization; tumor necrosis factor-alpha (TNF-alpha) ID TISSUE-PLASMINOGEN ACTIVATOR; NF-KAPPA-B; OPIOID RECEPTOR AGONIST; DOPAMINE-RECEPTORS; SIGNALING PATHWAY; NUCLEUS-ACCUMBENS; MICE LACKING; BRAIN; COCAINE; ADDICTION AB Background: There are few efficacious medications for drug dependence. We investigated the potential of Leu-Ile, which induces the expression of glial cell line-derived neurotrophic factor (GDNF) and tumor necrosis factor-alpha (TNF-alpha), as a novel therapeutic agent for methamphetamine (METH)-induced dependence. Methods: The levels of GDNF and TNF-alpha messenger RNA (mRNA) were determined by real-time reverse transcription polymerase chain reaction. Enzyme immunoassays and immunohistochemistry were employed to determine levels of these proteins. Effects of Leu-Ile on METH-induced rewarding effects and sensitization were investigated with conditioned place preference and locomotor activity tests. Extracellular dopamine (DA) levels and DA uptake into synaptosomes were examined with an in vivo microdialysis and trititated thymidine ([H-3]) DA uptake assay. Results: Leu-Ile induced the expression of not only GDNF but also TNF-alpha. Pretreatment with Leu-Ile blocked the acquisition of METH-induced place preference and sensitization. Interestingly, post-treatment with Leu-Ile attenuated them even after their development. An inhibitory effect of Leu-Ile on METH-induced place preference was observed in neither GDNF heterozygous nor TNF-alpha knockout mice. Leu-Ile inhibited DA release in the nucleus accumbens and the decrease in synaptosomal DA uptake in the midbrain induced by repeated METH treatment. Conclusions: These results suggest that Leu-Ile inhibits METH-induced rewarding effects and sensitization by regulating extracellular DA levels via the induction of GDNF and TNF-alpha expression. C1 Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Showa Ku, Nagoya, Aichi 4668560, Japan. Meijo Univ, Fac Pharm, Div Clin Sci Clin Pharm Practice Management & Res, Nagoya, Aichi 468, Japan. Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 500, Japan. Gifu Pharmaceut Univ, Lab Mol Biol, Gifu 500, Japan. Natl Canc Inst, Lab Cellular Carcinogenesis & Tumor Promot, Ctr Canc Res, Bethesda, MD USA. RP Nabeshima, T (reprint author), Nagoya Univ, Grad Sch Med, Dept Neuropsychopharmacol & Hosp Pharm, Showa Ku, Tsurumai 65, Nagoya, Aichi 4668560, Japan. EM tnabeshi@med.nagoya-u.ac.jp RI Nakajima, Akira/I-7077-2014; Niwa, Minae/G-5469-2011 OI Niwa, Minae/0000-0002-8784-7815 NR 49 TC 40 Z9 49 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 1 PY 2007 VL 61 IS 7 BP 890 EP 901 DI 10.1016/j.biopsych.2006.06.016 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 151NX UT WOS:000245298500009 PM 17046726 ER PT J AU Royt, PW Honeychuck, RV Pant, RR Rogers, ML Asher, LV Lloyd, JR Carlos, WE Belkin, HE Patwardhan, S AF Royt, Paulette W. Honeychuck, Robert V. Pant, Ramesh R. Rogers, Magnus L. Asher, Ludmila V. Lloyd, John R. Carlos, W. E. Belkin, Harvey E. Patwardhan, Swati TI Iron- and 4-hydroxy-2-alkylquinoline-containing periplasmic inclusion bodies of Pseudomonas aeruginosa: A chemical analysis SO BIOORGANIC CHEMISTRY LA English DT Article DE Pseudomonas aeruginosa; periplasmic inclusion bodies; iron; Pseudomonas quinolone signal; pseudan; 4-hydroxy-2-alkylquinoline; HAQ; PQS ID TO-CELL COMMUNICATION; QUINOLONE SIGNAL PQS; MEMBRANE-VESICLES; BACTERIAL-CELL; PROKARYOTES; CHELATOR AB Dark aggregated particles were seen on pellets of iron-rich, mid-logarithmic phase Pseudomonas aeruginosa. Transmission electron microscopy of these cells showed inclusion bodies in periplasmic vacuoles. Aggregated particles isolated from the spent medium of these cells contained iron as indicated by atomic absorption spectroscopy and by electron paramagnetic resonance spectroscopy that revealed Fe3+. Scanning electron microscopy/energy dispersive X-ray analysis of whole cells revealed the presence of iron-containing particles beneath the surface of the cell, indicating that the isolated aggregates were the intracellular inclusion bodies. Collectively, mass spectroscopy and nuclear magnetic resonance spectroscopy of the isolated inclusion bodies revealed the presence of 3,4-dihydroxy-2-heptylquinoline which is the Pseudomonas quinolone signaling compound (PQS) and an iron chelator; 4-hydroxy-2-heptylquinoline (pseudan VII), which is an iron chelator, antibacterial compound and precursor of PQS; 4-hydroxy-2-nonylquinoline (pseudan IX) which is an iron chelator and antibacterial compound; 4-hydroxy-2-methylquinoline (pseudan I), and 4-hydroxy-2-nonylquinoline N-oxide. (c) 2006 Elsevier Inc. All rights reserved. C1 George Mason Univ, Mol & Microbiol Dept, Fairfax, VA 22030 USA. George Mason Univ, Dept Chem & Biochem, Fairfax, VA 22030 USA. Walter Reed Army Inst Res, Div Pathol, Silver Spring, MD 20910 USA. NIDDK, DHHS, NIH, Bethesda, MD 20892 USA. USN, Res Lab, Washington, DC 20375 USA. US Geol Survey, Reston, VA 20192 USA. RP Royt, PW (reprint author), George Mason Univ, Mol & Microbiol Dept, Fairfax, VA 22030 USA. EM proyt@gmu.edu OI Belkin, Harvey/0000-0001-7879-6529 NR 27 TC 4 Z9 4 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 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD APR PY 2007 VL 35 IS 2 BP 175 EP 188 DI 10.1016/j.bioorg.2006.10.004 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 154RT UT WOS:000245525900006 PM 17126377 ER PT J AU Ansar, S Burlison, JA Hadden, MK Yu, XM Desino, KE Bean, J Neckers, L Audus, KL Michaelis, ML Blagg, BSJ AF Ansar, Sabah Burlison, Joseph A. Hadden, M. Kyle Yu, Xiao Ming Desino, Kelly E. Bean, Jennifer Neckers, Len Audus, Ken L. Michaelis, Mary L. Blagg, Brian S. J. TI A non-toxic Hsp90 inhibitor protects neurons from A beta-induced toxicity SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Hsp90; Alzheimer's disease; neuroprotection; inhibitors ID BLOOD-BRAIN-BARRIER; PLASMA-MEMBRANE CA2+-ATPASE; HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONES; NOVOBIOCIN ANALOGS; P-GLYCOPROTEIN; NEURODEGENERATION; EXPRESSION; INTERACTS; STRESS AB The molecular chaperones have been implicated in numerous neurodegenerative disorders in which the defining pathology is misfolded proteins and the accumulation of protein aggregates. In Alzheimer's disease, hyperphosphorylation of tau protein results in its dissociation from microtubules and the formation of pathogenic aggregates. An inverse relationship was demonstrated between Hsp90/Hsp70 levels and aggregated tau, suggesting that Hsp90 inhibitors that upregulate these chaperones could provide neuroprotection. We recently identified a small molecule novobiocin analogue, A4 that induces Hsp90 overexpression at low nanomolar concentrations and sought to test its neuroprotective properties. A4 protected neurons against A beta-induced toxicity at low nanomolar concentrations that paralleled its ability to upregulate Hsp70 expression. A4 exhibited no cytotoxicity in neuronal cells at the highest concentration tested, 10 mu M, thus providing a large therapeutic window for neuro protection. In addition, A4 was transported across BMECs in vitro, suggesting the compound may permeate the blood-brain barrier in vivo. Taken together, these data establish A4, a C-terminal inhibitor of Hsp90, as a potent lead for the development of a novel class of compounds to treat Alzheimer's disease. (c) 2007 Published by Elsevier Ltd. C1 Univ Kansas, Dept Pharmacol & Toxicol, Lawrence, KS 66045 USA. Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. Univ Kansas, Dept Pharmaceut Chem, Lawrence, KS 66047 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Blagg, BSJ (reprint author), Univ Kansas, Dept Pharmacol & Toxicol, Malott 5064,1251 Wescoe Hall Dr, Lawrence, KS 66045 USA. EM bblagg@ku.edu FU NCI NIH HHS [R01CA120458, U01CA39610]; NIA NIH HHS [AG027419, AG12993] NR 39 TC 68 Z9 72 U1 1 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 1 PY 2007 VL 17 IS 7 BP 1984 EP 1990 DI 10.1016/j.bmcl.2007.01.017 PG 7 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 158XE UT WOS:000245827900031 PM 17276679 ER PT J AU Kulkarni, SS Newman, AH AF Kulkarni, Santosh S. Newman, Amy Hauck TI Design and synthesis of novel heterobiaryl amides as metabotropic glutamate receptor subtype 5 antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID MGLU5 RECEPTOR; NONCOMPETITIVE ANTAGONISTS; ALLOSTERIC MODULATORS; ANXIOLYTIC ACTIVITY; BINDING POCKETS; POTENT; MPEP; 2-METHYL-6-(PHENYLETHYNYL)PYRIDINE; DISCOVERY; CATALYSTS AB A series of heterobiaryl amides was designed and synthesized as novel mGluR5 antagonists. The synthesis using palladium catalyzed Suzuki-Miyaura cross-coupling reactions provided art array of compounds with a range of in vitro activities. In particular, compound 9e, 4( 3,5-difluorophenyl)-N-(6-methylpyridin-1-yl)picolinamide, exhibited nanomolar affinity at the mGluR5 and will serve as a template for future drug design. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIDA, Med Chem Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 28 TC 23 Z9 23 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD APR 1 PY 2007 VL 17 IS 7 BP 2074 EP 2079 DI 10.1016/j.bmcl.2006.12.083 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 158XE UT WOS:000245827900048 PM 17336520 ER PT J AU Braga, J McNally, JG Carmo-Fonseca, M AF Braga, Jose McNally, James G. Carmo-Fonseca, Maria TI A reaction-diffusion model to study RNA motion by quantitative fluorescence recovery after photobleaching SO BIOPHYSICAL JOURNAL LA English DT Article ID LIVING CELLS; SCANNING MICROPHOTOLYSIS; DYNAMIC INTERACTION; PROTEIN DYNAMICS; GENE-EXPRESSION; BINDING; MOBILITY; KINETICS; NUCLEUS; COMPLEXES AB Fluorescence recovery after photobleaching (FRAP) is a powerful technique to study molecular dynamics inside living cells. During the past years, several laboratories have used FRAP to image the motion of RNA-protein and other macromolecular complexes in the nucleus and cytoplasm. In the case of mRNAs, there is growing evidence indicating that these molecules assemble into large ribonucleoprotein complexes that diffuse throughout the nucleus by Brownian motion. However, estimates of the corresponding diffusion rate yielded values that differ by up to one order of magnitude. In vivo labeling of RNA relies on indirect tagging with a fluorescent probe, and here we show how the binding affinity of the probe to the target RNA influences the effective diffusion estimates of the resulting complex. We extend current reaction-diffusion models for FRAP by allowing for diffusion of the bound complex. This more general model can be used to fit any fluorescence recovery curve involving two interacting mobile species in the cell (a fluorescent probe and its target substrate). The results show that interpreting FRAP data in light of the new model reconciles the discrepant mRNA diffusion-rate values previously reported. C1 Univ Lisbon, Fac Med, Inst Mol Med, P-1649028 Lisbon, Portugal. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Braga, J (reprint author), Univ Lisbon, Fac Med, Inst Mol Med, Av Prof Egas Moniz, P-1649028 Lisbon, Portugal. EM josebraga@fm.ul.pt RI Braga, Jose/J-2886-2013; OI Braga, Jose/0000-0002-2255-6486; Carmo-Fonseca, Maria/0000-0002-3402-7143 NR 44 TC 40 Z9 41 U1 0 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2007 VL 92 IS 8 BP 2694 EP 2703 DI 10.1529/biophysj.106.096693 PG 10 WC Biophysics SC Biophysics GA 149RJ UT WOS:000245164000009 PM 17259280 ER PT J AU Davis, JS Epstein, ND AF Davis, Julien S. Epstein, Neal D. TI Mechanism of tension generation in muscle: An analysis of the forward and reverse rate constants SO BIOPHYSICAL JOURNAL LA English DT Article ID RABBIT PSOAS MUSCLE; FREE-ENERGY TRANSDUCTION; LASER TEMPERATURE-JUMP; HUXLEY-SIMMONS PHASE-2; 3-HELIX BUNDLE PROTEIN; RATE-LIMITING STEP; FORCE GENERATION; PHOSPHATE RELEASE; SKELETAL-MUSCLE; STRIATED-MUSCLE AB Tension generation in muscle occurs during the attached phase of the ATP-powered cyclic interaction of myosin heads with thin. laments. The transient nature of tension-generating intermediates and the complexity of the mechanochemical cross-bridge cycle have impeded a quantitative description of tension generation. Recent experiments performed under special conditions yielded a sigmoidal dependence of fiber tension on temperature - a unique case that simplifies the system to a two-state transition. We have applied this two-state analysis to kinetic data obtained from biexponential laser temperature-jump tension transients. Here we present the forward and reverse rate constants for de novo tension generation derived from analysis of the kinetics of the fast laser temperature-jump phase tau(2) (equivalent of the length-jump phase 2(slow)). The slow phase tau(3) is temperature-independent indicating coupling to rather than a direct role in, de novo tension generation. Increasing temperature accelerates the forward, and slows the reverse, rate constant for the creation of the tension-generating state. Arrhenius behavior of the forward and anti-Arrhenius behavior of the reverse rate constant is a kinetic signature of multistate multipathway protein-folding reactions. We conclude that locally unfolded tertiary and/or secondary structure of the actomyosin cross-bridge mediates the power stroke. C1 NHLBI, Mol Physiol Sect, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Davis, JS (reprint author), NHLBI, Mol Physiol Sect, Mol Cardiol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM davisjs@nhlbi.nih.gov NR 53 TC 10 Z9 10 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2007 VL 92 IS 8 BP 2865 EP 2874 DI 10.1529/biophysj.106.101477 PG 10 WC Biophysics SC Biophysics GA 149RJ UT WOS:000245164000024 PM 17259275 ER PT J AU Efrat, A Chernomordik, LV Kozlov, MM AF Efrat, Avishay Chernomordik, Leonid V. Kozlov, Michael M. TI Point-like protrusion as a prestalk intermediate in membrane fusion pathway SO BIOPHYSICAL JOURNAL LA English DT Article ID MODEL; BILAYERS AB The widely accepted pathway of membrane fusion begins with the fusion stalk representing the initial intermediate of hemifusion. The lipid structures preceding hemifusion and their possible influence on fusion kinetics were not addressed. Here, we suggest the point-like protrusion as a prestalk fusion intermediate, which has energy lower than that of stalk and, therefore, does not limit the fusion rate. We demonstrate that by calculating the energy of the point-like protrusion, which depends on the lipid monolayer elastic parameters and the strength of the intermembrane hydration repulsion. The point-like protrusion completes the fusion-through-hemifusion model of membrane merger. C1 Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. Holon Inst Technol, Fac Sci, Holon, Israel. NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Kozlov, MM (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. EM michk@post.tau.ac.il NR 9 TC 40 Z9 41 U1 2 U2 14 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD APR PY 2007 VL 92 IS 8 BP L61 EP L63 DI 10.1529/biophysj.106.103341 PG 3 WC Biophysics SC Biophysics GA 149RJ UT WOS:000245164000001 PM 17277178 ER PT J AU Jeffries, NO AF Jeffries, Neal O. TI Multiple comparisons distortions of parameter estimates SO BIOSTATISTICS LA English DT Article DE bootstrap; effect size; multiple comparisons ID BIAS AB In experiments involving many variables, investigators typically use multiple comparisons procedures to determine differences that are unlikely to be the result of chance. However, investigators rarely consider how the magnitude of the greatest observed effect sizes may have been subject to bias resulting from multiple testing. These questions of bias become important to the extent investigators focus on the magnitude of the observed effects. As an example, such bias can lead to problems in attempting to validate results, if a biased effect size is used to power a follow-up study. An associated important consequence is that confidence intervals constructed using standard distributions may be badly biased. A bootstrap approach is used to estimate and adjust for the bias in the effect sizes of those variables showing strongest differences. This bias is not always present; some principles showing what factors may lead to greater bias are given and a proof of the convergence of the bootstrap distribution is provided. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Jeffries, NO (reprint author), NINDS, NIH, MSC 1430,10 Ctr Dr, Bethesda, MD 20892 USA. EM neal.jeffries@nih.gov NR 3 TC 6 Z9 6 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD APR PY 2007 VL 8 IS 2 BP 500 EP 504 DI 10.1093/biostatistics/kxl025 PG 5 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 154MP UT WOS:000245512000026 PM 16971376 ER PT J AU Hummon, AB Lim, SR Difilippantonio, MJ Ried, T AF Hummon, Amanda B. Lim, Sharlene R. Difilippantonio, Michael J. Ried, Thomas TI Isolation and solubilization of proteins after TRIzol((R)) extraction of RNA and DNA from patient material following prolonged storage SO BIOTECHNIQUES LA English DT Article ID SAMPLES AB A systems approach is being applied in many areas of the biological sciences, particularly in cancer research. The coordinated, simultaneous extraction of DNA, RNA, and proteins from a single sample is crucial for accurate correlations between genomic aberrations and their consequences on the transcriptome and proteome. We present an approach to extract and completely solubilize tip to 98% of the total protein recovered from archived samples following TRIZOL (R) isolation of RNA and DNA. We also demonstrate using polyacrylamide gel electrophoresis (PAGE) and Western blot analysis that the proteins, representing both a wide molecular weight range and some posttranslational modifications, such as protein phosphorylation, remain stable in phenol-ethanol for tip to 3 years at -20 degrees C. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Berkeley, CA USA. RP Hummon, AB (reprint author), NCI, Canc Res Ctr, NIH, 50 South Dr,Room 1408, Bethesda, MD 20892 USA. EM hummona@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 10 TC 83 Z9 87 U1 2 U2 20 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 2007 VL 42 IS 4 BP 467 EP + DI 10.2144/000112401 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 203BD UT WOS:000248949200024 PM 17489233 ER PT J AU Salafia, CM Zhang, J Miller, RK Charles, AK Shrout, P Sun, WY AF Salafia, Carolyn M. Zhang, Jun Miller, Richard K. Charles, Adrian K. Shrout, Patrick Sun, Wenyu TI Placental growth patterns affect birth weight for given placental weight SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the Teratology-Society CY JUN 25-30, 2005 CL St Pete Beach, FL SP Teratol Soc DE placenta; birth weight; feto-placental weight ratio; chorionic plate; National Collaborative Perinatal Project ID GESTATIONAL-AGE INFANTS; FETAL WEIGHT; RATIO; RESTRICTION; PREGNANCY; FLOW AB BACKGROUND: An important contributor to fetal growth is growth of the placenta, the fetus' sole source of nutrients and oxygen. Here we use placental growth measures (larger and smaller disk diameters, reflecting the laterally expanding chorionic plate, and disk thickness) to test the hypothesis that placental growth patterns, while associated with placental weight and birth weight, measure placental functional efficiency, and will have independent effects on the feto-placental weight ratio (FPR). METHODS: Placental measures were available from 23,313 participants in the Collaborative Perinatal Project delivered between 34 and 43 completed weeks. Continuous variables were analyzed by regression for associations with placental weight, birth weight, and FPR, to further explore effects of placental growth patterns on the FPR (lateral chorionic plate growth and chorionic disk thickness were grouped as low, normal, and high values). The relationships of the nine resultant combinations of placental growth categories to the FPR using birth weight adjusted for gestational age, infant gender, parity, and African American race were analyzed (ANCIVA). RESULTS: As chorionic disk area and thickness increased, birth weight and placental weight increased, and the FPR decreased (each p < .0001) after adjustment for gestational age, parity, race, and infant gender. Small, thin placental disks had an adjusted FPR of 8.46; the largest, thickest placentas had an adjusted FPR of 6.33. The nine categories of FPRs were significantly different, consistent with chorionic plate area and disk thickness combining to determine the FPR. CONCLUSIONS: Patterns of placental growth, relating to different functional dimensions of the placenta, deliver a different birth weight for a given placental weight. C1 Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, Coll Phys & Surg, New York, NY 10032 USA. NYU, Dept Psychol, New York, NY 10003 USA. NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med, Dept Obstet & Gynecol, Rochester, NY USA. Princess Margaret Mem Hosp, Dept Pathol, Perth, WA, Australia. RP Salafia, CM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, Coll Phys & Surg, 722 W 168th St, New York, NY 10032 USA. EM cs536@columbia.edu OI Charles, Adrian/0000-0002-3193-1065 FU NIMH NIH HHS [1 K23 MH067857-01] NR 29 TC 34 Z9 36 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD APR PY 2007 VL 79 IS 4 BP 281 EP 288 DI 10.1002/bdra.20345 PG 8 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 156AZ UT WOS:000245621600005 PM 17286292 ER PT J AU Pinsky, PF Crawford, ED Kramer, BS Andriole, GL Gelmann, EP Grubb, R Greenlee, R Gohagan, JK AF Pinsky, Paul F. Crawford, E. David Kramer, Barnett S. Andriole, Gerald L. Gelmann, Edward P. Grubb, Robert Greenlee, Robert Gohagan, John K. TI Repeat prostate biopsy in the Prostate, Lung, Colorectal and Ovarian cancer screening trial SO BJU INTERNATIONAL LA English DT Article DE digital rectal examination; prostate cancer; prostate-specific antigen; repeat prostate biopsy; screening ID INTRAEPITHELIAL NEOPLASIA; NEGATIVE BIOPSY; MEN AB OBJECTIVE To determine patterns of repeat prostate biopsy in a cohort of men undergoing prostate cancer screening who have a negative initial biopsy. SUBJECTS AND METHODS The Prostate, Colorectal, Lung, and Ovarian (PLCO) cancer screening trial is an ongoing study the prostate component of which consists of six annual screens with measurements of prostate-specific antigen (PSA) level and a digital rectal examination (DRE). The diagnostic follow-up of positive screening results is done by the subject's healthcare provider outside the purview of the PLCO. We analysed the experience of repeat biopsy in men in the PLCO with an initial negative biopsy. Men were divided by indication for initial biopsy into those with suspicious PSA levels and those with suspicious DRE findings. RESULTS The probability of having a repeat biopsy within 3 years of initial biopsy was 43% for 1736 men with suspicious PSA levels and 13% for 1025 men with suspicious DRE findings. Rates of third and fourth biopsy after a previous negative biopsy were similar to the initial repeat biopsy rate in PSA-positive men. Most men had a repeat biopsy only after having an additional round of screening. The PSA level and PSA velocity determined after initial biopsy were independent risk factors for a repeat biopsy, both in PSA-positive and DRE-positive men. High-grade prostatic intraepithelial neoplasia was a risk factor for repeat biopsy before any repeat PSA or DRE testing. CONCLUSION The experience of this cohort should be generally representative of patterns of care for repeat biopsy in men undergoing periodic screening. These data can provide context to the debate over optimum practices for repeat biopsy. C1 NCI, Div Canc Prevent, NIH, DHHS, Bethesda, MD USA. NCI, Off Dis Prevent, NIH, DHHS, Bethesda, MD USA. Univ Colorado, Hlth Sci Ctr, Dept Urol Oncol, Denver, CO 80202 USA. Washington Univ, Div Urol Surg, St Louis, MO 63130 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. RP Pinsky, PF (reprint author), 6130 Execut Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pp4f@nih.gov NR 13 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD APR PY 2007 VL 99 IS 4 BP 775 EP 779 DI 10.1111/j.1464-410X.2006.06708.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 147BD UT WOS:000244977500016 PM 17223921 ER PT J AU Gojo, I Jiemjit, A Trepel, JB Sparreboom, A Figg, WD Rollins, S Tidwell, ML Greer, J Chung, EJ Lee, MJ Gore, SD Sausville, EA Zwiebel, J Karp, JE AF Gojo, Ivana Jiemjit, Anchalee Trepel, Jane B. Sparreboom, Alex Figg, William D. Rollins, Sandra Tidwell, Michael L. Greer, Jacqueline Chung, Eun Joo Lee, Min-Jung Gore, Steven D. Sausville, Edward A. Zwiebel, James Karp, Judith E. TI Phase 1 and pharmacologic study of MS-275, a histone deacetylase inhibitor, in adults with refractory and relapsed acute leukemias SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; SUBEROYLANILIDE HYDROXAMIC ACID; TRANS-RETINOIC ACID; SYNERGISTICALLY INDUCES APOPTOSIS; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; AGENT SODIUM PHENYLBUTYRATE; BONE-MARROW-TRANSPLANTATION; VIVO ANTITUMOR-ACTIVITY; MYELODYSPLASTIC SYNDROMES AB MS-275 is a benzamide derivative with potent histone deacetylase (HDAC) inhibitory and antitumor activity in preclinical models. We conducted a phase 1 trial of orally administered MS-275 in 38 adults with advanced acute leukemias. Cohorts of patients were treated with MS-275 initially once weekly x 2, repeated every 4 weeks from 4 to 8 mg/m(2), and after 13 patients were treated, once weekly x 4, repeated every 6 weeks from 8 to 10 mg/m(2). The maximum-tolerated dose was 8 mg/m(2) weekly for 4 weeks every 6 weeks. Dose-limiting toxicities (DLTs) included infections and neurologic toxicity manifesting as unsteady gait and somnolence. Other frequent non-DLTs were fatigue, anorexia, nausea, vomiting, hypoalbuminemia, and hypocalcemia. Treatment with MS-275 induced increase in protein and histone H3/H4 acetylation, p21 expression, and caspase-3 activation in bone marrow mononuclear cells. No responses by classical criteria were seen. Our results show that MS-275 effectively inhibits HDAC in vivo in patients with advanced myeloid leukemias and should be further tested, preferably in patients with less-advanced disease. C1 Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. NCI, Bethesda, MD 20892 USA. RP Gojo, I (reprint author), Univ Maryland, Marlene & Stewart Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM igojo@umm.edu RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 FU NCI NIH HHS [U01 CA070095, U01 CA69854, U01 CA70095] NR 68 TC 179 Z9 190 U1 1 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 APR 1 PY 2007 VL 109 IS 7 BP 2781 EP 2790 DI 10.1182/blood-2006-05-021873 PG 10 WC Hematology SC Hematology GA 156HP UT WOS:000245639000026 PM 17179232 ER PT J AU Oh, K Shen, T Le Gros, G Min, B AF Oh, Keunhee Shen, Tao Le Gros, Graham Min, Booki TI Induction of Th2 type immunity in a mouse system reveals a novel immunoregulatory role of basophils SO BLOOD LA English DT Article ID HUMAN IGE SYNTHESIS; MAST-CELLS; T-CELLS; PARASITE ANTIGEN; B-CELLS; IL-4; RELEASE; DIFFERENTIATION; INTERLEUKIN-4; INFLAMMATION AB While production of cytokines such as IL-12 by activated dendritic cells supports development of Th1 type immunity, a source of early IL-4 that is responsible for Th2 immunity is not well understood. We now show that coculture of basophils could promote a robust Th2 differentiation upon stimulation of naive CD4 T cells primarily via IL-4. Th2 promotion by basophils was also observed even when naive CD4 T cells were stimulated in a Th1-promoting condition or when fully differentiated Th1 phenotype effector CD4 T cells were restimulated. IL-4-deficient basophils failed to induce Th2 differentiation but suppressed Th1 differentiation. It was subsequently revealed that the IL-4-deficient basophils must engage cell-to-cell contact to exert the inhibitory effect on Th1 differentiation. Stimulation of naive CD4 T cells within an in vivo environment of increased basophil generation supported development of Th2 type immunity. Taken together, our results suggest that basophils may provide an important link for the development of Th2 immunity. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, Cleveland, OH 44195 USA. Med Res Inst, Wellington, New Zealand. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Min, B (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Immunol, 9500 Euclid Ave,NB 30, Cleveland, OH 44195 USA. EM minb@ccf.org RI Le Gros, Graham/C-6725-2011 NR 24 TC 79 Z9 83 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 APR 1 PY 2007 VL 109 IS 7 BP 2921 EP 2927 DI 10.1182/blood-2006-07-037739 PG 7 WC Hematology SC Hematology GA 156HP UT WOS:000245639000044 PM 17132717 ER PT J AU Kraft, ARM Krux, F Schimmer, S Ohlen, C Greenberg, PD Dittmer, U AF Kraft, Anke R. M. Krux, Frank Schimmer, Simone Ohlen, Claes Greenberg, Philip D. Dittmer, Ulf TI CpG oligodeoxynucleotides allow for effective adoptive T-cell therapy in chronic retroviral infection SO BLOOD LA English DT Article ID DENDRITIC CELLS; RESPONSES; IMMUNOTHERAPY; RECEPTOR; MICE; DEFICIENCY; EXPANSION; ANTIGEN; VIRUS; DNA AB Adoptive T-cell therapy in cancer or chronic viral infections is often impeded by the development of functional impairment of the transferred cells. To overcome this therapeutic limitation we combined adoptive transfer of naive, virus-specific CD8(+) T cells with immunostimulative CpG oligodeoxynucleotides (ODNs) in mice chronically infected with the Friend retrovirus. The CpG-ODN co-injection prevented the T cells from developing functional defects in IFN gamma and granzyme production and degranulation of cytotoxic molecules. Thus, the transferred T cells were able to reduce chronic viral loads when combined with CpG-ODNs. This strategy provides a new approach for developing successful adoptive T-cell therapy against chronic infections. C1 Univ Duisburg Essen, Inst Virol, Essen, Germany. NCI, SAIC, Frederick, MD 21701 USA. Univ Washington, Dept Med & Immunol, Seattle, WA 98195 USA. RP Dittmer, U (reprint author), Univ Duisburg Essen, Inst Virol, Essen, Germany. EM ulf.dittmer@uni-due.de NR 24 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2007 VL 109 IS 7 BP 2982 EP 2984 DI 10.1182/blood-2006-06-022178 PG 3 WC Hematology SC Hematology GA 156HP UT WOS:000245639000052 PM 17148590 ER PT J AU Lim, U Wang, SS Hartge, P Cozen, W Kelemen, LE Chanock, S Davis, S Blair, A Schenk, M Rothman, N Lan, Q AF Lim, Unhee Wang, Sophia S. Hartge, Patricia Cozen, Wendy Kelemen, Linda E. Chanock, Stephen Davis, Scott Blair, Aaron Schenk, Maryjean Rothman, Nathaniel Lan, Qing TI Gene-nutrient interactions among determinants of folate and one-carbon metabolism on the risk of non-Hodgkin lymphoma: NCI-SEER Case-Control Study SO BLOOD LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE GENE; CYTOPLASMIC SERINE HYDROXYMETHYLTRANSFERASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; MTHFR POLYMORPHISMS; COLORECTAL-CANCER; THYMIDYLATE SYNTHASE; MALIGNANT-LYMPHOMA; ALTERS SUSCEPTIBILITY; ESCHERICHIA-COLI; MULTIPLE-MYELOMA AB We previously reported a lower risk of non-Hodgkin lymphoma (NHL) associated with high consumption of vitamin B6 and methionine, dietary determinants of one-carbon metabolism. Evidence has linked genetic variants involved in one-carbon metabolism to NHL. We investigated 30 polymorphisms in 18 genes for their main effect on NHL among 1141 incident cases and 949 population-based controls and examined gene-nutrient interactions in a subgroup of 386 cases and 319 controls who provided detailed food-frequency information. Odds ratios (ORs) and 95% confidence intervals (Cis) were adjusted for age, sex, and race. We observed a decreased risk of NHL overall with BHMT Ex8+453A>T and increased risk with CBS Ex13+41C>T, FPGS Ex15-263T>C, and SHMT1 Ex12+138C>T and Ex12+236C>T. Furthermore, significant gene-nutrient interactions limited the protective association comparing high versus low vitamin B6 to FPGS Ex15-263T>C CC (OR=0.22; 95% Cl = 0.10-0.52), MTHFS IVS2-1411T>G TT/TG (OR = 0.54; 95% Cl = 0.36-0.81), and MTR Ex26-20A>G AA (OR = 0.55; 95% Cl = 0.35-0.86) genotypes, and the protective association of methionine to FTHFD Ex10-40G>T GG (OR = 0.63; 95% Cl = 0.44-0.91), MTHFR Ex8-62A> C CC (OR = 0.13; 95% Cl = 0.04-0.39), and MTRR Ex5+136T>CTT (OR = 0.67; 95%Cl = 0.47-0.97) genotypes. Warranting replication, our finding of gene-nutrient interactions in one-carbon metabolism supports their etiologic involvement in lymphomagenesis. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. NCI, Core Genotyping Facil, Ctr Adv Technol,Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH,DHHS, Rockville, MD 20852 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Wayne State Univ, Dept Family Med, Detroit, MI 48202 USA. Karmanos Canc Inst, Detroit, MI USA. RP Lim, U (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execeut Blvd,EPS 320, Rockville, MD 20852 USA. EM limu@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01 PC065064, N01 PC067008, N01 PC067009, N01 PC067010] NR 65 TC 57 Z9 62 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 APR 1 PY 2007 VL 109 IS 7 BP 3050 EP 3059 DI 10.1182/blood-2006-07-034330 PG 10 WC Hematology SC Hematology GA 156HP UT WOS:000245639000061 PM 17119116 ER PT J AU Hsu, LL Champion, HC Campbell-Lee, SA Bivalacqua, TJ Manci, EA Diwan, BA Schimel, DM Cochard, AE Wang, XD Schechter, AN Noguchi, CT Gladwin, MT AF Hsu, Lewis L. Champion, Hunter C. Campbell-Lee, Sally A. Bivalacqua, Trinity J. Manci, Elizabeth A. Diwan, Bhalchandra. A. Schimel, Daniel M. Cochard, Audrey E. Wang, Xunde Schechter, Alan N. Noguchi, Constance T. Gladwin, Mark T. TI Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability SO BLOOD LA English DT Article ID TRANSGENIC-KNOCKOUT MICE; IN-VIVO MEASUREMENT; SYNTHASE ACTIVITY; BETA-THALASSEMIA; OXYHEMOGLOBIN DESATURATION; CATHETERIZATION TECHNIQUE; THERAPEUTIC IMPLICATIONS; ENDOTHELIAL DYSFUNCTION; ARTERIAL-HYPERTENSION; FLOW ABNORMALITIES AB Pulmonary hypertension is a highly prevalent complication of sickle cell disease and is a strong risk factor for early mortality. However, the pathophysiologic mechanisms leading to pulmonary vasculopathy remain unclear. Transgenic mice provide opportunities for mechanistic studies of vascular pathophysiology in an animal model. By microcardiac catheterization, all mice expressing exclusively human sickle hemoglobin had pulmonary hypertension, profound pulmonary and systemic endothelial dysfunction, and vascular instability characterized by diminished responses to authentic nitric oxide (NO), NO donors, and endothelium-dependent vasodilators and enhanced responses to vasoconstrictors. However, endothelium-independent vasodilation in sickle mice was normal. Mechanisms of vasculopathy in sickle mice involve global dysregulation of the NO axis: impaired constitutive nitric oxide synthase activity (NOS) with loss of endothelial NOS (eNOS) dimerization, increased NO scavenging by plasma hemoglobin and superoxide, increased arginase activity, and depleted intravascular nitrite reserves. Light microscopy and computed tomography revealed no plexogenic arterial remodeling or thrombi/emboli. Transplanting sickle marrow into wild-type mice conferred the same phenotype, and similar pathobiology was observed in a nonsickle mouse model of acute alloimmune hemolysis. Although the time course is shorter than typical pulmonary hypertension in human sickle cell disease, these results demonstrate that hemolytic anemia is sufficient to produce endothelial dysfunction and global dysregulation of NO. C1 Drexel Univ, Coll Med, St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Philadelphia, PA 19134 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Illinois, Dept Pathol, Chicago, IL 60680 USA. Univ S Alabama, Sickle Cell Pathol Unit, Mobile, AL 36688 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21701 USA. NINDS, Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Hsu, LL (reprint author), Drexel Univ, Coll Med, St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Erie Ave Front St, Philadelphia, PA 19134 USA. EM lhsu@mail.nih.gov RI Hsu, Lewis/A-3360-2008; OI Schechter, Alan N/0000-0002-5235-9408 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 88 TC 134 Z9 136 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 2007 VL 109 IS 7 BP 3088 EP 3098 DI 10.1182/blood-2006-08-039438 PG 11 WC Hematology SC Hematology GA 156HP UT WOS:000245639000067 PM 17158223 ER PT J AU Wadhwa, S Bi, YM Ortiz, AT Embree, MC Kilts, T Iozzo, R Opperman, LA Young, MF AF Wadhwa, Sunil Bi, Yanming Ortiz, Ana T. Embree, Mildred C. Kilts, Tina Iozzo, Renato Opperman, Lynne A. Young, Marian F. TI Impaired posterior frontal sutural fusion in the biglycan/decorin double deficient mice SO BONE LA English DT Article DE small proteoglycans; biglycan; decorin; cranial suture; mouse ID LEUCINE-RICH PROTEOGLYCANS; OSTEOBLAST DIFFERENTIATION; EXTRACELLULAR-MATRIX; TARGETED DISRUPTION; DECORIN; EXPRESSION; GROWTH; BONE; DLX5; TISSUES AB Biglycan (Bgn) and decorin (Den) are highly expressed in numerous tissues in the craniofacial complex. However, their expression and function in the cranial sutures are unknown. In order to study this, we first examined the expression of biglycan and decorin in the posterior frontal suture (PFS), which predictably fuses between 21 and 45 days post-natal and in the non-fusing sagittal (S) suture from wild-type (Wt) mice. Our data showed that Bgn and Den were expressed in both cranial sutures. We then characterized the cranial suture phenotype in Bgn deficient, Den deficient, Bgn/Dcn double deficient, and Wt mice. At embryonic day 18.5, alizarin red/alcian blue staining showed that the Bgn/Dcn double deficient mice had hypomineralization of the frontal and parietal craniofacial bones. Histological analysis of adult mice (45-60 days post-natal) showed that the Bgn or Dcn deficient mice had no cranial suture abnormalities and immunohistochemistry staining showed increased production of Den in the PFS from Bgn deficient mice. To test possible compensation of Den in the Bgn deficient sutures, we examined the Bgn/Dcn double deficient mice and found that they had impaired fusion of the PFS. Semi-quantitative RT-PCR analysis of RNA from 35 day-old mice revealed increased expression of Bmp-4 and Dlx-5 in the PFS compared to their non-fusing S suture in Wt tissues and decreased expression of Dlx-5 in both PF and S sutures in the Bgn/Dcn double deficient mice compared to the Wt mice. Failure of PFS fusion and hypomineralization of the calvaria in the Bgn/Dcn double deficient mice demonstrates that these extracellular matrix proteoglycans could have a role in controlling the formation and growth of the cranial vault. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Connecticut, Ctr Hlth, Sch Dent Med, Div Orthodont,Dept Craniofacial Sci, Farmington, CT 06030 USA. NIDCR, Mol Biol Bones & Teeth Sect, Craniofacial & Skeletal Dis Branch, DHHS,NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Anat & Cell Biol, Philadelphia, PA 19107 USA. Texas A&M Univ Syst, Hlth Sci Ctr, Ctr Craniofacial Res & Diag, Baylor Coll Dent, Dallas, TX 75246 USA. RP Wadhwa, S (reprint author), Univ Connecticut, Ctr Hlth, Sch Dent Med, Div Orthodont,Dept Craniofacial Sci, Farmington, CT 06030 USA. EM Wadhwa@uchc.edu OI Opperman, Lynne/0000-0002-6200-7799; Iozzo, Renato/0000-0002-5908-5112 FU Intramural NIH HHS; NIDCR NIH HHS [K22 DE017193] NR 36 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2007 VL 40 IS 4 BP 861 EP 866 DI 10.1016/j.bone.2006.11.003 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153GI UT WOS:000245419800008 PM 17188951 ER PT J AU Chesnick, IE Avallone, FA Leapman, RD Landis, WJ Eidelman, N Potter, K AF Chesnick, Ingrid E. Avallone, Francis A. Leapman, Richard D. Landis, William J. Eidelman, Naomi Potter, Kimberlee TI Evaluation of bioreactor-cultivated bone by magnetic resonance microscopy and FTIR micro spectroscopy SO BONE LA English DT Article DE bone; bioreactor; collagen; mineral; magnetic resonance microscopy; FTIR microspectroscopy ID MICROSPECTROSCOPIC ANALYSIS; ARTICULAR-CARTILAGE; CELL-CULTURES; IR MICROSCOPY; TISSUE; MINERALIZATION; CALCIFICATION; CALCIUM; WATER; FLOW AB We present a three-dimensional mineralizing model based on a hollow fiber bioreactor (HFBR) inoculated with primary osteoblasts isolated from embryonic chick calvaria. Using non-invasive magnetic resonance microscopy (MRM), the growth and development of the mineralized tissue around the individual fibers were monitored over a period of 9 weeks. Spatial maps of the water proton MRM properties of the intact tissue, with 78 mu m resolution, were used to determine changes in tissue composition with development. Unique changes in the mineral and collagen content of the tissue were detected with high specificity by proton density (PD) and magnetization transfer ratio (MTR) maps, respectively. At the end of the growth period, the presence of a bone-like tissue was verified by histology and the formation of poorly crystalline apatite was verified by selected area electron diffraction and electron probe X-ray microanalysis. FTIR microspectroscopy confirmed the heterogeneous nature of the bone-like tissue formed. FTIR-derived phosphate maps confirmed that those locations with the lowest PD values contained the most mineral, and FTIR-derived collagen maps confirmed that bright pixels on NITR maps corresponded to regions of high collagen content. In conclusion, the spatial mapping of tissue constituents by FTIR micro spectroscopy corroborated the findings of non-invasive MRM measurements and supported the role of MRM in monitoring the bone formation process in vitro. (c) 2006 Elsevier Inc. All rights reserved. C1 Armed Forces Inst Pathol, Magnet Resonance Microscopy Facil, Dept Biophys, Rockville, MD 20850 USA. Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20306 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. Northeastern Ohio Univ Coll Med & Pharm, Dept Microbiol Immunol & Biochem, Rootstown, OH 44272 USA. Natl Inst Stand & Technol, Paffenbarger Res Ctr, Amer Dent Assoc Hlth Fdn, Gaithersburg, MD 20899 USA. RP Potter, K (reprint author), Armed Forces Inst Pathol, Magnet Resonance Microscopy Facil, Dept Biophys, 1413 Res Blvd, Rockville, MD 20850 USA. EM potterk@afip.osd.mil FU Intramural NIH HHS; NIAMS NIH HHS [R01 AR051446-02, R01 AR041452, R01 AR041452-09, AR51446, R01 AR051446, AR41452]; NIH HHS [Z01 OD010327-08] NR 57 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2007 VL 40 IS 4 BP 904 EP 912 DI 10.1016/j.bone.2006.10.020 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153GI UT WOS:000245419800013 PM 17174620 ER PT J AU Wallace, JM Rajachar, RM Allen, MR Bloomfield, SA Robey, PG Young, MF Kohn, DH AF Wallace, Joseph M. Rajachar, Rupak M. Allen, Matthew R. Bloomfield, Susan A. Robey, Pamela G. Young, Marian F. Kohn, David H. TI Exercise-induced changes in the cortical bone of growing mice are bone- and gender-specific SO BONE LA English DT Article DE mechanical properties; pQCT; matrix changes; tibia; femur ID COMPUTED-TOMOGRAPHY PQCT; BIGLYCAN-DEFICIENT MICE; MECHANICAL-PROPERTIES; STRESS-FRACTURES; IN-VIVO; CLIMBING EXERCISE; MOUSE SKELETON; C57BL/6J MICE; FEMORAL BONE; RISK-FACTORS AB Fracture risk and mechanical competence of bone are functions of bone mass and tissue quality, which in turn are dependent on the bone's mechanical environment. Male mice have a greater response to non-weight-bearing exercise than females, resulting in larger, stronger bones compared with control animals. The aim of this study was to test the hypothesis that short-term weight-bearing running during growth (21 days starting at 8 weeks of age; 30 min/day; 12 m/min; 5 degrees incline-, 7 days/week) would similarly have a greater impact on cross-sectional geometry and mechanical competence in the femora and tibiae of male mice versus females. Based on the orientation of the legs during running and the proximity of the tibia to the point of impact, this response was hypothesized to be greatest in the tibia. Exercise-related changes relative to controls were assayed by four-point bending tests, while volumetric bone mineral density and cross-sectional geometry were also assessed. The response to running was bone- and gender-specific, with male tibiae demonstrating the greatest effects. In male tibiae, periosteal perimeter, endocortical perimeter, cortical area, medial-lateral width and bending moment of inertia increased versus control mice suggesting that while growth is occurring in these mice between 8 and I I weeks of age, exercise accelerated this growth resulting in a greater increase in bone tissue over the 3 weeks of the study. Exercise increased tissue-level strain-to-failure and structural post-yield deformation in the male tibiae, but these post-yield benefits came at the expense of decreased yield deformation, structural and tissue-level yield strength and tissue-level ultimate strength. These results suggest that exercise superimposed upon growth accelerated growth-related increases in tibial cross-sectional dimensions. Exercise also influenced the quality of this forming bone, significantly impacting structural and tissue-level mechanical properties. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biol & Mat Sci, Ann Arbor, MI 48109 USA. Natl Inst Dent & Craniofacial Res, NIH, Craniofacial & Skeletal Dis Branch, Dept Hlth & Human Serv, Bethesda, MD USA. Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX 77834 USA. RP Kohn, DH (reprint author), Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA. EM jmwallac@umich.edu; rupakr@u.washington.edu; matallen@iupui.edu; sbloom@hlkn.tamu.edu; probey@dir.nidcr.nih.gov; myoung@dir.nidcr.nih.gov; dhkohn@umich.edu RI Wallace, Joseph/G-7906-2012; Robey, Pamela/H-1429-2011; Allen, Matthew/A-8799-2015 OI Robey, Pamela/0000-0002-5316-5576; Allen, Matthew/0000-0002-1174-9004 FU NIDCR NIH HHS [T32 DE007057, T32 DE007057-28, T32-DE07057]; NIDDK NIH HHS [R90 DK071506, R90 DK071506-03, R90-DK071506] NR 59 TC 71 Z9 74 U1 2 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD APR PY 2007 VL 40 IS 4 BP 1120 EP 1127 DI 10.1016/j.bone.2006.12.002 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 153GI UT WOS:000245419800039 PM 17240210 ER PT J AU Van Der Hilst, JCH Van Der Meer, JWM Drenth, JPH Simon, A AF Van Der Hilst, J. C. H. Van Der Meer, J. W. M. Drenth, J. P. H. Simon, A. TI AL amyloidosis enhances development of amyloid A amyloidosis SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Letter ID FIBRILS C1 Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, Nijmegen, Netherlands. Radboud Univ Nijmegen, Med Ctr, Dept Gastroenterol & Hepatol, Nijmegen, Netherlands. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Van Der Hilst, JCH (reprint author), Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, Geert Grooteplein 8,POB 9101, Nijmegen, Netherlands. EM j.vanderhilst@aig.umcn.nl RI Simon, Anna/D-3757-2009; Drenth, J.P.H./H-8025-2014; van der Meer, Jos/C-8521-2013 OI Simon, Anna/0000-0002-6141-7921; van der Meer, Jos/0000-0001-5120-3690 NR 10 TC 4 Z9 4 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0007-0963 EI 1365-2133 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD APR PY 2007 VL 156 IS 4 BP 748 EP 749 DI 10.1111/j.1365-2133.2006.07709.x PG 2 WC Dermatology SC Dermatology GA 148UC UT WOS:000245099400024 PM 17263824 ER PT J AU Hill, A Reid, SA Rother, RP Gladwin, MT Collinson, PO Gaze, DC Lowe, A Guthrie, A Sivananthan, MU Hillmen, P AF Hill, A. Reid, S. A. Rother, R. P. Gladwin, M. T. Collinson, P. O. Gaze, D. C. Lowe, A. Guthrie, A. Sivananthan, M. U. Hillmen, P. TI High definition contrast-enhanced MR imaging in paroxysmal nocturnal haemoglobinuria (PNH) suggests a high frequency of subclinical thrombosis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 47th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 30-MAY 02, 2007 CL Bournemouth, ENGLAND SP British Soc Haematol C1 Leeds Gen Infirm, Dept Haematol, Leeds, W Yorkshire, England. Univ Leeds, LIGHT, Leeds, W Yorkshire, England. NIH, Vasc Therapeut Sect, Bethesda, MD 20892 USA. St George Hosp, Dept Chem Pathol, London, England. Leeds Gen Infirm, Dept Radiol, Leeds, W Yorkshire, England. 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 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2007 VL 137 SU 1 MA 92 BP 30 EP 31 PG 2 WC Hematology SC Hematology GA 173WB UT WOS:000246902100091 ER PT J AU Hill, A Schubert, J Duhrsen, U Young, NS Elebute, M Szer, J Gianfaldoni, G Socie, G Hillmen, P Mojcik, CF Rother, RP Muus, P AF Hill, A. Schubert, J. Duhrsen, U. Young, N. S. Elebute, M. Szer, J. Gianfaldoni, G. Socie, G. Hillmen, P. Mojcik, C. F. Rother, R. P. Muus, P. TI TRIUMPH, a randomized placebo-controlled phase III trial, demonstrates that the terminal complement inhibitor eculizurnab improves anaemia in PNH SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 47th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 30-MAY 02, 2007 CL Bournemouth, ENGLAND SP British Soc Haematol C1 Leeds Teaching Hosp NHS Trust, Leeds, W Yorkshire, England. Univ Saarland, Sch Med, D-6650 Homburg, Germany. Univ Hosp, Essen, Germany. NHLBI, NIH, Bethesda, MD 20892 USA. St George Hosp, London, England. Royal Melbourne Hosp, Melbourne, Vic, Australia. Azienda Osped Univ Careggi, Florence, Italy. Hosp St Louis, INSERM, Paris, France. Alex Pharmaceut Inc, Cheshire, CT USA. Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands. RI Muus, P./L-4539-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2007 VL 137 SU 1 MA 101 BP 33 EP 34 PG 2 WC Hematology SC Hematology GA 173WB UT WOS:000246902100100 ER PT J AU Hillmen, P Hill, A Muus, P Duhrsen, U Risitano, AM Schubert, J Young, NS Schrezenmeier, H Szer, J Brodsky, RA Socie, G Rollins, SA Rother, RP Bell, L Luzzatto, L AF Hillmen, P. Hill, A. Muus, P. Duhrsen, U. Risitano, A. M. Schubert, J. Young, N. S. Schrezenmeier, H. Szer, J. Brodsky, R. A. Socie, G. Rollins, S. A. Rother, R. P. Bell, L. Luzzatto, L. TI The terminal complement inhibitor eculizumab reduces thrombosis in patients with paroxysmal nocturnal haemoglobinuria SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Meeting Abstract CT 47th Annual Scientific Meeting of the British-Society-for-Haematology CY APR 30-MAY 02, 2007 CL Bournemouth, ENGLAND SP British Soc Haematol C1 Leeds Teaching Hosp NHS Trust, Dept Haematol, Leeds, W Yorkshire, England. Radboud Univ Med Ctr, Nijmegen, Netherlands. Univ Hosp, Essen, Germany. Med Federico Univ 2, Naples, Italy. Univ Saarland, Sch Med, D-6650 Homburg, Germany. NHLBI, NIH, Bethesda, MD 20892 USA. Inst Klin Transfus & Immunogenet, Helmholtzstr, Germany. Royal Melbourne Hosp, Melbourne, Vic, Australia. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Hosp St Louis, INSERM, Paris, France. Alex Pahrmaceut Inc, Cheshire, CT USA. Ist Toscano Tumori, Florence, Italy. RI Muus, P./L-4539-2015 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 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2007 VL 137 SU 1 MA 102 BP 34 EP 34 PG 1 WC Hematology SC Hematology GA 173WB UT WOS:000246902100101 ER PT J AU Ng, D Toure, O Fontaine, L McMaster, ML Goldin, LR Caporaso, N Toro, JR AF Ng, David Toure, Ousmane Fontaine, Laura McMaster, Mary L. Goldin, Lynn R. Caporaso, Neil Toro, Jorge R. TI No association of ARLTS1 polymorphisms and risk for familial chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Letter DE familial chronic lymphocytic leukaemia; ARLTS1 mutation analysis C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Westat Res Inc, Rockville, MD USA. RP Ng, D (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. EM toroj@mail.nih.gov FU Intramural NIH HHS NR 6 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2007 VL 137 IS 2 BP 173 EP 175 DI 10.1111/j.1365-2141.2007.06544.x PG 4 WC Hematology SC Hematology GA 149NE UT WOS:000245152800014 PM 17391501 ER PT J AU Lacey, JV Leitzmann, MF Chang, SC Mouw, T Hollenbeck, AR Schatzkin, A Brinton, LA AF Lacey, James V., Jr. Leitzmann, Michael F. Chang, Shih-Chen Mouw, Traci Hollenbeck, Albert R. Schatzkin, Arthur Brinton, Louise A. TI Endometrial cancer and menopausal hormone therapy in the National Institutes of Health-AARP Diet and Health Study cohort SO CANCER LA English DT Article DE estrogen; progestin; endometrial carcinoma; uterine cancer; epidemiology ID ESTROGEN PLUS PROGESTIN; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; UNITED-STATES; RISK; TRIAL AB BACKGROUND. Menopausal hormone therapy formulations for women without hysterectomy have included estrogen plus progestin for years, but endometrial cancer risks associated with the use of sequential and continuous estrogen-plus-progestin regimens remain unclear. METHODS. The National Institutes of Health-AARP Diet and Health Study included 73,211 women who were ages 50 years to 71 years at baseline and who completed 2 questionnaires (1995-1996 and 1996-1997). Linkage to state cancer registries and mortality indices identified 433 incident endometrial cancers through 2000. Using proportional hazards regression, the authors estimated relative risks (RRs) and 95% confidence intervals (95% CIs) relative to never-use of hormone therapy. RESULTS. In 51,312 women who never used hormones or only used estrogen-plus-progestin regimens at doses consistent with current practice, neither sequential estrogen plus progestin (daily estrogen plus progestin for 10-14 days per cycle: RR, 0.74; 95% CI, 0.39-1.40) nor continuous estrogen plus progestin (daily estrogen plus progestin for >= 20 days per cycle: RR, 0.80; 95% CI, 0.55-1.15) had any statistically significant association with endometrial cancer. Long durations (>= 5 years) of sequential regimen use (RR, 0.79; 95% CI, 0.38-1.66) and of continuous regimen use (RR, 0.85; 95% CI, 0.53-1.36) were not associated with endometrial cancer. CONCLUSIONS. Confirmation that these estrogen-plus-progestin regimens neither increase nor decrease the risk of endometrial cancer could influence menopausal symptom management for women who are considering estrogen-plus-progestin therapy. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA. AARP, Washington, DC USA. RP Lacey, JV (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7234, Rockville, MD 20852 USA. EM jimlacey@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS NR 27 TC 22 Z9 22 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2007 VL 109 IS 7 BP 1303 EP 1311 DI 10.1002/cncr.22525 PG 9 WC Oncology SC Oncology GA 150PP UT WOS:000245229000011 PM 17315161 ER PT J AU Posadas, EM Liel, MS Kwitkowski, V Minasian, L Godwin, AK Hussain, MM Espina, V Wood, BJ Steinberg, SM Kohn, EC AF Posadas, Edwin M. Liel, Meghan S. Kwitkowski, Virginia Minasian, Lori Godwin, Andrew K. Hussain, Mahrukh M. Espina, Virginia Wood, Bradford J. Steinberg, Seth M. Kohn, Elise C. TI A phase II and pharmacodynamic study of gefitinib in patients with refractory or recurrent epithelial ovarian cancer SO CANCER LA English DT Article DE ovarian cancer; epidermal growth factor receptor; gefitinib; proteomics; protein array ID EPIDERMAL-GROWTH-FACTOR; RECEPTOR TYROSINE KINASE; CELL LUNG-CANCER; PROTEIN MICROARRAYS; IMMUNOHISTOCHEMICAL EXPRESSION; CLINICAL-TRIALS; EGF RECEPTOR; THERAPY; INHIBITOR; CARCINOMA AB BACKGROUND. The primary objective of this study was to evaluate the biochemical effects of gefitinib on its target signal-transduction pathways in patients with recurrent epithelial ovarian cancer (EOC). The secondary objectives included assessing clinical activity and toxicity and determining the association between biochemical and clinical outcomes. METHODS. Twenty-four heavily pretreated patients with EOC who had good end-organ function and performance status and who had measurable disease received gefitinib 500 mg daily. Prospectively planned core-needle tumor biopsies were obtained before treatment and after 4 weeks. Protein expression of total and phosphorylated (p) epidermal growth factor receptor (EGFR), protein kinase B (AKT), and extracellular regulated kinase (ERK) was quantified in microdissected tumor cells using tissue lysate array proteomics. RESULTS. All tumor samples had detectable levels of EGFR and p-EGFR. A decrease in the quantity of both EGFR and p-EGFR was observed with gefitinib therapy in > 50% of patients. This was not associated with clinical benefit, nor were responses observed. However, trends for increased gastrointestinal and skin toxicity were observed with greater phosphorylation or quantities of EGFR, ERK, and AKT in tumor samples (P <= .05). Gefitinib had limited clinical activity as monotherapy despite documented target inhibition. CONCLUSIONS. The results from this study demonstrated that gefitinib inhibited the phosphorylation of EGFR in EOC tumor cells, providing proof of target in a clinical setting. Combinatorial therapy with molecular therapeutics against complementary targets may prove successful. C1 NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Dept Med Oncol, Div Med Sci, Philadelphia, PA 19111 USA. NIH, Dept Diagnost Radiol, WG Magnuson Clin Ctr, Bethesda, MD USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,MSC1500, Bethesda, MD 20892 USA. EM ek1b@nih.gov OI Espina, Virginia/0000-0001-5080-5972 FU Intramural NIH HHS [Z01 SC009375-13]; NCI NIH HHS [P50 CA83638, P50 CA083638] NR 43 TC 77 Z9 81 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD APR 1 PY 2007 VL 109 IS 7 BP 1323 EP 1330 DI 10.1002/cncr.22545 PG 8 WC Oncology SC Oncology GA 150PP UT WOS:000245229000013 PM 17330838 ER PT J AU Posadas, EM Undevia, S Manchen, E Wade, JL Colevas, AD Karrison, T Vokes, EE Stadler, WM AF Posadas, Edwin M. Undevia, Samir Manchen, Elizabeth Wade, James L. Colevas, A. Dimitrios Karrison, Theodore Vokes, Everett E. Stadler, Walter M. TI A phase II study of ixabepilone (BMS-247550) in metastatic renal-cell carcinoma SO CANCER BIOLOGY & THERAPY LA English DT Article DE renal cell carcinoma; ixabepilone; chemo therapy; clinical trial; microtubule inhibitor ID EPOTHILONE-B-ANALOG; PROSTATE-CANCER; SOLID TUMORS; TRIAL; INHIBITOR; TAXANE AB Introduction: Ixabepilone (BMS-247550) is a semi-synthetic analog of epothilone B that has been characterized as a microtubule stabilizing agent with a mechanism of action distinct from taxanes. Suggestion of activity in renal cell carcinoma (RCC) has been seen in early clinical studies. Methods: Eligible patients had metastatic RCC as well as ECOG performance status 0-2 and normal organ function. Patients received ixabepilone at a dose of 40 mg/m(2) intravenously over three hours every 21 days. There was no restriction on RCC histology or prior treatment type, but prior treatment with tubule inhibitors was not allowed. The primary endpoint was RECIST defined response and radiographic evaluations were performed every three cycles. Toxicity evaluations utilized CTCAE v3.0 and were performed every cycle. Using a Simon two-stage optimal design with alpha = 0.1, beta = 0.1, a null hypothesized response rate of 0.05 and an alternative response rate of 0.2, an initial 12 patients were to be accrued with full accrual of 37 patients if at least one response were observed. Results: A median of five cycles were administered. No objective responses were observed in the first 12 evaluable patients, and six patients showed stable disease for more than 18 weeks on therapy. Median time to progression among those with objective progression was nine weeks. One patient experienced grade 4 anemia and lymphopenia. Grade 3 adverse events included lymphopenia, neutropenia, leukopenia, diarrhea, and infection. Common grade 2 toxicities included alopecia, fatigue and anemia. Conclusion: Ixabepilone administered at a dose of 40 mg/m(2) every 21 days should not be advanced for further study in metastatic RCC. Given previous results, however, other dosing schedules may be worthy of further investigation. C1 Univ Chicago, Med Sect Hematol Oncol, Chicago, IL 60637 USA. Univ Chicago Phase II Consortium, Chicago, IL USA. Natl Canc Inst, Canc Therapeut Evaluat Program, Bethesda, MD USA. RP Posadas, EM (reprint author), Univ Chicago, Med Sect Hematol Oncol, 5841 S Maryland Ave,MC 2115, Chicago, IL 60637 USA. EM eposadas@medicine.bsd.uchicago.edu NR 29 TC 18 Z9 19 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD APR PY 2007 VL 6 IS 4 BP 490 EP 493 PG 4 WC Oncology SC Oncology GA 191AR UT WOS:000248102700009 PM 17457044 ER PT J AU Pommier, Y AF Pommier, Yves TI Finding the interface - More than an image SO CANCER BIOLOGY & THERAPY LA English DT Biographical-Item C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Ctr Canc Res, NIH, Bldg 37,Rm 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD APR PY 2007 VL 6 IS 4 BP 620 EP 623 PG 4 WC Oncology SC Oncology GA 191AR UT WOS:000248102700027 PM 18027439 ER PT J AU Davis, SR Meltzer, PS AF Davis, Sean R. Meltzer, Paul S. TI Modeling synovial sarcoma: Timing is everything SO CANCER CELL LA English DT Editorial Material AB Synovial sarcoma is characterized by the presence of a fusion protein involving SYT and SSX2. In this issue of Cancer Cell, Haldar et al. have genetically engineered a mouse model of this disease. They show that expression of the SYT-SSX2 fusion gene yields a highly penetrant and representative model of human synovial sarcoma, but only if expression occurs in a particular biologic context. The mouse model will be a valuable resource for studying tumor biology but is also a striking example of how important understanding of normal tissue and developmental biology is to our understanding of cancer. C1 NCI, Ctr Canc Res, Genet Branch, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NCI, Ctr Canc Res, Genet Branch, 37 Convent Dr, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 NR 6 TC 11 Z9 11 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD APR PY 2007 VL 11 IS 4 BP 305 EP 307 DI 10.1016/j.ccr.2007.03.016 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 157PH UT WOS:000245732000002 PM 17418406 ER PT J AU Li, DH Day, RS Bondy, ML Sinha, R Nguyen, NT Evans, DB Abbruzzese, JL Hassan, MM AF Li, Donghui Day, Rena Sue Bondy, Melissa L. Sinha, Rashmi Nguyen, Nga T. Evans, Douglas B. Abbruzzese, James L. Hassan, Manal M. TI Dietary mutagen exposure and risk of pancreatic cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; HETEROCYCLIC AMINES; BREAST-CANCER; MEAT INTAKE; CARCINOGEN; COOKING; RATS; BENZO(A)PYRENE; ASSOCIATIONS; INDUCTION AB To investigate the association between dietary exposure to food mutagens and risk of pancreatic cancer, we conducted a hospital-based case-control study at the University of Texas M. D. Anderson Cancer Center during June 2002 to May 2006. A total of 626 cases and 530 noncancer controls were frequency matched for race, sex and age (+/- 5 years). Dietary exposure information was collected via personal interview using a meat preparation questionnaire. A significantly greater portion of the cases than controls showed a preference to well-done pork, bacon, grilled chicken, and pan-fried chicken, but not to hamburger and steak. Cases had a higher daily intake of food mutagens and mutagenicity activity (revertants per gram of daily meat intake) than controls did. The daily intakes of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (DiMeIQx) and benzo(a)pyrene (BaP), as well as the mutagenic activity, were significant predictors for pancreatic cancer (P= 0.008, 0.031, and 0.029, respectively) with adjustment of other confounders. A significant trend of elevated cancer risk with increasing DiMeIQx intake was observed in quintile analysis (P-trend = 0.024). A higher intake of dietary mutagens (those in the two top quintiles) was associated with a 2-fold increased risk of pancreatic cancer among those without a family history of cancer but not among those with a family history of cancer. A possible synergistic effect of dietary mutagen exposure and smoking was observed among individuals with the highest level of exposure (top 10%) to PhIP and BaP. P-interaction = 0.09 and 0.099, respectively. These data support the hypothesis that dietary mutagen exposure alone and in interaction with other factors contribute to the development of pancreatic cancer. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastroenterol Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Surg Oncol, Houston, TX 77030 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Li, DH (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gastroenterol Med Oncol, 1515 Holcombe Blvd,Unit 426, Houston, TX 77030 USA. EM dli@mdanderson.org RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [CA84581, CA98380, R01 CA098380, R03 CA084581]; NIEHS NIH HHS [ES07784, P30 ES007784] NR 48 TC 30 Z9 31 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2007 VL 16 IS 4 BP 655 EP 661 DI 10.1158/1055-9965.EPI-06-0993 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 157PN UT WOS:000245732600004 PM 17416754 ER PT J AU Gunter, MJ Hayes, RB Chatterjee, N Yeager, M Welch, R Schoen, RE Yakochi, L Schatzkin, A Peters, U AF Gunter, Marc J. Hayes, Richard B. Chatterjee, Nilanjan Yeager, Meredith Welch, Robert Schoen, Robert E. Yakochi, Lance Schatzkin, Arthur Peters, Ulrike TI Insulin resistance-related genes and advanced left-sided colorectal adenoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RECEPTOR SUBSTRATE-1 GENE; IGF-BINDING PROTEIN-3; GROWTH-FACTOR (IGF)-I; DIABETES-MELLITUS; CANCER RISK; C-PEPTIDE; FACTOR-I; HAPLOTYPE; WOMEN; ASSOCIATIONS AB Background: Insulin resistance has been linked with colorectal neoplasia through a number of mechanistic and observational studies. Allelic variants of genes encoding components of the insulin pathway, including insulin (INS), insulin receptor (INSR), and insulin receptor substrate-1 and insulin receptor substrate-2 (IRS1 and IRS2) have been associated with hyperinsulinemia and insulin resistance and may, therefore, predict susceptibility to colorectal neoplasia. Methods: We investigated whether single nucleotide polymorphisms (SNP) in the INS, INSR, IRS1, and IRS2 genes are associated with risk of advanced left-sided colorectal adenoma, a cancer precursor. We analyzed 20 SNPs in a largely Caucasian study population comprising 766 cases with advanced adenomas of the distal colon and 771 controls, all of whom had undergone flexible sigmoidoscopy as part of the screening arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Results: Overall, we found limited evidence for a role of gene variants of the insulin signaling pathway and prevalence of advanced colorectal adenoma. We observed a statistically significant interaction between INSR genotypes and body mass index (BMI) with colorectal adenoma prevalence (P value for global test = 0.003) and suggestion of an interaction between INSR genotypes and glycemic load (P value for global test = 0.06); however, exploration of the interaction of BMI and glycemic load with the individual SNPs in INSR did not suggest a single SNP that may explain the significance of these global tests of interaction and did not yield any consistent patterns. Conclusion: These findings do not provide strong evidence for associations between polymorphic variation in genes of the insulin signaling pathway and advanced left-sided colorectal adenoma. Evidence for interaction between INSR variants and BMI and glycemic load for risk of advanced left-sided colorectal adenoma requires independent confirmation, and genotyping of INSR across a broader region and at greater density may be necessary to fully elucidate the nature of these interactions. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med & Epidemiol, Pittsburgh, PA USA. Pacific Hlth Res Inst, Honolulu, HI USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Gunter, MJ (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM mgunter@aecom.yu.edu OI Hayes, Richard/0000-0002-0918-661X NR 37 TC 13 Z9 13 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2007 VL 16 IS 4 BP 703 EP 708 DI 10.1158/1055-9965.EPI-06-0849 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 157PN UT WOS:000245732600010 PM 17416760 ER PT J AU Chang, SC Lacey, JV Brinton, LA Hartge, P Adams, K Mouw, T Carroll, L Hollenbeck, A Schatzkin, A Leitzmann, MF AF Chang, Shih-Chen Lacey, James V., Jr. Brinton, Louise A. Hartge, Patricia Adams, Kenneth Mouw, Traci Carroll, Leslie Hollenbeck, Albert Schatzkin, Arthur Leitzmann, Michael F. TI Lifetime weight history and endometrial cancer risk by type of menopausal hormone use in the NIH-AARP diet and health study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BODY-FAT DISTRIBUTION; REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; MASS INDEX; FOLLOW-UP; ESTROGEN; COHORT; ASSOCIATION; OBESITY; SIZE AB Obesity and menopausal estrogen therapy are established risk factors for endometrial cancer. However, the joint effects of obesity and menopausal hormone therapy on endometrial cancer risk are incompletely understood. We addressed this issue in a cohort of 103,882 women ages 50 to 71 years at baseline in 1995 to 1996. During a median of 4.6 years, which contributed to a total of 455,304 person-years of follow-up through 2000, 677 cases of endometrial cancer were ascertained. Both baseline body mass index (BMI) and adult weight gain were associated with increased endometrial cancer risk. The multivariate relative risk (RR) comparing obese with normal weight women (BMI > 30 versus < 25 kg/m(2)) was 3.03 [95% confidence interval (95% CI), 2.50-3.68]. Compared with women with stable weight (gained or lost < 5 kg) between age 18 and baseline, women who gained >= 20 kg had a RR of 2.75 (95% Cl, 1.96-3.86). Menopausal Introduction hormone therapy significantly modified the relations of BMI (Pinteraction < 0.001) and adult weight gain (P-interaction = 0.004) to endometrial cancer risk. Compared with normal weight, the RRs for obesity were 5.41 (95% Cl, 4.01-7.29) among women who never used menopausal hormone therapy, 2.53 (95% Cl, 1.21-5.30) among former menopausal hormone therapy users, and 1.44 (95% Cl, 1.00-2.05) among current users. Compared with a stable weight between age 18 and baseline, the RRs for weight gain of !20 kg among never users and ever users of menopausal hormone therapy were 5.35 (95% Cl, 3.01-9.52) and 1.43 (95% Cl, 0.96-2.15), respectively. We conclude that both current adiposity and adult weight gain are associated with substantial increases in the risk of endometrial cancer, with relations particularly evident among never users of menopausal hormone therapy. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. AARP, Washington, DC USA. RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Suite 320,Execut Plaza S,MSC 7232, Bethesda, MD 20892 USA. EM leitzmann@mail.nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 35 TC 62 Z9 67 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2007 VL 16 IS 4 BP 723 EP 730 DI 10.1158/1055-9965.EPI-06-0675 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 157PN UT WOS:000245732600013 PM 17416763 ER PT J AU Suuriniemi, M Agalliu, I Schaid, DJ Johanneson, B McDonnell, SK Iwasaki, L Stanford, JL Ostrander, EA AF Suuriniemi, Miia Agalliu, Ilir Schaid, Daniel J. Johanneson, Bo McDonnell, Shannon K. Iwasaki, Lori Stanford, Janet L. Ostrander, Elaine A. TI Confirmation of a positive association between prostate cancer risk and a locus at chromosome 8q24 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROGNOSTIC-SIGNIFICANCE; GENETIC SUSCEPTIBILITY; DOMINANT INHERITANCE; AGGRESSIVENESS LOCUS; ALLELIC IMBALANCE; LINKAGE; FAMILIES; SCAN; DISEASE; SWEDEN AB Background: Family-based linkage studies, association studies, and studies of tumors have highlighted human chromosome 8q as a genomic region of interest for prostate cancer susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) and a microsatellite marker, was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. samples. Although the data were provocative, the U.S. samples were not population based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the United States. Methods: We analyzed both markers in a population-based, case-control study of middle-aged men from King County, Washington. Results: Overall, there was a significant positive association between the A allele of the SNP rs1447295 and prostate Introduction cancer risk [odds ratio, 1.4; 95% confidence interval (95% CI), 1.1-2.0] but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with high Gleason scores. Adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening history, the adjusted odds ratios were 1.4 (95% CI, 1.1-1.8) for the A allele of the SNP and 1.9 (95% Cl, 1.2-2.8) for the -10 allele of the microsatellite. Conclusions: These data suggest that the locus on chromosome 8q24 harbors a genetic variant associated with prostate cancer and that the microsatellite marker is a stronger risk factor for aggressive prostate cancers defined by poorly differentiated tumor morphology. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Div Publ Hlth Sci, Fred Hutchinson Canc Res Ctr, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA USA. Mayo Clin & Mayo Fdn, Div Biostat, Rochester, MN USA. RP Ostrander, EA (reprint author), NHGRI, Canc Genet Branch, NIH, 50 South Dr,Room 5351, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 40 TC 71 Z9 73 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2007 VL 16 IS 4 BP 809 EP 814 DI 10.1158/1055-9965.EPI-06-1049 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 157PN UT WOS:000245732600025 PM 17416775 ER PT J AU Castle, PE Sadorra, M Garcia, FAR Cullen, AP Lorincz, AT Mitchell, AL Whitby, D Chuke, R Kornegay, JR AF Castle, Philip E. Sadorra, Mark Garcia, Francisco A. R. Cullen, Allison P. Lorincz, Attila T. Mitchell, Amy L. Whitby, Denise Chuke, Ronald Kornegay, Janet R. TI Mouthwash as a low-cost and safe specimen transport medium for human papillomavirus DNA testing of cervicovaginal specimens SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CERVICAL-CANCER; HYBRID-CAPTURE-2; REPRODUCIBILITY; WORLDWIDE; CYTOLOGY; ASSAY AB The usefulness of mouthwash as a transport medium for cervical specimens for carcinogenic human papillomavirus (HPV) DNA testing has not been evaluated. Two cervical specimens were collected from each of 34 patients, with one placed in mouthwash (Scope, Proctor and Gamble, Inc.) and the other in a liquid cytology medium commonly used for HPV DNA testing in alternating order. Paired specimens were tested by a PCR assay for carcinogenic HPV and a PCR HPV genotyping assay for 37 HPV types at 0, 3, and 6 weeks after collection; the results of the HPV genotyping assay were categorized into HPV risk groups according to cancer risk (HPV-16 > HPV-18 > other carcinogenic HPV types > noncarcinogenic HPV types > negative). After 4 months of storage, specimens were tested using a second, non-PCR test for carcinogenic HPV. We observed a >= 94% total agreement and kappa values of >= 0.88 between media at each time point for PCR-detected carcinogenic HPV. We observed a >= 74% total agreement,. >= 0.62 unweighted kappa(r), and >= 0.75 linearly weighted r, between media at each time point for PCR-detected HPV cancer risk category. Finally, we observed an 88% total agreement and kappa of 0.77 between media for carcinogenic HPV detection using a second test after 4 months of storage. We suggest that mouthwash might be used as a low-cost, safe, nonflammable storage and transport medium for cervical specimens for HPV DNA testing in cervical cancer screening programs. C1 NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Roche Mol Syst, Alameda, CA USA. Univ Arizona, Hlth Sci Ctr, Tucson, AZ 85721 USA. Digene Corp, Gaithersburg, MD USA. Sci Applicat Int Corp, Frederick, MD USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Bldg,Room 5004,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov FU Intramural NIH HHS NR 17 TC 4 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2007 VL 16 IS 4 BP 840 EP 843 DI 10.1158/1055-9965.EPI-06-0909 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 157PN UT WOS:000245732600031 PM 17416781 ER PT J AU Lonn, S Inskip, PD Pollak, MN Weinstein, SJ Virtamo, J Albanes, D AF Lonn, Stefan Inskip, Peter D. Pollak, Michael N. Weinstein, Stephanie J. Virtamo, Jarmo Albanes, Demetrius TI Glioma risk in relation to serum levels of insulin-like growth factors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROSTATE-CANCER RISK; FACTOR-I RECEPTOR; LUNG-CANCER; BINDING PROTEIN-3; BREAST-CANCER; BETA-CAROTENE; MALE SMOKERS; INSULIN-LIKE-GROWTH-FACTOR-1; COHORT; MARKER AB Several studies have suggested that insulin-like growth factors (IGF) are related to cancer risk. We investigated the associations between serum levels of IGF-I and IGF-binding protein-3 and glioma risk. A nested case-control study was conducted within a cancer prevention study, including 29,133 men (ages 50-69 years). In total, 22 glioma cases and 400 randomly selected controls were included. Serum samples were collected a minimum of 5 years before cancer diagnosis. Serum concentrations were measured using ELISA and divided into tertiles based on measurements among controls. Odds ratios and 95% confidence intervals were calculated using the lowest tertile as the reference category. No statistical association was detected between glioma and IGF-binding protein-3. IGF-I was inversely associated with glioma when comparing the lowest tertile with the other tertiles combined (odds ratio, 0.3; 95% confidence interval, 0.1-0.7). The results encourage future research on IGFs in relation to brain tumors in larger studies. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. McGill Univ, Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ H3T 1E2, Canada. Natl Publ Hlth Inst, Dept Hlth Promot & Chron Dis Prevent, Helsinki, Finland. RP Lonn, S (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Room 7053,6120 Execut Blvd, Bethesda, MD 20892 USA. EM Lstefan@mail.nih.gov RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015 OI Pollak, Michael/0000-0003-3047-0604; FU CCR NIH HHS [N01-RC-45035, N01-RC-37004]; Intramural NIH HHS; NCI NIH HHS [N01-CN-45165] NR 26 TC 13 Z9 13 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2007 VL 16 IS 4 BP 844 EP 846 DI 10.1158/1055-9965.EPI-06-1010 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 157PN UT WOS:000245732600032 PM 17416782 ER PT J AU Chan, T Chen, Z Hao, S Xu, S Yuan, J Saxena, A Qureshi, M Zheng, C Xiang, J AF Chan, T. Chen, Z. Hao, S. Xu, S. Yuan, J. Saxena, A. Qureshi, M. Zheng, C. Xiang, J. TI Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat shock protein 70 gene-transfected tumor cells in early phase of apoptosis SO CANCER GENE THERAPY LA English DT Article DE HSP70; apoptosis; DC vaccine; antitumor immunity ID HEAT-SHOCK PROTEINS; ANTIGEN-PRESENTING CELLS; ANTITUMOR IMMUNITY; IN-VIVO; GP96 PREPARATIONS; OVER-EXPRESSION; NECROSIS-FACTOR; RECEPTOR; MATURATION; HSP70 AB The dual role of heat shock protein 70 (HSP70), as antigenic peptide chaperone and danger signal, makes it especially important in dendritic cell (DC)-based vaccination. In this study, we investigated the impacts of apoptotic transgenic MCA/ HSP tumor cells expressing HSP70 on DC maturation, T- cell stimulation and vaccine efficacy. We found that DCs with phagocytosis of MCA/ HSP in early phase of apoptosis expressed more pMHC I complexes, stimulated stronger cytotoxic T lymphocyte (CTL) responses (40% specific killing at an E: T cell ratio of 50) and induced immune protection in 90% of mice against MCA tumor cell challenge, compared with 25% specific CTL killing activity and 60% immune protection seen in mice immunized with DC with phagocytosis of MCA/HSP in late phase of apoptosis (P < 0.05). Similar results were confirmed in another EG7 tumor model also expressing HSP70. Taken together, our data demonstrate that HSP70 on apoptotic tumor cells stimulate DC maturation, and DC with phagocytosis of apoptotic tumor cells expressing HSP70 in early phase of apoptosis more efficiently induced tumor- specific CTL responses and immunity than DCs with phagocytosis of apoptotic tumor cells in late phase of apoptosis. These results may have an important impact in designing DC-based antitumor vaccines. Cancer Gene Therapy (2007) 14, 409 - 420. doi: 10.1038/ sj. cgt. 7701025; published online 19 January 2007. C1 Univ Saskatchewan, Dept Oncol, Res Unit, Saskatchewan Ctr Agcy,Coll Med, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Coll Med, Dept Immunol, Saskatchewan Ctr Agcy,Res Unit, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Coll Med, Dept Pathol, Saskatchewan Ctr Agcy,Res Unit, Saskatoon, SK S7N 4H4, Canada. NIDR, Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. RP Xiang, J (reprint author), Univ Saskatchewan, Dept Oncol, Res Unit, Saskatchewan Ctr Agcy,Coll Med, 20 Campus Dr, Saskatoon, SK S7N 4H4, Canada. EM jxiang@scf.sk.ca NR 59 TC 15 Z9 21 U1 2 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD APR PY 2007 VL 14 IS 4 BP 409 EP 420 DI 10.1038/sj.cgt.7701025 PG 12 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 146JQ UT WOS:000244930700009 PM 17235354 ER PT J AU Brenner, BM Stoler, DL Rodriguez, L Karpenko, MJ Swede, H Petrelli, NJ Anderson, GR AF Brenner, Bruce M. Stoler, Daniel L. Rodriguez, Luz Karpenko, Matthew J. Swede, Helen Petrelli, Nicholas J. Anderson, Garth R. TI Allelic losses at genomic instability-associated loci in villous adenomas and adjacent colorectal cancers SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID SEQUENCE REPEAT) PCR; MICROSATELLITE INSTABILITY; FREQUENT LOSS; HETEROZYGOSITY; CARCINOMAS; REGIONS; OCCURS; TUMOR; CARCINOGENESIS; IDENTIFICATION AB Allelic imbalances in premalignant villous adenomas were compared with those in adjacent micro-dissected colorectal carcinoma that had arisen directly from the adenomas. Carcinoina-adenoma pairs were examined from 17 patients who underwent resections for colorectal cancer. In all, 28 microsatellite markers were examined, from regions of the genome where individual allelic losses have been associated with overall genomic instability in colorectal carcinomas. Microsatellite instability (MSI) was also evaluated for each marker in each tissue type. Loss of heterozygosity for multiple markers was found in 35% of adenomas and 65% of carcinomas; the average fractional allelic loss rate was 2.5 times higher in carcinomas than in adenomas. Of the 17 patients, 4 had MSI for > 30% of markers in both adenoma and carcinoma, with no significant differences between the two tissues. Markers with particularly high imbalance rates in adenomas were seen on chromosomes 11, 14, and 15. These findings provide further evidence that genomic instability is an ongoing process during carcinogenesis, with a markedly increased frequency of allelic losses seen in carcinomas, compared with adjacent adenomas. Markers on chromosomes 11, 14, and 15 may become valuable tools in the identification of patients destined to progress to colorectal carcinomas. (c) 2007 Elsevier Inc. All rights reserved. C1 Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USA. Univ Connecticut, Ctr Hlth, Div Surg, Farmington, CT 06030 USA. Roswell Pk Canc Inst, Dept Head & Neck Surg & Pathol, Buffalo, NY 14263 USA. NCI, Genet Branch, NNMC, Bethesda, MD 20892 USA. Ohio State Univ, Med Ctr, Dept Internal Med, Columbus, OH 43210 USA. Univ Connecticut, Ctr Hlth, Neag Canc Ctr, Farmington, CT USA. Helen F Graham Canc Ctr, Wilmington, DE USA. RP Anderson, GR (reprint author), Roswell Pk Canc Inst, Dept Canc Biol, Buffalo, NY 14263 USA. EM garth.anderson@roswellpark.org FU NCI NIH HHS [R01 CA074127-07, R01 CA074127, R01CA74127] NR 31 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD APR 1 PY 2007 VL 174 IS 1 BP 9 EP 15 DI 10.1016/j.cancergencyto.2006.11.001 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 148XW UT WOS:000245111700002 PM 17350461 ER PT J AU Ferrantini, M Capone, I Marincola, FM Parmiani, G Belardelli, F AF Ferrantini, Maria Capone, Imerio Marincola, Francesco M. Parmiani, Giorgio Belardelli, Filippo TI International meeting "Immunotherapy of Cancer: Challenges and Needs" SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Editorial Material DE cancer; vaccines; immunotherapy ID CD8(+) T-CELLS; MELANOMA; VACCINATION; RESPONSES AB The main aims of the international meeting "Immunotherapy of Cancer: Challenges and Needs" were to review the state of the art of cancer immunotherapy and to identify critical issues which deserve special attention for promoting progress of research in this field, with a particular focus on the perspectives of clinical research. Novel concepts and strategies for identifying, monitoring and predicting effective responses to cancer immunotherapy protocols were presented, focused on the use of adjuvants (CpG oligonucleotides) or cytokines (IFN-alpha) to enhance the efficacy of cancer vaccines. Moreover, the possible advantages of using different types of dendritic cells (for active immunization strategies) or T cells (for adoptive immunotherapy protocols) were debated. A consensus was achieved on the need for enhancing the efficacy of cancer vaccines or adoptive cell immunotherapy by combining these strategies with other anti-cancer treatments, including chemotherapy. Finally, initiatives for promoting clinical research by establishing a strategic cooperation in the field of cancer immunotherapy based on the active participation of all the relevant actors, including public institutions responsible of Public Health, National Cancer Institutes, industry, representatives of regulatory bodies, and patients' organizations were proposed. C1 Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, I-20133 Milan, Italy. RP Belardelli, F (reprint author), Ist Super Sanita, Dept Cell Biol & Neurosci, Viale Regina Elena 299, I-00161 Rome, Italy. EM belard@iss.it NR 10 TC 7 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD APR PY 2007 VL 56 IS 4 BP 581 EP 585 DI 10.1007/s00262-006-0251-6 PG 5 WC Oncology; Immunology SC Oncology; Immunology GA 132SK UT WOS:000243962300015 PM 17131119 ER PT J AU Schumacher, FR Feigelson, HS Cox, DG Haiman, CA Albanes, D Buring, J Calle, EE Chanock, SJ Colditz, GA Diver, WR Dunning, AM Freedman, ML Gaziano, JM Giovannucci, E Hankinson, SE Hayes, RB Henderson, BE Hoover, RN Kaaks, R Key, T Kolonel, LN Kraft, P Le Marchand, L Ma, J Pike, MC Riboli, E Stampfer, MJ Stram, DO Thomas, G Thun, MJ Travis, R Virtamo, J Andriole, G Gelmann, E Willett, WC Hunter, DJ AF Schumacher, Fredrick R. Feigelson, Heather Spencer Cox, David G. Haiman, Christopher A. Albanes, Demetrius Buring, Julie Calle, Eugenia E. Chanock, Stephen J. Colditz, Graham A. Diver, W. Ryan Dunning, Alison M. Freedman, Matthew L. Gaziano, John M. Giovannucci, Edward Hankinson, Sue E. Hayes, Richard B. Henderson, Brian E. Hoover, Robert N. Kaaks, Rudolf Key, Timothy Kolonel, Laurence N. Kraft, Peter Le Marchand, Loic Ma, Jing Pike, Malcolm C. Riboli, Elio Stampfer, Meir J. Stram, Daniel O. Thomas, Gilles Thun, Michael J. Travis, Ruth Virtamo, Jarmo Andriole, Gerald Gelmann, Edward Willett, Walter C. Hunter, David J. TI A common 8q24 variant in prostate and breast cancer from a large nested case-control study SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; BASE-LINE CHARACTERISTICS; GROWTH-FACTOR-I; LIFE-STYLE; GENES; POPULATIONS; PREDICTORS; CARCINOMA; COHORT; HEALTH AB Two recent studies independently identified polymorphisms in the 8q24 region, including a single nucleotide polymorphism (rsl447295), strongly associated with prostate cancer risk. Here, we replicate the overall association in a large nested case-control study from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium using 6,637 prostate cancer cases and 7,361 matched controls. We also examine whether this polymorphism is associated with breast cancer among 2,604 Caucasian breast cancer cases and 3,118 matched controls. The rs1447295 marker was strongly associated with prostate cancer among Caucasians (P = 1.23 x 10(-13)). When we exclude the Multiethnic Cohort samples, previously reported by Freedman et al., the association remains highly significant (P = 8.64 X 10(-13)). Compared with wild-type homozygotes, carriers with one copy of the minor allele had an ORAC = 1.34 (99% confidence intervals, 1.19-1.50) and carriers with two copies of the minor allele had an ORAA = 1.86 (99% confidence intervals, 1.30-2.67). Among African Americans, the genotype association was statistically significant in men diagnosed with prostate cancer at an early age (P = 0.011) and nonsignificant for those diagnosed at a later age (P = 0.924). This difference in risk by age at diagnosis was not present among Caucasians. We found no statistically significant difference in risk when tumors were classified by Gleason score, stage, or mortality. We found no association between rs1447295 and breast cancer risk (P = 0.590). Although the gene responsible has yet to be identified, the validation of this marker in this large sample of prostate cancer cases leaves little room for the possibility of a false-positive result. C1 Harvard Univ, Channing Lab, Brigham & Womens Hosp, Dept Med,Med Sch, 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. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Div Prevent Med, Brigham & Womens Hosp, Dept Med,Med Sch, Boston, MA 02115 USA. Harvard Univ, Div Aging, Brigham & Womens Hosp, Dept Med,Med Sch, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Natl Home Off, Atlanta, GA 30329 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Core Genotyping Facil, Gaithersburg, MD USA. Univ Cambridge, Dept Oncol, Cambridge, England. Int Agcy Res Canc, Hormones & Canc Grp, F-69372 Lyon, France. Int Agcy Res Canc, Unit Nutr & Canc, F-69372 Lyon, France. Univ Oxford, Epidemiol Unit, Canc Res United Kingdom, Oxford, England. Univ Hawaii, Ctr Canc Res, Honolulu, HI 96822 USA. Fdn Jean Dausset, Ctr Etude Polymorphisme Humain, Paris, France. Natl Publ Hlth Inst, Canc Prevent Unit, Helsinki, Finland. Washington Univ, Sch Med, Div Urol, St Louis, MO USA. Columbia Univ, Coll Phys & Surg, Milstein Hosp, Div Hematol & Oncol, New York, NY USA. RP Hunter, DJ (reprint author), Harvard Univ, Channing Lab, Brigham & Womens Hosp, Dept Med,Med Sch, 181 Longwood Ave, Boston, MA 02115 USA. EM dhunter@hsph.harvard.edu RI Cox, David/A-2023-2009; Albanes, Demetrius/B-9749-2015; Colditz, Graham/A-3963-2009; OI Cox, David/0000-0002-2152-9259; Colditz, Graham/0000-0002-7307-0291; Dunning, Alison Margaret/0000-0001-6651-7166; Hayes, Richard/0000-0002-0918-661X FU NCI NIH HHS [R01 CA097193, T32-CA-09001, UO1-CA98216, UO1-CA98233, UO1-CA98710, UO1-CA98758] NR 20 TC 102 Z9 105 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 2951 EP 2956 DI 10.1158/0008-5472.CAN-06-3591 PG 6 WC Oncology SC Oncology GA 156BM UT WOS:000245622900010 PM 17409400 ER PT J AU Wang, Y Woodgate, R McManus, TP Mead, S McCormick, JJ Maher, VM AF Wang, Yun Woodgate, Roger McManus, Terrence P. Mead, Samantha McCormick, J. Justin Maher, Veronica M. TI Evidence that in xeroderma pigmentosum variant cells, which lack DNA polymerase eta, DNA polymerase iota causes the very high frequency and unique spectrum of UV-induced mutations SO CANCER RESEARCH LA English DT Article ID HUMAN-FIBROBLASTS; TRANSLESION REPLICATION; ULTRAVIOLET-LIGHT; EXCISION REPAIR; STRAND BIAS; PHOTOPRODUCTS; BYPASS; DEFICIENT; RADIATION; LESIONS AB Xeroderma pigmentosum variant (XPV) patients have normal DNA excision repair, yet are predisposed to develop sunlightinduced cancer. They exhibit a 25-fold higher than normal frequency of UV-induced mutations and very unusual kinds (spectrum), mainly transversions. The primary defect in XPV cells is the lack of functional DNA polymerase (Pol) eta, the translesion synthesis DNA polymerase that readily inserts adenine nucleotides opposite photoproducts involving thymine. The high frequency and striking difference in kinds of UV-induced mutations in XPV cells strongly suggest that, in the absence of Pol eta, an abnormally error-prone polymerase substitutes. In vitro replication studies of Pol L show that it replicates past 5'T-T3' and 5'T-U3' cyclobutane pyrimidine dimers, incorporating G or T nucleotides opposite the 3' nucleotide. To test the hypothesis that Pol l causes the high frequency and abnormal spectrum of UV-induced mutations in XPV cells, we identified an unlimited lifespan XPV cell line expressing two forms of Pol (l), whose frequency of UV-induced mutations is twice that of XPV cells expressing one form. We eliminated expression of one form and compared the parental cells and derivatives for the frequency and kinds of UVinduced mutations. All exhibited similar sensitivity to the cytotoxicity of LTV(254 nm), and the kinds of mutations induced were identical, but the frequency of mutations induced in the derivatives was reduced to <= 50% that of the parent. These data strongly support the hypothesis that in cells lacking Polrl, Pol L is responsible for the high frequency and abnormal spectrum of UV-induced mutations, and ultimately their malignant transformation. C1 Michigan State Univ, Carcinogenesis Lab, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. NICHHD, Lab Genom Integr, NIH, Bethesda, MD 20892 USA. RP Maher, VM (reprint author), Michigan State Univ, Carcinogenesis Lab, Dept Biochem & Mol Biol, Food Safety & Toxicol Bldg, E Lansing, MI 48824 USA. EM maher@msu.edu FU Intramural NIH HHS; NCI NIH HHS [CA-91490] NR 30 TC 72 Z9 76 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 APR 1 PY 2007 VL 67 IS 7 BP 3018 EP 3026 DI 10.1158/0008-5472.CAN-06-3073 PG 9 WC Oncology SC Oncology GA 156BM UT WOS:000245622900018 PM 17409408 ER PT J AU Gayther, SA Song, H Ramus, SJ Kjaer, SK Whittemore, AS Quaye, L Tyrer, J Shadforth, D Hogdall, E Hogdall, C Blaeker, J DiCioccio, R McGuire, V Webb, PM Beesley, J Green, AC Whiteman, DC Goodman, MT Lurie, G Carney, ME Modugno, F Ness, RB Edwards, RP Moysich, KB Goode, EL Couch, FJ Cunningham, JM Sellers, TA Wu, AH Pike, MC Iversen, ES Marks, JR Garcia-Closas, M Brinton, L Lissowska, J Peplonska, B Easton, DF Jacobs, I Ponder, BAJ Schildkraut, J Pearce, CL Chenevix-Trench, G Berchuck, A Pharoah, PDP AF Gayther, Simon A. Song, Honglin Ramus, Susan J. Kjaer, Susan Krueger Whittemore, Alice S. Quaye, Lydia Tyrer, Jonathan Shadforth, Danielle Hogdall, Estrid Hogdall, Claus Blaeker, Jan DiCioccio, Richard McGuire, Valerie Webb, Penelope M. Beesley, Jonathan Green, Adele C. Whiteman, David C. Goodman, Marc T. Lurie, Galina Carney, Michael E. Modugno, Francesmary Ness, Roberta B. Edwards, Robert P. Moysich, Kirsten B. Goode, Ellen L. Couch, Fergus J. Cunningham, Julie M. Sellers, Thomas A. Wu, Anna H. Pike, Malcolm C. Iversen, Edivin S. Marks, Jeffrey R. Garcia-Closas, Montserrat Brinton, Louise Lissowska, Jolanta Peplonska, Beata Easton, Douglas F. Jacobs, Ian Ponder, Bruce A. J. Schildkraut, Joellen Pearce, C. Leigh Chenevix-Trench, Georgia Berchuck, Andrew Pharoah, Paul D. P. CA Australian Ovarian Canc Study Grp Australian Canc Study Ovarian Ovarian Canc Assoc Consortium TI Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer SO CANCER RESEARCH LA English DT Article ID PROGESTERONE-RECEPTOR GENE; BREAST-CANCER; ANDROGEN RECEPTOR; ASSOCIATION SCANS; COMMON VARIANTS; REPAIR GENES; RISK; D1; OVEREXPRESSION; INACTIVATION AB High-risk susceptibility genes explain < 40% of the excess risk of familial ovarian cancer. Therefore, other ovarian cancer susceptibility genes are likely to exist. We have used a single nucleotide polymorphism (SNP)-tagging approach to evaluate common variants in 13 genes involved in cell cycle control-CCATD1, CCAV2. CCN7D3, CCAE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN24. CDKN2B, CDKN2C, and CDKN2D-and risk of invasive epithelial ovarian cancer. We used a two-stage, multicenter, case-control study. In stage 1, 88 SNPs that tag common variation in these genes were genotped in three studies from the United Kingdom, United States, and Denmark (similar to 1,500 cases and 2,500 controls). Genotype frequencies in cases and controls were compared using logistic regression. In stage 2, eight other studies from Australia, Poland, and the United States (similar to 2,000 cases and similar to 3,200 controls) were genotyped for the five most significant SNPs from stage 1. No SNP was significant in the stage 2 data alone. Using the combined stages 1 and 2 data set, CDKN2A rs3731257 and CDKN1B rs2066827 were associated with disease risk (unadjusted P trend = 0.008 and 0.036, respectively), but these were not significant after adjusting for multiple testing. Carrying the minor allele of these SNPs was found to be associated with reduced risk OR, 0.91 (0.85-0.98) for rs3731257; and OR, 0.93 (0.87-0.995) for rs20668271. In conclusion, we have found evidence that a single tagged SNP in both the CDKN2A and CDKN1B genes may be associated with reduced ovarian cancer risk. This study highlights the need for multicenter collaborations for genetic association studies. C1 UCL, Translat Res Labs, Windeyer Inst, London W1T 4JF, England. Univ Cambridge, Canc Res United Kingdom, Dept Oncol, Strangeways Res Lab, Cambridge, England. Univ Cambridge, Canc Res United Kingdom, Genet Epidemiol Unit, Strangeways Res Lab, Cambridge, England. Danish Canc Soc, Copenhagen, Denmark. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Copenhagen, Copenhagen, Denmark. Aarhus Univ Hosp, Skejby, DK-8000 Aarhus, Denmark. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. Univ Hawaii, Ctr Canc Res, Honolulu, HI 96822 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Hlth, Inst Canc, Pittsburgh, PA 15261 USA. Mayo Clin, Coll Med, Rochester, MN USA. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Duke Univ, Med Ctr, Durham, NC USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. M Sklodowska Curie Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland. Ctr Canc, Warsaw, Poland. Nofer Inst Occupat Med, Lodz, Poland. Peter MacCallum Canc Inst, Melbourne, Vic 3000, Australia. RP Gayther, SA (reprint author), UCL, Translat Res Labs, Windeyer Inst, 46 Cleveland St, London W1T 4JF, England. EM s.gayther@ucl.ac.uk RI Susan, Ramus/C-1607-2008; Peplonska, Beata/F-6004-2010; Webb, Penelope/D-5736-2013; Jacobs, Ian/F-1743-2013; Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015; Bowtell, David/H-1007-2016; Whiteman, David/P-2728-2014; Green, Adele/P-2736-2014; OI Lissowska, Jolanta/0000-0003-2695-5799; Webb, Penelope/0000-0003-0733-5930; Jacobs, Ian/0000-0002-8112-4624; Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton, Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525; Whiteman, David/0000-0003-2563-9559; Green, Adele/0000-0002-2753-4841; Kjaer, Susanne/0000-0002-8347-1398; Ramus, Susan/0000-0003-0005-7798 FU Intramural NIH HHS; NCI NIH HHS [CA63464, CA14089, CA16056, CA17054, CA61132, CA71766, K07-CA80668, N01-PC-67010, R01CA095023, R03-CA113148] NR 40 TC 58 Z9 59 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 3027 EP 3035 DI 10.1158/0008-5472.CAN-06-3261 PG 9 WC Oncology SC Oncology GA 156BM UT WOS:000245622900019 PM 17409409 ER PT J AU Jin, W Yun, C Hobbie, A Martin, MJ Sorensen, PHB Kim, SJ AF Jin, Wook Yun, Chohee Hobbie, Amy Martin, Matthew J. Sorensen, Poul H. B. Kim, Seong-Jin TI Cellular transformation and activation of the phosphoinositide-3-kinase-Akt cascade by the ETV6-NTRK3 chimeric tyrosine kinase requires c-Src SO CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FIBROBLAST-GROWTH-FACTOR; FACTOR-I RECEPTOR; ABL-RELATED GENE; SIGNAL-TRANSDUCTION; CONGENITAL FIBROSARCOMA; AKT ACTIVATION; BREAST-CANCER; FUSION; PROTEIN AB The ETV6-NTRK3 (EN) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages, functions as a constitutively active protein-tyrosine kinase. ETV6-NTRK expression leads to the constitutive activation of two major effector pathways of wild-type NTRK3, namely, the Ras-mitogen-activated protein kinase (MAPK) mitogenic pathway and the phosphoinositide-3-kinase (PI3K)Akt pathway mediating cell survival, and both are required for EN transformation. However, it remains unclear how ETV6-NTRK3 activates Ras-Erk1/2 and/or PI3K-Akt cascades. Here, we define some aspects of the molecular mechanisms regulating ETV6-NTRK-dependent Ras-Erk1/2 and PI3K-Akt activation. We show that ETV6-NTRK3 associates with c-Src, and that treatment with SU6656, a c-Src inhibitor, completely blocks ETV6-NTRK-transforming activity. Treatment of NIH3T3 cells expressing ETV6-NTRK3 with SU6656 attenuated the activation of Ras-Erk1/2 and PI3K-Akt. Suppression of c-Src by RNA interference in NIH3T3-ETV6-NTRK3 cells resulted in markedly decreased expression of cyclin D1 and suppression of activation of Ras-Erk1/2 and PI3K-Akt. However, in Src-deficient cells, the ETV6-NTRK3 failed to activate the PI3K-Atk pathway, but not the Ras-Erk1/2 pathway. Therefore, these data indicate that ETV6-NTRK3 induces the PI3K-Akt cascade through the activation of c-Src. C1 NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada. Gachon Univ Med & Sci, Lee Gil Ya Canc & Diabet Inst, Inchon, South Korea. RP Kim, SJ (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room B1106,41 Lib Dr, Bethesda, MD 20892 USA. EM Kims@mail.nih.gov FU Intramural NIH HHS NR 48 TC 13 Z9 14 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 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 3192 EP 3200 DI 10.1158/0008-5472.CAN-06-3526 PG 9 WC Oncology SC Oncology GA 156BM UT WOS:000245622900037 PM 17409427 ER PT J AU Yang, DF Thangaraju, M Greeneltch, K Browning, DD Schoenlein, PV Tamura, T Ozato, K Ganapathy, V Abrams, SI Liu, KB AF Yang, Dafeng Thangaraju, Muthusamy Greeneltch, Kristy Browning, Darren D. Schoenlein, Patricia V. Tamura, Tomohiko Ozato, Keiko Ganapathy, Vadivel Abrams, Scott I. Liu, Kebin TI Repression of IFN regulatory factor 8 by DNA methylation is a molecular determinant of apoptotic resistance and metastatic phenotype in metastatic tumor cells SO CANCER RESEARCH LA English DT Article ID SEQUENCE-BINDING-PROTEIN; FAS LIGAND INTERACTIONS; COLON-CARCINOMA CELLS; GENE-EXPRESSION; MEDIATED CYTOTOXICITY; INTERFERON-GAMMA; IMMUNE ESCAPE; MYELOID CELLS; DEATH FACTOR; ICSBP GENE AB Apoptotic resistance is often associated with metastatic phenotype in tumor cells and is considered a hallmark of tumor progression. In this study, IFN regulatory factor 8 (IRF8) expression was found to be inversely correlated with an apoptotic-resistant and metastatic phenotype in human colon carcinoma cell lines in vitro. This inverse correlation was further extended to spontaneously arising primary mammary carcinoma and lung metastases in a mouse tumor model in vivo. Exogenous expression of IRFS in the metastatic tumor cell line restored, at least partially, the sensitivity of the tumor cells to Fas-mediated apoptosis, and disruption of IRFS function conferred the poorly metastatic tumors with enhanced apoptotic resistance and metastatic capability. DNA demethylation restored IRF8 expression and sensitized the metastatic tumor cells to Fas-mediated apoptosis. Analysis of genomic DNA isolated from both primary and metastatic tumor cells with methylation-sensitive PCR revealed hyper-methylation of the IRFS promoter in metastatic tumor cells but not in primary tumor cells. Taken together, our data suggest that IRFS is both an essential regulator in Fas-mediated apoptosis pathway and a metastasis suppressor in solid tumors and that metastatic tumor cells use DNA hypermethylation to repress IRF8 expression to evade apoptotic cell death and to acquire a metastatic phenotype. C1 Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. Med Coll Georgia, Dept Cellular Biol & Anat, Augusta, GA 30912 USA. NCI, Tumor Immunol & Biol Lab, NICHHD, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Liu, KB (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, 1459 Laney Walker Blvd, Augusta, GA 30912 USA. EM Kliu@mcg.edu OI Liu, Kebin/0000-0003-1965-7240 FU Intramural NIH HHS NR 48 TC 50 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 APR 1 PY 2007 VL 67 IS 7 BP 3301 EP 3309 DI 10.1158/0008-5472.CAN-06-4068 PG 9 WC Oncology SC Oncology GA 156BM UT WOS:000245622900049 PM 17409439 ER PT J AU Su, YP Ortiz, J Liu, SH Bugge, TH Singh, R Leppla, SH Frankel, AE AF Su, Yunpeng Ortiz, Janelle Liu, Shihui Bugge, Thomas H. Singh, Ravibhushan Leppla, Stephen H. Frankel, Arthur E. TI Systematic urokinase-activated anthrax toxin therapy produces regressions of subcutaneous human non-small cell lung tumor in athymic nude mice SO CANCER RESEARCH LA English DT Article ID PLASMINOGEN-ACTIVATOR; ANTITUMOR-ACTIVITY; BREAST-CANCER; LETHAL FACTOR; RECEPTOR; GROWTH; COMBINATION; IMMUNOTOXIN; PROTEIN; MODEL AB The novel recombinant anthrax toxin, PrAgU2/FP59, composed of the urokinase- activated protective antigen and a fusion protein of Pseadomonas exotoxin and lethal factor was tested for anti-lung cancer efficacy in an in vivo human tumor model. Male athymic nude mice (age 4-6 weeks) were inoculated s.c. with 10 million H1299 non-small cell lung cancer (NSCLC) cells in the left flank. When tumor volumes reached 200 mm(3) (6-8 days), i.p. injection of 100 mu L saline or different ratios and doses of PrAgU2/FP59 in 100 mu L saline were given every 3 days for four doses and an additional dose at day 29. Animals were monitored twice daily and tumor measurements were made by calipers. The maximum tolerated doses of PrAgU2/FP59 differed dependent on the ratios of PrAgU2 to FP59 over the range of 3:1 to 25:1, respectively. At tolerated doses, tumor regressions were seen in all animals. Complete histologic remission lasting 60 days occurred in 30% of animals. PrAgU2/171359 showed dramatic anti-NSCLC efficacy and warrants further clinical development for therapy of patients with advanced NSCLC. C1 Scott & White Mem Hosp & Clin, Inst Canc Res, Temple, TX 76502 USA. NIAID, Bacterial Toxins & Therapeut Sect, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. RP Frankel, AE (reprint author), Scott & White Mem Hosp & Clin, Inst Canc Res, 5701 S Airport Rd, Temple, TX 76502 USA. EM afrankel@swmail.sw.org NR 41 TC 25 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 3329 EP 3336 DI 10.1158/0008-5472.CAN-06-4642 PG 8 WC Oncology SC Oncology GA 156BM UT WOS:000245622900052 PM 17409442 ER PT J AU Petricoin, EF Espina, V Araujo, RP Midura, B Yeung, C Wan, XL Eichler, GS Johann, DJ Qualman, S Tsokos, M Krishnan, K Helman, LJ Liotta, LA AF Petricoin, Emanuel F., III Espina, Virginia Araujo, Robyn P. Midura, Brieanne Yeung, Choh Wan, Xiaolin Eichler, Gabriel S. Johann, Donald J., Jr. Qualman, Stephen Tsokos, Maria Krishnan, Kartik Helman, Lee J. Liotta, Lance A. TI Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival SO CANCER RESEARCH LA English DT Article ID CHILDRENS-ONCOLOGY-GROUP; MAMMALIAN TARGET; PROTEIN MICROARRAYS; ALVEOLAR RHABDOMYOSARCOMA; KINASE; TRANSLATION; INHIBITION; GROWTH; PHOSPHORYLATION; DIFFERENTIATION AB Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains similar to 60%. A critical goal is to identify, functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) TV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser 473 (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBPI Thr 37/46 (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser(1108) (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr(389) (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR path-way proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy. C1 NCI, NIH, US FDA, Ctr Biol Evaluat & Res,Off Cellular & Gene Therap, Bethesda, MD 20892 USA. NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, NIH, Dept Pediat Oncol, Bethesda, MD 20892 USA. NCI, NIH, Genom & Bioinformat Grp, Mol Pharmacol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. Columbus Childrens Hosp, Dept Pathol, Columbus, OH USA. RP Espina, V (reprint author), George Mason Univ, Ctr Appl Proteom & Mol Med, 10900 Univ Blvd MS 1A9, Manassas, VA 20110 USA. EM vespina@gmu.edu OI Espina, Virginia/0000-0001-5080-5972 FU Intramural NIH HHS NR 44 TC 140 Z9 146 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2007 VL 67 IS 7 BP 3431 EP 3440 DI 10.1158/0008-5472.CAN-06-1344 PG 10 WC Oncology SC Oncology GA 156BM UT WOS:000245622900064 PM 17409454 ER PT J AU Cheung, MC Haynes, AE Meyer, RM Stevens, A Imrie, KR AF Cheung, Matthew C. Haynes, Adam E. Meyer, Ralph M. Stevens, Adrienne Imrie, Kevin R. CA Hematology Dis Site Grp TI Rituximab in lymphoma: A systematic review and consensus practice guideline from Cancer Care Ontario SO CANCER TREATMENT REVIEWS LA English DT Review DE rituximab; non-Hodgkin's lymphoma; systematic review; practice guidelines ID B-CELL LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; NON-HODGKINS-LYMPHOMA; PROSPECTIVE RANDOMIZED-TRIAL; MONOCLONAL-ANTIBODY THERAPY; STUDY-GROUP GLSG; FOLLICULAR LYMPHOMA; LOW-GRADE; SIGNIFICANTLY INCREASES; PROLONGED TREATMENT AB Rituximab is the first antibody-based therapy approved in cancer. The role of this treatment for non-Hodgkin's lymphoma has evolved significantly since its introduction. We aimed to systematically review the literature on rituximab in non-Hodgkin's lymphoma and provide consensus guidelines as to the rational use of this agent. Validated methodology from the Cancer Care Ontario Program in Evidence-Based Care was applied. A comprehensive literature search was completed by reviewers from the Hematology Disease Site Group of Cancer Care Ontario. Data were abstracted from randomized controlled trials of rituximab-containing regimens for patients with non-Hodgkin's lymphoma. Twenty-three randomized controlled trials (RCTs) of rituximab-based therapy were analyzed. Consistent and clinically important benefits in progression-free and overall survival and were seen in the following settings: (1) addition of rituximab to combination chemotherapy for initial treatment of diffuse large B-cell lymphoma and other aggressive B-cell lymphomas; (2) addition of rituximab to combination chemotherapy for initial and subsequent treatment of follicular lymphoma and other indolent B-cell lymphomas; and (3) use of rituximab alone as extended maintenance therapy in patients with indolent B-cell Lymphomas who have responded to initial treatment. The consensus opinion of the Hematotogy Disease Site Group is that rituximab is recommended for these indications. (c) 2006 Elsevier Ltd. All rights reserved. C1 McMaster Univ, Canc Care Ontario Program, Hamilton, ON L8S 4L8, Canada. Sunnybrook Hlth Sci Ctr, Dept Hematol, Toronto, ON M4N 3M5, Canada. Sunnybrook Hlth Sci Ctr, Dept Med Oncol, Toronto, ON M4N 3M5, Canada. NCI, Canada Clin Trials Grp, Kingston, ON K7L 3N6, Canada. Queens Univ, Kingston, ON K7L 3N6, Canada. RP Imrie, KR (reprint author), McMaster Univ, Canc Care Ontario Program, Hamilton, ON L8S 4L8, Canada. EM matthew.cheung@utoronto.ca; haynesa@mcmaster.ca; RMeyer@ctg.queensu.ca; kevin.imrie@utoronto.ca NR 46 TC 33 Z9 34 U1 1 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD APR PY 2007 VL 33 IS 2 BP 161 EP 176 DI 10.1016/j.ctrv.2006.10.005 PG 16 WC Oncology SC Oncology GA 150JW UT WOS:000245213900005 PM 17240533 ER PT J AU Lan, Q Zheng, TZ Chanock, S Zhang, YW Shen, M Wang, SS Berndt, SI Zahm, SH Holford, TR Leaderer, B Yeager, M Welch, R Hosgood, D Boyle, P Rothman, N AF Lan, Qing Zheng, Tongzhang Chanock, Stephen Zhang, Yawei Shen, Min Wang, Sophia S. Berndt, Sonja I. Zahm, Shelia H. Holford, Theodore R. Leaderer, Brian Yeager, Meredith Welch, Robert Hosgood, Dean Boyle, Peter Rothman, Nathaniel TI Genetic variants in caspase genes and susceptibility to non-Hodgkin lymphoma SO CARCINOGENESIS LA English DT Article ID BREAST-CANCER; COMMON VARIANT; REDUCED RISK; CASP10 GENE; MUTATIONS; ASSOCIATION; ACTIVATION; APOPTOSIS; CONNECTICUT; POPULATION AB The caspase proteins are essential for the regulation of normal B cell development and regulation of apoptosis. We investigated five single nucleotide polymorphisms in four key caspase genes, CASP3 [Ex8-280C > A (rs6948) and Ex8+567T > C (rs1049216)], CASP8 Ex14-271A > T (rs13113), CASP9 Ex5+32G > A (rs1052576) and CASP10 Ex3-171A > G (rs3900115) to determine whether they alter risk for non-Hodgkin lymphoma (NHL) in a population-based case-control study of women in Connecticut (461 cases and 535 controls). Variants in CASP3 and CASP9 were significantly associated with a decreased risk for NHL, particularly follicular lymphoma [e.g. CASP3 Ex8+567T > C odds ratio (OR)(CC+TC) = 0.4, 95% confidence interval (CI) = 0.3-0.7; and CASP9 Ex5+32G > A ORAA+AG = 0.6, 95% CI = 0.4-1.0]. Further, variants in CASP3, CASP8 and CASP10 were associated with a decreased risk of marginal zone lymphoma and variants in CASP3 and CASP10 were associated with a lower risk of chronic lymphocytic leukemia and related subtypes. The striking protective associations observed for polymorphisms in all four genes for NHL and/or one or more subtypes suggest that genetic variation in CASP genes may play an important role in the etiology of NHL. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS,MSC 7240, Bethesda, MD 20892 USA. Yale Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. NCI, NIH, Pediat Oncol Branch, Canc Res Ctr,DHHS, Bethesda, MD 20892 USA. Int Agcy Res Canc, Lyon, France. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS,MSC 7240, 6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Boyle, Peter/A-4380-2014; Zahm, Shelia/B-5025-2015 OI Boyle, Peter/0000-0001-6251-0610; FU Intramural NIH HHS; NCI NIH HHS [CA62006] NR 27 TC 43 Z9 49 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2007 VL 28 IS 4 BP 823 EP 827 DI 10.1093/carcin/bgl196 PG 5 WC Oncology SC Oncology GA 152HE UT WOS:000245351500008 PM 17071630 ER PT J AU Bernig, T Boersma, BJ Howe, TM Welch, R Yadavalli, S Staats, B Mechanic, LE Chanock, SJ Ambs, S AF Bernig, Toralf Boersma, Brenda J. Howe, Tiffany M. Welch, Robert Yadavalli, Sunita Staats, Brian Mechanic, Leah E. Chanock, Stephen J. Ambs, Stefan TI The mannose-binding lectin (MBL2) haplotype and breast cancer: an association study in African-American and Caucasian women SO CARCINOGENESIS LA English DT Article ID TUMOR-ASSOCIATED MACROPHAGES; HARDY-WEINBERG EQUILIBRIUM; 3' UNTRANSLATED REGION; HUMAN MAST-CELLS; GENETIC-VARIATION; LINKAGE DISEQUILIBRIUM; MOLECULAR EPIDEMIOLOGY; ACTIVATES COMPLEMENT; DISEASE ASSOCIATIONS; SEQUENCE VALIDATION AB Common genetic variants in cancer-related genes contribute to breast cancer. The innate immune system plays a crucial role in the immune surveillance against malignancies, thus it is plausible that genetic variations in key genes of the innate immunity such as the mannose-binding lectin (MBL), MBL2, could influence the risk for breast cancer. We investigated the association of MBL2 genotypes with breast cancer and conducted a comprehensive genotype and haplotype analysis of 26 MBL2 single nucleotide polymorphisms (SNPs) in a case-control study of breast cancer [166 African-American (AA) case patients versus 180 controls and 127 Caucasian (CAU) case patients versus 137 controls]. We observed that the A allele of the 3'-UTR SNP Ex4-1067 (NCBI SNP ID: rs10824792) was significantly associated with a decreased disease risk in AA women [odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.27-0.81]. Haplotype analysis of MBL2 showed that the frequency of the corresponding 3' haplotype TATAAC (Ex4-1483, Ex4-1067, Ex4-1047, Ex4-901, Ex4-710, 3238bp 3' STP) was lower in cases than controls among AA women (0.15 versus 0.21; P = 0.02) suggesting a protective effect after adjusting for covariates (OR = 0.51, 95% CI = 0.29-0.88, P = 0.018). In conclusion, this study presents preliminary evidence that common genetic variants in the 3'-UTR of MBL2 might influence the risk for breast cancer in AA women, probably in interaction with the 5' secretor haplotypes that are associated with high concentrations of MBL. C1 NCI, Ctr Canc Res, Lab Human Carcinogenesis, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Sect Genom Variat, Peidat Oncol Branch,NIH, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA. RP Ambs, S (reprint author), NCI, Ctr Canc Res, Lab Human Carcinogenesis, NIH, Bldg 37-Room 3050B, Bethesda, MD 20892 USA. EM ambss@mail.nih.gov RI Boersma, Brenda/A-9270-2009 OI Boersma, Brenda/0000-0002-8992-2735 FU Intramural NIH HHS NR 80 TC 17 Z9 17 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2007 VL 28 IS 4 BP 828 EP 836 DI 10.1093/carcin/bgl198 PG 9 WC Oncology SC Oncology GA 152HE UT WOS:000245351500009 PM 17071626 ER PT J AU Zhang, DY Li, JX Wu, KJ Ouyang, WM Ding, J Liu, ZG Costa, M Huang, CS AF Zhang, Dongyun Li, Jingxia Wu, Kangjian Ouyang, Weiming Ding, Jin Liu, Zheng-gang Costa, Max Huang, Chuanshu TI JNK1, but not JNK2, is required for COX-2 induction by nickel compounds SO CARCINOGENESIS LA English DT Article ID COLLECTING DUCT CELLS; FACTOR-KAPPA-B; CYCLOOXYGENASE-2 EXPRESSION; NUCLEAR-FACTOR; KINASE; ACTIVATION; CANCER; INFLAMMATION; TARGET; ROLES AB Activation of the signaling pathways leading to gene expression regulation is critical in the carcinogenic effects of nickel exposure. In the present study, we found nickel exposure could induce cyclooxygenase-2 (COX-2) expression at transcriptional and protein levels in both human bronchoepithelial cells (Beas-2B) and murine embryonic fibroblasts (MEFs). We further provided direct evidence for the specific involvement of the JNK1 signaling pathway in the COX-2 induction using specific gene knockout approaches. Our results demonstrated that COX-2 induction by nickel was impaired in JNK1(-/-) MEFs, but not in JNK2(-/-) MEFs. Moreover, re-constitutional expression of JNK1 restored COX-2 induction, confirming the specific requirement of JNK1 in COX-2 induction. Further investigation revealed that JNK1 mediated the nickel-induced COX-2 expression in a c-Jun/AP-1-dependent manner. Ectopic expression of TAM67, a c-Jun dominant negative mutant, also suppressed the COX-2 induction. Our results demonstrate that the JNK1/c-Jun/AP-1 pathway, but not the JNK2 pathway, plays a critical role in nickel-induced COX-2 expression. C1 NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA. NCI, NIH, Cell & Canc Biol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Huang, CS (reprint author), NYU, Sch Med, Nelson Inst Environm Med, 57 Old Forge Rd, Tuxedo Pk, NY 10987 USA. EM chuanshu@env.med.nyu.edu RI costa, max/H-1754-2012; OI Huang, Chuanshu/0000-0003-4133-5096 FU NCI NIH HHS [R01 CA103180, R01 CA094964, R01 CA112557]; NIEHS NIH HHS [R01 ES012451] NR 52 TC 15 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD APR PY 2007 VL 28 IS 4 BP 883 EP 891 DI 10.1093/carcin/bgl186 PG 9 WC Oncology SC Oncology GA 152HE UT WOS:000245351500015 PM 17065197 ER PT J AU Jaikumar, S Zhuang, Z Mannan, P Vortmeyer, AO Furuta, M Dickerman, R Bedanova, J Lonser, RR Walbridge, S Weil, RJ Lobanenkov, VV Oldfield, EH Pack, SD AF Jaikumar, Sivakumar Zhuang, Zhengping Mannan, Poonam Vortmeyer, Alexander O. Furuta, Makoto Dickerman, Rob Bedanova, Julia Lonser, Russell R. Walbridge, Stuart Weil, Robert J. Lobanenkov, Victor V. Oldfield, Edward H. Pack, Svetlana D. TI Interspecies comparative genomic hybridization (I-CGH) - A new twist to study animal tumor models SO CELL CYCLE LA English DT Article DE brain; glioblastoma multiforme; model; primate; radiation therapy; induced tumor; universal CGH ID HUMAN GLIOBLASTOMA-MULTIFORME; GROWTH-FACTOR RECEPTOR; SITU HYBRIDIZATION; GENETIC ALTERATIONS; CHROMOSOMAL-ABNORMALITIES; MACACA-MULATTA; HUMAN GLIOMAS; SOLID TUMORS; CELL-LINES; DELETIONS AB Animal models of human diseases are widely used to address questions of tumor development. Selection of a particular animal model depends upon a variety of factors, among them: animal cost, species lifespan and hardiness; availability of biomolecular and genetic tools for that species; and evolutionary distance from humans. In spite of the growth in genomic data in the past several years, many animal models cannot yet be studied extensively due to gaps in genetic mapping, sequencing and functional analyses. Thus, alternative molecular genetic approaches are needed. We have designed an interspecies comparative genomic hybridization approach to analyze genetic changes in radiation - induced brain tumors in the non - human primate, Macaca mulatta. Using homologies between the primate and human genomes, we adapted widely - available CGH techniques to generate cytogenetic profiles of malignant gliomas in four monkey tumors. Losses and gains were projected onto the corresponding homologous chromosomal regions in the human genome, thus directly translating the status of the monkey gliomas into human gene content. This represents a novel method of comparative interspecies cytogenetic mapping that permits simultaneous analysis of genomic imbalances of unknown sequences in disparate species and correlation with potential or known human disease - related genes. C1 NIAID, NIH, Immunopathol Lab, Rockville, MD 20852 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Pack, SD (reprint author), NIAID, NIH, Immunopathol Lab, 6540 Fishers Lane,Twinbrook 1 Bldg,Room 1329A, Rockville, MD 20852 USA. EM spack@niaid.nih.gov RI Pack, Svetlana/C-2020-2014; OI Lobanenkov, Victor/0000-0001-6665-3635 NR 42 TC 0 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD APR 1 PY 2007 VL 6 IS 7 BP 836 EP 842 PG 7 WC Cell Biology SC Cell Biology GA 155LB UT WOS:000245577800016 PM 17377495 ER PT J AU Scoltock, AB Heimlich, G Cidlowski, JA AF Scoltock, A. B. Heimlich, G. Cidlowski, J. A. TI Glucocorticoids inhibit the apoptotic actions of UV-C but not Fas ligand in hepatoma cells: direct evidence for a critical role of Bcl-x(L) SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; UV-C; Fas ligand; Bcl-x(L); glucocorticoids ID MAMMARY EPITHELIAL-CELLS; SIGNALING COMPLEX DISC; BCL-X GENE; CYTOCHROME-C; DEATH; RECEPTOR; DEXAMETHASONE; EXPRESSION; PATHWAYS; ACTIVATION AB Our laboratory has shown that glucocorticoids can inhibit apoptosis in rat hepatoma cells; however, the mechanisms are incompletely understood. To address this issue we sought to determine if glucocorticoid inhibition is effective when death is induced by stimuli that more selectively activate either the intrinsic (UV-C) or extrinsic (FasL) apoptotic pathways. Using flow cytometric analysis, we show that pretreatment of HTC cells with dexamethasone (Dex) inhibits UV-C-but not FasL-induced apoptosis. This inhibition requires Dex pretreatment and can be abrogated by the glucocorticoid antagonist RU486 indicating glucocorticoid receptor-mediated action. Dex increases anti-apoptotic Bcl-x(L) at both mRNA and protein levels. The Bcl-x(L) protein level remains elevated even after apoptosis induction with either UV-C or FasL although only UV-C-induced cell death is inhibited. Repression of Bcl-x(L) protein with siRNA abrogates the anti-apoptotic effect of glucocorticoids. Together these data provide direct evidence that Bcl-x(L) mediates glucocorticoid inhibition of UV-C induced apoptosis. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.nih.gov FU Intramural NIH HHS NR 43 TC 12 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD APR PY 2007 VL 14 IS 4 BP 840 EP 850 DI 10.1038/sj.cdd.4402071 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 148UV UT WOS:000245102900020 PM 17170751 ER PT J AU Pierson, TC Xu, Q Nelson, S Oliphant, T Nybakken, GE Fremont, DH Diamond, MS AF Pierson, Theodore C. Xu, Qing Nelson, Steevenson Oliphant, Theodore Nybakken, Grant E. Fremont, Daved H. Diamond, Michael S. TI The stoichiometry of antibody-mediated neutralization and enhancement of west nile virus infection SO CELL HOST & MICROBE LA English DT Article ID HUMANIZED MONOCLONAL-ANTIBODY; FLAVIVIRUS ENVELOPE PROTEIN; BORNE ENCEPHALITIS-VIRUS; YELLOW-FEVER VIRUS; DENGUE VIRUS; DEPENDENT ENHANCEMENT; DOMAIN-III; CRYSTAL-STRUCTURE; CELL LINE; SURFACE EPITOPES AB Antibody binding to the icosahedral arrangement of envelope proteins on the surface of flaviviruses can result in neutralization or enhancement of infection. We evaluated how many antibodies must bind to a given epitope on West Nile virus (WNV) to achieve neutralization. The most potent monoclonal antibodies (mAbs) block infection at concentrations that result in low occupancy of accessible sites on the virion, with neutralization occurring when as few as 30 of 180 envelope proteins are bound. In contrast, weakly neutralizing mAbs recognize fewer sites on the virion and require almost complete occupancy to inhibit WNV infection. For all mAbs studied, enhancement of infection is possible in cells bearing activating Fc-gamma receptors when the number of mAbs docked to the virion is not sufficient for neutralization. Thus, neutralization is best described by a model requiring "multiple hits" with the cumulative functional outcome determined by interplay between antibody affinity and epitope accessibility. C1 NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. RP Pierson, TC (reprint author), NIH, Viral Pathogenesis Sect, Viral Dis Lab, Bldg 10, Bethesda, MD 20892 USA. EM piersontc@mail.nih.gov FU Intramural NIH HHS [Z01 AI000957-03]; NCRR NIH HHS [F31 RR05074, F31 RR005074]; NIAID NIH HHS [U01 AI061373-01, U01 AI061373] NR 66 TC 152 Z9 157 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD APR PY 2007 VL 1 IS 2 BP 135 EP 145 DI 10.1016/j.chom.2007.03.002 PG 11 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 221BT UT WOS:000250203100008 PM 18005691 ER PT J AU Schieke, SM Finkel, T AF Schieke, Stefan M. Finkel, Toren TI TOR and aging: Less is more SO CELL METABOLISM LA English DT Editorial Material ID LIFE-SPAN; PATHWAY; YEAST AB Metabolism and mitochondrial activity are thought to be important determinants of life span. A new study in this issue of Cell Metabolism (Bonawitz et al., 2007) suggests that the TOR pathway controls mitochondrial respiration in yeast and that the harder mitochondria work, the longer yeast live. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 9 TC 17 Z9 17 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD APR PY 2007 VL 5 IS 4 BP 233 EP 235 DI 10.1016/j.cmet.2007.03.005 PG 3 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 154CJ UT WOS:000245484100003 PM 17403368 ER PT J AU Yang, YZ AF Yang, Yingzi TI Xom as a novel partner of Lef/Tcfs during dorsal-ventral patterning of the Xenopus embryo SO CELL RESEARCH LA English DT Editorial Material ID INDUCTION C1 NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. RP Yang, YZ (reprint author), NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NR 10 TC 3 Z9 6 U1 0 U2 1 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD APR PY 2007 VL 17 IS 4 BP 307 EP 308 DI 10.1038/cr.2007.29 PG 2 WC Cell Biology SC Cell Biology GA 169RM UT WOS:000246609400014 PM 17435774 ER PT J AU Wang, RX Han, GC Wang, JA Song, L Chen, GJ Xu, RA Yu, M Qian, JH Shen, BF Li, Y AF Wang, Renxi Han, Gencheng Wang, Jianan Song, Lun Chen, Guojiang Xu, Ruonan Yu, Ming Qian, Jiahua Shen, Beifen Li, Yan TI The role of STAT3 in antigen-IgG inducing regulatory CD4(+)Foxp3(+)T cells SO CELLULAR IMMUNOLOGY LA English DT Article DE STAT3; tolerance; Foxp3; treg cells; NOD mice ID GLUTAMIC-ACID DECARBOXYLASE; NONOBESE DIABETIC MICE; T-CELLS; DENDRITIC CELLS; FUSION PROTEINS; INNATE IMMUNITY; GENE-THERAPY; B-CELLS; CD4(+)CD25(+); TOLERANCE AB Unraveling the events that control the suppressive function of regulatory T (Treg) cells is extremely important because it will enable investigators to manipulate these cells to inhibit or enhance their functions as necessary. One of the members of the Signal Transducer and Activators of Transcription (STATs) family, STAT3, has emerged as a negative regulator of inflammatory responses. Here, we study the role of STAT3 in Treg cell induction. We found that GAD-IgG-transduced splenocytes induce a CD4(+)Foxp3(+)Treg cell increase in NOD mice. In parallel with the Treg cell increase, an IL-6-STAT3 signal pathway is activated. When STAT3 activation is blocked, GAD-specific tolerance disappears, the percentage of Treg cells decreases and IL-10 secretion is reduced in the splenocytes of NOD mice recipients of GAD-IgG-transduced splenocytes. Our findings indicate that transcription factor STAT3 plays an important role in immune tolerance. (C) 2007 Elsevier Inc. All rights reserved. C1 Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Beijing 100850, Peoples R China. NCI, NIH, Bethesda, MD 20892 USA. RP Li, Y (reprint author), Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Taiping Rd 27, Beijing 100850, Peoples R China. EM liyan62033@yahoo.com.cn NR 40 TC 7 Z9 8 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR PY 2007 VL 246 IS 2 BP 103 EP 109 DI 10.1016/j.cellimm.2007.07.001 PG 7 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 208GR UT WOS:000249308300006 PM 17697673 ER PT J AU Voth, DE Heinzen, RA AF Voth, Daniel E. Heinzen, Robert A. TI Lounging in a lysosome: the intracellular lifestyle of Coxiella burnetii SO CELLULAR MICROBIOLOGY LA English DT Review ID ACUTE Q-FEVER; PNEUMOPHILA DOT/ICM SYSTEM; NUCLEOTIDE-EXCHANGE FACTOR; IV SECRETION SYSTEM; HOST-CELL DEATH; LEGIONELLA-PNEUMOPHILA; PHASE-II; MYCOBACTERIUM-TUBERCULOSIS; PERITONEAL-MACROPHAGES; BACTERIAL PHAGOCYTOSIS AB Most intracellular parasites employ sophisticated mechanisms to direct biogenesis of a vacuolar replicative niche that circumvents default maturation through the endolysosomal cascade. However, this is not the case of the Q fever bacterium, Coxiella burnetii. This hardy, obligate intracellular pathogen has evolved to not only survive, but to thrive, in the harshest of intracellular compartments: the phagolysosome. Following internalization, the nascent Coxiella phagosome ultimately develops into a large and spacious parasitophorous vacuole (PV) that acquires lysosomal characteristics such as acidic pH, acid hydrolases and cationic peptides, defences designed to rid the host of intruders. However, transit of Coxiella to this environment is initially stalled, a process that is apparently modulated by interactions with the autophagic pathway. Coxiella actively participates in biogenesis of its PV by synthesizing proteins that mediate phagosome stalling, autophagic interactions, and development and maintenance of the mature vacuole. Among the potential mechanisms mediating these processes is deployment of a type IV secretion system to deliver effector proteins to the host cytosol. Here we summarize our current understanding of the cellular events that occur during parasitism of host cells by Coxiella. C1 NIAID, Coxiella Pathogenesis Sect, Lab Intracellular Parasites, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Lab Intracellular Parasites, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 115 TC 127 Z9 130 U1 2 U2 19 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2007 VL 9 IS 4 BP 829 EP 840 DI 10.1111/j.1462-5822.2007.00901.x PG 12 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 145RJ UT WOS:000244881900002 PM 17381428 ER PT J AU Alkhalil, A Hill, DA Desai, SA AF Alkhalil, Abdulnaser Hill, David A. Desai, Sanjay A. TI Babesia and plasmodia increase host erythrocyte permeability through distinct mechanisms SO CELLULAR MICROBIOLOGY LA English DT Article ID SURFACE ANION CHANNEL; FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; MALARIA PARASITE; PERMEATION PATHWAYS; TRANSPORT; BOVIS; MEMBRANE; NUCLEOSIDE; COMPONENTS AB Human erythrocytes infected with Plasmodium falciparum have markedly increased permeability to diverse solutes, many of which may be mediated by an unusual small conductance ion channel, the plasmodial surface anion channel (PSAC). Because these increases may be essential for parasite survival in the bloodstream, an important question is whether other intraerythrocytic parasites induce similar ion channels. Here, we examined this question using human erythrocytes infected with Babesia divergens, a distantly related apicomplexan parasite that can cause severe disease in immunocompromised humans. Osmotic lysis experiments after enrichment of infected erythrocytes with a new method revealed that these parasites also increase host permeability to various organic solutes. These permeability changes differed significantly from those induced by P. falciparum in transport rates, selectivity profiles and temperature dependence. Cell-attached and whole-cell patch-clamp experiments confirmed and extended these differences because neither PSAC-like channels nor significant increases in whole-cell anion conductance were seen after B. divergens infection. While both babesia and plasmodia increase host erythrocyte permeability to a diverse collection of organic solutes, they utilize fundamentally different mechanisms. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009; OI Hill, David/0000-0001-9286-4268 FU Intramural NIH HHS [Z01 AI000882-07] NR 36 TC 25 Z9 26 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2007 VL 9 IS 4 BP 851 EP 860 DI 10.1111/j.1462-5822.2006.00834.x PG 10 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 145RJ UT WOS:000244881900005 PM 17087736 ER PT J AU Liu, SH Leung, HJ Leppla, SH AF Liu, Shihui Leung, Howard J. Leppla, Stephen H. TI Characterization of the interaction between anthrax toxin and its cellular receptors SO CELLULAR MICROBIOLOGY LA English DT Article ID CAPILLARY MORPHOGENESIS PROTEIN-2; INFANTILE SYSTEMIC HYALINOSIS; ADP-RIBOSYLATING TOXINS; PROTECTIVE ANTIGEN; CRYSTAL-STRUCTURE; KINASE-KINASE; LETHAL FACTOR; TUMOR ENDOTHELIUM; CELLS; IDENTIFICATION AB Mutations in capillary morphogenesis gene 2 (CMG2), one of the two closely related proteins that act as anthrax toxin receptors, cause two rare human autosomal recessive conditions, juvenile hyaline fibromatosis (JHF) and infantile systemic hyalinosis (ISH). Here we demonstrate that CMG2 proteins with certain JHF- and ISH-associated single amino acid substitutions in their von Willebrand factor A domain or transmembrane region do not function as anthrax toxin receptors. However, an ISH-associated CMG2 variant having a truncated cytosolic domain does still function as an anthrax receptor, and in fact makes cells hyper-sensitive to toxin, distinguishing the roles of CMG2 in physiology and anthrax pathology. Site-specific mutagenesis was used to characterize the role that domain 2 of the anthrax toxin protective antigen (PA) plays in interaction with CMG2, focusing on the interaction between the PA 2 beta(3)-2 beta(4) loop and a pocket (Glu-122 pocket) adjacent to the metal ion-dependent adhesion site in CMG2. Substitutions that disrupted the salt bridge between PA Arg-344 and CMG2 Glu-122 decreased the affinity of PA to CMG2 three- to fourfold. Furthermore, mutation of CMG2 Tyr-119 (within the Glu-122 pocket) to His lowered the pH threshold for PA prepore-to-pore conversion in the endocytic pathway. C1 NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, Bethesda, MD 20892 USA. RP Liu, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, Lab Bacterial Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM shliu@niaid.nih.gov FU Intramural NIH HHS [Z99 AI999999, Z01 AI000929-05] NR 33 TC 40 Z9 41 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD APR PY 2007 VL 9 IS 4 BP 977 EP 987 DI 10.1111/j.1462-5822.2006.00845.x PG 11 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 145RJ UT WOS:000244881900015 PM 17381430 ER PT J AU Kim, WH Lee, JW Suh, YH Lee, HJ Lee, SH Oh, YK Gao, B Jung, MH AF Kim, Won-Ho Lee, June Woo Suh, Young Ho Lee, Hyun Jung Lee, Seung Hee Oh, Yeo Kyoung Gao, Bin Jung, Myeong Ho TI AICAR potentiates ROS production induced by chronic high glucose: Roles of AMPK in pancreatic beta-cell apoptosis SO CELLULAR SIGNALLING LA English DT Article DE type 2 diabetes; apoptosis; AMPK; glucokinase; high glucose; AICAR ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; N-TERMINAL KINASE; FATTY-ACID; GLUT4 TRANSLOCATION; SKELETAL-MUSCLE; STIMULATION; REPERFUSION; ISLETS; STRESS AB We previously demonstrated that chronic high glucose (33.3 mM) induced beta-cell dysfunction and apoptosis through glucokinase (GCK) downregulation, but the exact mechanisms involved remain unclear. Here, we show that prolonged exposure of 5-aminoimidazole-4-carboxamide (AICA)-riboside potentiated apoptosis induced by high glucose in MIN6N8 pancreatic beta-cells, correlating with enhanced GCK downregulation and decreased production of ATP and insulin. These events are potentiated in AMPK-overexpressing cells, but are prevented in cells transfected with mutant dominant-negative AMPK (AMPK-K45R). Furthermore, AMPK activation increases production of reactive oxygen species (ROS) and loss of mitochondria membrane potential induced by high glucose, which is significantly inhibited by treatment with compound C or by AMPK-K45R overexpression. Overexpression of GCK prevents apoptosis; decreased cellular ATP and insulin secretion, and ROS production enhanced by AICAR, but does not affect AMPK activation. Similar results are obtained using isolated primary islet cells. Collectively, these data demonstrate that AMPK activation potentiates beta-cell apoptosis induced by chronic high glucose through augmented GCK downregulation mediated by enhanced ROS production. (c) 2006 Elsevier Inc. All rights reserved. C1 Natl Int Hlth, Ctr Biomed Sci, Div Metab Dis, Seoul 122701, South Korea. Natl Int Hlth, Ctr Biomed Sci, Div Intractable Dis, Seoul 122701, South Korea. NIAAA, Lab Physiol Studies, Sect Liver Biol, NIH, Bethesda, MD 20892 USA. RP Jung, MH (reprint author), Natl Int Hlth, Ctr Biomed Sci, Div Metab Dis, 194 Tongillo, Seoul 122701, South Korea. EM jung0603@nih.go.kr NR 39 TC 61 Z9 65 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD APR PY 2007 VL 19 IS 4 BP 791 EP 805 DI 10.1016/j.cellsig.2006.10.004 PG 15 WC Cell Biology SC Cell Biology GA 148KP UT WOS:000245073600014 PM 17127032 ER PT J AU Lu, GW Chen, J Espinoza, LA Garfield, S Toshiyuki, S Akiko, H Huppler, A Wang, QJ AF Lu, Ganwei Chen, Jun Espinoza, Luis A. Garfield, Susan Toshiyuki, Saito Akiko, Havashi Huppler, Anna Wang, Q. Jane TI Protein kinase D 3 is localized in vesicular structures and interacts with vesicle-associated membrane protein 2 SO CELLULAR SIGNALLING LA English DT Article DE PKD3; localization; vesicle; trafficking; VAMP2; phorbol ester ID PROTEIN-KINASE-D; TRANS-GOLGI NETWORK; MEMBRANE-FUSION; PLASMA-MEMBRANE; SNARE PROTEINS; INTRACELLULAR REDISTRIBUTION; NEUROTRANSMITTER RELEASE; GLUCOSE-TRANSPORT; SYNAPTIC VESICLE; PHORBOL ESTERS AB Protein kinase D localizes in the Golgi and regulates protein transport from the Golgi to the plasma membrane. In the present study, we found that PKD3, a novel member of the PKD family, and its fluorescent protein fusions localized in the Golgi and in the vesicular structures that are in part marked by endosome markers. Fluorescent recovery after photobleaching (FRAP) showed that the PKD3-associated vesicular structures were constantly forming and dissolving, reflecting active subcellular structures. FRAP on plasma membrane-located PKD3 indicated a slower recovery of PKD3 fluorescent signal compared to those of PKC isoforms, implying a different targeting mechanism at the plasma membrane. VAMP2, the vesicle-localized v-SNARE, was later identified as a novel binding partner of PKD3 through yeast two-hybrid screening. PKD3 directly interacted with VAMP2 in vitro and in vivo, and colocalized in part with VAMP2 vesicles in cells. PKD3 did not phosphorylate VAMP-GFP and the purified GST-VAMP2 protein in in vitro phosphorylation assays. Rather, PKD3 was found to promote the recruitment of VAMP2 vesicles to the plasma membrane in response to PMA, while the kinase dead PKD3 abolished this effect. Thus, the kinase activity of PKD3 was required for PMA-induced plasma membrane trafficking of VAMP2. In summary, our findings suggest that PKD3 localizes to vesicular structures that are part of the endocytic compartment. The vesicular distribution may be attributed in part to the direct interaction between PKD3 and vesicle-associated membrane protein VAMP2, through which PKD3 may regulate VAMP2 vesicle trafficking by facilitating its recruitment to the target membrane. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Mol Mech Tumor Promot Sect, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Natl Inst Radiol Sci, Genome Res Grp, Inage Ku, Chiba 2638555, Japan. RP Wang, QJ (reprint author), Univ Pittsburgh, Dept Pharmacol, E1354 Biomed Sci Tower, Pittsburgh, PA 15261 USA. EM qjw1@pitt.edu RI Wang, Qiming/B-6064-2012 FU NIDDK NIH HHS [1 R01 DK066168-01] NR 39 TC 19 Z9 22 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD APR PY 2007 VL 19 IS 4 BP 867 EP 879 DI 10.1016/j.cellsig.2006.10.012 PG 13 WC Cell Biology SC Cell Biology GA 148KP UT WOS:000245073600021 PM 17196367 ER PT J AU van Breemen, RB Fong, HHS Farnsworth, NR AF van Breemen, Richard B. Fong, Harry H. S. Farnsworth, Norman R. TI The role of quality assurance and standardization in the safety of botanical dietary supplements SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PC-SPES; LIQUID-CHROMATOGRAPHY; CIMICIFUGA-RACEMOSA; PROSTATE-CANCER; GINSENG; IDENTIFICATION; CONTAMINATION; CONSTITUENTS; HEALTH; TRENDS C1 Univ Illinois, UIC, NIH, Ctr Bot Dietary,Dept Med Chem & Pharmacognosy,Col, Chicago, IL 60612 USA. RP van Breemen, RB (reprint author), Univ Illinois, UIC, NIH, Ctr Bot Dietary,Dept Med Chem & Pharmacognosy,Col, 8333 S Wood St, Chicago, IL 60612 USA. EM breemen@uic.edu FU NCCIH NIH HHS [P50 AT000155, P50 AT000155-090003, P50 AT00155, P50 AT000155-099004] NR 31 TC 20 Z9 21 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2007 VL 20 IS 4 BP 577 EP 582 DI 10.1021/tx7000493 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 157AD UT WOS:000245690100003 PM 17362032 ER PT J AU Yagi, H Frank, H Seidel, A Jerina, DM AF Yagi, Haruhiko Frank, Heinrich Seidel, Albrecht Jerina, Donald M. TI Synthesis and absolute configuration of cis- and trans-opened cyclopenta[cd]pyrene 3,4-oxide N-2-deoxyguanosine adducts: Conversion to phosphoramidites for oligonucleotide synthesis SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBON; 7,8-DIOL 9,10-EPOXIDE ADDUCTS; TUMOR-INITIATING ACTIVITY; DNA-ADDUCTS; DEOXYGUANOSINE; CYCLOPENTAPYRENE; BENZOPYRENE; EPOXIDE; ACID; CYCLOPENTAPYRENE AB Fluorinated alcohols such as trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) catalyze addition of the N-2-amino group of O-6-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine (3) to cyclopenta[cd]pyrene 3,4-oxide (CPPO). The reaction occurs via a carbocation intermediate at C-3 such that cis- and trans-opened dGuo adducts are formed in a combined yield of similar to 37% together with the 4-ketone and a cis-opened solvent adduct. Fluorinated alcohol-mediated regioselective substitution at C-3 of the CPP cis- (11) and trans-3,4-dihydrodiol diacetates (15) with the N-2-amino group of 3 proceeded smoothly to give the O-6-allyl di-(tert-butyldimethylsilyl) cis- and trans-opened dGuo-adduct acetates (8a, b and 9a,b) in 75-85% yields. The cis-opened adducts predominated (56-70%) from both 11 and 15. Interestingly, trans-3-acetoxy-4-bromo-3,4-dihydro-CPP and 3 in TFE or HFP gave a mixture of 8a,b and 9a,b in 75-85% yield with cis:trans adduct ratios similar to those observed for 11 and 15. This observation is consistent with initial formation of a cyclic acetoxonium intermediate ollowed by formation of the same carbocation as that derived from 11 or 15. Absolute configurations of 8a,b and 9a,b were assigned by using enantiomerically pure (+)-trans-[3S.4S]-dihydrodiol as the starting material, which afforded a single cis-[3R,4S]-dGuo adduct and a single trans-[3S,4S]-dGuo adduct. The optically active trans-3,4-dihydrodiols were obtained by HPLC separation of their bis-(-)-menthoxyacetates. Their absolute configuration was determined by several empirical methods in addition to application of the exciton chirality CD method to their bis-(p-N,N-dimethylamino)benzoates. Removal of all blocking groups from the protected cis- and trans-opened dGuo adducts (8a,b and 9a,b) in three steps (overall yields of > 70%) gave the free dGuo adducts, which are useful markers for DNA-binding studies. Adducts 8a, b and 9a,b were also converted to the appropriately protected phosphoramidites in three steps (overall yields of 72-81%). C1 NIDDK, Sect Oxidat Mechanisms, NIH, Lab Bioorgan Chem, Bethesda, MD 20892 USA. Grimmer Fdn, Biochem Inst Environm Carcinogens, D-22927 Grosshansdorf, Germany. RP Jerina, DM (reprint author), NIDDK, Sect Oxidat Mechanisms, NIH, Lab Bioorgan Chem, Bldg 8A,Rm 1A01, Bethesda, MD 20892 USA. EM dmjerina@nih.gov FU Intramural NIH HHS NR 42 TC 3 Z9 3 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2007 VL 20 IS 4 BP 650 EP 661 DI 10.1021/tx600286z PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 157AD UT WOS:000245690100013 PM 17355153 ER PT J AU Goldstein, DS Sharabi, Y Karp, BI Bentho, O Saleem, A Pacak, K Eisenhofer, G AF Goldstein, David S. Sharabi, Yehonatan Karp, Barbara I. Bentho, Oladi Saleem, Ahmed Pacak, Karel Eisenhofer, Graeme TI Cardiac sympathetic denervation preceding motor signs in Parkinson disease SO CLINICAL AUTONOMIC RESEARCH LA English DT Article DE Parkinson disease; sympathetic nervous system; baroreflex; heart; imaging techniques; autonomic nervous system ID MULTIPLE SYSTEM ATROPHY; CARDIOVASCULAR DYSAUTONOMIA; ORTHOSTATIC HYPOTENSION; CATECHOLAMINES; FAILURE AB There is substantial interest in identifying biomarkers to detect early Parkinson disease (PD). Cardiac noradrenergic denervation and attenuated baroreflex-cardiovagal function occur in de novo PD, but whether these abnormalities can precede PD has been unknown. Here we report the case of a patient who had profoundly decreased left ventricular myocardial 6-[F-18]fluorodopamine-derived radioactivity and low baroreflex-cardiovagal gain, 4 years before the onset of symptoms and signs of PD. The results lead us to hypothesize that cardiac noradrenergic denervation and decreased baroreflex-cardiovagal function may occur early in the pathogenesis of PD. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Clin Neurosci Program, Bethesda, MD USA. Natl Inst Child Hlth & Dev, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10 Room 6N252, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov FU Intramural NIH HHS [Z99 NS999999] NR 23 TC 52 Z9 53 U1 0 U2 2 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD APR PY 2007 VL 17 IS 2 BP 118 EP 121 DI 10.1007/s10286-007-0396-1 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 168JZ UT WOS:000246522200012 PM 17334896 ER PT J AU Eiseman, JL Guo, JX Ramanathan, RK Belani, CP Solit, DB Scher, HI Ivy, SP Zuhowski, EG Egorin, MJ AF Eiseman, Julie L. Guo, Jianxia Ramanathan, Ramesh K. Belani, Chandra P. Solit, David B. Scher, Howard I. Ivy, S. Percy Zuhowski, Eleanor G. Egorin, Merrill J. TI Evaluation of plasma insulin-like growth factor binding protein 2 and Her-2 extracellular domain as biomarkers for 17-allylamino-17-demethoxygeldanamycin treatment of adult patients with advanced solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol ID FACTOR-BINDING PROTEIN-2; ACUTE LYMPHOBLASTIC-LEUKEMIA; EPITHELIAL OVARIAN-CANCER; HUMAN-BREAST CANCER; II IGF-II; PHASE-I; CEREBROSPINAL-FLUID; PROSTATE-CANCER; ELEVATED LEVELS; NEU ONCOGENE AB Purpose: Interaction of 17-allylamino-17-demethoxygeldanamycin (17-AAG) with heat shock protein 90 results in proteasomal degradation of many proteins, including Her-2-neu, with subsequent decreased expression of insulin-like growth factor binding protein-2 (IGFBP-2). Concentrations of both IGFBP-2 and Her-2 extracellular domain (Her-2 ECD) in sera of mice bearing BT474 human breast cancer xenografts decrease after 17-AAG treatment. We investigated whether this phenomenon occurred in patients. Materials and Methods: Eight to 15 plasma samples were obtained between 0 and 72 h from 27 patients treated with single-agent 17-AAG at doses between 10 and 307 mg/m(2) and 18 patients treated with 17-AAG at doses between 220 and 450 mg/m(2) combined with 70 to 75 mg/m(2) of clocetaxel. Pretreatment plasma samples were also obtained from 12 healthy volunteers. Plasma IGFBP-2 and Her-2 ECD concentrations were quantitated by ELISA. Results: Pretreatment plasma IGFBP-2 concentrations in patients (171 +/- 116 ng/mL) were 2-fold higher than those in healthy volunteers (85 +/- 44 ng/mL; P < 0.05). Following 17-AAG treatment, there were no consistent dose-dependent or time-dependent changes in plasma IGFBP-2 and Her-2 ECD concentrations. IGFBP-2 concentrations decreased by >= 40% in 8 patients, increased 2- to 5-fold in 8 patients, and remained essentially unchanged in 29 patients. Her-2 ECD concentrations decreased by >= 40% in 10 patients, increased 1.5- to 5-fold in 2 patients, and remained essentially unchanged in 25 patients. Conclusions: As previously reported, IGFBP-2 concentrations in plasma of cancer patients are significantly higher than those in healthy volunteers. In contrast to a mouse model, 17-AAG treatment was not consistently associated with decreases in IGFBP-2 or Her-2 ECD concentrations in patient plasma. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15261 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA. RP Eiseman, JL (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Room G27B,Hillman Res Pavil,5117 Ctr Ave, Pittsburgh, PA 15213 USA. EM eisemanj@msx.upmc.edu OI Belani, Chandra/0000-0001-5049-5329 FU NCI NIH HHS [P30CA47904, UO1-CA-099168, UO1-CA69855]; NCRR NIH HHS [M01 RR 00056] NR 47 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2121 EP 2127 DI 10.1158/1078-0432.CCR-06-2286 PG 7 WC Oncology SC Oncology GA 156PG UT WOS:000245660800024 PM 17404095 ER PT J AU Varticovski, L Hollingshead, MG Robles, AI Wu, XL Cherry, J Munroe, DJ Lukes, L Anver, MR Carter, JP Borgel, SD Stotler, H Bonomi, CA Nunez, NP Hursting, SD Qiao, WH Deng, CXX Green, JE Hunter, KW Merlino, G Steeg, PS Wakefield, LM Barrett, JC AF Varticovski, Lyuba Hollingshead, Melinda G. Robles, Ana I. Wu, Xiaolin Cherry, James Munroe, David J. Lukes, Luanne Anver, Miriam R. Carter, John P. Borgel, Suzanne D. Stotler, Howard Bonomi, Carrie A. Nunez, Nomeli P. Hursting, Stephen D. Qiao, Wenhui Deng, Chuxia X. Green, Jeff E. Hunter, Kent W. Merlino, Glenn Steeg, Patricia S. Wakefield, Lalage M. Barrett, J. Carl TI Accelerated preclinical testing using transplanted tumors from genetically engineered mouse breast cancer models SO CLINICAL CANCER RESEARCH LA English DT Article ID CLINICAL DRUG DEVELOPMENT; GENE-EXPRESSION; TRANSGENIC MICE; IN-VITRO; ORTHOTOPIC MODELS; MAMMARY-TUMORS; NUDE-MICE; CELL-LINE; SCID MICE; PROGRESSION AB Purpose: The use of genetically engineered mouse (GEM) models for preclinical testing of anticancer therapies is hampered by variable tumor latency, incomplete penetrance, and complicated breeding schemes. Here, we describe and validate a transplantation strategy that circumvents some of these difficulties. Experimental Design: Tumor fragments from tumor-bearing MMTV-PyMT or cell suspensions from MMTV-PyMT, -Her2/neu, -wnt1, -wnt1/p53(+/-), BRCA1/p53(+/-), and C3(1) T-Ag mice were transplanted into the mammary fat pad or s.c. into naive syngeneic or immunosuppressed mice. Tumor development was monitored and tissues were processed for histopathology and gene expression profiling. Metastasis was scored 60 days after the removal of transplanted tumors. Results: PyMT tumor fragments and cell suspensions from anterior glands grew faster than posterior tumors in serial passages regardless of the site of implantation. Microarray analysis revealed genetic differences between these tumors. The transplantation was reproducible using anterior tumors from multiple GEM, and tumor growth rate correlated with the number of transplanted cells. Similar morphologic appearances were observed in original and transplanted tumors. Metastasis developed in >90% of mice transplanted with PyMT 40% with BRCA1/p53(+/-) and wntl/p53(+/-), and 15% with Her2/neu tumors. Expansion of PyMT and wnt1 tumors by serial transplantation for two passages did not lead to significant changes in gene expression. PyMT-transplanted tumors and anterior tumors of transgenic mice showed similar sensitivities to cyclophosphamide and paclitaxel. Conclusions: Transplantation of GEM tumors can provide a large cohort of mice bearing mammary tumors at the same stage of tumor development and with defined frequency of metastasis in a well-characterized molecular and genetic background. C1 NCI, Ctr Canc Res, Frederick, MD 21701 USA. Div Canc Treatment & Diag, Dev Therapeut Program, Frederick, MD USA. Sci Applicat Int Corp, Frederick Inc, Frederick, MD USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Varticovski, L (reprint author), 37 Convent Dr,Room 3060, Bethesda, MD 20892 USA. EM varticol@mail.nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 37 TC 35 Z9 35 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2168 EP 2177 DI 10.1158/1078-0432.CCR-06-0918 PG 10 WC Oncology SC Oncology GA 156PG UT WOS:000245660800030 PM 17404101 ER PT J AU Granville, CA Warfel, N Tsurutani, J Hollander, MC Robertson, M Fox, SD Veenstra, TD Issaq, HJ Linnoila, RI Dennis, PA AF Granville, Courtney A. Warfel, Noel Tsurutani, Junji Hollander, M. Christine Robertson, Matthew Fox, Stephen D. Veenstra, Timothy D. Issaq, Haleem J. Linnoila, R. Ilona Dennis, Phillip A. TI Identification of a highly effective rapamycin schedule that markedly reduces the size, multiplicity, and phenotypic progression of tobacco carcinogen-induced murine lung tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID BREAST-CANCER; GENETIC SUSCEPTIBILITY; MAMMALIAN TARGET; AKT ACTIVATION; BETA-CAROTENE; K-RAS; PREVENTION; TRIAL; MICE; INHIBITION AB Purpose: Human and murine preneoplastic lung lesions induced by tobacco exposure are characterized by increased activation of the Akt/mammalian target of rapamycin (mTOR) pathway, suggesting a role for this pathway in lung cancer development. To test this, we did studies with rapamycin, an inhibitor of mTOR, in A/J mice that had been exposed to the tobacco-specific carcinogen 4- (methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Experimental Design: Tumorigenesis was induced by i.p. injection of NNK, and rapamycin was administered 1 or 26 weeks after NNK administration. Biomarkers associated with mTOR inhibition were assessed in lung and/or surrogate tissues using immunohistochemistry and immunoblotting. Rapamycin levels were measured using mass spectroscopy. Results: Rapamycin was administered on a daily (5 of 7 days) regimen beginning 26 weeks after NNK decreased tumor size, proliferative rate, and mTOR activity. Multiplicity was not affected. Comparing this regimen with an every-other-clay (clod) regimen revealed that rapamycin levels were better maintained with qod administration, reaching a nadir of 16.4 ng/mL, a level relevant in humans. When begun 1 week after NNK, this regimen was well tolerated and decreased tumor multiplicity by 90%. Tumors that did develop showed decreased phenotypic progression and a 74% decrease in size that correlated with decreased proliferation and inhibition of mTOR. Conclusions: Tobacco carcinogen - induced lung tumors in A/J mice are dependent upon mTOR activity because rapamycin markedly reduced the development and growth of tumors. Combined with the Food and Drug Administration approval of rapamycin and broad clinical experience, these studies provide a rationale to assess rapamycin in trials with smokers at high risk to develop lung cancer. C1 NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20889 USA. NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. George Washington Univ, Inst Biomed Sci, Washington, DC USA. Sci Applicat Int Corp, Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD USA. RP Dennis, PA (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Room 5101,Bldg 8,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov FU NCI NIH HHS [N01-CO1244] NR 44 TC 63 Z9 67 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2007 VL 13 IS 7 BP 2281 EP 2289 DI 10.1158/1078-0432.CCR-06-2570 PG 9 WC Oncology SC Oncology GA 156PG UT WOS:000245660800042 PM 17404113 ER PT J AU Hortin, GL AF Hortin, Glen L. TI A new era in protein quantification in clinical laboratories: Application of liquid chromatography-tandem mass spectrometry SO CLINICAL CHEMISTRY LA English DT Editorial Material ID ABSOLUTE QUANTIFICATION; PROTEOMICS; STANDARDS; SERUM; PEPTIDES C1 NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Dept Lab Med, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 15 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2007 VL 53 IS 4 BP 543 EP 544 DI 10.1373/clinchem.2006.083857 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 156ID UT WOS:000245640400001 PM 17405946 ER PT J AU Marcovina, S Bowsher, RR Miller, WG Staten, M Myers, G Caudill, SP Campbell, SE Steffes, MW AF Marcovina, Santica Bowsher, Ronald R. Miller, W. Greg Staten, Myrlene Myers, Gary Caudill, Samuel P. Campbell, Scott E. Steffes, Michael W. CA Insulin Standardization Workgrp TI Standardization of insulin immunoassays: Report of the American Diabetes Association Workgroup SO CLINICAL CHEMISTRY LA English DT Article ID PROINSULIN AB Background: Circulating insulin concentration in serum or plasma provides important information for the estimation of insulin secretion and insulin resistance. Currently, lack of standardization of insulin assays hinders efforts to achieve consistent measures for treatment guidelines. Methods: A Workgroup convened by the American Diabetes Association evaluated 12 different commercial insulin methods from 9 manufacturers. Results: The within-assay CVs ranged from 3.7% to 39.0%, with 7 of 10 assays having a CV <= 10.6%. The among-assay CVs ranged from 12% to 66%, with a median value of 24%. A common insulin reference preparation did not change the among-assay CV and failed to improve harmonization of results among assays. Results from 6 of 10 assays agreed within the total error of 32% that is allowable based on biological variability criteria. Seven of 10 assays recovered insulin added to a serum pool within 15.5% of the expected concentration. in 9 of 10 methods, there was < 2% cross-reactivity with intact human proinsulin, and 8 of 10 methods had < 3% cross-reactivity with split (32, 33) proinsulin. For 9 of 10 assays, the cross-reactivity of des (64,65) proinsulin exceeded 40%. Overall, most assays had acceptable imprecision and specificity for insulin. Conclusion: The discordance in test results for commercial insulin reagent sets is likely multifactorial and Will 9 require a continuing effort to understand the differences and achieve the desired consistency and harmonization among commercial immunoassays. (c) 2007 American Association for Clinical Chemistry. C1 Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Washington, NW Lipid Metab & Diabet Res Lab, Seattle, WA 98195 USA. LINCO Diagnost Serv, St Charles, MO USA. B2S Consulting, Beech Grove, IN USA. Virginia Commonwealth Univ, Dept Pathol, Richmond, VA 23284 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Lab Serv, Atlanta, GA USA. Amer Diabet Assoc, Alexandria, VA USA. RP Steffes, MW (reprint author), Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. EM steff001@umn.edu NR 8 TC 61 Z9 62 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2007 VL 53 IS 4 BP 711 EP 716 DI 10.1373/clinchem.2006.082214 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 156ID UT WOS:000245640400023 PM 17272483 ER PT J AU Levey, AS Coresh, J Greene, T Marsh, J Stevens, LA Kusek, JW Van Lente, F AF Levey, Andrew S. Coresh, Josef Greene, Tom Marsh, Jane Stevens, Lesley A. Kusek, John W. Van Lente, Frederick CA Chronic Kidney Dis Epidemiolo TI Expressing the modification of diet in renal disease study equation for estimating glomerular filtration rate with standardized serum creatinine values SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Nephrology CY NOV 08-13, 2005 CL Philadelphia, PA SP Amer Soc Nephrol ID CHRONIC KIDNEY-DISEASE; COCKCROFT-GAULT EQUATIONS; PREDICTIVE PERFORMANCE; POSITION STATEMENT; GFR; FORMULA; TRANSPLANTATION; CLASSIFICATION; CALIBRATION; CLEARANCE AB Purpose: We sought to reexpress the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation for estimation of glomerular filtration rate (GFR) using serum creatinine (S-cr) standardized to reference methods. Methods: Serum specimens included creatinine reference materials prepared by the College of American Pathologists (CAP), traceable to primary reference material at the NIST, with assigned values traceable to isotope dilution mass spectrometry (IDMS), a calibration panel prepared by the Cleveland Clinic Research Laboratory (CCRL), and frozen samples from the MDRD Study. Split specimens were measured at the CCRL using the Roche enzymatic and Beckman CX3 kinetic alkaline picrate assays. Results: Roche enzymatic assay results on CAP samples were comparable to IDMS-assigned values. Beckman CX3 assay results in 2004-2005 were significantly higher than but highly correlated with simultaneous. Roche enzymatic assay results (r(2) = 0.9994 on 40 CCRL samples) and showed minimal but significant upward drift from Beckman CX3 assay results during the MDRD Study in 1989-1991 (r(2) = 0.9987 in 253 samples). Combining these factors, standardized S-cr = 0.95 X original MDRD Study S-cr. The reexpressed 4-variable MDRD Study equation for S-cr (mg/dL) is GFR = 175 X standardized S-cr(-1.154) X age(-0.203) x 1.212 (if black) X 0.742 (if female), and for S-cr (mu mol/L) is GFR = 30849 X standardized S-cr(-1.154) X age(-0.203) X 1.212 (if black) X 0.742 (if female) [GFR in mL . min(-1) . (1.73 m(2))(-1)]. Conclusion: When the calibration Of S-cr methods is traceable to the S-cr reference system, GFR should be estimated using the MDRD Study equation that has been reexpressed for standardized S-cr. (c) 2007 American Association for Clinical Chemistry. C1 Tufts Univ, New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. NIDDKD, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH 44195 USA. RP Stevens, LA (reprint author), Tufts Univ, New England Med Ctr, Div Nephrol, 750 Washington St,Box 391, Boston, MA 02111 USA. EM lstevens1@tufts-nemc.org FU NIDDK NIH HHS [U01 DK 35073, U01 DK 053869, U01 DK 067651] NR 38 TC 830 Z9 866 U1 2 U2 20 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2007 VL 53 IS 4 BP 766 EP 772 DI 10.1373/clinchem.2006.077180 PG 7 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 156ID UT WOS:000245640400031 PM 17332152 ER PT J AU Bruce, B Khanna, G Ren, L Landberg, G Jirstrom, K Powell, C Borczuk, A Keller, ET Wojno, KJ Meltzer, P Baird, K McClatchey, A Bretscher, A Hewitt, SM Khanna, C AF Bruce, Benjamin Khanna, Gaurav Ren, Ling Landberg, Goran Jirstrom, Karin Powell, Charles Borczuk, Alain Keller, Evan T. Wojno, Kirk J. Meltzer, Paul Baird, Kristin McClatchey, Andrea Bretscher, Anthony Hewitt, Stephen M. Khanna, Chand TI Expression of the cytoskeleton linker protein ezrin in human cancers SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ezrin; merlin; immunohistochemistry; tissue microarray; biomarker; prognosis ID NF2 TUMOR-SUPPRESSOR; C-TERMINAL DOMAIN; ERM PROTEINS; TISSUE MICROARRAY; STROMAL CELLS; METASTASIS; MERLIN; BINDING; HEMANGIOBLASTOMA; TUMORIGENESIS AB Expression of the metastasis-associated protein, ezrin, in over 5,000 human cancers and normal tissues was analyzed using tissue microarray immunohistochemistry. Ezrin staining was compared between cancers and their corresponding normal tissues, between cancers of epithelial and mesenchymal origin, in the context of the putative inhibitor protein, merlin, and against clinicopathological data available for breast, lung, prostate cancers and sarcomas. Ezrin was found in most cancers and normal tissues at varying levels of intensity. In general ezrin was expressed at higher levels in sarcomas than in carcinomas. By normalizing the expression of ezrin in each cancer using ezrin expression found in the corresponding normal tissue, significant associations between ezrin were found in advancing histological grade in sarcomas (P = 0.02) and poor outcome in breast cancer (P = 0.025). Clinicopathologic associations were not changed by simultaneous assessment of ezrin and merlin in each patient sample for the cancer types examined. These data support a role for ezrin in the biology of human cancers and the need for additional studies in breast cancer and sarcoma patients that may validate ezrin as a marker of cancer progression and as a potential target for cancer therapy. C1 NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD USA. Lund Univ, Malmo Univ Hosp, S-20502 Malmo, Sweden. Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA. NHGRI, Canc Genet Branch, Bethesda, MD USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Dept Pathol, Charlestown, MA USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY USA. Natl Canc Inst, Ctr Canc Res, Pathol Lab, Tissue Army Res Program, Bethesda, MD USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Bethesda, MD 20892 USA. EM khannac@mail.nih.gov RI Keller, Evan/M-1446-2016; OI Keller, Evan/0000-0002-7592-7535; POWELL, CHARLES/0000-0003-3509-891X; Hewitt, Stephen/0000-0001-8283-1788 FU Intramural NIH HHS; NCI NIH HHS [1P50 CA69568, P01 CA093900] NR 33 TC 70 Z9 89 U1 1 U2 9 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD APR PY 2007 VL 24 IS 2 BP 69 EP 78 DI 10.1007/s10585-006-9050-x PG 10 WC Oncology SC Oncology GA 162QM UT WOS:000246103400001 PM 17370041 ER PT J AU Nelson, JM Chiller, TM Powers, JH Angulo, FJ AF Nelson, Jennifer M. Chiller, Tom M. Powers, John H. Angulo, Frederick J. TI Fluoroquinolone-resistant Campylobacter species and the withdrawal of fluoroquinolones from use in poultry: A public health success story SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID JEJUNI INFECTIONS; UNITED-STATES; RISK-FACTORS; CIPROFLOXACIN; QUINOLONE; COLI; SUSCEPTIBILITY; IDENTIFICATION; CONSEQUENCES; SALMONELLA AB Campylobacter species cause 1.4 million infections each year in the United States. Fluoroquinolones (e.g., ciprofloxacin) are commonly used in adults with Campylobacter infection and other infections. Fluoroquinolones (e.g., enrofloxacin) are also used in veterinary medicine. Human infections with fluoroquinolone- resistant Campylobacter species have become increasingly common and are associated with consumption of poultry. These findings, along with other data, prompted the US Food and Drug Administration to propose the withdrawal of fluoroquinolone use in poultry in 2000. A lengthy legal hearing concluded with an order to withdraw enrofloxacin from use in poultry (effective in September 2005). Clinicians are likely to continue to encounter patients with fluoroquinolone- resistant Campylobacter infection and other enteric infection because of the continued circulation of fluoroquinolone- resistant Campylobacter species in poultry flocks and in persons returning from foreign travel who have acquired a fluoroquinolone- resistant enteric infection while abroad. Judicious use of fluoroquinolones and other antimicrobial agents in human and veterinary medicine is essential to preserve the efficacy of these important chemotherapeutic agents. C1 Ctr Dis Control & Prevent, Enter Dis Epidemiol Branch, Div Foodborne Bacterial & Mycot Dis, Natl Ctr Zoonot Vectorborne & Enter Dis, Atlanta, GA 30333 USA. NIAID, NIH, Bethesda, MD 20892 USA. Atlanta Res & Educ Fdn, Atlanta, GA USA. RP Angulo, FJ (reprint author), Ctr Dis Control & Prevent, Enter Dis Epidemiol Branch, Div Foodborne Bacterial & Mycot Dis, Natl Ctr Zoonot Vectorborne & Enter Dis, 1600 Clifton Rd,MS D-63, Atlanta, GA 30333 USA. EM fangulo@cdc.gov NR 33 TC 155 Z9 167 U1 0 U2 22 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 APR 1 PY 2007 VL 44 IS 7 BP 977 EP 980 DI 10.1086/512369 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 143KY UT WOS:000244721600017 PM 17342653 ER PT J AU Zajicek, A Giacoia, GP AF Zajicek, A. Giacoia, G. P. TI Obstetric clinical pharmacology: Coming of age SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID PREGNANCY; PHARMACOKINETICS; TRANSPORT AB Little is known about changes in drug disposition and effect during pregnancy. In this issue, which is devoted to maternal and child health, Andrew and colleagues(1) from the University of Washington present research describing significant changes in the disposition of amoxicillin during pregnancy. The clinical significance is the potential for inadequate dosing during pregnancy of compounds that are renally cleared. Further research is needed to guide the appropriate, safe, and effective medical treatment of pregnant women. In 2003, the National Institute of Child Health and Human Development (NICHD) formed the Obstetric Pharmacology Research Units Network. This network serves in part as a proof-of-concept platform, to demonstrate that clinical investigations can be performed in pregnant women. C1 NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. RP Zajicek, A (reprint author), NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA. EM zajiceka@mail.nih.gov NR 9 TC 19 Z9 19 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2007 VL 81 IS 4 BP 481 EP 482 DI 10.1038/sj.clpt.2007.6100136 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 153LJ UT WOS:000245435900004 PM 17375105 ER PT J AU Dye, BA Barker, LK Selwitz, RH Lewis, BG Wu, T Fryar, CD Ostchega, Y Beltran, ED Ley, E AF Dye, B. A. Barker, L. K. Selwitz, R. H. Lewis, B. G. Wu, T. Fryar, C. D. Ostchega, Y. Beltran, E. D. Ley, E. TI Overview and quality assurance for the National Health and Nutrition Examination Survey (NHANES) oral health component, 1999-2002 SO COMMUNITY DENTISTRY AND ORAL EPIDEMIOLOGY LA English DT Article DE data reliability; dental public health; epidemiology; NHANES; oral health; quality assurance ID RELIABILITY; KAPPA; AGREEMENT AB The Oral Health Component of the 1999-2002 National Health and Nutrition Examination Survey (NHANES) is a collaborative effort between the National Institute of Dental and Craniofacial Research (NIDCR), the National Center for Chronic Disease Prevention and Health Promotion, Division of Oral Health (NCCDPHP/DOH), and the National Center for Health Statistics (NCHS). The current NHANES is designed as a continuous survey with data released on a 2-year cycle to represent the civilian, non-institutionalized population of the US. Oral health data are currently available for 8082 and 9010 persons aged >= 2 years who participated in the 1999-2000 and 2001-2002 NHANES, respectively. This article provides background information on previous national examination surveys with oral health content. It also provides general analytical considerations, oral health content information, and evaluations of data quality in terms of examiner reliability statistics (percent agreements, kappa, and correlation coefficients) for the 1999-2002 NHANES Oral Health Component. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Univ Maryland, Sch Dent, Baltimore, MD 21201 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Oral Hlth, Atlanta, GA USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ Minnesota, Duluth, MN 55812 USA. Westat Corp, Rockville, MD USA. RP Dye, BA (reprint author), NHANES Program, NCHS, CDC, 3311 Toledo Rd,RM 4416, Hyattsville, MD 20782 USA. EM bfd1@cdc.gov NR 18 TC 34 Z9 34 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-5661 J9 COMMUNITY DENT ORAL JI Community Dentist. Oral Epidemiol. PD APR PY 2007 VL 35 IS 2 BP 140 EP 151 DI 10.1111/j.1600-0528.2007.00310.x PG 12 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 140YF UT WOS:000244542100007 PM 17331155 ER PT J AU Gladwin, M AF Gladwin, M. TI Unraveling the reactions of nitrite and hemoglobin in signaling, physiology and therapeutics SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-MOLECULAR & INTEGRATIVE PHYSIOLOGY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1095-6433 J9 COMP BIOCHEM PHYS A JI Comp. Biochem. Physiol. A-Mol. Integr. Physiol. PD APR PY 2007 VL 146 IS 4 SU S MA 1 BP S159 EP S159 DI 10.1016/j.cbpa.2007.01.325 PG 1 WC Biochemistry & Molecular Biology; Physiology; Zoology SC Biochemistry & Molecular Biology; Physiology; Zoology GA 157VD UT WOS:000245748600267 ER PT J AU Wang, ZS Maier, A Leopold, DA Logothetis, NK Liang, HL AF Wang, Zhisong Maier, Alexander Leopold, David A. Logothetis, Nikos K. Liang, Hualou TI Single-trial evoked potential estimation using wavelets SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE wavelet; single-trial; evoked potential; local field potential (LFP); multiunit activity (MUA); translation-invariant; structure-from-motion (SFM); LMS; RLS; Wiener ID TRANSFORM; FILTERS AB In this paper we present conventional and tran slation-invariant (TI) wavelet-based approaches for single-trial evoked potential estimation based on intracortical recordings. We demonstrate that the wavelet-based approaches outperform several existing methods including the Wiener filter, least mean square (LMS), and recursive least squares (RLS), and that the TI wavelet-based estimates have higher SNR and lower RMSE than the conventional wavelet-based estimates. We also show that multichannel averaging significantly improves the evoked potential estimation, especially for the wavelet-based approaches. The excellent performances of the wavelet-based approaches for extracting evoked potentials are demonstrated via examples using simulated and experimental data. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX 77030 USA. NIH, Unit Cognit Neurophysiol & Imaging, Bethesda, MD 20892 USA. Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany. RP Liang, HL (reprint author), Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, 7000 Fannin,Suite 600, Houston, TX 77030 USA. EM Hualou.Liang@uth.tmc.edu RI Maier, Alexander/B-7489-2009; OI Maier, Alexander/0000-0002-7250-502X; Leopold, David/0000-0002-1345-6360 FU NIMH NIH HHS [R01 MH072034, R03 MH067776]; NINDS NIH HHS [R01 NS054314] NR 16 TC 37 Z9 42 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD APR PY 2007 VL 37 IS 4 BP 463 EP 473 DI 10.1016/j.compbiomed.2006.08.011 PG 11 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 149OL UT WOS:000245156200004 PM 16987507 ER PT J AU Choi, IY Lee, SP Garwood, M Ugurbil, K Merkle, H AF Choi, In-Young Lee, Sang-Pil Garwood, Michael Ugurbil, Kamil Merkle, Hellmut TI Simple partial volume transceive coils for in vivo H-1 MR studies at high magnetic fields SO CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING LA English DT Article DE RF coil; MRI and MRS; high-field; very-high frequency (VHF); ultra-high frequency (UHF) ID HUMAN BRAIN; H-1-NMR SPECTROSCOPY; ADIABATIC PULSES; GABA; NMR; ARRAY; TESLA AB The development of simple radiofrequency (RF) coils for magnetic resonance (MR) of the human brain is still of high interest in the engineering of systems for which phased arrays are not yet available. Particularly, high-field MR studies will benefit from conflgurations with simple coils that are easy to build and require only a few RF parts for operation (e.g., quadrature hybrids). in this article we describe selected simple transmit/receive (transceive) partial volume coil assemblies for human brain studies at high magnetic fields of 3, 4, and 7 T (130, 170, and 300 MHz). To characterize coil performance, the experimental results of MRI of phantoms, anatomical MRI, and singlevoxel MRS of healthy human volunteers are presented. (c) 2007 Wiley Periodicals, Inc. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66160 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. Univ Minnesota, Dept Radiol, Ctr Magnet Resonance Res, Minneapolis, MN 55455 USA. RP Merkle, H (reprint author), NINDS, NIH, 10 Ctr Dr,MSC-1065,Bldg 10 B1D728, Bethesda, MD 20892 USA. EM merkleh@mail.nih.gov OI Lee, Phil/0000-0002-2087-8887 NR 25 TC 2 Z9 2 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-5031 J9 CONCEPT MAGN RESON B JI Concepts Magn. Reson. Part B PD APR PY 2007 VL 31B IS 2 BP 71 EP 85 DI 10.1002/cmr.b.20086 PG 15 WC Chemistry, Physical; Instruments & Instrumentation; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Chemistry; Instruments & Instrumentation; Physics; Spectroscopy GA 159RA UT WOS:000245882700002 ER PT J AU Beauchamp, MS Martin, A AF Beauchamp, Michael S. Martin, Alex TI Grounding object concepts in perception and action: Evidence from fMRI studies of tools SO CORTEX LA English DT Article DE manipulable objects; human visual cortex; conceptual representation; middle temporal gyrus; functional; magnetic resonance imaging ID CATEGORY-SPECIFIC DEFICITS; MANIPULATABLE OBJECTS; SEMANTIC MEMORY; BRAIN-DAMAGE; NEURAL BASIS; AREA MT; KNOWLEDGE; MOTION; CORTEX; COLOR AB Studies of categories of objects, including tools, have spurred the development of the sensory-motor model of object concept representation. According to this model, information about objects is represented in the same neural subsystems that are active when we perceive and use them. In turn, this model has provided insight into the brain mechanisms of tool use. For tools, three types of information are especially important for identification: the characteristic motion with which they move (such as the up and down motion of a hammer), their visual form, and the way that they are manipulated. Evidence from neuropsychological, non-human primates, and neuroimaging studies suggest a mapping between specific brain regions and these fundamental identifying properties of tools. We focus on neuroimaging studies of the left posterior middle temporal gyrus. This brain region is active both when subjects perceive moving tools and when they answer questions about tools, and is responsive to the type of visual motion characteristic of tools: rigid, unarticulated motion. We describe a simple model that explains how low-level receptive field properties like those known to exist in area MT/V5 could give rise to the high-level category-related representations observed in functional imaging experiments. C1 NIMH, IRP, Sect Cognit Neuropsychol, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, IRP, Sect Cognit Neuropsychol, Lab Brain & Cognit, 10 Ctr Dr,MSC 1366,Bldg 10,Room 4C104, Bethesda, MD 20892 USA. EM alex.martin@nih.gov RI martin, alex/B-6176-2009 FU Intramural NIH HHS NR 65 TC 83 Z9 83 U1 0 U2 8 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD APR PY 2007 VL 43 IS 3 BP 461 EP 468 DI 10.1016/S0010-9452(08)70470-2 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 169QI UT WOS:000246606300017 PM 17533768 ER PT J AU Petanceska, SS AF Petanceska, Suzana S. TI Exploring the links between obesity and Alzheimer's disease SO CURRENT ALZHEIMER RESEARCH LA English DT Editorial Material ID RISK C1 NIA, Neurosci & Neuropsychol Aging Program, Bethesda, MD 20892 USA. RP Petanceska, SS (reprint author), NIA, Neurosci & Neuropsychol Aging Program, 7201 Wisconsin Ave, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD APR PY 2007 VL 4 IS 2 BP 95 EP 96 DI 10.2174/156720507780362218 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156BH UT WOS:000245622400001 PM 17430229 ER PT J AU Launer, LJ AF Launer, Lenore J. TI Next steps in Alzheimer's disease research: Interaction between epidemiology and basic science SO CURRENT ALZHEIMER RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Exploring the Links between Obesity and Alzheimers Disease CY JUN 20-21, 2006 CL Bethesda, MD ID MILD COGNITIVE IMPAIRMENT; MIDLIFE BLOOD-PRESSURE; POPULATION-BASED COHORT; JAPANESE-AMERICAN MEN; WHITE-MATTER LESIONS; RISK-FACTORS; DIABETES-MELLITUS; CARDIOVASCULAR DETERMINANTS; INCIDENT DEMENTIA; ELDERLY PERSONS AB Epidemiologic studies have provided important clues about the etiology, prognosis and options for prevention and treatment of AD, and sub-clinical changes in cognition and brain structure. A brief review is given of what we have learned from epidemiologic studies of risk factors and natural history. This is followed by a discussion of how these findings could inform the design of basic research strategies that may further the translation of bench science to the clinic and public health arena. C1 NIA, LEDB, NIH, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, LEDB, NIH, 7201 Wisconsin Ave,Rm 3C-309, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov FU Intramural NIH HHS NR 46 TC 12 Z9 12 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD APR PY 2007 VL 4 IS 2 BP 141 EP 143 DI 10.2174/156720507780362155 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156BH UT WOS:000245622400009 PM 17430237 ER PT J AU Abraham, KM AF Abraham, Kristin M. TI Animal models of obesity and metabolic syndrome: Potential tools for Alzheimer's disease research SO CURRENT ALZHEIMER RESEARCH LA English DT Article; Proceedings Paper CT Workshop on Exploring the Links between Obesity and Alzheimers Disease CY JUN 20-21, 2006 CL Bethesda, MD DE metabolic syndrome; insulin resistance; obesity; Alzheimer's disease; animal models ID INSULIN-RESISTANCE; MICE; INSIGHTS; IMPACT AB Emerging evidence suggests that components of the metabolic syndrome either in isolation or in aggregate may impact the onset or severity of neurodegenerative processes, including those physiologic changes that lead to Alzheimer's Disease (AD). Several animal models that were originally designed to interrogate the metabolic syndrome are readily available. These models can now be used to support studies that may provide new mechanistic links between the metabolic syndrome and neurodegeneration. In addition, animal strains currently being generated and phenotyped through the efforts of an array of NIDDK-supported projects are likely to provide novel and better tools to advance Alzheimer's disease research in the near future. C1 NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, Bethesda, MD 20892 USA. RP Abraham, KM (reprint author), NIDDK, Div Diabet Endocrinol & Metab Dis, NIH, 6707 Democracy Blvd Rm 795, Bethesda, MD 20892 USA. EM abrahamk@mail.nih.gov NR 10 TC 4 Z9 4 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2050 J9 CURR ALZHEIMER RES JI Curr. Alzheimer Res. PD APR PY 2007 VL 4 IS 2 BP 145 EP 146 DI 10.2174/156720507780362209 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 156BH UT WOS:000245622400010 PM 17430238 ER PT J AU Boasso, A Shearer, GM AF Boasso, Adriano Shearer, Gene M. TI How does indoleamine 2,3-dioxygenase contribute to HIV-mediated immune dysregulation SO CURRENT DRUG METABOLISM LA English DT Review DE indoleamine 2,3-dioxygenase; HIV; immune suppression ID HUMAN-IMMUNODEFICIENCY-VIRUS; REGULATORY T-CELLS; PRIMARY HUMAN MACROPHAGES; NONOBESE DIABETIC MICE; DENDRITIC CELLS; TRYPTOPHAN CATABOLISM; INTERFERON-GAMMA; INFECTED PATIENTS; MONONUCLEAR PHAGOCYTES; LYMPHOCYTE-ACTIVATION AB Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressive activity, which could contribute to the immune dysfunction observed in HIV-infected patients. In this review we discuss the immune mechanisms that could mediate the HIV-induced increase of IDO activity (such as IFN-gamma, IFN-alpha, CTLA-4/B7 and direct viral exposure). We then consider the current knowledge of IDO-mediated immune suppressive mechanisms with regard to different cell types (CD4(+) T cells, CD8(+) T cells, natural killer cells, B cells and regulatory T cells), from the perspective of their potential consequences for the HIV-infected host. HIV-induced, IDO-mediated trp catabolism may contribute to the perpetuation of HIV infection into its chronic phase by dampening efficient immune anti-viral responses. Therapeutic approaches aimed at manipulating this powerful immune suppressive mechanism might be considered in the setting of HIV infection. C1 NCI, NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Boasso, A (reprint author), NCI, NIH, Expt Immunol Branch, Bldg 10,Room 4B36,10 Ctr Dr MSC-1360, Bethesda, MD 20892 USA. EM boassoa@mail.nih.gov OI Boasso, Adriano/0000-0001-9673-6319 NR 106 TC 40 Z9 43 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2002 J9 CURR DRUG METAB JI Curr. Drug Metab. PD APR PY 2007 VL 8 IS 3 BP 217 EP 223 DI 10.2174/138920007780362527 PG 7 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 158EJ UT WOS:000245773700006 PM 17430110 ER PT J AU Chou, JY Mansfield, BC AF Chou, Janice Y. Mansfield, Brian C. TI Gene therapy for type I glycogen storage diseases SO CURRENT GENE THERAPY LA English DT Review ID ADENOASSOCIATED VIRUS VECTORS; INFLAMMATORY-BOWEL-DISEASE; COLONY-STIMULATING FACTOR; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; DEPENDENT ADENOVIRAL VECTORS; GLUCOSE-6-PHOSPHATE TRANSPORTER; LIVER-TRANSPLANTATION; AAV VECTORS; MURINE GLUCOSE-6-PHOSPHATASE; NEUTROPHIL DYSFUNCTION AB The type I glycogen storage diseases (GSD-1) are a group of related diseases caused by a deficiency in the glucose-6-phosphatase-alpha (G6Pase-alpha) system, a key enzyme complex that is essential for the maintenance of blood glucose homeostasis between meals. The complex consists of a glucose-6-phosphate transporter (G6PT) that translocates glucose-6-phosphate from the cytoplasm into the lumen of the endoplasmic reticulum, and a G6Pase-a catalytic unit that hydrolyses the glucose-6-phosphate into glucose and phosphate. A deficiency in G6Pase-alpha causes GSD type Ia (GSD-1a) and a deficiency in G6PT causes GSD type Ib (GSD-Ib). Both GSD-Ia and GSD-Ib patients manifest a disturbed glucose homeostasis, while GSD-Ib patients also suffer symptoms of neutropenia and myeloid dysfunctions. G6Pase-alpha and G6PT are both hydrophobic endoplasmic reticulum-associated transmembrane proteins that can not expressed in soluble active forms. Therefore protein replacement therapy of GSD-I is not an option. Animal models of GSD-Ia and GSD-Ib that mimic the human disorders are available. Both adenovirus- and adeno-associated virus (AAV)-mediated gene therapies have been evaluated for GSD-Ia in these model systems. While adenoviral therapy produces only short term corrections and only impacts liver expression of the gene, AAV-mediated therapy delivers the transgene to both the liver and kidney, achieving longer term correction of the GSD-Ia disorder, although there are substantial differences in efficacy depending on the AAV serotype used. Gene therapy for GSD-Ib in the animal model is still in its infancy, although an adenoviral construct has improved the metabolic profile and myeloid function. Taken together further refinements in gene therapy may hold long term benefits for the treatment of type I GSD disorders. C1 NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Correlog Syst Inc, Rockville, MD 20850 USA. RP Chou, JY (reprint author), NICHHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov FU Intramural NIH HHS [Z01 HD000912-28] NR 90 TC 16 Z9 16 U1 2 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 J9 CURR GENE THER JI Curr. Gene Ther. PD APR PY 2007 VL 7 IS 2 BP 79 EP 88 DI 10.2174/156652307780363152 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 152EB UT WOS:000245342600001 PM 17430128 ER PT J AU Misteli, T Dernburg, AF AF Misteli, Tom Dernburg, Abby F. TI Chromosomes and expression mechanisms - Everything old is new again SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Editorial Material C1 NCI, NIH, Bethesda, MD 20892 USA. Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov; afdernburg@lbl.gov OI Dernburg, Abby/0000-0001-8037-1079 NR 0 TC 2 Z9 2 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2007 VL 17 IS 2 BP 85 EP 87 DI 10.1016/j.gde.2007.03.001 PG 3 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 162LW UT WOS:000246089900001 ER PT J AU Zhang, Y Oliver, B AF Zhang, Yu Oliver, Brian TI Dosage compensation goes global SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID REMODELING COMPLEX NURF; HISTONE H4 ACETYLATION; X-CHROMOSOMAL GENES; DROSOPHILA-MELANOGASTER; CHROMATIN-STRUCTURE; MSL COMPLEX; AUTOSOMAL TRISOMY; HIGH-RESOLUTION; DOWN-SYNDROME; MOUSE MODEL AB In many organisms, females have two X chromosomes whereas males have just one. This natural X chromosome monosomy is not lethal, because of dosage compensation. Although numerous elegant genetic, biochemical and cytological experiments have been used to build up the mechanistic framework describing this specialized transcriptional control, dosage compensation is a chromosome-wide regulatory mechanism and is best studied at that level. Microarray techniques give us the chance to look simultaneously at the expression of all the genes in response to dose. These approaches have resolved old controversies, suggested new questions, and promise to give us a more clear and comprehensive understanding of an old problem in molecular and cell biology. C1 NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Oliver, B (reprint author), NIDDKD, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. EM oliver@helix.nih.gov FU Intramural NIH HHS NR 50 TC 25 Z9 25 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2007 VL 17 IS 2 BP 113 EP 120 DI 10.1016/j.gde.2007.02.002 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 162LW UT WOS:000246089900006 PM 17307352 ER PT J AU Chadwick, LH Wade, PA AF Chadwick, Lisa Helbling Wade, Paul A. TI MeCP2 in Rett syndrome: transcriptional repressor or chromatin architectural protein? SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID DNA METHYLATION; MOUSE MODEL; HISTONE DEACETYLASE; BDNF TRANSCRIPTION; UBE3A EXPRESSION; GENE-EXPRESSION; MUTANT MICE; MUTATIONS; CLUSTER; BRAIN AB Rett syndrome is a progressive neurological disorder caused by mutations in the methyl-DNA binding protein MeCP2. The longstanding model depicting MeCP2 as a transcriptional repressor predicts that the Rett syndrome phenotype probably results from misregulation of MeCP2 target genes. Somewhat unexpectedly, the identification of such targets has proven challenging. The recent identification of two MeCP2 targets, BDNF and DLX5, are suggestive of two very different roles for this protein - one as a classical repressor protein, and the other as a mediator of a complex, specialized chromatin structure. C1 Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. RP Wade, PA (reprint author), Natl Inst Environm Hlth Sci, Lab Mol Carcinogenesis, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM wadep2@niehs.nih.gov FU Intramural NIH HHS NR 38 TC 27 Z9 28 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD APR PY 2007 VL 17 IS 2 BP 121 EP 125 DI 10.1016/j.gde.2007.02.003 PG 5 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 162LW UT WOS:000246089900007 PM 17317146 ER PT J AU Storz, G Haas, D AF Storz, Gisela Haas, Dieter TI A guide to small RNAs in microorganisms SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Ecole Polytech Fed Lausanne, Dept Microbiol Fondamentale, CH-1015 Lausanne, Switzerland. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, 18 Lib Dr, Bethesda, MD 20892 USA. EM storz@helix.nih.gov; Dieter.Haas@unil.ch OI Storz, Gisela/0000-0001-6698-1241 NR 1 TC 17 Z9 18 U1 1 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 2007 VL 10 IS 2 BP 93 EP 95 DI 10.1016/j.mib.2007.03.017 PG 3 WC Microbiology SC Microbiology GA 166AP UT WOS:000246349600002 ER PT J AU Gropman, AL Elsea, S Duncan, WC Smith, ACM AF Gropman, Andrea L. Elsea, Sarah Duncan, Wallace C., Jr. Smith, Ann C. M. TI New developments in Smith-Magenis syndrome (del 17p11.2) SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE chromosome 17p11.2; circadian rhythm; interstitial deletion; RAI1; Smith-Magenis syndrome ID COMMON VARIABLE IMMUNODEFICIENCY; GENE DELETION SYNDROME; IN-SITU HYBRIDIZATION; HOGG-DUBE-SYNDROME; INTERSTITIAL DELETION; SPONTANEOUS PNEUMOTHORAX; MALADAPTIVE BEHAVIOR; CRITICAL INTERVAL; CIRCADIAN-RHYTHM; IGA DEFICIENCY AB Purpose of review Recent clinical, neuroimaging, sleep, and molecular I cytogenetic studies have provided new insights into the mechanisms leading to the Smith-Magenis phenotype and are summarized in this review. Recent findings Cross sectional studies of patients with Smith-Magenis syndrome have found evidence for central and peripheral nervous system abnormalities, neurobehavioral disturbances, and an inverted pattern of melatonin secretion leading to circadian rhythm disturbance. A common chromosome 17p11.2 deletion interval spanning approximately 3.5 Mb is identified in about 70% of individuals with chromosome deletion. Recently heterozygous point mutations in the RAI1 gene within the Smith-Magenis syndrome critical region have been reported in Smith-Magenis syndrome patients without detectable deletion by fluorescent in-situ hybridization. Patients with intragenic mutations in RAI1 as well as those with deletions share most but not all aspects of the phenotype. Summary Findings from molecular cytogenetic analysis suggest that other genes or genetic background may play a role in altering the functional availability of RAI1 for downstream effects. Further research into additional genes in the Smith-Magenis syndrome critical region will help define the role they play in modifying features or severity of the Smith-Magenis syndrome phenotype. More research is needed to translate advances in clinical research into new treatment options to address the sleep and neurobehavioral problems in this disorder. C1 Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. George Washington Univ, Washington, DC 20052 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pediat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Oncol, Washington, DC 20057 USA. RP Gropman, AL (reprint author), Childrens Natl Med Ctr, Dept Neurol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM agropman@cnmc.org RI SMITH, ANN C.M./C-1122-2008 FU Intramural NIH HHS NR 64 TC 33 Z9 35 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD APR PY 2007 VL 20 IS 2 BP 125 EP 134 DI 10.1097/WCO.0b013e3280895dba PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 152UT UT WOS:000245388200002 PM 17351481 ER PT J AU Shapiro, BA Yingling, YG Kasprzak, W Bindewald, E AF Shapiro, Bruce A. Yingling, Yaroslava G. Kasprzak, Wojciech Bindewald, Eckart TI Bridging the gap in RNA structure prediction SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID SECONDARY STRUCTURE PREDICTION; PARALLEL GENETIC ALGORITHM; STRUCTURES INCLUDING PSEUDOKNOTS; DYNAMIC-PROGRAMMING ALGORITHM; FREE-ENERGY MINIMIZATION; CONTEXT-FREE GRAMMARS; TELOMERASE RNA; WEB SERVER; COMPUTER-SIMULATION; PARTITION-FUNCTION AB The field of RNA structure prediction has experienced significant advances in the past several years, thanks to the availability of new experimental data and improved computational methodologies. These methods determine RNA secondary structures and pseudoknots from sequence alignments, thermodynamics-based dynamic programming algorithms, genetic algorithms and combined approaches. Computational RNA three-dimensional modeling uses this information in conjunction with manual manipulation, constraint satisfaction methods, molecular mechanics and molecular dynamics. The ultimate goal of automatically producing RNA three-dimensional models from given secondary and tertiary structure data, however, is still not fully realized. Recent developments in the computational prediction of RNA structure have helped bridge the gap between RNA secondary structure prediction, including pseudoknots, and three-dimensional modeling of RNA. C1 NCI Frederick, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, NCI Frederick, Frederick, MD 21702 USA. RP Shapiro, BA (reprint author), NCI Frederick, Ctr Canc Res, Nanobiol Program, Bldg 469,Room 150, Frederick, MD 21702 USA. EM bshapiro@ncifcrf.gov RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 FU Intramural NIH HHS; NCI NIH HHS [N01 CO12400] NR 72 TC 109 Z9 114 U1 0 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD APR PY 2007 VL 17 IS 2 BP 157 EP 165 DI 10.1016/j.sbi.2007.03.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 165UI UT WOS:000246330900003 PM 17383172 ER PT J AU Luo, T Xu, YH Hoffman, TL Zhang, TL Schilling, T Sargent, TD AF Luo, Ting Xu, Yanhua Hoffman, Trevor L. Zhang, Tailin Schilling, Thomas Sargent, Thomas D. TI Inca: a novel p21-activated kinase-associated protein required for cranial neural crest development SO DEVELOPMENT LA English DT Article DE cartilage; PAK; cortical actin; cytoskeleton; wound healing; craniofacial; Tfap2a; ectomesenchyme; neural crest; Xenopus; zebrafish ID TRANSCRIPTION FACTOR AP-2; CORTICAL ACTIN SKELETON; EARLY XENOPUS EMBRYOS; HOMEOBOX GENES; INDUCTION; SIGNALS; LAEVIS; ACTIVATION; CELLS; MORPHOGENESIS AB Inca (induced in neural crest by AP2) is a novel protein discovered in a microarray screen for genes that are upregulated in Xenopus embryos by the transcriptional activator protein Tfap2a. It has no significant similarity to any known protein, but is conserved among vertebrates. In Xenopus, zebrafish and mouse embryos, Inca is expressed predominantly in the premigratory and migrating neural crest (NC). Knockdown experiments in frog and fish using antisense morpholinos reveal essential functions for Inca in a subset of NC cells that form craniofacial cartilage. Cells lacking Inca migrate successfully but fail to condense into skeletal primordia. Overexpression of Inca disrupts cortical actin and prevents formation of actin 'purse strings', which are required for wound healing in Xenopus embryos. We show that Inca physically interacts with p21-activated kinase 5 (PAK5), a known regulator of the actin cytoskeleton that is co-expressed with Inca in embryonic ectoderm, including in the NC. These results suggest that Inca and PAK5 cooperate in restructuring cytoskeletal organization and in the regulation of cell adhesion in the early embryo and in NC cells during craniofacial development. C1 NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Pediat, Div Human Genet & Birth Defects, Irvine, CA 92697 USA. RP Sargent, TD (reprint author), NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. EM tsargent@nih.gov FU Intramural NIH HHS; NIDCR NIH HHS [DE 13828]; NINDS NIH HHS [NS 41353] NR 61 TC 23 Z9 23 U1 1 U2 4 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 APR 1 PY 2007 VL 134 IS 7 BP 1279 EP 1289 DI 10.1242/dev.02813 PG 11 WC Developmental Biology SC Developmental Biology GA 144YM UT WOS:000244832500005 PM 17314132 ER PT J AU Cohen, TV Kosti, O Stewart, CL AF Cohen, Tatiana V. Kosti, Ourania Stewart, Colin L. TI The nuclear envelope protein MAN1 regulates TGF beta signaling and vasculogenesis in the embryonic yolk sac SO DEVELOPMENT LA English DT Article DE nuclear envelope; vasculogenesis; Man1 (Lemd3); TGF beta ID GROWTH-FACTOR-BETA; MEMBRANE PROTEIN; LEM-DOMAIN; TRANSCRIPTION FACTORS; ENDOTHELIAL-CELLS; STEM-CELLS; LAMIN-A/C; ANGIOGENESIS; MICE; RECEPTOR AB MAN1 is an integral protein of the inner nuclear membrane of the nuclear envelope (NE). MAN1 interacts with SMAD transcription factors, which in turn are regulated by the Transforming growth factor beta (TGF beta) superfamily of signaling molecules. To determine the role of MAN1 in mouse development, we used a gene-trap embryonic stem cell clone to derive mice with a functional mutation in MAN1 (Man1GT/GT). Expression of Man1 during early development is initially low but increases at embryonic day 9.5 (E9.5). Coincident with this increase, homozygous gene-trapped Man1 (Man1(GT/GT)) embryos die by E10.5. Examination of mutant embryos and tetraploid rescue experiments reveals that abnormal yolk-sac vascularization is the probable cause of lethality. We also established embryonic stem cell lines and their differentiated derivatives that are homozygous for the Man1(GT) allele. Using these lines, we show that the Man1GT allele results in increased phosphorylation, nuclear localization and elevated levels of SMAD transcriptional activity, predominantly of SMAD2/3, which are regulated by the ALK5 signaling pathway. Our studies identify a previously uncharacterized role for an integral nuclear envelope protein in the regulation of yolk-sac angiogenesis by TGF beta signaling and reveal that the NE has an essential role in regulating transcription factor activity during mouse development. C1 NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. EM stewartc@ncifcrf.gov FU Intramural NIH HHS NR 74 TC 38 Z9 39 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR 1 PY 2007 VL 134 IS 7 BP 1385 EP 1395 DI 10.1242/dev.02816 PG 11 WC Developmental Biology SC Developmental Biology GA 144YM UT WOS:000244832500014 PM 17329363 ER PT J AU Liu, ZH Lenardo, MJ AF Liu, Zhihua Lenardo, Michael J. TI Reactive oxygen species regulate autophagy through redox-sensitive proteases SO DEVELOPMENTAL CELL LA English DT Editorial Material ID CELL-DEATH AB Starvation induces autophagy through a signal transduction pathway that is not fully understood. In a recent issue of The EMBO Journal, Scherz-Shouval and colleagues (Scherz-Shouval et al., 2007) show that reactive oxygen species (ROS) occurring during starvation serve as signaling molecules that initiate autophagy. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Liu, ZH (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM lenardo@nih.gov; liuzhi@niaid.nih.gov NR 9 TC 50 Z9 53 U1 4 U2 12 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD APR PY 2007 VL 12 IS 4 BP 484 EP 485 DI 10.1016/j.devcel.2007.03.016 PG 2 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 158SY UT WOS:000245816100005 PM 17419989 ER PT J AU Hanson, RL Craig, DW Millis, MP Yeatts, KA Kobes, S Pearson, JV Lee, AM Knowler, WC Nelson, RG Wolford, JK AF Hanson, Robert L. Craig, David W. Millis, Meredith P. Yeatts, Kimberly A. Kobes, Sayuko Pearson, John V. Lee, Anne M. Knowler, William C. Nelson, Robert G. Wolford, Johanna K. TI Identification of PVT1 as a candidate gene for end-stage renal disease in type 2 diabetes using a pooling-based genonte-wide single nucleotide polymorphism association study SO DIABETES LA English DT Article ID WHOLE-GENOME ASSOCIATION; MILD MENTAL IMPAIRMENT; PIMA-INDIANS; POOLED DNA; LINKAGE DISEQUILIBRIUM; FAMILIAL PREDISPOSITION; NEPHROPATHY; LOCI; MICROARRAYS; MELLITUS AB To identify genetic variants contributing to end-stage renal disease (ESRD) in type 2 diabetes, we performed a genome-wide analysis of 115,352 single nucleotide polymorphisms (SNPs) in pools of 105 unrelated case subjects with ESRD and 102 unrelated control subjects who have had type 2 diabetes for >= 10 years without macroalbuminuria. Using a sliding window statistic of ranked SNPs, we identified a 200-kb region on 8q24 harboring three SNPs showing substantial differences in allelic frequency between case and control pools. These SNPs were genotyped in individuals comprising each pool, and strong evidence for association was found with rs2720709 (P = 0.000021; odds ratio 2.57 [95% CI 1.66-3.96]), which is located in the plasmacytoma variant translocation gene PVT1. We sequenced all exons, exon-intron boundaries, and the promoter of PVT1 and identified 47 variants, 11 of which represented nonredundant markers with minor allele frequency >= 0.05. We subsequently genotyped these 11 variants and an additional 87 SNPs identified through public databases in 319-kb flanking rs2720709 (similar to 1 SN-P/3.5 kb); 23 markers were associated with ESRD at P < 0.01. The strongest evidence for association was found for rs2648875 (P = 0.0000018; 2.97 [1.90-4.65]), which maps to intron 8 of PVT1. Together, these results suggest that PVT1 may contribute to ESRD susceptibility in diabetes. C1 Translat Genom Res Inst, Phoenix, AZ 85004 USA. NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85016 USA. RP Wolford, JK (reprint author), Translat Genom Res Inst, 445 North 5th St, Phoenix, AZ 85004 USA. EM jwolford@tgen.org RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015; Pearson, John/F-2249-2011 OI Hanson, Robert/0000-0002-4252-7068; Pearson, John/0000-0003-0904-4598 FU Intramural NIH HHS NR 44 TC 74 Z9 84 U1 2 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2007 VL 56 IS 4 BP 975 EP 983 DI 10.2337/db06-1072 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157CW UT WOS:000245697200009 PM 17395743 ER PT J AU Lachin, JM Christophi, CA Edelstein, SL Ehrmann, DA Hamman, RF Kahn, SE Knowler, WC Nathan, DM AF Lachin, John M. Christophi, Costas A. Edelstein, Sharon L. Ehrmann, David A. Hamman, Richard F. Kahn, Steven E. Knowler, William C. Nathan, David M. CA DPP Res Grp TI Factors associated with diabetes onset during metformin versus placebo therapy in the Diabetes Prevention Program SO DIABETES LA English DT Article ID LIFE-STYLE INTERVENTION; ORAL GLUCOSE-TOLERANCE; BETA-CELL FUNCTION; INSULIN-SECRETION; MELLITUS; SENSITIVITY; RISK AB In the Diabetes Prevention Program, treatment of subjects with impaired glucose tolerance with metformin > 3.2 years reduced the risk of developing type 2 diabetes by 30% compared with placebo. This study describes the mechanisms of this effect. In proportional hazards regression models with 2,155 subjects, changes in weight, the insulinogenic index (IGR), fasting insulin, and proinsulin were predictive of diabetes, though to different degrees within each group. The mean change in weight, fasting insulin, and proinsulin, but not IGR, differed between groups during the study. The 1.7-kg weight loss with metformin versus a 0.3-kg gain with placebo alone explained 64% of the beneficial metformin effect on diabetes risk. Adjustment for weight, fasting insulin, proinsulin, and other metabolic factors combined explained 81% of the beneficial metformin effect, but it remained nominally significant (P = 0.034). After the addition of changes in fasting glucose, 99% of the group effect was explained and is no longer significant. Treatment of high-risk subjects with metformin results in modest weight loss and favorable changes in insulin sensitivity and proinsulin, which contribute to a reduction in the risk of diabetes apart from the associated reductions in fasting glucose. C1 George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, Rockville, MD 20852 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Colorado, Sch Med, Denver, CO USA. VA PUget Sound Hlth Care Syst, Dept Internal Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NIDDKD, Phoenix, AZ 85016 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lachin, JM (reprint author), George Washington Univ, Ctr Biostat, Diabet Prevent Program Coordinating Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA. EM dppmail@biostat.bsc.gwu.edu OI Lachin, John/0000-0001-9838-2841; Kahn, Steven/0000-0001-7307-9002 FU Intramural NIH HHS; NIDDK NIH HHS [U01 DK048489, U01 DK048489-06] NR 24 TC 30 Z9 32 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2007 VL 56 IS 4 BP 1153 EP 1159 DI 10.2337/db06-0918 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157CW UT WOS:000245697200030 PM 17395752 ER PT J AU Looker, HC Nelson, RG Chew, E Klein, R Klein, BEK Knowler, WC Hanson, RL AF Looker, Helen C. Nelson, Robert G. Chew, Emily Klein, Ronald Klein, Barbara E. K. Knowler, William C. Hanson, Robert L. TI Genome-wide linkage analyses to identify loci for diabetic retinopathy SO DIABETES LA English DT Article ID ASSESSING GENETIC-LINKAGE; PIMA-INDIANS; UNITED-STATES; VISUAL IMPAIRMENT; PAIR ANALYSIS; RISK-FACTORS; PREVALENCE; DIAGNOSIS; MELLITUS; POLYMORPHISM AB Hyperglycemia and long duration of diabetes are widely recognized risk factors for diabetic retinopathy, but inherited susceptibility may also play a role because retinopathy aggregates in families. A genome-wide linkage analysis was conducted in 211 sibships in which >= 2 siblings had diabetes and retinal photographs were available from a longitudinal study. These sibships were a subset of 322 sibships who had participated in a previous linkage study of diabetes and related traits; they comprised 607 diabetic individuals in 725 sibpairs. Retinal photographs were graded for presence and severity of diabetic retinopathy according to a modification of the Airlie House classification system. The grade for the worse eye was adjusted for age, sex, and diabetes duration and analyzed as a quantitative trait. Heritability of diabetic retinopathy in this group was 18% (95% Cl 2-36). A genome-wide linkage analysis using variance components modeling found evidence of linkage on chromosome 1p. Using single-point analysis, the peak logarithm of odds (LOD) was 3.1 for marker D1S3669 (34.2 cM), whereas with multipoint analysis the peak LOD was 2.58 at 35 cM. No other areas of suggestive linkage were found. We propose that an area on chromosome 1 may harbor a gene or genes conferring susceptibility to diabetic retinopathy. C1 NIDDKD, PECRB, Phoenix, AZ 85014 USA. NEI, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI 53706 USA. RP Hanson, RL (reprint author), NIDDKD, PECRB, 1550 e Indian Sch Rd, Phoenix, AZ 85014 USA. EM rhanson@mail.nih.gov RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS [Z99 EY999999]; NEI NIH HHS [R01 EY015286] NR 45 TC 48 Z9 52 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2007 VL 56 IS 4 BP 1160 EP 1166 DI 10.2337/db06-1299 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 157CW UT WOS:000245697200031 PM 17395753 ER PT J AU Horton, JK Wilson, SH AF Horton, Julie K. Wilson, Samuel H. TI Hypersensitivity phenotypes associated with genetic and synthetic inhibitor-induced base excision repair deficiency SO DNA REPAIR LA English DT Review DE base excision repair; DNA polymerase beta; XRCC1; PARP-1; PARP inhibitor ID DNA-POLYMERASE-BETA; STRAND BREAK REPAIR; MAMMALIAN-CELL EXTRACTS; COLON-CANCER CELLS; POLY(ADP-RIBOSE) POLYMERASE; LONG-PATCH; INDUCED CYTOTOXICITY; METHYL METHANESULFONATE; DISPLACEMENT SYNTHESIS; REVERSE-TRANSCRIPTASE AB Single-base lesions in DNA are repaired predominantly by base excision repair (BER). DNA polymerase beta (pol beta) is the polymerase of choice in the preferred single-nucleotide BER pathway. The characteristic phenotype of mouse fibroblasts with a deletion of the pol beta gene is moderate hypersensitivity to monofunctional alkylating agents, e.g., methyl methanesulfonate (MMS). Increased sensitivity to MMS is also seen in the absence of pol beta partner proteins XRCC1 and PARP-1, and under conditions where BER efficiency is reduced by synthetic inhibitors. PARP activity plays a major role in protection against MMS-induced cytotoxicity, and cells treated with a combination of non-toxic concentrations of MMS and a PARP inhibitor undergo cell cycle arrest and die by a Chk1-dependent apoptotic pathway. Since BER-deficient cells and tumors are similarly hypersensitive to the clinically used chemotherapeutic methylating agent temozolomide, modulation of DNA damage-induced cell signaling pathways, as well as BER, are attractive targets for potentiating chemotherapy (c) 2006 Elsevier B.V. All rights reserved. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM wilson5@niehs.nih.gov FU Intramural NIH HHS [Z01 ES050159-11] NR 125 TC 48 Z9 50 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 1 PY 2007 VL 6 IS 4 BP 530 EP 543 DI 10.1016/j.dnarep.2006.10.016 PG 14 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 155HD UT WOS:000245567600013 PM 17113833 ER PT J AU Wilson, DM Bohr, VA AF Wilson, David M., III Bohr, Vilhelm A. TI The mechanics of base excision repair, and its relationship to aging and disease SO DNA REPAIR LA English DT Review DE DNA damage; base excision repair; aging; cancer; neurodegeneration ID DNA-POLYMERASE-BETA; WERNER-SYNDROME PROTEIN; STRAND-BREAK REPAIR; PURIFIED HUMAN PROTEINS; GROUP-B PROTEIN; HUMAN APURINIC ENDONUCLEASE; COUPLING FACTOR CSB/ERCC6; OXIDATIVELY DAMAGED DNA; COCKAYNE-SYNDROME; MITOCHONDRIAL-DNA AB Base excision repair (BER) is the major pathway responsible for averting the mutagenic and cytotoxic effects of spontaneous hydrolytic, oxidative, and non-enzymatic alkylation DNA damage. In particular, this pathway recognizes and repairs base modifications, such as uracil and 8-hydroxyguanine, as well as abasic sites and DNA single-strand breaks. In this review, we outline the basic mechanics of the BER process, and describe the potential association of this pathway with aging and age-related disease, namely cancer and neurodegeneration. (c) 2006 Elsevier B.V. All rights reserved. C1 NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. EM BohrV@grc.nia.nih.gov FU Intramural NIH HHS NR 185 TC 193 Z9 195 U1 0 U2 26 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD APR 1 PY 2007 VL 6 IS 4 BP 544 EP 559 DI 10.1016/j.dnarep.2006.10.017 PG 16 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 155HD UT WOS:000245567600014 PM 17112792 ER PT J AU DeLozier, TC Kissling, GE Coulter, SJ Dai, D Foley, JF Bradbury, JA Murphy, E Steenbergen, C Zeldin, DC Goldstein, JA AF DeLozier, Tracy C. Kissling, Grace E. Coulter, Sherry J. Dai, Diana Foley, Julie F. Bradbury, J. Alyce Murphy, Elizabeth Steenbergen, Charles Zeldin, Darryl C. Goldstein, Joyce A. TI Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues SO DRUG METABOLISM AND DISPOSITION LA English DT Article; Proceedings Paper CT Experimental Biology 2006 Meeting CY APR 01-05, 2006 CL San Francisco, CA SP Amer Assoc Anatomists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut ID SOLUBLE EPOXIDE HYDROLASE; EPOXYGENASE-DERIVED EICOSANOIDS; EPOXYEICOSATRIENOIC ACIDS; ARACHIDONIC-ACID; ENDOTHELIAL-CELLS; CYTOCHROME-P450 ENZYMES; HYPERPOLARIZING FACTORS; CORONARY-ARTERIES; GENE-EXPRESSION; BLOOD-PRESSURE AB The cytochrome P450 ( P450) enzymes CYP2C8, CYP2C9, and CYP2J2 metabolize arachidonic acid to epoxyeicosatrienoic acids, which are known to be vital in regulation of vascular tone and cardiovascular homeostasis. Because there is limited information regarding the relative expression of these P450 enzymes in cardiovascular tissues, this study examined the expression of CYP2C8, CYP2C9, and CYP2J2 mRNA and protein in human heart, aorta, and coronary artery samples by real-time polymerase chain reaction, immunoblotting, and immunohistochemistry. CYP2J2 and CYP2C9 mRNA levels were highly variable in human hearts, whereas CYP2C8 mRNA was present in lower abundance. CYP2J2 mRNA was approximately 10(3) times higher than CYP2C9 or CYP2C8 in human heart. However, CYP2C9 mRNA was more abundant than CYP2J2 or CYP2C8 in one ischemic heart. In human aorta, mean CYP2C9 mRNA levels were similar to 50 times higher than that of CYP2J2 and 5-fold higher than that of CYP2C8. In human coronary artery, mean values for CYP2C9 mRNA were similar to 2-fold higher than that of CYP2J2 mRNA and 6-fold higher than that of CYP2C8 mRNA. Immunoblotting results show relatively high levels of CYP2J2 and CYP2C8 protein in human hearts, which was confirmed by immunohistochemistry. CYP2C9 protein was also detected at high levels in one ischemic heart by immunoblotting. CYP2C9 was present at higher levels than CYPJ2 in aorta and coronary artery, whereas CYP2C8 protein was below the limits of detection. The expression of CYP2J2 and CYP2C8 in human heart, and CYPC9 and CYP2J2 in aorta and coronary artery is consistent with a physiological role for these enzymes in these tissues. C1 NIEHS, Human Metab Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27706 USA. RP Goldstein, JA (reprint author), NIEHS, Human Metab Sect, Lab Pharmacol & Chem, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM goldste1@niehs.nih.gov RI Goldstein, Joyce/A-6681-2012; OI Coulter, Sherry/0000-0002-2732-3470 FU Intramural NIH HHS [Z01 ES021024-26]; NHLBI NIH HHS [R01 HL039752] NR 41 TC 79 Z9 86 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD APR PY 2007 VL 35 IS 4 BP 682 EP 688 DI 10.1124/dmd.106.012823 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 149XB UT WOS:000245179100024 PM 17220242 ER PT J AU Miller, JL Kang, SM AF Miller, Jeri L. Kang, Seon M. TI Preliminary ultrasound observation of lingual movement patterns during nutritive versus non-nutritive sucking in a premature infant SO DYSPHAGIA LA English DT Article DE sucking; nutritive sucking; non-nutritive sucking; prematurity; deglutition; deglutition disorders ID PRETERM INFANTS; TUBE; ORGANIZATION; FEEDINGS AB Term neonates must suck, swallow, and respire in a coordinated manner during successful oral feeding. When infants are born prematurely, these skills may not be fully mature. To stimulate sucking responses, premature infants are offered pacifiers under the premise that non-nutritive sucking experiences facilitate oral feeding readiness. This case reported examined the lingual-hyoid mechanics of non-nutritive suck (NNS) patterns with a pacifier versus nutritive suck (NS) during a bottle feed in a premature infant using a noninvasive ultrasound imaging technique as a pilot to discern aspects of oral feeding candidacy. Lingual patterns during NS resulted in significantly greater displacements and excursions than NNS (p < 0.0001) in both anterior and posterior regions of the tongue (p < 0.0001). In addition, the angle of hyoid movement during NNS was significantly smaller (p < 0.05) than the angle recorded during NS tasks. Unlike an expected neonatal sucking pattern of horizontal anterior-posterior movements of the tongue body, vertical tongue body excursions occurred as described in the literature of representing a 6-9-month developmental skill level. Through the integration of semiautomatic computerized analyses of tongue surface configurations and hyoid activity, these data may enhance knowledge of oral swallowing function in developing preterm neonates. C1 NIH, Dept Rehabil Med, Phys Disabil Branch, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIH, Dept Rehabil Med, Phys Disabil Branch, Bldg 10 CRC RM 1-1469,10 Ctr Dr MSC 1604, Bethesda, MD 20892 USA. EM jmiller@cc.nih.gov NR 32 TC 26 Z9 28 U1 1 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0179-051X J9 DYSPHAGIA JI Dysphagia PD APR PY 2007 VL 22 IS 2 BP 150 EP 160 DI 10.1007/s00455-006-9058-z PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 144UE UT WOS:000244821000012 PM 17294300 ER PT J AU Mishra, RK Kizer, JR Palmieri, V Roman, MJ Galloway, JM Fabsitz, RR Lee, ET Best, LG Devereux, RB AF Mishra, Rakesh K. Kizer, Jorge R. Palmieri, Vittorio Roman, Mary J. Galloway, James M. Fabsitz, Richard R. Lee, Elisa T. Best, Lyle G. Devereux, Richard B. TI Utility of the myocardial performance index in a population with high prevalences of obesity, diabetes, and hypertension: The strong heart study SO ECHOCARDIOGRAPHY-A JOURNAL OF CARDIOVASCULAR ULTRASOUND AND ALLIED TECHNIQUES LA English DT Article ID LEFT-VENTRICULAR FUNCTION; DOPPLER-DERIVED INDEX; AMERICAN-INDIANS; TEI-INDEX; CARDIOVASCULAR-DISEASE; INDEPENDENT PREDICTOR; DIASTOLIC FUNCTION; ECHOCARDIOGRAPHIC-ASSESSMENT; ARTERIAL-HYPERTENSION; ELDERLY ADULTS AB Introduction: The myocardial performance index (MPI) introduced by Tei, a Doppler-derived echocardiographic measure that reflects both left ventricular (LV) systolic and diastolic function, has been shown to have prognostic value in several clinical settings, including myocardial infarction and congestive heart failure. There are scant data on the correlates and prognostic value of MPI in a population without overt cardiovascular (CV) disease. Methods: We investigated clinical and physiologic correlates of MPI, as assessed from echocardiographic Doppler recordings in 1,862 American Indian participants free of coronary or valvular disease or LV systolic dysfunction in the population-based strong heart study (SHS). We then assessed the prognostic value of MPI for incident CV events, including nonfatal stroke, coronary heart disease, congestive heart failure, and CV death. Results: The study population was 59 +/- 8 years old (66% women); 48% had diabetes, 44% hypertension, and 54% were obese. In univariable analyses, MPI (mean = 0.24 +/- 0.17) showed significant negative associations with creatinine clearance, C-reactive protein (CRP), LV ejection fraction (EF), mitral valve E- and A-wave velocities, cardiac index (CI), stroke index (SI) and stroke index/pulse pressure (SI/PP), and significant positive associations with serum creatinine and total peripheral resistance index (TPRI) (all P < 0.05). There were no significant associations of MPI with hypertension or diabetes status, systolic or diastolic blood pressure, body mass index, hemoglobin A1C or LV mass. After adjusting for age, sex, diabetes, and hypertension, MPI remained weakly but significantly correlated with CRP, EF, CI, SI, SI/PP, mitral E- and A-wave velocities, and TPRI. MPI did not predict fatal and nonfatal CV events (risk ratio 1.06 per unit MPI, 95% C.I. 0.56-2.04; P = 0.85) at a mean follow-up of 7.1 +/- 2.2 years. Conclusions: In a population-based sample of adults with high prevalence of diabetes, hypertension, and obesity but without overt CV disease, MPI has weak associations with clinical and physiologic determinants of cardiac function. Moreover, MPI does not provide prognostic information for CV events in this population. Though conceptually attractive as a global measure of cardiac function, MPI has limited utility in a high-risk population without clinical CV disease. C1 Cornell Univ, Weill Med Coll, New York, NY USA. Univ Arizona, Tucson, AZ USA. NHLBI, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. RP Mishra, RK (reprint author), New York Presbyterian Hosp, Div Cardiol, 525 E 68th St, New York, NY 10021 USA. EM rkm2001@med.cornell.edu OI Palmieri, Vittorio/0000-0003-3732-524X FU NCRR NIH HHS [M10RR0047-34]; NHLBI NIH HHS [HL41642, HL41652, HL65521, HL41654] NR 39 TC 18 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-2822 J9 ECHOCARDIOGR-J CARD JI Echocardiography-J. Cardiovasc. Ultrasound Allied Tech. PD APR PY 2007 VL 24 IS 4 BP 340 EP 347 DI 10.1111/j.1540-8175.2007.00415.x PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 148DZ UT WOS:000245056000003 PM 17381641 ER PT J AU Marietta, C Brooks, PJ AF Marietta, Cheryl Brooks, Philip J. TI Transcriptional bypass of bulky DNA lesions causes new mutant RNA transcripts in human cells SO EMBO REPORTS LA English DT Article DE RNA polymerase; Cockayne syndrome; xeroderma; pigmentosum; cyclopurine ID POLYMERASE-II; COUPLED REPAIR; XERODERMA PIGMENTOSUM; TRANSLESION SYNTHESIS; COCKAYNE-SYNDROME; IN-VIVO; ELONGATION; RECOGNITION; COMPLEX; BINDING AB Here, we characterize the mutant transcripts resulting from bypass of an 8,5'-cyclo-2'-deoxyadenosine (cyclo-dA) or cyclobutane pyrimidine dimer (CPD) by human RNA polymerase II (Pol II) in vivo. With the cyclo-dA lesion, we observed two new types of mutant transcripts. In the first type, the polymerase inserted uridine opposite the lesion and then misincorporated adenosine opposite the template deoxyadenosine downstream (50) of the lesion. The second type contained deletions of 7, 13 or 21 nucleotides (nt) after uridine incorporation opposite the lesion. The frequency of the different types of transcript from the cyclo-dA lesion in mutant human cell lines suggests that the Cockayne syndrome B protein affects the probability of deletion transcript formation. With the CPD-containing construct, we also detected rare transcripts containing 12 nt deletions. These results indicate that RNA pol II in living human cells can bypass helix-distorting DNA lesions that are substrates for nucleotide excision repair, resulting in transcriptional mutagenesis. C1 NIAAA, Neurogenet Lab, Mol Neurobiol Sect, Bethesda, MD 20892 USA. RP Brooks, PJ (reprint author), NIAAA, Neurogenet Lab, Mol Neurobiol Sect, 5625 Fishers Lane,Room S3-32,MSC 9412, Bethesda, MD 20892 USA. EM pjbrooks@mail.nih.gov FU Intramural NIH HHS [Z01 AA000083-14] NR 25 TC 50 Z9 50 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD APR PY 2007 VL 8 IS 4 BP 388 EP 393 DI 10.1038/sj.embor.7400932 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 152KA UT WOS:000245359700019 PM 17363972 ER PT J AU Kim, JS Bailey, MJ Ho, AK Moller, M Gaildrat, P Klein, DC AF Kim, Jong-So Bailey, Michael J. Ho, Anthony K. Moller, Morten Gaildrat, Pascaline Klein, David C. TI Daily rhythm in pineal phosphodiesterase (PDE) activity reflects adrenergic/3 ',5 '-cyclic adenosine 5 '-monophosphate induction of the PDE4B2 variant SO ENDOCRINOLOGY LA English DT Article ID SEROTONIN N-ACETYLTRANSFERASE; CAMP-SPECIFIC PHOSPHODIESTERASE; CYCLIC-AMP PHOSPHODIESTERASES; BETA-ADRENERGIC STIMULATION; ACTIVATED PROTEIN-KINASE; ORPHAN NUCLEAR RECEPTOR; RAT PINEALOCYTES; MELATONIN SYNTHESIS; CIRCADIAN EXPRESSION; MOLECULAR-CLONING AB The pineal gland is a photoneuroendocrine transducer that influences circadian and circannual dynamics of many physiological functions via the daily rhythm in melatonin production and release. Melatonin synthesis is stimulated at night by a photoneural system through which pineal adenylate cyclase is adrenergically activated, resulting in an elevation of cAMP. cAMP enhances melatonin synthesis through actions on several elements of the biosynthetic pathway. cAMP degradation also appears to increase at night due to an increase in phosphodiesterase (PDE) activity, which peaks in the middle of the night. Here, it was found that this nocturnal increase in PDE activity results from an increase in the abundance of PDE4B2 mRNA (similar to 5-fold; doubling time, similar to 2 h). The resulting level is notably higher (> 6-fold) than in all other tissues examined, none of which exhibit a robust daily rhythm. The increase in PDE4B2 mRNA is followed by increases in PDE4B2 protein and PDE4 enzyme activity. Results from in vivo and in vitro studies indicate that these changes are due to activation of adrenergic receptors and a cAMP-dependent protein kinase A mechanism. Inhibition of PDE4 activity during the late phase of adrenergic stimulation enhances cAMP and melatonin levels. The evidence that PDE4B2 plays a negative feedback role in adrenergic/cAMP signaling in the pineal gland provides the first proof that cAMP control of PDE4B2 is a physiologically relevant control mechanism in cAMP signaling. C1 NICHHD, Sect Neuroendocrinol, Off Sci Director, NIH, Bethesda, MD 20892 USA. Univ Alberta, Dept Physiol, Fac Med, Edmonton, AB T6G 2H7, Canada. Univ Copenhagen, Panum Inst, Inst Med Anat, DK-2200 Copenhagen, Denmark. RP Klein, DC (reprint author), NICHHD, Sect Neuroendocrinol, Off Sci Director, NIH, Bldg 49,Room 6A82, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov FU Intramural NIH HHS NR 66 TC 24 Z9 24 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2007 VL 148 IS 4 BP 1475 EP 1485 DI 10.1210/en.2006-1420 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 147GZ UT WOS:000244992700004 PM 17204557 ER PT J AU Klover, P Hennighausen, L AF Klover, Peter Hennighausen, Lothar TI Postnatal body growth is dependent on the transcription factors signal transducers and activators of transcription 5a/b in muscle: A role for autocrine/paracrine insulin-like growth factor I SO ENDOCRINOLOGY LA English DT Article ID IGF-I; SEXUAL-DIMORPHISM; BONE-GROWTH; HORMONE; STAT5B; MICE; GH; INACTIVATION; EXPRESSION; SYSTEM AB The transcription factors signal transducers and activators of transcription (STAT)5a and STAT5b (STAT5) are essential mediators of many actions of GH, including transcription of the IGF-I gene. Here, we present evidence that skeletal muscle STAT5 is important for postnatal growth and suggest that this is conveyed by the production of localized IGF-I. To investigate the role of STAT5 signaling in skeletal muscle, mice with a skeletal-muscle-specific deletion of the Stat5a and Stat5b genes (Stat5MKO mice) were used. IGF-I mRNA levels were reduced by 60% in muscle tissue of these mice. Despite only a 15% decrease in circulating IGF-I, 8-wk-old male Stat5MKO mice displayed approximately 20% reduction in body weight that was accounted for by a reduction in lean mass. The skeletons of Stat5MKO mice were found to be smaller than controls, indicating the growth defect was not restricted to skeletal muscle. These results demonstrate an as yet unreported critical role for STAT5 in skeletal muscle for local IGF-I production and postnatal growth and suggest the skeletal muscle as a major site of GH action. C1 NIDDK, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Klover, P (reprint author), 8 Ctr Dr,Bldg 8,Room 107, Bethesda, MD 20892 USA. EM kloverp@mail.nih.gov FU Intramural NIH HHS NR 29 TC 63 Z9 71 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 APR PY 2007 VL 148 IS 4 BP 1489 EP 1497 DI 10.1210/en.2006-1431 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 147GZ UT WOS:000244992700006 PM 17158201 ER PT J AU Harvey, CB Bassett, JHD Maruvada, P Yen, PM Williams, GR AF Harvey, Clare B. Bassett, J. H. Duncan Maruvada, Padma Yen, Paul M. Williams, Graham R. TI The rat thyroid hormone receptor (TR) Delta beta 3 displays cell-, TR isoform-, and thyroid hormone response element-specific actions SO ENDOCRINOLOGY LA English DT Article ID LIGAND-BINDING DOMAIN; GENE-EXPRESSION; BETA-RECEPTOR; TRANSCRIPTIONAL REGULATION; DIFFERENTIAL EXPRESSION; COACTIVATOR RECRUITMENT; POSTNATAL-DEVELOPMENT; MOLECULAR-BASIS; T-3 RECEPTORS; ALPHA-GENE AB The THRB gene encodes the well-described thyroid hormone ( T-3) receptor ( TR) isoforms TR beta 1 and TR beta 2 and two additional variants, TR beta 3 and TR Delta beta 3, of unknown physiological significance. TR beta 1, TR beta 2, and TR beta 3 are bona fide T-3 receptors that bind DNA and T-3 and regulate expression of T-3-responsive target genes. TR Delta beta 3 retains T-3 binding activity but lacks a DNA binding domain and does not activate target gene transcription. TR Delta beta 3 can be translated from a specific TR Delta beta 3 mRNA or is coexpressed with TR beta 3 from a single transcript that contains an internal TR Delta beta 3 translation start site. In these studies, we provide evidence that the TR beta 3/Delta beta 3 locus is present in rat but not in other vertebrates, including humans. We compared the activity of TR beta 3 with other TR isoforms and investigated mechanisms of action of TR Delta beta 3 at specific thyroid hormone response elements ( TREs) in two cell types. TR beta 3 was the most potent isoform, but TR potency was TRE dependent. TR Delta beta 3 acted as a cell-specific and TRE-dependent modulator of TR beta 3 when coexpressed at low concentrations. At higher concentrations, TR Delta beta 3 was a TRE-selective and cell-specific antagonist of TR alpha 1, -beta 1, and -beta 3. Both TR beta 3 and TR Delta beta 3 were expressed in the nucleus in the absence and presence of hormone, and their actions were determined by cell type and TRE structure, whereas TR Delta beta 3 actions were also dependent on the TR isoform with which it interacted. Analysis of these complex responses implicates a range of nuclear corepressors and coactivators as cell-, TR isoform-, and TRE-specific modulators of T-3 action. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Mol Endocrinol Grp, Ctr Clin Sci, London W12 0NN, England. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Div Med, Ctr Clin Sci, London W12 0NN, England. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC, Ctr Clin Sci, London W12 0NN, England. NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol, Baltimore, MD 21224 USA. RP Williams, GR (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Mol Endocrinol Grp, Ctr Clin Sci, London W12 0NN, England. EM graham.williams@imperial.ac.uk FU Medical Research Council [G108/502, G0501486]; Wellcome Trust [076584, 50570] NR 67 TC 21 Z9 22 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2007 VL 148 IS 4 BP 1764 EP 1773 DI 10.1210/en.2006-1248 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 147GZ UT WOS:000244992700036 PM 17218414 ER PT J AU Kan, HD London, SJ Chen, GH Zhang, YH Song, GX Zhao, NQ Jiang, LL Chen, BH AF Kan, Haidong London, Stephanie J. Chen, Guohai Zhang, Yunhui Song, Guixiang Zhao, Naiqing Jiang, Lili Chen, Bingheng TI Differentiating the effects of fine and coarse particles on daily mortality in Shanghai, China SO ENVIRONMENT INTERNATIONAL LA English DT Article DE air pollution; fine particles; coarse particles; PM2.5; mortality ID PARTICULATE AIR-POLLUTION; GENERALIZED ADDITIVE-MODELS; TIME-SERIES DATA; EPIDEMIOLOGIC EVIDENCE; TRANSITION-METALS; ORGANIC-COMPOUNDS; COACHELLA VALLEY; EUROPEAN CITIES; SULFUR-DIOXIDE; APHEA PROJECT AB The findings on health effects of ambient fine particles (PM2.5) and coarse particles (PM10-2.5) remain inconsistent. In China, PM2.5 and PM10-2.5 are not the criteria air pollutants, and their monitoring data are scarce. There have been no epidemiological studies of health effects of PM2.5 and PM10-2.5 simultaneously in China. We conducted a time series study to examine the acute effects of PM2.5 and PM10-2.5 on daily mortality in Shanghai, China from Mar. 4, 2004 to Dec. 31, 2005. We used the generalized additive model (GAM) with penalized splines to analyze the mortality, air pollution and covariate data. The average concentrations of PM2.5 and PM10-2.5 were 56.4 mu g/m(3) and 52.3 mu g/m(3) in our study period, and PM2.5 constituted around 53.0% of the PM10 mass. Compared with the Global Air Quality Guidelines set by World Health Organization (10 mu g/m(3) for annual mean) and U.S. National Ambient Air Quality Standards (15 mu g/m(3) for annual mean), the PM2.5 level in Shanghai was much higher. We found that PM2.5 was associated with the death rates from all causes and from cardiorespiratory diseases in Shanghai. We did not find a significant effect of PM10-2.5 on mortality outcomes. A10 mu g/m(3) increase in the 2-day moving average (lag01) concentration of PM2.5 corresponded to 0.36% (95% Cl 0.11%, 0.61%), 0.41% (95% Cl 0.01%, 0.82%) and 0.95% (95% Cl 0.16%, 1.73%) increase of total, cardiovascular and respiratory mortality. For PM10-2.5, the effects were attenuated and less precise. Our analyses provide the first statistically significant evidence in China that PM2.5 has an adverse effect on population health and strengthen the rationale for further limiting levels of PM2.5 in outdoor air in Shanghai. (c) 2006 Elsevier Ltd. All rights reserved. C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Fudan Univ, Sch Publ Hlth, Dept Environm Hlth, Shanghai 200032, Peoples R China. Shanghai Environm Monitoring Ctr, Shanghai 200030, Peoples R China. Shanghai Municipal Ctr Dis Control & Prevent, Shanghai 200336, Peoples R China. Fudan Univ, Dept Hlth Stat, Sch Publ Hlth, Shanghai 200032, Peoples R China. RP Kan, HD (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM haidongkan@gmail.com RI Wang, Linden/M-6617-2014; OI London, Stephanie/0000-0003-4911-5290 FU Intramural NIH HHS [Z01 ES043012-09] NR 76 TC 152 Z9 190 U1 5 U2 76 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 J9 ENVIRON INT JI Environ. Int. PD APR PY 2007 VL 33 IS 3 BP 376 EP 384 DI 10.1016/j.envint.2006.12.001 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 152NT UT WOS:000245369400012 PM 17229464 ER PT J AU Walker, VE Poirier, MC AF Walker, Vernon E. Poirier, Miriam C. TI Special issue on health risks of perinatal exposure to nucleoside reverse transcriptase inhibitors SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; HPRT LYMPHOCYTE MUTANTS; IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN LYMPHOBLASTOID-CELLS; BONE-MARROW MICRONUCLEI; TO-CHILD TRANSMISSION; HIV-INFECTED MOTHERS; IN-VITRO EXPOSURE; MITOCHONDRIAL TOXICITY; CORD BLOOD C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. NCI, Carcinogen DNA Interact Sect, LCCTP, NIH, Bethesda, MD 20892 USA. RP Walker, VE (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrost Dr SE, Albuquerque, NM 87108 USA. EM vwalker@lrri.org; poirierm@dc37a.nci.nih.gov NR 64 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 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 159 EP 165 DI 10.1002/em.20296 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100001 PM 17358025 ER PT J AU Divi, RL Haverkos, KJ Humsi, JA Shockley, ME Thamire, C Nagashima, K Olivero, OA Poirier, MC AF Divi, Rao L. Haverkos, Kathryn J. Humsi, Juliette A. Shockley, Marie E. Thamire, Chandrasekhar Nagashima, Kunio Olivero, Ofelia A. Poirier, Miriam C. TI Morphological and molecular course of mitochondrial pathology in cultured human cells exposed long-term to zidovudine SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE NCI cDNA microarray; mitochondrial gene mini array; JC1 staining; mitochondrial DNA quantity; lipodystrophy; electron microscopy ID REVERSE-TRANSCRIPTASE INHIBITORS; ACTIVE ANTIRETROVIRAL THERAPY; NUCLEOSIDE-ANALOG; ANTIVIRAL DRUGS; BINDING PROTEIN; DNA; TOXICITY; EXPRESSION; DEPLETION; AIDS AB Long-term use of antiretroviral nucleoside reverse transcriptase inhibitors (NRTIs) as therapy for human immunodeficiency virus-1 (HIV-1) infection is limited by mitochondrial toxicity. Here we document mitochondrial pathology during the long-term culture of human HeLa cells in the presence or absence of the NRTI Zidovudine((R)) (AZT, 800 mu M) for up to 77-possages (p), with samples taken at early (p5-p11), middle (p36 and p37), and late (p70-p77) passages. Samples were analyzed for changes in mitochondrial morphology, mitochondrial (mt)DNA quantity, nuclear and mitochondrial gene expression, and mitochondrial membrane potential. Mitochondria showed abnormal proliferation at p5 and abnormal morphology >= p36. mtDNA quantity was increased at p5 and p11, and 65% depleted at p71. Hierarchical clustering of nuclear gene expression, examined at p37 by the NO cDNA microarray in AZT-exposed cells, showed down-regulation of 13 out of 16 lipid-metabolizing genes, and upregulation of most oxidative phosphorylation (OXPHOS) genes. OXPHOS genes encoded by mtDNA, examined at p5, p36, and p75 using the Mitochondrial Gene Mini Array, revealed upregulation of genes coding for polypeptides of NADH dehydrogenase, ATP synthase, and cytochrome c oxiclase. Mitochondrial membrane potential, monitored by JC1 staining, was elevated at p10 and p32, and essentially completely absent at p7l. The data show that during chronic exposure of HeLa cells to AZT, a compensatory response was induced at the earlier passages (p5-p37), and by p71 there was widespread mitochondrial morphological damage, severe mtDNA depletion, and a substantial loss of mitochondrial membrane potential. Environ. Mal. Mutagen. 48:179-189, 2007. Published 2006 Wiley-Liss, Inc. C1 NCI, Cacinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. NCI, SAIC, Frederick, MD 21702 USA. RP Divi, RL (reprint author), NCI, Cacinogen DNA Interact Sect, NIH, Bldg 37,Rm 4032B,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM divir@exchange.nih.gov FU Intramural NIH HHS NR 40 TC 29 Z9 29 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 179 EP 189 DI 10.1002/em.20245 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100004 PM 16894629 ER PT J AU Chan, SSL Santos, JH Meyer, JN Mandavilli, BS Cook, DL McCash, CL Kissling, GE Nyska, A Foley, JF van Houten, B Copeland, WC Walker, VE Witt, KL Bishop, JB AF Chan, Sherine S. L. Santos, Janine H. Meyer, Joel N. Mandavilli, Bhaskar S. Cook, Dennis L., Jr. McCash, Consuelo L. Kissling, Grace E. Nyska, Abraham Foley, Julie F. van Houten, Bennett Copeland, William C. Walker, Vernon E. Witt, Kristine L. Bishop, Jack B. TI Mitochondrial toxicity in hearts of CD-1 mice following perinatal exposure to AZT, 3TC, or AZT/3TC in combination SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE mitochondrial DNA; mutations; cardiomyopathy; nucleoside reverse transcriptase inhibitors; Combivir; PCR ID DNA POLYMERASE-ALPHA; ANTIVIRAL NUCLEOSIDE ANALOGS; VIRUS REVERSE-TRANSCRIPTASE; ANTI-HIV DEOXYNUCLEOTIDES; MOUSE PUPS; IN-UTERO; UNINFECTED INFANTS; OXIDATIVE STRESS; SKELETAL-MUSCLE; PATAS MONKEYS AB Antiretroviral therapies based on nucleoside reverse transcriptase inhibitors (NRTIs), like zidovudine (3'-azido-3'-deoxythymidine; AZT) and lamivudine ((-)2',3'-dideoxy-3'-thiacytidine; 3TC), markedly reduce mother-to-child transmission of the human immunodeficiency virus (HIV). However, AZT induces damage in nuclear DNA of mice exposed in utero and postnatally, and mitochondrial DNA (mtDNA) damage has been observed in both human and mouse neonates following perinatal exposure to AZT and AZT/3TC in combination. To provide animal data modeling the NRTI-induced heart damage reported in human infants, we treated pregnant CD-1 mice throughout gestation and treated their pups by direct gavage from postnatal day (PND) 4 through PND 28 with daily doses of 150 mg/kg body weight (bw)/day AZT, 75 mg/ kg bw/day 3TC, 125/62.5 mg/kg bw/day AZT/ 3TC, or the vehicle control. Half the pups were euthanized on PND 28; the remainder received no further dosing, and were euthanized at week 10. Heart tissue was collected, total DNA was extracted, and mtDNA copy number relative to nuclear DNA copy number, mtDNA damage, and mtDNA mutation assays were performed using PCRbased methods. Analyses revealed increases in mtDNA lesions in 4-week-old males and females treated with AZT or 3TC, but not in 10-week-old mice, suggesting that the damage resolved after treatment ceased. Interestingly, 10-week-old females treated with AZT/3TC had significant increases in mtDNA damage. Point mutations were elevated in 10-week-old females treated with AZT or AZT/3TC, but not 3TC; no increases in mutations were seen in either gender at 4 weeks of age. Our data suggest that AZT/3TC combination treatment produces greater mtDNA damage than either agent individually, and that female mice are more sensitive than males to AZT/3TC-induced mtDNA damage. Environ. Mal. Mutagen. 48:190-200, 2007. Published 2006 Wiley-Liss, Inc. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Toxicol Operat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Bishop, JB (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, POB 12233,MD EC-01, Res Triangle Pk, NC 27709 USA. EM bishop@niehs.nih.gov FU NHLBI NIH HHS [R01 HL072727]; NIEHS NIH HHS [P30ES012072, N01-ES-75409] NR 51 TC 30 Z9 31 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 APR-MAY PY 2007 VL 48 IS 3-4 BP 190 EP 200 DI 10.1002/em.20191 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100005 PM 16395692 ER PT J AU Divi, RL Leonard, SL Kuo, MM Nagashima, K Thamire, C St Claire, MC Wade, NA Walker, VE Poirier, MC AF Divi, Rao L. Leonard, Sarah L. Kuo, Maryanne M. Nagashima, Kunio Thamire, Chandrasekhar St. Claire, Marisa C. Wade, Nancy A. Walker, Vernon E. Poirier, Miriam C. TI Transplacentally exposed human and monkey newborn infants show similar evidence of nucleoside reverse transcriptase inhibitor-induced mitochondrial toxicity SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE HIV-1; AZT; 3TC; d4T; ddl; electron microscopy; mitochondrial DNA; umbilical cord; cord blood ID ERYTHROCEBUS-PATAS MONKEYS; IN-UTERO; UNINFECTED INFANTS; ANTIVIRAL DRUGS; INFECTED WOMEN; CORD BLOOD; DNA; ZIDOVUDINE; DYSFUNCTION; LAMIVUDINE AB Effective reduction in maternal-fetal human immunodeficiency virus-1 (HIV-1) transmission has been achieved by administration of nucleoside reverse transcriptase inhibitors (NRTls) during pregnancy, and although most exposed children are clinically normal at birth, mitochondrial dysfunction has been reported. To examine mitochondrial integrity on a molecular level, we evaluated mitochondrial morphology by electron microscopy (EM) and mitochondrial DNA (mtDNA) quantity in umbilical cords and cord blood from NRTI-exposed and unexposed human and monkey newborns. Human subjects included infants born to HIV-1-infected mothers who received Combivir (Zidovudine [AZT] plus Lamivudine [3TC]) (n=9) or AZT plus Didanosine [ddl] (n=2) during pregnancy, and infants born to HIV-1-uninfected mothers (n=7). NRTI-exposed Erythrocebus patas monkey dams (n= 3 per treatment group) were given human-equivalent dosing regimens containing 3TC, AZT/3TC, AZT/ ddl, or Stavudine (d4T)/3TC during gestation. Four infants born to unexposed patas dams served as controls. Mitochondria in umbilical cord endothelial cells from NRTI-exposed monkey and human infants showed substantial abnormal pathology by EM, the extent of which was quantified from coded photomicrographs and shown to be different (P < 0.05) from the unexposed monkey and human newborns. Significant (P < 0.05) mtDNA depletion was found in umbilical cords from both human and monkey NRTIexposed infants and in human, but not in monkey, cord blood leukocytes. For umbilical cords, an increase in mitochondrial morphological damage correlated with reduction in mtDNA quantity in fetal monkeys (r=0.94). The treatment-induced mitochondrial compromise in infant monkeys ranked as follows: d4T/3TC > AZT/ddl > AZT/3TC > 3TC. The study demonstrates that transplacental NRTI exposures induce similar mitochondrial damage in cord blood and umbilical cords taken from retroviraluninfected monkey infants and from human infants born to HIV-1-infected women. Environ. Mol. Mutagen. 48:201-209, 2007. (c) 2006 Wiley-Liss, Inc. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. SAIC, NCI Frederick, Frederick, MD USA. Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. Bioqual Inc, Rockville, MD USA. Albany Med Ctr, Albany, NY USA. Lovelace Resp Res Inst, Albuquerque, NM USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Room 4032,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov FU Intramural NIH HHS; PHS HHS [R01 HLO 72727] NR 25 TC 31 Z9 32 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 201 EP 209 DI 10.1002/em.20201 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100006 PM 16538687 ER PT J AU Olivero, OA AF Olivero, Ofelia A. TI Mechanisms of genotoxicity of nucleoside reverse transcriptase inhibitors SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE nucleoside analogs; genotoxicity; antiretrovirals ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN LYMPHOBLASTOID-CELLS; MITOCHONDRIAL-DNA POLYMERASE; HUMAN LYMPHOID-CELLS; BONE-MARROW-CELLS; TELOMERASE ACTIVITY; THYMIDINE KINASE; IN-VITRO; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; 3-AZIDO-2,3-DIDEOXYTHYMIDINE AZT AB Nucleoside analogs were first approved by the U.S. Food and Drug Administration for use against HIV-AIDS in 1987. Since then, these agents, now commonly referred to as nucleoside reverse transcriptase inhibitors (NRTIs), have become essential components of the Highly Active Antiretroviral Therapy (HAART) drug combinations used for treatment of Human Immunodeficiency Virus-1 (HIV-1) infections. Their antiretroviral activity is likely two-fold: incorporation of the drug into viral DNA and inhibition of the viral reverse transcriptase. However, incorporation of the drug into host nuclear and mitochondrial DNA may be largely responsible for dose-limiting toxicities. Azidothymidine (AZT, 3'-azido-3'-deoxythymidine, zidovudine), the first NRTI approved for the therapy of HIV-1, is incorporated into DNA, causes mutations in the hypoxonthine-guanine phosphoribosyl-transferase (HPRT) and thymidine kinase (TK) genes, and induces micronuclei, chromosomal aberrations, sister chromatid exchange, shortened telomeres, and other genotoxic effects in cultured cells. Genomic instability would be predicted as a consequence of these events. Metabolic pathways that result in the phosphorylation of AZT play a crucial role in AZT-DNA incorporation, and may be altered after prolonged treatment. For example, thymidine kinase 1, the enzyme responsible for AZT mono-phosphorylation, is down-regulated during long-term exposure and appears to be associated with AZT-induced replication inhibition and the accumulation of cells in S-phose. Detailed information on the mechanisms underlying NRTI-associated antiretroviral efficacy, toxicity, and metabolic resistance were not available when AZT was first approved for use as an antiretroviral agent. Current insights, based on 15 years of research, may lead to intervention strategies to attenuate toxicity without altering drug efficacy. Environ. Mal. Mutagen. 48:215-223, 2007. Published 2006 Wiley-Liss, Inc. C1 NCI, Carcinogen DNA Interact Sect, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. RP Olivero, OA (reprint author), NCI, Carcinogen DNA Interact Sect, Lab Cellular Carcinogenesis & Tumor Promot, NIH, 37 Convent Dr,MSC 4255,Bldg 37 Rm 4032B, Bethesda, MD 20892 USA. EM oliveroo@exchange.nih.gov NR 81 TC 68 Z9 70 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 215 EP 223 DI 10.1002/em.20195 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100008 PM 16395695 ER PT J AU Torres, SM Walker, DM Carter, MM Cook, DL McCash, CL Cordova, EM Olivero, OA Poirier, MC Walker, VE AF Torres, Salina M. Walker, Dale M. Carter, Meghan M. Cook, Dennis L., Jr. McCash, Consuelo L. Cordova, Edmund M. Olivero, Ofelia A. Poirier, Miriam C. Walker, Vernon E. TI Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE HPRT; TK; nucleoside analog; transplacental ID ETHYL-N-NITROSOUREA; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; BONE-MARROW MICRONUCLEI; HPRT LYMPHOCYTE MUTANTS; REVERSE-TRANSCRIPTASE; DNA INCORPORATION; MITOCHONDRIAL DYSFUNCTION; NUCLEOSIDE ANALOGS; T-LYMPHOCYTES AB Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (KC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12-18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 mu M), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 mu M, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 mu M, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children. Environ. Mal. Mutagen. 48:224-238, 2007. (c) 2007 Wiley-Liss, Inc. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Walker, VE (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM vwalker@lrri.org FU NCI NIH HHS [1 R01 CA95741]; NHLBI NIH HHS [1 R01 HL72727] NR 56 TC 36 Z9 38 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 224 EP 238 DI 10.1002/em.20264 PG 15 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100009 PM 17358033 ER PT J AU Dobrovolsky, VN Shaddock, JG Mittelstaedt, RA Bishop, ME Lewis, SM Lee, FW Aidoo, A Leakey, JEA Dunnick, JK Heflich, RH AF Dobrovolsky, Vasily N. Shaddock, Joseph G. Mittelstaedt, Roberta A. Bishop, Michelle E. Lewis, Sherry M. Lee, Fei W. Aidoo, Anane Leakey, Julian E. A. Dunnick, June K. Heflich, Robert H. TI Frequency of Hprt mutant lymphocytes and micronucleated erythrocytes in p53-haplodeficient mice treated perinatally with AZT and AZT in combination with 3TC SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE nucleoside analog reverse transcriptase inhibitors; reticulocytes; normochromatic erythrocytes; transplacental exposure; neonatal exposure ID IMMUNODEFICIENCY-VIRUS TYPE-1; MATERNAL-INFANT TRANSMISSION; TRANSGENIC MOUSE MODELS; ETHYL-N-NITROSOUREA; REVERSE-TRANSCRIPTASE; DNA-POLYMERASE; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; MITOCHONDRIAL TOXICITY; NUCLEOSIDE ANALOG; TK(+/-) MICE AB Azidothymidine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) that is used for reducing mother-to-child transmission of human immunodeficiency virus 1. Combinations of AZT and 3'-thiacyticline (3TC) are even more effective than AZT alone. AZT, however, is a mutagen and carcinogen in rodent models and 3TC can increase the genotoxicity of AZT. Since p53 plays a key role in human and mouse tumorigenesis, p53-haplodeficient mice are currently being evaluated as a model for assessing the carcinogenicity of perinatal exposure to NRTIs. In the present study, male C57BL/6 p53(+/+) and p53(-/-) mice were mated with C3H p53(+/+) females; the pregnant females were treated on gestation day 12 through parturition with 40, 80, and 160 mg/kg of AZT or a combination of 160 mg/kg AZT and 100 mg/kg 3TC (AZT-3TC); the p53(+/+) and p53(+/-) offspring were treated daily after birth through postnatal day (PND) 28. The frequencies of micronucleated reticulocytes (MN-RETs) and micronucleated normochromatic erythrocytes (MN-NCEs) were determined on PNDI, PND 10, and PND28; the frequency of Hprt mutant lymphocytes was measured on PND28. The frequencies of MN-RETs and MN-NCEs were increased in treated animals at all time points; there were no differences in the responses of p53(+/+) and p53(+/-) animals treated with identical doses of NRTIs. After correction for clonal expansion, both AZT and AZT-3TC treatments induced small but significant increases in the frequency of Hprt mutant lymphocytes in p53(+/-) mice, but not in p53(+/+) mice. The data indicatethatp53 haplodeficiency affects the genotoxicity of NRTIs; thus, p53(+/-) mice may be a sensitive model for evaluating the carcinogenicity of perinatal exposure to NRTIs. Environ. Mol. Mutagen. 48:270-282, 2007. Published 2007 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, US FDA, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, US FDA, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT 120, Jefferson, AR 72079 USA. EM vasily.dobrovolsky@fda.hhs.gov NR 50 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 270 EP 282 DI 10.1002/em.20280 PG 13 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100013 PM 17358030 ER PT J AU Walker, DM Malarkey, DE Seilkop, SK Ruecker, FA Funk, KA Wolfe, MJ Treanor, CP Foley, JF Hahn, FF Hardisty, JF Walker, VE AF Walker, Dale M. Malarkey, David E. Seilkop, Steven K. Ruecker, Frederick A. Funk, Kathleen A. Wolfe, Marilyn J. Treanor, Christopher P. Foley, Julie F. Hahn, Fletcher F. Hardisty, Jerry F. Walker, Vernon E. TI Transplacental carcinogenicity of 3 '-azido-3 '-deoxythymidine in B6C3F1 mice and f344 rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE carcinogenicity; mice; pregnancy; rats; zidovudine ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN LYMPHOBLASTOID-CELLS; HPRT LYMPHOCYTE MUTANTS; BONE-MARROW-CELLS; IN-UTERO EXPOSURE; ANTIRETROVIRAL THERAPY; DNA INCORPORATION; PREGNANT-WOMEN; CONGENITAL-MALFORMATIONS; ZIDOVUDINE TREATMENT AB The prophylactic use of zidovudine (3'-azido-3'-deoxythymidine, AZT) during pregnancy greatly reduces transmission of HIV-1 from infected mothers to their infants; however, the affinity of host cell DNA polymerases for AZT also allows for its incorporation into host cell DNA, predisposing to cancer development. To expand upon previous transplacental carcinogenesis assays performed in CD-1 mice, the transplacental carcinogenicity of AZT was evaluated in a second mouse strain and a second rodent species. Date-mated female mice and rats were gavaged daily with 0, 80, 240, or 480 mg AZT/kg bw during the last 7 days of gestation. At 2 years postpartum, male and female B6C3Fl mouse and F344 rat offspring (n=44-46 of each sex and species/treatment group) were necropsied for gross and microscopic tissue examinations. Under the conditions of these two-year studies, there was clear evidence of carcinogenic activity based upon significant dose-related trends and increases in the incidences of hemangiosarcoma in male mice and mononuclear cell leukemia in female rats. There was some evidence of carcinogenic activity in the livers of male mice based upon a positive trend and an increased incidence of hepatic carcinoma in the high-dose AZT group. The incidence of gliomas in female rats exceeded the historical background rates for gliomas in F344 rats. P53 overexpression was detected in some AZT-treated mouse neoplasms. These and other cancer-related findings confirm and extend those of previous transplacental carcinogenicity studies of AZT in mice, support the need for long-term followup of nucleoside reverse transcriptase inhibitor (NRTI)-exposed children, and indicate the necessity for effective protective strategies against NRTI-induced side effects. Environ. Mal. Mutagen. 48:283-298, 2007. (c) 2007 Wiley-Liss, Inc. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. Expt Pathol Labs Inc, Herndon, VA USA. Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC USA. SKS Consulting Serv, Siler City, NC USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA. Univ New Mexico, Coll Pharmacol, Albuquerque, NM 87131 USA. RP Walker, VE (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM vwalker@lrri.org FU NCI NIH HHS [R01CA95741]; NICHD NIH HHS [R01HD33648] NR 52 TC 27 Z9 27 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 283 EP 298 DI 10.1002/em.20297 PG 16 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100014 PM 17358026 ER PT J AU Hong, HHL Dunnick, J Herbert, R Devereux, TR Kim, Y Sills, RC AF Hong, Hue-Hua L. Dunnick, June Herbert, Ronald Devereux, Theodora R. Kim, Yongbaek Sills, Robert C. TI Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from Swiss (CD-1) male mice exposed transplacentally to AZT SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE 3 '-azido-3 '-deoxythymidine; AZT; transplacental carcinogenesis; lung cancer; Swiss mice; K-ras oncogene; p53 tumor suppressor gene ID TUMOR-SUPPRESSOR GENE; OXIDATIVE DNA-DAMAGE; B6C3F1 MICE; MOLECULAR PATHOGENESIS; MITOCHONDRIAL TOXICITY; O-NITROTOLUENE; HIGH-FREQUENCY; IN-UTERO; MUTATIONS; MOUSE AB A transplacental carcinogenicity study was conducted by exposing pregnant Swiss (CD-1) mice to 0, 50, 100, 200, or 300 mg of 3'-azido-3'-deoxythymidine (AZT)/kg bw/day, through a 18 to 19 day gestation [National Toxicology Program, NIH Pub. No. 04-4458, 2004]. The incidences of alveolar/bronchiolar adenomas and carcinomas, in the 200 and 300 mg/kg male treatment groups, were significantly greater than that of the controls. In the present study, we evaluated the benign and malignant lung neoplasms from this bioassay for point mutations, in the K-ras and p53 cancer genes that are often mutated in human lung tumors. K-ros and p53 mutations were detected by cycle sequencing of polymerose chain reaction-amplified DNA, isolated from formalin-fixed, paraffin-embedded neoplasms. K-ros mutations were detected in 25 of 38 (66%) of the AZT-induced lung tumors, and the predominant mutations were codon 12 G-T transversions. p53 mutations were detected in 32 of 38 (84%) of the AZT-induced lung tumors, with the predominant mutations being exon 8, codon 285 A-T transversions, and exon 6, codon 198 T-A transversions. No K-ros or p53 mutations were detected in five tumors, examined from control mice. The patterns of mutations identified in the lung tumors suggest that incorporation of AZT or its metabolites into DNA, oxidative stress, and genomic instability may be the contributing factors to the mutation profile and development of lung cancer in these mice. Environ. Mal. Mutagen. 48:299-306, 2007. Published 2006 Wiley-Liss, Inc. C1 NIEHS, Mol Pathol Grp, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. RP Hong, HHL (reprint author), NIEHS, Mol Pathol Grp, Lab Expt Pathol, MD E1-07,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM hong@niehs.nih.gov NR 51 TC 22 Z9 22 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 299 EP 306 DI 10.1002/em.20197 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100015 PM 16395694 ER PT J AU Meng, QX Olivero, OA Fasco, MJ Bellisario, R Kaminsky, L Pass, KA Wade, NA Abrams, EJ Nesel, CJ Ness, RB Bigbee, WL O'Neill, JP Walker, DM Poirier, MC Walker, VE AF Meng, Quanxin Olivero, Ofelia A. Fasco, Michael J. Bellisario, Ronald Kaminsky, Laurence Pass, Ken A. Wade, Nancy A. Abrams, Elaine J. Nesel, Carol J. Ness, Roberta B. Bigbee, William L. O'Neill, J. Patrick Walker, Dale M. Poirier, Miriam C. Walker, Vernon E. CA Study Team TI Plasma and cellular markers of 3 '-azido-3 '-dideoxythymidine (AZT) metabolism as indicators of DNA damage in cord blood mononuclear cells from infants receiving prepartum NRTIs SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE AZT-DNA incorporation; lamivudine; 3TC-DNA incorporation; transplacental genotoxicity; zidovudine ID HUMAN-IMMUNODEFICIENCY-VIRUS; HPRT MUTANT FREQUENCIES; INTRACELLULAR ZIDOVUDINE; REVERSE-TRANSCRIPTASE; 3-AZIDO-2,3-DIDEOXYTHYMIDINE AZT; RESPONSE RELATIONSHIPS; T-LYMPHOCYTES; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHOSPHORYLATION; GENOTOXICITY AB Several systemic and cellular markers of 3'-azido-3'-dideoxythymidine (AZT) metabolism and AZT incorporation into nuclear DNA were measured in cord blood from uninfected infants born to HIV-1 -infected mothers receiving prepartum therapies based on AZT or AZT in combination with 2',3'-dideoxy-3'thiacytidine (3TC). In addition, the relationships among these pharmacological end points, levels of AZT-DNA incorporation, and the previously reported mutagenic responses in these infants were evaluated. AZT- and 3TC-specific radioimmunoassays (RIAs), or HPLC coupled with AZT-RIA, were used to measure plasma levels of AZT and the AZTglucuronide, and cellular levels of AZT, phosphorylated AZT, and DNA incorporation of AZT or 3TC in cord blood mononuclear cells from treated infants compared with unexposed controls born to HIV-uninfected mothers. Fewer infants had detectable AZT-DNA incorporation levels in the group exposed to AZT (71%; n=7) compared with those receiving AZT-3TC (100%; n=21), and the mean AZT-DNA incorporation for AZT-exposed infants (14.6 +/- 6.3 AZT/10(6) nucleotides) was significantly lower than that in AZT-3TC exposed infants (51.6 +/- 10.2 AZT/ 10(6) nucleoticles; P=0.028). Low levels of 3TCDNA incorporation found in a few AZT-3TCexposed newborns correlated with AZT-DNA incorporation values in the same samples. Among the metabolites studied, there were positive correlations between levels of AZT-diphosphate and AZT-triphosphate, and AZT-triphosphate and AZT-DNA incorporation, in nucleoside analog-exposed infants. Levels of AZT-DNA incorporation, however, did not correlate well with the reported frequencies of somatic mutations in the some population of nucleoside anglog-treated children. While these data support the continued use of AZT-based therapies during pregnancy, infants receiving prepartum AZT should be monitored long-term for adverse health effects. Enviran. Mol. Mutagen. 48:307-321, 2007. (c) 2007Wiley-Liss, Inc. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA. NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Albany Med Ctr, Dept Pediat, Albany, NY USA. Columbia Univ, Dept Pediat, Coll Phys & Surg, New York, NY 10027 USA. Harlem Hosp Med Ctr, New York, NY 10037 USA. Westat Corp, Rockville, MD USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. Univ Vermont, Genet Lab, Burlington, VT 05405 USA. Univ New Mexico, Coll Pharmacol, Albuquerque, NM 87131 USA. RP Walker, VE (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM vwalker@lrri.org FU NCI NIH HHS [R01CA95741]; NICHD NIH HHS [R01 HD33648] NR 64 TC 22 Z9 22 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 307 EP 321 DI 10.1002/em.20298 PG 15 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100016 PM 17358024 ER PT J AU Witt, KL Cunningham, CK Patterson, KB Kissling, GE Dertinger, SD Livingston, E Bishop, JB AF Witt, Kristine L. Cunningham, Coleen K. Patterson, Kristine B. Kissling, Grace E. Dertinger, Stephen D. Livingston, Elizabeth Bishop, Jack B. TI Elevated frequencies of micronucleated erythrocytes in infants exposed to zidovudine in utero and postpartum to prevent mother-to-child transmission of HIV SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE AZT; antiretroviral; chromosome damage; transplacental exposure; nucleoside analogues; mutagenicity ID BONE-MARROW MICRONUCLEI; HPRT LYMPHOCYTE MUTANTS; PERIPHERAL-BLOOD; GENETIC-DAMAGE; CYTOGENETIC DAMAGE; DNA INCORPORATION; DIRECT GAVAGE; MICE; 3'-AZIDO-3'-DEOXYTHYMIDINE; GENOTOXICITY AB Zidovudine-based antiretroviral therapies (ARTs) for treatment of HIV-infected pregnant women have markedly reduced mother-to-child transmission of the human immunodeficiency virus (HIV-1) from similar to 25% to < 1%. However, zidovudine (ZDV; AZT), a nucleoside analogue, induces chromosomal damage, gene mutations, and cancer in animals following direct or transplacental exposure. To determine if chromosomal damage is induced by ZDV in infants exposed transplacentally, we evaluated micronucleated reticulocyte frequencies (%MN-RET) in 16 HIV-infected ART-treated mother-infant pairs. Thirteen women received prenatal ART containing ZDV; three received ART without ZDV. All infants received ZDV for 6 weeks postpartum. Venous blood was obtained from women at delivery and from infants at 1-3 days, 4-6 weeks, and 4-6 months of life; cord blood was collected immediately after delivery. Ten cord blood samples (controls) were obtained from infants of HIV-uninfected women who did not receive ART. %MN-RET was measured using a single laser 3-color flow cytometric system. Tenfold increases in %MNRET were seen in women and infants who received ZDV-containing ART prenatally; no increases were detected in three women and infants who received prenatal ART without ZDV. Specifically, mean %MNRET in cord blood of ZDV-exposed infants was 1.67 +/- 0.34 compared with 0.16 +/- 0.06 in non-ZDV ART-exposed infants (P=0.006) and 0.12 +/- 0.02 in control cord bloods (P < 0.0001). %MN-RET in ZDV-exposed newborns decreased over the first 6 months of life to levels comparable to cord blood controls. These results demonstrate that transplacental ZDV exposure is genotoxic in humans. Long-term monitoring of HIV-uninfected ZDV-exposed infants is recommended to ensure their continued health. Environ. Mol. Mutagen. 48:322-329, 2007. Published 2007 Wiley-Liss, Inc. C1 NIEHS, Environm Toxicol Program, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA. Litron Labs, Rochester, NY USA. RP Bishop, JB (reprint author), NIEHS, Environm Toxicol Program, Natl Toxicol Program, POB 12233,Mail Drop EC-01, Res Triangle Pk, NC 27709 USA. EM bishop@niehs.nih.gov FU Intramural NIH HHS [Z99 ES999999, 001-1376-259] NR 40 TC 40 Z9 41 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 APR-MAY PY 2007 VL 48 IS 3-4 BP 322 EP 329 DI 10.1002/em.20266 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100017 PM 17358032 ER PT J AU Escobar, PA Olivero, OA Wade, NA Abrams, EJ Nesel, CJ Ness, RB Day, RD Day, BW Meng, QX O'Neill, JP Walker, DM Poirier, MC Walker, VE Bigbee, WL AF Escobar, Patricia A. Olivero, Ofelia A. Wade, Nancy A. Abrams, Elaine J. Nesel, Carol J. Ness, Roberta B. Day, Richard D. Day, Billy W. Meng, Quanxin O'Neill, J. Patrick Walker, Dale M. Poirier, Miriam C. Walker, Vernon E. Bigbee, William L. CA Study Team TI Genotoxicity assessed by the Comet and GPA assays following in vitro exposure of human lymphoblastoid cells (H9) or perinatal exposure of mother-child pairs to AZT or AZT-3TC SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE AZT-DNA incorporation; Comet assay; glycophorin A mutations; lamivudine; transplacental mutagenicity; zidovudine ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCED DNA-DAMAGE; HPRT LYMPHOCYTE MUTANTS; BONE-MARROW MICRONUCLEI; SOMATIC MUTATIONS; POLYMERASE BETA; MICE; 3'-AZIDO-3'-DEOXYTHYMIDINE; ZIDOVUDINE; FREQUENCY AB The genotoxicity of zidovudine (AZT) based treatments was investigated in human H9 lymphoblastoid cells in an in vitro study and in red blood cells (RBCs) from perinatally exposed HIV-1-infected mothers and their infants in an observational cohort study. Exposure of H9 cells for 24 hr to AZT produced dose-dependent increases in Comet assay tail moment (TM) when electrophoresed at pH 13.0, but not at pH 12.1 or pH 8.0, suggesting that DNA damage was via alkali-labile lesions and not double-stranded DNA strand breaks. The TM dose response at pH 13.0 correlated directly with AZT-DNA incorporation determined by AZT-radioimmunoassay. Levels of DNA damage in utero, measured by Comet assay TM, were similar in cord blood mononuclear cells of nucleoside analogexposed newborns (n=43) and unexposed controls (n=40). In contrast, the glycophorin A (GPA) somatic cell mutation assay (which screens for large-scale DNA damage in RBCs) showed clear evidence that GPA N/N variants, arising from chromosome loss and duplication, somatic recombination, and gene conversion, were significantly elevated in mother-child pairs receiving prepartum AZT plus lamivudine (3TC). Cord blood from newborns exposed to AZT-3TC had GPA N/ N variant frequencies of 4.7 +/- 0.7 (mean +/- SE) x 10(-6) RBCs (n=26 infants) compared with 2.2 +/- 0.3 x 10(-6) RBCs for unexposed controls (n= 30 infants; P < 0.001). Elevations in GPA N/N variants generally persisted through 1 year of age in nucleoside analog-exposed children. Overall, the mutagenic effects found in mother-child pairs receiving AZT-based treatments justify their surveillance for long-term genotoxic consequences. Environ. Mol. Mutagen. 48:330-343, 2007. (c) 2007Wiley-Liss, Inc. C1 Lovelace Resp Res Inst, Albuquerque, NM 87108 USA. Univ Vermont, Genet Lab, Burlington, VT 05405 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15260 USA. NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Chldrens Hosp, Albany Med Ctr, Dept Pediat, Albany, NY USA. Columbia Univ, Coll Phys & Surg, Dept Pediat, New York, NY 10027 USA. Harlem Hosp Med Ctr, New York, NY 10037 USA. Westat Corp, Rockville, MD USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA. SUNY Albany, Wadsworth Ctr, Albany, NY 12222 USA. RP Walker, VE (reprint author), Lovelace Resp Res Inst, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA. EM vwalker@lrri.org FU NCI NIH HHS [R01 CA95741]; NICHD NIH HHS [R01 HD33648, R01 HD33016] NR 58 TC 36 Z9 38 U1 1 U2 6 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 APR-MAY PY 2007 VL 48 IS 3-4 BP 330 EP 343 DI 10.1002/em.20285 PG 14 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100018 PM 17358027 ER PT J AU Hennig, B Ettinger, AS Jandacek, RJ Koo, S McClain, C Seifried, H Silverstone, A Watkins, B Suk, WA AF Hennig, Bernhard Ettinger, Adrienne S. Jandacek, Ronald J. Koo, Sung McClain, Craig Seifried, Harold Silverstone, Allen Watkins, Bruce Suk, William A. TI Using nutrition for intervention and prevention against environmental chemical toxicity and associated diseases SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE antioxidants; diet; disease; environmental toxicants; nutrition; pollutants; prevention ID ARYL-HYDROCARBON RECEPTOR; NONALCOHOLIC STEATOHEPATITIS; PGE(2) PRODUCTION; LIVER-DISEASE; CELLS; ACTIVATION; CANCER; CHOLESTEROL; MODULATION; NUTRIENTS AB BACKGROUND: Nutrition and lifestyle are well-defined modulators of chronic diseases. Poor dietary habits (such as high intake of processed foods rich in fat and low intake of fruits and vegetables), as well as a sedentary lifestyle dearly contribute to today's compromised quality of life in the United States. It is becoming increasingly clear that nutrition can modulate the toxicity of environmental pollutants. OBJECTIVES: Our goal in this commentary is to discuss the recommendation that nutrition should be considered a necessary variable in the study of human disease associated with exposure to environmental pollutants. DISCUSSION: Certain diets can contribute to compromised health by being a source of exposure to environmental toxic pollutants. Many of these pollutants are fat soluble, and thus fatty foods often contain higher levels of persistent organics than does vegetable matter. Nutrition can dictate the lipid milieu, oxidative stress, and antioxidant status within cells. The modulation of these parameters by an individual's nutritional status may have profound affects on biological processes, and in turn influence the effects of environmental pollutants to cause disease or dysfunction. For example, potential adverse health effects associated with exposure to polychlorinated biphenyls may increase as a result of ingestion of certain dietary fats, whereas ingestion of fruits and vegetables, rich in antioxidant and anti-inflammatory nutrients or bioactive compounds, may provide protection. CONCLUSIONS: We recommend that future directions in environmental health research explore this nutritional paradigm that incorporates a consideration of the relationships between nutrition and lifestyle, exposure to environmental toxicants, and disease. Nutritional interventions may provide the most sensible means to develop primary prevention strategies of diseases associated with many environmental toxic insults. C1 Univ Kentucky, Coll Agr, Mol & Cell Nutr Lab, Lexington, KY 40536 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH USA. Univ Connecticut, Dept Nutr Sci, Storrs, CT USA. Univ Louisville, Dept Med, Div Gastroenterol Hepatol, Louisville, KY 40292 USA. NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA. SUNY Upstate Med Univ, Dept Microbiol & Immunol, Syracuse, NY USA. Purdue Univ, Dept Food Sci, Lipid Chem & Mol Biol Lab, W Lafayette, IN 47907 USA. NIEHS, Ctr Risk & Integrated Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Hennig, B (reprint author), Univ Kentucky, Coll Agr, Mol & Cell Nutr Lab, Rm 591,Wethington Hlth Sci Bldg,900 S Limestone, Lexington, KY 40536 USA. EM bhennig@uky.edu FU NIEHS NIH HHS [P42 ES007380, P42 ES 007380] NR 32 TC 35 Z9 37 U1 1 U2 12 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 APR PY 2007 VL 115 IS 4 BP 493 EP 495 DI 10.1289/ehp.9549 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800025 PM 17450213 ER PT J AU Lee, WJ Alavania, MCR Hoppin, JA Rusiecki, JA Kamel, F Blair, A Sandler, DP AF Lee, Won Jin Alavania, Michael C. R. Hoppin, Jane A. Rusiecki, Jennifer A. Kamel, Freya Blair, Aaron Sandler, Dale P. TI Mortality among pesticide applicators exposed to chlorpyrifos in the agricultural health study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chlorpyrifos; farmers; injuries; insecticides; mortality; suicide ID UNITED-STATES; SEROTONERGIC MECHANISMS; CHRONIC DIETARY; BLOOD-PRESSURE; RISK-FACTORS; MALE FARMERS; SUICIDE; DEPRESSION; RATS; CANCER AB BACKGROUND: Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited.. OBJECTIVE: To evaluate whether agricultural chlorpyrifos exposure was associated with mortality, we examined deaths among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina. METHODS: A total of 55,071 pesticide applicators were included in this analysis. Detailed pesticide exposure data and other information were obtained from self-administered questionnaires completed at the time of enrollment (1993-1997). Lifetime chlorpyrifos use was divided into tertiles. Poisson regression analysis was used to evaluate the exposure-response relationships between chlorpyrifos use and causes of death after adjustment for potential confounders. RESULTS: A total of 1,851 deaths (588 among chlorpyrifos users) were observed during the study period, 1993-2001. The relative risk (RR) of death from all causes combined among applicators exposed to chlorpyrifos was slightly lower than that for nonexposed applicators (RR = 0.90; 95% confidence interval, 0.8 1-1.01). For most causes of death analyzed, there was no evidence or an exposure-response relationship. However, the relative risks for mortality from suicide and nonmotor-vehicle accidents were increased 2-fold in the highest category of chlorpyrifos exposure days. CONCLUSIONS: Our findings of a possible association between chlorpyrifos use and external causes of death were based on small numbers. However, the findings may reflect a link between chlorpyrifos and depression or other neurobehavioral symptoms that deserves further evaluation. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Sandler, DP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM sandler@mail.nih.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 64 TC 29 Z9 30 U1 3 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 APR PY 2007 VL 115 IS 4 BP 528 EP 534 DI 10.1289/ehp.9662 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800032 PM 17450220 ER PT J AU Lein, PJ Yang, DR Bachstetter, AD Tilson, HA Harry, GJ Mervis, RF Kodavanti, PRS AF Lein, Pamela J. Yang, Dongren Bachstetter, Adam D. Tilson, Hugh A. Harry, G. Jean Mervis, Ronald F. Kodavanti, Prasada Rao S. TI Ontogenetic alterations in molecular and structural correlates of dendritic growth after developmental exposure to polychlorinated Biphenyls SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE dendritogenesis; developmental neurotoxicology; learning and memory; molecular markers; polychlorinated biphenyls ID THYROID HORMONE-LIKE; ENVIRONMENTAL PCB MIXTURE; CEREBELLAR GRANULE CELLS; FETAL-RAT BRAIN; PYRAMIDAL CELLS; MORPHOLOGICAL ALTERATIONS; SYNAPTIC PLASTICITY; RYANODINE RECEPTORS; COMMERCIAL MIXTURE; MENTAL-RETARDATION AB OBJECTIVE: Perinatal exposure to polychlorinated biphenyls (PCBs) is associated with decreased IQ scores, impaired learning and memory, psychomotor difficulties, and attentional deficits in children. It is postulated that these neuropsychological deficits reflect altered patterns of neuronal connectivity. To test this hypothesis, we examined the effects of developmental PCB exposure on dendritic growth. METHODS: Rat dams were gavaged from gestational day 6 through postnatal day (PND) 21 with vehicle (corn oil) or the commercial PCB mixture Aroclor 1254 (6 mg/kg/day). Dendritic growth and molecular markers were examined in pups during development. RESULTS: Golgi analyses of CA1 hippocampal pyramidal neurons and cerebellar Purkinge cells indicated that developmental exposure to PCBs caused a pronounced age-related increase in dendritic growth. Thus, even though dendritic lengths were significantly attenuated in PCB-treated animals at PND22, the rate of growth was accelerated at later ages such that by PND60, dendritic growth was comparable to or even exceeded that observed in vehicle controls. Quantitative reverse transcriptase polymerase chain reaction analyses demonstrated that from PND4 through PND21, PCBs generally increased expression of both spinophilin and RC3/neurogranin mRNA in the hippocampus, cerebellum, and cortex with the most significant increases observed in the cortex. CONCLUSIONS: This study demonstrates that developmental PCB exposure alters the ontogenetic profile of dendritogenesis in critical brain regions, supporting the hypothesis that disruption of neuronal connectivity contributes to neuropsychological deficits seen in exposed children. C1 US EPA, Cellular & Mol Toxicol Branch, Div Neurotoxicol, NHEERL,ORD, Res Triangle Pk, NC 27711 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR USA. Neurostruct Res Labs, Tampa, FL USA. Univ S Florida, Ctr Excellence Aging & Brain Repair, Coll Med, Tampa, FL USA. Univ S Florida, Coll Med, Dept Neurosurg, Tampa, FL USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Kodavanti, PRS (reprint author), US EPA, Cellular & Mol Toxicol Branch, Div Neurotoxicol, NHEERL,ORD, B 105-06, Res Triangle Pk, NC 27711 USA. EM kodavanti.prasada@epa.gov FU Intramural NIH HHS [Z99 ES999999]; NICHD NIH HHS [HD 40936, R03 HD040936]; NINDS NIH HHS [NS 046649, R01 NS046649] NR 96 TC 41 Z9 41 U1 2 U2 8 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2007 VL 115 IS 4 BP 556 EP 563 DI 10.1289/ehp.9773 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800036 PM 17450224 ER PT J AU Pezzoli, K Tukey, R Sarabia, H Zaslavsky, I Miranda, ML Suk, WA Lin, A Ellisman, M AF Pezzoli, Keith Tukey, Robert Sarabia, Hiram Zaslavsky, Ilya Miranda, Marie Lynn Suk, William A. Lin, Abel Ellisman, Mark TI The NIEHS environmental health sciences data resource portal: Placing advanced technologies in service to vulnerable communities SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE community-linked research; cyberinfrastructure; disaster; environmental justice; GIS; grid; health disparities; integrative research; Katrina; telescience ID HURRICANE KATRINA; CYBERINFRASTRUCTURE; TOXICOGENOMICS; ONTOLOGY; SYSTEMS AB BACKGROUND: Two devastating hurricanes ripped across the Gulf Coast of the United States daring 2005. The effects of Hurricane Katrina were especially severe: The human and environmental health impacts on New Orleans, Louisiana, and other Gulf Coast communities will be felt for decades to come. The Federal Emergency Management Agency (FEMA) estimates that Katrina's destruction disrupted the lives of roughly 650,000 Americans. Over 1,300 people died. The projected economic costs for recovery and reconstruction are likely to exceed $125 billion. OBJECTIVES: The NIEHS (National Institute of Environmental Health Sciences) Portal aims to provide decision makers with the data, information, and the tools they need to a) monitor human and environmental health impacts of disasters; b) assess and reduce human exposures to contaminants; and c) develop science-based remediation, rebuilding, and repopulation strategies.. METHODS: The NIEHS Portal combines advances in geographic information systems (GIS), data mining/integration, and visualization technologies through new forms of grid-based (distributed, web-accessible) cyberinfirastructure. RESULTS: The scale and complexity of the problems presented by Hurricane Katrina made it evident that no stakeholder alone could tackle them and that there is a need for greater collaboration. The NIEHS Portal provides a collaboration-enabling, information-laden base necessary to respond to environmental health concerns in the Gulf Coast region while advancing integrative multidisciplinary research. CONCLUSIONS: The NIEHS Portal is poised to serve as a national resource to track environmental hazards following natural and man-made disasters, focus medical and environmental response and recovery resources in areas of greatest need, and function as a test bed for technologies that will help advance environmental health sciences research into the modern scientific and computing era. C1 Univ Calif San Diego, Urban Studies & Planning Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA. Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92093 USA. Duke Univ, Nicholas Sch Environm & Earth Sci, Durham, NC USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Calif San Diego, Natl Ctr Microsurg & Imaging Res, Ctr Res Biol Syst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Pezzoli, K (reprint author), Univ Calif San Diego, Urban Studies & Planning Program, 9500 Gilman Dr,0517, La Jolla, CA 92093 USA. EM kpezzoli@ucsd.edu RI Smith, Barry/A-9525-2011 OI Smith, Barry/0000-0003-1384-116X FU NCRR NIH HHS [P41 RR 008605, P41 RR 004050, P41 RR004050, P41 RR008605]; NIEHS NIH HHS [3P42 ES 010337-07S1, 5P42 ES 010356-07S1, P42 ES 010337, P42 ES010337, P42 ES010356] NR 40 TC 10 Z9 10 U1 2 U2 10 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2007 VL 115 IS 4 BP 564 EP 571 DI 10.1289/ehp/9817 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800037 PM 17450225 ER PT J AU Auman, JT Chou, J Gerrish, K Huang, Q Jayadev, S Blanchard, K Paules, RS AF Auman, J. Todd Chou, Jeff Gerrish, Kevin Huang, Qihong Jayadev, Supriya Blanchard, Kerry Paules, Richard S. TI Identification of genes implicated in methapyrilene-induced hepatotoxicity by comparing differential gene expression in target and nontarget tissue SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE DNA microarray; gene expression; hepatotoxicity; liver; methapyrilene; toxicogenomics ID CONSTITUTIVE ANDROSTANE RECEPTOR; ENDOPLASMIC-RETICULUM STRESS; PREGNANE-X-RECEPTOR; UNFOLDED PROTEIN RESPONSE; OXIDATIVE STRESS; LIVER-INJURY; MOUSE-LIVER; RAT LIVERS; ER STRESS; IN-VITRO AB BACKGROUND: Toxicogenomics experiments often reveal thousands of transcript alterations that are related to multiple processes, making it difficult to identify key gene changes that are related to the toxicity of interest. OBJECTIVES: The objective of this study was to compare gene expression changes in a nontarget tissue to the target tissue for toxicity to help identify toxicity-related genes. METHODS: Male rats were given the hepatotoxicant methapyrilene at two dose levels, with livers and kidneys removed 24 hr after one, three, and seven doses for gene expression analysis. To identify gene changes likely to be related to toxicity, we analyzed genes on the basis of their temporal pattern of change using a program developed at the National Institute of Environmental Health Sciences, termed "EPIG" (extracting gene expression patterns and identifying co-expressed genes). RESULTS: High-dose methapyrilene elicited hepatic damage that increased in severity with the number of doses, whereas no treatment-related lesions were observed in the kidney. High-dose methapyrilene elicited thousands of gene changes in the liver at each time point, whereas many fewer gene changes were observed in the kidney. EPIG analysis identified patterns of gene expression correlated to the observed toxicity, including genes associated with endoplasmic reticulum stress and the unfolded protein response. CONCLUSIONS: By factoring in dose level, number of doses, and tissue into the analysis of gene expression elicited by methapyrilene, we were able to identify genes likely to not be implicated in toxicity, thereby allowing us to focus on a subset of genes to identify toxicity-related processes. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Paules, RS (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,POB 12233,Mail Drop D2-03, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov FU Intramural NIH HHS NR 43 TC 13 Z9 13 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2007 VL 115 IS 4 BP 572 EP 578 DI 10.1289/ehp.9396 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800038 PM 17450226 ER PT J AU Wu, H Romieu, I Sienra-Monge, JJ del Rio-Navarro, BE Anderson, DM Dunn, EW Steiner, LL Lara-Sanchez, ID London, SJ AF Wu, Hao Romieu, Isabelle Sienra-Monge, Juan-Jose del Rio-Navarro, Blanca Estela Anderson, Daniel M. Dunn, Erin W. Steiner, Lori L. Lara-Sanchez, Irma del Carmen London, Stephanie J. TI Parental smoking modifies the relation between genetic variation in tumor necrosis factor-alpha (TNF) and childhood asthma SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergy; asthma; atopy; environmental tobacco smoke; genetic predisposition to disease; lymphotoxin-alpha (LTA); ozone; secondhand smoke; single nucleotide polymorphism (SNP); tumor necrosis factor-alpha (TNF) ID GENOME-WIDE SEARCH; ATOPIC ASTHMA; ENVIRONMENT INTERACTIONS; LINKAGE DISEQUILIBRIUM; ASSOCIATION ANALYSES; QUANTITATIVE TRAIT; POLYMORPHISM; POPULATION; SUSCEPTIBILITY; CHILDREN AB BACKGROUND: Polymorphisms in the proinflammatory cytokine genes tumor necrosis factor-alpha (TNT) and. lymphotoxin-alpha (LTA, also called TNF-beta) have been associated with asthma and atopy in some studies. Parental smoking is a consistent risk factor for childhood asthma. Secondhand smoke and ozone both stimulate TNF production. OBJECTIVES: Our goal was to investigate whether genetic variation in TNF and L TA is associated with asthma and atopy and whether the association is modified by parental smoking in a Mexican population with high ozone exposure. METHODS: We genotyped six tagging single nucleotide polymorphisms (SNPs) in TNF and L TA, including functional variants, in 596 nuclear families consisting of asthmatics 4-17 years of age and their parents in Mexico City. Atopy was determined by skin prick tests. RESULTS: The A allele of the TNF-308 SNP was associated with increased risk of asthma [relative risk (RR) = 1.54; 95% confidence interval (CI), 1.04-2.28], especially among children of nonsmoking parents (RR = 2.06, 95% Cl, 1.19-3.55; p for interaction = 0.09). Similarly, the A allele of the TNF-238 SNP was associated with increased asthma risk among children of nonsmoking parents (RR = 2.21; 95% Cl, 1.14-4.30; p for interaction = 0.01). LTA SNPs were not associated with asthma. Haplotype analyses reflected the single SNP findings in magnitude and direction. TNF and LTA SNPs were not associated with the degree of atopy. CONCLUSIONS: Our results suggest that genetic variation in TNF may contribute to childhood asthma and that associations may be modified by parental smoking. C1 NIEHS, Biol Res Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Natl Inst Publ Hlth, Cuernavaca, Morelos, Mexico. Hosp Infantil Mexico Dr Federico Gomez, Mexico City, DF, Mexico. Roche Mol Syst, Dept Human Genet, Alameda, CA USA. NIEHS, Epidemiol Branch, Div Intramural Res, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP London, SJ (reprint author), NIEHS, Biol Res Lab, Div Intramural Res, NIH,Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM london2@niehs.nih.gov OI London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [Z01 ES 49019, Z01 ES049019] NR 77 TC 35 Z9 36 U1 0 U2 2 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 APR PY 2007 VL 115 IS 4 BP 616 EP 622 DI 10.1289/ehp.9740 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800045 PM 17450233 ER PT J AU Kulich, M Rericha, V Rericha, R Shore, DL Sandler, DP AF Kulich, Michal Rericha, Vladimir Rericha, Robert Shore, David L. Sandler, Dale P. TI Lymphohematopoietic malignancies in uranium miners: Kulich et al. respond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID CASE-COHORT; LEUKEMIA; EXPOSURE C1 Charles Univ Prague, Fac Math & Phys, Prague, Czech Republic. Hlth Inst Uranium Ind, Pribram, Czech Republic. Ctr Epidemiol Studies, Pribram, Czech Republic. Westat Corp, Durham, NC USA. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Kulich, M (reprint author), Charles Univ Prague, Fac Math & Phys, Prague, Czech Republic. EM kulich@karlin.mff.cuni.cz RI Kulich, Michal/B-1483-2013 OI Kulich, Michal/0000-0002-2812-8968 NR 5 TC 0 Z9 0 U1 0 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2007 VL 115 IS 4 BP A184 EP A185 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800004 ER PT J AU Schwartz, DA AF Schwartz, David A. TI A new venue for the Director's perspective SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2007 VL 115 IS 4 BP A182 EP A182 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 153DV UT WOS:000245412800002 PM 17450190 ER PT J AU Galperin, MY AF Galperin, Michael Y. TI Mycobacterial genomes for all tastes: from BCG to biodegradation of naphtalene and pyrene SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN BH72; TRICHOMONAS-VAGINALIS; VINYL-CHLORIDE; SP. NOV.; BACTERIUM; SEQUENCE; PYR-1; ARCHAEBACTERIUM; HYDROGENOSOMES C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 43 TC 2 Z9 2 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD APR PY 2007 VL 9 IS 4 BP 839 EP 845 DI 10.1111/j.1462-2920.2007.01275.x PG 7 WC Microbiology SC Microbiology GA 144DQ UT WOS:000244776200001 PM 17359256 ER PT J AU Gasior, M French, A Joy, MT Tang, RS Hartman, AL Rogawski, MA AF Gasior, Maciej French, Amy Joy, Michelle T. Tang, Rebecca S. Hartman, Adam L. Rogawski, Michael A. TI The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid SO EPILEPSIA LA English DT Article DE ketogenic diet; acetone; acetone metabolites; pentylenetetrazol; 4-aminopyridine; seizure ID ANTIEPILEPTIC DRUGS; MICE; EPILEPSY; EFFICACY; SEIZURES; RAT; MECHANISMS; CHEMISTRY; MODELS AB Background: Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet. The anticonvulsant mechanism of acetone is unknown, but it is metabolized to several bioactive substances that could play a role. Methods: Acetone and its major metabolites-acetol, 1,2-propanediol, methylglyoxal, and pyruvic acid-were assessed for anticonvulsant activity in two mouse seizure models. Various doses of the substances administered intraperitoneally were characterized for their ability to elevate the threshold for clonic seizures induced by intravenous infusion of pentylenetetrazol (PTZ) and for protection against tonic seizures induced by subcutaneous bolus administration of 4-aminopyridine (4-AP). The inverted-screen test was used to assess acute neurological toxicity. Results: Acetone (1-32 mmol/kg, i.p.), in a dose-dependent fashion, elevated the PTZ threshold and conferred protection against 4-AP seizures (ED50, 26.3 mmol/kg). Effective doses of acetone (10-32 mmol/kg) did not cause motor impairment in the inverted-screen test (TD50, 45.7 mmol/kg). In doses 10-fold greater than the minimally effective dose of acetone (3.2 mmol/kg), the metabolites acetol, 1,2-propanediol, and pyruvic acid were inactive in the PTZ model. At higher doses that produced motor impairment, acetol and 1,2-propanediol (but not pyruvic acid) did elevate the PTZ threshold. Methylglyoxal had both proconvulsant and anticonvulsant actions, and had substantial toxicity, producing respiratory distress, motor impairment, and death. None of the acetone metabolites protected against 4-AP seizures. Conclusions: This study confirms the broad-spectrum anticonvulsant properties of acetone and indicates that the seizure protection conferred is unlikely to result from its major metabolic products. C1 Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, John M Freeman Pediat Epilepsy Ctr, Baltimore, MD 21287 USA. RP Rogawski, MA (reprint author), Univ Calif Davis, Dept Neurol, 4860 Y St, Sacramento, CA 95817 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU Intramural NIH HHS NR 35 TC 38 Z9 40 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD APR PY 2007 VL 48 IS 4 BP 793 EP 800 DI 10.1111/j.1528-1167.2007.01026.x PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 155UW UT WOS:000245604900019 PM 17386058 ER PT J AU Huster, D Gawrisch, K AF Huster, Daniel Gawrisch, Klaus TI Festschrift to recognize the contribution of Klaus Arnold to the field of biophysics on the occasion of his 65th birthday SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Editorial Material C1 Univ Halle Wittenberg, Inst Biotechnol, D-06120 Halle, Germany. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Huster, D (reprint author), Univ Halle Wittenberg, Inst Biotechnol, Kurt Mothes Str 3, D-06120 Halle, Germany. EM daniel.huster@biochemtech.uni-halle.de; gawrisch@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD APR PY 2007 VL 36 IS 4-5 BP 261 EP 261 DI 10.1007/s00249-007-0128-4 PG 1 WC Biophysics SC Biophysics GA 158WO UT WOS:000245826200001 ER PT J AU Huster, D Gawrisch, K AF Huster, Daniel Gawrisch, Klaus TI Biography of Klaus Arnold SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Biographical-Item C1 Univ Halle Wittenberg, Inst Biotechnol, D-06120 Halle, Germany. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Huster, D (reprint author), Univ Halle Wittenberg, Inst Biotechnol, Kurt Mothes Str 3, D-06120 Halle, Germany. EM daniel.huster@biochemtech.uni-halle.de; gawrisch@helix.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD APR PY 2007 VL 36 IS 4-5 BP 263 EP 264 DI 10.1007/s00249-007-0127-5 PG 2 WC Biophysics SC Biophysics GA 158WO UT WOS:000245826200002 PM 17265019 ER PT J AU Gawrisch, K Gaede, HC Mihailescu, M White, SH AF Gawrisch, Klaus Gaede, Holly C. Mihailescu, Mihaela White, Stephen H. TI Hydration of POPC bilayers studied by H-1-PFG-MAS-NOESY and neutron diffraction SO EUROPEAN BIOPHYSICS JOURNAL WITH BIOPHYSICS LETTERS LA English DT Article DE POPC; lipid; membrane; hydration; NMR; neutron diffraction ID NUCLEAR-MAGNETIC-RESONANCE; X-RAY-DIFFRACTION; LIPID-BILAYERS; PHOSPHOLIPID HYDRATION; CROSS-RELAXATION; JOINT REFINEMENT; MODEL MEMBRANES; EGG LECITHIN; DOUBLE-BONDS; WATER AB The stability of lipid bilayers is ultimately linked to the hydrophobic effect and the properties of water of hydration. Magic angle spinning (MAS) nuclear Overhauser enhancement spectroscopy (NOESY) with application of pulsed magnetic field gradients (PFG) was used to study the interaction of water with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine bilayers in the fluid phase. NOESY cross-relaxation between water and polar groups of lipids, but also with methylene resonances of hydrophobic hydrocarbon chains, has been observed previously. This observation led to speculations that substantial amounts of water may reside in the hydrophobic core of bilayers. Here, the results of a quantitative analysis of cross-relaxation in a lipid 1-palmitoyl-2-oleoyl-sn-glycero-3 phosphocholine (POPC)/water mixture are reported. Coherences were selected via application of pulsed magnetic field gradients. This technique shortens acquisition times of NOESY spectra to 20 min and reduces t(1)-spectral noise, enabling detection of weak crosspeaks, like those between water and lipids, with higher precision than with non-gradient NOESY methods. The analysis showed that water molecules interact almost exclusively with sites of the lipid-water interface, including choline, phosphate, glycerol, and carbonyl groups. The lifetime of lipid-water associations is rather short, on the order of 100 ps, at least one order of magnitude shorter than the lifetime of lipid-lipid associations. The distribution of water molecules over the lipid bilayer was measured at identical water content by neutron diffraction. Water molecules penetrate deep into the interfacial region of bilayers but water concentration in the hydrophobic core is below the detection limit of one water molecule per lipid, in excellent agreement with the cross-relaxation data. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM gawrisch@helix.nih.gov RI White, Stephen/B-1053-2009; Gaede, Holly/B-7392-2015 OI White, Stephen/0000-0001-8540-7907; Gaede, Holly/0000-0003-4444-4394 FU Intramural NIH HHS [Z01 AA000003-15]; NCRR NIH HHS [R01 RR014812, RR14812] NR 50 TC 66 Z9 67 U1 1 U2 26 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7571 J9 EUR BIOPHYS J BIOPHY JI Eur. Biophys. J. Biophys. Lett. PD APR PY 2007 VL 36 IS 4-5 BP 281 EP 291 DI 10.1007/s00249-007-0142-6 PG 11 WC Biophysics SC Biophysics GA 158WO UT WOS:000245826200004 PM 17333162 ER PT J AU Kim, Y Choi, JY Lee, KM Park, SK Ahn, SH Noh, DY Hong, YC Kang, D Yoo, KY AF Kim, Yeonju Choi, Ji-Yeob Lee, Kyoung-Mu Park, Sue Kyung Ahn, Sei-Hyun Noh, Dong-Young Hong, Yun-Chul Kang, Daehee Yoo, Keun-Young TI Dose-dependent protective effect of breast-feeding against breast cancer among ever-lactated women in Korea SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE breast-feeding; breast neoplasms; case-control studies; Korea ID REPRODUCTIVE FACTORS; RISK; HISTORY; WHITE; AGE AB Lactation might have a crucial role in an extraordinary increase in breast cancer incidence in Korea, as the proportion of mothers who practised breast-feeding fell dramatically. This hospital-based case-control analysis has been carried out since 1997 to evaluate whether lactation is associated with breast cancer risk in Korean women. Among the eligible study participants, a total of 753 histologically confirmed incident cases and an equal number of controls were included in the analysis. The risk was estimated using unconditional logistic regression models. Family history, older at menopause, more full-term pregnancies increased the risk of breast cancer. Breast cancer risk decreased according to the total months of breast-feeding (P for trend = 0.03). Average duration of breast-feeding of 11-12 months reduced risk of breast cancer by 54% compared with the duration of 1-4 months (odds ratio, 0.46; 95% confidence interval, 0.30-0.70). The decreasing risk trend according to average months of breast-feeding was also statistically significant (P for trend = 0.02). Moreover, a reduced risk of breast cancer was apparent when analysis was restricted to the first breast-fed child (P for trend = 0.006). This study confirms that lactation has an apparent dose-dependent protective effect against breast cancer in Korean women. C1 Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea. Seoul Natl Univ, Coll Med, Dept Surg, Seoul 110799, South Korea. Univ Ulsan, Coll Med, Asan Med Ctr, Dept Surg, Seoul, South Korea. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Natl Canc Ctr, Goyang, South Korea. RP Yoo, KY (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, 28 Yongon Dong, 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; Hong, Yun-Chul/J-5725-2012; Yoo, Keun-Young/J-5548-2012; Park, Sue Kyung/J-2757-2012; Kim, Yeonju/D-8948-2013 NR 31 TC 28 Z9 28 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD APR PY 2007 VL 16 IS 2 BP 124 EP 129 DI 10.1097/01.cej.0000228400.07364.52 PG 6 WC Oncology SC Oncology GA 144KS UT WOS:000244795500005 PM 17297388 ER PT J AU Onder, G Liperoti, R Russo, A Capoluongo, E Minucci, A Lulli, P Cesari, M Maggio, M Bernabei, R Landi, F AF Onder, Graziano Liperoti, Rosa Russo, Andrea Capoluongo, Ettore Minucci, Angelo Lulli, Paola Cesari, Matteo Maggio, Marcello Bernabei, Roberto Landi, Francesco TI Use of ACE inhibitors is associated with elevated levels of IGFBP-3 among hypertensive older adults: results from the IlSIRENTE study SO EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE ace inhibitors; hypertension; IGF-1; IGFBP-3; older adults ID GROWTH-FACTOR-I; CONVERTING ENZYME-INHIBITORS; IGF BINDING PROTEIN-3; MINIMUM DATA SET; HEART-FAILURE; PHYSICAL FUNCTION; MUSCLE STRENGTH; SKELETAL-MUSCLE; COMMUNITY; MEDICATIONS AB Objective Several studies in vitro or in rodent models have suggested a potential relationship between angiotensin-converting enzyme (ACE) inhibition and the insulin-like growth factor 1 (IGF-1) axis. However, this relationship has only rarely been investigated in humans. The aim of the present cross-sectional study was to assess the association of ACE inhibitors with free IGF-1 and IGFBP-3 in the blood of older hypertensive adults. Methods Data are from the baseline evaluation of the ilSIRENTE study, which enrolled 364 subjects aged 80 or older. For the present study we selected a subpopulation of 264 hypertensive participants without congestive heart failure. Free IGF-1 and IGFBP-3 in the blood were measured by a radioimmunoassay method. Analyses of covariance were performed to evaluate the differences in free IGF-1 and IGFBP-3 levels according to the use of ACE inhibitors. Results The mean age of participants was 85.7 years (SD: 4.9), 170 (64%) were women and 123 (47%) were using an ACE inhibitor. Following adjustment for potential confounders, the concentration of free IGF-1 was slightly, but not significantly higher among ACE inhibitor users than among non-users (0.74 vs. 0.65 ng/mL; p=0.20). In contrast, ACE inhibitor users had a significantly higher IGFBP-3 serum levels than non-users (4821 vs. 4330 ng/mL; p=0.005). In addition, the concentration of IGFBP-3 was significantly higher among ACE inhibitors users than among non-users of antihypertensive drugs (p=0.02) and users of other antihypertensive drugs (p=0.01). Conclusion Among hypertensive older adults, ACE inhibitors use is associated with higher IGFBP-3 levels. C1 Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Policlin A Gemelli, I-00168 Rome, Italy. Univ Cattolica Sacro Cuore, Dept Geriatr, I-00168 Rome, Italy. Univ Cattolica Sacro Cuore, Inst Biochem & Clin Biochem, I-00168 Rome, Italy. Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. RP Onder, G (reprint author), Univ Cattolica Sacro Cuore, Ctr Med Invecchiamento, Policlin A Gemelli, Lgo F Vito 1, I-00168 Rome, Italy. EM graziano_onder@rm.unicatt.it RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 30 TC 14 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0031-6970 J9 EUR J CLIN PHARMACOL JI Eur. J. Clin. Pharmacol. PD APR PY 2007 VL 63 IS 4 BP 389 EP 395 DI 10.1007/s00228-007-0262-z PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144UI UT WOS:000244821400008 PM 17273834 ER PT J AU Kaji, P Carrasquillo, JA Linehan, WM Chen, CC Eisenhofer, G Pinto, PA Lai, EW Pacak, K AF Kaji, Priya Carrasquillo, Jorge A. Linehan, W. Marston Chen, Clara C. Eisenhofer, Graeme Pinto, Peter A. Lai, Edwin W. Pacak, Karel TI The role of 6-[F-18]fluorodopamine positron emission tomography in the localization of adrenal pheochromocytoma associated with von Hippel-Lindau syndrome SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID I-131 METAIODOBENZYLGUANIDINE SCINTIGRAPHY; HIPPEL-LINDAU-DISEASE; METASTATIC PHEOCHROMOCYTOMA; DIAGNOSTIC LOCALIZATION; PET; MANAGEMENT; TUMORS; PARAGANGLIOMA; NEUROBLASTOMA AB Objective: [I-123/131]metaiodobenzylguanidine (MIBG) scintigraphy is considered as the gold standard in the localization of pheochromocytoma. However, this method has less optimal sensitivity for the detection of pheochromocytoma associated with von Hippel-Lindau (VHL). Our preliminary results suggest that this is partially due to the low expression of cell membrane norepinephrine transporter system in VHL-related pheochromocytoma cells. Another probable cause may be the low affinity that [I-123/131]MIBG has for these cells. Recently, 6-[F-18]fluorodopamine ([F-18]DA) positron emission tomography (PET) has been introduced as a novel functional imaging modality with high sensitivity for pheochromocytoma. Therefore, we investigated whether [F-18]DA PET is more effective than [I-123/131]MIBG scintigraphy in the diagnostic localization of VHL-related adrenal pheochromocytoma. Materials and methods: In this study, we evaluated seven VHL patients in whom adrenal pheochromocytomas were confirmed by histopathology results. Adrenal pheochromocytomas were localized using computed tomography (CT), magnetic resonance imaging (MRI), [I-123/13]MIBG scintigraphy and [F-18]DA PET. Results: [F-18]DA PET localized pheochromocytoma in all the seven patients, as did in CT. In contrast, three out of the seven had negative results utilizing [I-123/131]MIBG scintigraphy and one out of the six patients had negative MRI results. Conclusions: [F-18]DA PET was found to show more promising results when compared with [I-123/131]MIBG scintigraphy in the diagnostic localization of VHL-related adrenal pheochromocytoma, with a 100% rate of localization. Thus, [F-18]DA PET in conjunction with CT/MRI should be considered as an effective method for the proper localization of VHL-related adrenal pheochromocytoma. C1 NICHHD, Reprod Biol & Med Branch, Sect Med Neuroendocrinol, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Reprod Biol & Med Branch, Sect Med Neuroendocrinol, Bldg 10,CRC,1 East,Room 1-340,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 FU Intramural NIH HHS NR 29 TC 40 Z9 40 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD APR PY 2007 VL 156 IS 4 BP 483 EP 487 DI 10.1530/EJE-06-0712 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 160DC UT WOS:000245917700012 PM 17389464 ER PT J AU Nosheny, RL Ahmed, F Yakovlev, A Meyer, EM Ren, K Tessarollo, L Mocchetti, I AF Nosheny, Rachel L. Ahmed, Farid Yakovlev, Alexander Meyer, Edwin M. Ren, Ke Tessarollo, Lino Mocchetti, Italo TI Brain-derived neurotrophic factor prevents the nigrostriatal degeneration induced by human immunodeficiency virus-1 glycoprotein 120 in vivo SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE apoptosis; BDNF; chemokine receptors; HIV protein; neuroprotection; rAAV; substantia nigra ID CHEMOKINE RECEPTOR CXCR4; NERVE GROWTH-FACTOR; NEURONAL CELL-DEATH; COAT PROTEIN GP120; NEURAL STEM-CELLS; RAT-BRAIN; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS; ROTATIONAL BEHAVIOR; SEROTONERGIC AXONS AB Glycoprotein 120 (gp120) from the T-tropic strain of the human immunodeficiency virus type 1 has been shown to cause neuronal apoptosis through activation of the chemokine receptor CXCR4. Therefore, reducing CXCR4 expression may prevent gp120-mediated apoptosis. Brain-derived neurotrophic factor (BDNF) is known to reduce both gp120 neurotoxicity and CXCR4 expression in vitro. The scope of this work is to establish whether BDNF is neuroprotective against gp120 in vivo and, if so, whether this effect correlates with its ability to down-regulate CXCR4. Serotype 2 adeno-associated viral vector encoding for BDNF (rAAV-BDNF) or control vector was microinjected into the striata of adult rats. Two weeks later gp120 was injected into the same striatum, and apoptosis determined. Pretreatment with rAAV-BDNF prior to gp120 microinjection prevented caspase-3 activation as well as in situ terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling in the striatum and substantia nigra. In addition, rAAV-BDNF reversed the loss of tyrosine hydroxylase immunoreactivity induced by gp120 in both areas. CXCR4 expression was then determined by immunohistochemistry and RT-PCR, and found to be decreased in striata of rAAV-BDNF-treated rats. Conversely, BDNF heterozygous mice exhibited an increase in CXCR4 mRNA levels compared to wild-type littermates. Our data suggest that down-regulation of CXCR4 expression may contribute to the neuroprotective activity of BDNF against gp120 toxicity in the basal ganglia. C1 Georgetown Univ, Dept Neurosci, Washington, DC 20057 USA. Univ Florida, Dept Pharmacol & Therapeut, Gainesville, FL 32611 USA. NCI, Neural Dev Grp, Frederick, MD 21701 USA. RP Mocchetti, I (reprint author), Georgetown Univ, Dept Neurosci, EP04,New Rs Bldg,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM moccheti@georgetown.edu FU Intramural NIH HHS; NINDS NIH HHS [NS046234, NS047977, NS040670] NR 65 TC 34 Z9 34 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2007 VL 25 IS 8 BP 2275 EP 2284 DI 10.1111/j.1460-9568.2007.05506.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 157SX UT WOS:000245742300004 PM 17445226 ER PT J AU Steel, JC Cavanagh, HMA Burton, MA Abu-Asab, MS Tsokos, M Morris, JC Kalle, WHJ AF Steel, Jason C. Cavanagh, Heather M. A. Burton, Mark A. Abu-Asab, Mones S. Tsokos, Maria Morris, John C. Kalle, Wouter H. J. TI Increased tumor localization and reduced immune response to adenoviral vector formulated with the liposome DDAB/DOPE SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE adenovirus; liposomes; AL complexes; immuno-protection; neutralizing antibodies ID VIRUS THYMIDINE KINASE; GENE-TRANSFER; BETA-GALACTOSIDASE; CATIONIC LIPOSOME; IN-VITRO; TRANSDUCTION EFFICIENCY; NEUTRALIZING ANTIBODY; TRANSGENE EXPRESSION; CANCER-CELLS; COMPLEXES AB We aimed to increase the efficiency of adenoviral vectors by limiting adenoviral spread from the target site and reducing unwanted host immune responses to the vector. We complexed adenoviral vectors with DDAB-DOPE liposomes to form adenovirus-liposomal (AL) complexes. AL complexes were delivered by intratumoral injection in an immunocompetent subcutaneous rat tumor model and the immunogenicity of the AL complexes and the expression efficiency in the tumor and other organs was examined. Animals treated with the AL complexes had significantly lower levels of p-galactosidase expression in systemic tissues compared to animals treated with the naked adenovirus (NA) (P < 0.05). The tumor to non-tumor ratio of P-galactosidase marker expression was significantly higher for the AL complex treated animals. NA induced significantly higher titers of adenoviral-specific antibodies compared to the AL complexes (P < 0.05). The AL complexes provided protection (immunoshielding) to the adenovirus from neutralizing antibody. Forty-seven percent more p-galactosidase expression was detected following intratumoral injection with AL complexes compared to the NA in animals pre-immunized with adenovirus. Conclusions: Complexing of adenovirus with liposomes provides a simple method to enhance tumor localization of the vector, decrease the immunogenicity of adenovirus, and provide protection of the virus from pre-existing neutralizing antibodies. (c) 2007 Elsevier B.V. All rights reserved. C1 NCI, Ctr Canc Res, Canc Gene Therapy Grp, Metab Branch,NIH, Bethesda, MD 20892 USA. Charles Sturt Univ, Sch Biomed Sci, Wagga Wagga, NSW 2678, Australia. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Steel, JC (reprint author), NCI, Ctr Canc Res, Canc Gene Therapy Grp, Metab Branch,NIH, Bldg 10,Rm 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM jason_steel@nih.gov RI Steel, Jason/D-1805-2013; OI Steel, Jason/0000-0003-3608-7542; kalle, wouter/0000-0003-0142-8589; Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS NR 37 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD APR PY 2007 VL 30 IS 5 BP 398 EP 405 DI 10.1016/j.ejps.2006.12.004 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 158SX UT WOS:000245816000005 PM 17275269 ER PT J AU Bekris, LM Shephard, C Janer, M Graham, J McNeney, B Shin, J Zarghami, M Griffith, W Farin, F Kavanagh, TJ Lernmark, A AF Bekris, L. M. Shephard, C. Janer, M. Graham, J. McNeney, B. Shin, J. Zarghami, M. Griffith, W. Farin, F. Kavanagh, T. J. Lernmark, A. TI Glutamate cysteine ligase catalytic subunit promoter polymorphisms and associations with type 1 diabetes age-at-onset and GAD65 autoantibody levels SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE type 1 diabetes; GCLC; promoter polymorphisms; glutathione ID GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; CHRONIC BERYLLIUM DISEASE; ISLET-CELL ANTIBODIES; OXIDATIVE STRESS; GLUTATHIONE BIOSYNTHESIS; ANTIOXIDANT ENZYMES; ACID DECARBOXYLASE; MISSENSE MUTATION; INDUCED APOPTOSIS; RESPONSE ELEMENT AB The purpose of this study was to test the hypothesis that glutamate cysteine ligase catalytic subunit (GCLC) promoter polymorphisms are susceptibility factors for type 1 diabetes (T1D), T1D age-at-onset and T1D autoantibodies. T1D patients and control subjects from the Swedish Childhood Diabetes Registry and the Swedish Diabetes Incidence Study registry were geno-typed for two GCLC promoter polymorphisms; the GCLC -129C to T single nucleotide polymorphism (GCLC - 129 SNP) and the GCLC GAG trinucleotide repeat polymorphism (GCLC TNR). Glutamate decarboxylase antibody (GAD65Ab) positive T1D patients with the GCLC - value, < 0.05) compared to the GCLC - 129 SNP C/C genotype. T1D patients with an age-at-onset of 14-35 years who possess the GCLC - 129 SNP T/T genotype have a higher GAD65Ab index than T1D patients with the GCLC - 129 SNP C/C genotype (p-value < 0.05). In addition, T1D patients with an age-at-onset of 14-35 years possess the GCLC TNR 7/8 genotype at a lower frequency than the control subjects (OR, 0.33,95%CI, 0.13-0.82). The GCLC - 129 SNP and GCLC TNR appear to be in linkage disequilibrium (p-value < 0.0001). These results suggest that GCLC promoter polymorphisms may influence GAD65Ab levels and may influence the age at which T1D is diagnosed. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA. Univ Washington, NIEHS Ctr Ecogenet & Environm Hlth, Seattle, WA 98195 USA. Inst Syst Biol, Seattle, WA USA. Simon Fraser Univ, Dept Stat & Actuarial Sci, Burnaby, BC V5A 1S6, Canada. RP Bekris, LM (reprint author), Univ Washington, Dept Med, Box 358280, Seattle, WA 98195 USA. NR 66 TC 14 Z9 14 U1 0 U2 0 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD APR PY 2007 VL 115 IS 4 BP 221 EP 228 DI 10.1055/s-2007-970574 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170UX UT WOS:000246692700002 PM 17479437 ER PT J AU Davis, MD Beck, RW Home, PD Sandow, J Ferris, FL AF Davis, M. D. Beck, R. W. Home, P. D. Sandow, J. Ferris, F. L. TI Early retinopathy progression in four randomized trials comparing insulin glargine and NPH insulin SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE diabetic retinopathy; insulin glargine ID DEPENDENT DIABETES-MELLITUS; MUSCLE-CELLS; 4-YEAR INCIDENCE; GLUCOSE CONTROL; THERAPY; COMPLICATIONS; HYPOGLYCEMIA; DIAGNOSIS; HOE-901; AGE AB Early worsening of diabetic retinopathy, characterized by cotton wool spots, intraretinal microvascular abnormalities and/or macular edema, can occur following improvement of glycemic control. In four randomized 28- to 52-week clinical trials comparing insulin glargine and NPH insulin in regard to glycemic control and frequency of hypoglycemia, ophthalmologic examinations and fundus photographs were included to assess frequency of early worsening of retinopathy or other early adverse ocular effects. Retinopathy progression rates at 28 weeks were 7-12% by clinical examination and 3-8% by photographic grading; corresponding rates of clinically significant macular edema (CSME) were 1-8% and 1-4%, respectively. Optic disc swelling was not observed clinically or in photographs. Two of the 24 possible comparisons (four trials, three outcomes, two assessment methods), both of which were photographic assessments in type 2 diabetes, were in/near the nominally significant range and favored NPH insulin: 28-week rates of >= 3-step retinopathy progression (insulin glargine: 16/213,7.5 %; NPH insulin: 6/220,2.7%; p=0.028) and 52-week CSME rates (26/233, 11.2% and 14/214, 6.5%, respectively; p=0.098). Because the between-treatment differences were small and inconsistent across trials and assessment methods, and because overall rates were consistent with the natural course of diabetic retinopathy, we conclude that it is unlikely that insulin glargine carries a higher risk of early worsening or other early adverse effect than NPH insulin. These trials tended to exclude a large early adverse effect, such as optic disc swelling, but cannot assess longer-term effects: a 5-year randomized trial of insulin glargine versus NPH insulin has been initiated.Data from this manuscript have been presented as posters and published in abstract form at the European Association for the Study of Diabetes 2001 (Diabetologia 44(Suppl1):I-IV(A287), 2001) and the Latin American Diabetes Association 2001 (11-15 November 2001, Punta del Este, Uruguay; Poster 180) congresses. C1 Univ Wisconsin, Fundus Photog Rading Ctr, Dept Ophthalmol & Visual Sci, Madison, WI 53711 USA. Jaeb Ctr Hlth Res, Tampa, FL USA. Newcastle Univ, Sch Med Sci Diabet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Sanofi Aventis, Frankfurt, Germany. NEI, Div Biometry & Epidemiol, Bethesda, MD 20892 USA. RP Davis, MD (reprint author), Univ Wisconsin, Fundus Photog Rading Ctr, Dept Ophthalmol & Visual Sci, 406 Sci Dr, Madison, WI 53711 USA. EM davis@rc.ophth.wisc.edu NR 20 TC 13 Z9 16 U1 0 U2 1 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 EI 1439-3646 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD APR PY 2007 VL 115 IS 4 BP 240 EP 243 DI 10.1055/s-2007-970577 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170UX UT WOS:000246692700005 PM 17479440 ER PT J AU Ramot, Y Lewis, DA Ortel, TL Streicker, M Moser, G Elmore, S Ward, SM Peddada, S Nyska, A AF Ramot, Yuval Lewis, Deborah A. Ortel, Thomas L. Streicker, Mike Moser, Glenda Elmore, Susan Ward, Sandra M. Peddada, Shyamal Nyska, Abraham TI Age and dose sensitivities in the 2-butoxyethanol F344 rat model of hemolytic anemia and disseminated thrombosis SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE animal models; 2-butoxyethanol; hemolysis; microvascular thrombosis; sickle cell disease ID GLYCOL MONOBUTYL ETHER; SICKLE-CELL-DISEASE; RED-BLOOD-CELLS; ORDER-RESTRICTED INFERENCE; BUTOXYACETIC ACID; FEMALE RATS; INHALATION EXPOSURE; HUMAN-ERYTHROCYTES; ENDOTHELIAL-CELLS; THALASSEMIA MAJOR AB In hemolytic disorders, such as sickle cell disease and beta-thalassemia, the mechanisms of thrombosis are poorly understood. Appropriate animal models would increase the understanding of the pathophysiology of thrombosis. We previously reported that rats exposed to 2-butoxyethanol (2-BE) developed hemolytic anemia and disseminated thrombosis resembling sickle cell disease and beta-thalassemia. To characterize our model further, we investigated age- and dose-related differences in sensitivity to 2-BE. We exposed groups of 6- and 12-week-old F344 rats (5 animals/ group) to 62.5, 125, and 250 mg/kg/day of 2-BE for up to 4 days. Blood was collected on days 2-4 for complete blood count and measurement of intracellular adhesion molecule-1 (ICAM-1). Histopathological evaluation was performed to find evidence of disseminated thrombosis. The maximum hemolytic response, resulting in decreased erythrocyte count and higher mean cell volume (MCV) occurred in the 12-week-old rats treated with the highest dose of 2-BE (250 mg/kg, p < 0.0001). The highest increase in ICAM-1 levels occurred in the 12-week-old rats treated with 125 and 250mg/kg 2-BE (p < 0.0001). No intravascular thrombi were noted in the 6-week-old 2-BE-treated animals. The majority of intravascular thrombi occurred in the 12-week-old rats treated with 250 mg/kg 2-BE. Because our findings show age- and dose-related sensitivities, we suggest that 12-week-old rats and doses of 250 mg/kg be used in the 2-BE model. (c) 2006 Elsevier GmbH. All rights reserved. C1 Hebrew Univ Jerusalem, Hadassah Med Ctr, Jerusalem, Israel. Duke Univ, Med Ctr, Div Hematol, Durham, NC USA. ILS, Res Triangle Pk, NC USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), Haharuv 18,POB 184, IL-23840 Timrat, Israel. EM anyska@bezeqint.net RI Peddada, Shyamal/D-1278-2012 NR 62 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD APR PY 2007 VL 58 IS 5 BP 311 EP 322 DI 10.1016/j.etp.2006.11.003 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 165HI UT WOS:000246294600005 PM 17261363 ER PT J AU Kansaku, K Carver, B Johnson, A Matsuda, K Sadato, N Hallett, M AF Kansaku, Kenji Carver, Benjamin Johnson, Ari Matsuda, Keiji Sadato, Norihiro Hallett, Mark TI The role of the human ventral premotor cortex in counting successive stimuli SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; NUMERICAL COGNITION; HUMAN BRAIN; PARIETAL; NUMBER; REPRESENTATION; CONJUNCTION; MOVEMENTS; QUANTITY; AREAS AB Adult humans have the ability to count large numbers of successive stimuli exactly. What brain areas underlie this uniquely human process? To identify the candidate brain areas, we first used functional magnetic resonance imaging, and found that the upper part of the left ventral premotor cortex was preferentially activated during counting of successive sensory stimuli presented 10-22 times, while the area was not activated during small number counting up to 4. We then used transcranial magnetic stimulation to assess the necessity of this area, and found that stimulation of this area preferentially disrupted subjects' exact large number enumeration. Stimulation to the area affected neither subjects' number word perception nor their ability to perform a non-numerical sequential letter task. While further investigation is necessary to determine the precise role of the left ventral premotor cortex, the results suggest that the area is indispensably involved for large number counting of successive stimuli, at least for the types of tasks in this study. C1 Res Inst Natl Rehabil Ctr Persons Disabil, Cognit Funct Sect, Dept Rehabil Sensory Funct, Tokorozawa, Saitama 3598555, Japan. Natl Inst AIST, Neurosci Res Inst, Tsukuba, Ibaraki 3058568, Japan. Natl Inst Physiol Sci, Div Cerebral Integrat, Dept Cerebral Res, Okazaki, Aichi 4448585, Japan. Natl Inst Neurol Disorders & Stroke, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Kansaku, K (reprint author), Res Inst Natl Rehabil Ctr Persons Disabil, Cognit Funct Sect, Dept Rehabil Sensory Funct, 4-1 Namiki, Tokorozawa, Saitama 3598555, Japan. EM kansakuk@rehab.go.jp FU Intramural NIH HHS NR 34 TC 15 Z9 15 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD APR PY 2007 VL 178 IS 3 BP 339 EP 350 DI 10.1007/s00221-006-0736-8 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 148VQ UT WOS:000245105500006 PM 17051376 ER PT J AU Jamieson, HA Hilmer, SN Cogger, VC Warren, A Cheluvappa, R Abernethy, DR Everitt, AV Fraser, R de Cabo, R Le Couteur, DG AF Jamieson, Hamish A. Hilmer, Sarah N. Cogger, Victoria C. Warren, Alessandra Cheluvappa, Rajkumar Abernethy, Darrell R. Everitt, Arthur V. Fraser, Robin de Cabo, Rafael Le Couteur, David G. TI Caloric restriction reduces age-related pseudocapillarization of the hepatic sinusoid SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE liver sinusoidal endothelial cell; pseudocapillarization; caloric restriction; aging; caveolin-1; liver; fenestrations ID OXIDATIVE STRESS; LIVER SIEVE; RAT-LIVER; ATHEROSCLEROSIS; ENDOTHELIUM; CIRRHOSIS AB Age-related changes in the hepatic sinusoid, called pseudocapillarization, may contribute to the pathogenesis of dyslipidemia. Caloric restriction (CR) is a powerful model for the study of aging because it extends lifespan. We assessed the effects of CR on the hepatic sinusoid to determine whether pseudocapillarization is preventable and hence a target for the prevention of age-related dyslipidemia. Livers from young (6 months) and old (24 months) CR and ad libitum fed (AL) F344 rats were examined using electron microscopy and immunohistochemistry. In old age, there was increased thickness of the liver sinusoidal endothelium and reduced endothelial fenestration porosity. In old CR rats, endothelial thickness was less and fenestration porosity was greater than in old AL rats. Immunohistochemistry showed that CR prevented age-related decrease in caveolin-1 expression and increase in peri-sinusoidal collagen IV staining, but did not alter the age-related increase of von Willebrand's factor. CR reduces age-related pseudocapillarization of the hepatic sinusoid and correlates with changes in caveolin-1 expression. (c) 2006 Elsevier Inc. All rights reserved. C1 NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. Concord Hosp, Ctr Educ & Res Ageing, Concord, NSW 2139, Australia. Concord Hosp, ANZAC Med Res Inst, Concord, NSW 2139, Australia. Royal N Shore Hosp, Dept Aged Care & Clin Pharmacol, St Leonards, NSW 2065, Australia. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Univ Otago, Christchurch Sch Med, Dept Pathol, Christchurch, New Zealand. RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM deCaboRa@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; de Cabo, Rafael/J-5230-2016; OI de Cabo, Rafael/0000-0002-3354-2442; Hilmer, Sarah/0000-0002-5970-1501; , rafael/0000-0003-2830-5693 FU Intramural NIH HHS [Z99 AG999999] NR 18 TC 25 Z9 27 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD APR PY 2007 VL 42 IS 4 BP 374 EP 378 DI 10.1016/j.exger.2006.11.004 PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 154AB UT WOS:000245478100015 PM 17204388 ER PT J AU Feinendegen, LE Pollycove, M Neumann, RD AF Feinendegen, Ludwig E. Pollycove, Myron Neumann, Ronald D. TI Whole-body responses to low-level radiation exposure: New concepts in mammalian radiobiology SO EXPERIMENTAL HEMATOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Recent Advances in Radiation Effects, Hematopoiesis and Malignancy in honor of Eugene P Cronkite CY MAY 10-13, 2006 CL Brookhaven Natl Lab, Upton, NY HO Brookhaven Natl Lab ID LOW-DOSE EXPOSURE; SISTER-CHROMATID EXCHANGES; DOUBLE-STRAND BREAKS; BONE-MARROW CELLS; PROTECTIVE RESPONSES; TRITIATED THYMIDINE; IONIZING-RADIATION; HUMAN-LYMPHOCYTES; ALPHA-PARTICLES; IRRADIATION AB This review of low dose-induced whole-body effects, especially cancer, shows: 1) Biological systems appear in hierarchy levels of organization, from atoms to molecules, to cells, to tissues and organs, to the whole system; 2) System responses to low-level exposures depend on: quality and number of energy depositions in tissue micromasses (microdoses) being potential triggers to damage and protection; time interval between two microdose events per exposed micromass, that determines cellular responses to the preceding microdose; and responses to microdose events in the system being the target, with the balance between damage and benefit determining the net effect; 3) System responses to acute or chronic low-level exposures evolve from damage to the basic molecular level, mainly to DNA of stem cells, and from adaptive responses that may occur in the whole body. Damage may propagate to successive higher levels of organization, meeting protective barriers which may become upregulated by adaptive responses. The balance between damage and protection at each level per individual depends on tissue dose. At single tissue doses below congruent to 0.1 Gy net benefit tends to outweigh detriment. Thus, progression of damage to clinical disease is not linear; 4) Quality and extent of system responses are under genetic control. Thus, system net responses expectedly vary among individuals; 5) The balance between health risk and benefit of low-level exposure for a given individual may become predictable by gene-expression profiles in control and irradiated cells of this individual; and 6) Clinical trials applying individualized low-level irradiation are justified. (c) 2007 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Univ Dusseldorf, Dept Nucl Med, D-4000 Dusseldorf, Germany. Brookhaven Natl Lab, Upton, NY 11973 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Feinendegen, LE (reprint author), Univ Dusseldorf, Dept Nucl Med, D-4000 Dusseldorf, Germany. EM feinendegen@gmx.net NR 54 TC 70 Z9 77 U1 1 U2 7 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 APR PY 2007 VL 35 IS 4 SU 1 BP 37 EP 46 DI 10.1016/j.exphem.2007.01.011 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 155LA UT WOS:000245577700008 PM 17379086 ER PT J AU Shofer, S Badea, C Auerbach, S Schwartz, DA Johnson, GA AF Shofer, Scott Badea, Cristian Auerbach, Scott Schwartz, David A. Johnson, G. Allan TI A micro-computed tomography-based method for the measurement of pulmonary compliance in healthy and bleomycin-exposed mice SO EXPERIMENTAL LUNG RESEARCH LA English DT Article DE microCT; pulmonary compliance; pulmonary fibrosis ID SMALL ANIMALS; LUNG; FIBROSIS; CT AB Micro-computed tomography (microCT) is being increasingly used to examine small animal models of pulmonary injury. The authors have developed a microCT technique suitable for the determination of pulmonary compliance in injured mice. Lung volumes in normal mice were radio-graphically determined at end-inspiration and end-expiration and pulmonary compliance was calculated at 2 time points 2 weeks apart, whereas a second group of mice were given bleomycin and imaged 3 weeks following drug administration. Compliance measurements were validated using a commercially available ventilator system. MicroCT pulmonary compliance measurements are suitable for longitudinal measurements, and correlate with physiologic measurements of pulmonary compliance. C1 Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care, Durham, NC 27710 USA. Duke Univ, Med Ctr, Ctr Vivo Microscopy, Durham, NC 27710 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Shofer, S (reprint author), Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care, Box 3221, Durham, NC 27710 USA. EM scott.shofer@duke.edu RI Badea, Cristian/B-6681-2011; OI Badea, Cristian/0000-0002-1850-2522; Johnson, G.Allan/0000-0002-7606-5447 FU NCI NIH HHS [R24 CA092656-06, R24 CA092656]; NCRR NIH HHS [P41 RR005959, P41 RR005959-18]; NIEHS NIH HHS [ES011961, P30 ES011961, P30 ES011961-01A1] NR 23 TC 19 Z9 19 U1 1 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0190-2148 J9 EXP LUNG RES JI Exp. Lung Res. PD APR-MAY PY 2007 VL 33 IS 3-4 BP 169 EP 183 DI 10.1080/01902140701364458 PG 15 WC Respiratory System SC Respiratory System GA 180PX UT WOS:000247379100004 PM 17558678 ER PT J AU Madan, RA Arlen, PM Gulley, JL AF Madan, Ravi A. Arlen, Philip M. Gulley, James L. TI PANVAC (TM)-VF: poxviral-based vaccine therapy targeting CEA and MUC1 in carcinoma SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Article DE cancer vaccine; carcinoembryonic antigen; carcinoma; CEA; epithelial mucin 1; MUC1; TRICOM ID ANTIGEN-PRESENTING CELLS; HUMAN CARCINOEMBRYONIC ANTIGEN; COLONY-STIMULATING FACTOR; CYCLOOXYGENASE-2 INHIBITOR CELECOXIB; FAMILIAL ADENOMATOUS POLYPOSIS; INDEPENDENT PROSTATE-CANCER; METASTATIC RENAL-CANCER; T-LYMPHOCYTE EPITOPE; RANDOMIZED PHASE-II; HUMAN-TUMOR-MARKER AB PANVAC (TM) is a cancer vaccine therapy delivered through two viral vectors recombinant vaccinia and recombinant fowlpox - which are given sequentially. Both vectors contain transgenes for the tumor-associated antigens epithelial mucin 1 and carcinoembryonic antigen, which are altered or overexpressed in most carcinomas. The vectors also contain transgenes for three human T cell costimulatory molecules required to enhance immune response: B7.1, intracellular adhesion molecule-1 and leukocyte function-associated antigen-3. PANVAC is injected subcutaneously and processed by the body's antigen-presenting cells. Preclinical studies have demonstrated the efficacy of PANVAC in inducing both carcinoembryonic antigen- and mucin 1-specific cytotoxic T lymphocyte responses in vitro and in murine models. Other strategies that enhance the immune response include the use of granulocyte-macrophage colony-stimulating factor and a prime-boost administration sequence. Clinical trials have demonstrated PANVAC's safety and its ability to induce antigen-specific T cell responses. Early clinical trials are evaluating PANVAC alone and in combination with conventional chemotherapy and/or radiation. Studies to date hold promise for the use of PANVAC as a means to stimulate the immune system against malignancies and to provide clinical benefit. C1 NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 FU Intramural NIH HHS NR 91 TC 35 Z9 38 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 APR PY 2007 VL 7 IS 4 BP 543 EP 554 DI 10.1517/14712598.7.4.543 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 152NV UT WOS:000245369600012 PM 17373905 ER PT J AU Krumpe, LRH Mori, T AF Krumpe, Lauren R. H. Mori, Toshiyuki TI Potential of phage-displayed peptide library technology to identify functional targeting peptides SO EXPERT OPINION ON DRUG DISCOVERY LA English DT Review DE library; peptide; phage display; targeting AB Combinatorial peptide library technology is a valuable resource for drug discovery and development. Several peptide drugs developed through phage-displayed peptide library technology are presently in clinical trials and the authors envision that phage-displayed peptide library technology will assist in the discovery and development of many more. This review attempts to compile and summarize recent literature on targeting peptides developed through peptide library technology, with special emphasis on novel peptides with targeting capacity evaluated in vivo. C1 [Mori, Toshiyuki] Takeda Pharmaceut Co Ltd, Biomed Res Labs, Div Pharmaceut Res, Yodogawa Ku, Osaka 5328686, Japan. [Krumpe, Lauren R. H.] NCI, SAIC Frederick Inc, Mol Targets Dev Program, Frederick, MD 21702 USA. RP Mori, T (reprint author), Takeda Pharmaceut Co Ltd, Biomed Res Labs, Div Pharmaceut Res, Yodogawa Ku, 2-17-85 Jusohonmachi, Osaka 5328686, Japan. EM Mori_Toshiyuki2@takeda.co.jp FU NIH, National Cancer Institute, Center for Cancer Research FX This Research was supported (in part) by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 116 TC 12 Z9 13 U1 2 U2 13 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1746-0441 EI 1746-045X J9 EXPERT OPIN DRUG DIS JI Expert. Opin. Drug Discov. PD APR PY 2007 VL 2 IS 4 BP 525 EP 537 DI 10.1517/17460441.2.4.525 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA V12RQ UT WOS:000207616700009 PM 20150977 ER PT J AU Hope, WW Shoham, S Walsh, TJ AF Hope, William W. Shoham, Shmuel Walsh, Thomas J. TI The pharmacology and clinical use of caspofungin SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE Aspergillus; Candida; caspofungin; echinocandin; glucan; pharmacodynamics; pharmacokinetics ID CANDIDA-ALBICANS BIOFILMS; EXPERIMENTAL PULMONARY ASPERGILLOSIS; VITRO PHARMACODYNAMIC PROPERTIES; ANTIFUNGAL DRUG CASPOFUNGIN; LIPOSOMAL AMPHOTERICIN-B; IN-VITRO; 1,3-BETA-D-GLUCAN SYNTHASE; CRYPTOCOCCUS-NEOFORMANS; INVASIVE ASPERGILLOSIS; MURINE MODEL AB Caspofungin was the first echinocandin to be licensed for the treatment of invasive fungal infections. Caspofungin has in vitro and in vivo activity against Candida spp. and Aspergillus spp., which constitute the majority of medically important opportunistic fungal pathogens. Caspofungin inhibits the synthesis of the 1,3-beta-glucan, with resultant osmotic instability and lysis. The pharmacology of caspofungin is relatively complex. Trafficking of drug into tissues is an important determinant of the shape of the concentration-time relationship. Caspofungin has demonstrated efficacy in experimental models of invasive candidiasis and aspergillosis, which reflect its activity in the treatment of oropharyngeal, esophageal and disseminated candidiasis, as well as salvage therapy for patients with invasive aspergillosis. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM waisht@mail.nih.gov OI Hope, William/0000-0001-6187-878X NR 84 TC 21 Z9 25 U1 1 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD APR PY 2007 VL 3 IS 2 BP 263 EP 274 DI 10.1517/17425255.3.2.263 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 167VK UT WOS:000246480400010 PM 17428155 ER PT J AU Lau, CY Velasco, PP Johnston, MI AF Lau, Chuen-Yen Velasco, Peter P. Johnston, Margaret I. TI A new era in HIV vaccine development SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Article DE AIDS vaccine; collaboration; HIV vaccine; product development ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIBODY-RESPONSE; NEUTRALIZING ANTIBODIES; ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; GATES-FOUNDATION; RHESUS MACAQUES; AIDS VIRUSES; SOLUBLE CD4; GP120 AB Since the identification of HIV in 1984, the search for a safe and effective vaccine has been relentless. While investigator-initiated research has provided substantial information regarding HIV disease and pathogenesis, and over two dozen drugs are licensed in the USA to treat HIV, the global epidemic continues unabated. Early in HIV vaccine research, the pharmaceutical industry took the initiative to produce products for clinical testing. As the likelihood of a quick success decreased, private investment waned. The public sector responded with novel mechanisms to engage industry while continuing to support academic investigators. HIV vaccine research continues to rely on the creativity of individual investigators, as well as collaborations that vary in size and complexity and offer opportunities for the efficient use of resources and accelerated progress. C1 NIH, NIAID, Div Aids, Vaccine Res Program, Bethesda, MD 20817 USA. RP Lau, CY (reprint author), NIH, NIAID, Div Aids, Vaccine Res Program, 6700 B Rockledge Dr, Bethesda, MD 20817 USA. EM lauc@niaid.nih.gov NR 62 TC 2 Z9 3 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD APR PY 2007 VL 5 IS 2 BP 205 EP 215 DI 10.1586/14787210.5.2.205 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 226DS UT WOS:000250568300014 PM 17402836 ER PT J AU Fox, E Bates, SE AF Fox, Elizabeth Bates, Susan E. TI Tariquidar (XR9576): a P-glycoprotein drug efflux pump inhibitor SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE MDR; multidrug resistance; P-glycoprotein; tariquidar ID ACUTE MYELOID-LEUKEMIA; CELL LUNG-CANCER; PHASE-I TRIAL; MULTIDRUG-RESISTANCE MODULATOR; BLOOD-BRAIN-BARRIER; ZOSUQUIDAR TRIHYDROCHLORIDE LY335979; SOUTHWEST-ONCOLOGY-GROUP; GENE-EXPRESSION; MDR1 GENE; PSC 833 AB P-glycoprotein actively transports structurally unrelated compounds out of cells, conferring the multidrug resistance phenotype in cancer. Tariquidar is a potent, specific, noncompetitive inhibitor of P-glycoprotein. Tariquidar inhibits the ATPase activity of P-glycoprotein, suggesting that the modulating effect is derived from the inhibition of substrate binding, inhibition of ATP hydrolysis or both. In clinical trials, tariquidar is tolerable and does not have significant pharmacokinetic interaction with chemotherapy. In patients, inhibition of P-glycoprotein has been demonstrated for 48 h after a single dose of tariquidar. Studies to assess a possible increase in toxicity of chemotherapy and the impact of P-glycoprotein inhibition on tumor response and patient outcome are ongoing. Tariquidar can be considered an ideal agent for testing the role of P-glycoprotein inhibition in cancer. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Fox, E (reprint author), NCI, Pediat Oncol Branch, 10-CRC,1-5750,MSC 1101,10 Ctr Dr, Bethesda, MD 20892 USA. EM foxb@mail.nih.gov NR 107 TC 154 Z9 164 U1 5 U2 26 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD APR PY 2007 VL 7 IS 4 BP 447 EP 459 DI 10.1586/14737140.7.4.447 PG 13 WC Oncology SC Oncology GA 160GJ UT WOS:000245928600006 PM 17428165 ER PT J AU Bennett, N Ellis, J Bonville, C Rosenberg, H Domachowske, J AF Bennett, Nicholas Ellis, John Bonville, Cynthia Rosenberg, Helene Domachowske, Joseph TI Immunization strategies for the prevention of pneumovirus infections SO EXPERT REVIEW OF VACCINES LA English DT Review DE bovine respiratory syncytial virus bronchiolitis; immunization; pneumonia virus of mice; respiratory syncytial virus ID RESPIRATORY SYNCYTIAL VIRUS; CONGENITAL HEART-DISEASE; T-CELL RESPONSES; PNEUMONIA VIRUS; MATERNAL ANTIBODIES; INACTIVATED VACCINE; IMMUNE GLOBULIN; MESSENGER-RNA; BRONCHOPULMONARY DYSPLASIA; REDUCES HOSPITALIZATION AB Pneumoviruses, which are viruses of the family Paromyxoviridae, subfamily Pneumovirinae, are pathogens that infect the respiratory tract of their host species. The human pneumovirus pathogen, human respiratory syncytial virus (RSV), has counterparts that infect cows (bovine RSV), sheep (ovine RSV), goats (caprine RSV) and rodents (pneumonia virus of mice). Each pneumovirus is host specific and results in a spectrum of disease, ranging from mild upper-respiratory illness to severe bronchiolitis and pneumonia with significant morbidity and mortality. Given the public health burden caused by human RSV and the concomitant agricultural impact of bovine RSV, these two viruses are considered as prime targets for the development of safe and effective vaccines. In this review, we describe the strategies used to develop vaccines against human and bovine RSV and introduce the pneumonia virus mouse model as a novel and invaluable tool for preclinical studies and new vaccine strategies. C1 SUNY Upstate Med Univ, Dept Pediat, Syracuse, NY 13210 USA. Univ Saskatchewan, Dept Vet Microbiol, Saskatoon, SK S7N 5B4, Canada. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Domachowske, J (reprint author), SUNY Upstate Med Univ, Dept Pediat, 750 E Adams St, Syracuse, NY 13210 USA. EM domachoj@upstate.edu NR 102 TC 8 Z9 8 U1 1 U2 3 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2007 VL 6 IS 2 BP 169 EP 182 DI 10.1586/14760584.6.2.169 PG 14 WC Immunology SC Immunology GA 158UV UT WOS:000245821400014 PM 17408367 ER PT J AU Dell'Agnola, C Biragyn, A AF Dell'Agnola, Chiara Biragyn, Arya TI Clinical utilization of chemokines to combat cancer: the double-edged sword SO EXPERT REVIEW OF VACCINES LA English DT Review DE angiogenesis; cancer; chemotaxis; metastases; tumor escape ID REGULATORY T-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; MONOCYTE CHEMOATTRACTANT PROTEIN-1; CD26/DIPEPTIDYL PEPTIDASE-IV; LYMPH-NODE METASTASIS; HUMAN BREAST-CANCER; MACROPHAGE-DERIVED CHEMOKINE; SUPPRESSES TUMOR-GROWTH; MATURE DENDRITIC CELLS; NON-HODGKINS-LYMPHOMA AB Chemokines are a small group of related chemo-attractant peptides that play an essential role in the homeostatic maintenance of the immune system. They control the recruitment of cells needed for the induction and activation of innate and adaptive immune responses. However, tumors also utilize chemokines to actively progress and evade immunosurveillance. In fact, chemokines are involved directly or indirectly in almost every aspect of tumorigenesis. They mediate survival and metastatic spread of tumors, promote new blood vessel formation (neovascularization) and induce an immunosuppressive microenvironment via recruitment of immunosuppressive cells. As a result, a number of therapeutic strategies have been proposed to target almost every step of the chemokine/chemokine receptor involvement in tumors. Yet, despite occasional success stories, most of them appear to be ineffective or impractical, presumably due to 'nonspecific' harm of cells needed for the elimination of tumor escapees and maintenance of immunological memory. The strategy would only be effective if it also promoted antitumor adaptive immune responses capable of combating a residual disease and tumor relapse. C1 NIA, Immunol Lab, Gerontol Res Ctr, Immunotherapeut Unit, Baltimore, MD 21224 USA. Univ Verona, Dept Clin & Expt Med, Div Oncol, Osped Policlin GB Rossi, I-37134 Verona, Italy. RP Biragyn, A (reprint author), NIA, Immunol Lab, Gerontol Res Ctr, Immunotherapeut Unit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM biragyna@mail.nih.gov FU Intramural NIH HHS [Z01 AG000770-04] NR 206 TC 26 Z9 26 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2007 VL 6 IS 2 BP 267 EP 283 DI 10.1586/14760584.6.2.267 PG 17 WC Immunology SC Immunology GA 158UV UT WOS:000245821400022 PM 17408375 ER PT J AU Costin, GE Hearing, VJ AF Costin, Gertrude-E. Hearing, Vincent J. TI Human skin pigmentation: melanocytes modulate skin color in response to stress SO FASEB JOURNAL LA English DT Review DE hyperpigmentation; UV radiation; aging; melanocyte photoprotection ID ESTROGEN-RECEPTOR-BETA; CULTURED HUMAN MELANOCYTES; STEM-CELL FACTOR; PROOPIOMELANOCORTIN-DERIVED PEPTIDES; FIBROBLAST-GROWTH-FACTOR; ULTRAVIOLET-B RADIATION; HUMAN KERATINOCYTES; STIMULATING FACTOR; HUMAN EPIDERMIS; CYCLIC-AMP AB All organisms, from simple invertebrates to complex human beings, exist in different colors and patterns, which arise from the unique distribution of pigments throughout the body. Pigmentation is highly heritable, being regulated by genetic, environmental, and endocrine factors that modulate the amount, type, and distribution of melanins in the skin, hair, and eyes. In addition to its roles in camouflage, heat regulation, and cosmetic variation, melanin protects against UV radiation and thus is an important defense system in human skin against harmful factors. Being the largest organ of the body that is always under the influence of internal and external factors, the skin often reacts to those agents by modifying the constitutive pigmentation pattern. The focus of this review is to provide an updated overview of important physiological and biological factors that increase pigmentation and the mechanisms by which they do so. We consider endocrine factors that induce temporary ( e. g., during pregnancy) or permanent ( e. g., during aging) changes in skin color, environmental factors ( e. g., UV), certain drugs, and chemical compounds, etc. Understanding the mechanisms by which different factors and compounds induce melanogenesis is of great interest pharmaceutically ( as therapy for pigmentary diseases) and cosmeceutically ( e. g., to design tanning products with potential to reduce skin cancer risk). C1 Avon Prod Inc, New Technol Dept, Global R&D, Suffern, NY 10901 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Costin, GE (reprint author), Avon Prod Inc, New Technol Dept, Global R&D, 1 Avon Pl, Suffern, NY 10901 USA. EM gertrude.costin@avon.com FU Intramural NIH HHS NR 146 TC 310 Z9 324 U1 11 U2 57 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 APR PY 2007 VL 21 IS 4 BP 976 EP 994 DI 10.1096/fj.06-6649rev PG 19 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156LS UT WOS:000245650400003 PM 17242160 ER PT J AU Bagnasco, L Tortolina, L Biasotti, B Castagnino, N Ponassi, R Tomati, V Nieddu, E Stier, G Malacarne, D Parodi, S AF Bagnasco, L. Tortolina, L. Biasotti, B. Castagnino, N. Ponassi, R. Tomati, V. Nieddu, E. Stier, G. Malacarne, D. Parodi, S. TI Inhibition of a protein-protein interaction between INI1 and c-Myc by small peptidomimetic molecules inspired by Helix-1 of c-Myc: identification of a new target of potential antineoplastic interest SO FASEB JOURNAL LA English DT Article DE inhibitors ID MYC/MAX DIMERIZATION; CELL-GROWTH; DNA-BINDING; SEQUENCE; MAX; TRANSFORMATION; TRANSCRIPTION; APOPTOSIS AB c-Myc is a transcription modulator protooncogene. When overexpressed, it becomes an important contributor to the multi-hit process of malignant transformation. In two earlier papers in this journal (see refs. 19, 20) we reported that retro-inverso peptidomimetic molecules inspired by the Helix-1 of c-Myc motif could be sequence-specific antiproliferative agents active in the low micromolar range. We also found that our peptides were not opening the four-alpha-helix Myc:Max bundle. Their antiproliferative activity in cancer cell lines needs the presence of side chains projecting outside of the bundle in the corresponding native H1 motif. This observation suggested interference with an external partner. In this study we investigated the INI1:Myc interaction. INI1 is a subunit of the SWI/SNF complex (component of the enhanceosome surrounding Myc:Max heterodimer). The INI1:Myc interaction was confirmed via pull down, ELISA, and fluorescence anisotropy assays. According to the length of INI1 fragments used, we calculated K(d)s ranging between 1.3 x 10(-6) and 4.8 x 10(-7) M. The three different techniques applied showed that the INI1:Myc interaction was also the target of our retro-inverso peptidomimetic molecules, which seem to bind specifically at INI1. A Myc binding, 21aa INI1 fragment (minimum interacting sequence), could inspire the synthesis of a new class of more selective c-Myc inhibitors. C1 Univ Genoa, Dept Oncol Biol & Genet, I-16132 Genoa, Italy. Natl Canc Inst, Expt Oncol Lab, IST, Genoa, Italy. ISO, Genoa, Italy. Univ Genoa, Dept Pharmaceut Sci, Genoa, Italy. EMBL Heidelberg, Struct & Computat Biol Unit, Heidelberg, Germany. RP Bagnasco, L (reprint author), Univ Genoa, Dept Oncol Biol & Genet, L go R Benzi 10, I-16132 Genoa, Italy. EM luca.bagnasco@unige.it NR 23 TC 15 Z9 16 U1 0 U2 5 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 APR PY 2007 VL 21 IS 4 BP 1256 EP 1263 DI 10.1096/fj.06-7082com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 156LS UT WOS:000245650400029 PM 17215484 ER PT J AU Abdala, APL Koizumi, H Rybak, IA Smith, JC Paton, JFR AF Abdala, Ana Paula Lima Koizumi, Hidehiko Rybak, Ilya A. Smith, Jeffrey C. Paton, Julian F. R. TI The 3-2-1 state respiratory rhythm generator hypothesis revealed by microsectioning, reduced extracellular chloride and alterations in arterial gas tensions in the in situ rat SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Bristol, Bristol BS8 1TD, Avon, England. Osaka Univ, Sch Dent, Osaka, Japan. Drexel Univ, Sch Biomed Engn, Philadelphia, PA 19129 USA. NINDS, Neural Control Lab, NIH, Cellular & Syst Neurobiol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2007 VL 21 IS 5 BP A557 EP A558 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504428 ER PT J AU Abdalla, NH Fedorova, I Moriguchi, T Majchrzak, S Martino, C Hoshiba, J Salem, N AF Abdalla, Nahed Hussein Fedorova, Irina Moriguchi, Tom Majchrzak, Sharon Martino, Carmine Hoshiba, Junji Salem, Norman, Jr. TI The use of artificial rearing of infant mice from day 2 of life: One generation model of n-3 fatty acid deficiency SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA, NIH, Rockville, MD 20852 USA. Wakanaga Pharmaceut, Hiroshima, Japan. Okayama Univ, Okayama, Japan. RI Majchrzak, Sharon/F-1830-2013 OI Majchrzak, Sharon/0000-0001-8934-7294 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A321 EP A321 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502393 ER PT J AU Adragna, NC Zhang, J Lauf, PK AF Adragna, Norma C. Zhang, Jing Lauf, Peter K. TI Functional characteristics of K-Cl cotransport (COT) in vascular smooth muscle cells (VSMCs) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Wright State Univ, Boonsoft Sch Med, Dayton, OH 45435 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1335 EP A1335 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705039 ER PT J AU Ahanchi, SS Pearce, CG Kapadia, MR Jiang, Q Martinez, J Saavedra, JE Keefer, LK Kibbe, MR AF Ahanchi, Sadaf Sadie Pearce, Charlie G. Kapadia, Muneera R. Jiang, Qun Martinez, Janet Saavedra, Joseph E. Keefer, Larry K. Kibbe, Melina R. TI Improved efficacy of a nitric oxide-eluting therapy in diabetes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Northwestern Univ, Div Vasc Surg, Chicago, IL 60611 USA. Mt Sinai Hosp, Dept Surg, Chicago, IL 60608 USA. SAIC Frederick, BRP, Frederick, MD 21702 USA. NCI, LCC CCR, Frederick, MD 21702 USA. RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A18 EP A18 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500084 ER PT J AU Ait-Ali, D Turquier, V Grumolato, L Yon, L Mounien, L Jegou, S Derambure, C Salier, JP Eiden, LE Vaudry, H Anouar, Y AF Ait-Ali, D. Turquier, V. Grumolato, L. Yon, L. Mounien, L. Jegou, S. Derambure, C. Salier, J. P. Eiden, L. E. Vaudry, H. Anouar, Y. TI TNF-alpha signaling through NF-kappa B in chromaffin cells-identification of novel targets with suppression subtractive hybridization study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIMH, SMN, LCMR, NIH, Bethesda, MD 20892 USA. Univ Rouen, IFRMP 23, INSERM, U413, Rouen, France. Fac Med Pharm, INSERM, U519, IFRMP 23, Rouen, France. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2007 VL 21 IS 5 BP A287 EP A288 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502226 ER PT J AU Albert, A Edrington, T Bennett, M AF Albert, Arlene Edrington, Thomas Bennett, Michael TI Effect of opsin on the thermal stability of rhodopsin in bovine rod outer segment disk membranes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Connecticut, Storrs, CT 06269 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A422 EP A422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503333 ER PT J AU Alipanah, N Ferrucci, L Sun, K Fried, LP Walston, J Varadhan, R Guralnik, JM Semba, RD AF Alipanah, Narges Ferrucci, Luigi Sun, Kai Fried, Linda P. Walston, Jeremy Varadhan, Ravi Guralnik, Jack M. Semba, Richard D. TI Relationship of antioxidant nutrients with oxidative protein damage among older women living in the community SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA. NIH, NIA, Epidemiol Demography & Biometry Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A727 EP A727 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505625 ER PT J AU Amaral, J Notari, L Stetler-Stevnson, W Becerra, SP AF Amaral, Juan Notari, Luigi Stetler-Stevnson, William Becerra, S. Patricia TI Gelatinase-medliated proteolysis of pigment epithelium-derived factor (PEDF) is pH dependent SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NEI, NIH, Sect Prot Struct Funct, Bethesda, MD 20892 USA. CCCB, NCI NIH, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A648 EP A649 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505258 ER PT J AU Anderson, AL Sahyoun, NR Harris, TB Tylavsky, FA Goodpaster, BH Lee, JS Sellmeyer, DE AF Anderson, Amy Louise Sahyoun, Nadine R. Harris, Tamara B. Tylavsky, Frances A. Goodpaster, Bret H. Lee, Jung Sun Sellmeyer, Deborah E. TI Dietary glycemic index and load and risk of type 2 diabetes in older adults SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NIH, Natl Inst Aging, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15238 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15238 USA. Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94115 USA. RI Sahyoun, Nadine/G-2608-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A116 EP A116 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500553 ER PT J AU Andrews, KW Roseland, J Zhao, C Schweitzer, A Holden, J Perry, C Dwyer, J Piccian, MF Fisher, K Saldanha, L Yetley, E Douglass, L AF Andrews, Karen W. Roseland, Janet Zhao, Cuiwei Schweitzer, Amy Holden, Joanne Perry, Charles Dwyer, Johanna Piccian, Mary Frances Fisher, Kenneth Saldanha, Leila Yetley, Elizabeth Douglass, Larry TI Comparison of label vs. analytical values for 23 vitamins and minerals in adult multivitamin/mineral (MVM) products for the Dietary Supplement Ingredient Database (DSID) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 USDA ARS, Beltsville Agr Res Ctr, Beltsville Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. NIH, Off Dietary Supplements, Bethesda, MD 20895 USA. Univ Maryland, Biometr Program, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2007 VL 21 IS 5 BP A52 EP A52 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500250 ER PT J AU Andric, SA Stojkov, NJ Janjic, MM Stojilkovic, SS Kostic, TS AF Andric, Silvana A. Stojkov, Natasa J. Janjic, Marija M. Stojilkovic, Stanko S. Kostic, Tatjana S. TI Involvement of nitric oxide-cGMP signaling in Leyding cell stress response SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Fac Sci, Novi Sad 21000, Serbia. NIH, NICHD, ERRB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A622 EP A622 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505125 ER PT J AU Asemu, G Fishbein, K Canuto, H Spencer, R Soldatov, N Abernethy, D AF Asemu, Girma Fishbein, Kenneth Canuto, Holly Spencer, Richard Soldatov, Nikolai Abernethy, Darrell TI Development of cardiomyopathy in response to chronic beta-adrenegric stimulation of transgenic mouse overexpressing the exon-22 isoform of the human Ca(nu)1.2 channel (alpha 1C) subunit as revealed by magnetic resonance imaging SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A583 EP A583 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504546 ER PT J AU Astorga, BO Pelis, RM Wunz, TM Perry, JA Pritchard, JR Wright, SH AF Astorga, Bethzaida Olivia Pelis, Ryan M. Wunz, Theresa M. Perry, Jennifer A. Pritchard, John R. Wright, Stephen H. TI Molecular basis for the differential sensitivity of OCT2 and OAT1 toward Hg2+ SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Arizona, Tucson, AZ 85719 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A908 EP A908 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701269 ER PT J AU Bales, CW McCrory, M Zheng, J Champagne, C Gilhooly, C Hannah, J Racette, S Martin, C Obert, K Das, S Delany, J Mandel, S Rochon, J Roberts, S Schechtman, K AF Bales, Connie W. McCrory, M. Zheng, J. Champagne, C. Gilhooly, C. Hannah, J. Racette, S. Martin, C. Obert, K. Das, S. Delany, J. Mandel, S. Rochon, J. Roberts, S. Schechtman, K. TI Quality of self-selected diets of non-obese participants in a randomized controlled trial of caloric restriction (CR): the CALERIE study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Duke Univ, Med Ctr, Durham, NC 27710 USA. Tufts Univ, Boston, MA 02111 USA. Washington Univ, St Louis, MO 63108 USA. Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. NIA, Bethesda, MD 20892 USA. Duke Clin Res Inst, Durham, NC 27715 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 5 BP A155 EP A155 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501178 ER PT J AU Banerjee, R Basu, NK Garza, A Owens, IS AF Banerjee, Rajat Basu, Nikhil K. Garza, Amanda Owens, Ida S. TI Determination of possible UDP binding sites in UGT1A10 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NICHD, HDB, SGDDM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1002 EP A1002 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702156 ER PT J AU Basu, NK Mitra, PS Garza, A Basu, M Banerjee, R Owens, IS AF Basu, Nikhil Kumar Mitra, Partha S. Garza, Amanda Basu, Mousumi Banerjee, Rajat Owens, Ida S. TI Understanding how phoshorylation of the UDP-Glueuronosyltransferase system controls and protects against chemical toxins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NICHD, HDB, SGDD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1021 EP A1021 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702252 ER PT J AU Batkai, S Osei-Hyiaman, D El-Assal, O Mukhopadhyay, P Mohanraj, R Huffman, JW Gao, B Kunos, G Pacher, P AF Batkai, Sandor Osei-Hyiaman, Douglas El-Assal, Osama Mukhopadhyay, Partha Mohanraj, Rajesh Huffman, John W. Gao, Bin Kunos, George Pacher, Pal TI The role of the endocannabinoid system in liver ischemia reperfusion injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA LPS, NIH, Bethesda, MD 20854 USA. Clemson Univ, Howard L Hunter Chem Lab, Clemson, SC 29634 USA. RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; NR 0 TC 5 Z9 5 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A807 EP A807 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700341 ER PT J AU Beek, J Ferrucci, L Sun, K Fried, LP Walston, J Varadhan, R Guralnik, J Semba, R AF Beek, Justine Ferrucci, Luigi Sun, Kai Fried, Linda P. Walston, Jeremy Varadhan, Ravi Guralnik, Jack Semba, Richard TI Low serum selenium concentrations are associated with poor grip strength among older women living in the community. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Harbor Hosp, NIH, NIA, Clin Res Branch Longitudinal Studies Sect, Baltimore, MD 21225 USA. NIH, NIA, Epidemiol Demography & Biometry Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A717 EP A717 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505576 ER PT J AU Bennett, MP Mitchell, DC AF Bennett, Michael Paul Mitchell, Drake C. TI Membrane order controls both rhodopsin thermal denaturation kinetics and MetaII formation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA, NIH, LMBB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A242 EP A242 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502007 ER PT J AU Biacsi, RE Kumari, D Usdin, K AF Biacsi, Rea Erika Kumari, Daman Usdin, Karen TI Histone deacetylase and DNA methylase inhibitors in the treatment of fragile X syndrome? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIDDK, NIH, LMCB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A989 EP A989 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702091 ER PT J AU Bien, C Chang, Y Lee, HS Kwon-Chung, J Espenshade, P AF Bien, Clara Chang, Yuri Lee, Hyeseung Kwon-Chung, June Espenshade, Peter TI Cryptococcus neoformans sterol regulatory element binding protein (Sre1p), a virulence factor that functions in oxygen sensing and sterol homeostasis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIH, Lab Clin Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A608 EP A608 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505059 ER PT J AU Boukari, H Sackett, D Nossal, R AF Boukari, Hacene Sackett, Dan Nossal, Ralph TI Tubulin-Dolastatin rings undergo rouleau aggregation while cryptophycin-tubulin rings are non-interacting SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2007 VL 21 IS 5 BP A630 EP A630 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505165 ER PT J AU Boukari, H Shiu, B Banerjee, S Silver, J Youle, RJ Bezrukov, SM Rostovtseva, TK AF Boukari, Hacene Shiu, Brian Banerjee, Soojay Silver, Jonathan Youle, Richard J. Bezrukov, Sergey M. Rostovtseva, Tatiana K. TI Fluorescence based studies of endophilin B proteins and their interactions with lipid membranes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NICHHD, NIH, LIMB, Bethesda, MD 20892 USA. NICHHD, NIH, LPSB, Bethesda, MD 20892 USA. NINDS, NIH, SNB, Bethesda, MD 20892 USA. NIAID, NIH, BVS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A258 EP A258 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502083 ER PT J AU Buchanan, SK Lukacik, P Grizot, S Ghirlando, R Ali, MMU Barnard, TJ Jakes, KS Kienker, PK Esser, L AF Buchanan, Susan K. Lukacik, Petra Grizot, Sylvestre Ghirlando, Rodolfo Ali, Maruf M. U. Barnard, Travis J. Jakes, Karen S. Kienker, Paul K. Esser, Lothar TI Transport of proteins across membranes: structure of the colicin I receptor bound to colicin Ia SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIDDK, NIH, LMB, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Physiol & Biophys, Bronx, NY 10461 USA. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RI Ghirlando, Rodolfo/A-8880-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 5 BP A148 EP A148 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501144 ER PT J AU Calderon, FS Kim, HY AF Calderon, Frances Suiyin Kim, Hee-Yong TI Docosahexaenoic acid decreases apoptosis of hippocampal neurons SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA, NIH, Mol Signalling Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A989 EP A989 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702092 ER PT J AU Camberg, JL Hoskins, JR Wickner, S AF Camberg, Jodi L. Hoskins, Joel R. Wickner, Sue TI ClpXP degrades the bacterial cell division protein FtsZ SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1024 EP A1025 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702269 ER PT J AU Cao, H Kelly, MA Kari, F Dawson, HD Coves, S Roussel, AM Anderson, RA AF Cao, Heping Kelly, Meghan A. Kari, Frank Dawson, Harry D. Coves, Sara Roussel, Anne M. Anderson, Richard A. TI Green tea increases the anti-inflammatory tristetraprolin and decreases the pro-inflammatory tumor necrosis factor mRNA levels in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 USDA ARS, Beltsville Human Nutr Res Ctr, Nutrient Requirements & Funct Lab, Beltsville, MD 20705 USA. NIEHS, DHHS NIH, Res Triangle Pk, NC 27709 USA. Unilever France, F-92842 Rueil Malmaison, France. Univ Grenoble 1, F-38700 La Tronche, France. RI Dawson, Harry/H-8242-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 5 BP A165 EP A166 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501225 ER PT J AU Carlson, BA Shrimali, RK Irons, R Park, JM Hatfield, DL AF Carlson, Bradley A. Shrimali, Rajeev K. Irons, Robert Park, Jin Mo Hatfield, Dolph L. TI Targeted removal of the selenocysteine tRNA ([Ser]Sec) gene (trsp) in mouse macrophages SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NCI, LCP, CCR, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Harvard Med Sch, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A717 EP A718 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505579 ER PT J AU Carter, JJ Lahousse, S Roper, N de la Monte, S AF Carter, Jade Jesika Lahousse, Stephanie Roper, Nitin de la Monte, Suzanne TI Ethanol inhibition of aspartvl-(asparaginyl)-p-hydroxylase: Relevance to impaired neuronal migration in fetal alcohol syndrome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Brown Univ, Providence, RI 02903 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Rhode Isl Hosp, Providence, RI 02903 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2007 VL 21 IS 5 BP A75 EP A75 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500357 ER PT J AU Cebova, M Knowles, CJ Jackson, S Pinz, IM AF Cebova, Martina Knowles, Catherine J. Jackson, Shelley Pinz, Ilka M. TI Low TNF alpha expression protects the mouse heart from palmitate induced systolic dysfunction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Ctr Mol Med, Maine Med Ctr Res Inst, Scarborough, ME 04074 USA. Natl Inst Drug Abuse, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 6 BP A1425 EP A1425 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705458 ER PT J AU Chantler, PD Melenovsky, V Schulman, SP Gerstenblith, G Fleg, JL Becker, L Ferrucci, L Lakatta, EG Najjar, SS AF Chantler, Paul David Melenovsky, Vojtech Schulman, Steven P. Gerstenblith, Gary Fleg, Jerome L. Becker, Lewis Ferrucci, Luigi Lakatta, Edward G. Najjar, Samer S. TI Synergistic effects of systolic hypertension and female sex on the arterial-ventricular coupling ratio SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIA, LCS, GRC, Baltimore, MD 21224 USA. JHMI, Baltimore, MD 21287 USA. NIH, NHLBI, Bethesda, MD 20892 USA. NIH, CRB, Baltimore, MD 21225 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 6 BP A1260 EP A1260 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704245 ER PT J AU Chavakis, T Choi, EY Xie, CP Chavakis, E Gahmberg, C Bianchi, M Nawroth, P Orlova, V AF Chavakis, Triantafyllos Choi, EunYoung Xie, Changping Chavakis, Emmanouil Gahmberg, Carl Bianchi, Marco Nawroth, Peter Orlova, Valeria TI A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Natl Canc Inst, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Heidelberg, Heidelberg, Germany. Univ Frankfurt, D-6000 Frankfurt, Germany. Univ Helsinki, Helsinki, Finland. Ist Sci San Raffaele, I-20132 Milan, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2007 VL 21 IS 5 BP A126 EP A126 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501036 ER PT J AU Chavakis, T Celeste, A Orlova, V Nussenzweig, A Economopoulou, M AF Chavakis, Triantafyllos Celeste, Arkady Orlova, Valeria Nussenzweig, Andre Economopoulou, Matina TI Histone H2AX functions in hypoxia-driven neovascularisation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NEI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A14 EP A14 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500065 ER PT J AU Chen, C Ma, XC Malfatti, MA Krausz, KW Kimura, S Felton, JS Idle, JR Gonzalez, FJ AF Chen, Chi Ma, Xiaochao Malfatti, Michael A. Krausz, Kristopher W. Kimura, Shioko Felton, James S. Idle, Jeffery R. Gonzalez, Frank J. TI A metabolomic investigation of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) metabolism in the mouse SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA 94551 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A813 EP A813 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700365 ER PT J AU Chen, YP Jetten, AM Goldstein, JA AF Chen, Yuping Jetten, Anton M. Goldstein, Joyce A. TI The retinoic acid receptor-related orphan receptor (ROR) regulates human CYP2C8 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIEHS, LRB, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1183 EP A1183 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708703438 ER PT J AU Choi, EY Gahmberg, C Chavakis, T AF Choi, Eun Young Gahmberg, Carl Chavakis, Triantafyllos TI Regulation of LFA-1-integrin-mediated leukocyte recruitment by Cbl-b and 14-3-3 proteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Natl Canc Inst, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Helsinki, Helsinki, Finland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A126 EP A126 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501035 ER PT J AU Choi, W Miyamura, Y Wolber, R Hearing, VJ AF Choi, Wonseon Miyamura, Yoshinori Wolber, Rainer Hearing, Vincent J. TI Regulation of melanogenic paracrine and autocrine factors of human skin in vivo by repetitive UV radiation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. Dept Skin Res, Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A621 EP A621 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505119 ER PT J AU Chou, CL Morris, RG Yu, MJ Wall, SM Knepper, MA AF Chou, C. L. Morris, R. G. Yu, M. J. Wall, S. M. Knepper, M. A. TI Role of NKCC1 in vasopressin-induced cell swelling in renal collecting duct cell SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NHLBI, NIH, Bethesda, MD 20892 USA. Emory Univ, Atlanta, GA 30322 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A964 EP A964 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701534 ER PT J AU Chung, JY Williams, R Guerrero, N Lim, L Tuttle, K Takikita, M Lu, YL Hewitt, SM AF Chung, Joon-Yong Williams, Reginald Guerrero, Natalie Lim, Langston Tuttle, Kimberly Takikita, Mikiko Lu, Yuling Hewitt, Stephen M. TI Comprehensive analysis of fundamental RNA quality factors in archival tissue SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NCI, ATC, NIH, Bethesda, MD 20892 USA. Panom Inc, Fremont, CA 94555 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1147 EP A1147 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708703271 ER PT J AU Cleland, MM Ryu, SW Karbowski, M Youle, R AF Cleland, Megan Marie Ryu, Seung-Wook Karbowski, Mariusz Youle, Richard TI State of GTPase cycle dictates mobility and localization of large mitochondrial GTPases, Mfn1 and 2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NINDS, NIH, Biochem Sect, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Maryland, Ctr Med Biotechnol, Inst Biotechnol, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A661 EP A661 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505318 ER PT J AU Coelho, S Passeron, T Miyamura, Y Hearing, VJ AF Coelho, Sergio Passeron, Thierry Miyamura, Yoshinori Hearing, Vincent J. TI Practical methods for detecting inelanocytes in the skin and their responses to UV SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A774 EP A774 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700189 ER PT J AU Cohen, LA Vamai, P Balla, T Donaldson, JG AF Cohen, Lee Ann Vamai, Peter Balla, Tamas Donaldson, Julie G. TI Complexity of ARF function in the cell periphery SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NHLBI, NIH, LCB, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 5 BP A617 EP A617 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505102 ER PT J AU Combs, GF Watts, JC Scheett, AJ Johnson, LK Davis, CD Milner, JA AF Combs, Gerald F., Jr. Watts, Jennifer C. Scheett, Angela J. Johnson, Luann K. Davis, Cindy D. Milner, John A. TI Selenium status of a cohort of healthy Americans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. NCI, Div Canc Prevent & Control, Rockville, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A105 EP A105 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500503 ER PT J AU Dayhoff-Brannigan, ME Ferrucci, L Sun, K Fried, LP Walston, J Varadhan, R Guralnik, J Semba, RD AF Dayhoff-Brannigan, Margaret E. Ferrucci, Luigi Sun, Kai Fried, Linda P. Walston, Jeremy Varadhan, Ravi Guralnik, Jack Semba, Richard D. TI Oxidative protein damage is associated with elevated serum interleukin-6 levels among older moderately to severely disabled women living in the community SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA. NIA, NIH, Gateway Bldg, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A739 EP A740 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700024 ER PT J AU De Soto, JA Xiao, CY Deng, CX AF De Soto, Joseph Angel Xiao, Cuiying Deng, Chu-Xia TI The enhancement of paclitaxel cytotoxicity in hereditary and sporadic breast cancer by the poly(ADP) ribose pollymerase inhibitor AG14361 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIDDK, NIH, GDDB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 5 BP A437 EP A437 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503406 ER PT J AU Demar, JC Martino, C Lefkowitz, W Salem, N AF DeMar, James Charles, Jr. Martino, Carmine Lefkowitz, William Salem, Norman, Jr. TI Effect of dietary docosahexaenoic acid on the in vivo net biosynthesis of docosahexaenoic acid from a-linolenic acid, in rat tissues SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A239 EP A239 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501584 ER PT J AU Deng, Y Kim, YW Philpott, C AF Deng, Yi Kim, Youngwoo Philpott, Caroline TI Ubiquitin-dependent trafficking of Arn1, the ferrichrome transporter of Saccharomyces cerevisiae SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIDDK, NIH, Liver Dis Sect, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A244 EP A244 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502019 ER PT J AU Devonshire, AL Lauretani, F Bus, A Chia, C Ling, S Ferrucci, L AF Devonshire, Ashley Lynn Lauretani, Fulvio Bus, Angelo Chia, Chee Ling, Shari Ferrucci, Luigi TI Metabolic correlates of aging muscle: Data from the Baltimore longitudinal study of aging SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIA, Clin Res Branch, Baltimore, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Tuscany Reg Hlth Agcy, Florence, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A927 EP A927 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701360 ER PT J AU Dmitrieva, NI Zhou, XM Nussenzweig, A Burg, MB AF Dmitrieva, Natalia I. Zhou, Xiaoming Nussenzweig, Andre Burg, Maurice B. TI Lack of Ku86 and water restriction both increase P16(INK4) expression in renal inner medullary cells in vivo. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NHLBI, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A962 EP A962 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701525 ER PT J AU Doyle, SM Hoskins, JR Wickner, S AF Doyle, Shannon M. Hoskins, Joel R. Wickner, Suc TI The role of the DnaK system in regulating the ClpB AAA plus ATPase chaperone activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2007 VL 21 IS 6 BP A1023 EP A1023 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702263 ER PT J AU Duma, D Fernandes, D Assreuy, J AF Duma, Danielle Fernandes, Daniel Assreuy, Jamil TI NOS1-derived nitric oxide as a signaling effector for the initiation of systemic inflammatory reaction in sepsis models SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Univ Fed Santa Catarina, Ctr Biol Sci, Florianopolis, SC, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A441 EP A441 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503427 ER PT J AU Eisner, C Kim, SM Briggs, J Schnermann, J AF Eisner, Christoph Kim, Soo Mi Briggs, Josie Schnermann, Jurgen TI Effects of AMP on core body temperature in A1 adenosine receptor and CD73 knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NIDDK, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A1312 EP A1312 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708704489 ER PT J AU Elliott, MS Morris, RC AF Elliott, Mark Stuart Morris, Rana C. TI Zymergomics: Integration of bioinformatics and process laboratory biochemistry SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 George Washington Univ, Washington, DC 20037 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A297 EP A297 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502273 ER PT J AU Ely, MA Williams, C Schnetz, M Burg, M Ferraris, J AF Ely, Megan Annette Williams, Chester Schnetz, Michael Burg, Maurice Ferraris, Joan TI Role of the AP-1 factors, c-Fos and c-Jun, in high NaCl-induced activation of the osmoprotective transcription factor, TonEBP/OREBP SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A962 EP A962 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701523 ER PT J AU Endo, Y Beauchamp, E Toretsky, JA Uren, A Rubin, JS AF Endo, Yoshimi Beauchamp, Elspeth Toretsky, Jeffrey A. Uren, Aykut Rubin, Jeffrey S. TI Wnt-3a stimulates neurite outgrowth in Ewing sarcoma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NCI, Bethesda, MD 20892 USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2007 VL 21 IS 6 BP A991 EP A991 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702100 ER PT J AU Erickson, HS Gillespie, JW Asante, J Rodriguez-Canales, J Josephson, JW Gannot, G Pinto, PA Linehan, WM Choyke, PL Chuaqui, RF Hewitt, SM Emmert-Buck, MR AF Erickson, Heidi S. Gillespie, John W. Asante, Jeremiah Rodriguez-Canales, Jaime Josephson, John W. Gannot, Gallya Pinto, Peter A. Linehan, W. Marston Choyke, Peter L. Chuaqui, Rodrigo F. Hewitt, Stephen M. Emmert-Buck, Michael R. TI Clinical pathogenetics prostate tissue relational database SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Pathogenet Unit, Bethesda, MD 20892 USA. Urol Oncol Branch, Bethesda, MD 20892 USA. Mol Imaging Program, Bethesda, MD 20892 USA. NCI, NIH, TARP, Bethesda, MD 20892 USA. SAIC Frederick Inc, NCI, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A64 EP A64 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500307 ER PT J AU Evezich, M Solages, F Gilhooly, C Eldridge, G Huang, T Gehrke, M Roberts, S Saltzman, E Fuss, P Koutoubi, S Murdoch, S McCrory, M AF Evezich, Maribeth Solages, F. Gilhooly, C. Eldridge, G. Huang, T. Gehrke, M. Roberts, S. Saltzman, E. Fuss, P. Koutoubi, S. Murdoch, S. McCrory, M. TI Eating pattern and dietary composition association with insulin resistance (IR) markers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Bastyr Univ, Sch Nutr & Exercise Sci, Kenmore, WA 98028 USA. Tufts Univ, Boston, MA 02111 USA. NICHD, Rockville, MD 20847 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A6 EP A6 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500031 ER PT J AU Fedorova, IM Hussein, N Di Martino, C Moriguchi, T Majchrzak, S Salem, N AF Fedorova, Irina M. Hussein, Nahed Di Martino, Carmine Moriguchi, Toru Majchrzak, Sharon Salem, Norman, Jr. TI N-3 fatty acid deficient diet affects mice spatial learning in the Barnes circular maze. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA, NIH, Rockville, MD 20852 USA. RI Majchrzak, Sharon/F-1830-2013 OI Majchrzak, Sharon/0000-0001-8934-7294 NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2007 VL 21 IS 5 BP A321 EP A321 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502392 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 FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. Ctr Neutron Res, NIST, Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A237 EP A237 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501575 ER PT J AU Ferre, S Justinova, Z Franco, R Goldberg, SR AF Ferre, Sergi Justinova, Zuzana Franco, Rafael Goldberg, Steven R. TI Adenosine A2A-cannabinoid CB1 receptor heteromers. Implications for the rewarding effects of cannabinoids SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIDA, IRP, NIH, DHHS, Baltimore, MD 21224 USA. Univ Barcelona, Dept Biochem & Mol Biol, Barcelona 08028, Spain. RI Franco, Rafael/C-3694-2015 OI Franco, Rafael/0000-0003-2549-4919 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A410 EP A410 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503277 ER PT J AU Franco, R Cidlowski, JA AF Franco, Rodrigo Cidlowski, John A. TI A primary regulatory role for glutathione transport in FasL-induced apoptosis in Jurkat cells. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIEHS, NIH, Lab Signal Transduction, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A257 EP A257 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502082 ER PT J AU Free, RB Hazelwood, LA Spalding, HN Cabrera, DM Sibley, DR AF Free, R. Benjamin Hazelwood, Lisa A. Spalding, Heather N. Cabrera, David M. Sibley, David R. TI Sorting nexin-25, a novel member of the dopamine receptor signalplex, up-regulates D-1, and D-2 dopamine receptor expression in HEK293 cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NINDS, NIH, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. RI Cabrera, David/I-1013-2014 NR 0 TC 0 Z9 0 U1 1 U2 1 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 APR PY 2007 VL 21 IS 5 BP A423 EP A423 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503341 ER PT J AU Fricks, IP Maddileti, S Lazarowski, ER Nicholas, RA Jacobson, KA Harden, TK AF Fricks, Ingrid P. Maddileti, Savitri Lazarowski, Eduardo R. Nicholas, Robert A. Jacobson, Kenneth A. Harden, T. Kendall TI UDP is an antagonist at the hP2Y14 receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A424 EP A424 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503346 ER PT J AU Fuda, H Javitt, NB Strott, CA AF Fuda, Hirotoshi Javitt, Norman B. Strott, Charles A. TI Novel role of human cholesterol sulfotransferase (SULT2B1b) in oxysterol metabolism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NICHD, NIH, Bethesda, MD USA. NYU Med Ctr, Div Gastroenterol, New York, NY 10016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A240 EP A240 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501589 ER PT J AU Gagarina, V Carlberg, A Pereira-Mouries, L Hall, DJ AF Gagarina, Viktoria Carlberg, Alyssa Pereira-Mouries, Lucilia Hall, David J. TI COMP blocks death in human chondrocytes by elevating the IAP family of antiapoptotic proteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NIAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 5 BP A134 EP A134 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501072 ER PT J AU Gallardo, P Burg, MB Ferraris, JD AF Gallardo, Pedro Burg, Maurice B. Ferraris, Joan D. TI Rac1 and p38 contribute to signaling high NaCl-induced movement of Tonicity Enhanced Binding Protein (TonEBP) from cytoplasm to nucleus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A961 EP A962 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701521 ER PT J AU Gallazzini, M Ferraris, JD Burg, MB AF gallazzini, morgan Ferraris, Joan D. Burg, Maurice B. TI Identification of Gpdp5 as a glycerophosphocholine phosphodiesterase (GPC-PDE) involved in osmotic regulation of GPC. SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NHLBI, NIH, LKEM, Bethesda, MD 20892 USA. RI Gallazzini, Morgan/E-5465-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A962 EP A962 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708701526 ER PT J AU Gawrisch, K Eldho, NV Kimura, T Mihailescu, M AF Gawrisch, Klaus Eldho, Nadukkudy V. Kimura, Tomohiro Mihailescu, Mihaela TI Structure, dynamics, and location of the endocannabinoid 2-AG in lipid bilayers - an NMR and neutron diffraction study SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIAAA, NIH, Bethesda, MD 92697 USA. Univ Calif Irvine, Inst Med Sci, Dept Physiol & Biophys, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 6 BP A984 EP A984 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702066 ER PT J AU Gerdin, M Eiden, L AF Gerdin, Matthew Eiden, Lee TI PACAP acts through a cyclic AMP-initiated ERK activation pathway independent of PKA and requiring calcium co-signaling for transcription linked to differentiation in PC12-G cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIMH, NIH, Lab Cell & Mol Regulat, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A792 EP A792 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700271 ER PT J AU Gillespie, J Moore, H Dang, H Player, A Wang, Y David, K Spangenberg, J Vaught, J Schneider, J Erickson, H Barker, A Compton, C AF Gillespie, John Moore, Helen Dang, Hien Player, Audrey Wang, Yonghong David, Kerstin Spangenberg, Joerg Vaught, Jim Schneider, Julie Erickson, Heidi Barker, Anna Compton, Carolyn TI The NCI biospecimen research network SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 SAIC Frederick Inc, Natl Canc Inst Frederick, ATC, Gaithersburg, MD 20877 USA. NCI, Bethesda, MD 20892 USA. NCI, ATC, Gaithersburg, MD 20877 USA. Indivumed GmbH, D-22297 Hamburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A388 EP A388 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503176 ER PT J AU Goldberg, SR Munzar, P Tanda, G Redhi, GH Justinova, Z AF Goldberg, Steven R. Munzar, Patrik Tanda, Gianluigi Redhi, Godfrey H. Justinova, Zuzana TI Maintenance and reinstatement of THC self-administration behavior under a second-order schedule of reinforcement in squirrel monkeys SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIDA, IRP, NIH, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. NIDA, IRP, NIH, Psychobiol Sect, Baltimore, MD 21224 USA. Alexza, Palo Alto, CA 94303 USA. Univ Maryland, Sch Med, MPRC, Baltimore, MD 21228 USA. RI Tanda, Gianluigi/B-3318-2009 OI Tanda, Gianluigi/0000-0001-9526-9878 NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2007 VL 21 IS 5 BP A409 EP A409 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503274 ER PT J AU Gonzales, PA Pisitkun, T Star, RA Wang, NS Knepper, MA AF Gonzales, Patricia A. Pisitkun, Trairak Star, Robert A. Wang, Nam Sun Knepper, Mark A. TI Large-scale LC-MS/MS identification of proteins excreted in urinary exosomes: Gender differences SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Maryland, College Pk, MD 20742 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RI Wang, Nam Sun/E-4253-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 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 APR PY 2007 VL 21 IS 6 BP A1416 EP A1416 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708705418 ER PT J AU Guenther, PM Reeve, BB Reedy, J Krebs-Smith, SM Basiotis, PP AF Guenther, Patricia M. Reeve, Bryce B. Reedy, Jill Krebs-Smith, Susan M. Basiotis, P. Peter TI Evaluation of the psychometric properties of the revised Healthy Eating Index SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 USDA, Ctr Nutr Policy & Promot, Alexandria, VA 22302 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A52 EP A52 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500248 ER PT J AU Hatae, N Iwamura, T Stojilkovic, SS AF Hatae, Noriyuki Iwamura, Tatsunori Stojilkovic, Stanko S. TI Role of protein kinase C in desensitization of rat endothelin A receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Natl Inst Hlth, Sect Cell Signaling, Bethesda, MD 20892 USA. Matsuyama Univ, Dept Med Chem, Matsuyama, Ehime, Japan. Gifu Pharmaceut Univ, Dept Pharmaceut Chem, Gifu, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A791 EP A792 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700270 ER PT J AU Hazelwood, LA Free, RB Cabrera, DM Neiman, J Quinn, S Sibley, DR AF Hazelwood, Lisa Ann Free, R. Benjamin Cabrera, David M. Neiman, Jill Quinn, Steven Sibley, David R. TI Reciprocal modulation of function between the D-1 and D-2 dopamine receptors and the Na+/K+-ATPase, a novel member of the dopamine receptor signalplex SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NINDS, NIH, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. RI Cabrera, David/I-1013-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A423 EP A423 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708503342 ER PT J AU Head, J Shen, D Zhou, M Garfinkel, R Chan, CC AF Head, James Shen, Defen Zhou, Min Garfinkel, Richard Chan, Chi-Chao TI Expression of clusterin and VEGF in diabetic retinopathy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NEI, Immunol Lab, Immunopathol Sect, Bethesda, MD 20892 USA. NIH, Clin Res Training Program, Bethesda, MD 20892 USA. Retina Grp Washington, Chevy Chase, MD 20815 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A130 EP A130 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708501054 ER PT J AU Heredia, R Holden, H Becerra, SP AF Heredia, Raul Holden, Haley Becerra, S. Patricia TI The phospholipase activity of a pigment epithelium-derived factor (PEDF) receptor implies mechanisms of action for cell survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NEI, NIH, Sect Prot Struct & Funct, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A249 EP A249 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502042 ER PT J AU Hoenerhoff, MJ Datta, S Dimri, GP Simpson, MR Green, JE AF Hoenerhoff, Mark James Datta, Syamal Dimri, Goberdhan P. Simpson, Mark R. Green, Jeff E. TI The polycomb group protein Bmi-1 collaborates with H-Ras to promote cellular proliferation and transformation of mammary epithelial cells in vitro, and development of poorly differentiated mammary tumors in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Evanston, IL 60201 USA. Canc Res Ctr, Comparat Mol Pathol Unit, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A79 EP A79 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500373 ER PT J AU Hong, HHL Ton, TT Kim, Y Wakamatsu, N Sills, RC AF Hong, Hue-Hua Lily Ton, T. T. Kim, Y. Wakamatsu, N. Sills, R. C. TI Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from B6C3F1 mice exposed to cumene SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIEHS, NIH, LEP, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 6 BP A757 EP A757 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700109 ER PT J AU Hoskins, JR Doyle, SM Miller, JJ Wickner, S AF Hoskins, Joel R. Doyle, Shannon M. Miller, Jonathan J. Wickner, Sue TI Protein remodeling by ClpB AAA plus ATPase independent of the DnaK/Hsp70 chaperone system SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 NIH, NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 APR PY 2007 VL 21 IS 6 BP A1025 EP A1025 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702272 ER PT J AU Howard, CT Ferrucci, L Sun, K Fried, LP Walston, J Varadhan, R Guralnik, J Semba, RD AF Howard, Caitlin Therese Ferrucci, Luigi Sun, Kai Fried, Linda P. Walston, Jeremy Varadhan, Ravi Guralnik, Jack Semba, Richard D. TI Oxidative protein damage is associated with poor grip strength among older women living in the community SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Johns Hopkins Sch Med, Baltimore, MD 21205 USA. Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA. NIH, NIA, Demography & Biometry Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A685 EP A686 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505431 ER EF