FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kurella, M Chertow, GM Fried, LF Cummings, SR Harris, T Simonsick, E Satterfield, S Ayonayon, H Yaffe, K AF Kurella, M Chertow, GM Fried, LF Cummings, SR Harris, T Simonsick, E Satterfield, S Ayonayon, H Yaffe, K TI Chronic kidney disease and cognitive impairment in the elderly: The health, aging, and body composition study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID CARDIOVASCULAR HEALTH; RISK-FACTORS; HEMODIALYSIS-PATIENTS; RENAL-INSUFFICIENCY; PLASMA HOMOCYSTEINE; ALZHEIMERS-DISEASE; SERUM CREATININE; OLDER-ADULTS; DEMENTIA; STROKE AB Previous studies suggest a link between chronic kidney disease (CKD) and cognitive impairment, Whether he longitudinal course of cognitive impairment differs among people with or without CKD is unknown. Data collected in 3034 elderly individuals who participated in the Health, Aging, and Body Composition study were analyzed. Cognitive function was assessed with the Modified Mini-Mental State Exam (3MS) at baseline and then 2 and 4 yr after baseline. Cognitive impairment was defined as a 3MS score < 80 or a decline in 3MS > 5 points after 2 or 4 yr of follow-up among participants with baseline 3MS scores >= 80. Participants with CKD, defined as an estimated GFR (eGFR) < 60 ml/min per 1.73 m(2), were further divided into two eGFR strata. Unadjusted mean baseline 3MS scores and mean declines in 3MS scores over 4 yr were significantly more pronounced for participants with lower baseline eGFR. More advanced stages of CKD were associated with an increased risk for cognitive impairment: Odds ratio (OR) 1.32 (95% confidence interval [Cl] 1.03 to 1.69) and OR 2.43 (95% Cl, 1.38 to 4.29) for eGFR 45 to 59 ml/min per 1.73 m(2) and < 45 ml/min per 1.73 m(2), respectively, adjusted for case mix, baseline 3MS scores, and other potential confounders. CKD is associated with an increased risk for cognitive impairment in the elderly that cannot be fully explained by other well-established risk factors. Studies aimed at understanding the mechanism(s) responsible for cognitive impairment in CKD and efforts to interrupt this decline are warranted. C1 Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Med, Div Neurol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Med, Div Psychiat, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Nephrol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Neurol, San Francisco, CA 94118 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Div Psychiat, San Francisco, CA 94118 USA. Vet Affairs Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. San Francisco Coordinating Ctr, San Francisco, CA USA. NIA, Intramural Res Program, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. RP Kurella, M (reprint author), Univ Calif San Francisco, Dept Med, Div Nephrol, Laurel Hts,3333 Calif St,Suite 430, San Francisco, CA 94118 USA. EM kurella@itsa.ucsf.eclu RI Kurella Tamura, Manjula/C-8284-2014 OI Kurella Tamura, Manjula/0000-0001-5227-2479 FU NIA NIH HHS [N01-AG-6-2106, AG00888, N01-AG-6-2101, N01-AG-6-2103]; NIDDK NIH HHS [R01 DK01005, R01 DK58411] NR 31 TC 191 Z9 198 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUL PY 2005 VL 16 IS 7 BP 2127 EP 2133 DI 10.1681/ASN.2005010005 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 939BK UT WOS:000230046900032 PM 15888561 ER PT J AU Spasovski, MS Simjanovska, LJ Taleski, V Petrova, N Lazetic, L Popeska, Z Gaydos, CA Quinn, TC Efremov, GD AF Spasovski, MS Simjanovska, LJ Taleski, V Petrova, N Lazetic, L Popeska, Z Gaydos, CA Quinn, TC Efremov, GD TI Screening of Chlamydia trachomatis urogenital infections among the male and female population of the Republic of Macedonia SO JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY LA English DT Article DE amplicor assay; Chlamydia trachomatis; DNA PCR analysis; screening; urine samples ID PELVIC INFLAMMATORY DISEASE; PREVALENCE; WOMEN AB Background Noninvasive urine screening for Chlamydia trachomatis infections offers a valuable public health tool, that could be of vast importance in Chlamydia control programs. Objective The goal was to determine the prevalence of C. trachomatis infections among a sexually active population, to define the epidemiological factors associated with it, and to develop potential selective screening strategies among asymptomatic individuals in the Republic of Macedonia, using a highly sensitive and specific DNA amplification method for C. trachomatis. Study design A total of 1435 urine samples, divided into two main groups: asymptomatic individuals (n = 1210) and symptomatic patients (n = 225), were tested. Samples from the asymptomatic group were collected during routine screening programs, while the symptomatic group consisted of patients with symptoms of urogenital tract infection, attending sexually transmitted diseases (STD) clinics. The presence of C trachomatis was determined using commercial AMPLICOR C. trachomatis Assay (Roche Diagnostic Systems, Inc., Branchburg, NJ, USA). Results The prevalence of C trachomatis infections among different groups was: recruits 0%, soldiers 0.4%, policemen 3.5%, clerks 4.6%, pregnant women 4%, and students 4.4%. The average prevalence for both groups (asymptomatic and symptomatic) was 2.3% [95% confidence interval (Cl): 1.5-3.1%]. The average prevalence for the asymptomatic group was 1.6% (95% CI: 0.8-2.4%), while the average prevalence for the symptomatic group was 6.2% (95% CI: 3.1-9.3%) which were significantly different (P = 0.00003). Conclusion Testing first void urine specimens by AMPLICOR C. trachomatis assay is a highly sensitive and specific method for diagnosing C. trachomatis infections in men and women. This method provides health care workers and public health officials with a new molecular amplification assay that uses noninvasive urine specimens for population-based screening purposes. The prevalence of C. trachomatis was relatively low among asymptomatic individuals. However, selective screening strategies are highly recommended for testing the student population in the Republic of Macedonia. C1 Macedonian Acad Sci & Arts, Res Ctr Genet Engn & Biotechnol, Skopje 1000, Macedonia. Hlth Ctr Skopje, Dept Dermatovenerol, Skopje 1000, Macedonia. Mil Hosp, Skopje 1000, Macedonia. Univ Svv Kiril & Metodij, Fac Med, Skopje 1000, Macedonia. Univ Sv Kiril & Metodij, Student Policlin Ctr, Skopje 1000, Macedonia. Fac Nat Sci, Skopje 1000, Macedonia. NIAID, NIH, Baltimore, MD 21205 USA. RP Efremov, GD (reprint author), Macedonian Acad Sci & Arts, Res Ctr Genet Engn & Biotechnol, Ave Krste Misirkov 2,POB 428, Skopje 1000, Macedonia. EM gde@manu.edu.mk RI Gaydos, Charlotte/E-9937-2010 NR 15 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0926-9959 J9 J EUR ACAD DERMATOL JI J. Eur. Acad. Dermatol. Venereol. PD JUL PY 2005 VL 19 IS 4 BP 427 EP 430 DI 10.1111/j.1468-3083.2005.01204.x PG 4 WC Dermatology SC Dermatology GA 948PY UT WOS:000230729400006 PM 15987287 ER PT J AU Banks, MA Cogdill, KW Selden, CR Cahn, MA AF Banks, MA Cogdill, KW Selden, CR Cahn, MA TI Complementary competencies: public health and health sciences librarianship SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID INFORMATION-MANAGEMENT; LIBRARY; NEEDS AB Objectives: The authors sought to identify opportunities for partnership between the communities of public health workers and health sciences librarians. Methods: The authors review competencies in public health and health sciences librarianship. They highlight previously identified public health informatics competencies and the Medical Library Association's essential areas of knowledge. Based on points of correspondence between the two domains, the authors identify specific opportunities for partnership. Results: The points of correspondence between public health and health sciences librarianship are reflected in several past projects involving both communities. These previous collaborations and the services provided by health sciences librarians at many public health organizations suggest that some health sciences librarians may be considered full members of the public health workforce. Opportunities remain for productive collaboration between public health workers and health sciences librarians. Conclusions: Drawing on historical and contemporary experience, this paper presents an initial framework for forming collaborations between health sciences librarians and members of the public health workforce. This framework may stimulate thinking about how to form additional partnerships between members of these two communities. C1 NYU, Med Ctr, Med Lib, New York, NY 10016 USA. Natl Lib Med, Bethesda, MD 20894 USA. RP Banks, MA (reprint author), NYU, Med Ctr, Med Lib, 550 1st Ave, New York, NY 10016 USA. EM banksm01@library.med.nyu.edu; cogdilk@mail.nlm.nih.gov; selden@nlm.nih.gov; cahn@nlm.nih.gov OI Cogdill, Keith/0000-0002-9863-1657 NR 41 TC 10 Z9 10 U1 1 U2 7 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD JUL PY 2005 VL 93 IS 3 BP 338 EP 347 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 948GU UT WOS:000230704900006 PM 16059423 ER PT J AU Antonellis, A Nangle, LA Lee-Lin, SQ Maduro, V Ionasescu, V Zuchner, S Vance, JM Saifi, M Lupski, JR Sumner, C Fischbeck, KH Schimmel, P Green, ED AF Antonellis, A Nangle, LA Lee-Lin, SQ Maduro, V Ionasescu, V Zuchner, S Vance, JM Saifi, M Lupski, JR Sumner, C Fischbeck, KH Schimmel, P Green, ED TI Functional analyses of glycyl-TRNA synthetase mutations reveal a putative link between protein synthesis defects and neurodegeneration SO JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM LA English DT Meeting Abstract CT Meeting of the Peripheral Nerve Society CY JUL, 2005 CL Tuscany, ITALY SP Peripheral Nerve Soc C1 NHGRI, NIH, Bethesda, MD USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA USA. Univ Iowa, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. Duke Univ, Ctr Human Genet, Inst Genom Sci & Policy, Durham, NC 27706 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NINDS, NIH, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1085-9489 J9 J PERIPHER NERV SYST JI J. Peripher. Nerv. Syst. PD JUL PY 2005 VL 10 SU 1 BP 1 EP 2 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 942YY UT WOS:000230320000004 ER PT J AU Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E AF Momosaki, S Umemura, T Scudamore, CH Kojiro, M Alter, HJ Tabor, E TI SEN virus infection in patients with hepatocellular carcinoma SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatocellular carcinoma; SEN virus; 'silent' hepatitis B virus ID LIVER-DISEASE; SURFACE-ANTIGEN; HEPATITIS; BLOOD AB Although most cases of hepatocellular carcinoma (HCC) are associated with either the hepatitis B or C viruses (HBV, HCV), about 10-20% of HCCs occur in patients with chronic hepatitis that is aetiologically undefined. The aim of the present study was to determine the prevalence of the transfusion-transmitted SEN virus (SEN-V) in patients with HCC, including those patients who do not otherwise appear to be infected with HBV or HCV. Fragments of SEN-V subtypes D and H were amplified separately by PCR from the sera of 50 patients with HCC (31 from Canada and 19 from Japan) as well as from HCC and adjacent nontumourous liver tissues from eight of the Canadian patients. SEN-V DNA was found in the serum of 10 of 31 (32%) Canadian patients and eight of 19 (42%) Japanese patients [overall, 18 of 50 (36%) HCC patients]. SEN-V DNA was detected in the serum of 10 of 23 (43%) HCC patients with antibody to HCV (anti-HCV), six of 11 (55%) with hepatitis B surface antigen (HBsAg), and two of 16 (12%) without detectable anti-HCV or HBsAg. Twenty-three HCC patients in this study had 'silent HBV,' characterized by the detection of HBV DNA in the absence of HBsAg; eight of these (35%) also had SEN-V infections. SEN-V DNA was detected in HCC patients most typically in those with coexistent HBV or HCV infection. SEN-V was found in only one of seven HCC patients without HBV (without HBsAg or HBV DNA) or HCV and thus does not appear to be an important cause of 'cryptogenic' HCC. C1 US FDA, Div Emerging & Transfus Dis, Bethesda, MD USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. NIH, Div Transfus Med, Bethesda, MD USA. Univ British Columbia, Dept Surg, Vancouver, BC V6T 1W5, Canada. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 15 TC 4 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JUL PY 2005 VL 12 IS 4 BP 435 EP 438 DI 10.1111/j.1365-2893.2005.00618.x PG 4 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 938MJ UT WOS:000230007200014 PM 15985016 ER PT J AU Kallstrom, G Warfield, KL Swenson, DL Mort, S Panchal, RG Ruthel, G Bavari, S Aman, MJ AF Kallstrom, G Warfield, KL Swenson, DL Mort, S Panchal, RG Ruthel, G Bavari, S Aman, MJ TI Analysis of Ebola virus and VLP release using an immunocapture assay SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Ebola; VLP; VP40; NP; filovirus; diagnostic; ELISA ID MATRIX PROTEIN VP40; NONHUMAN-PRIMATES; PARTICLES; MARBURG; VACCINE; NUCLEOPROTEIN; GLYCOPROTEIN; INFECTION; TRAFFICKING; ASSOCIATION AB Ebola virus (EBOV), an emerging pathogen, is the causative agent of a rapidly progressive hemorrhagic fever with high mortality rates. There are currently no approved vaccines or treatments available for Ebola hemorrhagic fever. Standard plaque assays are currently the only reliable techniques for enumerating the virus. Effective drug-discovery screening as well as target identification and validation require simple and more rapid detection methods. This report describes the development of a rapid ELISA that measures virus release with high sensitivity. This assay detects both Ebola virus and EBOV-like particles (VLPs) directly from cell-culture supernatants with the VP40 matrix protein serving as antigen. Using this assay, the contribution of the EBOV nucleocapsid (NC) proteins in VLP release was determined. These findings indicate that a combination of NC proteins together with the envelope components is optimal for VLP formation and release, a finding that is important for vaccination with Ebola VLPs. Furthermore, this assay can be used in surrogate models in non-biocontainment environment, facilitating both basic research on the mechanism of EBOV assembly and budding as well as drug-discovery research. (c) 2005 Elsevier B.V. All rights reserved. C1 USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. NCI, Dev Therapeut Program, SAIC, Ft Detrick, MD 21702 USA. RP Aman, MJ (reprint author), USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. EM Javad.Aman@amedd.army.mil NR 30 TC 25 Z9 26 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUL PY 2005 VL 127 IS 1 BP 1 EP 9 DI 10.1016/j.jviromet.2005.02.015 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 931AA UT WOS:000229457000001 PM 15893559 ER PT J AU Wu, L Kong, WP Nabel, GJ AF Wu, L Kong, WP Nabel, GJ TI Enhanced breadth of CD4 T-cell immunity by DNA prime and adenovirus boost immunization to human immunodeficiency virus Env and Gag immunogens SO JOURNAL OF VIROLOGY LA English DT Article ID REPLICATION-DEFECTIVE ADENOVIRUS; VACCINIA VIRUS; RHESUS-MONKEYS; LYMPHOCYTE RESPONSES; GENETIC IMMUNIZATION; NONHUMAN-PRIMATES; ANKARA VACCINE; RECOMBINANT; PROTECTION; CHALLENGE AB A variety of gene-based vaccination approaches have been used to enhance the immune response to viral pathogens. Among them, the ability to perform heterologous immunization by priming with DNA and boosting with replication-defective adenoviral (ADV) vectors encoding foreign antigens has proven particularly effective in eliciting enhanced cellular and humoral immunity compared to either agent alone. Because adenoviral vector immunization alone can elicit substantial cellular and humoral immune responses in a shorter period of time, we asked whether the immune response induced by the prime-boost immunization was different from adenoviral vaccines with respect to the potency and breadth of T-cell recognition. While DNA/ADV immunization stimulated the CD8 response, it was directed to the same epitopes in Gag and Env immunogens of human immunodeficiency virus as DNA or ADV alone. In contrast, the CD4 response to these immunogens diversified after DNA/ADV immunization compared to each vector alone. These findings suggest that the diversity of the CD4 immune response is increased by DNA/ADV prime-boost vaccination and that these components work synergistically to enhance T-cell epitope recognition. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. EM gnabel@nih.gov FU NIAID NIH HHS [Z01 AI005002-04] NR 51 TC 59 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8024 EP 8031 DI 10.1128/JVI.79.13.8024-8031.2005 PG 8 WC Virology SC Virology GA 936PA UT WOS:000229866700008 PM 15956548 ER PT J AU Chiu, WL Szajner, P Moss, B Chang, W AF Chiu, WL Szajner, P Moss, B Chang, W TI Effects of a temperature sensitivity mutation in the J1R protein component of a complex required for vaccinia virus assembly SO JOURNAL OF VIROLOGY LA English DT Article ID VIRAL MEMBRANE-PROTEIN; FORM IMMATURE VIRIONS; F10 KINASE; ELECTRON MICROSCOPY; ENVELOPE PROTEIN; DENSE VIROPLASM; CELL-SURFACE; A30L PROTEIN; MORPHOGENESIS; MUTANTS AB Vaccinia virus J1R protein is required for virion morphogenesis (W. L. Chin and W. Chang, J. Virol. 76:9575-9587, 2002). In this work, we further characterized the J1R protein of wild-type vaccinia virus and compared it with the protein encoded by the temperature-sensitive mutant virus Cts45. The mutant Cts45 was found to contain a Pro-to-Ser substitution at residue 132 of the J1R open reading frame, which is responsible for a loss-of-function phenotype. The half-life of the J1R-P132S mutant protein was comparable at both 31 and 39 degrees C, indicating that the P132S mutation did not affect the stability of the J1R protein. We also showed that the J1R protein interacts with itself in the virus-infected cells. The N-terminal region of the J1R protein, amino acids (aa) 1 to 77, interacted with the C-terminal region, aa 84 to 153, and the P132 mutation did not abolish this interaction, as determined by two-hybrid analysis. Furthermore, we demonstrated that J1R protein is part of a viral complex containing the A30L, G7L, and F10L proteins in virus-infected cells. In immunofluorescence analyses, wild-type J1R protein collocalized with the A30L, G7L, and F10L proteins in virus-infected cells but the loss-of-function P132 mutant did not. Furthermore, without a functional J1R protein, rapid degradation of A30L and the 15-kDa forms of the G7L and F10L proteins was observed in cells infected with Cts45 at 39 degrees C. This study thus demonstrated the importance of the J1R protein in the formation of a viral assembly complex required for morphogenesis. C1 Acad Sinica, Inst Mol Biol, Taipei 11529, Taiwan. NIAID, Viral Dis Lab, NIH, Bethesda, MD USA. RP Chang, W (reprint author), Acad Sinica, Inst Mol Biol, 128,Sec 2 Acad Rd, Taipei 11529, Taiwan. EM mbwen@ccvax.sinica.edu.tw NR 43 TC 9 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8046 EP 8056 DI 10.1128/JVI.79.13.8046-8056.2005 PG 11 WC Virology SC Virology GA 936PA UT WOS:000229866700010 PM 15956550 ER PT J AU Schmitz, JE Johnson, RP McClure, HM Manson, KH Wyand, MS Kuroda, MJ Lifton, MA Khunkhun, RS McEvers, KJ Gillis, J Piatak, M Lifson, JD Grosschupff, G Racz, P Tenner-Racz, K Rieber, EP Kuus-Reichel, K Gelman, RS Letvin, NL Montefiori, DC Ruprecht, RM Desrosiers, RC Reimann, KA AF Schmitz, JE Johnson, RP McClure, HM Manson, KH Wyand, MS Kuroda, MJ Lifton, MA Khunkhun, RS McEvers, KJ Gillis, J Piatak, M Lifson, JD Grosschupff, G Racz, P Tenner-Racz, K Rieber, EP Kuus-Reichel, K Gelman, RS Letvin, NL Montefiori, DC Ruprecht, RM Desrosiers, RC Reimann, KA TI Effect of CD8(+) lymphocyte depletion on virus containment after simian immunodeficiency virus SIVmac251 challenge of live attenuated SIVmac239 Delta 3-vaccinated rhesus macaques SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CYTOTOXIC-T-LYMPHOCYTE; HIV-1/SIV CHIMERIC VIRUS; NEUTRALIZING ANTIBODIES; IMMUNE-RESPONSES; PATHOGENIC SIVMAC239; VAGINAL CHALLENGE; MUCOSAL CHALLENGE; CELL DEPLETION; HIV VACCINES AB Although live attenuated vaccines can provide potent protection against simian immunodeficiency virus (SIV) and simian-human immunodeficiency virus challenges, the specific immune responses that confer this protection have not been determined. To test whether cellular immune responses mediated by CD8(+) lymphocytes contribute to this vaccine-induced protection, we depleted rhesus macaques vaccinated with the live attenuated virus SIVmac239 Delta 3 of CD8(+) lymphocytes and then challenged them with SIVmac251 by the intravenous route. While vaccination did not prevent infection with the pathogenic challenge virus, the postchallenge levels of virus in the plasmas of vaccinated control animals were significantly lower than those for unvaccinated animals. The depletion of CD8(+) lymphocytes at the time of challenge resulted in virus levels in the plasma that were intermediate between those of the vaccinated and unvaccinated controls, suggesting that CD8(+) cell-mediated immune responses contributed to protection. Interestingly, at the time of challenge, animals expressing the Mamu-A*01(+) major histocompatibility complex class I allele showed significantly higher frequencies of SIV-specific CD8' T-cell responses and lower neutralizing antibody titers than those in Mamu-A*01(-) animals. Consistent with these findings, the depletion of CD8' lymphocytes abrogated vaccine-induced protection, as judged by the peak postchallenge viremia, to a greater extent in Mamu-A*01(+) than in Manni-A*01(-) animals. The partial control of postchallenge viremia after CD8' lymphocyte depletion suggests that both Immoral and cellular immune responses induced by live attenuated SIV vaccines can contribute to protection against a pathogenic challenge and that the relative contribution of each of these responses to protection may be genetically determined. C1 Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Primedica Corp, Worcester, MA 01536 USA. NCI, SAIC, AIDS Vaccine Program, Retroviral Pathogenesis Lab, Frederick, MD 21702 USA. Bernhard Nocht Inst Trop Med, Hamburg, Germany. Tech Univ Dresden, Inst Immunol, D-8027 Dresden, Germany. Beckman Ctr, San Diego, CA 92121 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Schmitz, JE (reprint author), Harvard Univ, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr, Sch Med, RE-113,330 Brookline Ave, Boston, MA 02215 USA. EM jschmitz@bidmc.harvard.edu FU NCI NIH HHS [N01-CO-124000]; NCRR NIH HHS [R24 RR016001, K26 RR000168, P51 RR000168, R01 RR014180, RR00168, RR13150, RR14180, RR16001]; NIAID NIH HHS [AI060354, AI062412, AI35365, AI48394, N01AI30034, P01 AI035365, P30 AI060354, R01 AI048394, R01 AI062412, U01 AI035365] NR 55 TC 98 Z9 98 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8131 EP 8141 DI 10.1128/JVI.79.13.8131-8141.2005 PG 11 WC Virology SC Virology GA 936PA UT WOS:000229866700018 PM 15956558 ER PT J AU Hibbert, CS Rein, A AF Hibbert, CS Rein, A TI Preliminary physical mapping of RNA-RNA linkages in the genomic RNA of Moloney murine leukemia virus SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA VIRUS; IN-VITRO; NUCLEOCAPSID PROTEIN; MOLECULAR-WEIGHT; DIMER FORMATION; CIS ELEMENTS; DIMERIZATION; HIV-1; SITE; MATURATION AB Retrovirus particles contain two copies of their genomic RNA, held together in a dimer by linkages which presumably consist of a limited number of base pairs. In an effort to localize these linkages, we digested deproteinized RNA from Moloney murine leukemia virus (MLV) particles with RNase H in the presence of oligodeoxynucleotides complementary to specific sites in viral RNA. The cleaved RNAs were then characterized by nondenaturing gel electrophoresis. We found that fragments composed of nucleotides 1 to 754 were dimeric, with a linkage as thermostable as that between dimers of intact genomic RNA. In contrast, there was no stable linkage between fragments consisting of nucleotides 755 to 8332. Thus, the most stable linkage between monomers is on the 5' side of nucleotide 754. This conclusion is in agreement with earlier electron microscopic analyses of partially denatured viral RNAs and with our study (C. S. Hibbert, J. Mirro, and A. Rein, J. Virol. 78:10927-10938, 2004) of encapsidated nonviral mRNAs containing inserts of viral sequence. We obtained similar results with RNAs from immature MLV particles, in which the dimeric linkage is different from that in mature particles and has not previously been localized. The 5' and 3' fragments of cleaved RNA are all held together by thermolabile linkages, indicating the presence of tethering interactions between bases 5' and bases 3' of the cleavage site. When RNAs from mature particles were cleaved at nucleotide 1201, we detected tethering interactions spanning the cleavage site which are intramonomeric and are as strong as the most stable linkage between the monomers. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Rein, A (reprint author), NCI, HIV Drug Resistance Program, POB B, Frederick, MD 21702 USA. EM rein@ncifcrf.gov NR 32 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8142 EP 8148 DI 10.1128/JVI.79.13.8142-8148.2005 PG 7 WC Virology SC Virology GA 936PA UT WOS:000229866700019 PM 15956559 ER PT J AU Troyer, JL Pecon-Slattery, J Roelke, ME Johnson, W VandeWoude, S Vazquez-Salat, N Brown, M Frank, L Woodroffe, R Winterbach, C Winterbach, H Hemson, G Bush, M Alexander, KA Revilla, E O'Brien, SJ AF Troyer, JL Pecon-Slattery, J Roelke, ME Johnson, W VandeWoude, S Vazquez-Salat, N Brown, M Frank, L Woodroffe, R Winterbach, C Winterbach, H Hemson, G Bush, M Alexander, KA Revilla, E O'Brien, SJ TI Seroprevalence and genomic divergence of circulating strains of Feline immunodeficiency virus among Felidae and Hyaenidae species SO JOURNAL OF VIROLOGY LA English DT Article ID LIONS PANTHERA-LEO; FREE-RANGING LIONS; DOMESTIC CAT; PHYLOGENETIC ASPECTS; GENETIC DIVERSITY; MANDRILLUS-SPHINX; SEQUENCE-ANALYSIS; VIRAL-INFECTIONS; AFRICAN LIONS; LENTIVIRUS AB Feline immunodeficiency virus (FIV) infects numerous wild and domestic feline species and is closely related to human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV). Species-specific strains of FIV have been described for domestic cat (Felis catus), puma (Puma concolor), lion (Panthera leo), leopard (Panthera pardus), and Pallas' cat (Otocolobus manul). Here, we employ a three-antigen Western blot screening (domestic cat, puma, and lion FIV antigens) and PCR analysis to survey worldwide prevalence, distribution, and genomic differentiation of FIV based on 3,055 specimens from 35 Felidae and 3 Hyaenidae species. Although FIV infects a wide variety of host species, it is confirmed to be endemic in free-ranging populations of nine Felidae and one Hyaenidae species. These include the large African carnivores (lion, leopard, cheetah, and spotted hyena), where FIV is widely distributed in multiple populations; most of the South American felids (puma, jaguar, ocelot, margay, Geoffroy's cat, and tigrina), which maintain a lower FIV-positive level throughout their range; and two Asian species, the Pallas' cat, which has a species-specific strain of FIV, and the leopard cat, which has a domestic cat FIV strain in one population. Phylogenetic analysis of FIV proviral sequence demonstrates that most species for which FIV is endemic harbor monophyletic, genetically distinct species-specific FIV strains, suggesting that FIV transfer between cat species has occurred in the past but is quite infrequent today. C1 Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. SAIC, ISRP Program, Ft Detrick, MD 21702 USA. Univ Calif Berkeley, Museum Vertebrate Zool, Laikipia Predator Project, Berkeley, CA 94720 USA. Univ Calif Davis, Dept Wildlife Fish & Conservat Biol, Davis, CA 95616 USA. Tau Consultants Pty Ltd, Maun, Botswana. Univ Oxford, Dept Zool, Wildlife Conservat Res Unit, Oxford OX1 2JD, England. Smithsonian Inst, Natl Zool Pk, Conservat & Res Ctr, Front Royal, VA 22630 USA. Ctr Conservat African Resources Anim Communities, Kasane, Botswana. CSIC, Dept Appl Biol, Estac Biol Donana, E-41080 Seville, Spain. RP O'Brien, SJ (reprint author), Natl Canc Inst, Lab Genom Divers, Ft Detrick, MD 21702 USA. EM obrien@ncifcrf.gov RI Revilla, Eloy/B-5100-2008; Alexander, Kathleen/A-9765-2010; Troyer, Jennifer/B-8415-2012; Johnson, Warren/D-4149-2016; CSIC, EBD Donana/C-4157-2011 OI Revilla, Eloy/0000-0001-5534-5581; Alexander, Kathleen/0000-0001-7338-5341; Johnson, Warren/0000-0002-5954-186X; CSIC, EBD Donana/0000-0003-4318-6602 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 38 TC 86 Z9 88 U1 3 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8282 EP 8294 DI 10.1128/JVI.79.13.8282-8294.2005 PG 13 WC Virology SC Virology GA 936PA UT WOS:000229866700034 PM 15956574 ER PT J AU Rosati, M von Gegerfelt, A Roth, P Alicea, C Valentin, A Robert-Guroff, M Venzon, D Montefiori, DC Markham, P Felber, BK Pavlakis, GN AF Rosati, M von Gegerfelt, A Roth, P Alicea, C Valentin, A Robert-Guroff, M Venzon, D Montefiori, DC Markham, P Felber, BK Pavlakis, GN TI DNA vaccines expressing different forms of simian immunodeficiency virus antigens decrease viremia upon SIVmac251 challenge SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTE; CELLULAR IMMUNE-RESPONSES; RHESUS-MONKEYS; IN-VIVO; IFN-GAMMA; NONHUMAN-PRIMATES; VIRAL REPLICATION; SIV CHALLENGE; GENETIC IMMUNIZATION; PROTEIN EXPRESSION AB We have tested the efficacy of DNA immunization as a single vaccination modality for rhesus macaques followed by highly pathogenic SIVmac251 challenge. To further improve immunogenicity of the native proteins, we generated expression vectors producing fusion of the proteins Gag and Env to the secreted chemokine MCP3, targeting the viral proteins to the secretory pathway and to a beta-catenin (CATE) peptide, targeting the viral proteins to the intracellular degradation pathway. Macaques immunized with vectors expressing the MCP3-tagged fusion proteins developed stronger antibody responses. Following mucosal challenge with pathogenic SIVmac251, the vaccinated animals showed a statistically significant decrease in viral load (P = 0.010). Interestingly, macaques immunized with a combination of vectors expressing three forms of antigens (native protein and MCP3 and CATE fusion proteins) showed the strongest decrease in viral load (P = 0.0059). Postchallenge enzyme-linked immunospot values for Gag and Env as well as gag-specific T-helper responses correlated with control of viremia. Our data show that the combinations of DNA vaccines producing native and modified forms of antigens elicit more balanced immune responses able to significantly reduce viremia for a long period (8 months) following pathogenic challenge with SIVmac251. C1 NCI Frederick, Vaccine Branch, Human Retrovirus Sect, Frederick, MD 21702 USA. NCI Frederick, Vaccine Branch, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Biostat & Data Management Sect, Bethesda, MD USA. Duke Univ, Ctr Med, Durham, NC USA. Adv BioSci Labs Inc, Kensington, MD USA. RP Pavlakis, GN (reprint author), NCI Frederick, Vaccine Branch, Human Retrovirus Sect, Bldg 535,Rm 210, Frederick, MD 21702 USA. EM pavlakis@ncifcrf.gov RI Venzon, David/B-3078-2008 NR 75 TC 70 Z9 71 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 13 BP 8480 EP 8492 DI 10.1128/JVI.79.13.8480-8492.2005 PG 13 WC Virology SC Virology GA 936PA UT WOS:000229866700051 PM 15956591 ER PT J AU Barouch, DH Yang, ZY Kong, WP Korioth-Schmitz, B Sumida, SM Truitt, DM Kishko, MG Arthur, JC Miura, A Mascola, JR Letvin, NL Nabel, GJ AF Barouch, DH Yang, ZY Kong, WP Korioth-Schmitz, B Sumida, SM Truitt, DM Kishko, MG Arthur, JC Miura, A Mascola, JR Letvin, NL Nabel, GJ TI A human T-cell leukemia virus type 1 regulatory element enhances the immunogenicity of human immunodeficiency virus type 1 DNA vaccines in mice and nonhuman primates SO JOURNAL OF VIROLOGY LA English DT Article ID GENETIC IMMUNIZATION; IMMUNE-RESPONSES; IN-VIVO; RHESUS MACAQUES; PATHOGENIC SIV; R REGION; GM-CSF; INFECTION; EXPRESSION; ANTIGEN AB Plasmid DNA vaccines elicit potent and protective immune responses in numerous small-animal models of infectious diseases. However, their immunogenicity in primates appears less potent. Here we investigate a novel approach that optimizes regulatory elements in the plasmid backbone to improve the immunogenicity of DNA vaccines. Among various regions analyzed, we found that the addition of a regulatory sequence from the R region of the long terminal repeat from human T-cell leukemia virus type 1 (HTLV-1) to the cytomegalovirus (CMV) enhancer/promoter increased transgene expression 5- to 10-fold and improved cellular immune responses to human immunodeficiency virus type 1 (HIV-1) antigens. In cynomolgus monkeys, DNA vaccines containing the CMV enhancer/promoter with the HTLV-1 R region (CMV/R) induced markedly higher cellular immune responses to HIV-1 Env from clades A, B, and C and to HIV-1 Gag-Pol-Nef compared with the parental DNA vaccines. These data demonstrate that optimization of specific regulatory elements can substantially improve the immunogenicity of DNA vaccines encoding multiple antigens in small animals and in nonhuman primates. This strategy could therefore be explored as a potential method to enhance DNA vaccine immunogenicity in humans. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Room 4502,Bldg 40,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov RI Korioth-Schmitz, Birgit/M-7816-2015; OI Korioth-Schmitz, Birgit/0000-0002-5271-9223; Arthur, Janelle/0000-0002-4796-0207 FU NIAID NIH HHS [R01 AI058727, AI-58727] NR 40 TC 82 Z9 88 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 8828 EP 8834 DI 10.1128/JVI.79.14.8828-8834.2005 PG 7 WC Virology SC Virology GA 941LM UT WOS:000230216300016 PM 15994776 ER PT J AU Smed-Sorensen, A Lore, K Vasudevan, J Louder, MK Andersson, J Mascola, JR Spetz, AL Koup, RA AF Smed-Sorensen, A Lore, K Vasudevan, J Louder, MK Andersson, J Mascola, JR Spetz, AL Koup, RA TI Differential susceptibility to human immunodeficiency virus type 1 infection of myeloid and plasmacytoid dendritic cells SO JOURNAL OF VIROLOGY LA English DT Article ID VITRO HIV-1 INFECTION; IN-VITRO; LANGERHANS CELLS; T-CELLS; PHYSIOLOGICAL STIMULI; MIGRATORY CAPACITY; IFN-ALPHA; DC-SIGN; CD4(+); INDIVIDUALS AB Human immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) plays an important role in HIV-1 transmission and pathogenesis. Here, we studied the susceptibility of ex vivo-isolated CD11c(+) myeloid DCs (MDCs) and CD123(+) plasmacytoid DCs (PDCs) to HIV-1 infection and the function of these cells early after infection. Both DC subsets were susceptible to CCR5- and CXCR4-using HIV-1 isolates (BaL and IIIB, respectively). However, MDCs were more susceptible to HIV-1(BaL) infection than donor-matched PDCs. In addition, HIV-1(BaL) infected MDCs more efficiently than HIV-1(IIIB), whereas PDCs were equally susceptible to both isolates. While exposure to HIV-1 alone resulted in only weak maturation of DCs, Toll-like receptor 7/8 ligation induced full maturation in both infected and uninfected DCs. Maturation did not increase HIV-1 replication in infected DO, and infected DCs retained their ability to produce tumor necrosis factor alpha after stimulation. Both HIV-1 isolates induced alpha interferon production exclusively in PDCs, irrespective of productive infection. In conclusion, PDCs and MDCs were susceptible to HIV-1 infection, but neither displayed functional defects as a consequence of infection. The difference in susceptibility of PDCs and MDCs to HIV-1 may have implications for HIV-1 transmission and DC-mediated transfer of HIV-1 to T cells. C1 Karolinska Inst, Ctr Infect Med, Dept Med, S-14186 Stockholm, Sweden. NIAID, Vaccine Res Ctr, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, BSL 3 Virol Lab, NIH, Bethesda, MD 20892 USA. RP Smed-Sorensen, A (reprint author), Huddinge Univ Hosp, Karolinska Inst, Ctr Infect Med, Dept Med, F59, S-14186 Stockholm, Sweden. EM Anna.Smed.Sorensen@medhs.ki.se RI Spetz, Anna-Lena/C-3543-2016 OI Spetz, Anna-Lena/0000-0003-3964-9512 FU Intramural NIH HHS NR 43 TC 139 Z9 141 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 8861 EP 8869 DI 10.1128/JVI.79.14.8861-8869.2005 PG 9 WC Virology SC Virology GA 941LM UT WOS:000230216300019 PM 15994779 ER PT J AU Reimann, KA Parker, RA Seaman, MS Beaudry, K Beddall, M Peterson, L Williams, KC Veazey, RS Montefiori, DC Mascola, JR Nabel, GJ Letvin, NL AF Reimann, KA Parker, RA Seaman, MS Beaudry, K Beddall, M Peterson, L Williams, KC Veazey, RS Montefiori, DC Mascola, JR Nabel, GJ Letvin, NL TI Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS MACAQUES; MACACA-MULATTA; AIDS VACCINE; CHINESE; FASCICULARIS; MONKEYS; ORIGIN; HIV; PATHOGENESIS; RETROVIRUS AB Because most studies of AIDS pathogenesis in nonhuman primates have been performed in Indian-origin rhesus macaques (Macaca mulatta), little is known about lentiviral pathogenicity and control of virus replication following infection of alternative macaque species. Here, we report the consequences of simian-human immunodeficiency virus SHIV-89.6P and SIVmac251 infection in cynomolgus (Macacafascicularis) and rhesus macaques of Chinese origin. Compared to the pathogenicity of the same viruses in Indian rhesus macaques, both cynomolgus and Chinese rhesus macaques showed lower levels of plasma virus. By 9 to 10 months after infection, both viruses became undetectable in plasma more frequently in cynomolgus than in either Chinese or Indian rhesus macaques. Furthermore, after SHIV-89.6P infection, CD4(+) T-cell numbers declined less and survival was longer in cynomolgus and Chinese rhesus macaques than in Indian rhesus macaques. This attenuated pathogenicity was associated with gamma interferon ELISPOT responses to Gag and Env that were generated earlier and of higher frequency in cynomolgus than in Indian rhesus macaques. Cynomolgus macaques also developed higher titer neutralizing antibodies against SHIV-89.6 at 10 and 20 weeks postinoculation than Indian rhesus macaques. These studies demonstrate that the pathogenicity of nonhuman primate lentiviruses varies markedly based on the species or geographic origin of the macaques infected and suggest that the cellular immune responses may contribute to the control of pathogenicity in cynomolgus macaques. While cynomolgus and Chinese rhesus macaques provide alternative animal models of lentiviral infection, the lower levels of viremia in cynomolgus macaques limit the usefulness of infection of this species for vaccine trials that utilize viral load as an experimental endpoint. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02215 USA. Tulane Natl Primate Res Ctr, Covington, LA 70433 USA. Duke Univ, Ctr Med, Durham, NC 27710 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Reimann, KA (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, 330 Brookline Ave, Boston, MA 02215 USA. EM kreimann@bidmc.harvard.edu FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR000168]; NHLBI NIH HHS [HL059747, R01 HL059747]; NIAID NIH HHS [AI060354, P30 AI060354]; NINDS NIH HHS [NS037654, NS040237, R01 NS037654, R01 NS040237]; PHS HHS [23XS046A] NR 20 TC 90 Z9 94 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 8878 EP 8885 DI 10.1128/JVI.79.14.8878-8885.2005 PG 8 WC Virology SC Virology GA 941LM UT WOS:000230216300021 PM 15994781 ER PT J AU McPhillips, MG Ozato, K McBride, AA AF McPhillips, MG Ozato, K McBride, AA TI Interaction of bovine papillomavirus E2 protein with Brd4 stabilizes its association with chromatin SO JOURNAL OF VIROLOGY LA English DT Article ID LATENT NUCLEAR ANTIGEN; FUNCTIONAL INTERACTION; MITOTIC CHROMOSOMES; BROMODOMAIN PROTEIN; TRANSCRIPTIONAL REGULATORS; TRANSACTIVATION DOMAIN; EPISOMAL MAINTENANCE; HISTONE ACETYLATION; DNA-REPLICATION; GENE-EXPRESSION AB The bovine papillomavirus E2 protein maintains and segregates the viral extrachromosomal genomes by tethering them to cellular mitotic chromosomes. E2 interacts with a cellular bromodomain protein, Brd4, to mediate the segregation of viral genomes into daughter cells. Brd4 binds acetylated histones and has been observed to diffusely coat mitotic chromosomes in several cell types. In this study, we show that in mitotic C127 cells, Brd4 diffusely coated the condensed chromosomes. However, in the presence of the E2 protein, E2 and Brd4 colocalized in punctate dots that were randomly distributed over the chromosomes. A similar pattern of E2 and Brd4 colocalization on mitotic chromosomes was observed in CV-1 cells, whereas only a faint chromosomal coating of Brd4 was detected in the absence of the E2 protein. Therefore, the viral E2 protein relocalizes and/or stabilizes the association of Brd4 with chromosomes in mitotic cells. The colocalization of E2 and Brd4 was also observed in interphase cells, indicating that this protein-protein interaction persists throughout the cell cycle. The interaction of E2 with Brd4 greatly stabilized the association of Brd4 with interphase chromatin. In both mitotic and interphase cells, this stabilization required a transcriptionally competent transactivation domain, but not the DNA binding function of the E2 protein. Thus, the E2 protein modulates the chromatin association of Brd4 during both interphase and mitosis. This study demonstrates that the segregation of papillomavirus genomes is not simply due to the passive hitchhiking of the E2/genome complex with a convenient cellular chromosomal protein. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 137,4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI McBride, Alison/0000-0001-5607-5157 NR 57 TC 69 Z9 71 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 8920 EP 8932 DI 10.1128/JVI.79.14.8920-8932.2005 PG 13 WC Virology SC Virology GA 941LM UT WOS:000230216300026 PM 15994786 ER PT J AU Joos, B Trkola, A Fischer, M Kuster, H Rusert, P Leemann, C Boni, R Oxenius, A Price, DA Phillips, RE Wong, JK Hirschel, B Weber, R Gunthard, HF AF Joos, B Trkola, A Fischer, M Kuster, H Rusert, P Leemann, C Boni, R Oxenius, A Price, DA Phillips, RE Wong, JK Hirschel, B Weber, R Gunthard, HF TI Low human immunodeficiency virus envelope diversity correlates with low in vitro replication capacity and predicts spontaneous control of plasma viremia after treatment interruptions SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL RESPONSES; STRUCTURED TREATMENT INTERRUPTIONS; POTENT ANTIRETROVIRAL THERAPY; CHEMOKINE GENE VARIANT; EARLY HIV-1 INFECTION; DISEASE PROGRESSION; TYPE-1 INFECTION; VIRAL LOAD; INTERNATIONAL METAANALYSIS; COMPREHENSIVE ANALYSIS AB Genetic diversity of viral isolates in human immunodeficiency virus (HIV)-infected individuals varies substantially. However, it remains unclear whether HIV-related disease progresses more rapidly in patients harboring virus swarms with low or high diversity and, in the same context, whether high or low diversity is required to induce potent humoral and cellular immune responses. To explore whether viral diversity predicts virologic control, we studied HIV-infected patients who received antiretroviral therapy (ART) for years before undergoing structured treatment interruptions (STI). Viral diversity before initiation of ART and the ability of the patients to contain viremia after STI and final cessation of treatment was evaluated. Seven out of 21 patients contained plasma viremia at low levels after the final treatment cessation. Clonal sequences encompassing the envelope C2V3C3 domain derived from plasma prior to treatment, exhibited significantly lower diversity in these patients compared to those derived from patients with poor control of viremia. Viral diversity pre-ART correlated with the viral replication capacity of rebounding virus isolates during STI. Neutralizing antibody activity against autologous virus was significantly higher in patients who controlled viremia and was associated with lower pretreatment diversity. No such association was found with binding antibodies directed to gp120. In summary, lower pretreatment viral diversity was associated with spontaneous control of viremia, reduced viral replication capacity and higher neutralizing antibody titers, suggesting a link between viral diversity, replication capacity, and neutralizing antibody activity. C1 Univ Zurich Hosp, Dept Med, Div Infect Dis, CH-8091 Zurich, Switzerland. Hosp Epidemiol, Zurich, Switzerland. NZR Natl Ctr Retroviruses, Zurich, Switzerland. ETH, Swiss Fed Inst Technol, Inst Microbiol, Zurich, Switzerland. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Oxford, Nuffield Dept Med, Oxford, England. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Hosp Geneva, Div Infect Dis, Geneva, Switzerland. RP Gunthard, HF (reprint author), Univ Zurich Hosp, Dept Med, Div Infect Dis, Ramistr 100, CH-8091 Zurich, Switzerland. EM huldrych.guenthard@usz.ch RI Joos, Beda/D-5547-2009; gunthard, huldrych/F-1724-2011; Kuster, Herbert/A-3912-2013; Infektiologie, USZ/A-6921-2011; Price, David/C-7876-2013; SHCS, all/G-4072-2011; SHCS, ch/G-4077-2011; SHCS, only/G-4080-2011; Weber, Rainer/D-5175-2012; Oxenius, Annette/G-7794-2015; Trkola, Alexandra/K-2115-2012 OI Joos, Beda/0000-0002-3082-8875; gunthard, huldrych/0000-0002-1142-6723; Price, David/0000-0001-9416-2737; Trkola, Alexandra/0000-0003-1013-876X FU Medical Research Council [G108/441]; NIAID NIH HHS [R37 AI036082, R37 AI36082] NR 100 TC 35 Z9 35 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 9026 EP 9037 DI 10.1128/JVI.79.14.9026-9037.2005 PG 12 WC Virology SC Virology GA 941LM UT WOS:000230216300036 PM 15994796 ER PT J AU Ott, DE Coren, LV Gagliardi, TD Nagashima, K AF Ott, DE Coren, LV Gagliardi, TD Nagashima, K TI Heterologous late-domain sequences have various abilities to promote budding of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID INFECTIOUS-ANEMIA VIRUS; ROUS-SARCOMA-VIRUS; LATE ASSEMBLY DOMAIN; UBIQUITIN-PROTEASOME SYSTEM; PROTEIN-SORTING PATHWAY; PARTICLE RELEASE; GAG POLYPROTEIN; MULTIVESICULAR BODY; TSG101; HIV-1 AB Retroviral late (L) domains present within Gag act in conjunction with cellular proteins to efficiently release virions from the surface of the cell. Three different critical core sequences have been identified as required elements for L-domain function: PPPY, PTAP (also PSAP), and YPDL, with different retroviruses utilizing one or two of these core sequences. The human immunodeficiency virus type 1 (HIV-1) L domain is centered around a PTAP sequence in the p6 region of Gag. To assess the ability of heterologous L-domain sequences to be functionally interchanged for those in full-length HIV-1, we produced a series of constructs that replaced PTAP-containing p6(Gag) sequences with those of PPPY- or YPDL-based L domains. While previous studies had found that L domains are interchangeable in other retroviruses, most of the sequences introduced into p6(Gag) failed to substitute for PTAP-mediated L-domain function. One exception was the 11-amino-acid p2b sequence of Rous sarcoma virus (RSV) Gag, which could fully restore HIV-1 budding, while a PPPPY sequence exchange alone did not. This suggests that the RSV L domain consists of more than simply its core L-domain sequence. The HIV-p2b chimera was as infectious as the wild type, produced normal virions, and was sensitive to proteasome inhibitors. These results show that L-domain sequences are not necessarily interchangeable. Thus, HIV-1 Gag might have a more stringent requirement for L-domain function than the other retroviruses previously studied. C1 Natl Canc Inst, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Natl Canc Inst, Res Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Ott, DE (reprint author), Natl Canc Inst, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM ott@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 62 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 9038 EP 9045 DI 10.1128/JVI.79.14.9038-9045.2005 PG 8 WC Virology SC Virology GA 941LM UT WOS:000230216300037 PM 15994797 ER PT J AU Thio, CL Mosbruger, T Astemborski, J Greer, S Kirk, GD O'Brien, SJ Thomas, DL AF Thio, CL Mosbruger, T Astemborski, J Greer, S Kirk, GD O'Brien, SJ Thomas, DL TI Mannose binding lectin genotypes influence recovery from hepatitis B virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER AIDS COHORT; VIRAL CLEARANCE; HOMOSEXUAL-MEN; GENE-MUTATIONS; DRUG-USERS; TNF-ALPHA; PROTEIN; SUSCEPTIBILITY; POLYMORPHISMS AB Mannose binding lectin (MBL) is a central component of the innate immune response and thus may be important for determining hepatitis B virus (HBV) persistence. Since single-nucleotide polymorphisms (SNPs) in the gene encoding MBL (mbl2) alter the level of functional MBL, we hypothesized that mbl2 genotypes are a determinant of HBV persistence or recovery from viral infection. We tested this hypothesis by using a nested case control design with 189 persons with HBV persistence matched to 338 individuals who had naturally recovered from HBV infection. We determined genotypes of two promoter and three exon 1 SNPs in mbl2 and grouped these genotypes according to the amount of functional MBL production. We found that the promoter SNP -221C, which leads to deficient MBL production, was more common in those subjects with viral persistence (odds ratio [OR], 1.38; 95% confidence interval [CI], 1.01 to 1.89; P = 0.04). Those subjects homozygous for the combination of promoter and exon I genotypes associated with the highest amount of functional MBL had significantly increased odds of recovery from infection (OR, 0.55; 95% CI, 0.37 to 0.84; P = 0.005). Conversely, those homozygous for the combination of promoter and exon 1 genotypes which produce the lowest amount of functional MBL were more likely to have viral persistence (OR, 1.76; 95% CI, 1.02 to 3.01; P = 0.04). These data are consistent with the hypothesis that functional MBL plays a central role in the pathogenesis of acute hepatitis B. C1 Johns Hopkins Univ, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Thio, CL (reprint author), 1503 E Jefferson St, Baltimore, MD 21231 USA. EM cthio@jhmi.edu RI Kirk, Gregory/A-8484-2009 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NCRR NIH HHS [5-M01-RR-00722, M01 RR000722]; NIAID NIH HHS [U01 AI035042, U01 AI035039, U01 AI035040, U01 AI035041, U01 AI035043, U01 AI037613, U01 AI037984, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35042, UO1-AI-35043, UO1-AI-37613, UO1-AI-37984]; NIDA NIH HHS [DA00441, DA04334, DA12568, K08 DA000441, R01 DA004334, R01 DA012568, R37 DA004334, R56 DA004334, R56 DA012568]; NIDDK NIH HHS [DK56415, R01 DK056415] NR 34 TC 59 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 9192 EP 9196 DI 10.1128/JVI.79.14.9192-9196.2005 PG 5 WC Virology SC Virology GA 941LM UT WOS:000230216300053 PM 15994813 ER PT J AU Farrell, KB Eiden, MV AF Farrell, KB Eiden, MV TI Dissection of gammaretroviral receptor function by using type III phosphate transporters as models SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ENVELOPE GLYCOPROTEINS; SURFACE GLYCOPROTEIN; EXTRACELLULAR DOMAIN; BINDING DOMAIN; PIT2 RECEPTOR; FUSION; ENTRY; INFECTION; IDENTIFICATION AB Gammaretroviruses that enter cells via binding to a surface receptor use one of two fundamental mechanisms. In the first, binding of the virus particle to its cognate receptor is followed by fusion and internalization. The second, less common mechanism requires the addition of an accessory protein in order to achieve fusion and entry into the target cells; this protein is usually the soluble form of the envelope protein containing the receptor-binding domain (RBD). For some viruses, such as amphotropic marine leukemia virus (A-MLV), particles with fusion-defective envelope proteins can enter cells in the presence of their own RBD or that of another viral envelope, regardless of its cognate receptor, suggesting that these viruses share a common entry mechanism. A notable exception is gibbon ape leukemia virus (GALV). Fusion-impaired GALV envelope mutants can be trans-activated for infectivity only by GALV RBDs. Using dually functional GALV/A-MLV receptors, we examined the role of receptor with respect to which RBD could overcome fusion impaired virus entry. C1 NIMH, Cellular & Mol Biol Lab, Sect Mol Virol, NIH, Bethesda, MD 20892 USA. RP Eiden, MV (reprint author), NIMH, Cellular & Mol Biol Lab, Sect Mol Virol, NIH, Bldg 49,Room 5A32,49 Convent Dr,MSC 4483, Bethesda, MD 20892 USA. EM eidenm@mail.nih.gov NR 22 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 9332 EP 9336 DI 10.1128/JVI.79.14.9332-9336.2005 PG 5 WC Virology SC Virology GA 941LM UT WOS:000230216300069 PM 15994829 ER PT J AU Chen, JB Rhodes, TD Hu, WS AF Chen, JB Rhodes, TD Hu, WS TI Comparison of the genetic recombination rates of human immunodeficiency virus type 1 in macrophages and T cells SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; IN-VIVO; VIRAL REPLICATION; TARGET-CELLS; RNA; CONSEQUENCES; DETERMINES; EXPRESSION; INFECTION; FREQUENCY AB Human immunodeficiency virus type 1 (HIV-1) exhibits a high level of genetic variation generated by frequent mutation and genetic recombination during reverse transcription. We have measured HIV-1 recombination rates in T cells in one round of virus replication. It was recently proposed that HIV-1 recombines far more frequently in macrophages than in T cells. In an attempt to delineate the mechanisms that elevate recombination, we measured HIV-1 recombination rates in macrophages at three different marker distances. Surprisingly, the recombination rates were comparable in macrophages and in T cells. In addition, we observed similar recombination rates in two monocytic cell lines regardless of the differentiation status. These results indicate that HIV-1 undergoes similar numbers of recombination events when infecting macrophages and T cells. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Rm 336, Ft Detrick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 NR 27 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 9337 EP 9340 DI 10.1128/JVI.79.14.9337-9340.2005 PG 4 WC Virology SC Virology GA 941LM UT WOS:000230216300070 PM 15994830 ER PT J AU Miyazato, A Sheleg, S Iha, H Li, Y Jeang, KT AF Miyazato, A Sheleg, S Iha, H Li, Y Jeang, KT TI Evidence for NF-kappa B- and CBP-independent repression of p53's transcriptional activity by human T-Cell leukemia virus type 1 tax in mouse embryo and primary human fibroblasts SO JOURNAL OF VIROLOGY LA English DT Article ID ELEMENT-BINDING PROTEIN; I TAX; TRANSACTIVATION FUNCTION; TRANSFORMING PROTEIN; KINASE COMPLEX; HTLV-I; ACTIVATION; GENE; GAMMA; LYMPHOCYTES AB The human T-cell leukemia virus type 1 (HTLV-1) Tax oncoprotein can repress the transcriptional activity of the tumor suppressor protein p53. However, it remains controversial whether Tax requires NF-kappa B factors/activity and/or p300/CBP` in order to inactivate p53 function. To address this issue, we have investigated Tax's effect on p53's transcriptional activation in I kappa B-kinase-deficient mouse embryonic fibroblasts (MEFs); some of which are entirely silent for Tax-induced NF-kappa B activity. We found that, in IKK alpha(-/-), IKK beta(-/-), and IKK gamma(-/-) MEFs, p53 activation of a prototypic responsive plasmid (pG13-luciferase) was repressed by wild-type Tax. Curiously, p53's activity in MEFs was also repressed by a p300/CBP-binding deficient Tax protein. Our results highlight the complex nature of Tax-mediated repression of p53-activity, which requires further investigation. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 34 TC 27 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2005 VL 79 IS 14 BP 9346 EP 9350 DI 10.1128/JVI.79.14.9346-9350.2005 PG 5 WC Virology SC Virology GA 941LM UT WOS:000230216300072 PM 15994832 ER PT J AU Biggar, RJ AF Biggar, RJ TI Vaginal cleansing and the gold standard SO JOURNAL OF WOMENS HEALTH LA English DT Editorial Material ID GROUP-B STREPTOCOCCI; CLINICAL-TRIAL; CHLORHEXIDINE DISINFECTION; PERIPARTAL INFECTION; TRANSMISSION; IRRIGATION; PREVENTION; MORBIDITY; LABOR C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Prevent, Bethesda, MD 20814 USA. RP Biggar, RJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Prevent, Bethesda, MD 20814 USA. EM biggarb@mail.mich.gov NR 10 TC 3 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD JUL PY 2005 VL 14 IS 6 BP 531 EP 533 DI 10.1089/jwh.2005.14.531 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 971SE UT WOS:000232404000013 PM 16115008 ER PT J AU Jayachandran, M Karnicki, K Miller, RS Owen, WG Korach, KS Miller, VM AF Jayachandran, M Karnicki, K Miller, RS Owen, WG Korach, KS Miller, VM TI Platelet characteristics change with aging: role of estrogen receptor beta SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HORMONE REPLACEMENT THERAPY; VENOUS THROMBOEMBOLISM; EXPRESSION; AGGREGATION; POPULATION; DISORDERS; GENE; 17-BETA-ESTRADIOL; MEGAKARYOCYTES; ASSOCIATION AB Estrogen receptor beta (PER) is the predominant estrogen receptor in platelets. Experiments were designed to define phenotypic changes in platelets with aging following deletion of beta ER (beta ERKO). Blood was collected from wild-type and beta ERKO female mice at 4-7 (young) and 24-25 (aged) months of age. In young animals, total number of platelets, number of platelets containing RNA (reticulated platelets), aggregation, dense body adenosine triphosphate secretion, and alpha granular secretion were the same in both groups. With aging, total number of platelets decreased but reticulated platelets increased in beta ERKO mice; aggregation and dense granule adenosine triphosphate secretion decreased whereas basal expression of fibrinogen receptors increased with age in wild-type and beta ERKO mice. Basal expression of P-selectin and annexin V binding increased with aging only in beta ERKO mice; thrombin did not increase expression in these mice. Therefore, deletion of beta ER is associated with specific platelet functions, which are expressed only with age-associated reproductive senescence. C1 Mayo Clin, Coll Med, Dept Surg, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Physiol & Biophys, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Hematol Res Sect, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Miller, VM (reprint author), Mayo Clin, Coll Med, Dept Surg, 200 1st St SW, Rochester, MN 55905 USA. EM miller.virginia@mayo.edu OI Korach, Kenneth/0000-0002-7765-418X FU NHLBI NIH HHS [HL51736] NR 32 TC 24 Z9 25 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 815 EP 819 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900001 PM 16079202 ER PT J AU Metter, EJ Schrager, M Ferrucci, L Talbot, LA AF Metter, EJ Schrager, M Ferrucci, L Talbot, LA TI Evaluation of movement speed and reaction time as predictors of all-cause mortality in men SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID AGE-RELATED DECLINE; MUSCLE STRENGTH; PARKINSONS-DISEASE; HEALTHY-MEN; SARCOPENIA; POWER; PERFORMANCE; WOMEN; MOBILITY; OLD AB Muscle power is associated with mortality independent of strength, suggesting that movement speed and coordination convey health-related information. We hypothesized that movement speed is a marker of longevity. Our participants included 1196 men who performed a tapping and/or auditory simple (respond to a sound) and disjunctive (respond to a higher pitched sound) reaction-time tasks while participating in the Baltimore Longitudinal Study of Aging. Mortality was assessed over 40 years. Tapping time was associated with mortality (relative risk [RR] = 1.34 per minute, 95% confidence interval [CI], 1.05-1.70) adjusted for age, and persisted with adjustments for arm strength and power. Simple (RR = 1.17 per 100 ms, 95% CI, 1.03-1.32) and disjunctive (RR = 1.14 per 100 ms, 95% CI, 1.03-1.27) reaction times but not their difference (RR = 1.04 per 100 ms, 95% CI, 0.92-1.19) were associated with mortality after adjustments for age, neurological/psychiatric and neck/arm pain histories. Age-associated impairments in motor control systems but not the decision to move affects longevity. C1 Harbor Hosp, NIA, Clin Res Branch, Baltimore, MD 21225 USA. Uniformed Serv Univ Hlth Sci, Grad Sch Nursing, Bethesda, MD 20814 USA. RP Metter, EJ (reprint author), NIA, 3001 S Hanover St, Baltimore, MD 21225 USA. EM MetterJ@grc.nia.nih.gov NR 39 TC 20 Z9 21 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 840 EP 846 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900004 PM 16079205 ER PT J AU Hicks, GE Simonsick, EM Harris, TB Newman, AB Weiner, DK Nevitt, MA Tylavsky, FA AF Hicks, GE Simonsick, EM Harris, TB Newman, AB Weiner, DK Nevitt, MA Tylavsky, FA TI Cross-sectional associations between trunk muscle composition, back pain, and physical function in the health, aging and body composition study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Gerontological-Society-of-America CY NOV 21-25, 2003 CL San Diego, CA SP Gerontol Soc Amer ID LOWER-EXTREMITY PERFORMANCE; SKELETAL-MUSCLE; LUMBAR SPINE; WOMEN; STRENGTH; MASS; MEN; FAT; COORDINATION; ATTENUATION AB Background. Associations between trunk muscle composition and physical function have not been examined previously in older adults. We hypothesized that lower trunk muscle area and attenuation (higher fat infiltration) are associated with decreased functional capacity. Methods. The study sample consisted of a biracial cohort of well functioning men (739) and women (788) aged 70-79 from the Pittsburgh site of the Health, Aging and Body Composition (Health ABC) study. Computed tomography was used to measure trunk muscle area (cm(2)) and muscle attenuation (Hounsfield Unit [HU]) of the following muscle groups: lumbar paraspinals, lateral abdominals, and rectus abdominis. An average score was calculated for both trunk area and attenuation. The Health ABC Physical Performance Battery (PPB) and its individual components (usual and narrow walk, chair stands, and standing balance) were used to measure functional capacity. Results. Linear regression analyses adjusting for demographic factors, height, body fat, thigh muscle composition, disease status, and low back pain (LBP) found that average trunk muscle area was not associated with any element of functional capacity (p > .10), whereas average trunk muscle attenuation was positively associated with the Health ABC Physical Performance Battery (p <.05) and chair stands (p <.001). Participants reporting higher LBP severity during the past year had lower muscle attenuation (p <.001 for trend), but there was no difference in average trunk muscle area according to LBP status. Conclusions. Findings suggest a link between trunk muscle composition and history of LBP as well as reduced functional capacity in older adults. Improving trunk muscle quality may lead to reduced LBP severity and improved functional status. C1 NIA, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. RP Hicks, GE (reprint author), Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, 100 Penn St, Baltimore, MD 21201 USA. EM ghicks@som.umaryland.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 21 TC 60 Z9 60 U1 1 U2 8 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 882 EP 887 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900011 PM 16079212 ER PT J AU Boyd, CM Xue, QL Guralnik, JM Fried, LP AF Boyd, CM Xue, QL Guralnik, JM Fried, LP TI Hospitalization and development of dependence in activities of daily living in a cohort of disabled older women: The women's health and aging study I SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; FUNCTIONAL STATUS; GERIATRIC EVALUATION; DEPRESSIVE SYMPTOMS; RISK-FACTORS; DISABILITY; COMMUNITY; DECLINE; CARE; OUTCOMES AB Background. Changes in self-reported function in older adults are known to occur in the 2 weeks prior to, during, and in the first few months after hospitalization. The long-term outcome of hospitalization on functional status in disabled older adults is not known. The objective of this study was to determine whether hospitalization predicts long-term Activities of Daily Living (ADL) dependence in previously ADL independent, although disabled, older women. Methods. The Women's Health and Aging Study I is a population-based, prospective cohort study of disabled, community-dwelling women >= 65 years old. We evaluated participants who were independent in ADLs at baseline and excluded women with incident stroke, lower extremity joint surgery, amputation, or hip fracture. We examined the association between self-reported incident hospitalization at three consecutive 6-month intervals and incident dependence in at least one ADL at 18 months (n = 595). Results. Of 595 women evaluated, 32% had at least one hospitalization. Women who were hospitalized were more likely to become dependent in ADLs than were women who were not hospitalized (17% vs 8%, p =.001). In a multivariate model, hospitalization was independently predictive of development of ADL dependence that persisted at 18 months after baseline (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.7-5.8), adjusting for age, race, education, baseline walking speed, difficulty with ADLs, self-reported health status, depressive symptoms, cognitive status, and presence of congestive heart failure, diabetes, or pulmonary disease. Increasing numbers of 6-month intervals with hospitalizations were independently predictive of higher risk in an adjusted model: one (OR, 2.3; 95% CI. 1.1-4.6), two (OR, 5.8; 95% CI, 2.4-14.4), and three (OR, 12.5; 95% CL 2.7-57.6). Conclusions. These results suggest that hospitalization has an independent and dose-response effect on loss of ADL independence in disabled older women over an 18-month period. C1 Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NIA, Bethesda, MD 20892 USA. RP Boyd, CM (reprint author), Ctr Aging & Hlth, 2024 E Monument St,Suite 2-700, Baltimore, MD 21205 USA. EM cyboyd@jhmi.edu FU NIA NIH HHS [T32-AG00120, 1 RO1 AG 19905-1, N0-1AG-1-2112] NR 48 TC 55 Z9 57 U1 3 U2 7 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 888 EP 893 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900012 PM 16079213 ER PT J AU Perera, S Studenski, S Chandler, JM Guralnik, JM AF Perera, S Studenski, S Chandler, JM Guralnik, JM TI Magnitude and patterns of decline in health and function in 1 year affect subsequent 5-year survival SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE-MEASURES; LIVING OLDER PERSONS; WOMENS HEALTH; PREDICTIVE-VALIDITY; ELDERLY PERSONS; DISABILITY; MORTALITY; ADULTS; RISK AB Background. Indicators of physical function and health status can predict important outcomes in older persons, but little is known about the meaning of change in these measures. This study assessed the magnitude and patterns of change occurring in I year in six measures of health and function and estimated the effects on survival for 5 years. Methods. This prospective cohort study was based in two health care systems. Data were collected during home visits at baseline and every 3 months for I year. Subsequent deaths occurring within 5 years were ascertained using the National Death Index. Results. Of 439 older adults, 89 (20%) died within the subsequent 5 years. The optimal magnitude of decline to predict 5-year mortality was 0.1 meters/second for gait speed, I point for the Short Physical Performance Battery, and 0.05 points for Euroqol. Independent contributions were found for decline in gait speed (p =.001 to .002), Short Physical Performance Battery (p.014 to .026), global health (p < .001), and activities of daily living (p =.005 to .019). More than one half of the episodes of decline were transient. Persistent decline in I year consistently predicted death. and transient decline in gait speed and global health increased mortality risk compared with no change. Conclusions. A decline in gait speed of 0.1 m/s or I point in the Short Physical Performance Battery within I year increased the subsequent 5-year mortality rate. Transient declines in gait speed and self-reported health are as common as persistent declines and affect mortality risk. C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Pittsburgh VA Healthcare Syst, Pittsburgh, PA 15260 USA. Merck Res Labs, Blue Bell, PA USA. NIA, Bethesda, MD 20892 USA. RP Studenski, S (reprint author), 3471 5th Ave,Suite 500, Pittsburgh, PA 15213 USA. EM studenskis@msx.dept-med.pitt.edu RI Perera, Subashan/D-7603-2014 FU NIA NIH HHS [AG14635] NR 38 TC 53 Z9 56 U1 3 U2 13 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUL PY 2005 VL 60 IS 7 BP 894 EP 900 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 951TC UT WOS:000230952900013 PM 16079214 ER PT J AU Ogbureke, KUE Fisher, LW AF Ogbureke, KUE Fisher, LW TI Renal expression of SIBLING proteins and their partner matrix metalloproteinases (MMPs) SO KIDNEY INTERNATIONAL LA English DT Article DE kidney; SIBLING; MMP; osteopontin; BSP; DSPP; DMP1; MEPE ID CALCIUM-OXALATE CRYSTALS; EPITHELIAL-CELLS; MAMMARY-GLAND; OSTEOPONTIN EXPRESSION; INTERSTITIAL FIBROSIS; REGULATED EXPRESSION; BONE SIALOPROTEIN; URINARY-EXCRETION; TISSUE INHIBITOR; FETAL MEMBRANES AB Background. Three members of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins have recently been shown to bind and activate specific promatrix metalloproteinases (MMPs) and to overcome the inhibition of tissue inhibitors of MMPs (TIMPs). Although usually associated with mineralized tissues, we have shown that the SIBLINGs and their MMP partners, when known, are coexpressed in salivary gland ductal cells. The present study examined the expression patterns of both the SIBLINGs and their MMP partners in adult kidney. Methods. The expression patterns of all five SIBLINGs known to date, and their MMP partners were determined in monkey kidney using immunohistochemistry and in situ hybridization techniques. Results. Bone sialoprotein (BSP) and its partner, MMP-2, were coexpressed in both the proximal and distal tubules. Osteopontin, as previously shown, was expressed in the distal tubules while its partner MMP-3 was expressed in both the proximal tubule and distal tubles. Dentin matrix protein-1 (DMP1) and MMP-9 were coexpressed throughout the nephron, including both parietal cells of Bowman's capsule and the thin limb of the loop of Henle. Dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal tubule, and proximal tubule, respectively. Conclusion. In contrast to salivary gland in which all SIBLINGs and their MMP partners were coexpressed throughout the length of the ducts, these proteins were differentially expressed within the normal adult nephron. We hypothesize that the cells use the SIBLING/MMP pairs in the normal turnover of cell surface proteins and/or pericellular matrix proteins such as those in basement membranes. C1 Natl Inst Dent & Craniofacial Res, Matrix Biochem Sect, Cranioskeletal Dis Branch, NIH,DHHS, Bethesda, MD 20982 USA. RP Fisher, LW (reprint author), Natl Inst Dent & Craniofacial Res, Matrix Biochem Sect, Cranioskeletal Dis Branch, NIH,DHHS, 30 Convent Dr,Bldg 30,Room 223, Bethesda, MD 20982 USA. EM lfisher@dir.nidcr.nih.gov NR 55 TC 99 Z9 105 U1 0 U2 5 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUL PY 2005 VL 68 IS 1 BP 155 EP 166 DI 10.1111/j.1523-1755.2005.00389.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 933NE UT WOS:000229636800014 PM 15954904 ER PT J AU Saika, S Yamanaka, O Ikeda, K Kim-Mitsuyama, S Flanders, KC Yoo, JY Roberts, AB Nishikawa-Ishida, I Ohnishi, Y Muragaki, Y Ooshima, A AF Saika, S Yamanaka, O Ikeda, K Kim-Mitsuyama, S Flanders, KC Yoo, JY Roberts, AB Nishikawa-Ishida, I Ohnishi, Y Muragaki, Y Ooshima, A TI Inhibition of p38MAP kinase suppresses fibrotic reaction of retinal pigment epithelial cells SO LABORATORY INVESTIGATION LA English DT Article DE proliferative vitreoretinopathy; gene therapy; adenovirus; retinal pigment epithelial cell; transforming growth factor beta; p38 mitogen-activated kinase ID GROWTH-FACTOR-BETA; ACTIVATED PROTEIN-KINASE; TGF-BETA; MAP KINASE; PROLIFERATIVE VITREORETINOPATHY; GENE-EXPRESSION; MESENCHYMAL TRANSITION; CELLULAR MIGRATION; DERMAL FIBROBLASTS; STELLATE CELLS AB Proliferative vitreoretinopathy ( PVR) is one of the major causes of the failure of retinal detachment surgery. Its pathogenesis includes a fibrotic reaction by the retinal pigment epithelium and other retina-derived non-neural cells, leading to fixation of the detached retina. We examined the role of p38 mitogen-activated protein kinase ( MAPK) in transforming growth factor ( TGF)-beta 2-dependent enhancement of the fibrogenic reaction in a human retinal pigment epithelial cell line, ARPE-19, and also evaluated the therapeutic efficacy of inhibiting p38MAPK by adenoviral gene transfer of dominant-negative ( DN) p38MAPK in a mouse model of PVR. Exogenous TGF-beta 2 activates p38MAPK in ARPE-19 cells. It also suppresses cell proliferation, but this was unaffected by addition of the p38MAPK inhibitor, SB202190. SB202190 interfered with TGF-beta 2-dependent cell migration and production of collagen type I and fibronectin, but had no effect on basal levels of these activities. While SB202190 did not affect phosphorylation of the C-terminus of Smads2/3, it did suppress the transcriptional activity of Smads3/4 as indicated by a reporter gene, CAGA12-Luc. Gene transfer of DN-p38MAPK attenuated the post-retinal detachment fibrotic reaction of the retinal pigment epithelium in vivo in mice, supporting its effectiveness in preventing/treating PVR. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. Osaka City Univ, Grad Sch Med, Dept Anat, Abeno Ku, Osaka 558, Japan. Kumamoto Univ, Grad Sch Med Sci, Dept Pharmacol & Mol Therapeut, Kumamoto, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Wakayama Med Univ, Dept Pathol, Wakayama, Japan. RP Saika, S (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp NR 51 TC 45 Z9 52 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD JUL PY 2005 VL 85 IS 7 BP 838 EP 850 DI 10.1038/labinvest.3700294 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 936XD UT WOS:000229887900004 PM 15924151 ER PT J AU Morton, LM Zheng, TZ Holford, TR Holly, EA Chiu, BCH Costantini, AS Stagnaro, E Willett, EV Dal Maso, L Serraino, D Chang, ET Cozen, W Davis, S Severson, RK Bernstein, L Mayne, ST Dee, FR Cerhan, JR Hartge, P AF Morton, LM Zheng, TZ Holford, TR Holly, EA Chiu, BCH Costantini, AS Stagnaro, E Willett, EV Dal Maso, L Serraino, D Chang, ET Cozen, W Davis, S Severson, RK Bernstein, L Mayne, ST Dee, FR Cerhan, JR Hartge, P CA InterLymph Consortium TI Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis SO LANCET ONCOLOGY LA English DT Article ID CHEMOPREVENTIVE AGENT RESVERATROL; UNITED-STATES; OLDER WOMEN; CANCER; TOBACCO; MEN; POPULATION; CLASSIFICATION; EPIDEMIOLOGY; MORTALITY AB Background Previous epidemiological studies of the relation between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) have been inconsistent, probably because of small sample sizes of individual studies that result from stratification by NHL subtype and type of alcoholic beverage. We aimed to assess the role of alcohol consumption in NHL with sufficient sample size to analyse by both type of alcoholic beverage and disease subtype. Methods We obtained original data from nine case-control studies from the USA, UK, Sweden, and Italy in the International Lymphoma Epidemiology Consortium (InterLymph), yielding a pooled study population of 15175 individuals (6492 cases and 8683 controls). We derived odds ratios (OR) and 95% Cl from unconditional logistic regression models, controlling for study Centre and other confounding factors. Heterogeneity between studies was assessed by comparison of results from joint fixed-effects logistic regression and two-stage random effects logistic regression, and by calculation of Wald chi(2) statistics. Findings People who drank alcohol had a lower risk of NHL than did non-drinkers (OR 0 . 83 [95% Cl 0 . 76-0.89]). Compared with non-drinkers, risk estimates were lower for current drinkers than for former drinkers (0 . 73 [0 . 64-0.84] vs 0 . 95 [0.80-1.14]), but risk did not decrease with increasing alcohol consumption. The protective effect of alcohol did not vary by beverage type, but did change with NHL subtype. The lowest risk estimates were recorded for Burkitt's lymphoma (0 . 51 [0 . 33-0.77]). Interpretation People who drink alcoholic beverages might have a lower risk of NHL than those who do not, and this risk might vary by NHL subtype. Further study designs are needed to determine whether confounding lifestyle factors or immunomodulatory effects of alcohol explain this association. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Sci Inst Tuscany, Ctr Study & Prevent Canc, Occupat & Environm Epidemiol Unit, Florence, Italy. Natl Inst Canc Res, Environm Epidemiol & Biostat Unit, Genoa, Italy. Univ York, Dept Hlth Sci, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. Aviano Canc Ctr, Epidemiol & Biostat Unit, I-33081 Aviano, Italy. Inst Shelter & Cure Sci Character, Natl Inst Infect Dis, Dept Epidemiol, Rome, Italy. Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Univ Iowa, Carver Coll Med, Dept Pathol, Iowa City, IA USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. RP Morton, LM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-7055, Rockville, MD 20852 USA. EM mortonli@mail.nih.gov RI Kane, Eleanor/B-4349-2009; Chang, Ellen/G-5700-2010; Chang, Ellen/E-3168-2010; Morton, Lindsay/B-5234-2015; OI Morton, Lindsay/0000-0001-9767-2310; Cerhan, James/0000-0002-7482-178X; Serraino, Diego/0000-0003-0565-8920; dal maso, luigino/0000-0001-6163-200X FU NCI NIH HHS [PC 67009, CA 10349, CA 45614, CA 50850, CA 51086, CA 62006, CA 69269, CA 89745, PC 65064, PC 67008, PC 67010, PC 71105] NR 54 TC 90 Z9 97 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUL PY 2005 VL 6 IS 7 BP 469 EP 476 DI 10.1016/S1470-2045(05)70214-X PG 8 WC Oncology SC Oncology GA 943PV UT WOS:000230367100016 PM 15992695 ER PT J AU Semmes, OJ Cazares, LH Ward, MD Qi, L Moody, M Maloney, E Morris, J Trosset, MW Hisada, M Gygi, S Jacobson, S AF Semmes, OJ Cazares, LH Ward, MD Qi, L Moody, M Maloney, E Morris, J Trosset, MW Hisada, M Gygi, S Jacobson, S TI Discrete serum protein signatures discriminate between human retrovirus-associated hematologic and neurologic disease SO LEUKEMIA LA English DT Article DE myelopathy; proteomics; diagnostics ID PROSTATE-CANCER; HAPTOGLOBIN; PROTEOMICS; CARCINOMA; ALPHA-1-ANTITRYPSIN; PROFILES; LEUKEMIA; JAPAN AB The human T-cell leukemia virus type I (HTLV-I) is the causative agent for adult T-cell leukemia (ATL) and HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 5% of infected individuals will develop either disease and currently there are no diagnostic tools for early detection or accurate assessment of disease state. We have employed high- throughput expression profiling of serum proteins using mass spectrometry to identify protein expression patterns that can discern between disease states of HTLV-I- infected individuals. Our study group consisted of 42 ATL, 50 HAM/TSP, and 38 normal controls. Spectral peaks corresponding to peptide ions were generated from MS-TOF data. We applied Classification and Regression Tree analysis to build a decision algorithm, which achieved 77% correct classification rate across the three groups. A second cohort of 10 ATL, 10 HAM and 10 control samples was used to validate this result. Linear discriminate analysis was performed to verify and visualize class separation. Affinity and sizing chromatography coupled with tandem mass spectrometry was used to identify three peaks specifically overexpressed in ATL: an 11.7 kDa fragment of alpha trypsin inhibitor, and two contiguous fragments (19.9 and 11.9 kDa) of haproglobin-2. To the best of our knowledge, this is the first application of protein profiling to distinguish between two disease states resulting from a single infectious agent. C1 Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Ctr Biomed Prote, Norfolk, VA 23507 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Coll William & Mary, Dept Math, Williamsburg, VA 23185 USA. Harvard Univ, Sch Med, Prote Ctr, Boston, MA 02115 USA. NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Semmes, OJ (reprint author), Eastern Virginia Med Sch, Dept Microbiol & Mol Cell Biol, Ctr Biomed Prote, 700 W Olney Rd, Norfolk, VA 23507 USA. EM semmesoj@evms.edu NR 22 TC 24 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2005 VL 19 IS 7 BP 1229 EP 1238 DI 10.1038/sj.leu.2403781 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 937WR UT WOS:000229957400018 PM 15889159 ER PT J AU Kumar, S Raje, N Hideshima, T Ishitsuka, K Roccaro, A Shiraishi, N Hamasaki, M Yasui, H Munshi, N Richardson, P Figg, WD Anderson, KC AF Kumar, S Raje, N Hideshima, T Ishitsuka, K Roccaro, A Shiraishi, N Hamasaki, M Yasui, H Munshi, N Richardson, P Figg, WD Anderson, KC TI Antimyeloma activity of two novel N-substituted and tetraflourinated thalidomide analogs SO LEUKEMIA LA English DT Article DE neoplasia; therapy; signal transduction; apoptosis; angiogenesis ID BONE-MARROW ANGIOGENESIS; MULTIPLE-MYELOMA CELLS; PROGNOSTIC VALUE; THERAPY; RESISTANCE; GROWTH AB Thalidomide alone or in combination with steroids has significant activity in multiple myeloma (MM). However, given its teratogenic potential, analogs have been synthesized, retaining the anti- MM activity without these side effects. We examined the anti- MM activity of two thalidomide analogs, CPS11 and CPS49. Direct cytotoxicity of the drugs on myeloma cell lines and patient myeloma cells was examined using thymidine uptake. Tumor cell apoptosis was evaluated by flow cytometry as well as Western blotting for caspase and PARP cleavage. Cellular signaling events were examined by immuno-blotting for phosphorylated proteins. Both drugs inhibit proliferation of several MM cell lines sensitive and resistant to conventional therapies. They decrease secretion of IL-6, IGF, and VEGF by marrow stromal cells. Importantly, they inhibit proliferation of MM cells adherent to stromal cells. These drugs induce caspase- mediated apoptosis in MM cell lines, as well as patient MM cells. They inhibit the PI3K/Akt and JAK/STAT (signal transducers and activators of transcription) pathways in MM cells and are antiangiogenic in matrigel- based assays. CPS11 and CPS49 have potent antimyeloma activity and can overcome protective effects of the tumor microenvironment. They have potent antiangiogenic activity and direct effect on bone marrow stroma. These encouraging preclinical data provide the basis for further evaluation in the clinic. C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, VA Boston Healthcare Syst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin, Div Hematol, Rochester, MN USA. NCI, Mol Pharmacol Sect, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Anderson, KC (reprint author), Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, VA Boston Healthcare Syst, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Kumar, Shaji/A-9853-2008; Figg Sr, William/M-2411-2016; OI Kumar, Shaji/0000-0001-5392-9284; Roccaro, Aldo/0000-0002-1872-5128 FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947]; PHS HHS [P0-78378] NR 20 TC 29 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUL PY 2005 VL 19 IS 7 BP 1253 EP 1261 DI 10.1038/sj.leu.2403776 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 937WR UT WOS:000229957400021 PM 15858615 ER PT J AU Lim, SY Loewke, J Doherty, JD Salem, N AF Lim, SY Loewke, J Doherty, JD Salem, N TI Preferential effect of lead exposure during lactation on non-essential fatty acids in maternal organs SO LIPIDS LA English DT Article ID ARACHIDONIC-ACID; DIETARY LEAD; DEFICIENCY; CHILDREN; LIVER; PEROXIDATION; MEMBRANE; RODENTS; LIPIDS AB This study determined the effects of lead exposure during the lactational period on maternal organ FA compositions in rat dams that were fed either an n-3 adequate (n-3 Adq) or deficient (n-3 Def) diet prior to conception. On giving birth, dams were subdivided into four groups in a 2 x 2 design with n-3 FA supply and Pb exposure as the dependent variables. Pb acetate (0.2 wt%) was administered in the drinking water from the time they gave birth to weaning 3 wk later. Following weaning, the dams were decapitated. and the liver, plasma, kidney, brain, and retina analyzed for FA composition. The n-3 deficient diets markedly decreased the percentages of total n-3 FA, including docosahexaenoic acid (DNA), and increased total n-6 FA including both arachidonic (AA) and n-6 docosapentaenoic acids in all tissues (P < 0.05). The principal effects of Pb occurred in the liver and plasma, where 20-32% losses in total FA concentration concurrent with increased relative percentages of AA (P < 0.05) were observed. In kidney, the percentages of AA and DHA also increased after Pb exposure (P < 0.05) with lesser effects in the nervous system. There was a diet x Pb interaction for liver, plasma, and retinal 20-C n-6 PUFA (P < 0.05). Generally, shorter-chain saturated and monounsaturated FA concentrations were decreased after Pb exposure. An analysis of the changes in the tissue concentrations induced by Pb indicated that the increases in the percentages of PUFA likely reflected a preferential loss of non-EFA. The mechanisms by which Pb affects saturated and monounsaturated FA concentration are unknown. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Korea Maritime Univ, Div Marine Environm & Biosci, Pusan, South Korea. US EPA, Off Pesticide Programs, Div Hlth Effects, Washington, DC 20460 USA. RP 5625 Fishers Ln,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov NR 22 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0024-4201 EI 1558-9307 J9 LIPIDS JI Lipids PD JUL PY 2005 VL 40 IS 7 BP 685 EP 693 DI 10.1007/s11745-005-1431-z PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 960OS UT WOS:000231603600005 PM 16196419 ER PT J AU Brock, M Hooker, C Engels, E Moore, R Gillison, M Herman, J Alberg, A Yung, R Yang, S Brahmer, J AF Brock, M Hooker, C Engels, E Moore, R Gillison, M Herman, J Alberg, A Yung, R Yang, S Brahmer, J TI HIV and lung cancer patients: Why such poor survival? SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S178 EP S178 DI 10.1016/S0169-5002(05)80736-6 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801164 ER PT J AU Dennis, P Tsurutani, J Fukuoka, J Tsurutani, H Shih, J Hewitt, S Jen, J AF Dennis, P Tsurutani, J Fukuoka, J Tsurutani, H Shih, J Hewitt, S Jen, J TI Evaluation of two phosphorylation sites establishes Akt activation as a poor prognostic factor for all stages of NSCLC tumors SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S278 EP S278 DI 10.1016/S0169-5002(05)81100-6 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802086 ER PT J AU Gauthier, I Ding, K Winton, T Shepherd, F Livingston, R Johnson, D Rigas, J Whitehead, M Graham, B Seymour, L AF Gauthier, I Ding, K Winton, T Shepherd, F Livingston, R Johnson, D Rigas, J Whitehead, M Graham, B Seymour, L TI Do hemoglobin (Hb) levels influence outcomes of adjuvant chemotherapy (ACT) with cisplatin/vinorelbine in patients (pts) with completely resected non small cell lung cancer (NSCLC)? The JBR.10 trial experience SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 NCI, Canada Clin Trials Grp, Kingston, ON, Canada. SW Oncol Grp, Seattle, WA USA. Eastern Cooperat Oncol Grp, Nashville, TN USA. Canc & Leukemia Grp B, Chicago, IL USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S280 EP S280 DI 10.1016/S0169-5002(05)81108-0 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802094 ER PT J AU Jen, J AF Jen, J TI Chromosomal amplification as a molecular marker to predict neoplastic potential in fine needle aspiration biopsies of spiral CT identified small lung modules SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN ID IMBALANCES C1 NCI, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S180 EP S180 DI 10.1016/S0169-5002(05)80744-5 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801172 ER PT J AU Karp, D Lee, S Keller, S Johnson, D Kucuk, O Clamon, G Marks, R Johnston, M Okawara, G Ruckdeschel, J AF Karp, D Lee, S Keller, S Johnson, D Kucuk, O Clamon, G Marks, R Johnston, M Okawara, G Ruckdeschel, J TI Interim report: A phase III randomized double blind chemoprevention trial of selenium supplementation in persons with resected stage I non small cell lung cancer SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Vanderbilt Univ, Nashville, TN 37240 USA. Univ Iowa Hlth Care, Iowa City, IA USA. Mayo Clin, Rochester, MN 55905 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S181 EP S181 DI 10.1016/S0169-5002(05)80746-9 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801174 ER PT J AU Leighl, N Laurie, S Knox, J Ellis, P Shepherd, F Burkes, R Pond, G Zwiebel, J Moore, M AF Leighl, N Laurie, S Knox, J Ellis, P Shepherd, F Burkes, R Pond, G Zwiebel, J Moore, M TI Phase I/II study of GTI-2040 plus docetaxel as second-line treatment in advanced non-small cell lung cancer (NSCLC) SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Princess Margaret Hosp, Phase Consortium 2, Toronto, ON, Canada. Ottawa Reg Canc Ctr, Ottawa, ON K1Y 4K7, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S256 EP S256 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802005 ER PT J AU Linnoila, I Kim, H Wang, X Dakir, E DeMayo, F AF Linnoila, I Kim, H Wang, X Dakir, E DeMayo, F TI Validation of genes associated with achaete-scute homologue-1 that regulate the growth of pulmonary neuroendocrine carcinomas in mice and men SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 NCI, NIH, Rockville, MD USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S135 EP S135 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801001 ER PT J AU Pandey, J Jacks, T Jakowlew, SB AF Pandey, J Jacks, T Jakowlew, SB TI Modulation of tumorigenesis and tumor progression in a K-ras mutated mouse model of lung cancer in the presence of TGF-beta 1 heterozygosity SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 NCI, Cell & Canc Biol Branch, Epithelial Carcinogeneisis Lab, NIH, Rockville, MD USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S72 EP S72 DI 10.1016/S0169-5002(05)80351-4 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800226 ER PT J AU Pandya, K Levy, D Hidalgo, M Cohen, R Lee, M Dancey, J Schiller, J Johnson, D AF Pandya, K Levy, D Hidalgo, M Cohen, R Lee, M Dancey, J Schiller, J Johnson, D TI A randomized phase II ECOG trial of two dose levels of temsirolimus (CCI-779) in patients with extensive stage small cell lung cancer in remission after induction therapy SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Univ Rochester, Rochester, NY 14627 USA. Dana Farber Canc Inst, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. Vanderbilt Univ, Nashville, TN 37240 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S54 EP S54 DI 10.1016/S0169-5002(05)80292-2 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800167 ER PT J AU Parra, HS Zucali, R Favaretto, A Grossi, F Fusi, A Marangolo, M Del Conte, G Ceribelli, A Bearz, A Ceresoli, G AF Parra, HS Zucali, R Favaretto, A Grossi, F Fusi, A Marangolo, M Del Conte, G Ceribelli, A Bearz, A Ceresoli, G TI A phase II study of pemetrexed and carboplatin as front-line chemotherapy in patients with malignant pleural mesothelioma (MPM) SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Ist Clin Humanitas, Dept Oncol, Milan, Italy. Univ Hosp, Dept Oncol, Padua, Italy. Natl Canc Inst, Dept Oncol, Genoa, Italy. Natl Canc Inst, Dept Oncol, I-20133 Milan, Italy. S Maria Hosp, Dept Oncol, Ravenna, Italy. Azienda Osped Triestina, Dept Oncol, Trieste, Italy. Ist Regina Elena, Dept Oncol, I-00161 Rome, Italy. Natl Canc Inst, Dept Oncol, Aviano, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S229 EP S229 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307801349 ER PT J AU Russo, P Cesario, A Catassi, A Paolucci, M Ognio, E Michele, C Doria-Miglietta, G Servent, D Dominioni, L Granone, P AF Russo, P Cesario, A Catassi, A Paolucci, M Ognio, E Michele, C Doria-Miglietta, G Servent, D Dominioni, L Granone, P TI Preclinical antitumor activity of alpha-Cobratoxin, an alpha7-nicotinic receptor inhibitor, in human malignant mesothelioma: A potential drug against a fatal cancer disease? SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Natl Canc Inst, Genoa, Italy. Catholic Univ, Rome, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S388 EP S388 DI 10.1016/S0169-5002(05)81507-7 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802493 ER PT J AU Schrump, D Nguyen, D Fischette, M Zhao, M Hong, J Chen, G Kunst, T Hancox, A Figg, W Pishchik, V AF Schrump, D Nguyen, D Fischette, M Zhao, M Hong, J Chen, G Kunst, T Hancox, A Figg, W Pishchik, V TI Targeting the epigenome for lung cancer therapy SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 NCI, Thorac Oncol Sect, Surg Branch, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S6 EP S6 DI 10.1016/S0169-5002(05)80136-9 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307800011 ER PT J AU Tomita, M Wright, J Kellogg, R Parisot, N Clark, M Li, X Davies, M Kashala, O Trehu, E Murren, J AF Tomita, M Wright, J Kellogg, R Parisot, N Clark, M Li, X Davies, M Kashala, O Trehu, E Murren, J TI Phase I study of topotecan and bortezomib (Vc) with pharmacolkinetic and pharmacodynamic correlates SO LUNG CANCER LA English DT Meeting Abstract CT 11th World Conference on Lung Cancer CY JUL 03-06, 2005 CL Barcelona, SPAIN C1 Yale Univ, Sch Med, New Haven, CT 06520 USA. Natl Canc Inst, Bethesda, MD USA. Millenium Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD JUL PY 2005 VL 49 SU 2 BP S329 EP S329 DI 10.1016/S0169-5002(05)81291-7 PG 1 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 956NV UT WOS:000231307802277 ER PT J AU Nossal, R AF Nossal, R TI Mechanical aspects of clathrin cage formation SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE clathrin; elasticity; endocytosis; self-assembly; triskelia ID COATED VESICLES; PROTEINS; BINDING; PITS AB The principal component of the coats of endocytic vesicles involved in the receptor-mediated uptake of materials from the surfaces of eucaryotic cells is a protein known as clathrin. Clathrin normally appears as a three-legged trimer joined at a common hub (a 'triskelion') which, under appropriate conditions, co-assembles with other triskelia to form variably-sized polyhedra ('cages', or 'baskets') that contain pentagonal and hexagonal faces. The size distribution of the cages can be described by a simple energetic model which contains, as a parameter, the flexural rigidity, EI, of the edges (struts) of the baskets. By comparing the values of EI thus obtained with similar quantities determined by analyzing electron micrographs of isolated triskelia (A. J. Jin, R. Nossal, Biophys. J 2000, 78, 1183), we infer that one role of clathrin-associated proteins known as 'assembly proteins' is to link the inter-twined legs of neighboring triskelia to prevent slippage when the cages are stressed. C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Nossal, R (reprint author), NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM nossalr@mail.nih.gov NR 24 TC 4 Z9 4 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 17 EP 25 DI 10.1002/masy.200550902 PG 9 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400003 ER PT J AU Geissler, E Hecht, AM Rochas, C Horkay, F Basser, PJ AF Geissler, E Hecht, AM Rochas, C Horkay, F Basser, PJ TI Light, small angle neutron and X-ray scattering from gels SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE counter-ion cloud; DNA; dynamic light scattering; neutralized polymer gels; polymer gels; small angle neutron scattering ID POLYMER GELS; DNA; CONDENSATION; HYDROGELS; CATIONS AB This paper gives two examples of experiments that demonstrate the power of small angle scattering techniques in the study of swollen polymer networks. First, it is shown how the partly ergodic character of these systems is directly detected by neutron spin echo experiments. The observed total field correlation function of the intensity scattered from a neutral gel allows the ergodic contribution to be directly distinguished from the non ergodic part, at values of transfer wave vector q that lie well beyond the range of dynamic light scattering. The results can be compared with those obtained at much lower q from visible light scattering. Second, a recent application of small angle X-ray (SAXS) and neutron (SANS) scattering is described for a polyelectrolyte molecule, DNA, in semi-dilute solutions under near-physiological conditions. For these observations, the divatent ion normally present, calcium, is replaced by an equivalent ion, strontium. The comparison between SANS and SAXS yields a quantitative picture of the cloud of divalent counter-ions around the central DNA core. At physiological conditions, the cloud is thinner than that predicted on the basis of the Debye screening length but thicker than if the counter-ions were condensed on the DNA chain. C1 Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NICHD, Lab Integrat & Med Biophys, Sect Tissue Biophys & Biomimet, NIH, Bethesda, MD 20892 USA. RP Geissler, E (reprint author), Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, BP 87, F-38402 St Martin Dheres, France. RI Basser, Peter/H-5477-2011 NR 20 TC 3 Z9 3 U1 0 U2 20 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 27 EP 37 DI 10.1002/masy.200550903 PG 11 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400004 ER PT J AU Basser, PJ Horkay, F AF Basser, PJ Horkay, F TI Toward a constitutive law of cartilage: A polymer physics perspective SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE aggregate; cartilage; collagen; composite; constitutive; ECM; osmotic; pressure; proteoglycan; swelling ID ARTICULAR-CARTILAGE; POROUS-MEDIA; CONSOLIDATION; PRESSURE AB To describe load bearing and lubrication of cartilage requires treating its collagen network and proteoglycan (PG) phases separately in a constitutive law of the tissue. We propose a framework for developing such an empirical constitutive law that treats the cartilage extracellular matrix (ECM) as a composite medium, with a PG phase that exerts a swelling pressure, and a collagen network phase that restrains it. We compare and contrast this model to a biornechanical constitutive law that aggregates the collagen and PG phases into a single "solid-like" elastic tissue matrix, and show that aggregation obscures essential differences in the physical-chemical properties of the collagen and PG constituents as well as their distinct biological roles within cartilage's ECM. We also relate moduli in the aggregate constitutive model to quantities measured in an osmotic stress titration experiment. C1 NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Basser, PJ (reprint author), NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, 13 S Dr, Bethesda, MD 20892 USA. RI Basser, Peter/H-5477-2011 NR 18 TC 4 Z9 4 U1 0 U2 3 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 53 EP 64 DI 10.1002/masy.200550905 PG 12 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400006 ER PT J AU Li, WJ Tuan, RS AF Li, WJ Tuan, RS TI Polymeric scaffolds for cartilage tissue engineering SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE biodegradable; biomaterials; cartilage tissue engineering; matrix ID MESENCHYMAL STEM-CELLS; GROWTH-FACTOR-I; SYNTHETIC BIODEGRADABLE POLYMERS; FULL-THICKNESS DEFECTS; ARTICULAR-CARTILAGE; CHONDROITIN SULFATE; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSDERMAL PHOTOPOLYMERIZATION; HUMAN CHONDROCYTES; HYALURONIC-ACID AB Polymeric scaffolds are three-dimensional, porous structures that may be used as a vehicle to deliver cells or therapeutic factors to repair tissue defects. Both biodegradable and non-biodegradable polymers have been developed for this purpose. In this review, we survey the polymers that have been investigated for cartilage tissue engineering and discuss the critical parameters for successful applications in the future. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. EM Tuanr@mail.nih.gov RI Li, Wan-Ju/A-7002-2008 NR 56 TC 21 Z9 21 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 65 EP 75 DI 10.1002/masy.200550906 PG 11 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400007 ER PT J AU Tasaki, I AF Tasaki, I TI Abrupt structural changes in polyanionic gels evoked by Na-Ca ion exchange: Their biological implications SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE excitability; gel; ion exchange; Na-Ca; polyanionic ID SQUID GIANT-AXON; POLYELECTROLYTES; EXCITABILITY; BINDING; MODEL AB Anionic polyelectrolyte gels, synthetic or natural, undergo abrupt structural changes when the monovalent counterions in the gel, e.g., Na+, are replaced with divalent cations, et, Ca2+. These structural changes are caused by the preferential binding of Ca2+ to the polyelectrolyte chains and the ability of Ca2+ to form crosslinks between two neighboring chains. Strong lyotropic (Hofmeister) effects of anions, such as fluoride, phosphate, aspartate and chloride, on the repetitiveness of abrupt structural changes in the gel strands are demonstrated. These findings have important biological implications. C1 NICHD, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Tasaki, I (reprint author), NICHD, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 2 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 97 EP 104 DI 10.1002/masy.200550909 PG 8 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400010 ER PT J AU Boukari, H Sackett, DL Nossal, R AF Boukari, H Sackett, DL Nossal, R TI Probing the hydrodynamic behavior of drug-induced tubulin rings by fluorescence correlation spectroscopy SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE cryptophycin; dolastatin; fluorescence correlation spectroscopy; microtubules; tubulin rings ID MACROMOLECULES; MICROTUBULE; RESOLUTION; TRANSPORT AB We describe fluorescence correlation spectroscopy measurements of tubulin polymers composed of tubulin and either of two cytotoxic peptides dolastatin 10 and cryptophycin 1. These peptides inhibit tubulin polymerization into microtubules, a major component of cellular networks, and instead induce the formation of predominantly single-walled tubulin rings. We determine ratios of the hydrodynamic diameter of dolastatin-tubulin or cryptophycin-tubulin polymers to that of tubulin dimers, which are compared with corresponding ratios calculated for two simple models: 1) a circular ring made with N contiguous spherical beads and 2) a circular ring constructed with N non-spherical monomers, each monomer being represented by 21-minibeads. We find that the computed ratios from the 21-minibead representation agree well with the measured ones when N = 28 and N = 16 for dolastatin-tubulin and cryptophycin-tubulin ring polymers, respectively. That is, the rings are made with 14 and 8 tubulin dimers, confirming the numbers derived by other techniques. The present results further support the applicability of theories that have been developed for calculating hydrodynamic properties of supramolecular biological structures. C1 NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Boukari, H (reprint author), NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. EM boukarih@mail.nih.gov; sackettd@mail.nih.gov; rjn@helix.nih.gov NR 19 TC 0 Z9 0 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 211 EP 220 DI 10.1002/masy.200550921 PG 10 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400022 ER PT J AU Michelman-Ribeiro, A Boukari, H Nossal, R Horkay, F AF Michelman-Ribeiro, A Boukari, H Nossal, R Horkay, F TI Fluorescence correlation spectroscopy study of probe diffusion in poly(vinyl alcohol) solutions and gels SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE cross-linking; diffusion; fluorescence correlation spectroscopy; inhomogeneities; poly(vinyl alcohol) gel ID AQUEOUS-SOLUTIONS; HYDROGELS; DYNAMICS AB In this study, we demonstrate how the diffusion of probe particles in aqueous poly(vinyl alcohol) (PVA) solutions and gels is affected by: (i) the presence of cross-links, (ii) the cross-link density, (iii) the polymer concentration. We apply fluorescence correlation spectroscopy (FCS) to measure the diffusion time of a rhodamine-based fluorescent particle (TAMRA) and TAMRA-labeled dextran in PVA solutions and gels prepared at various polymer concentrations (1% to 8.6% w/v) and cross-link densities (1/400 to 1/50 cross-link monomers per PVA monomers). The measurements indicate that the probe particles are slowed down with increasing polymer concentration and with increasing cross-link density. Also, FCS can detect differences in the diffusion times measured in "fresh" and "aged" PVA solutions. We find that FCS provides a quantitative measure of network inhomogeneities. C1 LIMB, NIH, Bethesda, MD 20892 USA. Boston Univ, Dept Phys, Boston, MA 02215 USA. RP Michelman-Ribeiro, A (reprint author), LIMB, NIH, Bethesda, MD 20892 USA. EM michelma@mail.nih.gov; boukarih@mail.nih.gov; rjn@helix.nih.gov; horkayf@mail.nih.gov NR 13 TC 5 Z9 5 U1 0 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 221 EP 229 DI 10.1002/masy.200550922 PG 9 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400023 ER PT J AU Pomerance, A Matthews, J Ferguson, M Urbach, JS Losert, W AF Pomerance, A Matthews, J Ferguson, M Urbach, JS Losert, W TI Actin polymerization in a thermal gradient SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE actin; microrheology; polymerization transition; thermal gradient AB Actin polymerization was studied as a function of temperature and in controlled thermal gradients. In the absence of a thermal gradient, we observe a polymerization transition with a temperature increase of less than 10K, and we verify that microrheology provides a local measure of the polymerized fraction. Both of these results are in good agreement with prior observations. Thermal gradients allow us to generate polymerization gradients. This polymerization gradient induces motion in embedded microspheres that is not seen in control samples. C1 Univ Maryland, Inst Phys Sci & Technol, Dept Phys, College Pk, MD 20742 USA. Univ Maryland, Inst Res Elect & Appl Phys, College Pk, MD 20742 USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Phys, Washington, DC 20057 USA. RP Losert, W (reprint author), Univ Maryland, Inst Phys Sci & Technol, Dept Phys, College Pk, MD 20742 USA. EM wlosert@glue.umd.edu RI Ferguson, Matthew/C-4140-2014; OI Ferguson, Matthew/0000-0003-0760-757X; Urbach, Jeffrey/0000-0002-1593-520X NR 18 TC 2 Z9 2 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 231 EP 242 DI 10.1002/masy.200550923 PG 12 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400024 ER PT J AU Lin-Gibson, S Bencherif, S Antonucci, JM Jones, RL Horkay, F AF Lin-Gibson, S Bencherif, S Antonucci, JM Jones, RL Horkay, F TI Synthesis and characterization of poly(ethylene glycol) dimethacrylate hydrogels SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE gel structure; hydrogel; MALDI-TOF MS; mechanical properties; neutron scattering; poly(ethylene glycol); SANS ID NEUTRON-SCATTERING; CHONDROCYTES; CARTILAGE AB Facile synthesis and detailed characterization of photopolymerizable and biocompatible poly(ethylene glycol) dimethacrylates (PEGDM) and their hydrogels are described. Combined analyses of H-1 NMR and MALDI-TOF MS confirmed the formation of prepolymers of high purity and narrow mass distribution (PD < 1.02). A systematic investigation into the structure and mechanical properties of PEGDM hydrogels was performed to characterize the relationships between the network structure and get properties. Small-angle neutron scattering was used to characterize the structural features of hydrogels with respect to their semidilute solution precursors. A well-defined structural length scale (correlation length) manifested as a maximum in the scattering intensity was observed for hydrogels derived from high molecular mass PEGDMs and/or high oligomer mass fractions. Hydrogels derived from lower molecular mass PEGDMs and/or low oligomer mass fractions exhibited multiple correlation lengths suggesting the formation of inhomogeneous gel structures. The shear moduli, determined from uniaxial compression measurement, showed that the gel structures correlate well with the gel mechanical properties. C1 Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. NICHD, Sect Tissue Biophys & Biomimet, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Lin-Gibson, S (reprint author), Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. EM slgibson@nist.gov OI BENCHERIF, SIDI/0000-0002-7704-5608 NR 13 TC 12 Z9 12 U1 1 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 243 EP 254 DI 10.1002/masy.200550924 PG 12 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400025 ER PT J AU Ma, W Chen, S Fitzgerald, W Maric, D Lin, HJ O'Shaughnessy, TJ Kelly, J Liu, XH Barker, JL AF Ma, W Chen, S Fitzgerald, W Maric, D Lin, HJ O'Shaughnessy, TJ Kelly, J Liu, XH Barker, JL TI Three-dimensional collagen gel networks for neural stem cell-based neural tissue engineering SO MACROMOLECULAR SYMPOSIA LA English DT Article; Proceedings Paper CT 17th Polymer-Networks-Group Meeting CY AUG 15-19, 2004 CL Bethesda, MD SP Natl Inst Hlth, IUPAC, Natl Inst Standards & Technol DE biopolymers; bioreactor; collagen gels; matrix; neural stem cell ID CENTRAL-NERVOUS-SYSTEM; MICROGRAVITY AB Stem and progenitor cells isolated from the embryonic rat cerebral cortex were immobilized by matrix entrapment in three-dimensional (3D) Type I collagen gels, and cultured in serum-free medium containing basic fibroblast growth factor. The cells trapped within the collagen networks actively proliferated and formed clone-like aggregates. Neurons were the first differentiated cells to appear within the aggregates, followed by generation of astrocytes and oligodendrocytes. In addition, necrotic cores were developed as the aggregate diameter increased and cell viability declined significantly after 3 weeks in culture. To overcome these problems, the cell-collagen constructs were transferred to Rotary Wall Vessel bioreactors for up to 10 weeks. In the rotary culture, the collagen gels compacted 3-4 folds and a long-term growth and differentiation of neural stem and progenitor cells was dynamically maintained. Remarkably, the cell-collagen constructs formed a complex two-layered structure that superficially emulated to a certain extent the cerebral cortex of the embryonic brain in architecture and functionality. The engineered 3D tissue-like constructs displaying characteristic properties of neuronal circuits may have potential use in tissue replacement therapy for injured brain and spinal cord. C1 USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. Wyle Labs, Bethesda, MD 20892 USA. NASA, NIH, Ctr Dimens Tissue Culture 3, Bethesda, MD 20892 USA. NICHD, Lab Cellular & Mol Biophys, NICHHD, NIH, Bethesda, MD 20892 USA. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. RP Ma, W (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. EM wma@cbmse.nrl.navy.mil NR 10 TC 7 Z9 7 U1 0 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1022-1360 J9 MACROMOL SYMP JI Macromol. Symp. PD JUL PY 2005 VL 227 BP 327 EP 333 DI 10.1002/masy.200550933 PG 7 WC Polymer Science SC Polymer Science GA 959AX UT WOS:000231490400034 ER PT J AU Hu, TCC Christian, TF Aletras, AH Taylor, JL Koretsky, AP Arai, AE AF Hu, TCC Christian, TF Aletras, AH Taylor, JL Koretsky, AP Arai, AE TI Manganese enhanced magnetic resonance imaging of normal and ischemic canine heart SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE manganese; myocardial perfusion; myocardial ischemia; myocardial viability; safety ID PERFUSED RAT-HEART; DIPYRIDOXYL DIPHOSPHATE; CONTRAST ENHANCEMENT; MRI; MNDPDP; MNCL2; MYOCARDIUM; INJECTION; KINETICS; SAFETY AB The ability of MnCl2 to enhance canine myocardium and to delineate ischemic areas is demonstrated. A dose-response curve was measured using T-1 weighted images in 11 dogs. MnCl2 (36,113, 360, and 3600 mu mol) was infused over a period of 3 min. Signal intensity increased linearly with MnCl2 dose. At 113 mu mol (similar to 10 mu mol/kg) the steady-state increase in intensity averaged 212 +/- 34 %. No significant physiologic effects due to the infused MnCl2 were detected except at the highest dose where there was a cardiac depressive effect. Ischemia was induced by occluding the left anterior descending coronary artery in 5 dogs. At an infused dose of 113 mu mol, MnCl2 clearly demarcated the ischemic zone during coronary occlusion. Contrast enhancement in the ischemic zone was less than 30 % compared with normal tissue (P < 0.03). In conclusion, the intracellular contrast agent MnCl2 enhances the canine heart and shows promise in detecting ischemia at doses that do not cause adverse cardiac effects. Published 2005 Wiley-Liss, Inc. C1 NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NINDS, Lab Funct & Mol Imaging, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Arai, AE (reprint author), NHLBI, Cardiac Energet Lab, Dept Hlth & Human Serv, NIH, Bldg 10,Room B1D416,MSC 1061, Bethesda, MD 20892 USA. EM araia@nih.gov RI Koretsky, Alan/C-7940-2015; OI Koretsky, Alan/0000-0002-8085-4756; Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [Z01 NS002989-08] NR 22 TC 22 Z9 22 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUL PY 2005 VL 54 IS 1 BP 196 EP 200 DI 10.1002/mrm.20516 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 938OX UT WOS:000230013800025 PM 15968667 ER PT J AU Matsumoto, S Utsumi, H Aravalluvan, T Matsumoto, K Matsumoto, A Devasahayam, N Sowers, AL Mitchell, JB Subramanian, S Krishna, MC AF Matsumoto, S Utsumi, H Aravalluvan, T Matsumoto, K Matsumoto, A Devasahayam, N Sowers, AL Mitchell, JB Subramanian, S Krishna, MC TI Influence of proton T-1 on oxymetry using Overhauser enhanced magnetic resonance imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE Overhauser enhanced MRI; in vivo oximetry; proton T-1; image artifact; tumor hypoxia ID IN-VIVO OXYMETRY; TUMOR; OXYGENATION; OXIMETRY; TIME AB In Overhauser enhanced magnetic resonance imaging (OMRI) for in vivo measurement of oxygen partial pressure (pO(2)), a paramagnetic contrast agent is introduced to enhance the proton signal through dynamic nuclear polarization. A uniform proton T-1 is generally assumed for the entire region of interest for the computation of PO2 using OMRI. It is demonstrated here, by both phantom and in vivo (mice) imaging, that such an assumption may cause erroneous estimate of PO2. A direct estimate of pixel-wise T-1 is hampered by the poor native MR intensities, owing to the very low Zeeman field (15-20 mT) in OMRI. To circumvent this problem, a simple method for the pixel-wise mapping of proton T-1 using the OMRI scanner is described. A proton T-1 image of a slice through the center of an SCC tumor in a mouse clearly shows a range of T-1 distribution (0.2 similar to 1.6 s). Computation of PO2 images using pixel-wise T-1 values promises oximetry with minimal artifacts by OMRI. Published 2005 Wiley-Liss, Inc. C1 NCI, Radiol Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Kyushu Univ, Grad Sch Pharmaceut Sci, Lab Biofunct Sci, Fukuoka 812, Japan. RP Krishna, MC (reprint author), NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM murali@helix.nih.gov NR 17 TC 13 Z9 14 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUL PY 2005 VL 54 IS 1 BP 213 EP 217 DI 10.1002/mrm.20564 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 938OX UT WOS:000230013800028 PM 15968662 ER PT J AU Li, S Shen, J AF Li, S Shen, J TI Integrated RF probe for in vivo multinuclear spectroscopy and functional imaging of rat brain using an 11.7 Tesla 89 mm bore vertical microimager SO MAGNETIC RESONANCE MATERIALS IN PHYSICS BIOLOGY AND MEDICINE LA English DT Article DE RF coil; rat brain; fMRI; in vivo spectroscopy; vertical bore magnet ID NUCLEAR MAGNETIC-RESONANCE; 9.4 T; FMRI; MRI; NMR; GLUTAMATE; ANIMALS; GLUCOSE; INVIVO; MOUSE AB To acquire high quality in vivo NMR data from rat brain using a vertical 89-mm bore magnet, specially designed NMR probes with integrated RF coils and animal handling capability are required. An RE probe design that is also capable of rat head fixation, body support and suitable for physiology monitoring and maintenance was constructed for an 89 mm bore, 11.7 T, vertical microimager which is equipped with a 57-mm i.d. gradient insert. Design concept and practical aspects of probe construction are described in detail. The device allows accurate and highly reproducible positioning of rat head inside the magnet while providing excellent RF performance. Typical results from fMRI, localized in vivo proton and multinuclear spectroscopy using this probe system are presented. C1 NIMH, NIH, Mol Imaging Branch, Bethesda, MD 20892 USA. NIMH, NIH, Magnet Resonance Spect Core Facil, Bethesda, MD 20892 USA. RP Li, S (reprint author), NIMH, NIH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000,Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov NR 31 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0968-5243 J9 MAGN RESON MATER PHY JI Magn. Reson. Mat. Phys. Biol. Med. PD JUL PY 2005 VL 18 IS 3 BP 119 EP 127 DI 10.1007/s10334-005-0103-y PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 962HJ UT WOS:000231721400004 PM 16007474 ER PT J AU Tsang, S Sun, ZH Luke, B Stewart, C Lum, N Gregory, M Wu, XL Subleski, M Jenkins, NA Copeland, NG Munroe, DJ AF Tsang, S Sun, ZH Luke, B Stewart, C Lum, N Gregory, M Wu, XL Subleski, M Jenkins, NA Copeland, NG Munroe, DJ TI A comprehensive SNP-based genetic analysis of inbred mouse strains SO MAMMALIAN GENOME LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; FUTURE-PROSPECTS; SPEED CONGENICS; GENOME; DISCOVERY; LOCI; MICE; MAP AB Dense genetic maps of mammalian genomes facilitate a variety of biological studies including the mapping of polygenic traits, positional cloning of monogenic traits, mapping of quantitative or qualitative trait loci, marker association, allelic imbalance, speed congenic construction, and evolutionary or phylogenetic comparison. In particular, single nucleotide polymorphisms (SNPs) have proved useful because of their abundance and compatibility with multiple high-throughput technology platforms. SNP genotyping is especially suited for the genetic analysis of model organisms such as the mouse because biallelic markers remain fully informative when used to characterize crosses between inbred strains. Here we report the mapping an genotyping of 673 SNPs (including 519 novel SNPs) in 55 of the most commonly used mouse strains. These data have allowed us to construct a phylogenetic tree that correlates and expands known genealogical relationships and clarifies the origin of strains previously having an uncertain ancestry. All 55 inbred strains are distinguishable genetically using this SNP panel. Our data reveal an uneven SNP distribution consistent with a mosaic pattern of inheritance and provide some insight into the changing dynamics of the physical architecture of the genome. Furthermore, these data represent a valuable resource for the selection of markers and the design of experiments that require the genetic distinction of any pair of mouse inbred strains such as the generation of congenic mice, positional cloning, and the mapping of quantitative or qualitative trait loci. C1 NCI, SAIC Frederick, Lab Mol Technol, Frederick, MD 21701 USA. NCI, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Munroe, DJ (reprint author), NCI, SAIC Frederick, Lab Mol Technol, 915 Tollhouse Ave,Suite 211, Frederick, MD 21701 USA. EM dmunroe@mail.ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 20 TC 27 Z9 29 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD JUL PY 2005 VL 16 IS 7 BP 476 EP 480 DI 10.1007/s00335-005-0001-7 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 958JH UT WOS:000231440100001 PM 16151692 ER PT J AU Hardison, AL Lichten, L Banerjee-Basu, S Becker, TS Burgess, SM AF Hardison, AL Lichten, L Banerjee-Basu, S Becker, TS Burgess, SM TI The zebrafish gene claudinj is essential for normal ear function and important for the formation of the otoliths SO MECHANISMS OF DEVELOPMENT LA English DT Article DE tight junctions; Otoliths; zebrafish; claudin; deafness; vestibular defects ID RECESSIVE DEAFNESS DFNB29; TIGHT-JUNCTION STRANDS; INSERTIONAL MUTAGENESIS; CELLS; EXPRESSION; OCCLUDIN; BARRIER; PROTEINS; ENCODES; BINDING AB We have identified a mutation in the zebrafish gene claudinj generated by retroviral integration. Mutant embryos display otoliths severely reduced in size, no response to tapping stimulus, and an inability to balance properly suggesting vestibular and hearing dysfunction. Antisense in situ hybridization to the cldnj gene showed expression first in the otic placode and later asymmetric expression in the otic vesicle. Morpholino inhibition of claudinj expression showed similar defects in otolith formation. Phylogenetic analysis of claudin sequences from multiple species demonstrates that claudinj was part of a gene expansion that began in the common ancestor of fish and humans, but additional fish specific gene duplications must have also occurred. Published by Elsevier Ireland Ltd. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Bergen, Sars Ctr, Bergen, Norway. RP Burgess, SM (reprint author), NHGRI, Genome Technol Branch, NIH, Bldg 50,Room 5537,50 South Dr, Bethesda, MD 20892 USA. EM burgess@mail.nih.gov RI Becker, Thomas/A-3125-2012; OI Burgess, Shawn/0000-0003-1147-0596 NR 34 TC 26 Z9 26 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4773 J9 MECH DEVELOP JI Mech. Dev. PD JUL PY 2005 VL 122 IS 7-8 BP 949 EP 958 DI 10.1016/j.mod.2005.03.009 PG 10 WC Developmental Biology SC Developmental Biology GA 952XK UT WOS:000231039200008 PM 15925497 ER PT J AU Yabroff, KR Warren, JL Knopf, K Davis, WW Brown, ML AF Yabroff, KR Warren, JL Knopf, K Davis, WW Brown, ML TI Estimating patient time costs associated with colorectal cancer care SO MEDICAL CARE LA English DT Article DE patient time; health care costs; health services research; patient time; cost and cost analysis; colorectal neoplasms; Medicare; SEER program ID FEE-FOR-SERVICE; SEER-MEDICARE DATA; BREAST-CANCER; CERVICAL-CANCER; TRAVEL; THERAPY; STAGE; ENROLLEES; DIAGNOSIS; PROGRAM AB Background: Nonmedical costs of care, such as patient time associated with travel to, waiting for, and seeking medical care, are rarely measured systematically with population-based data. Objectives: The purpose of this study was to estimate patient time costs associated with colorectal cancer care. Methods: We identified categories of key medical services for colorectal cancer care and then estimated patient time associated with each service category using data from national surveys. To estimate average service frequencies for each service category, we used a nested case control design and SEER-Medicare data. Estimates were calculated by phase of care for cases and controls, using data from 1995 to 1998. Average service frequencies were then combined with estimates of patient time for each category of service, and the value of patient time assigned. Net patient time costs were calculated for each service category, summarized by phase of care, and compared with previously reported net direct costs of colorectal cancer care. Results: Net patient time costs for the 3 phases of colorectal cancer care averaged $4592 (95% confidence interval [CI] $4427-4757) over the 12 months of the initial phase, $2788 (95% CI $2614-2963) over the 12 months of the terminal phase, and $25 (95% Cl: $23-26) per month in the continuing phase of care. Hospitalizations accounted for more than two thirds of these estimates. Patient time costs were 19.3% of direct medical costs in the initial phase, 15.8% in the continuing phase, and 36.8% in the terminal phase of care. Conclusions: Patient time costs are an important component of the costs of colorectal cancer care. Application of this method to other tumor sites and inclusion of other components of the costs of medical care will be important in delineating the economic burden of cancer in the United States. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. DeCesaris Canc Inst, Annapolis Oncol Ctr, Annapolis, MD USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM yabroffr@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 40 TC 46 Z9 48 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUL PY 2005 VL 43 IS 7 BP 640 EP 648 DI 10.1097/01.mlr.0000167177.45020.4a PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 940QJ UT WOS:000230158700002 PM 15970778 ER PT J AU Olden, K White, SL AF Olden, K White, SL TI Health-related disparities: Influence of environmental factors SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID CANCER INCIDENCE; POLYMORPHISMS; GENE; DISEASE; SEQUENCE; GENOME; SUSCEPTIBILITY; POPULATION; AMERICANS; FINLAND AB There is substantial evidence showing differences in frequency in various environmental response genes, which play a role in susceptibility for disease or adverse health outcomes from exposure to drugs or environmental xenobiotics. The prediction is that disparities in health in the United States grow because of two converging phenomena: growth of minority populations and expansion of the ranks of poverty. Tinkering with genes either to cure a disease or to correct predispositions will likely be less successful and more costly than primary prevention efforts that emphasize environmental protection and remediation. C1 US Dept HHS, Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. N Carolina Cent Univ, Dept Biol, Durham, NC 27707 USA. RP Olden, K (reprint author), US Dept HHS, Natl Inst Environm Hlth Sci, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM olden@niehs.nih.gov NR 42 TC 47 Z9 48 U1 2 U2 6 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0025-7125 EI 1557-9859 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 2005 VL 89 IS 4 BP 721 EP + DI 10.1016/j.mcna.2005.02.001 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 938WU UT WOS:000230034900002 PM 15925646 ER PT J AU Cargill, VA Stone, VE AF Cargill, VA Stone, VE TI HIV/AIDS: A minority health issue SO MEDICAL CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-INFECTED PATIENTS; AIDS CLINICAL-TRIALS; PROTEASE INHIBITORS; P-GLYCOPROTEIN; DRUG-USERS; ANTIRETROVIRAL THERAPY; AFRICAN-AMERICANS; UNITED-STATES; SERVICE USE AB HIV infection disproportionately affects racial and ethnic minority populations in the United States. The reasons for this disproportionate impact are complex, and intertwined with many confounding issues that also disproportionately affect racial and ethnic minorities. Superimposed on these factors are the unique cultural beliefs and contexts that influence behavior, health beliefs in general, and HIV infection in particular. As the epidemic continues in these communities, presentations of plicated by the presence of other chronic portionate in these communities, Failure broad-based prevention interventions for ties virtually ensures that HIV transmission in communities already severely affected. HIV infection are diseases that are disproportionate to achieve successful racial and ethnic minorities virtually ensures that HIV transmission will continue unabated in communities already severely affected. C1 NIH, Off AIDS Res, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. RP Cargill, VA (reprint author), NIH, Off AIDS Res, 2 Ctr Dr,Room 4E20, Bethesda, MD 20892 USA. EM vc52x@nih.gov NR 70 TC 70 Z9 71 U1 2 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0025-7125 J9 MED CLIN N AM JI Med. Clin. N. Am. PD JUL PY 2005 VL 89 IS 4 BP 895 EP + DI 10.1016/j.mcna.2005.03.005 PG 20 WC Medicine, General & Internal SC General & Internal Medicine GA 938WU UT WOS:000230034900011 PM 15925655 ER PT J AU Sumner, AE Vega, GL Genovese, DJ Finley, KB Bergman, RN Boston, RC AF Sumner, AE Vega, GL Genovese, DJ Finley, KB Bergman, RN Boston, RC TI Normal triglyceride levels despite insulin resistance in African Americans: role of lipoprotein lipase SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID VISCERAL ADIPOSE-TISSUE; SEX-DIFFERENCES; UNITED-STATES; RISK-FACTORS; OBESITY; PLASMA; ATHEROSCLEROSIS; CHOLESTEROL; PREVALENCE; ADULTS AB Lipoprotein lipase (LPL), the enzyme responsible for hydrolyzing triglyceride (TG) in plasma lipoproteins, is a key regulator of plasma TG levels. In Caucasians, postheparin-LPL (PH-LPL) activity is impaired in the presence of insulin resistance and leads to elevated TG levels. However, African Americans are often both insulin-resistant and normotriglyceridemic. But in African Americans, the effect of insulin resistance on PH-LPL activity has not been studied. In African Americans, if insulin resistance is not associated with a decrease in PH-LPL activity, this could account for the simultaneous presence of insulin resistance and normotriglyceridemia. Therefore, our goal was to determine in African Americans the relationship between insulin resistance and PH-LPL activity. In a crosssectional study of 107 nondiabetic African Americans (57 men and 50 women; age mean SD, 35 8 years, range 22-50 years; body mass index 31.6 +/- 7.9 kg/m(2), range 18.5-54.7 kg/m(2)), fasting TG levels and PH-LPL activity were determined. Visceral adipose tissue was measured by abdominal computed tomographic scan. Insulin resistance was determined by the insulin sensitivity index (SI). Subjects were divided into tertiles by S-I. The range of S, in each tertile was 12.75 to 3.99, 3.87 to 2.20, 2.06 to 0.17 mU (.) L-1 (.) min(-1). Insulin resistance was defined as being in the third tertile. TG levels in the men and women were 82.2 +/- 35.5 versus 56.4 +/- 30.1 mg/dL, P <.001. There were no sex difference in PH-LPL activity (8.9 +/- 2.5 vs 9.6 +/- 3.2 mmol/h per liter, P =.30) or S, (3.65 2.59 vs 3.23 +/- 1.89 L (.) mU(-1) (.) min, P =.49). Although 47% of the subjects were obese, only 4% of subjects had hypertriglyceridemia TG >= 150 mg/dL). By 2 separate analyses, PH-LPL was a major determinant of TG levels. First, there was a significant inverse correlation between PH-LPL activity and TG levels (men: r = -0.46, P <.001; women: r = -0.28, P =.046). Second, in the multiple regression analysis with TG as the dependent variable and PH-LPL, age, sex, S-1, and visceral adipose tissue as independent variables, adjusted R-2 was 54% and the effect of PH-LPL on TG levels was highly significant(P <.001). However, insulin resistance did not appear to influence PH-LPL activity. This is demonstrated in 3 ways: first, PH-LPL activity was not different in the S, tertiles (9.10 +/- 2.75, 9.52 +/- 2.91, 9.13 +/- 2.89 mmol/h per liter, P =.78); the correlation between PH-LPL and S, was not significant (men: r = 0.09, P =.51; women: r = -0.03, P =.78), and a multiple regression with PH-LPL as the dependent variable and age, SI, body mass index, and sex as independent variables, adjusted R 2 Was < 2% and the contribution of S, was not significant (P =.53). Hence, in African Americans, increased PH-LPL activity is associated with a decrease in TG levels. The lack of an effect of insulin resistance on PH-LPL could allow LPL to clear TG even in the presence of insulin resistance and explain the coexistence of insulin resistance and normotriglyceridemia in African Americans. (c) 2005 Published by Elsevier Inc. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Univ So Calif, Keck Sch Med, Dept Physiol, Los Angeles, CA 90033 USA. Univ Penn, Sch Vet Med, Biomath Unit, Philadelphia, PA 19104 USA. RP Sumner, AE (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM annes@intra.niddk.nih.gov FU NIDDK NIH HHS [DK27619, DK29867] NR 32 TC 47 Z9 47 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2005 VL 54 IS 7 BP 902 EP 909 DI 10.1016/j.metabol.2005.03.001 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 942KS UT WOS:000230281900010 PM 15988699 ER PT J AU Eskandari, F Mistry, S Martinez, PE Torvik, S Kotila, C Sebring, N Drinkard, BE Levy, C Reynolds, JC Csako, G Gold, PW Horne, M Cizza, G AF Eskandari, F Mistry, S Martinez, PE Torvik, S Kotila, C Sebring, N Drinkard, BE Levy, C Reynolds, JC Csako, G Gold, PW Horne, M Cizza, G TI Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk - The POWER Study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; FIBRINOLYTIC-ACTIVITY; CUSHINGS-SYNDROME; HYPERCOAGULABLE STATE; MYOCARDIAL-INFARCTION; DISEASE; OBESITY; ADULTS; ATHEROSCLEROSIS; MORTALITY AB Major depressive disorder (MDD) is. one of the most common psychiatric illnesses in the adult population. It is often associated with an increased risk of cardiovascular disease. We measured body fat distribution as well as plasminogen activator inhibitor-1 (PAI-1) concentration and factor VIII (fVIII) activity at 8:00 Am and 8:00 PM in 45 premenopausal women with MDD vs 28 healthy controls (age, 37 +/- 6.8 vs 35 +/- 6.5; weight [kg], 75.3 +/- 17.2 vs 67.9 +/- 10.2; mean SD] participating in a prospective study of bone turnover, the POWER Study. At the time of evaluation, women with MDD were mildly depressed and mostly in clinical remission on antidepressants. After adjusting for body weight, women with MDD had greater waist circumference and abdominal fat as well as significantly higher evening (8:00 Pm) PAI-1 and fVIII levels than controls. Even when age-, race-, and body mass index-matched subsets were compared, the MDD group continued to exhibit statistically higher PAI-1 and fVIII levels. The observed alterations in body fat distribution (increased abdominal fat) and prothrombotic factors (increased PAI-1 and fVIII) may be in part responsible for the increased risk of cardiovascular disease reported in association with major depression. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIMH, Sect Neuroendocrine Immunol & Behav, Integrat Neural Immune Program, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Med, Div Clin & Mol Endocrinol, Cleveland, OH 44106 USA. NIH, Ctr Clin, Dept Nutr, BED,Nucl Med Dept, Bethesda, MD 20892 USA. NCI, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Cizza, G (reprint author), NIDDK, Clin Endocrine Sect, Clin Endocrinol Branch, NIH, Bldg 10,CRC,Room 6-3940, Bethesda, MD 20892 USA. EM cizzag@intra.niddk.nih.gov FU Intramural NIH HHS NR 31 TC 44 Z9 47 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUL PY 2005 VL 54 IS 7 BP 918 EP 924 DI 10.1016/j.metabol.2005.02.006 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 942KS UT WOS:000230281900012 PM 15988701 ER PT J AU Xu, XJ Dong, YM Abraham, EG Kocan, A Srinivasan, P Ghosh, AK Sinden, RE Ribeiro, JMC Jacobs-Lorena, M Kafatos, FC Dimopoulos, G AF Xu, XJ Dong, YM Abraham, EG Kocan, A Srinivasan, P Ghosh, AK Sinden, RE Ribeiro, JMC Jacobs-Lorena, M Kafatos, FC Dimopoulos, G TI Transcriptome analysis of Anopheles stephensi-Plasinodium berghei interactions SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE Plasmodium; Anopheles; gene expression ID EXPRESSION DATA-ANALYSIS; PLASMODIUM-FALCIPARUM; MALARIA PARASITES; GENE-EXPRESSION; BLOOD MEAL; CIRCUMSPOROZOITE PROTEIN; RHOPTRY PROTEIN; VECTOR MOSQUITO; MIDGUT INVASION; A-DOMAIN AB Simultaneous rnicroarray-based transcription analysis of 4987 Anopheles stephensi midgut and plasmodium berghei infection stage specific cDNAs was done at seven successive time points: 6, 20 and 40 h, and 4, 8, 14 and 20 days after ingestion of malaria infected blood. The study reveals the molecular components of several Anopheles processes relating to blood digestion, midgut expansion and response to Plasmodium-infected blood such as digestive enzymes, transporters, cytoskeletal and structural components and stress and immune responsive factors. In parallel, the analysis provide detailed expression patterns of Plasmodium genes encoding essential developmental and metabolic factors and proteins implicated in interaction with the mosquito vector and vertebrate host such its kinases, transcription and translational factors, cytoskeletal components and a variety of surface proteins, some of which are potent vaccine targets, Temporal correlation between transcription profiles of both organisms identifies putative gene clusters of interacting processes, such as Plasmodium invasion of the midgut epithelium, Anopheles immune responses to Plasmodium infection, and apoptosis and expulsion of invaded midgut cells from the epithelium. Intriguing transcription patterns for highly variable Plasmodium surface antigens may indicate parasite strategies to avoid recognition by the mosquito's immune surveillance system. (c) 2005 Elsevier B.V. All rights reserved. C1 Johns Hopkins Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Manrochem Ltd, Huddersfield HD1 5JP, W Yorkshire, England. Univ London Imperial Coll Sci & Technol, Dept Biol Sci, London SW7 2AZ, England. NIAID, Parasit Dis Lab, Med Entomol Sect, NIH, Bethesda, MD 20892 USA. European Mol Biol Lab, Heidelberg, Germany. RP Dimopoulos, G (reprint author), Johns Hopkins Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. EM gdimopou@jhsph.edu OI Dimopoulos, George/0000-0001-6755-8111; Ribeiro, Jose/0000-0002-9107-0818 NR 51 TC 41 Z9 47 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD JUL PY 2005 VL 142 IS 1 BP 76 EP 87 DI 10.1016/j.molbiopara.2005.02.013 PG 12 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 934TU UT WOS:000229732300008 PM 15907562 ER PT J AU Govind, CK Yoon, S Qiu, HF Govind, S Hinnebusch, AG AF Govind, CK Yoon, S Qiu, HF Govind, S Hinnebusch, AG TI Simultaneous recruitment of coactivators by Gcn4p stimulates multiple steps of transcription in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID RNA-POLYMERASE-II; SACCHAROMYCES-CEREVISIAE; REMODELING COMPLEX; SRB MEDIATOR; CHROMATIN; YEAST; ACTIVATOR; SWI/SNF; SAGA; ELONGATION AB Transcriptional activation by Gcn4p is dependent on the coactivators SWI/SNF, SAGA, and Srb Mediator, which are recruited by Gcn4p and stimulate assembly of the preinitiation complex (PIC) at the ARG1 promoter in vivo. We show that recruitment of all three coactivators is nearly simultaneous with binding of Gcn4p at ARG1 and is followed quickly by PIC formation and elongation by RNA polymerase II (Pol II) through the open reading frame. Despite the simultaneous recruitment of coactivators, rapid recruitment of SWI/SNF depends on the histone acetyltransferase (HAT) subunit of SAGA (Gcn5p), a non-HAT function of SAGA, and on Mediator. SAGA recruitment in turn is strongly stimulated by Mediator and the RSC complex. Recruitment of Mediator, by contrast, occurs independently of the other coactivators; at ARG1. We confirm the roles of Mediator and SAGA in TATA binding protein (TBP) recruitment and demonstrate that all four coactivators under study enhance Pol II recruitment or promoter clearance following TBP binding. We also present evidence that SWI/SNF and SAGA stimulate transcription elongation downstream from the promoter. These functions can be limited to discrete time intervals, providing evidence for multiple stages in the induction process. Our findings reveal a program of coactivator recruitment and PIC assembly that distinguishes Gcn4p from other yeast activators studied thus far. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A,Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov NR 44 TC 77 Z9 77 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 13 BP 5626 EP 5638 DI 10.1128/MCB.25.13.5626-5638.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 937IX UT WOS:000229918900030 PM 15964818 ER PT J AU Paul, BD Fu, LZ Buchholz, DR Shi, YB AF Paul, BD Fu, LZ Buchholz, DR Shi, YB TI Coactivator recruitment is essential for liganded thyroid hormone receptor to initiate amphibian metamorphosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID XENOPUS-LAEVIS METAMORPHOSIS; IN-VIVO ANALYSIS; NUCLEAR-RECEPTOR; COREPRESSOR COMPLEX; TRANSCRIPTIONAL COACTIVATOR; MICE LACKING; INTESTINAL DEVELOPMENT; EMBRYONIC-DEVELOPMENT; POSTNATAL-DEVELOPMENT; FROG METAMORPHOSIS AB Thyroid hormone receptors (TRs) can repress or activate target genes depending on the absence or presence of thyroid hormone (T3), respectively. This hormone-dependent gene regulation is mediated by recruitment of corepressors in the absence of T3 and coactivators in its presence. Many TR-interacting coactivators have been characterized in vitro. In comparison, few studies have addressed the developmental roles of these cofactors in vivo. We have investigated the role of coactivators in transcriptional activation by TR during postembryonic tissue remodeling by using amphibian metamorphosis as a model system. We have previously shown that steroid receptor coactivator 3 (SRC3) is expressed and upregulated during metamorphosis, suggesting a role in gene regulation by liganded TR. Here, we have generated transgenic tadpoles expressing a dominant negative form of SRC3 (F-dnSRC3). The transgenic tadpoles exhibited normal growth and development throughout embryogenesis and premetamorphic stages. However, transgenic expression of F-dnSRC3 inhibits essentially all aspects of T3-induced metamorphosis, as well as natural metamorphosis, leading to delayed or arrested metamorphosis or the formation of tailed frogs. Molecular analysis revealed that F-dnSRC3 functioned by blocking the recruitment of endogenous coactivators to 13 target genes without affecting corepressor release, thereby preventing the T3-dependent gene regulation program responsible for tissue transformations during metamorphosis. Our studies thus demonstrate that coactivator recruitment, aside from corepressor release, is required for T3 function in development and further provide the first example where a specific coactivator-dependent gene regulation pathway by a nuclear receptor has been shown to underlie specific developmental events. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 18T,Rm 106, Bethesda, MD 20892 USA. EM shi@helix.nih.gov NR 79 TC 39 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 13 BP 5712 EP 5724 DI 10.1128/MCB.25.13.5712.-5724.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 937IX UT WOS:000229918900037 PM 15964825 ER PT J AU Jiao, XM Zhang, N Xu, XH Oppenheim, JJ Jin, T AF Jiao, XM Zhang, N Xu, XH Oppenheim, JJ Jin, T TI Ligand-induced partitioning of human CXCR1 chemokine receptors with lipid raft microenvironments facilitates G-protein-dependent signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HUMAN INTERLEUKIN-8 RECEPTOR; MEMBRANE MICRODOMAINS; CELL-ACTIVATION; BETA-ARRESTINS; CHOLESTEROL; NEUTROPHIL; PHOSPHORYLATION; DIMERIZATION; DYNAMICS; IDENTIFICATION AB Ligand binding to a chemokine receptor triggers signaling events through heterotrimeric G-proteins. The mechanisms underlying receptor-mediated G-protein activation in the heterogeneous microenvironments of the plasma membrane are unclear. Here, using live-cell fluorescence resonance energy transfer imaging to detect the proximity between CXCR1-cyan fluorescent protein (CFP) and fluorescence probes that label lipid raft or non-lipid raft microdomains and using fluorescence recovery after photobleaching analysis to measure the lateral diffusion of CXCR1-CFP, we found that interleukin-8 induces association between the receptors and lipid raft microenvironments. Disruption of lipid rafts impaired G-protein-dependent signaling, such as Ca2+ responses and phosphatidylinositol 3-kinase activation, but had no effect on ligand-binding function and did not completely abolish ligand-induced receptor phosphorylation. Our results suggest a novel mechanism by which ligand binding to CXCR1 promotes lipid raft partitioning of receptors and facilitates activation of heterotrimeric G-proteins. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21701 USA. RP Jin, T (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklwan Dr,Twinbrook 2, Rockville, MD 20852 USA. EM tjin@niaid.nih.gov FU NIAID NIH HHS [Z01 AI000928-03, Z01 AI000916-04] NR 47 TC 33 Z9 34 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 13 BP 5752 EP 5762 DI 10.1128/MCB.25.13.5752-5762.2005 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 937IX UT WOS:000229918900040 PM 15964828 ER PT J AU Fu, Z Schroeder, MJ Shabanowitz, J Kaldis, P Togawa, K Rustgi, AK Hunt, DF Sturgill, TW AF Fu, Z Schroeder, MJ Shabanowitz, J Kaldis, P Togawa, K Rustgi, AK Hunt, DF Sturgill, TW TI Activation of a nuclear Cdc2-related kinase within a mitogen-activated protein kinase-like TDY motif by autophosphorylation and cyclin-dependent protein kinase-activating kinase SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL-ASSOCIATED KINASE; MOLECULAR-CLONING; MAP KINASE; BUDDING YEAST; GERM-CELLS; S PHASE; IDENTIFICATION; LOCALIZATION; EXPRESSION; PHOSPHORYLATION AB Male germ cell-associated kinase (MAK) and intestinal cell kinase (ICK) are nuclear Cdc2-related kinases with nearly identical N-terminal catalytic domains and more divergent C-terminal noncatalytic domains. The catalytic domain is also related to mitogen-activated protein kinases (MAPKs) and contains a corresponding TDY motif. Nuclear localization of ICK requires subdomain XI and interactions of the conserved Arg-272, but not kinase activity or, surprisingly, any of the noncatalytic domain. Further, nuclear localization of ICK is required for its activation. ICK is activated by dual phosphorylation of the TDY motif. Phosphorylation of Tyr-159 in the TDY motif requires ICK autokinase activity but confers only basal kinase activity. Full activation requires additional phosphorylation of Thr-157 in the TDY motif. Coexpression of ICK with constitutively active MEK1 or MEK5 fails to increase ICK phosphorylation or activity, suggesting that MEKs are not involved. ICK and MAK are related to Ime2p in budding yeast, and cyclin-dependent protein kinase-activating kinase Cak1p has been placed genetically upstream of Ime2p. Recombinant Cak1p phosphorylates Thr-157 in the TDY motif of recombinant ICK and activates its activity in vitro. Coexpression of ICK with wild-type CAK1 but not kinase-inactive CAK1 in cells also increases ICK phosphorylation and activity. Our studies establish ICK as the prototype for a new group of MAPK-like kinases requiring dual phosphorylation at TDY motifs. C1 Univ Virginia, Sch Med, Dept Pharmacol, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Internal Med, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Chem, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Dept Pathol, Charlottesville, VA 22908 USA. NCI, Mouse Canc Genet Program, Ft Detrick, MD 21702 USA. Univ Penn, Div Gastroenterol, Ctr Canc, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Div Gastroenterol, Ctr Canc, Dept Genet, Philadelphia, PA 19104 USA. RP Sturgill, TW (reprint author), Univ Virginia, Sch Med, Dept Pharmacol, 1300 Jefferson Pk Ave, Charlottesville, VA 22908 USA. EM Thomas_Sturgill@virginia.edu RI Kaldis, Philipp/G-2714-2010; Hunt, Donald/I-6936-2012 OI Kaldis, Philipp/0000-0002-7247-7591; Hunt, Donald/0000-0003-2815-6368 FU NIGMS NIH HHS [R01 GM062890, GM37537, GM62890, R01 GM037537] NR 46 TC 30 Z9 30 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUL PY 2005 VL 25 IS 14 BP 6047 EP 6064 DI 10.1128/MCB.25.14.6047-6064.2005 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 942EZ UT WOS:000230267000022 PM 15988018 ER PT J AU Petralia, RS Sans, N Wang, YX Wenthold, RJ AF Petralia, RS Sans, N Wang, YX Wenthold, RJ TI Ontogeny of postsynaptic density proteins at glutamatergic synapses SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Review ID CELL-ADHESION MOLECULE; LONG-TERM POTENTIATION; TRKB NEUROTROPHIN RECEPTORS; PRESYNAPTIC ACTIVE ZONE; CENTRAL-NERVOUS-SYSTEM; NMDA RECEPTOR; POSTNATAL-DEVELOPMENT; EXCITATORY SYNAPSES; SYNAPTIC PROTEINS; ULTRASTRUCTURAL-LOCALIZATION AB In glutamatergic synapses, glutamate receptors (GluRs) associate with many other proteins involved in scaffolding and signal transduction. The ontogeny of these postsynaptic density (PSD) proteins involves changes in their composition during development, paralleling changes in GluR type and function. In the CA1 region of the hippocampus, at postnatal day 2 (P2), many synapses already have a distinct PSD. We used immunoblot analysis, subcellular fractionation, and quantitative immunogold electron microscopy to examine the distribution of PSD proteins during development of the hippocampus. Synapses at P2 contained substantial levels of NR1 and NR2B and most GluR-associated proteins, including SAP102, SynGAP, the chain of proteins from GluRs/SAP102 through GKAP/Shank/Homer and metabotropic glutamate receptors, and the adhesion factors, cadherin, catenin, neuroligin, and Nr-CAM. Development was marked by substantial decreases in NR2B and SAP102 and increases in NR2A, PSD-95, AMPA receptors, and CaMKII. Other components showed more moderate changes. Published by Elsevier Inc. C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Petralia, RS (reprint author), NIDCD, Neurochem Lab, NIH, 50 S Dr,MSC 8027, Bethesda, MD 20892 USA. EM petralia@nidcd.nih.gov FU NIDCD NIH HHS [Z01 DC000003-17] NR 106 TC 139 Z9 145 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell. Neurosci. PD JUL PY 2005 VL 29 IS 3 BP 436 EP 452 DI 10.1016/j.mcn.2005.03.013 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 940BL UT WOS:000230118600009 PM 15894489 ER PT J AU Sauna, ZE Shukla, S Ambudkar, SV AF Sauna, ZE Shukla, S Ambudkar, SV TI Disulfiram, an old drug with new potential therapeutic uses for human cancers and fungal infections SO MOLECULAR BIOSYSTEMS LA English DT Review ID NF-KAPPA-B; MEDIATED MULTIDRUG-RESISTANCE; MITOCHONDRIAL ALDEHYDE DEHYDROGENASE; SUPEROXIDE-DISMUTASE PLAYS; HUMAN-MELANOMA CELLS; SMOOTH-MUSCLE-CELLS; MDR1 P-GLYCOPROTEIN; IN-VITRO; BREAST-CANCER; CYCLOPROPYLDIBENZOSUBERANE MODULATOR AB Disulfiram, a drug used to treat alcoholism, has recently been indicated to play a primary as well as an adjuvant role in the treatment of many cancers and in the reversal of fungal drug-resistance. This review discusses the molecular mechanism of action of disulfiram and its potential use in the treatment of disulfiram and its potential use in the treatment of human cancers and fungal infections. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH,DHHS, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Ambudkar, Suresh/B-5964-2008 NR 101 TC 51 Z9 53 U1 2 U2 6 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1742-206X J9 MOL BIOSYST JI Mol. Biosyst. PD JUL PY 2005 VL 1 IS 2 BP 127 EP 134 DI 10.1039/b504392a PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993TM UT WOS:000233978000003 PM 16880974 ER PT J AU Cavin, LG Wang, F Factor, VM Kaur, S Venkatraman, M Thorgeirsson, SS Arsura, M AF Cavin, LG Wang, F Factor, VM Kaur, S Venkatraman, M Thorgeirsson, SS Arsura, M TI Transforming growth factor-alpha inhibits the intrinsic pathway of c-myc-induced apoptosis through activation of nuclear factor-kappa B in murine hepatocellular carcinomas SO MOLECULAR CANCER RESEARCH LA English DT Article ID BCL-X-L; BREAST-CANCER; TRANSGENIC MICE; CONSTITUTIVE ACTIVATION; MEDIATED TRANSFORMATION; HEPATIC ONCOGENESIS; RELA/P65 SUBUNIT; LIVER NEOPLASIA; KINASE; CELLS AB Nuclear factor-kappa B (NF-kappa B) plays an important role during liver neoplastic development through transcriptional regulation of prosurvival genes, which then counteract the death-inducing signals elicited by the host immune response. The c-Myc proto-oncogene is frequently deregulated in liver tumors. Furthermore, enforced expression of c-Myc in the liver promotes the development of hepatocellular carcinomas, a process that is accelerated by coexpression with transforming growth factor-alpha (TGF-alpha). TGF-alpha/c-Myc-derived hepatocellular carcinomas display reduced apoptotic levels compared with those of single c-Myc transgenic hepatocellular carcinomas, suggesting that TGF-alpha provides a survival advantage to c-Myc-transformed hepatocytes. Given that TGF-alpha/c-Myc hepatocellular carcinomas display constitutive NF-kappa B activity, here, we have tested the hypothesis that enforced expression of TGF-alpha results in constitutive NF-kappa B activation and enhanced cell survival using TGF-alpha/c-Myc-derived hepatocellular carcinoma cell lines. We show that TGF-alpha induces NF-kappa B through the phosphatidylinositol 3-kinase/Akt axis in these bitransgenic hepatocellular carcinomas. Furthermore, we found that adenovirus-mediated inhibition of NF-kappa B activity impairs the ability of TGF-alpha/c-Myc-derived tumor cells to grow in an anchorage-independent fashion due to sensitization to c-Myc-induced apoptosis. Lastly, we show that NF-kappa B inhibits c-Myc-induced activation of caspase-9 and caspase-3 through up-regulation of the antiapoptotic target genes Bcl-X-L and X-linked inhibitor of apoptosis (XIAP). Overall, these results underscore a crucial role of NF-kappa B in disabling apoptotic pathways initiated by oncogenic transformation. C1 Univ Tennessee, Inst Canc,Coll Med, Dept Pharmacol, Ctr Anticanc Drug Res, Memphis, TN 38163 USA. NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Arsura, M (reprint author), Univ Tennessee, Inst Canc,Coll Med, Dept Pharmacol, Ctr Anticanc Drug Res, 874 Union Ave, Memphis, TN 38163 USA. EM marsura@utmem.edu FU NCI NIH HHS [CA 78616-S1] NR 53 TC 24 Z9 32 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD JUL PY 2005 VL 3 IS 7 BP 403 EP 412 DI 10.1158/1541-7786.MCR-04-0186 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 950RF UT WOS:000230874200005 PM 16046551 ER PT J AU Plasencia, C Dayam, R Wang, QC Pinski, J Burke, TR Quinn, DI Neamati, N AF Plasencia, C Dayam, R Wang, QC Pinski, J Burke, TR Quinn, DI Neamati, N TI Discovery and preclinical evaluation of a novel class of small-molecule compounds in hormone-dependent and -independent cancer cell lines SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID HIV-1 INTEGRASE; DRUG ABSORPTION; CONTAINING INHIBITORS; SURFACE PROPERTIES; APOPTOSIS; PHARMACOPHORE; PERMEABILITY; PREDICTION; RESISTANCE AB We discovered a series of salicylhydrazide class of compounds with remarkable anticancer activity against a panel of hormone receptor-positive and -negative cell lines. In the present study, we evaluated the in vitro activity of SC21 and SC23 against a range of human tumor cell types and the in vivo efficacy of compound SC21 in a PC3 human prostate cancer xenograft model in mice. We also determined the effects of SC21 on cell cycle regulation and apoptosis. Our in vitro results show that salicy1hydrazides are highly potent compounds effective in both hormone receptor-positive and -negative cancer cells. SC21 induced apoptosis and blocked the cell cycle in G(0)/G(1) or S phase, depending on the cell lines used and irrespective of p53, p21, pRb, and p16 status. SC21 effectively reduced the tumor growth in mice without apparent toxicity. Although the mechanism of action of SC21 is not completely elucidated, the effect on cell cycle, the induction of apoptosis and the activity against a panel of tumor cell lines of different origins prompted us to carry out an in-depth preclinical evaluation of SC21. C1 Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA. NIH, Med Chem Lab, Canc Res Ctr, Frederick, MD USA. RP Neamati, N (reprint author), Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM neamati@usc.edu RI Burke, Terrence/N-2601-2014; Quinn, David/F-4343-2015 OI Quinn, David/0000-0002-1411-0417 NR 31 TC 28 Z9 28 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUL PY 2005 VL 4 IS 7 BP 1105 EP 1113 DI 10.1158/1535-7163.MCT-04-0288 PG 9 WC Oncology SC Oncology GA 945XY UT WOS:000230537500009 PM 16020668 ER PT J AU Guler, G Iliopoulos, D Han, SY Fong, LYY Lubet, RA Grubbs, CJ Huebner, K AF Guler, G Iliopoulos, D Han, SY Fong, LYY Lubet, RA Grubbs, CJ Huebner, K TI Hypermethylation patterns in the Fhit regulatory region are tissue specific SO MOLECULAR CARCINOGENESIS LA English DT Article DE carcinogen-induced tumors; CpG island methylation; Fhit; methylation patterns ID DNA METHYLATION; BLADDER-CANCER; DEFICIENT MICE; FRAGILE SITES; LUNG-CANCER; GENE; EXPRESSION; TUMORS; EPIGENETICS; P16(INK4A) AB DNA hypermethylation is associated with decreased expression of tumor suppressor genes. We previously observed decreased Fhit expression and Fhit promoter region hypermethylation in rodent tumors induced by various carcinogens, and noted that the 5' regulatory regions in the promoter, exon 1, and intron 1 were differentially methylated, depending on the tissue of origin. Because different carcinogens were used for induction of tumors of the different organs, we could not conclude that the methylation patterns were tissue-specific. To determine if in rat tissues: (1) Fhit methylation status is related to expression levels and (2) Fhit methylation patterns were tissue- or carcinogen-specific, we examined Fhit methylation status and expression levels in DMBA- and MNU-induced benign and malignant mammary tumors. Fhit intron 1 was methylated in 3/9 DMBA and all of MNU-induced benign mammary tumors, in association with reduced Fhit expression levels; Fhit promoter and intron 1 were methylated in all DMBA and MNU-incluced carcinomas in association with highly reduced Fhit expression levels. Treatment of rat cancer cells in vitro with the DNA methyltransferase inhibitor, 5'-Aza-2'deoxycytidine, for 4 d, increased Fhit expression and altered the methylation status. Before treatment, both promoter and intron 1 regions were methylated; after treatment, only intron 1 remained methylated. Thus, in carcinogen-exposed rat tissues there is an overall association of Fhit expression with regulatory region methylation, and hypermethylation patterns did not vary with carcinogen. The specific patterns of hypermethylated CpGs in the Fhit regulatory regions thus appear to be tissue-specific. Published 2005 Wiley-Liss, Inc. C1 Thomas Jefferson Univ, Jefferson Med Coll, Kimmel Canc Ctr, Dept Microbiol Immunol, Philadelphia, PA 19107 USA. Natl Canc Inst, DCPC, Div Canc Prevent & Control, Bethesda, MD USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Iliopoulos, D (reprint author), Ohio State Univ, Ctr Comprehens Canc, Rm 463,410w 12th St, Columbus, OH 43210 USA. NR 32 TC 7 Z9 7 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD JUL PY 2005 VL 43 IS 3 BP 175 EP 181 DI 10.1002/mc.20100 PG 7 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 942FZ UT WOS:000230269600006 PM 15937960 ER PT J AU Dong, ZZ Arnold, RJ Yang, YY Park, MH Hrncirova, P Mechref, Y Novotny, MV Zhang, JT AF Dong, ZZ Arnold, RJ Yang, YY Park, MH Hrncirova, P Mechref, Y Novotny, MV Zhang, JT TI Modulation of differentiation-related gene 1 expression by cell cycle blocker mimosine, revealed by proteomic analysis SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID DNA METHYLATION CONTRIBUTES; EIF3 P170; N-MYC; TRANSCRIPTION FACTOR; PROTEIN-SYNTHESIS; PROSTATE-CANCER; TARGET GENE; INHIBITION; HYPUSINE; REPLICATION AB L-Mimosine, a plant amino acid, can reversibly block mammalian cells at late G 1 phase and has been found to affect translation of mRNAs of the cyclin-dependent kinase inhibitor p27, eIF3a (eIF3 p170), and ribonucleotide reductase M2. The effect of mimosine on the expression of these genes may be essential for the G 1 phase arrest. To determine additional genes that may be early respondents to the mimosine treatment, we performed two-dimensional gel electrophoretic analysis of [S-35] methionine-labeled cell lysates followed by identification of the altered protein spots by LC-tandem mass spectrometry. In this study, the synthesis of two protein spots (MIP42 and MIP17) was found to be enhanced by mimosine, whereas the formation of another protein spot (MSP17) was severely blocked following mimosine treatment. These protein spots, MIP42, MIP17, and MSP17, were identified to be differentiation-related gene 1 (Drg-1; also called RTP, cap43, rit42, Ndrg-1, and PROXY-1), deoxyhypusine-containing eIF5A intermediate, and mature hypusine-containing eIF5A, respectively. The effect of mimosine on eIF5A maturation was due to inhibition of deoxyhypusine hydroxylase, the enzyme catalyzing the final step of hypusine biosynthesis in eIF5A. The mimosine-induced expression of Drg-1 was mainly attributable to increased transcription likely by the c-Jun/AP-1 transcription factor. Because induction of Drg-1 is an early event after mimosine treatment and is observed before a notable reduction in the steady-state level of mature eIF5A, eIF5A does not appear to be involved in the modulation of Drg-1 expression. C1 Indiana Univ, Sch Med, IUCC, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Walther Canc Inst, Walther Oncol Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Dept Chem, Bloomington, IN 47405 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Indiana Univ, Sch Med, IUCC, Dept Pharmacol & Toxicol, 1044 W Walnut St,R4-166, Indianapolis, IN 46202 USA. EM jianzhan@iupui.edu RI Zhang, Jian-Ting/L-8334-2015; OI Mechref, Yehia/0000-0002-6661-6073 FU NCI NIH HHS [CA64539, CA94961] NR 56 TC 36 Z9 37 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 EI 1535-9484 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUL PY 2005 VL 4 IS 7 BP 993 EP 1001 DI 10.1074/mcp.M500044-MCP200 PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 943EG UT WOS:000230334500012 PM 15855174 ER PT J AU Kochetov, AV Sarai, A Rogozin, IB Shumny, VK Kolchanov, NA AF Kochetov, AV Sarai, A Rogozin, IB Shumny, VK Kolchanov, NA TI The role of alternative translation start sites in the generation of human protein diversity SO MOLECULAR GENETICS AND GENOMICS LA English DT Article DE human mRNAs; AUG context; subcellular localization; protein polymorphism ID EUKARYOTIC MESSENGER-RNAS; OPEN READING FRAMES; 5'-UNTRANSLATED REGIONS; INITIATING TRANSLATION; POTENTIAL SOURCE; HUMAN GENOME; AUG CODONS; SEQUENCE; GENE; MITOCHONDRIAL AB According to the scanning model, 40S ribosomal subunits initiate translation at the first (5' proximal) AUG codon they encounter. However, if the first AUG is in a suboptimal context, it may not be recognized, and translation can then initiate at downstream AUG(s). In this way, a single RNA can produce several variant products. Earlier experiments suggested that some of these additional protein variants might be functionally important. We have analysed human mRNAs that have AUG triplets in 5' untranslated regions and mRNAs in which the annotated translational start codon is located in a suboptimal context. It was found that 3% of human mRNAs have the potential to encode N-terminally extended variants of the annotated proteins and 12% could code for N-truncated variants. The predicted subcellular localizations of these protein variants were compared: 31% of the N-extended proteins and 30% of the N-truncated proteins were predicted to localize to subcellular compartments that differed from those targeted by the annotated protein forms. These results suggest that additional AUGs may frequently be exploited for the synthesis of proteins that possess novel functional properties. C1 Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. Novosibirsk State Univ, Novosibirsk 630090, Russia. Kyushu Inst Technol, Iizuka, Fukuoka 8208502, Japan. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Kochetov, AV (reprint author), Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. EM ak@bionet.nsc.ru RI Kochetov, Alex/R-9689-2016; OI Kochetov, Alex/0000-0003-3151-5181; Kolchanov, Nikolay/0000-0001-6800-8787; Shumny, Vladimir/0000-0003-1939-6140 NR 35 TC 34 Z9 36 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1617-4615 J9 MOL GENET GENOMICS JI Mol. Genet. Genomics PD JUL PY 2005 VL 273 IS 6 BP 491 EP 496 DI 10.1007/s00438-005-1152-7 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 949TB UT WOS:000230809900006 PM 15959805 ER PT J AU O'Leary, VB Mills, JL Pangilinan, F Kirke, PN Cox, C Conley, M Weiler, A Peng, K Shane, B Scott, JM Parle-McDermott, A Molloy, AM Brody, LC AF O'Leary, VB Mills, JL Pangilinan, F Kirke, PN Cox, C Conley, M Weiler, A Peng, K Shane, B Scott, JM Parle-McDermott, A Molloy, AM Brody, LC CA Birth Defects Res Grp TI Analysis of methionine synthase reductase polymorphisms for neural tube defects risk association SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE MTRR; MTR; MTHFR; folate; homocysteine; neural tube defects; polymorphism; spina bifida ID DOWN-SYNDROME; HOMOCYSTEINE REMETHYLATION; INCREASES RISK; SPINA-BIFIDA; METABOLISM; GENES; MUTATIONS; DISEASE; VARIANT; FOLATE AB Methionine synthase reductase (MTRR) regenerates methylated cobalamin levels from the oxidised cob(II)alamin form and in so doing plays a crucial role in maintaining the active state of methionine synthase (MTR). MTR is an essential enzyme catalyzing the conversion of homocysteine to methionine. Single nucleotide polymorphisms (SNPs) within the MTRR gene may potentially compromise MTR activity leading to elevated homocysteine levels, a known risk factor for neural tube defects (NTDs). We studied the MTRR polymorphisms 122M (66A -> G), S175L (524C -> T), and K350R (1049A -> G) as potential NTD risk factors in a large homogeneous Irish NTD population. Degree of risk was assessed via case/control comparison, log-linear analysis, and transmission disequilibrium testing. No association was found between NTDs and 122M in mothers (p=0.16, OR1.14 [0.95-1.38], n=447) or cases (p = 0.13, OR1.15 [0.96-1.38], n = 470) compared to controls (n = 476). A dominant 122M paternal effect was found through case/control comparison and log-linear modelling (p = 0.019) (goodness-of-fit p = 0.91, OR 1.46 [1.10-1.93], n = 423). No significant NTD association was found with S175L or K350R in cases or their parents and no interactions were observed between these polymorphisms and the D919G variant of MTR or the A222V variant of 5,10-methylenetetrahydrofolate reductase (MTHFR). We also compared the frequencies of 122M, S175L, and K350R in African-Americans versus American-Caucasians. The frequencies of 122M and K350R differed significantly between the two groups (p = 0.0005 and p = 0.0001, respectively). Our findings do not support an important role for these MTRR variants in NTDs. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NICHHD, Div Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHGRI, Genome Technol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. Univ Calif Berkeley, Dept Nutr Sci, Berkeley, CA 94720 USA. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. RP O'Leary, VB (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. EM olearyv@tcd.ie OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830 FU NHLBI NIH HHS [HL58991]; NICHD NIH HHS [HD23163]; NIDDK NIH HHS [DK42033] NR 26 TC 35 Z9 40 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUL PY 2005 VL 85 IS 3 BP 220 EP 227 DI 10.1016/j.ymgme.2005.02.003 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 945LI UT WOS:000230503600008 PM 15979034 ER PT J AU Parle-McDermott, A Pangilinan, F Mills, JL Signore, CC Molloy, AM Cotter, A Conley, M Cox, C Kirke, PN Scott, JM Brody, LC AF Parle-McDermott, A Pangilinan, F Mills, JL Signore, CC Molloy, AM Cotter, A Conley, M Cox, C Kirke, PN Scott, JM Brody, LC TI A polymorphism in the MTHFD1 gene increases a mother's risk of having an unexplained second trimester pregnancy loss SO MOLECULAR HUMAN REPRODUCTION LA English DT Article DE abortion; fetal death; second trimester; spontaneous; unexplained ID NEURAL-TUBE DEFECTS; DEHYDROGENASE-METHENYLTETRAHYDROFOLATE-CYCLOHYDROLASE; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; HUMAN SPONTANEOUS-ABORTION; TRIFUNCTIONAL ENZYME; FORMYLTETRAHYDROFOLATE SYNTHETASE; PLASMA HOMOCYSTEINE; FOLIC-ACID; PREECLAMPSIA; FOLATE AB Low maternal folate or vitamin B-12 status has been implicated in numerous pregnancy complications including spontaneous abortion. The primary aim of this study was to test a polymorphism within the trifunctional folate enzyme MTHFD1 (5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase, 10-formyltetrahydrofolate synthetase) for an association with a mother's risk of having an unexplained second trimester pregnancy loss. We genotyped 125 women who had at least one unexplained spontaneous abortion or intrauterine fetal death between 13 and 26 weeks gestation and 625 control women with no history of prior pregnancy loss. Our study is the first to identify an association between the MTHFD1 1958G -> A ( R653Q) polymorphism and the maternal risk of having an unexplained second trimester pregnancy loss. Women who are MTHFD1 1958AA homozygous have a 1.64-fold increased risk of having an unexplained second trimester loss compared to women who are MTHFD1 1958AG or 1958GG [ OR 1.64 ( 1.05-2.57), P = 0.03]. It has been reported that polymorphisms in 5,10-methylenetetrahydrofolate reductase ( MTHFR), 677C -> T ( A222V), transcobalamin II ( TCII), 776C -> G ( P259R), are associated with pregnancy loss. Both variants were tested in this study. Neither showed evidence of significantly affecting the maternal risk of having a second trimester pregnancy loss. In conclusion, the MTHFD1 1958AA genotype may be an important maternal risk factor to consider during pregnancy. C1 NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NICHHD, Div Epidemiol Stat & Prevent Res, US Dept HHS, NIH, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Coombe Womens Hosp, Dublin, Ireland. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. RP Brody, LC (reprint author), NHGRI, Mol Pathogenesis Sect, Genome Technol Branch, Bldg 50,Room 5306,50 South Dr,MSC 8004, Bethesda, MD 20892 USA. EM lbrody@helix.nih.gov OI Molloy, Anne/0000-0002-1688-9049 FU NICHD NIH HHS [N01-HD-3-3348] NR 37 TC 31 Z9 34 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1360-9947 J9 MOL HUM REPROD JI Mol. Hum. Reprod. PD JUL 1 PY 2005 VL 11 IS 7 BP 477 EP 480 DI 10.1093/molehr/gah204 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 959PK UT WOS:000231529900002 PM 16123074 ER PT J AU Sinha, R Cross, A Curtin, J Zimmerman, T McNutt, S Risch, A Holden, J AF Sinha, R Cross, A Curtin, J Zimmerman, T McNutt, S Risch, A Holden, J TI Development of a food frequency questionnaire module and databases for compounds in cooked and processed meats SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE cooking methods; food frequency questionnaire; heterocyclic aromatic amines; meat; preserved meat; polycyclic aromatic hydrocarbons; preserved meat ID HETEROCYCLIC AMINE CONTENT; GRILLED RED MEAT; NON-HEME IRON; WELL-DONE; COLORECTAL ADENOMAS; VARYING DEGREES; BREAST-CANCER; N-NITROSATION; LUNG-CANCER; RISK AB There is ample evidence from basic research and animal carcinogenicity studies that heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs) are mutagens and carcinogens. However, there was a paucity of human data due to a lack of appropriate investigative tools. We developed the first validated cooked meat module within a food frequency questionnaire (FFQ) in the United States of America and created databases to be used in conjunction with this FFQ to estimate intake of HCAs and benzo[a]pyrene, a marker of PAHs. It became clear that other aspects of meat may also contribute to carcinogenesis; in particular, we are pursuing two additional areas: processed meat and iron exposure in relation to cancer risk. To investigate these hypotheses, we have expanded the cooked meat module to include detailed information on processed meats and fish. In addition, we are developing two databases, one for total iron and heme iron in cooked meat and the other for nitrite, nitrate, and N-nitroso compounds in processed meats. In this report, we will outline the methods used to develop the meat questionnaires, the databases, a software package for generating the intake values, and the methods used to generate nutritional data from nationally representative samples. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Westat Corp, Rockville, MD USA. USDA ARS, BHNRC, NDL, BARC W Beltsville, W Beltsville, MD USA. RP Sinha, R (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 3046, Bethesda, MD 20892 USA. EM sinhar@nih.gov RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 42 TC 79 Z9 82 U1 2 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD JUL PY 2005 VL 49 IS 7 BP 648 EP 655 DI 10.1002/mnfr.200500018 PG 8 WC Food Science & Technology SC Food Science & Technology GA 947UA UT WOS:000230671600003 PM 15986387 ER PT J AU Venditto, VJ Regino, CAS Brechbiel, MW AF Venditto, Vincent J. Regino, Celeste Aida S. Brechbiel, Martin W. TI PAMAM dendrimer based macromolecules as improved contrast agents SO MOLECULAR PHARMACEUTICS LA English DT Review DE PAMAM dendrimers; macromolecular contrast agents; targeted imaging; magnetic resonance imaging; molecular relaxivity; biodistribution AB Dendrimers are an attractive platform for macromolecular imaging due to the presence of multiple terminal groups on the exterior of the molecule. Through application of appropriate metal ion chelates, large numbers of metal ions for imaging (paramagnetic or radioopaque) and therapy (radioactive particle emitters) may be conjugated to the dendrimer in combination with a targeting vector, through classic organic synthetic techniques. Thus, a large amount of these metal ions potentially may be site specifically delivered directly into the body with the dendrimer as the vehicle with the targeting vector directing the modified dendrimer. The development of targeted macromolecular agents with acceptable blood retention times and selective organ uptake then has the potential for various biological applications. A review of comparative studies of dendrimers with various externally appended imaging and targeting agents is presented herein. C1 [Venditto, Vincent J.; Regino, Celeste Aida S.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov NR 60 TC 121 Z9 123 U1 4 U2 29 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JUL-AUG PY 2005 VL 2 IS 4 BP 302 EP 311 DI 10.1021/mp050019e PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA V52JD UT WOS:000203538900007 PM 16053333 ER PT J AU Kang, MS Lisk, G Hollingworth, S Baylor, SM Desai, SA AF Kang, MS Lisk, G Hollingworth, S Baylor, SM Desai, SA TI Malaria parasites are rapidly killed by dantrolene derivatives specific for the plasmodial surface anion channel SO MOLECULAR PHARMACOLOGY LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; RED-BLOOD-CELLS; CHLORIDE CHANNELS; PERMEABILITY PATHWAYS; HOST ERYTHROCYTE; INVITRO CULTURES; TRANSPORT; PERMEATION; INHIBITORS; MEMBRANE AB Dantrolene was recently identified as a novel inhibitor of the plasmodial surface anion channel (PSAC), an unusual ion channel on Plasmodium falciparum-infected human red blood cells. Because dantrolene is used clinically, has a high therapeutic index, and has desirable chemical synthetic properties, it may be a lead compound for antimalarial development. However, dantrolene derivatives would need to preferentially interact with PSAC over the sarcoplasmic reticulum (SR) Ca2+ release channel to avoid unwanted side effects from antimalarial therapy. Furthermore, dantrolene's modest affinity for PSAC (K-m of 1.2 mu M) requires improvement. In this study, we tested 164 derivatives of dantrolene to examine whether these hurdles can be surmounted. A simple screen for PSAC block defined the minimal scaffold needed and identified compounds with >= 5-fold higher affinity. Single-channel patch-clamp recordings on infected human red blood cells with two derivatives also revealed increased blocking affinity that resulted from slower unbinding from a site on the extracellular face of PSAC. We tested these derivatives in a frog skeletal muscle contractility assay and found that, in contrast to dantrolene, they had little or no effect on SR Ca2+ release. Finally, these blockers kill in vitro parasite cultures at lower concentrations than dantrolene, consistent with an essential role for PSAC. Because, as a class, these derivatives fulfil the requirements for drug leads and can be studied with simple screening technology, more extensive medicinal chemistry is warranted to explore antimalarial development. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM sdesai@niaid.nih.gov RI Desai, Sanjay/B-7110-2009 FU Intramural NIH HHS [Z01 AI000882-07]; NINDS NIH HHS [NS17620] NR 35 TC 28 Z9 30 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2005 VL 68 IS 1 BP 34 EP 40 DI 10.1124/mol.104.010553 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 935RF UT WOS:000229798700005 PM 15843600 ER PT J AU Belinsky, MG Dawson, PA Shchaveleva, I Bain, LJ Wang, RX Ling, V Chen, ZS Grinberg, A Westphal, H Klein-Szanto, A Lerro, A Kruh, GD AF Belinsky, MG Dawson, PA Shchaveleva, I Bain, LJ Wang, RX Ling, V Chen, ZS Grinberg, A Westphal, H Klein-Szanto, A Lerro, A Kruh, GD TI Analysis of the in vivo functions of Mrp3 SO MOLECULAR PHARMACOLOGY LA English DT Article ID RESISTANCE-ASSOCIATED PROTEIN-3; BILE-ACID TRANSPORTER; CONSTITUTIVE ANDROSTANE RECEPTOR; BASOLATERAL HEPATOCYTE MEMBRANE; ORGANIC SOLUTE TRANSPORTER; ATP-DEPENDENT TRANSPORT; ALPHA-OST-BETA; OBSTRUCTIVE CHOLESTASIS; P-GLYCOPROTEIN; UP-REGULATION AB Multidrug resistance protein 3 (MRP3) is an ATP-binding cassette transporter that is able to confer resistance to anticancer agents such as etoposide and to transport lipophilic anions such as bile acids and glucuronides. These capabilities, along with the induction of the MRP3 protein on hepatocyte sinusoidal membranes in cholestasis and the expression of MRP3 in enterocytes, have led to the hypotheses that MRP3 may function in the body to protect normal tissues from etoposide, to protect cholestatic hepatocytes from endobiotics, and to facilitate bile-acid reclamation from the gut. To elucidate the role of Mrp3 in these processes, the Mrp3 gene (Abcc3) was disrupted by homologous recombination. Homozygous null animals were healthy and physically indistinguishable from wild-type mice. Mrp3(-/-) mice did not exhibit enhanced lethality to etoposide phosphate, although an analysis of transfected human embryonic kidney 293 cells indicated that the potency of murine Mrp3 toward etoposide ( similar to 2.0- to 2.5-fold) is comparable with that of human MRP3. After induction of cholestasis by bile duct ligation, Mrp3(-/-) mice had 1.5-fold higher levels of liver bile acids and 3.1-fold lower levels of serum bilirubin glucuronide compared with ligated wild-type mice, whereas significant differences were not observed between the respective sham-operated mice. Bile acid excretion, pool size, and fractional turnover rates were similar in Mrp3(-/-) and wild-type mice. We conclude that Mrp3 functions as an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes, that the pump does not play a major role in the enterohepatic circulation of bile acids and that the lack of chemosensitivity is probably attributable to functional redundancy with other pumps. C1 Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA. Univ Texas, Dept Biol Sci, El Paso, TX 79968 USA. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NICHHD, NIH, Bethesda, MD 20892 USA. RP Kruh, GD (reprint author), Fox Chase Canc Ctr, Div Med Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM Gary.Kruh@fccc.edu RI Klein-Szanto, Andres/E-6218-2010 FU NCI NIH HHS [CA06927, CA73728]; NIDDK NIH HHS [R01 DK047987, DK47987] NR 49 TC 109 Z9 111 U1 1 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2005 VL 68 IS 1 BP 160 EP 168 DI 10.1124/mol.104.010587 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 935RF UT WOS:000229798700019 PM 15814571 ER PT J AU Du, DY Raaka, BM Grimberg, H Lupu-Meiri, M Oron, Y Gershengorn, MC AF Du, DY Raaka, BM Grimberg, H Lupu-Meiri, M Oron, Y Gershengorn, MC TI Carboxyl tail cysteine mutants of the thyrotropin-releasing hormone receptor type 1 exhibit constitutive signaling: Role of palmitoylation SO MOLECULAR PHARMACOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CRYSTAL-STRUCTURE; PITUITARY-CELLS; XENOPUS OOCYTES; ACTIVE MUTANT; RHODOPSIN; RESIDUES; MUTATION; CALCIUM; HELIX-8 AB We studied the role of carboxyl tail cysteine residues and their palmitoylation in constitutive signaling by the thyrotropin-releasing hormone (TRH) receptor type 1 (TRH-R1) in transfected mammalian cells and in Xenopus laevis oocytes. To study palmitoylation, we inserted a factor Xa cleavage site within the third extracellular loop of TRH-R1, added a carboxyl-terminal C9 immunotag and expressed the mutant receptor in Chinese hamster ovary cells. We identified TRH-R1-specific palmitoylation in the transmembrane helix-7/carboxyl-tail receptor fragment mainly at Cys-335 and Cys-337. In contrast to a mutant truncated at Cys-335 that was reported previously to be constitutively active, a receptor truncated at Lys-338 (K338Stop), which preserves Cys-335 and Cys-337, and C337Stop and N336Stop, which preserve Cys-335, did not exhibit increased constitutive signaling. TRH-R1 mutants substituted singly by Gly or Ser at Cys-335 or Cys-337 did not exhibit constitutive signaling. By contrast, substitution of both cysteines (C335G/ C337G or C335S/C337S) yielded TRH-R1 mutants that exhibited marked constitutive signaling in mammalian cells. In the oocyte, constitutive signaling by C335G/ C337G resulted in homologous ( of C335G/ C337G) and heterologous ( of M1 muscarinic receptor) desensitization. Because both Cys-335 and Cys-337 have to be substituted or deleted for constitutive signaling, we propose that a single palmitoylation site in the proximal carboxyl tail is sufficient to constrain TRH-R1 in an inactive conformation. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, Ramat Aviv, Israel. RP Gershengorn, MC (reprint author), NIDDKD, Clin Endocrinol Branch, NIH, 50 South Dr,Room 4134, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov NR 28 TC 3 Z9 3 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUL PY 2005 VL 68 IS 1 BP 204 EP 209 DI 10.1124/mol.105.012641 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 935RF UT WOS:000229798700023 PM 15833733 ER PT J AU Szeszko, PR Lipsky, R Mentschel, C Robinson, D Gunduz-Bruce, H Sevy, S Ashtari, M Napolitano, B Bilder, RM Kane, JM Goldman, D Malhotra, AK AF Szeszko, PR Lipsky, R Mentschel, C Robinson, D Gunduz-Bruce, H Sevy, S Ashtari, M Napolitano, B Bilder, RM Kane, JM Goldman, D Malhotra, AK TI Brain-derived neurotrophic factor val66met polymorphism and volume of the hippocampal formation SO MOLECULAR PSYCHIATRY LA English DT Article DE hippocampus; BDNF; MRI; schizophrenia; gene; polymorphism ID BDNF MESSENGER-RNA; SCHIZOPHRENIC-PATIENTS; HUMAN-MEMORY; FACTOR GENE; ASSOCIATION; EXPRESSION; NEURONS; RATS; SIZE; DIFFERENTIATION AB Magnetic resonance (MR) imaging studies have identified hippocampal structural alterations in the pathogenesis of schizophrenia. Brain-derived neurotrophic factor (BDNF) is one of the neurotrophins that is widely expressed in the hippocampal formation and has been implicated in the neurobiology of schizophrenia. Polymorphisms in the BDNF gene may therefore confer risk for schizophrenia through hippocampal pathogenesis and/or making the hippocampus more susceptible to environmental insults. In this study, we investigated whether val66met, a functional and abundant missense polymorphism in the coding region of the BDNF gene, was associated with the volume of the hippocampal formation in 19 patients with first-episode schizophrenia and 25 healthy volunteers. A total of 124 contiguous T1-weighted coronal MR images (slice thickness=1.5 mm) were acquired through the whole head using a 3D Fast SPGR IR Prep sequence on a 1.5 T GE imaging system. Volumes of the right and left hippocampal formation were measured manually by an operator blind to group status and genotype. All participants were genotyped for the BDNF val66met locus. Mixed model analyses revealed a main effect of BDNF val66met genotype such that in the combined sample of patients and healthy volunteers, val/val homozygotes (N = 27) had larger volumes of the hippocampal formation compared to val/met heterozygotes (N = 17). In separate analyses by group, however, val66met genotype accounted for a greater proportion of the variance in the volume of the hippocampal formation in patients compared to healthy volunteers. These findings implicate genetic involvement of BDNF in variation of human hippocampal volume and suggest that this effect may be greater among patients compared to healthy volunteers. C1 N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Dept Psychiat Res, Glen Oaks, NY 11004 USA. Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. NIAAA, Rockville, MD 20852 USA. Neurol Klin Bad Aibling, Bad Aibling, Germany. Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. N Shore Long Isl Jewish Hlth Syst, Dept Radiol, New Hyde Pk, NY USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Geffen Sch Med, Los Angeles, CA USA. RP Szeszko, PR (reprint author), N Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp, Dept Psychiat Res, 75-59 263rd St, Glen Oaks, NY 11004 USA. EM szeszko@lij.edu RI Szeszko, Philip/G-9336-2013; Bilder, Robert/A-8894-2008; Goldman, David/F-9772-2010; OI Bilder, Robert/0000-0001-5085-7852; Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 FU NIMH NIH HHS [MH01760, MH01990, MH60004, MH60374, MH60575] NR 48 TC 245 Z9 253 U1 1 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 2005 VL 10 IS 7 BP 631 EP 636 DI 10.1038/sj.mp.4001656 PG 6 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 940IJ UT WOS:000230137000006 PM 15768049 ER PT J AU Weickert, CS Ligons, DL Romanczyk, T Ungaro, G Hyde, TM Herman, MM Weinberger, DR Kleinman, JE AF Weickert, CS Ligons, DL Romanczyk, T Ungaro, G Hyde, TM Herman, MM Weinberger, DR Kleinman, JE TI Reductions in neurotrophin receptor mRNAs in the prefrontal cortex of patients with schizophrenia SO MOLECULAR PSYCHIATRY LA English DT Article DE BDNF; NT-3; trkB; trkC; tyrosine kinase receptor; DLPFC ID DENDRITIC SPINE DENSITY; PYRAMIDAL NEURONS; GENE-EXPRESSION; GABAERGIC NEURONS; CORTICAL-NEURONS; RAT-BRAIN; VENTRAL MESENCEPHALON; PROTECTS HIPPOCAMPAL; INHIBITORY SYNAPSES; TRUNCATED RECEPTORS AB Patients with schizophrenia have reduced neurotrophin levels in their dorsolateral prefrontal cortex (DLPFC) compared to normal unaffected individuals. The tyrosine kinase-containing receptors, trkB and trkC, mediate the growth-promoting effects of neurotrophins and respond to changes in growth factor availability. We hypothesized that trkB and/or trkC expression would be altered in the DLPFC of patients with schizophrenia. We measured mRNA encoding the tyrosine kinase domain (TK+)-containing form of trkB and measured pan trkC mRNA in schizophrenics (N = 14) and controls (N = 15) using in situ hybridization. TrkB and trkC mRNAs were detected in large and small neurons in multiple cortical layers of the human DLPFC. We found significantly diminished expression of trkB(TK+) mRNA in large neurons in multiple cortical layers of patients as compared to controls, while small neurons also showed reductions in trkB(TK+) mRNA that did not reach statistical significance. In normals, strong positive correlations were found between trkB(TK+) mRNA levels and brain-derived neurotrophic factor (BDNF) mRNA levels among various neurons, while no correlation between BDNF and trkB(TK+) was found in patients with schizophrenia. TrkC mRNA was also reduced in the DLPFC of schizophrenics in large neurons in layers II, III, V and VI and in small neurons in layer IV. Since neurons in the DLPFC integrate and communicate signals to various cortical and subcortical regions, these reductions in growth factor receptors may compromise the function and plasticity of the DLPFC in schizophrenia. C1 NIMH, Clin Brain Disorders Branch, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA. RP Weickert, CS (reprint author), 10 Ctr Dr,Bldg 10-4N312,MSC 1385, Bethesda, MD 20892 USA. EM shannowc@intra.nimh.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011 NR 74 TC 108 Z9 113 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUL PY 2005 VL 10 IS 7 BP 637 EP 650 DI 10.1038/sj.mp.4001678 PG 14 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 940IJ UT WOS:000230137000007 PM 15940304 ER PT J AU Podsakoff, GM Engel, BC Carbonaro, DA Choi, C Smogorzewska, EM Bauer, G Selander, D Csik, S Wilson, K Betts, MR Richard, AKP Nabel, GJ Bishop, K King, S Schmidt, M von Kalle, C Church, JA Kohn, DB AF Podsakoff, GM Engel, BC Carbonaro, DA Choi, C Smogorzewska, EM Bauer, G Selander, D Csik, S Wilson, K Betts, MR Richard, AKP Nabel, GJ Bishop, K King, S Schmidt, M von Kalle, C Church, JA Kohn, DB TI Selective survival of peripheral blood lymphocytes in children with HIV-1 following delivery of an anti-HIV gene to bone marrow CD34(+) cells SO MOLECULAR THERAPY LA English DT Article ID VIRUS TYPE-1 REPLICATION; HUMAN T-CELLS; HIV-1-INFECTED DONORS; PROGENITOR CELLS; THERAPY; REV; ENGRAFTMENT; TRANSDUCTION; INHIBITION; EXPRESSION AB Two HIV-1-infected children on antiretroviral therapy were enrolled into a clinical study of retroviral-mediated transfer of a gene that inhibits replication of HIV-1, targeting bone marrow CD34(+) hematopoietic stem/progenitor cells. Two retroviral vectors were used, one encoding a "humanized" dominant-negative REV protein (huM10) that is a potent inhibitor of HIV-1 replication and one encoding a nontranslated marker gene (FX) to serve as an internal control for the level of gene marking. Peripheral blood mononuclear cells (PBMC) containing the huM10 gene or FX gene were detected by quantitative PCR at frequencies of approximately 1/10,000 in both subjects for the first 1-3 months following re-infusion of the gene-transduced bone marrow, but then were at or below the limits of detection (< 1/1,000,000) at most times over 2 years. In one patient, a reappearance of PBMC containing the huM10 gene, but not the FX gene, occurred concomitant with a rise in the HIV-1 viral load during a period of nonadherence to the antiretroviral regimen. Unique clones of gene-marked PBMC were detected by LAM-PCR during the time of elevated HIV-1 levels. These findings indicate that there was a selective survival advantage for PBMC containing the huM10 gene during the time of increased HIV-1 load. C1 Univ So Calif, Div Immunol Res, BMT, Childrens Hosp Los Angeles,Keck Sch Med, Los Angeles, CA 90027 USA. Washington Univ, Sch Med, St Louis, MO 63110 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Univ Freiburg, Dept Internal Med, D-79106 Freiburg, Germany. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Kohn, DB (reprint author), Univ So Calif, Div Immunol Res, BMT, Childrens Hosp Los Angeles,Keck Sch Med, Mailstop 62,4650 Sunset Blvd, Los Angeles, CA 90027 USA. EM dkohn@chla.usc.edu RI Kohn, Donald/N-5085-2016 OI Kohn, Donald/0000-0003-1840-6087 FU NCRR NIH HHS [MO1 RR-43]; NHLBI NIH HHS [HL54850]; NIAID NIH HHS [AI36606] NR 24 TC 54 Z9 57 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUL PY 2005 VL 12 IS 1 BP 77 EP 86 DI 10.1016/j.ymthe.2005.02.024 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 942KV UT WOS:000230282200015 PM 15963923 ER PT J AU Clarimon, J Johnson, J Djaldetti, R Hernandez, D Hattori, N Sroka, H Barhom, Y Singleton, A AF Clarimon, J Johnson, J Djaldetti, R Hernandez, D Hattori, N Sroka, H Barhom, Y Singleton, A TI Mutation of the Parkin gene in a Persian family: Clinical progression over a 40-year period SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; genetics; Parkin; PARK2; clinical heterogeneity ID RECESSIVE JUVENILE PARKINSONISM; DISEASE; PREVALENCE; EUROPE AB We report oil an Israeli family originating from Iran in which 4 of 7 brothers born from a consanguineous marriage had juvenile Parkinsonism. Linkage analysis of markers covering the autosomal recessive juvenile Parkinsonism (AR-JP, PARK2. Parkin gene, OMIM #602544) gene resulted in a maximal logarithm of odds score of 2.18. A homozygous deletion that expanded from exon 4 to exon 6 was identified in all the patients. Significant clinical heterogeneity was present between siblings. (c) 2005 Movement Disorder Society. C1 NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Juntendo Univ, Sch Med, Dept Neurol, Tokyo 113, Japan. Tel Aviv Univ, Sackler Sch Med, Felsenstein Res Ctr, IL-69978 Tel Aviv, Israel. RP Clarimon, J (reprint author), NIA, Mol Genet Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A1002,MSC 3707,35 Lincoln Dr, Bethesda, MD 20892 USA. EM clarimon@mail.nih.gov RI Johnson, Janel/A-7136-2010; Singleton, Andrew/C-3010-2009; OI Clarimon, Jordi/0000-0002-6824-6942 NR 12 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2005 VL 20 IS 7 BP 887 EP 890 DI 10.1002/mds.20495 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 947OZ UT WOS:000230657000018 PM 15852366 ER PT J AU McInerney-Leo, A AF McInerney-Leo, A TI Genetic testing in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Letter ID COMMON LRRK2 MUTATION C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP McInerney-Leo, A (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM amcinern@mail.nih.gov NR 7 TC 8 Z9 8 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD JUL PY 2005 VL 20 IS 7 BP 908 EP 909 DI 10.1002/mds.20509 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 947OZ UT WOS:000230657000026 PM 15884041 ER PT J AU Torres, MS White, JF Cazares, G Bergen, M Bischoff, JF Sullivan, RE AF Torres, MS White, JF Cazares, G Bergen, M Bischoff, JF Sullivan, RE TI A new species and its phylogenetic placement in the Didymella/Phoma complex (Phaeosphaeriaceae, Pleosporales) SO MYCOTAXON LA English DT Article DE Phoma billsii; Pleosporales; taxonomy ID GENUS PHOMA; SP-NOV; MONOGRAPH AB A proposed new species, Phoma billsii sp. nov., was obtained from soil samples from Hawaii. The features of this new species are described and it is distinguished from other species to which it is similar. Large subunit 28S rDNA sequences are employed to place this new species phylogenetically. Phoma billsii is placed in a Didymella/Phoma complex in family Phaeosphaeriaceae of the Pleosporales. Sequence similarity of ITS I rDNA was used to evaluate distinctness from similar species in Didymella and Phoma. A phylogenetic approach for classification of phomoid fungi is advocated. C1 Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Kean Univ, Ctr Sci & Technol, Union, NJ 07083 USA. RP Torres, MS (reprint author), Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. EM Jwhite@aesop.rutgers.edu RI White, James/C-2280-2009 NR 27 TC 8 Z9 8 U1 0 U2 3 PU MYCOTAXON LTD PI ITHACA PA PO BOX 264, ITHACA, NY 14851-0264 USA SN 0093-4666 J9 MYCOTAXON JI Mycotaxon PD JUL-SEP PY 2005 VL 93 BP 297 EP 308 PG 12 WC Mycology SC Mycology GA 981YA UT WOS:000233122700033 ER PT J AU Torres, MS Bergen, M Singh, S Bischoff, J Sullivan, RF White, JF AF Torres, MS Bergen, M Singh, S Bischoff, J Sullivan, RF White, JF TI Plenodomus morganjonesii sp nov and a discussion of the genus Plenodomus SO MYCOTAXON LA English DT Article DE Phoma; Pleosporales; scleroplectenchyma; taxonomy ID PHOMA AB Plenodomus morganjonesii was obtained from partially degraded leaves from New Jersey. It is described as a new species based on morphological, cultural and molecular characters that differ from other species to which it is similar. Analysis of the large subunit 28S rDNA sequences suggested that this new species is related to members of the family Leptosphaeriaceae in the Pleosporales. Separation of Plenodomus from Phoma is advocated in order to produce monophyletic genera of coelomycetes. C1 Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Kean Univ, Ctr Sci & Technol, Union, NJ 07083 USA. RP Torres, MS (reprint author), Rutgers State Univ, Dept Plant Biol & Pathol, New Brunswick, NJ 08901 USA. EM Jwhite@aesop.rutgers.edu RI White, James/C-2280-2009 NR 29 TC 5 Z9 6 U1 0 U2 1 PU MYCOTAXON LTD PI ITHACA PA PO BOX 264, ITHACA, NY 14851-0264 USA SN 0093-4666 J9 MYCOTAXON JI Mycotaxon PD JUL-SEP PY 2005 VL 93 BP 333 EP 343 PG 11 WC Mycology SC Mycology GA 981YA UT WOS:000233122700039 ER PT J AU Silver, J Ou, W AF Silver, J Ou, W TI Photoactivation of quantum dot fluorescence following endocytosis SO NANO LETTERS LA English DT Article ID LIVE CELLS; CDSE; NANOCRYSTALS; BLINKING; PROTEIN; CANCER AB We studied the fluorescence of quantum dots in cells. Coating quantum dots with cationic peptides caused them to be endocytosed and transported to lysosomes. After overnight incubation, their fluorescence apparently dimmed but became markedly "photoactivatable", increasing more than 3-fold within minutes on exposure to bright light, and decaying over hours in the dark. Photoactivation was greater in the presence of water than ethanol, and UV illumination compensated for lack of water during photoactivation. Dimming and photoactivation could affect the use of quantum dots as quantitative probes in vivo and lead to new uses, such as tracking molecular movement. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 338, Bethesda, MD 20892 USA. EM jsilver@nih.gov NR 20 TC 77 Z9 78 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1530-6984 J9 NANO LETT JI Nano Lett. PD JUL PY 2005 VL 5 IS 7 BP 1445 EP 1449 DI 10.1021/nl050808n PG 5 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied; Physics, Condensed Matter SC Chemistry; Science & Technology - Other Topics; Materials Science; Physics GA 946KP UT WOS:000230571300047 PM 16178255 ER PT J AU Andrews, PW Benvenisty, N McKay, R Pera, MF Rossant, J Semb, H Stacey, GN AF Andrews, PW Benvenisty, N McKay, R Pera, MF Rossant, J Semb, H Stacey, GN CA Steering Comm Int Stem Cell Initia TI The International Stem Cell initiative: toward benchmarks for human embryonic stem cell research SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID GENE-EXPRESSION; LINES; DIFFERENTIATION C1 Monash Univ, Monash Inst Med Res, Clayton, Vic 3800, Australia. Australian Stem Cell Ctr, Clayton, Vic 3800, Australia. Univ Sheffield, Dept Biomed Sci, Sheffield S10 2TN, S Yorkshire, England. Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Lund Univ, Dept Expt Med Sci, Sect Dev Biol, SE-22184 Lund, Sweden. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. RP Pera, MF (reprint author), Monash Univ, Monash Inst Med Res, Clayton, Vic 3800, Australia. EM p.w.andrews@sheffield.ac.uk; martin.pera@med.monash.edu.au RI PERA, MARTIN/A-9812-2012 OI PERA, MARTIN/0000-0001-6239-0428 NR 10 TC 61 Z9 64 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUL PY 2005 VL 23 IS 7 BP 795 EP 797 DI 10.1038/nbt0705-798 PG 3 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 944KT UT WOS:000230427700018 PM 16003358 ER PT J AU Difilippantonio, S Celeste, A Fernandez-Capetillo, O Chen, HT San Martin, BR Van Laethem, F Yang, YP Petukhova, GV Eckhaus, M Feigenbaum, L Manova, K Kruhlak, M Camerini-Otero, RD Sharan, S Nussenzweig, M Nussenzweig, A AF Difilippantonio, S Celeste, A Fernandez-Capetillo, O Chen, HT San Martin, BR Van Laethem, F Yang, YP Petukhova, GV Eckhaus, M Feigenbaum, L Manova, K Kruhlak, M Camerini-Otero, RD Sharan, S Nussenzweig, M Nussenzweig, A TI Role of Nbs1 in the activation of the Atm kinase revealed in humanized mouse models SO NATURE CELL BIOLOGY LA English DT Article ID NIJMEGEN-BREAKAGE-SYNDROME; DOUBLE-STRAND BREAKS; CLASS-SWITCH RECOMBINATION; FORKHEAD-ASSOCIATED DOMAIN; S-PHASE CHECKPOINT; DNA-DAMAGE; MRE11 COMPLEX; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; HISTONE H2AX AB Nijmegen breakage syndrome ( NBS) is a chromosomal fragility disorder that shares clinical and cellular features with ataxia telangiectasia. Here we demonstrate that Nbs1- null B cells are defective in the activation of ataxia- telangiectasia- mutated ( Atm) in response to ionizing radiation, whereas ataxia- telangiectasia- and Rad3- related ( Atr)- dependent signalling and Atm activation in response to ultraviolet light, inhibitors of DNA replication, or hypotonic stress are intact. Expression of the main human NBS allele rescues the lethality of Nbs1(-/-) mice, but leads to immunodeficiency, cancer predisposition, a defect in meiotic progression in females and cell- cycle checkpoint defects that are associated with a partial reduction in Atm activity. The Mre11 interaction domain of Nbs1 is essential for viability, whereas the Forkhead- associated ( FHA) domain is required for T- cell and oocyte development and efficient DNA damage signalling. Reconstitution of Nbs1 knockout mice with various mutant isoforms demonstrates the biological impact of impaired Nbs1 function at the cellular and organismal level. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Off Director, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Mem Sloan Kettering Canc Ctr, Mol Cytol Core Facil, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM andre_nussenzweig@nih.gov RI Fernandez-Capetillo, Oscar/H-3508-2015; Reina-San-Martin, Bernardo/I-9484-2016 OI Fernandez-Capetillo, Oscar/0000-0002-2690-6885; Reina-San-Martin, Bernardo/0000-0003-2083-6166 NR 52 TC 166 Z9 171 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUL PY 2005 VL 7 IS 7 BP 675 EP U56 DI 10.1038/ncb1270 PG 16 WC Cell Biology SC Cell Biology GA 941BX UT WOS:000230190800011 PM 15965469 ER PT J AU Fine, HA AF Fine, HA TI Radiotherapy plus adjuvant temozolomide for the treatment of glioblastoma - a paradigm shift SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE astrocytoma; glioblastoma; radiotherapy; survival; temozolomide ID ADULTS C1 NCI, NINDS, NIH, Neurooncol Branch, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NCI, NINDS, NIH, Neurooncol Branch, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD JUL PY 2005 VL 2 IS 7 BP 334 EP 335 DI 10.1038/ncponc0201 PG 2 WC Oncology SC Oncology GA 962QE UT WOS:000231746500003 PM 16075787 ER PT J AU Vogt, G Chapgier, A Yang, K Chuzhanova, N Feinberg, J Fieschi, C Boisson-Dupuis, S Alcais, A Filipe-Santos, O Bustamante, J de Beaucoudrey, L Al-Mohsen, I Al-Hajjar, S Al-Ghonaium, A Adimi, P Mirsaeidi, M Khalilzadeh, S Rosenzweig, S Martin, OD Bauer, TR Puck, JM Ochs, HD Furthner, D Engelhorn, C Mansouri, D Holland, SM Schreiber, RD Abel, L Cooper, DN Soudais, C Casanova, JL AF Vogt, G Chapgier, A Yang, K Chuzhanova, N Feinberg, J Fieschi, C Boisson-Dupuis, S Alcais, A Filipe-Santos, O Bustamante, J de Beaucoudrey, L Al-Mohsen, I Al-Hajjar, S Al-Ghonaium, A Adimi, P Mirsaeidi, M Khalilzadeh, S Rosenzweig, S Martin, OD Bauer, TR Puck, JM Ochs, HD Furthner, D Engelhorn, C Mansouri, D Holland, SM Schreiber, RD Abel, L Cooper, DN Soudais, C Casanova, JL TI Gains of glycosylation comprise an unexpectedly large group of pathogenic mutations SO NATURE GENETICS LA English DT Article ID INTERFERON-GAMMA-RECEPTOR; BACILLE CALMETTE-GUERIN; EXTRA N-GLYCOSYLATION; FIBRIN GEL FORMATION; HYPER-IGM SYNDROME; MYCOBACTERIAL INFECTION; FUNCTIONAL-CHARACTERIZATION; 1 DEFICIENCY; CD40 LIGAND; IFN-GAMMA AB Mutations involving gains of glycosylation have been considered rare, and the pathogenic role of the new carbohydrate chains has never been formally established. We identified three children with mendelian susceptibility to mycobacterial disease who were homozygous with respect to a missense mutation in IFNGR2 creating a new N- glycosylation site in the IFN gamma R2 chain. The resulting additional carbohydrate moiety was both necessary and sufficient to abolish the cellular response to IFN gamma. We then searched the Human Gene Mutation Database for potential gain- of- N- glycosylation missense mutations; of 10,047 mutations in 577 genes encoding proteins trafficked through the secretory pathway, we identified 142 candidate mutations ( similar to 1.4%) in 77 genes ( similar to 13.3%). Six mutant proteins bore new N- linked carbohydrate moieties. Thus, an unexpectedly high proportion of mutations that cause human genetic disease might lead to the creation of new N- glycosylation sites. Their pathogenic effects may be a direct consequence of the addition of N- linked carbohydrate. C1 Univ Paris 05, Necker Med Sch, INSERM, U550,Lab Human Genet Infect Dis, F-75015 Paris, France. Shanghai Med Univ 2, Ruijin Hosp, French Chinese Lab Genom & Life Sci, Shanghai, Peoples R China. Univ Cardiff Wales, Biostat & Bioinformat Unit, Cardiff CF14 4XN, Wales. Univ Cardiff Wales, Inst Med Genet, Cardiff CF14 4XN, Wales. Hop St Louis, Dept Immunopathol, F-75010 Paris, France. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Pediat Infect Dis Unit, Riyadh 11211, Saudi Arabia. King Faisal Specialist Hosp & Res Ctr, Dept Pediat, Immunol Unit, Riyadh 11211, Saudi Arabia. Shaheed Beheshti Univ Med Sci, Natl Res Inst TB & Lung Dis, Tehran 19556, Iran. NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Hosp Santa Creu & Sant Pau, Serv Immunol, Barcelona, Spain. NCI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Pediat, Seattle, WA 98109 USA. Klinikum Wels, Dept Pediat, A-4600 Wels, Austria. Hosp Sick Children, Dept Pediat, D-80337 Munich, Germany. Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. Hop Necker Enfants Malad, Pediat Immunol & Hematol Unit, F-75015 Paris, France. RP Casanova, JL (reprint author), Univ Paris 05, Necker Med Sch, INSERM, U550,Lab Human Genet Infect Dis, 156 Rue Vaugirard, F-75015 Paris, France. EM casanova@necker.fr RI Mirsaeidi, Mehdi/A-6448-2008; Mirsaeidi, Mehdi/D-8164-2011; Cooper, David/H-4384-2011; Schreiber, Robert/A-1276-2013; Vogt, Guillaume/L-6046-2015; soudais, claire/F-9756-2016; Calle-Martin, Oscar de la/Q-3353-2016; OI Cooper, David/0000-0002-8943-8484; Schreiber, Robert/0000-0001-6311-0432; Vogt, Guillaume/0000-0001-8192-1247; soudais, claire/0000-0002-4387-6649; Calle-Martin, Oscar de la/0000-0001-9717-053X; khalilzadeh, soheila/0000-0002-3365-2449; Chuzhanova, Nadia/0000-0002-4655-3618; Mirsaeidi, Mehdi/0000-0001-5298-8442; mansouri, davood/0000-0002-0564-8282 NR 50 TC 117 Z9 122 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUL PY 2005 VL 37 IS 7 BP 692 EP 700 DI 10.1038/ng1581 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 941EA UT WOS:000230196400015 PM 15924140 ER PT J AU Johansson, C Kelsall, BL AF Johansson, C Kelsall, BL TI Affecting the effectors: a kick in the gut? SO NATURE IMMUNOLOGY LA English DT Editorial Material ID RESPONSES IN-VIVO; T-CELL RESPONSES; COSTIMULATION; TOLERANCE C1 NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Johansson, C (reprint author), NIAID, Mucosal Immunobiol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM cjohansson@niaid.nih.gov; bkelsall@niaid.nih.gov NR 12 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD JUL PY 2005 VL 6 IS 7 BP 644 EP 646 DI 10.1038/ni0705-644 PG 4 WC Immunology SC Immunology GA 938BS UT WOS:000229975500005 PM 15970934 ER PT J AU Horig, H Marincola, E Marincola, FM AF Horig, H Marincola, E Marincola, FM TI Obstacles and opportunities in translational research SO NATURE MEDICINE LA English DT Editorial Material ID TUMOR-MARKERS; END-POINTS; CANCER; PRINCIPLES; DESIGN AB Traditional boundaries among basic research, clinical research and patient- oriented research are yielding to a single, continuous, bidirectional spectrum commonly termed 'translational research' or 'translational medicine.' These encompass ( i) the definition of guidelines for drug development or for the identification and validation of clinically relevant biomarkers; ( ii) experimental nonhuman and nonclinical studies conducted with the intent of developing principles for the discovery of new therapeutic strategies; ( iii) clinical investigations that provide a biological foundation for the development of improved therapies; ( iv) any clinical trial initiated in accordance with the above goals; and ( v) basic science studies that define the biological effects of therapeutics in humans. Although these goals are essentially no different from those of traditional academic clinical research, translational research emphasizes strategies to expedite their successful implementation. Unfortunately, several barriers that delay this process need to be surmounted to make translational research more than just an interesting concept. C1 NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Columbia Univ, Ctr Med, Dept Surg, Div Surg Sci, New York, NY 10032 USA. Sci Serv, Washington, DC 20036 USA. RP Marincola, FM (reprint author), NIH, Immunogenet Sect, Dept Transfus Med, Ctr Clin, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM fmarincola@cc.nih.gov NR 25 TC 51 Z9 55 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 705 EP 708 DI 10.1038/nm0705-705 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200013 PM 16015353 ER PT J AU Harlan, DM von Herrath, M AF Harlan, DM von Herrath, M TI Immune intervention with anti-CD3 in diabetes SO NATURE MEDICINE LA English DT Editorial Material ID MONOCLONAL-ANTIBODY; T-CELLS; ONSET; TRANSPLANTATION; AUTOIMMUNITY; REMISSION; MELLITUS; MICE AB Autoimmune processes that destroy insulin-producing cells in the pancreas cause type 1 diabetes. To prevent the disease, autoreactive immune cells need to be suppressed or eliminated without deleterious side effects. Results from a phase 2 clinical trial take steps in this direction. C1 NIDDK, Islet & Autoimmun Branch, NIH, Bethesda, MD 20812 USA. La Jolla Inst Allergy & Immunol, Immune Regulat Lab, San Diego, CA 92121 USA. RP Harlan, DM (reprint author), NIDDK, Islet & Autoimmun Branch, NIH, Bethesda, MD 20812 USA. EM davidmh@mail.nih.gov; matthias@liai.org NR 17 TC 9 Z9 9 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 716 EP 718 DI 10.1038/nm0705-716 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200018 PM 16015359 ER PT J AU Misteli, T Scaffidi, P AF Misteli, T Scaffidi, P TI Genome instability in progeria: when repair gets old SO NATURE MEDICINE LA English DT Editorial Material ID LAMIN-A; NUCLEAR ARCHITECTURE; ENVELOPE; ZMPSTE24; DEFECTS; DISEASE AB Genome instability and DNA repair defects have been discovered in the premature aging disease Hutchinson-Gilford progeria syndrome. These findings provide the first hint of a molecular mechanism for a group of human conditions caused by defects in the nuclear structural protein lamin A (pages 780 - 785). C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 11 TC 22 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 718 EP 719 DI 10.1038/nm0705-718 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200019 PM 16015360 ER PT J AU Edghill-Smith, Y Golding, H Manischewitz, J King, LR Scott, D Bray, M Nalca, A Hooper, JW Whitehouse, CA Schmitz, JE Reimann, KA Franchini, G AF Edghill-Smith, Y Golding, H Manischewitz, J King, LR Scott, D Bray, M Nalca, A Hooper, JW Whitehouse, CA Schmitz, JE Reimann, KA Franchini, G TI Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS; MONOCLONAL-ANTIBODY; CYNOMOLGUS MONKEYS; NONHUMAN-PRIMATES; LETHAL MONKEYPOX; ENVELOPE; GENE; CHALLENGE; EXPRESSION; INFECTION AB Vaccination with live vaccinia virus affords long- lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia- specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody- mediated depletion of B cells, but not CD4(+) or CD8(+) T cells, abrogated vaccine- induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long- lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax). C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA. So Res Inst, Frederick, MD 21701 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Div Viral Pathogenesis, Boston, MA 02215 USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Hooper, Jay/0000-0002-4475-0415 FU NCRR NIH HHS [R24 RR016001, RR016001]; NIAID NIH HHS [AI040101] NR 35 TC 182 Z9 182 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 740 EP 747 DI 10.1038/nm1261 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200030 PM 15951823 ER PT J AU Jones, SM Feldmann, H Stroher, U Geisbert, JB Fernando, L Grolla, A Klenk, HD Sullivan, NJ Volchkov, VE Fritz, EA Daddario, KM Hensley, LE Jahrling, PB Geisbert, TW AF Jones, SM Feldmann, H Stroher, U Geisbert, JB Fernando, L Grolla, A Klenk, HD Sullivan, NJ Volchkov, VE Fritz, EA Daddario, KM Hensley, LE Jahrling, PB Geisbert, TW TI Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses SO NATURE MEDICINE LA English DT Article ID VESICULAR STOMATITIS VIRUSES; HEMORRHAGIC-FEVER; GLYCOPROTEINS; VECTORS; INFECTIONS; CHILDREN; DISEASE AB Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein. A single intramuscular injection of the EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges. Notably, vaccine vector shedding was not detectable in the monkeys and none of the animals developed fever or other symptoms of illness associated with vaccination. The EBOV vaccine induced humoral and apparent cellular immune responses in all vaccinated monkeys, whereas the MARV vaccine induced a stronger humoral than cellular immune response. No evidence of EBOV or MARV replication was detected in any of the protected animals after challenge. Our data suggest that these vaccine candidates are safe and highly efficacious in a relevant animal model. C1 Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, Winnipeg, MB R3E 3R2, Canada. Univ Manitoba, Dept Immunol, Winnipeg, MB R3E 3R2, Canada. Univ Manitoba, Dept Med Microbiol, Winnipeg, MB R3E 3R2, Canada. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Univ Marburg, Inst Virol, D-35037 Marburg, Germany. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD USA. Univ Lyon 1, INSERM, U412, Filovirus Lab, F-69007 Lyon, France. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Feldmann, H (reprint author), Publ Hlth Agcy Canada, Special Pathogens Program, Natl Microbiol Lab, 1015 Arlington St, Winnipeg, MB R3E 3R2, Canada. EM Heinz_Feldmann@hc-sc.gc.ca RI Volchkov, Viktor/M-7846-2014 OI Volchkov, Viktor/0000-0001-7896-8706 NR 27 TC 293 Z9 313 U1 2 U2 57 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 786 EP 790 DI 10.1038/nm1258 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200036 PM 15937495 ER PT J AU Wakita, T Pietschmann, T Kato, T Date, T Miyamoto, M Zhao, ZJ Murthy, K Habermann, A Krausslich, HG Mizokami, M Bartenschlager, R Liang, TJ AF Wakita, T Pietschmann, T Kato, T Date, T Miyamoto, M Zhao, ZJ Murthy, K Habermann, A Krausslich, HG Mizokami, M Bartenschlager, R Liang, TJ TI Production of infectious hepatitis C virus in tissue culture from a cloned viral genome SO NATURE MEDICINE LA English DT Article ID NON-B HEPATITIS; EFFICIENT REPLICATION; SUBGENOMIC REPLICON; GENOTYPE 2A; NON-A; ENVELOPE PROTEIN; MOLECULAR CLONE; CDNA-CLONE; CHIMPANZEES; CELLS AB Hepatitis C virus (HCV) infection causes chronic liver diseases and is a global public health problem. Detailed analyses of HCV have been hampered by the lack of viral culture systems. Subgenomic replicons of the JFH1 genotype 2a strain cloned from an individual with fulminant hepatitis replicate efficiently in cell culture. Here we show that the JFH1 genome replicates efficiently and supports secretion of viral particles after transfection into a human hepatoma cell line (Huh7). Particles have a density of about 1.15 - 1.17 g/ml and a spherical morphology with an average diameter of about 55 nm. Secreted virus is infectious for Huh7 cells and infectivity can be neutralized by CD81-specific antibodies and by immunoglobulins from chronically infected individuals. The cell culture - generated HCV is infectious for chimpanzee. This system provides a powerful tool for studying the viral life cycle and developing antiviral strategies. C1 Tokyo Metropolitan Inst Neurosci, Dept Microbiol, Tokyo 1838526, Japan. Univ Heidelberg, Dept Mol Virol, D-69120 Heidelberg, Germany. Nagoya City Univ, Grad Sch Med Sci, Dept Clin Mol Informat Med, Nagoya, Aichi 4678601, Japan. NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. SW Fdn Biomed Res, San Antonio, TX 78227 USA. Univ Heidelberg, Dept Virol, D-69120 Heidelberg, Germany. RP Wakita, T (reprint author), Tokyo Metropolitan Inst Neurosci, Dept Microbiol, Tokyo 1838526, Japan. EM wakita@tmin.ac.jp RI Pietschmann, Thomas/E-9241-2015; Bartenschlager, Ralf/L-2582-2015 OI Pietschmann, Thomas/0000-0001-5138-6239; FU Intramural NIH HHS [Z01 DK054504-11, Z99 DK999999]; NHLBI NIH HHS [N01-HB-27091, N01HB27091] NR 29 TC 1853 Z9 1959 U1 7 U2 120 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2005 VL 11 IS 7 BP 791 EP 796 DI 10.1038/nm1268 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 942TB UT WOS:000230304200037 PM 15951748 ER PT J AU Goldman, D Oroszi, G Ducci, F AF Goldman, D Oroszi, G Ducci, F TI The genetics of addictions: Uncovering the genes SO NATURE REVIEWS GENETICS LA English DT Review ID POPULATION-BASED SAMPLE; SUBSTANCE USE DISORDERS; NATIONAL EPIDEMIOLOGIC SURVEY; ENVIRONMENTAL RISK-FACTORS; 5-HT1B RECEPTOR GENE; TRANSPORTER PROMOTER POLYMORPHISM; O-METHYLTRANSFERASE COMT; QUANTITATIVE TRAIT LOCI; TWINS REARED APART; ALCOHOL DEPENDENCE AB The addictions are common chronic psychiatric diseases that today are prevented and treated using relatively untargeted and only partially effective methods. The addictions are moderately to highly heritable, which is paradoxical because these disorders require use; a choice that is itself modulated by both genes and environment. The addictions are interrelated and related to other psychiatric diseases by common neurobiological pathways, including those that modulate reward, behavioural control and the anxiety or stress response. Our future understanding of addictions will be enhanced by the identification of genes that have a role in altered substance-specific vulnerabilities such as variation in drug metabolism or drug receptors and a role in shared vulnerabilities such as variation in reward or stress resiliency. C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. EM dgneuro@box-d.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 144 TC 448 Z9 460 U1 17 U2 97 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD JUL PY 2005 VL 6 IS 7 BP 521 EP 532 DI 10.1038/nrg1635 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 941WN UT WOS:000230245000010 PM 15995696 ER PT J AU Butler, M Ruder, A Carreon, T Waters, M Yeager, M Welch, R Chanock, S Schulte, P AF Butler, M Ruder, A Carreon, T Waters, M Yeager, M Welch, R Chanock, S Schulte, P TI Polymorphisms in DNA repair genes and susceptibility to primary intracranial brain gliomas SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 NIOSH, Cincinnati, OH 45226 USA. Natl Canc Inst, Gaithersburg, MD USA. RI Carreon, Tania/A-6548-2008; Waters, Martha/B-7441-2011; Ruder, Avima/I-4155-2012 OI Ruder, Avima/0000-0003-0419-6664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 19 BP 287 EP 287 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900025 ER PT J AU Walker, D Stiller, C Ries, L Bleyer, A Bendel, A AF Walker, D Stiller, C Ries, L Bleyer, A Bendel, A TI Age-related patterns in CNS tumor incidence with a focus on the adolescent and young adult population SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Univ Nottingham, Childrens Brain Tumor Res Ctr, Nottingham NG7 2RD, England. Childhood Canc Res Grp, Oxford, England. NCI, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Childrens Hosp & Clin, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 91 BP 305 EP 305 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900096 ER PT J AU Raizer, J Abrey, L Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M AF Raizer, J Abrey, L Wen, P Cloughesy, T Robins, IA Fine, HA Lieberman, F Puduvalli, VK Fink, KL Prados, M TI A phase I trial of OSI-774 (tarceva) in patients (pts) with recurrent malignant gliomas (MG) on enzyme inducing anti-convulsants: A North American Brain Tumor Consortium Trial SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. NCI, NIH, Neuro Oncol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 154 BP 320 EP 321 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900158 ER PT J AU Hendricks, W Coons, S Scheck, A Ramsey, KE Preul, M AF Hendricks, W Coons, S Scheck, A Ramsey, KE Preul, M TI Immunohistochemical screening based on gene expression profiles predictive of meningioma recurrence SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Barrow Neurol Inst, Phoenix, AZ 85013 USA. NINDS & NIMH Microarray Consortium, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 205 BP 333 EP 333 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900209 ER PT J AU Jeyapalan, S Pasternack, M Knipe, D Hochberg, FH Reilly, K AF Jeyapalan, S Pasternack, M Knipe, D Hochberg, FH Reilly, K TI Immune rejection of gliomas in a murine model SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 2nd Quadrennial Meeting of the World-Federation-of-Neuro-Oncology/6th Meeting of the European-Association-for-Neur-Oncology CY MAY 05-08, 2005 CL Edinburgh, SCOTLAND SP World Federat Neuro Oncol, European Assoc Neuro Oncol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NCI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2005 VL 7 IS 3 MA 354 BP 372 EP 372 PG 1 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 944XH UT WOS:000230463900354 ER PT J AU Cherubini, A Martin, A Andres-Lacueva, C Di Iorio, A Lamponi, M Mecocci, P Bartali, B Corsi, A Senin, U Ferrucci, L AF Cherubini, A Martin, A Andres-Lacueva, C Di Iorio, A Lamponi, M Mecocci, P Bartali, B Corsi, A Senin, U Ferrucci, L TI Vitamin E levels, cognitive impairment and dementia in older persons: the InCHIANTI study SO NEUROBIOLOGY OF AGING LA English DT Article DE vitamin E; antioxidant; cognitive impairment; dementia elderly; epidemiological study ID OXIDATIVE STRESS; ALZHEIMERS-DISEASE; ALPHA-TOCOPHEROL; NEURODEGENERATIVE DISEASES; DIETARY-INTAKE; ANTIOXIDANTS; PLASMA; HEALTH; TISSUE; SAMPLE AB There is conflicting evidence that antioxidants contribute to maintaining cognitive function in elderly subjects. We investigated whether vitamin E plasma levels are related to the presence of dementia and cognitive impairment in a population-based cohort study conducted in Italy. A total of 1033 participants aged at least 65 years received clinical and neuropsychological examinations, donated blood for vitamin E analysis and had their diets assessed. Participants with plasma vitamin E levels in the bottom tertile had a significantly higher probability of being demented (OR 2.6, 95% CI 1.0-7.1) and also of suffering from cognitive impairment (OR 2.2, 95% CI 1.2-4.2) compared to those in the highest vitamin E tertile after adjustment for age, gender, education, lipid levels, energy intake, vitamin E intake, and smoking. This study supports the notion that higher vitamin E plasma levels might provide significant protection against cognitive impairment and dementia in elderly subjects. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Perugia, Sch Med, Inst Gerontol & Geriatr, Dept Clin & Expt Med,Policlin Monteluce, I-06122 Perugia, Italy. Tufts Univ, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Barcelona, Dept Nutr & Food Sci, CeRTA, Barcelona, Spain. Univ G DAnnunzio, Dept Med & Aging, Lab Clin Epidemiol, Geriatr Unit, Chieti, Italy. INRCA, Lab Clin Epidemiol, Florence, Italy. NIA, NIH, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RP Cherubini, A (reprint author), Univ Perugia, Sch Med, Inst Gerontol & Geriatr, Dept Clin & Expt Med,Policlin Monteluce, Via Brunamonti,Padiglione E, I-06122 Perugia, Italy. EM acherub@unipg.it RI Andres-Lacueva, Cristina/J-3377-2012; OI Andres-Lacueva, Cristina/0000-0002-8494-4978; Cherubini, Antonio/0000-0003-0261-9897 NR 59 TC 54 Z9 54 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2005 VL 26 IS 7 BP 987 EP 994 DI 10.1016/j.neurobiolaging.2004.09.002 PG 8 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 908WN UT WOS:000227821000001 PM 15748776 ER PT J AU Mattison, JA Black, A Huck, J Moscrip, T Handy, A Tilmont, E Roth, GS Lane, MA Ingram, DK AF Mattison, JA Black, A Huck, J Moscrip, T Handy, A Tilmont, E Roth, GS Lane, MA Ingram, DK TI Age-related decline in caloric intake and motivation for food in rhesus monkeys SO NEUROBIOLOGY OF AGING LA English DT Article DE hunger; appetite; anorexia; metabolism; albumin; globulin; leptin ID TERM DIETARY RESTRICTION; BODY-COMPOSITION; MACACA-MULATTA; LEPTIN LEVELS; SERUM LEPTIN; ELDERLY POPULATION; SQUIRREL-MONKEYS; SEX-DIFFERENCES; ENERGY-BALANCE; PLASMA LEPTIN AB Human studies have documented age-related declines in caloric intake that are pronounced at advanced ages. We examined caloric intake from a longitudinal study of aging in 60 male and 60 female rhesus monkeys (Macaca mulatta) collected for up to 10 years. Monkeys were provided a standardized, nutritionally fortified diet during two daily meals, and intake was measured quarterly. About half of the monkeys were on a regimen of caloric restriction (CR) representing about a 30% reduction in caloric intake compared to controls (CON) of comparable age and body weight. CR was applied to determine if this nutritional intervention retards the rate of aging in monkeys similar to observations in other mammalian studies. Following reproductive maturity at 6 years of age, there was a consistent age-related decline in caloric intake in these monkeys. Although males had higher intake than females, and CON had higher intake compared to CR, the sex and diet differences converged at older ages (> 20 years); thus, older CR monkeys were no longer consuming 30% less than the CON. When adjusted for body weight. an age-related decline in caloric intake was still evident; however, females had higher intake compared to males while CR monkeys still consumed less food, and again differences converged at older ages. Motivation for food was assessed in 65 of the monkeys following at least 8 years in their respective diet groups. Using an apparatus attached to the home cage, following an overnight fast, monkeys were trained to reach out of their cage to retrieve a biscuit of their diet by pushing open a clear plastic door on the apparatus. The door was then locked, and thus the biscuit was irretrievable. The time spent trying to retrieve the biscuit was recorded as a measure of motivation for food. We observed an a.-e-related decline in this measure, but found no consistent differences in retrieval time between CR and CON groups of comparable age and time on diet. The results demonstrate an age-related decline in food intake and motivation for food in rhesus monkeys paralleling findings in humans; however, we found no evidence that monkeys on a long-term CR regimen were more motivated for food compared to CON. Examining the relationship of selected blood proteins to food intake following 7-11 years on the study, we found a negative con-elation between globulin and intake among males and females after accounting for differences in age. In addition, a positive correlation was observed between leptin and intake in males. Published by Elsevier Inc. C1 NIA, Gerontol Res Ctr, NIH, Lab Expt Gerontol, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Charles River Labs, Bethesda, MD 20892 USA. RP Ingram, DK (reprint author), NIA, Gerontol Res Ctr, NIH, Lab Expt Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM doni@vax.grc.nia.nih.gov RI Biguzzi, Felipe/E-4724-2015 NR 61 TC 25 Z9 27 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD JUL PY 2005 VL 26 IS 7 BP 1117 EP 1127 DI 10.1016/neurobiolaging.2004.09.013 PG 11 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 908WN UT WOS:000227821000017 PM 15748792 ER PT J AU Rohde, GK Barnett, AS Basser, PJ Pierpaoli, C AF Rohde, GK Barnett, AS Basser, PJ Pierpaoli, C TI Estimating intensity variance due to noise in registered images: Applications to diffusion tensor MRI SO NEUROIMAGE LA English DT Article DE image registration; interpolation; noise; variance; parameter estimation ID ECHO-PLANAR IMAGES; FMRI TIME-SERIES; HUMAN BRAIN; INTERPOLATION; REGISTRATION; DISTORTION; COEFFICIENT; UNCERTAINTY; ARTIFACTS; FEATURES AB Image registration techniques which require image interpolation are widely used in neuroimaging research. We show that signal variance in interpolated images differs significantly from the signal variance of the original images in native space. We describe a simple approach to compute the signal variance in registered images based on the signal variance and covariance of the original images, the spatial transformations computed by the registration procedure, and the interpolation or approximation kernel chosen. The method is general and could handle various sources of signal variability, such as thermal noise and physiological noise, provided that their effects can be assessed in the original images. Our approach is applied to diffusion tensor (DT) MRI data, assuming only thermal noise as the source of variability in the data. We show that incorrect noise variance estimates in registered diffusion-weighted images can affect DT parameters, as well as indices of goodness of fit such as chi-square maps. In addition to DT-MRI, we believe that this methodology would be useful any time parameter extraction methods are applied to registered or interpolated data, such as in relaxometry and functional MRI studies. (c) 2005 Elsevier Inc. All rights reserved. C1 NICHD, STBB, LIMB, NIH, Bethesda, MD 20892 USA. Univ Maryland, Appl Math & Sci Computac Program, College Pk, MD 20742 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Rohde, GK (reprint author), NICHD, STBB, LIMB, NIH, Bldg 13,Room 3w16,13 S Dr, Bethesda, MD 20892 USA. EM rohdeg@math.umd.edu RI Pierpaoli, Carlo/E-1672-2011; Basser, Peter/H-5477-2011 NR 46 TC 26 Z9 27 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUL 1 PY 2005 VL 26 IS 3 BP 673 EP 684 DI 10.1016/j.neuroimage.2005.02.023 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 941JM UT WOS:000230211100003 PM 15955477 ER PT J AU Gould, TD Manji, HK AF Gould, TD Manji, HK TI Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE manic-depressive illness; psychopharmacology; mania; depression; mood stabilizer; antidepressant ID FORCED SWIM TEST; EMERGING EXPERIMENTAL THERAPEUTICS; SINGLE NUCLEOTIDE POLYMORPHISM; IN-VIVO EVIDENCE; BIPOLAR DISORDER; PROTEIN-KINASE; MOOD STABILIZERS; SIGNALING PATHWAY; RAT HIPPOCAMPUS; BETA-CATENIN AB Despite many decades of clinical use, the therapeutic target of lithium remains uncertain. It is recognized that therapeutic concentrations of lithium, through competition with the similarly sized magnesium cation, inhibit the activity of select enzymes. Among these is glycogen synthase kinase-3 (GSK-3). Recent preclinical evidence, including biochemical, pharmacological, genetic, and rodent behavioral models, supports the hypothesis that inhibition of GSK-3 may represent a target for lithium's mood-stabilizing properties. Specifically, it has been demonstrated that lithium administration regulates multiple GSK-3 targets in vivo and that multiple additional classes of mood-stabilizing and antidepressant drugs regulate GSK-3 signaling. Pharmacological or genetic inhibition of GSK-3 results in mood stabilizer-like behavior in rodent models, and genetic association studies implicate GSK-3 as a possible modulator of particular aspects of bipolar disorder including response to lithium. Furthermore, numerous recent studies have provided a more complete understanding of GSK-3's role in diverse neurological processes strengthening the hypothesis that GSK-3 may represent a therapeutically relevant target of lithium. For example, GSK-3 is a primary regulator of neuronal survival, and cellular responses to glucocorticoids and estrogen may involve GSK-3-regulated pathways. While the preclinical evidence discussed in this review is encouraging, ultimate validation of GSK-3 as a therapeutically relevant target will require clinical trials of selective novel inhibitors. In this regard, as is discussed, there is a major effort underway to develop novel, specific, GSK-3 inhibitors. C1 NIMH, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Gould, TD (reprint author), NIMH, Mol Pathophysiol Lab, NIH, 9000 Rockville Pike,Bldg 35,Room 1C-912, Bethesda, MD 20892 USA. EM gouldt@mail.nih.gov FU Intramural NIH HHS NR 141 TC 242 Z9 250 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2005 VL 30 IS 7 BP 1223 EP 1237 DI 10.1038/sj.npp.1300731 PG 15 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 936UV UT WOS:000229881800001 PM 15827567 ER PT J AU Jiang, XY Xu, K Hoberman, J Tian, F Marko, AJ Waheed, JF Harris, CR Marini, AM Enoch, MA Lipsky, RH AF Jiang, XY Xu, K Hoberman, J Tian, F Marko, AJ Waheed, JF Harris, CR Marini, AM Enoch, MA Lipsky, RH TI BDNF variation and mood disorders: A novel functional promoter polymorphism and Val66Met are associated with anxiety but have opposing effects SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE brain-derived neurotrophic factor; gene; polymorphism; promoter; anxiety; depression ID LONG-TERM POTENTIATION; METHYL-D-ASPARTATE; ACTIVITY-DEPENDENT SECRETION; FAMILY-BASED ASSOCIATION; ELEMENT-BINDING PROTEIN; NEUROTROPHIC-FACTOR; BIPOLAR DISORDER; LINKAGE DISEQUILIBRIUM; TRANSCRIPTION FACTOR; NEURONAL PLASTICITY AB The brain-derived neurotrophic factor ( BDNF) gene is critical for neuronal function and survival, and is likely to be important in psychiatric disorders. In this study, we used single-nucleotide polymorphism ( SNP) discovery, functional analyses, and genetic association studies to better understand the potential role of BDNF sequence variation in behavior. Screening 480 unrelated individuals for SNPs and genotyping was performed in US Caucasian, American Indian, and African American populations. Lifetime DSM-III-R psychiatric diagnoses were assigned and the Tridimensional Personality Questionnaire ( TPQ) was administered to measure anxious temperament ( harm avoidance ( HA)) and novelty seeking ( NS). A novel SNP ( -281 C>A) in promoter 1 was discovered that had decreased DNA binding in vitro and decreased basal reporter gene activity in transfected rat hippocampal neurons. The frequency of the -281 A allele was 0.03 in a Caucasian sample, but was virtually absent in other populations. Association analyses in a community-based sample showed that individuals with the -281 A allele ( 13 heterozygotes) had lower TPQ HA ( F = 4.8, p<0.05). In contrast, the Met 66 allele was associated with increased HA ( F = 4.1, p = 0.02) and was most abundant in individuals with both anxiety disorders and major depression ( p < 0.05). Among the Val66Val homozygotes, individuals who were -281 CA heterozygotes had significantly lower HA than the -281 CC homozygotes ( p < 0.01). Our results suggest that in this population, the low activity -281 A allele may be protective against anxiety and psychiatric morbidity, whereas Met 66 may be a risk allele. C1 NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Human Genet, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. RP Lipsky, RH (reprint author), NIAAA, Mol Genet Sect, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA. EM rlipsky@mail.nih.gov OI Lipsky, Robert/0000-0001-7753-1473 FU NIAAA NIH HHS [Z01-AA00325] NR 45 TC 157 Z9 168 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUL PY 2005 VL 30 IS 7 BP 1353 EP 1361 DI 10.1038/sj.npp.1300703 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 936UV UT WOS:000229881800013 PM 15770238 ER PT J AU Kaminski, RM Shippenberg, TS Witkin, JM Rocha, BA AF Kaminski, RM Shippenberg, TS Witkin, JM Rocha, BA TI Genetic deletion of the norepinephrine transporter decreases vulnerability to seizures SO NEUROSCIENCE LETTERS LA English DT Article DE pentylenetetrazol; kainic acid; cocaine; norepinephrine transporter; seizures; knock-out mice ID AFFECTIVE-DISORDERS; MICE LACKING; EPILEPSY; COCAINE; RATS; ALPHA-2-ADRENOCEPTORS; 6-HYDROXYDOPAMINE; DEXMEDETOMIDINE; SUSCEPTIBILITY; CONVULSIONS AB Norepinephrine (NE) has been reported to modulate neuronal excitability and act as endogenous anticonvulsant. In the present study we used NE transporter knock-out mice (NET-KO), which are characterized by high levels of extracellular NE, to investigate the role of endogenous NE in seizure susceptibility. Seizure thresholds for cocaine (i.p.), pentylenetetrazol (i.v.) and kainic acid (i.v.) were compared in NET-KO, heterozygous (NET-HT) and wild type (NET-WT) female mice. The dose-response curve for cocaine-induced convulsions was significantly shifted to the right in NET-KO mice, indicating higher seizure thresholds. The threshold doses of pentylenetetrazol that induced clonic and tonic seizures were also significantly higher in NET-KO when compared to NET-WT mice. Similarly, NET-KO mice displayed higher resistance to convulsions engendered by kainic acid. For all drugs tested, the response of NET-HT mice was always intermediate. These data provide further support for a role of endogenous NE in the control of seizure susceptibility. Published by Elsevier Ireland Ltd. C1 NIDA, Integrat Neurosci Sect, IRP, Bethesda, MD 20892 USA. NIDA, Drug Dev Grp, IRP, Bethesda, MD 20892 USA. NIDA, Behav Neurosci Branch, IRP, Bethesda, MD 20892 USA. RP Kaminski, RM (reprint author), NIDA, Integrat Neurosci Sect, IRP, Bethesda, MD 20892 USA. EM kaminskr@mail.nih.gov FU NIDA NIH HHS [Z01 DA000398-10] NR 31 TC 29 Z9 29 U1 1 U2 2 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 JUL 1 PY 2005 VL 382 IS 1-2 BP 51 EP 55 DI 10.1016/j.neulet.2005.02.056 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 933VV UT WOS:000229661900010 PM 15911120 ER PT J AU Simon-Sanchez, J Hanson, M Singleton, A Hernandez, D McInerney, A Nussbaum, R Werner, J Gallardo, M Weiser, R Gwinn-Hardy, K Singleton, AB Clarimon, J AF Simon-Sanchez, J Hanson, M Singleton, A Hernandez, D McInerney, A Nussbaum, R Werner, J Gallardo, M Weiser, R Gwinn-Hardy, K Singleton, AB Clarimon, J TI Analysis of SCA-2 and SCA-3 repeats in Parkinsonism: Evidence of SCA-2 expansion in a family with autosomal dominant Parkinson's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Parkinson's disease; genetics; SCA; parkinsonism ID SPINOCEREBELLAR ATAXIA TYPE-2; CHINESE AB The spinocerebellar ataxias (SCAs) are progressive neurodegenerative disorders linked to more than 20 genetic loci. Most often, these diseases are caused by expansion of triplet repeats encoding polyglutamine (polyQ) tracts. The phenotype is variable and can cause a disease that overlaps clinically with Parkinson's disease (PD). L-Dopa-responsive parkinsonism with minimal cerebellar deficits has been described in SCA2 and SCA3. In order to define if mutation at these loci is a common cause of clinically defined parkinsonism we typed the SCA-2 and SCA-3 repeats for expansion in a series of 280 patients diagnosed with PD or parkinsonism. We identified one pathogenic expansion in SCA-2 in a North American family with autosomal dominant parkinsonism. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. CSIC, Inst Biomed Valencia, Dept Genom & Proteom, Unitat Genet Mol, E-46010 Valencia, Spain. NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Hosp Univ Caracas, Chacao Caracas 1060, Venezuela. RP Clarimon, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room IA100,MSC 3707,35 Lincoln Dr, Bethesda, MD 20892 USA. EM clarimon@mail.nih.gov RI Gwinn, Katrina/C-2508-2009; Singleton, Andrew/C-3010-2009; OI Clarimon, Jordi/0000-0002-6824-6942; Gwinn, Katrina/0000-0002-8277-651X NR 10 TC 22 Z9 24 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD JUL 1 PY 2005 VL 382 IS 1-2 BP 191 EP 194 DI 10.1016/j.neulet.2005.03.015 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 933VV UT WOS:000229661900037 PM 15911147 ER PT J AU Antonelli, G Bagnato, F Dianzani, F AF Antonelli, G Bagnato, F Dianzani, F TI Considerations on the development of serum antibodies to interferon-beta SO NEW MICROBIOLOGICA LA English DT Review DE interferon beta; antibody to interferon beta; multiple sclerosis; interferon beta treatment ID REMITTING MULTIPLE-SCLEROSIS; CHRONIC HEPATITIS-C; NEUTRALIZING ANTIBODIES; IFN-BETA; DISEASE-ACTIVITY; MS PATIENTS; NATURAL AUTOANTIBODIES; BINDING-ANTIBODIES; RELAPSING MS; DOUBLE-BLIND AB The phenomenon of antibodies to interferon (IFN) beta in patients with multiple sclerosis has attracted the attention of numerous research groups over the years, and has been examined from various different points of view. In this review we describe and discuss some of the aspects that we believe to be most worthy of consideration. The main considerations are as follows: There is a lack of substantial information on the biological/immunological phenomenon of neutralising antibodies in vivo development. Nevertheless, sufficient experimental data are available to provide a rationale for monitoring the presence of anti-IFN antibodies in patients treated with IFN beta; A standardised quantitative assay to detect antibody to IFNs must be agreed. Only when results can be compared, both in terms of the qualitative presence and quantitative measurement of antibodies, will it be possible to monitor fully the ability of antibodies to cause a relapse during treatment; Although there is increasing evidence to indicate that the development of antibodies to IFN beta may be associated with a failure of the beneficial effects of the therapy, the use of the seropositivity for neutralising antibodies to IFN beta as the only surrogate marker for clinical and therapeutic decision-making is questionable. C1 Univ Roma La Sapienza, Virol Sect, Dept Exptl Med & Pathol, I-00185 Rome, Italy. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Infect Dis, Rome, Italy. RP Antonelli, G (reprint author), Univ Roma La Sapienza, Virol Sect, Dept Exptl Med & Pathol, Viale Porta Tiburtina 28, I-00185 Rome, Italy. EM guido.antonelli@uniroma1.it NR 82 TC 8 Z9 8 U1 0 U2 0 PU EDIZIONI INTERNAZIONALI SRL PI PAVIA PA DIV EDIMES, EDIZIONI MEDICO SCIENTIFICHE PAVIA, VIA RIVIERA, PAVIA, 39-27100, ITALY SN 1121-7138 J9 NEW MICROBIOL JI New Microbiol. PD JUL PY 2005 VL 28 IS 3 BP 183 EP 192 PG 10 WC Microbiology SC Microbiology GA 969IK UT WOS:000232227600001 PM 16240689 ER PT J AU Ogmen, U Keskin, O Aytuna, AS Nussinov, R Gursoy, A AF Ogmen, U Keskin, O Aytuna, AS Nussinov, R Gursoy, A TI PRISM: protein interactions by structural matching SO NUCLEIC ACIDS RESEARCH LA English DT Article ID RECOGNITION SITES; INTERFACES; PREDICTION AB Prism (http://gordion.hpc.eng.ku.edu.tr/prism) is a website for protein interface analysis and prediction of putative protein-protein interactions. It is composed of a database holding protein interface structures derived from the Protein Data Bank (PDB). The server also includes summary information about related proteins and an interactive protein interface viewer. A list of putative protein-protein interactions obtained by running our prediction algorithm can also be accessed. These results are applied to a set of protein structures obtained from the PDB at the time of algorithm execution (January 2004). Users can browse through the non-redundant dataset of representative interfaces on which the prediction algorithm depends, retrieve the list of similar structures to these interfaces or see the results of interaction predictions for a particular protein. Another service provided is interactive prediction. This is done by running the algorithm for user input structures. C1 Koc Univ, Ctr Comp Biol & Informat, TR-34450 Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. NCI, Basic Res Program, Sci Applicat Int Corp Frederick Inc, LECB, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Keskin, O (reprint author), Koc Univ, Ctr Comp Biol & Informat, TR-34450 Istanbul, Turkey. EM okeskin@ku.edu.tr; agursoy@ku.edu.tr RI Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 19 TC 124 Z9 125 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2005 VL 33 SU 2 BP W331 EP W336 DI 10.1093/nar/gki585 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942GR UT WOS:000230271400067 PM 15991339 ER PT J AU Schneidman-Duhovny, D Inbar, Y Nussinov, R Wolfson, HJ AF Schneidman-Duhovny, D Inbar, Y Nussinov, R Wolfson, HJ TI PatchDock and SymmDock: servers for rigid and symmetric docking SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PROTEIN-PROTEIN DOCKING; MOLECULAR-SURFACE RECOGNITION; SHAPE COMPLEMENTARITY; GENETIC ALGORITHM; ELECTROSTATICS; CONFORMATIONS; DESOLVATION AB Here, we describe two freely available web servers for molecular docking. The PatchDock method performs structure prediction of protein-protein and protein-small molecule complexes. The SymmDock method predicts the structure of a homomultimer with cyclic symmetry given the structure of the monomeric unit. The inputs to the servers are either protein PDB codes or uploaded protein structures. The services are available at http://bioinfo3d.cs.tau.ac.il. The methods behind the servers are very efficient, allowing large-scale docking experiments. C1 Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Inst Mol Med, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Ft Detrick, MD 21702 USA. RP Wolfson, HJ (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. EM duhovka@tau.ac.il; wolfson@tau.ac.il RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 28 TC 583 Z9 598 U1 4 U2 33 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2005 VL 33 SU 2 BP W363 EP W367 DI 10.1093/nar/gki481 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942GR UT WOS:000230271400073 PM 15980490 ER PT J AU Shulman-Peleg, A Nussinov, R Wolfson, HJ AF Shulman-Peleg, A Nussinov, R Wolfson, HJ TI SiteEngines: recognition and comparison of binding sites and protein-protein interfaces SO NUCLEIC ACIDS RESEARCH LA English DT Article ID MOLECULAR-SURFACE; PATTERNS; IDENTIFICATION; TEMPLATES; EVOLUTION; SEQUENCE; FOLD AB Protein surface regions with similar physicochemical properties and shapes may perform similar functions and bind similar binding partners. Here we present two web servers and software packages for recognition of the similarity of binding sites and interfaces. Both methods recognize local geometrical and physicochemical similarity, which can be present even in the absence of overall sequence or fold similarity. The first method, SiteEngine (http:/bioinfo3d.cs.tau.ac.il/SiteEngine), receives as an input two protein structures and searches the complete surface of one protein for regions similar to the binding site of the other. The second, Interface-to-Interface (I2I)-SiteEngine (http:/bioinfo3d.cs.tau.ac.il/I2I-SiteEngine), compares protein-protein interfaces, which are regions of interaction between two protein molecules. It receives as an input two structures of protein-protein complexes, extracts the interfaces and finds the three-dimensional transformation that maximizes the similarity between two pairs of interacting binding sites. The output of both servers consists of a superimposition in PDB file format and a list of physicochemical properties shared by the compared entities. The methods are highly efficient and the freely available software packages are suitable for large-scale database searches of the entire PDB. C1 Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Inst Mol Med, Sackler Fac Med, IL-69978 Tel Aviv, Israel. NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Ft Detrick, MD 21702 USA. RP Shulman-Peleg, A (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. EM shulmana@tau.ac.il RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 21 TC 50 Z9 52 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL 1 PY 2005 VL 33 SU 2 BP W337 EP W341 DI 10.1093/nar/gki482 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942GR UT WOS:000230271400068 PM 15980484 ER PT J AU Davis, T Schoenfeldt, M Chevalier, SM AF Davis, T Schoenfeldt, M Chevalier, SM TI Current clinical trials in myelodysplastic syndrome - Referral resource SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID LENALIDOMIDE; THALIDOMIDE C1 NCI, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Davis, T (reprint author), NCI, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD JUL PY 2005 VL 19 IS 8 BP 1035 EP + PG 3 WC Oncology SC Oncology GA 052EM UT WOS:000238214300017 PM 16131045 ER PT J AU Stoll, BJ Hansen, NI Higgins, RD Fanaroff, AA Duara, S Goldberg, R Laptook, A Walsh, M Oh, W Hale, E AF Stoll, BJ Hansen, NI Higgins, RD Fanaroff, AA Duara, S Goldberg, R Laptook, A Walsh, M Oh, W Hale, E CA Natl Inst Child Health Human Dev TI Very low birth weight preterm infants with early onset neonatal sepsis - The predominance of Gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network 2002-2003 SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE early onset neonatal sepsis; Gram-negative infections ID B STREPTOCOCCAL DISEASE; INTENSIVE-CARE-UNIT; ANTIBIOTICS; PROPHYLAXIS; EXPERIENCE; ERA AB Background: Early onset neonatal sepsis (EOS, occurring in the first 72 hours of life) remains an important cause of illness and death among very low birth weight (VLBW) preterm infants. We previously reported a change in the distribution of pathogens associated with EOS from predominantly Gram-positive to primarily Gram-negative organisms. Objective: To compare rates of EOS and pathogens associated with infection among VLBW infants born at centers of the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network during 3 time periods: 1991-1993; 19982000; and 2002-2003. Study Design: Prospectively collected data from the NICHD Neonatal Research Network VLBW registry were retrospectively reviewed. Rates of blood culture confirmed EOS, selected maternal and infant variables and pathogens associated with infection were compared between 2002-2003 and 2 previously published cohorts. Results: During the past 13 years, overall rates of EOS have remained stable (15-19 per 1000 live births of infants 401-1500 g). More than one-half of early infections in the 2002-2003 cohort were caused by Gram-negative organisms (53%), with Escherichia coli the most common organism (41%). Rates of group B streptococcal infections remain low (1.8 per 1000 live births). Between 19911993 and 1998-2000, there was a significant increase in rates of E. C1 Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NICHHD, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Univ Miami, Dept Neonatol, Miami, FL 33152 USA. Duke Univ, Ctr Med, Durham, NC USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. RP Stoll, BJ (reprint author), Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA. FU NICHD NIH HHS [U10 HD27853, U10 HD19897, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216, U10 HD36790, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689] NR 15 TC 160 Z9 164 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUL PY 2005 VL 24 IS 7 BP 635 EP 639 DI 10.1097/01.inf.0000168749.82105.64 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 946WO UT WOS:000230604200012 PM 15999007 ER PT J AU Aleksa, K Matsell, D Krausz, K Gelboin, H Ito, S Koren, G AF Aleksa, K Matsell, D Krausz, K Gelboin, H Ito, S Koren, G TI Cytochrome P450 3A and 2B6 in the developing kidney: implications for ifosfamide nephrotoxicity SO PEDIATRIC NEPHROLOGY LA English DT Article DE kidney; CYP3A; CYP2B6; ifosfamide; nephrotoxicity; ontogeny; enantioselective metabolism ID PROSTAGLANDIN ENDOPEROXIDE SYNTHETASE; SITE-DIRECTED MUTAGENESIS; HUMAN LIVER-MICROSOMES; N-DECHLOROETHYLATION; CLINICAL PHARMACOKINETICS; DEVELOPMENTAL EXPRESSION; MONOCLONAL-ANTIBODY; CHEMICAL-STABILITY; DRUG-METABOLISM; RABBIT KIDNEY AB Repeated administration of agents (e.g., cancer chemotherapy) that can cause drug-induced nephrotoxicity may lead to acute or chronic renal damage. This will adversely affect the health and well-being of children, especially when the developing kidney is exposed to toxic agents that may lead to acute glomerular, tubular or combined toxicity. We have previously shown that the cancer chemotherapeutic ifosfamide ( IF) causes serious renal damage substantially more in younger children ( less than 3 years of age) than among older children. The mechanism of the age-related IF-induced renal damage is not known. Our major hypothesis is that renal CYP P450 expression and activity are responsible for IF metabolism to the nephrotoxic chloroacetaldehyde. Presently, the ontogeny of these catalytic enzymes in the kidney is sparsely known. The presence of CYP3A4, 3A5 and 2B6 was investigated in human fetal, pediatric and adult kidney as was the metabolism of IF ( both R-IF and S-IF enantiomers) by renal microsomes to 2-dechloroethylifosfamide (2-DCEIF) and 3-dechloroethylifosfamide (3-DCEIF). Our analysis shows that CYP 3A4 and 3A5 are present as early as 8 weeks of gestation. IF is metabolized in the kidney to its two enantiomers. This metabolism can be inhibited with CYP 3A4/5 and 2B6 specific monoclonal inhibitory antibodies, whereby the CYP3A4/5 inhibitory antibody decreased the production of R-3-DCEIF by 51%, while the inhibitory CYP2B6 antibody decreased the production of S-2-DCEIF and S-3-DCEIF by 44 and 43%, respectively, in patient samples. Total renal CYP content is approximately six-fold lower than in the liver. C1 Hosp Sick Children, Div Clin Pharmacol & Toxicol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON, Canada. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Women & Childrens Hosp British Colombia, Vancouver, BC, Canada. RP Koren, G (reprint author), Hosp Sick Children, Div Clin Pharmacol & Toxicol, 555 Univ Ave, Toronto, ON M5G 1X8, Canada. EM gkoren@sickkids.ca NR 68 TC 42 Z9 43 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUL PY 2005 VL 20 IS 7 BP 872 EP 885 DI 10.1007/s00467-004-1807-3 PG 14 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 936XG UT WOS:000229888200006 PM 15875221 ER PT J AU Vohr, BR Msall, ME Wilson, D Wright, LL McDonald, S Poole, WK AF Vohr, BR Msall, ME Wilson, D Wright, LL McDonald, S Poole, WK TI Spectrum of gross motor function in extremely low birth weight children with cerebral palsy at 18 months of age SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Pediatrics/Ambulatory-Pediatric-Association/Society- for-Pediatric-Research CY MAY 12-16, 2000 CL BOSTON, MA SP Amer Acad Pediat, Ambulatory Pediat Assoc, Soc Pediat Res DE extremely low birth weight; neurologic outcome; cerebral palsy; gross motor function; development; sequelae ID INFANTS; RELIABILITY; OUTCOMES; SYSTEM AB Objective. The purpose of this study was to evaluate the relationship between cerebral palsy (CP) diagnoses as measured by the topographic distribution of the tone abnormality with level of function on the Gross Motor Function Classification System (GMFCS) and developmental performance on the Bayley Scales of Infant Development II (BSID-II). It was hypothesized that (1) the greater the number of limbs involved, the higher the GMFCS and the lower the BSID-II Motor Scores and (2) there would be a spectrum of function and skill achievement on the GMFCS and BSID-II Motor Scores for children in each of the CP categories. Methods. A multicenter, longitudinal cohort study was conducted of 1860 extremely low birth weight (ELBW) infants who were born between August 1, 1995 and February 1, 1998, and evaluated at 18 to 22 months' corrected age. Children were categorized into impairment groups on the basis of the typography of neurologic findings: spastic quadriplegia, triplegia, diplegia, hemiplegia, monoplegia, hypotonic and/or athetotic CP, other abnormal neurologic findings, and normal. The neurologic category then was compared with GMFCS level and BSID-II Motor Scores. Results. A total of 282 (15.2%) of the 1860 children evaluated had CP. Children with more limbs involved had more abnormal GMFCS levels and lower BSID-II scores, reflecting more severe functional limitations. However, for each CP diagnostic category, there was a spectrum of gross motor functional levels and BSID-II scores. Although more than 1 (26.6%) in 4 of the children with CP had moderate to severe gross motor functional impairment, 1 (27.6%) in 4 had motor functional skills that allowed for ambulation. Conclusions. Given the range of gross motor skill outcomes for specific types of CP, the GMFCS is a better indicator of gross motor functional impairment than the traditional categorization of CP that specifies the number of limbs with neurologic impairment. The neurodevelopmental assessment of young children is optimized by combining a standard neurologic examination with measures of gross and fine motor function ( GMFCS and Bayley Psychomotor Developmental Index). Additional studies to examine longer term functional motor and adaptive-functional developmental skills are required to devise strategies that delineate therapies to optimize functional performance. C1 Brown Univ, Women & Infants Hosp, Providence, RI 02905 USA. Univ Chicago, Comer Childrens Hosp, Chicago, IL 60637 USA. Univ Chicago, La Rabida Childrens Hosp, Chicago, IL 60637 USA. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. NICHHD, Bethesda, MD 20892 USA. RTI Int, Res Triangle Pk, NC USA. RP Vohr, BR (reprint author), Brown Univ, Women & Infants Hosp, 101 Dudley St, Providence, RI 02905 USA. EM betty_vohr@brown.edu FU NCRR NIH HHS [M01 RR 08084, M01 RR 00997, M01 RR 00750, M01 RR 06022, M01 RR 00070]; NICHD NIH HHS [U10 HD27856, U10 HD21364, U10 HD27881, U10HD27904, U10 HD27853, U10 HD27871, U10 HD21385, U10 HD21397, U10 HD27851, U10 HD21415, U10 HD21373, U10 HD27880, U01 HD19897] NR 26 TC 45 Z9 46 U1 1 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2005 VL 116 IS 1 BP 123 EP 129 DI 10.1542/peds.2004-1810 PG 7 WC Pediatrics SC Pediatrics GA 941IC UT WOS:000230207500042 PM 15995042 ER PT J AU Million, M Maillot, C Adelson, DA Nozu, T Gauthier, A Rivier, J Chrousos, GP Bayati, A Mattsson, H Tache, Y AF Million, M Maillot, C Adelson, DA Nozu, T Gauthier, A Rivier, J Chrousos, GP Bayati, A Mattsson, H Tache, Y TI Peripheral injection of sauvagine prevents repeated colorectal distension-induced visceral pain in female rats SO PEPTIDES LA English DT Article DE antalarmin; sauvagine; CRF; visceral pain; colorectal distension; female Fisher rats ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; RECEPTOR ANTAGONIST; UROTENSIN-I; RECTAL DISTENSION; CRF1 RECEPTOR; PARAVENTRICULAR NUCLEUS; TYPE-1 RECEPTOR; NMDA RECEPTORS; FOS EXPRESSION AB We investigated the effects of peripheral injection of sauvagine, a CRF(2) > CRF(1) receptor (corticotropin-releasing factor) agonist compared with CRF, on two sets of tonic colorectal distension (CRDs 30, 40, 50 mmHg, 3-min on/off)-induced visceromotor response (VMR) measured as area under the curve (AUC) of abdominal muscle contraction in conscious female rats. Sauvagine (10 or 20 mu g/kg, s.c.) abolished the 226.7 +/- 64.3 % and 90.4 +/- 38.1 % increase in AUC to the 2nd CRD compared with the 1st CRD (performed 30 min before) in female Fisher and Sprague-Dawley (SD) rats, respectively. CRF had no effect while the CRF1 antagonist, antalarmin (20 mg/kg, s.c.), alone or with sauvagine, blocked the enhanced response to the 2nd CRD, performed 60 min after the 1st CRD, and reduced further the AUC by 33.5 +/- 23.3 % and 63.5 +/- 7.2 %, respectively in Fisher rats. These data suggest that peripheral CRF receptor activation exerts antinociceptive effects on CRD-induced visceral pain, whereas CRF(1) contributes to visceral sensitization. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, CURE, VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, VA Greater Los Angeles Healthcare Syst, Div Digest Dis,Ctr Neurovisceral Sci & Womens Hlt, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, San Diego, CA 92186 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. AstraZeneca R&D, S-43183 Molndal, Sweden. RP Million, M (reprint author), Univ Calif Los Angeles, CURE, VA Greater Los Angeles Healthcare Syst, Digest Dis Res Ctr, CURE Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM mmuluget@ucla.edu OI Adelson, David/0000-0002-4623-6030 FU NIDDK NIH HHS [DK-57238-01A1S1, R01 DK-33061, R01 DK-57238, P50 DK 64539, DK26741] NR 70 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL PY 2005 VL 26 IS 7 BP 1188 EP 1195 DI 10.1016/j.peptides.2005.02.004 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 940PE UT WOS:000230155600012 PM 15949637 ER PT J AU Hand, D Eiden, LE AF Hand, D Eiden, LE TI Human sorbin is generated via splicing of an alternative transcript from the ArgBP2 gene locus SO PEPTIDES LA English DT Article ID RAT; BIOSYNTHESIS AB We demonstrate that the human sorbin polypeptide is generated via splicing of an alternative transcript from the ArgBP2 gene locus. Previous studies have demonstrated that the central 139 amino acid region of the porcine sorbin polypeptide exhibits 95 % homology to part of the human ArgBP2 protein. Yet neither the sorbin N- nor C-terminus has been identified in ArgBP2 or any other protein to date. Using computational analysis, we locate the sorbin N- and C-termini in the human ArgBP2 gene locus, and demonstrate that they are spliced to the 5' and 3' ends of the 95 % homologous region. In addition, several sequence anomalies were identified in the putative human sorbin cDNA (AF396457). Thus, a revised human sorbin nucleotide sequence is proposed. Published by Elsevier Inc. C1 NIMH, Natl Inst Hlth, Mol Neurosci Sect, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIMH, Natl Inst Hlth, Mol Neurosci Sect, 36 Convent Dr,MSC 4090,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD JUL PY 2005 VL 26 IS 7 BP 1278 EP 1282 DI 10.1016/j.peptides.2005.01.016 PG 5 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 940PE UT WOS:000230155600023 PM 15949647 ER PT J AU Berger, VW Matthews, JR AF Berger, VW Matthews, JR TI DConducting today's trials by tomorrow's standards SO PHARMACEUTICAL STATISTICS LA English DT Editorial Material ID CLINICAL-TRIALS C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Richmond, VA USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Execut Pl N,Suite 3131,6130 Execut Blvd,MSC 7354, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2005 VL 4 IS 3 BP 155 EP 159 DI 10.1002/pst.176 PG 5 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 970HG UT WOS:000232295300002 ER PT J AU Pick, CG Chernes, Y Rigai, T Rice, KC Schreiber, S AF Pick, CG Chernes, Y Rigai, T Rice, KC Schreiber, S TI The antinociceptive effect of zolpidem and zopiclone in mice SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE zopiclone; zolpidem; opioids; hotplate; mice; antinociception; drugs interaction ID OMEGA-RECEPTOR SUBTYPES; THERAPEUTIC-EFFICACY; PHARMACOKINETIC PROPERTIES; BEHAVIORAL PHARMACOLOGY; SEVERE INSOMNIA; A RECEPTORS; BENZODIAZEPINES; DEPENDENCE; AWARENESS; ABUSE AB Zolpidem and zopiclone are two of a newer hypno-sedative class of drugs, the "Z compounds". Their use for the treatment of short-term insomnia has been expanding constantly during the last two decades. The "Z compounds" are considered to cause less significant rebound insomnia or tolerance than the conventional hypnotic benzodiazepines. Their possible antinociceptive effect and interaction with the opioid system has not been studied yet. Our results demonstrate a significant difference between the antinociceptive properties of zopiclone and zolpidem when injected s.c. in the hotplate analgesic assay in mice. Zopiclone induced a weak, dose-dependent antinociceptive effect, antagonized only by the alpha(2)-adrenergic receptor antagonist yohimbine. Zolpidem induced a weak, biphasic dose-dependent antinociceptive effect, antagonized primarily by the non-selective opioid antagonist naloxone and by yohimbine. The weak antinociceptive effect of both drugs, evident only at very high doses (far beyond those used clinically to induce sleep), implies no clinical use for zopiclone or zolpidem in the management of pain. However, the possible interaction of zolpidem with the opioid system should be further investigated (in behavioral models, which do not overlap with the acute-pain antinociception model we used), both for possible side effects in special populations (i.e. elderly) and for possible drug-drug interactions, in order to minimize possible hazards and maximize clinical beneficial effects of its use for sleep. (c) 2005 Elsevier Inc. All rights reserved. C1 Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. Chaim Sheba Med Ctr, Div Psychiat, IL-52621 Tel Hashomer, Israel. NIDDK, Med Chem Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. Tel Aviv Sourasky Med Ctr, Dept Psychiat, Tel Aviv, Israel. RP Pick, CG (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel. EM pickc@post.tau.ac.il RI Schreiber, Shaul/E-5821-2010; Pick, Chaim/D-4789-2009 OI Schreiber, Shaul/0000-0002-2189-0693; NR 52 TC 9 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 2005 VL 81 IS 3 BP 417 EP 423 DI 10.1016/j.pbb.2005.02.013 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 951ZH UT WOS:000230970400001 PM 15913749 ER PT J AU Winter, JC Eckler, JR Rice, KC Rabin, RA AF Winter, JC Eckler, JR Rice, KC Rabin, RA TI Serotonergic/glutamatergic interactions: Potentiation of phencyclidine-induced stimulus control by citalopram SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE drug discrimination; phencyclidine; citalopram; SB 242084; SDZ SER 082; rat ID LYSERGIC-ACID DIETHYLAMIDE; 5-HT1A SEROTONIN RECEPTORS; RAT PREFRONTAL CORTEX; DISCRIMINATIVE STIMULUS; M-CHLOROPHENYLPIPERAZINE; EXTRACELLULAR GLUTAMATE; HALLUCINOGENIC DRUGS; R-CITALOPRAM; ANTAGONIST; LSD AB Previous investigations in our laboratory have found that the stimulus effects of the hallucinogenic serotonergic agonists DOM and LSD are potentiated by phencyclidine [PCP], a non-competitive NMDA antagonist. Also suggestive of behaviorally significant serotonergic/glutamatergic interactions is our finding that stimulus control by both PCP and LSD is partially antagonized by the mGlu2/3 agonist, LY 379268. These observations coupled with the fact that the stimulus effects of LSD and DOM are potentiated by selective serotonin reuptake inhibitors [SSRIs] led us in the present investigation to test the hypothesis that stimulus control by PCP is potentiated by the SSRI, citalopram. Stimulus control was established with PCP [3.0 mg/kg; 30 min pretreatment time] in a group of 12 rats. A two-lever, fixed ratio 10, positively reinforced task with saline controls was employed. Potentiation by citalopram of an intermediate dose of PCP was observed. In an attempt to establish the mechanism by which citalopram might interact with PCP, subsequent experiments examined the effects on that interaction of antagonists at serotonergic receptors. It was found that the selective 5-HT2C-selective antagonists, SDZ SER 082 and SB 242084, significantly, albeit only partially, blocked the effects of citalopram on PCP. In agreement with our previous conclusions regarding the interaction of citalopram with DOM, the present data suggest that potentiation of the stimulus effects of PCP by citalopram are mediated in part by agonist activity at 5-HT2C receptors. (c) 2005 Elsevier Inc. All rights reserved. C1 SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, Buffalo, NY 14214 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Winter, JC (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Pharmacol & Toxicol, 102 Farber Hall, Buffalo, NY 14214 USA. EM jcwinter@buffalo.edu FU NIDA NIH HHS [R56 DA003385, DA 03385, R01 DA003385-17, F30 DA14238, R01 DA003385, F30 DA014238] NR 65 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUL PY 2005 VL 81 IS 3 BP 694 EP 700 DI 10.1016/j.pbb.2005.03.022 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 951ZH UT WOS:000230970400034 PM 15970314 ER PT J AU Krishnamoorthy, G Webb, SP Nguyen, T Chowdhury, PK Halder, M Wills, NJ Carpenter, S Kraus, GA Gordon, MS Petrich, JW AF Krishnamoorthy, G Webb, SP Nguyen, T Chowdhury, PK Halder, M Wills, NJ Carpenter, S Kraus, GA Gordon, MS Petrich, JW TI Synthesis of hydroxy and methoxy perylene quinones, their spectroscopic and computational characterization, and their antiviral activity SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MOLECULAR-ORBITAL METHODS; HYPERICIN-INDUCED PHOTOTOXICITY; INTRAMOLECULAR PROTON-TRANSFER; DEGENERATE PERTURBATION-THEORY; HUMAN-IMMUNODEFICIENCY-VIRUS; EXCITED-STATE PROCESSES; GAUSSIAN-TYPE BASIS; PROTEIN-KINASE-C; ATOM TRANSFER; INTRACELLULAR ACIDIFICATION AB Hydroxy and methoxy perylene quinones are synthesized in an attempt to isolate the essential spectroscopic and biological features of light-induced antiviral agents such as hypericin and hypocrellin. Unlike their naturally occurring counterparts, these synthetic quinones bear the carbonyl, hydroxyl, and methoxy groups in the "bay region." The hydroxy and methoxy compounds have rich absorption spectra with broad features in the visible (similar to 450-800 nm) and relatively more intense and narrow features at wavelengths <= 350 nm. High-level ab initio quantum mechanical calculations assign the features in the absorption spectra to electronic transitions from S-0 to S-2 and to higher-lying electronic states. The calculations indicate that in the ground state the trans dihydroxy isomer is 12.5 kcal/mol lower in energy than the cis dihydroxy isomer and is thus the only species present. The lowest-energy trans methoxy ground state isomer and the lowest-energy cis methoxy ground state isomer are found to be degenerate. An additional cis methoxy isomer 6.3 kcal/mol higher in energy than the global minimum is assumed to contribute to the spectrum and is also considered. Finally, the synthetic compounds exhibit similar light-induced antiviral activity to each other, but significantly less than that of hypericin. C1 Iowa State Univ, Dept Chem, Ames, IA 50011 USA. SAIC Frederick, Adv Biomed Comp Ctr, Natl Canc Inst, Frederick, MD USA. Iowa State Univ, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. RP Webb, SP (reprint author), Iowa State Univ, Dept Chem, Ames, IA 50011 USA. EM jwp@iastate.edu; mark@si.fi.ameslab.gov; simonw@ncifcrf.gov RI Petrich, Jacob/L-1005-2015; OI Chowdhury, Pramit/0000-0002-9593-2577 FU NCI NIH HHS [N01-CO-12400] NR 83 TC 9 Z9 9 U1 0 U2 13 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0031-8655 EI 1751-1097 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUL-AUG PY 2005 VL 81 IS 4 BP 924 EP 933 DI 10.1562/2004-11-23-RA-378R1.1 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 957KB UT WOS:000231367600028 PM 15884972 ER PT J AU Shrader, JA Popovich, JM Gracey, GC Danoff, JV AF Shrader, JA Popovich, JM Gracey, GC Danoff, JV TI Navicular drop measurement in people with rheumatoid arthritis: Interrater and intrarater reliability SO PHYSICAL THERAPY LA English DT Article DE digital height gauge; foot pronation; navicular height; single-limb stance; skin marking error ID MEDIAL LONGITUDINAL ARCH; CRUCIATE LIGAMENT INJURY; EXCESSIVE PRONATION; REARFOOT MOTION; FOOT ORTHOSES; HIGH-SCHOOL; HINDFOOT; MANAGEMENT; EXERCISE; WALKING AB Background and Purpose. Navicular drop (ND) measurement may be a valuable examination technique for patients with rheumatoid arthritis (RA). However, no data exist on reliability for this technique in patients with RA. The purposes of this study were: (1) to determine interrater and intrarater reliability of ND measurements in people with RA, (2) to compare ND values of people with RA with published normative data, and (3) to investigate ND measurement error associated with the use of skin markings. Subjects. Ten women (20 feet) with RA consented to participate. Methods. Patients completed demographic and function questionnaires. Navicular height (NH) measurements were taken by 2 physical therapists and I physical therapist student, following four 1-hour training sessions, using standardized methods and a digital height gauge. Four different NH measurements were taken 3 times on each foot by each of the 3 examiners during a morning session and then repeated during an afternoon session on the same day. Navicular drop values were calculated, including ND1 (as reported in the literature), ND2 (compensating for skin error), and ND3 (single-limb stance). Intraclass correlation coefficients (ICCs) and standard errors of measurement (SEMs) were used to establish reliability. Results. Means (+/- SD) for each ND measure for sessions 1 and 2, respectively, were as follows: ND1=8.36 +/- 5.29 min and 8.29 +/- 5.24 mm, ND2=9.95 +/- 5.44 mm and 9.57 +/- 5.37 mm. The ICCs (2,1 and 2,k, respectively) for all interrater measurements ranged from .67 to .92 (SEM = 2.0 -3.3 mm) and from .85 to .97 (SEM = 1.1-2.0 mm). The ICCs (2,1 and 2,k, respectively) for intrarater measurements ranged from .73 to .95 (SEM=1.3-2.8 mm) and from .90 to .98 (SEM=0.7-1.6 mm). Paired t tests showed the means of ND1 and ND2 for each examiner and for both sessions were significantly different. Discussion and Conclusion. The results suggest that ND measurements for people with RA can be taken reliably by clinicians with varied experience. The ND values for our subjects were slightly greater than reported normal values of 6 to 8 mm. Error associated with skin markings was statistically significant for all sessions and examiners. C1 NIH, Phys Therapy Sect, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr,Dept Hlth & Human Se, Bethesda, MD 20892 USA. Univ So Calif, Dept Biokinesiol & Phys Therapy, Musculoskeletal Biomech Res Lab, Los Angeles, CA USA. George Washington Univ, Sch Publ Hlth, Dept Exercise Sci, Washington, DC USA. RP Shrader, JA (reprint author), NIH, Phys Therapy Sect, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr,Dept Hlth & Human Se, 10 Ctr Dr,CRC Rm 1-1469, Bethesda, MD 20892 USA. EM joseph_shrader@nih.gov NR 41 TC 14 Z9 16 U1 0 U2 2 PU AMER PHYSICAL THERAPY ASSOC PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 USA SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD JUL PY 2005 VL 85 IS 7 BP 656 EP 664 PG 9 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA 941ZB UT WOS:000230251600005 PM 15982172 ER PT J AU Wheeler, DL White, BS Chetvernin, V Resenchuk, S Dombrowski, SM Pechous, SW Tatusova, T Ostell, J AF Wheeler, DL White, BS Chetvernin, V Resenchuk, S Dombrowski, SM Pechous, SW Tatusova, T Ostell, J TI Plant genome resources at the National Center for Biotechnology Information SO PLANT PHYSIOLOGY LA English DT Article ID ARABIDOPSIS-THALIANA; DATABASE; SEQUENCE; RICE; GENE; NCBI; MAIZE; WHEAT AB The National Center for Biotechnology Information (NCBI) integrates data from more than 20 biological databases through a flexible search and retrieval system called Entrez. A core Entrez database, Entrez Nucleotide, includes GenBank and is tightly linked to the NCBI Taxonomy database, the Entrez Protein database, and the scientific literature in PubMed. A suite of more specialized databases for genomes, genes, gene families, gene expression, gene variation, and protein domains dovetails with the core databases to make Entrez a powerful system for genomic research. Linked to the full range of Entrez databases is the NCBI Map Viewer, which displays aligned genetic, physical, and sequence maps for eukaryotic genomes including those of many plants. A specialized plant query page allow maps from all plant genomes covered by the Map Viewer to be searched in tandem to produce a display of aligned maps from several species. PlantBLAST searches against the sequences shown in the Map Viewer allow BLAST alignments to be viewed within a genomic context. In addition, precomputed sequence similarities, such as those for proteins offered by BLAST Link, enable fluid navigation from unannotated to annotated sequences, quickening the pace of discovery. NCBI Web pages for plants, such as Plant Genome Central, complete the system by providing centralized access to NCBI's genomic resources as well as links to organism-specific Web pages beyond NCBI. C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wheeler, DL (reprint author), Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM wheeler@ncbi.nlm.nih.gov NR 27 TC 8 Z9 10 U1 1 U2 3 PU AMER SOC PLANT BIOLOGISTS PI ROCKVILLE PA 15501 MONONA DRIVE, ROCKVILLE, MD 20855 USA SN 0032-0889 J9 PLANT PHYSIOL JI Plant Physiol. PD JUL PY 2005 VL 138 IS 3 BP 1280 EP 1288 DI 10.1104/pp.104.058842 PG 9 WC Plant Sciences SC Plant Sciences GA 944GM UT WOS:000230414800010 PM 16010002 ER PT J AU Reedy, J Haines, PS Campbell, MK AF Reedy, J Haines, PS Campbell, MK TI The influence of health behavior clusters on dietary change SO PREVENTIVE MEDICINE LA English DT Article DE fruits and vegetables; health behaviors; cluster analysis ID FOOD FREQUENCY QUESTIONNAIRES; HABITUAL PHYSICAL-ACTIVITY; LIFE-STYLE; FRAMINGHAM NUTRITION; CANCER PREVENTION; 24-HOUR RECALLS; HARVARD REPORT; UNITED-STATES; 7-DAY RECALL; COLON-CANCER AB Background. The goal of this study was to identify cancer preventive health behavior clusters and to determine if clusters responded differently to a year-long intervention to increase fruit and vegetable consumption. Methods. The North Carolina Strategies for Improving Diet, Exercise, and Screening (NC STRIDES) is a health communications intervention (n = 595) among colorectal cancer survivors and a comparison population. Cluster analysis was used to identify nonoverlapping groups based on fruit and vegetable intake (servings/day), physical activity (minutes/day), multivitamin use (yes/no), and body mass index (kg/m(2)). Logistic regression was performed to assess positive change in fruit and vegetable servings, using the healthiest cluster as the reference group. Results. Five clusters were formed; they differed significantly by health behaviors and demographics. Clusters I and 2 (those following the "Healthy Choices" and "Eating Well" patterns) were eating more than 5 A Day before the intervention (8.6 and 6.9 servings/day), and did not show any increase. Cluster 3 ("Physically Active") reported an increase of 1.3 servings/day to reach 5.4 servings/day, and Clusters 4 and 5 ("Average Americans" and "Most Challenged") improved one serving/day for final intakes of 5.2 and 5.0 servings/day. Conclusions. These findings illustrate some differences in magnitude of response to a fruit and vegetable intervention based on health behavior profiles. Creating clusters or other categories from baseline health behaviors may help to further improve targeting and/or tailoring in health promotion interventions. (c) 2004 Elsevier Inc. All rights reserved. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27599 USA. RP Reedy, J (reprint author), NCI, Div Canc Prevent, Bethesda, MD 20892 USA. EM reedyj@mail.nih.gov FU NCI NIH HHS [5-R01-CA81914-04, 3-R01-CA081914-04S1] NR 40 TC 30 Z9 31 U1 0 U2 14 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JUL PY 2005 VL 41 IS 1 BP 268 EP 275 DI 10.1016/j.ypmed.2004.11.005 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 933RY UT WOS:000229651800036 PM 15917021 ER PT J AU Torborg, CL Feller, MB AF Torborg, CL Feller, MB TI Spontaneous patterned retinal activity and the refinement of retinal projections SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE retinal projection; retinotopic map; optic tectum ID LATERAL GENICULATE-NUCLEUS; EYE-SPECIFIC SEGREGATION; NICOTINIC ACETYLCHOLINE-RECEPTOR; DEVELOPING MAMMALIAN RETINA; REGENERATING RETINOTECTAL PROJECTION; ACTIVITY-DEPENDENT REFINEMENT; SPONTANEOUS CA2+ TRANSIENTS; RODENT SUPERIOR COLLICULUS; RETINOTOPIC MAP REFINEMENT; VISUAL-SYSTEM DEVELOPMENT AB A characteristic feature of sensory circuits is the existence of orderly connections that represent maps of sensory space. A major research focus in developmental neurobiology is to elucidate the relative contributions of neural activity and guidance molecules in sensory map formation. Two model systems for addressing map formation are the retinotopic map formed by retinal projections to the superior colliculus (SC) (or its non-mammalian homolog, the optic tectum (OT)), and the eye-specific map formed by retinal projections to the lateral geniculate nucleus of the thalamus. In mammals, a substantial portion of retinotopic and eye-specific refinement of retinal axons occurs before vision is possible, but at a time when there is a robust, patterned spontaneous retinal activity called retinal waves. Though complete blockade of retinal activity disrupts normal map refinement, attempts at more refined perturbations, such as pharmacological and genetic manipulations that alter features of retinal waves critical for map refinement, remain controversial. Here we review: (1) the mechanisms that underlie the generation of retinal waves; (2) recent experiments that have investigated a role for guidance molecules and retinal activity in map refinement; and (3) experiments that have implicated various signaling cascades, both in retinal ganglion cells (RGCs) and their post-synaptic targets, in map refinement. It is likely that an understanding of retinal activity, guidance molecules, downstream signaling cascades, and the interactions between these biological systems will be critical to elucidating the mechanisms of sensory map formation. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, La Jolla, CA 92093 USA. NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Feller, MB (reprint author), Univ Calif San Diego, Div Biol Sci, Neurobiol Sect, La Jolla, CA 92093 USA. EM mfeller@ucsd.edu FU NINDS NIH HHS [NS13528] NR 176 TC 152 Z9 152 U1 1 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JUL PY 2005 VL 76 IS 4 BP 213 EP 235 DI 10.1016/j.pneurobio.2005.09.002 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 989PY UT WOS:000233687400001 PM 16280194 ER PT J AU Iuvone, PM Tosini, G Pozdeyev, N Haque, R Klein, DC Chaurasia, SS AF Iuvone, PM Tosini, G Pozdeyev, N Haque, R Klein, DC Chaurasia, SS TI Circadian clocks, clock networks, arylalkylarnine N-acetyltransferase, and melatonin in the retina SO PROGRESS IN RETINAL AND EYE RESEARCH LA English DT Review ID HYDROXYINDOLE-O-METHYLTRANSFERASE; CGMP-GATED CHANNELS; RAT PINEAL-GLAND; TRYPTOPHAN-HYDROXYLASE ACTIVITY; RECEPTOR-MEDIATED INHIBITION; SENSITIVE CALCIUM-CHANNELS; MESSENGER-RNA EXPRESSION; CYCLIC-AMP ACCUMULATION; JAPANESE-QUAIL RETINA; XENOPUS-LAEVIS RETINA AB Circadian clocks are self-sustaining genetically based molecular machines that impose similar to 24h rhythmicity on physiology and behavior that synchronize these functions with the solar day-night cycle. Circadian clocks in the vertebrate retina optimize retinal function by driving rhythms in gene expression, photoreceptor outer segment membrane turnover, and visual sensitivity. This review focuses on recent progress in understanding how clocks and light control arylalkylamine N-acetyltransferase (AANAT), which is thought to drive the daily rhythm in melatonin production in those retinas that synthesize the neurohormone; AANAT is also thought to detoxify arylalkylamines through N-acetylation. The review will cover evidence that cAMP is a major output of the circadian clock in photoreceptor cells; and recent advances indicating that clocks and clock networks occur in multiple cell types of the retina. (c) 2005 Elsevier Ltd. All rights reserved. C1 Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. Morehouse Sch Med, Inst Neurosci, Atlanta, GA 30310 USA. NICHD, Neuroendocrinol Lab, NIH, Bethesda, MD USA. RP Iuvone, PM (reprint author), Emory Univ, Sch Med, Dept Pharmacol, 1510 Clifton Rd,Rm 5107, Atlanta, GA 30322 USA. EM miuvone@pharm.emory.edu OI tosini, gianluca/0000-0003-3645-4533 FU NEI NIH HHS [EY04864, EY14764, R01 EY004864]; NIMH NIH HHS [MH062144]; NINDS NIH HHS [NS043459] NR 272 TC 190 Z9 193 U1 4 U2 18 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-9462 J9 PROG RETIN EYE RES JI Prog. Retin. Eye Res. PD JUL PY 2005 VL 24 IS 4 BP 433 EP 456 DI 10.1016/j.preteyeres.2005.01.003 PG 24 WC Ophthalmology SC Ophthalmology GA 923CA UT WOS:000228885100001 PM 15845344 ER PT J AU Wang, Z Mathias, A Stavrou, S Neville, DM AF Wang, Z Mathias, A Stavrou, S Neville, DM TI A new yeast display vector permitting free scFv amino termini can augment ligand binding affinities SO PROTEIN ENGINEERING DESIGN & SELECTION LA English DT Article DE CD3; FN18; pYD5; scFv; yeast display ID SINGLE-CHAIN IMMUNOTOXIN; T-CELL DEPLETION; SURFACE DISPLAY; SACCHAROMYCES-CEREVISIAE; ANTI-CD3 IMMUNOTOXIN; TOLERANCE INDUCTION; DIRECTED EVOLUTION; RHESUS MACAQUES; EXPRESSION; SECRETION AB Yeast surface display and sorting by flow cytometry are now widely used to direct the evolution of protein binding such as single-chain antibodies or scFvs. The available commercial yeast display vector pYD1 (Invitrogen) displays the protein of interest flanked on the N-terminus by Aga2, the disulfide of which binds the myristylated surface membrane protein Aga1. We have noted that two anti-CD3 epsilon scFvs expressed as fusion proteins suffer a 30- to 100-fold loss of affinity when placed NH2 terminal to either truncated toxins or human serum albumin. In the course of affinity maturing one of these scFv (FN18) using pYD1 we noted that the affinity towards the ectodomain of monkey CD3 epsilon gamma was too low to measure. Consequently we rebuilt pYD1 tethering the scFv off the NH2 terminus of Aga2. This display vector, pYD5, now gave a positive signal displaying FN18 scFv with its ligand, monkey CD3 epsilon gamma. The apparent equilibrium association constant of the higher affinity scFv directed at human CD3 epsilon gamma increased similar to 3-fold when displayed on pYD5 compared with pYD1. These data show that for certain yeast-displayed scFvs a carboxy-tethered scFv can result in increased ligand-scFv equilibrium association constants and thereby extend the low range of affinity maturation measurements. C1 NIMH, Sect Biophys Chem, Mol Biol Lab, Bethesda, MD 20892 USA. RP Neville, DM (reprint author), NIMH, Sect Biophys Chem, Mol Biol Lab, Bldg 10,36 Convent Dr, Bethesda, MD 20892 USA. EM davidn@mail.nih.gov NR 23 TC 19 Z9 22 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1741-0126 J9 PROTEIN ENG DES SEL JI Protein Eng. Des. Sel. PD JUL PY 2005 VL 18 IS 7 BP 337 EP 343 DI 10.1093/protein/gzi036 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 943IB UT WOS:000230345600004 PM 15976011 ER PT J AU Sharpe, S Yau, WM Tycko, R AF Sharpe, S Yau, WM Tycko, R TI Expression and purification of a recombinant peptide from the Alzheimer's beta-amyloid protein for solid-state NMR SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Alzheimer's; beta-amyloid; amyloid fibrils; solid-state NMR ID NUCLEAR-MAGNETIC-RESONANCE; ANGLE-SPINNING NMR; ESCHERICHIA-COLI; CORRELATION SPECTROSCOPY; ROTATING SOLIDS; ALPHA-SYNUCLEIN; SUPRAMOLECULAR STRUCTURE; STRUCTURAL CONSTRAINTS; DISTANCE MEASUREMENTS; MOLECULAR-STRUCTURE AB Fibrillar protein aggregates contribute to the pathology of a number of disease states. To facilitate Structural Studies of these amyloid fibrils, by solid-state NMR, efficient methods for the production of milligram quantities of isotopically labeled peptide are necessary. Bacterial expression of recombinant amyloid proteins and peptides allows uniform isotopic labeling, its well as other patterns of isotope incorporation. However, large-scale production of recombinant amyloidogenic peptides has proven particularly difficult, due to their inherent propensity for aggregation and the associated toxicity of fibrillar material, Yields of recombinant protein are further reduced by the small molecular weights or short amyloidogenic fragments. Here, we report high-yield expression and purification of a peptide comprising residues 11 26 of the Alzheimer's beta-amyloid protein (A beta(11) (26)). with homoserine lactone replacing serine at residue 26. Expression in inclusion bodies as a ketosteroid isomerase fusion protein and subsequent purification under denaturing conditions allows production of milligram quantities of uniformly labeled C-13- and N-15-labeled peptide, which forms amyloid fibrils suitable for solid-state NMR spectroscopy. Initial structural data obtained by atomic force microscopy, electron microscopy, and solid-state NMR measurements of A beta(11.26) fibrils are also presented. Published by Elsevier Inc. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Sharpe, S (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM Simon@intra.niddk.nih.gov NR 66 TC 38 Z9 40 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD JUL PY 2005 VL 42 IS 1 BP 200 EP 210 DI 10.1016/j.pep.2005.03.005 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 937HP UT WOS:000229915500027 PM 15939307 ER PT J AU Prasanna, MD Vondrasek, J Wlodawer, A Bhat, TN AF Prasanna, MD Vondrasek, J Wlodawer, A Bhat, TN TI Application of InChI to curate, index, and query 3-D structures SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS PROTEASE; DATA-BANK; INFECTIVITY AB The HIV structural database (HIVSDB) is a comprehensive collection of the structures of HIV protease, both of unliganded enzyme and of its inhibitor complexes. It contains abstracts and crystallographic data such as inhibitor and protein coordinates for 248 data sets, of which only 141 are from the Protein Data Bank (PDB). Efficient annotation, indexing, and querying of the inhibitor data is crucial for their effective use for technological and industrial applications. The application of IUPAC International Chemical Identifier (InChI) to index, curate, and query inhibitor structures HIVSDB is described. Published 2005 Wiley-Liss, Inc.* C1 NIST, Div Biotechnol, Gaithersburg, MD 20899 USA. Acad Sci Czech Republ, Inst Organ Chem & Biochem, Prague, Czech Republic. NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP Bhat, TN (reprint author), NIST, Div Biotechnol, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM bhat@nist.gov RI Vondrasek, JIri/A-4244-2008 NR 15 TC 20 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD JUL 1 PY 2005 VL 60 IS 1 BP 1 EP 4 DI 10.1002/prot.20469 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 930YY UT WOS:000229454200001 PM 15861385 ER PT J AU McDonough, J Marban, E AF McDonough, J Marban, E TI Optimization of IPG strip equilibration for the basic membrane protein mABC1 SO PROTEOMICS LA English DT Article DE 2-D gels; basic proteins; equilibration; IPG; membrane proteins ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; IMMOBILIZED PH GRADIENTS; DEPENDENT POTASSIUM CHANNELS; PROTEOMICS; SEPARATION; RESOLUTION; EFFECTORS; COMPLEX AB Many proteins with extreme physical properties, including basic and acidic proteins, membrane proteins, and very large proteins, present specific challenges to 2-DE separation. Using a pressure-blotting approach, we demonstrate that a basic integral membrane protein, mitochondrial ATP-binding cassette protein 1 (mABC1), focuses in the IPG strip, but fails to enter into the 2-D SDS-PAGE gel. Through modifying the equilibration conditions between the IPG strip and 2nd dimension, we demonstrate that only by increasing both the volume (from 3 to 6 mL for a 7-cm strip) and SDS concentration (from 2 to 10 %) of the equilibration buffer is migration of mABC1 into the 2nd dimension achieved. While 2-DE remains one of the core separation technologies of proteomic analysis, proteins that are extremely basic, hydrophobic, or of large mass present significant challenges to 2-DE separation due to aggregation, oxidation, precipitation, and the physical limitations of the 1-D IPG strip (for recent reviews, see [1-7]). Since the advent of commercially available I PG strips, numerous groups have experimented with IEF conditions using various detergents alone or in combination [8], alternative denaturants [9], and thiol oxidation agents [10] to improve protein focusing. Effective 2-DE separation of membrane proteins has been affected dramatically by these advances in protein solubilization, as well as improvements in isolation of membranes, delipidation, and active in-gel rehydration [11, for recent reviews see 4, 5, 7]. Since the development of commercially available basic IPG strips, the most significant advance in the separation of basic proteins has been the introduction of hydroxyethyldisulfides, either alone or in combination with DTT [10]. While hydrophobic proteins were once virtually absent from the 2-D gel, and basic proteins were only visible as dense streaks, now many groups are undertaking large-scale analyses of membranes and basic proteins. Using this base of experimental tools, we embarked on a proteomic analysis of cardiac mitocliondrial membranes, hoping to combine the knowledge gained from ongoing targeted protein chemistry and molecular biology studies with a broader-based proteomic analysis. Of particular interest is the inner mitochondrial membrane protein mABC1 (mitochondrial ATP-binding cassette protein 1), which may play a significant role in cardioprotection as part of the mitochondrial ATP-sensitive potassium channels [12-14]. Therefore, in designing our 2-DE approach, it was crucial to ensure that mABC1 is focused, observable, and quantifiable, despite being an integral membrane protein of p19.37. C1 Johns Hopkins Univ, Div Cardiol, NHLBI, Proteom Ctr, Baltimore, MD 21250 USA. RP Marban, E (reprint author), Johns Hopkins Univ, Div Cardiol, NHLBI, Proteom Ctr, 720 Rutland Ave,Ross 858, Baltimore, MD 21250 USA. EM marban@jhmi.edu FU NHLBI NIH HHS [N01-HV-28180] NR 22 TC 19 Z9 21 U1 0 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JUL PY 2005 VL 5 IS 11 BP 2892 EP 2895 DI 10.1002/pmic.200401155 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 952WJ UT WOS:000231036100018 PM 16075418 ER PT J AU Koenigsberg, HW Buchsbaum, MS Buchsbaum, BR Schneiderman, JS Tang, CY New, A Goodman, M Siever, LJ AF Koenigsberg, HW Buchsbaum, MS Buchsbaum, BR Schneiderman, JS Tang, CY New, A Goodman, M Siever, LJ TI Functional MRI of visuospatial working memory in schizotypal personality disorder: a region-of-interest analysis SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DORSOLATERAL PREFRONTAL CORTEX; SCHIZOPHRENIC SUBJECTS; PERFORMANCE; TASK; FMRI; DYSFUNCTION; RECOGNITION; ACTIVATION; WORDS AB Background. Functional MRI studies have begun to identify neural networks implicated in visuo-spatial working memory in healthy volunteers and patients with schizophrenia. The study of schizotypal personality disorder (SPD) provides regional analysis in unmedicated patients in the schizophrenia spectrum. Method. Unmedicated patients with SPD by DSM-IV criteria and normal controls were assessed with fMRI while performing a visuospatial working-memory task. It required the subjects to retain the location of three dots located on the circumference of an imaginary circle and then respond to a query display in which one dot was presented and the subject required to press a button to indicate whether the probe dot location was previously displayed. Subject groups did not differ significantly in spatial memory scores. The exact Talairach and Tournoux coordinates of brain areas previously reported to show activation with spatial memory tasks were assessed. Results. The majority of these locations showed BOLD response activation significantly less in patients during the memory retention period, including the left ventral prefrontal cortex, superior frontal gyrus, intraparietal cortex and posterior inferior gyrus. Regions in the right middle prefrontal and prestriate cortex showed greater activation at a trend level for patients with SPD than for normal controls. In addition, we replicated the findings of increased activation with the task in healthy volunteers in the premotor areas, ventral prefrontal cortex and parietal cortex. Conclusions. SPD patients show decreased activation compared to healthy volunteers in key frontal regions and we also provided a partial replication of findings reported in healthy subjects. C1 Bronx Vet Affairs Med Ctr, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Radiol, New York, NY USA. RP Koenigsberg, HW (reprint author), Bronx Vet Affairs Med Ctr, 130 W Kingsbridge, Bronx, NY 10468 USA. EM harold.koenigsberg@med.va.gov RI Schneiderman, Jason/E-1528-2013 OI Schneiderman, Jason/0000-0002-9313-0415 FU NCRR NIH HHS [5M01 RR00071] NR 31 TC 20 Z9 20 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUL PY 2005 VL 35 IS 7 BP 1019 EP 1030 DI 10.1017/S0033291705004393 PG 12 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 959EN UT WOS:000231500000010 PM 16045068 ER PT J AU Kudwa, AE Dominguez-Salazar, E Cabrera, DM Sibley, DR Rissman, EF AF Kudwa, AE Dominguez-Salazar, E Cabrera, DM Sibley, DR Rissman, EF TI Dopamine D5 receptor modulates male and female sexual behavior in mice SO PSYCHOPHARMACOLOGY LA English DT Article DE sexual behavior; dopamine; conditioned place preference; drugs; motivation; knockout mice; reward; attention deficit hyperactivity disorder ID CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS; MALE-RATS; PROGESTIN RECEPTOR; ESTROUS FEMALE; KNOCKOUT MICE; PREOPTIC AREA; D2 RECEPTORS; MUTANT MICE; COCAINE AB Rationale: Dopamine exerts its actions through at least five receptor (DAR) isoforms. In female rats, D5 DAR may be involved in expression of sexual behavior. We used a D5 knockout (D5KO) mouse to assess the role of D5 DAR in mouse sexual behavior. Both sexes of D5KO mice are fertile and exhibit only minor disruptions in exploratory locomotion, startle, and prepulse inhibition responses. Objective: This study was conducted to characterize the sexual behavior of male and female D5KO mice relative to their WT littermates. Methods: Female WT and D5KO littermates were ovariectomized and given a series of sexual behavior tests after treatment with estradiol benzoate (EB) and progesterone ( P). Once sexual performance was optimal the dopamine agonist, apomorphine (APO), was substituted for P. Male mice were observed in pair- and trio- sexual behavior tests. To assess whether the D5 DAR is involved in rewarding aspects of sexual behavior, WT and D5KO male mice were tested for conditioned place preference. Results: Both WT and D5KO females can display receptivity after treatment with EB and P, but APO was only able to facilitate receptivity in EB-primed WT, not in D5KO, mice. Male D5KO mice display normal masculine sexual behavior in mating tests. In conditioned preference tests, WT males formed a conditioned preference for context associated with either intromissions alone or ejaculation as the unconditioned stimulus. In contrast, D5KO males only showed a place preference when ejaculation was paired with the context. Conclusions: In females, the D5 DAR is essential for the actions of dopamine on receptivity. In males, D5 DAR influences rewarding aspects of intromissions. Taken together, the work suggests that the D5 receptor mediates dopamine's action on sexual behavior in both sexes, perhaps via a reward pathway. C1 Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Grad Program Neurosci, Charlottesville, VA 22908 USA. RP Rissman, EF (reprint author), Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. EM rissman@virginia.edu RI Cabrera, David/I-1013-2014 FU NICHD NIH HHS [HD072323]; NIMH NIH HHS [K02 MH01349, R01 MH57759] NR 56 TC 23 Z9 24 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2005 VL 180 IS 2 BP 206 EP 214 DI 10.1007/s00213-005-2150-5 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 934SX UT WOS:000229729800002 PM 15696326 ER PT J AU Jutkiewicz, EM Wood, SK Houshyar, H Hsin, LW Rice, KC Woods, JH AF Jutkiewicz, EM Wood, SK Houshyar, H Hsin, LW Rice, KC Woods, JH TI The effects of CRF antagonists, antalarmin, CP154,526, LWH234, and R121919, in the forced swim test and on swim-induced increases in adrenocorticotropin in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE CRF antagonists; forced swim test; rats; ACTH ID CORTICOTROPIN-RELEASING HORMONE; FACTOR(1) RECEPTOR ANTAGONIST; STRESS-RELATED DISORDERS; ENDOCRINE RESPONSES; MAJOR DEPRESSION; ANXIOLYTIC-LIKE; VASOPRESSIN; MODEL; ANTIDEPRESSANTS; BRAIN AB Rationale: Exposure to extreme stress has been suggested to produce long-term, detrimental alterations in the hypothalamic - pituitary - adrenal (HPA) axis leading to the development of mental disorders such as depression. Therefore, compounds that block the effects of stress hormones were investigated as potential therapeutics for depression. Objectives: In the present study, we compared the potential antidepressant-like effects of four CRF antagonists, antalarmin, CP154,526, R121919, and LWH234 ( at 3, 10, and 30 mg/kg i.p., 60 min prior to the forced swim test) and the corresponding effect on swim-induced HPA activation to better elucidate the relation between HPA activity and antidepressant activity. Methods: The antidepressant-like effects of the CRF antagonists and known antidepressants were determined in the rat forced swim test, and blood samples were obtained before and after swimming for the evaluation of adrenocorticotropin-releasing hormone ( ACTH) levels. Results: Antalarmin, CP154,526, and R121919 did not produce antidepressant-like effects in the forced swim test although these compounds decreased swim-induced increases in ACTH to various extents. In contrast, LWH234 reduced immobility in the forced swim test, without altering the swim-stress-induced ACTH response. However, this compound antagonized restraint-induced ACTH release. Conclusions: These data suggest that reducing stress-induced increases in HPA activity alone may not be sufficient to produce antidepressant-like activity; however, reductions in HPA activity may contribute to antidepressant actions of some treatments. In addition, it is proposed that CRF antagonists may alter differentially the HPA axis depending on the type of stressor used or behavioral measure evaluated. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Natl Taiwan Univ, Coll Med, Sch Pharm, Taipei 10018, Taiwan. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jutkiewicz, EM (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. EM ejutkiew@umich.edu OI HSIN, LING-WEI/0000-0001-5018-4491; Wood, Susan/0000-0001-5732-3335 FU NIDA NIH HHS [DA07267, DA14349, DA00254, T32 DA007267, R01 DA014349, P50 DA000254, K21 DA000254, P01 DA000254]; NIGMS NIH HHS [GM07767, T32 GM007767] NR 38 TC 54 Z9 55 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2005 VL 180 IS 2 BP 215 EP 223 DI 10.1007/s00213-005-2164-z PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 934SX UT WOS:000229729800003 PM 15696320 ER PT J AU Ghelardoni, S Bazinet, RP Rapoport, SI Bosetti, F AF Ghelardoni, S Bazinet, RP Rapoport, SI Bosetti, F TI Topiramate does not alter expression in rat brain of enzymes of arachidonic acid metabolism SO PSYCHOPHARMACOLOGY LA English DT Article DE arachidonic acid; brain; bipolar disorder; mood stabilizer; anticonvulsant; topiramate ID CULTURED HIPPOCAMPAL-NEURONS; BIPOLAR DISORDER; CHRONIC LITHIUM; PHOSPHOLIPASE A(2); CYCLOOXYGENASE ACTIVITY; DOCOSAHEXAENOIC ACID; SIGNAL-TRANSDUCTION; NERVOUS-SYSTEM; MODULATION; VALPROATE AB Rationale: When administered chronically to rats, drugs that are effective in bipolar disorder-lithium and the anticonvulsants, valproic acid and carbamazepine - have been shown to downregulate the expression of certain enzymes involved in brain arachidonic acid (AA) release and cyclooxygenase ( COX)-mediated metabolism. Phase II clinical trials with the anticonvulsant topiramate [2,3: 4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate] suggest that this drug may also be effective for bipolar disorder. Objectives: To see if topiramate has effects similar to those of the other three drugs, we administered topiramate to rats for 14 days at 20 mg/kg, p.o. twice daily. Results: Compared with p.o. vehicle, topiramate treatment did not significantly affect the brain activity or protein level of cytosolic phospholipase A(2), secretory PLA(2), or Ca2+-independent iPLA(2). Additionally, brain protein levels of COX-1, COX-2, 5-lipoxygenase, and cytochrome P450 epoxygenase were unchanged. Conclusions: These results suggest that topiramate does not modify expression of the enzymes involved in brain AA metabolism that have been shown to be targeted by lithium, valproic acid, or carbamazepine. If topiramate proves effective in bipolar disorder, it may not act by modulating brain AA metabolism. In view of the proven anticonvulsant effect of topiramate, our results also suggest that the AA cascade is not involved in the antiseizure properties of the drug. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 10,Rm 6N202, Bethesda, MD 20892 USA. EM frances@mail.nih.gov FU Intramural NIH HHS NR 51 TC 19 Z9 19 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0033-3158 EI 1432-2072 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUL PY 2005 VL 180 IS 3 BP 523 EP 529 DI 10.1007/s00213-005-2189-3 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 936XS UT WOS:000229889500015 PM 15719218 ER PT J AU Olson, MB Krantz, DS Kelsey, SF Pepine, CJ Sopko, G Handberg, E Rogers, WJ Gierach, GL McClure, CK Merz, CNB AF Olson, MB Krantz, DS Kelsey, SF Pepine, CJ Sopko, G Handberg, E Rogers, WJ Gierach, GL McClure, CK Merz, CNB CA WISE Study Grp TI Hostility scores are associated with increased risk of cardiovascular events in women undergoing coronary angiography: A report from the NHLBI-sponsored WISE study SO PSYCHOSOMATIC MEDICINE LA English DT Article DE hostility; cardiovascular events; women ID ACUTE MYOCARDIAL-INFARCTION; WESTERN COLLABORATIVE GROUP; FACTOR INTERVENTION TRIAL; HEART-DISEASE; ARTERY DISEASE; FOLLOW-UP; POSTMENOPAUSAL WOMEN; PSYCHOSOCIAL FACTORS; TOTAL MORTALITY; CHD INCIDENCE AB Objective: To evaluate hostility-related personality traits assessed by the Cook Medley Hostility Inventory and to relate these to the occurrence of adverse cardiac events in women with suspected myocardial ischemia. Methods: The cohort included 506 women with suspected coronary artery disease from the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. We examined individual components of the Cook Medley Hostility Score (CMHS) measuring cynicism, hostile affect, and aggressive responding, and a total CMHS (sum of these three) and associations with adverse events (defined as hospitalization for angina, nonfatal myocardial infarction, stroke, congestive heart failure (CHF) other vascular events and death) during 3 to 6 years follow-up using Cox proportional hazard modeling. Results: Women with adverse events had higher total CMHS (10.6 +/- 5.5) than women without any of these events (9.2 +/- 5. 1) p = .02. They also had poorer survival by Kaplan-Meier analysis (log-rank p < .05). Unadjusted Cox models showed that the individual scores of cynicism and aggressive responding and the total CMHS were associated with more adverse events (all p < .05). Women with total CMHS above the median had a 35% increase risk of an adverse event in comparison to women with lower scores. In a risk-adjusted Cox model, the hazard ratio for an adverse event was 1.5 (p = .03) for women with total CMHS above the median. Conclusion: In this cohort of women with suspected myocardial ischemia, higher Cook Medley scores reflecting cynicism, hostile affect, and aggressive responding were associated with poorer 3 to 6 year event-free survival and a higher risk of adverse events. After adjusting for risk factors and CAD, the association with risk for adverse events increased. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL USA. NHLBI, NIM, Bethesda, MD 20892 USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Cedars Sinai Med Ctr, Dept Med, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. RP Olson, MB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Room 127 Parran Hall,130 Desoto St, Pittsburgh, PA 15261 USA. EM molson@hs.pitt.edu RI Krantz, David/L-5364-2015; Gierach, Gretchen/E-1817-2016 OI Krantz, David/0000-0002-1671-1355; Gierach, Gretchen/0000-0002-0165-5522 FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, U01-HL64829, U01-HL64914, U01-HL64924] NR 45 TC 19 Z9 19 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2005 VL 67 IS 4 BP 546 EP 552 DI 10.1097/01.psy.0000170830.92263.4e PG 7 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 950AS UT WOS:000230830600006 PM 16046366 ER PT J AU Miller, FG Wendler, D AF Miller, FG Wendler, D TI Placebo research and the spirit of informed consent SO PSYCHOSOMATIC MEDICINE LA English DT Letter C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 2 Z9 2 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JUL-AUG PY 2005 VL 67 IS 4 BP 678 EP 678 DI 10.1097/01.psy.0000172146.62930.e2 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 950AS UT WOS:000230830600028 PM 16046388 ER PT J AU Bussey, TJ Saksida, LM AF Bussey, TJ Saksida, LM TI The perceptual-mnemonic/feature conjunction model of perirhinal cortex function SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION B-COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Experimental-Psychology-Society CY APR, 2004 CL Oxford, ENGLAND SP Expt Psychol Soc ID MEDIAL TEMPORAL-LOBE; RECOGNITION MEMORY; RHINAL CORTEX; OBJECT RECOGNITION; RHESUS-MONKEYS; VISUAL-DISCRIMINATION; CONNECTIONIST MODEL; DECLARATIVE MEMORY; TO-SAMPLE; LESIONS AB The perirhinal cortex was once thought to be "silent cortex", virtually ignored by researchers interested in the neurobiology of learning and memory. Following studies of brain damage associated with cases of amnesia, perirhinal cortex is now widely regarded as part of a "medial temporal lobe (MTL) memory system". This system is thought to be more or less functionally homogeneous, having a special role in declarative memory, and making little or no contribution to other functions such as perception. In the present article, we summarize an alternative view. First, we propose that components of the putative MTL system such as the hippocampus and perirhinal cortex have distinct and dissociable functions. Second, we provide evidence that the perirhinal cortex has a role in visual discrimination. In addition, we propose a specific role for perirhinal cortex in visual discrimination: the contribution of complex conjunctive representations to the solution of visual discrimination problems with a high degree of "feature ambiguity". These proposals constitute a new view of perirhinal cortex function, one that does not assume strict modularity of function in the occipito-temporal visual stream, but replaces this idea with the notion of a hierarchical representational continuum. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. NIMH, Bethesda, MD 20892 USA. RP Bussey, TJ (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM t.bussey@psychol.cam.ac.uk RI Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016; OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 45 TC 100 Z9 100 U1 2 U2 8 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0272-4995 J9 Q J EXP PSYCHOL-B JI Q. J. Exp. Psychol. Sect. B-Comp. Physiol. Psychol. PD JUL-OCT PY 2005 VL 58 IS 3-4 BP 269 EP 282 DI 10.1080/02724990544000004 PG 14 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 958BA UT WOS:000231418500006 PM 16194969 ER PT J AU Murray, EA AF Murray, EA TI Perirhinal cortex and its neighbours in the medial temporal lobe: Contributions to memory and perception SO QUARTERLY JOURNAL OF EXPERIMENTAL PSYCHOLOGY SECTION B-COMPARATIVE AND PHYSIOLOGICAL PSYCHOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Experimental-Psychology-Society CY JUN, 2004 CL Univ Lancaster, Lancaster, ENGLAND SP Expt Psychol Soc HO Univ Lancaster ID VISUAL OBJECT RECOGNITION; LONG-TERM-MEMORY; MONKEY INFEROTEMPORAL CORTEX; SELECTIVE HIPPOCAMPAL DAMAGE; RHINAL CORTEX; RHESUS-MONKEYS; STIMULUS ASSOCIATION; PARAHIPPOCAMPAL CORTICES; FORNIX TRANSECTION; POSTRHINAL CORTEX AB As promised in the Introduction, this Special Issue presents several recurring themes concerning the perirhinal cortex and its neighbours within the medial temporal lobe (MTL). First, although orthodoxy insists that the diverse constituents of the MTL operate as a single functional entity, several papers presented here challenge that idea, although some defend it. Second, although many experts hold that the MTL subserves memory but not perception, several papers presented here point to a role for certain MTL structures in both. Third, although some researchers have invoked "species differences" to account for discrepant findings, several papers presented here document a striking convergence of findings in humans, nonhuman primates, and rodents. We close this Special Issue by highlighting these recurring themes, acknowledging discrepant findings and pointing to future research that might resolve some current controversies. C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. MRC, Cognit & Brain Sci Unit, Cambridge, England. Univ Oxford, Oxford OX1 2JD, England. RP NIMH, Neuropsychol Lab, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642; Graham, Kim/0000-0002-1512-7667 NR 87 TC 33 Z9 33 U1 0 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0272-4995 J9 Q J EXP PSYCHOL-B JI Q. J. Exp. Psychol. Sect. B-Comp. Physiol. Psychol. PD JUL-OCT PY 2005 VL 58 IS 3-4 BP 378 EP 396 DI 10.1080/02724990544000077 PG 19 WC Psychology, Biological; Physiology; Psychology; Psychology, Experimental SC Psychology; Physiology GA 958BA UT WOS:000231418500012 PM 16194975 ER PT J AU Elmore, JG Taplin, SH Barlow, WE Cutter, GR D'Orsi, CJ Hendrick, RE Abraham, LA Fosse, JS Carney, PA AF Elmore, JG Taplin, SH Barlow, WE Cutter, GR D'Orsi, CJ Hendrick, RE Abraham, LA Fosse, JS Carney, PA TI Does litigation influence medical practice? The influence of community radiologists' medical malpractice perceptions and experience on screening mammography SO RADIOLOGY LA English DT Article ID DEFENSIVE MEDICINE; BREAST-CANCER; NONSUED PHYSICIANS; REASONED ACTION; POPULATION; ATTITUDES; EDUCATION; OUTCOMES; TRIALS AB PURPOSE: To assess the relationship between radiologists' perception of and experience with medical malpractice and their patient-recall rates in actual community-based clinical settings. MATERIALS AND METHODS: All study activities were approved by the institutional review boards of the involved institutions, and patient and radiologist informed consent was obtained where necessary. This study was performed in three regions of the United States (Washington, Colorado, and New Hampshire). Radiologists who routinely interpret mammograms completed a mailed survey that included questions on demographic data, practice environment, and medical malpractice. Survey responses were linked to interpretive performance for all screening mammography examinations performed between January 1, 1996, and December 31, 2001. The odds of recall were modeled by using logistic regression analysis based on generalized estimating equations that adjust for study region. RESULTS: Of 181 eligible radiologists, 139 (76.8%) returned the survey with full consent. The analysis included 124 radiologists who had interpreted a total of 557 143 screening mammograms. Approximately half (64 of 122 [52.4%]) of the radiologists reported a prior malpractice claim, with 18 (14.8%) reporting mammography-related claims. The majority (n = 51 [81.0%]) of the 63 radiologists who responded to a question regarding the degree of stress caused by a medical malpractice claim described the experience as very or extremely stressful. More than three of every four radiologists (ie, 94 [76.4%] of 123) expressed concern about the impact medical malpractice has on mammography practice, with over half (72 [58.5%] of 123) indicating that their concern moderately to greatly increased the number of their recommendations for breast biopsies. Radiologists' estimates of their future malpractice risk were substantially higher than the actual historical risk. Almost one of every three radiologists (43 of 122 [35.3%]) had considered withdrawing from mammogram interpretation because of malpractice concerns. No significant association was found between recall rates and radiologists' experiences or perceptions of medical malpractice. CONCLUSION: U.S. radiologists are extremely concerned about medical malpractice and report that this concern affects their recall rates and biopsy recommendations. However, medical malpractice experience and concerns were not associated with recall or false-positive rates. Heightened concern of almost all radiologists may be a key reason that recall rates are higher in the United States than in other countries, but this hypothesis requires further study. ((c)) RSNA 2005. C1 Univ Washington, Harborview Med Ctr, Sch Med, Dept Internal Med, Seattle, WA 98104 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Canc Res & Biostat, Seattle, WA USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Emory Univ, Dept Radiol, Atlanta, GA 30322 USA. Northwestern Univ, Feinberg Sch Med, Lynn Sage Comprehens Breast Ctr, Chicago, IL 60611 USA. Dartmouth Coll, Off Med Educ, Hanover, NH USA. RP Elmore, JG (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, Dept Internal Med, 325 9Th Ave,Box 359780, Seattle, WA 98104 USA. EM jelmore@u.washington.edu FU AHRQ HHS [HS-10591, R01 HS010591]; NCI NIH HHS [1 U01 CA86082-01, 5 U01 CA63736-09, 5 U01 CA86076, K05 CA104699, R01 CA107623, R01 CA107623-04, U01 CA063731, U01 CA063736, U01 CA086076, U01 CA086082, U01 CA63731] NR 47 TC 53 Z9 53 U1 1 U2 6 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUL PY 2005 VL 236 IS 1 BP 37 EP 46 DI 10.1148/radiol.2361040512 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937DR UT WOS:000229905300006 PM 15987961 ER PT J AU Jardeleza, MS Chi, CC Shalaby, I de la Cruz, Z Shen, DF Green, WR AF Jardeleza, MS Chi, CC Shalaby, I de la Cruz, Z Shen, DF Green, WR TI Clinicopathologic and ultrastructural study of endogenous Klebsiella pneumoniae endophthalmitis SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE clinicopathologic correlation; endogenous endophthalmitis; Klebsiella pneumoniae endophthalmitis; transmission electron microscopy ID POLYMERASE-CHAIN-REACTION; BETA-LACTAMASE; BACTERIAL ENDOPHTHALMITIS; MICRODISSECTION; VITRECTOMY; SEQUENCE; PCR C1 Wilmer Eye Inst, Eye Pathol Lab, Baltimore, MD USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NEI, Immunopathol Sect, Bethesda, MD 20892 USA. Greater Baltimore Med Ctr, Baltimore, MD USA. RP Green, WR (reprint author), Johns Hopkins Univ Hosp, Eye Pathol Lab, Maumenee 427,600 N Wolfe St, Baltimore, MD 21287 USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUL-AUG PY 2005 VL 25 IS 5 BP 657 EP 662 DI 10.1097/00006982-200507000-00019 PG 6 WC Ophthalmology SC Ophthalmology GA 008AO UT WOS:000235012800019 PM 16077366 ER PT J AU Berger, VW Semanick, L AF Berger, VW Semanick, L TI Refining the assessment of the sensitivity and specificity of diagnostic tests, with applications to prostate cancer screening and non-small cell lung cancer staging SO REVISTA PANAMERICANA DE SALUD PUBLICA-PAN AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE neoplasms; diagnostic techniques and procedures; early diagnosis; neoplasm staging; sensitivity and specificity; predictive value of tests ID DIGITAL RECTAL EXAMINATION; ANTIGEN; TRIAL C1 NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. RP Berger, VW (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Execut Plaza N,Suite 3131,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. EM vb78c@nih.gov NR 14 TC 1 Z9 1 U1 0 U2 1 PU PAN AMERICAN HEALTH ORGANIZATION PI WASHINGTON PA 525 23RD ST NW, WASHINGTON, DC 20037 USA SN 1020-4989 J9 REV PANAM SALUD PUBL JI Rev. Panam. Salud Publica PD JUL PY 2005 VL 18 IS 1 BP 64 EP 70 DI 10.1590/S1020-49892005000600013 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 953AV UT WOS:000231048800010 PM 16105328 ER PT J AU Kruit, MC Launer, LJ van Buchem, MA Terwindt, GM Ferrari, MD AF Kruit, MC Launer, LJ van Buchem, MA Terwindt, GM Ferrari, MD TI MRI findings in migraine SO REVUE NEUROLOGIQUE LA English DT Article DE brain infarction; stroke; cerebral ischemia; cerebrovascular disorders; magnetic resonance imaging; demyelinating disease ID CEREBRAL WHITE-MATTER; ISCHEMIC-STROKE; RISK; PREVALENCE; LESIONS; METAANALYSIS; INFARCTS; PEOPLE AB Introduction. For long time, migraine has been considered to be an episodic, multifactorial, neurovascular disorder, without long-term consequences to the brain, although an association between migraine and clinical stroke and white matter hyperintense lesions has been suggested in numerous studies. Due to various methodological problems no definite conclusion could be drawn from these studies. State of the Art. Recently, data from a population-based cross-sectional MRI study were published, establishing migraine to be a true and independent risk factor for white matter lesions (in female migraine patients) and subdinical posterior circulation territory infarcts. Perspectives. The methodology and results of previous investigations of a relationship between migraine and clinical ischemic stroke, silent infarction and white matter lesions are reviewed, and integrated in the results from the new population-based MRI study. Conclusion. Brain infarction occurs far more frequently than expected in migraine patients, most pronounced in migraine with aura (8 percent have subdinical cerebellar infarcts), although most infarcts remain clinically silent. Female migraine patients are at increased risk of deep white matter lesions, independent of the effects of cardiovascular risk factors. The influence of migraine severity (attack frequency) on the risk of both types of lesions suggests a causal relationship between migraine severity and lesion load. Future studies are needed to assess whether these (probably) ischemic lesions have relevant (long-term) functional correlates. C1 Leiden Univ, Ctr Med, Dept Radiol, NL-2333 ZA Leiden, Netherlands. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. Leiden Univ, Ctr Med, Dept Neurol, Leiden, Netherlands. RP Kruit, MC (reprint author), Leiden Univ, Ctr Med, Dept Radiol, Albinusdreef 2, NL-2333 ZA Leiden, Netherlands. EM m.c.kruit@lumc.nl RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X NR 16 TC 24 Z9 26 U1 0 U2 1 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0035-3787 J9 REV NEUROL-FRANCE JI Rev. Neurol. PD JUL PY 2005 VL 161 IS 6-7 BP 661 EP 665 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 943HU UT WOS:000230344900008 PM 16141952 ER PT J AU Zitserman, VY Stojilkovich, KS Berezhkovskii, AM Bezrukov, SM AF Zitserman, VY Stojilkovich, KS Berezhkovskii, AM Bezrukov, SM TI Electrical conductivity of aqueous solutions of polyethylene glycol SO RUSSIAN JOURNAL OF PHYSICAL CHEMISTRY LA English DT Article ID SEMIDILUTE POLYMER-SOLUTIONS; HYDRODYNAMIC SCALING MODEL; STOKES-EINSTEIN LAW; SELF-DIFFUSION; POLY(ETHYLENE GLYCOL)S; PROBE DIFFUSION; ATOMIC TEST; 298.15 K; WATER; VISCOSITY AB New data on the electrical conductivity and viscosity of aqueous solutions of polyethylene glycol were obtained and used as reference data in studying the ionic channels of biological membranes. Over wide ranges of concentration and polymer molecular weight, conductivity was independent of the molecular weight for long chains and weakly depended on the molecular weight for short chains. Several models suggested in the literature for solving the general problem of the diffusion of a tracer in polymeric solutions are discussed. The processes responsible for a decrease in the mobility of ions were qualitatively analyzed to explain the weak conductivity sensitivity to the length of polymer chains. It is shown that experiments can be interpreted using the microviscosity concept. Microviscosity increases with the addition of a polymer much less rapidly than usual (macroscopic) viscosity. A simple empirical formula describing the dependence of conductivity on the polymer concentration is suggested. C1 Russian Acad Sci, IVTAN, Thermophys Ctr, Moscow 125412, Russia. NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Bethesda, MD 20892 USA. Russian Acad Sci, BP Konstantinov Nucl Phys Inst, Gatchina 188350, Leningradskaya, Russia. RP Zitserman, VY (reprint author), Russian Acad Sci, IVTAN, Thermophys Ctr, Izhorskaya Ul 13-19, Moscow 125412, Russia. EM vz1941@mail.ru NR 49 TC 2 Z9 2 U1 2 U2 2 PU INTERPERIODICA PI BIRMINGHAM PA PO BOX 1831, BIRMINGHAM, AL 35201-1831 USA SN 0036-0244 J9 RUSS J PHYS CHEM+ JI Russ. J. Phys. Chem. PD JUL PY 2005 VL 79 IS 7 BP 1083 EP 1089 PG 7 WC Chemistry, Physical SC Chemistry GA 943KS UT WOS:000230353000015 ER PT J AU Nabel, EG AF Nabel, EG TI A vision for the future: Opportunities and challenges - Notes from the Director National Heart, Lung, and Blood Institute SO SLEEP LA English DT Editorial Material C1 NHLBI, Off Director, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, Off Director, Bldg 31,Room 5A52,31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD JUL 1 PY 2005 VL 28 IS 7 BP 788 EP 789 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 945KP UT WOS:000230501700001 PM 16124652 ER PT J AU Vega-Bermudez, F Szczepanski, S Malow, B Sato, S AF Vega-Bermudez, F Szczepanski, S Malow, B Sato, S TI Sawtooth wave density analysis during REM sleep in temporal lobe epilepsy patients SO SLEEP MEDICINE LA English DT Article DE sawtooth waves; REM sleep; temporal lobe epilepsy; polysomnography AB Background and purpose: This study analyzes sawtooth waves (STW), a characteristic feature of rapid eye movement (REM) sleep, in temporal lobe epilepsy patients in order to test the hypothesis of STW dysfunction in this population. Methods: Polysomnographic records from 16 patients with temporal lobe epilepsy and 11 controls were scored for density (STW/h of REM sleep), duration (STW duration in s), and frequency of STW (waves/second within each STW complex). These measures were compared between both groups. Results: STW measures were significantly different in control vs. epilepsy patients; respectively, density was 60.8 vs. 20.9 waves/h (P < 0.005), average duration was 6.5 vs. 5.4 s (P < 0.005 cycles 1-4), and frequency was 2.75 vs. 2.61 Hz (P < 0.0005 across all cycles). Conclusions: Our measurements show a change in the density, duration and frequency of STW in patients with temporal lobe epilepsy compared to controls. Other parameters of REM sleep appear to be similar in both groups. These findings suggest a cortical influence on REM sleep either directly or through limbic-hypothalamic-brainstem connections. (c) 2005 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Mind Brain Inst, Baltimore, MD 21218 USA. NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Neurol, Nashville, TN USA. RP Vega-Bermudez, F (reprint author), Johns Hopkins Univ, Mind Brain Inst, 3400 N Charles St,338 Krieger Hall, Baltimore, MD 21218 USA. EM fvega@jhu.edu NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1389-9457 J9 SLEEP MED JI Sleep Med. PD JUL PY 2005 VL 6 IS 4 BP 367 EP 370 DI 10.1016/j.sleep.2005.02.005 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 948BC UT WOS:000230690000014 PM 15946900 ER PT J AU Alberts, MJ Latchaw, RE Selman, WR Shephard, T Hadley, MN Brass, LM Koroshetz, W Marler, JR Booss, J Zorowitz, RD Croft, JB Magnis, E Mulligan, D Jagoda, A O'Connor, R Cawley, CM Connors, JJ Rose-DeRenzy, JA Emr, M Warren, M Walker, MD AF Alberts, MJ Latchaw, RE Selman, WR Shephard, T Hadley, MN Brass, LM Koroshetz, W Marler, JR Booss, J Zorowitz, RD Croft, JB Magnis, E Mulligan, D Jagoda, A O'Connor, R Cawley, CM Connors, JJ Rose-DeRenzy, JA Emr, M Warren, M Walker, MD CA Brain Attack Coalition TI Recommendations for comprehensive stroke centers - A consensus statement from the brain attack coalition SO STROKE LA English DT Review DE cerebrovascular disorders; cerebral hemorrhage; healthcare systems; patient care; university medical centers ID AMERICAN-HEART-ASSOCIATION; DIGITAL-SUBTRACTION-ANGIOGRAPHY; CAROTID-ARTERY STENOSIS; MIDDLE CEREBRAL-ARTERY; ACUTE ISCHEMIC-STROKE; HEALTH-CARE PROFESSIONALS; ANEURYSMAL SUBARACHNOID HEMORRHAGE; MAGNETIC-RESONANCE ANGIOGRAPHY; DURAL SINUS THROMBOSIS; SPECIAL WRITING GROUP AB Background and Purpose - To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease. Summary of Review - A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors. Conclusions - There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include: (1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology; (2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography; (3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center. C1 Univ Calif Davis, Dept Radiol, Sacramento, CA 95817 USA. Univ Hosp Cleveland, Dept Neurosurg, Cleveland, OH 44106 USA. Neurosci Consultants, Richmond, VA USA. Univ Alabama, Dept Neurosurg, Birmingham, AL USA. VA Connecticut Healthcare Syst, Neurol Serv, New Haven, CT USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NINDS, Bethesda, MD 20892 USA. Dept Vet Affairs, Off Natl Director Neurol, West Haven, CT USA. Univ Penn, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. Miami Cardiac & Vasc Inst, Miami, FL USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Amer Stroke Assoc, Dallas, TX USA. Natl Stroke Assoc, Englewood, CO USA. Mt Sinai Sch Med, Dept Emergency Med, New York, NY USA. Christiana Care Hlth Syst, Newark, DE USA. Emory Univ, Dept Neurosurg, Atlanta, GA 30322 USA. OSF St Francis Med Ctr, Peoria, IL USA. RP Alberts, MJ (reprint author), Northwestern Univ, Sch Med, Stroke Program, 710 N Lake Shore Dr,Room 1420, Chicago, IL 60611 USA. EM m-alberts@northwestern.edu OI Zorowitz, Richard/0000-0001-8938-786X NR 268 TC 316 Z9 327 U1 3 U2 26 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUL PY 2005 VL 36 IS 7 BP 1597 EP 1616 DI 10.1161/01.STR.0000170622.07210.b4 PG 20 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 941BW UT WOS:000230190600053 PM 15961715 ER PT J AU Saugar, I Luque, D Ona, A Rodriguez, JF Carrascosa, JL Trus, BL Caston, JR AF Saugar, I Luque, D Ona, A Rodriguez, JF Carrascosa, JL Trus, BL Caston, JR TI Structural polymorphism of the major capsid protein of a double-stranded RNA virus: An amphipathic alpha helix as a molecular switch SO STRUCTURE LA English DT Article ID BURSAL-DISEASE-VIRUS; ICOSAHEDRAL VIRUSES; CRYSTAL-STRUCTURE; 3-DIMENSIONAL RECONSTRUCTION; ELECTRON CRYOMICROSCOPY; FUNCTIONAL IMPLICATIONS; ANGSTROM RESOLUTION; VP3; POLYMERASE; BINDING AB The infectious bursal disease virus T=13 viral particle is composed of two major proteins, VP2 and VP3. Here, we show that the molecular basis of the conformational flexibility of the major capsid protein precursor, pVP2, is an amphipatic alpha helix formed by the sequence GFKDIIRAIR. VP2 containing this a helix is able to assemble into the T=13 capsid only when expressed as a chimeric protein with an N-terminal His tag. An amphiphilic c, helix, which acts as a conformational switch, is thus responsible for the inherent structural polymorphism of VP2. The His tag mimics the VP3 C-terminal region closely and acts as a molecular triggering factor. Using cryo-electron microscopy difference imaging, both polypeptide elements were detected on the capsid inner surface. We propose that electrostatic interactions between these two morphogenic elements are transmitted to VP2 to acquire the competent conformations for capsid assembly. C1 CSIC, Dept Struct Macromol, E-28049 Madrid, Spain. CSIC, Dept Mol & Cellular Biol, E-28049 Madrid, Spain. NIAMSD, Struct Biol Res Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAMSD, Imaging Sci Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Caston, JR (reprint author), CSIC, Dept Struct Macromol, Campus Univ Autonoma Madrid, E-28049 Madrid, Spain. EM jrcaston@cnb.uam.es RI Caston, Jose/L-5896-2014; Luque, Daniel/I-6467-2015 OI Caston, Jose/0000-0003-2350-9048; Luque, Daniel/0000-0002-0151-6020 NR 50 TC 39 Z9 42 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JUL PY 2005 VL 13 IS 7 BP 1007 EP 1017 DI 10.1016/j.str.2005.04.012 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 949YG UT WOS:000230824200010 PM 16004873 ER PT J AU Gilbert, JG Newman, AH Gardner, EL Ashby, CR Heidbreder, CA Pak, AC Peng, XQ Xi, ZX AF Gilbert, JG Newman, AH Gardner, EL Ashby, CR Heidbreder, CA Pak, AC Peng, XQ Xi, ZX TI Acute administration of SB-277011A, NGB 2904, or BP 897 inhibits cocaine cue-induced reinstatement of drug-seeking behavior in rats: Role of dopamine D-3 receptors SO SYNAPSE LA English DT Article; Proceedings Paper CT Meeting of the Society-for-Neuroscience CY 2004 CL San Diego, CA SP Soc Neurosci DE addiction; BP 897; cocaine; cue; dopamine; D-3 receptor; drug-seeking; NGB 2904; reinstatement; relapse; SB-277011A ID NUCLEUS-ACCUMBENS CORE; CONDITIONED PLACE PREFERENCE; BASOLATERAL AMYGDALA; D3 RECEPTOR; PARTIAL AGONIST; SELECTIVE ANTAGONISM; D-AMPHETAMINE; DIFFERENTIAL INVOLVEMENT; MESSENGER-RNA; HIGH-AFFINITY AB Recent studies have shown that the novel dopamine (DA) D-3 receptor antagonists SB-277011A and NGB 2904 inhibit cocaine- and/or stress-induced reinstatement of drug-seeking behavior. The present study sought to determine if SB-277011A, NGB 2904, or BP-897 (a mixed D-3 agonist/antagonist) similarly inhibit cocaine-associated cue-induced reinstatement of drug-seeking behavior. Long-Evans rats were allowed to self-administer cocaine. Each cocaine infusion was paired with discrete conditioned cue-light and tone. Subsequently, drug-seeking (i.e., lever-pressing) behavior was extinguished in the absence of cocaine and cocaine-associated cues. Rats were then tested for cue-induced reinstatement of drug-seeking. We found that cocaine-associated cues evoked robust reinstatement of lever-pressing. Acute intraperitoneal (i.p.) administration of SB-277011A (6, 12, or 24 mg/kg) produced a dose-dependent inhibition of cue-induced reinstatement of drug-seeking behavior by 35, 65, and 85%, respectively, compared to vehicle-treated animals. Acute i.p. administration of NGB 2904 (0.1, 1.0, or 5.0 mg/kg) produced a 45, 30, and 70% inhibition of cue-induced reinstatement, respectively, compared to vehicle-treated animals. Acute i.p. administration of either 0.1 or 1 mg/kg of BP 897 did not produce a significant effect on cue-induced reinstatement, whereas a dose of 3 mg/kg produced a 70% inhibition of cue-induced reinstatement. These findings, combined with previous data, suggest that DA D3 receptor antagonism may underlie the inhibitory effects of SB-277011A and NGB 2904 on cocaine cue-induced reinstatement, while the effects of BP 897 may involve D-3 and non-D-3 receptor mechanisms. Published 2005 Wiley-Liss, Inc. C1 NIDA, Intramural Res Program, Neuropsychopharmacol Sect,Behav Neurosci Res Bran, NIH,DHHS, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Medicat Discovery Res Branch,Intramural Res Progr, NIH,DHHS, Baltimore, MD 21224 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. GlaxoSmithKline Pharmaceut, Ctr Excellence Drug Discovery Psychiat, Dept Neuropsychopharmacol, I-37135 Verona, Italy. RP Xi, ZX (reprint author), NIDA, Intramural Res Program, Neuropsychopharmacol Sect,Behav Neurosci Res Bran, NIH,DHHS, Bldg C,Room 394,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zxi@intra.nida.nih.gov OI PENG, XIAOQING/0000-0002-7272-5428 FU Intramural NIH HHS [Z99 DA999999] NR 88 TC 93 Z9 93 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUL PY 2005 VL 57 IS 1 BP 17 EP 28 DI 10.1002/syn.20152 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 928VF UT WOS:000229299100003 PM 15858839 ER PT J AU Francischetti, IMB Mather, TN Ribeiro, JMC AF Francischetti, IMB Mather, TN Ribeiro, JMC TI Tick saliva is a potent inhibitor of endothelial cell proliferation and angiogenesis SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE tick saliva; angiogenesis; wound healing; Ixodes scapularis; integrin ID FACTOR PATHWAY INHIBITOR; SMOOTH-MUSCLE-CELLS; IXODES-SCAPULARIS; TISSUE FACTOR; SNAKE-VENOM; INTEGRIN ALPHA(5)BETA(1); EXTRACELLULAR-MATRIX; ARTHROPOD SALIVA; LYME-DISEASE; FIBRONECTIN AB We report for the first time that saliva of the hard tick and Lyme disease vector, Ixodes scapularis, is a potent inhibitor of angiogenesis. Saliva (<= 1:500 dilutions) or salivary gland (0.1-0.5 pairs/assay) dose-dependently inhibits microvascular endothelial cell (MVEC) proliferation. Inhibition was also detected with the saliva of the cattle tick Boophilus microplus but not with the salivary gland of Anopheles gambiae, An. stephensi, Lutzomyia longipalpis, Phlebotomus papotasi, Aedes aegypti, Culex quinquefasciatus, and Cimex lectularius. Inhibition of MVEC proliferation by I. scopularis saliva was accompanied by a change in cell shape (shrinkage of the cytoplasm with loss of cell-cell interactions) and apoptosis which was estimated by expression of phosphatidylserine using the Apopercentage dye, and by a typical pattern of chromatin margination, condensation, and fragmentation as revealed by nuclear staining with Hoechst 33258. The effect of saliva appears to be mediated by endothelial cell alpha 5 beta 1 integrin, because monoclonal antibodies against this but not alpha v beta 3, alpha v beta 5, alpha 9 beta 1, or alpha 2 beta 1 integrins remarkably block its effect. In addition, SDS/PAGE shows that saliva specifically degrades purified alpha 5 beta 1 but not alpha v beta 5 or alpha v beta 3 integrins. Incubation of saliva with EDTA and 1,10-phenanthroline, but not phenylmethylsulfonyl fluoride (PMSF), inhibits saliva-dependent degradation of purified alpha 5 beta 1 integrin, suggesting that a metalloprotease is responsible for the activity. Finally, saliva at <= 1:1,000 dilutions blocks sprouting formation from chick embryo aorta implanted in Matrigel, an in vitro model of angiogenesis. These findings introduce the concept that tick saliva is a negative modulator of angiogenesis-dependent wound healing and tissue repair, therefore allowing ticks to feed for days. Inhibition of angiogenesis was hitherto an unidentified biologic property of the saliva of any blood-sucking arthropod studied so far. Its presence in tick saliva may be regarded as an additional source of angiogenesis inhibitors with potential applications for the study of both vector and vascular biology. C1 NIAID, Vector Biol Sect, LMVR, NIH, Bethesda, MD 20892 USA. Univ Rhode Isl, Ctr Vector Borne Dis, Kingston, RI 02881 USA. RP Francischetti, IMB (reprint author), NIAID, Vector Biol Sect, LMVR, NIH, 12735 Twinbrook Pkwy,Twinbrook 3,Room 2E28, Bethesda, MD 20892 USA. EM ifrancischetti@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 FU Intramural NIH HHS [Z01 AI000810-11, Z99 AI999999]; NIAID NIH HHS [R02 AI37230] NR 50 TC 51 Z9 52 U1 0 U2 5 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD JUL PY 2005 VL 94 IS 1 BP 167 EP 174 DI 10.1160/TH04-09-0566 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 945QG UT WOS:000230516600024 PM 16113800 ER PT J AU He, HL Olesnanik, K Nagy, R Liyanarachci, S Prasad, ML Stratakis, CA Kloos, RT de la Chapelle, A AF He, HL Olesnanik, K Nagy, R Liyanarachci, S Prasad, ML Stratakis, CA Kloos, RT de la Chapelle, A TI Allelic variation in gene expression in thyroid tissue SO THYROID LA English DT Article; Proceedings Paper CT 3rd Annual Conference on Frontiers in Cancer Preventive Research CY OCT 16-20, 2004 CL Seattle, WA SP Amer Assoc Canc Res ID CONGENITAL HYPOTHYROIDISM; IMPRINTED GENE; CARNEY COMPLEX; DUOX GENES; CARCINOMA; PAPILLARY; GENOME; GOITER; CANCER; SUSCEPTIBILITY AB Heritable allelic variation in gene expression may contribute to sporadic and familial disease, but is relatively unexplored. Papillary thyroid cancer (PTC) is characterized by strong heritability but predisposing genes have not been detected. Here we tested the hypothesis that inherited variation in allelic expression occurs in thyroid tissue and so might contribute to disease. We studied genes with a role in thyroid function, signaling, and/or tumorigenesis (PRKAR1A, DUOX1, IP3R1, ARGBP2, TPO, TG, and PEG10). We screened thyroid tissues from controls and patients with thyroid disease and lymphoblastoid cell lines from 40 healthy individuals. We demonstrated the robustness of the technique, a fluorescent dideoxy terminator-based method distinguishing the mRNA products of alleles in individuals who are heterozygous for a polymorphism in the transcript. We confirmed that the PEG10 gene transcript was derived only from one allele because of genetic imprinting. Three other genes, DUOX1, TPO, and ARGBP2 showed allelic variation in thyroid tissue and/or lymphoblastoid cells. Benign and malignant thyroid tissue from the same patient always gave concordant results. DUOX1 variation in expression was seen in 3 of 13 patients with PTC and 6 of 27 patients with benign disease. Further studies are needed to determine the significance of these and other allelic variations. C1 Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. Ohio State Univ, Dept Radiol, Comprehens Canc Ctr, Columbus, OH 43210 USA. NIH, Natl Inst Child Hlth & Human Dev, Dev Endocrinol Branch, Sect Genet & Endocrinol, Bethesda, MD USA. RP de la Chapelle, A (reprint author), Ohio State Univ, Human Canc Genet Program, 646 Med Res Facil,420 W 12th Ave, Columbus, OH 43210 USA. EM delachapelle-1@medctr.osu.edu NR 35 TC 11 Z9 11 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JUL PY 2005 VL 15 IS 7 BP 660 EP 667 DI 10.1089/thy.2005.15.660 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 953NU UT WOS:000231084100006 PM 16053381 ER PT J AU Li, L Prabhakaran, K Mills, EM Borowitz, JL Isom, GE AF Li, L Prabhakaran, K Mills, EM Borowitz, JL Isom, GE TI Enhancement of cyanide-induced mitochondrial dysfunction and cortical cell necrosis by uncoupling protein-2 SO TOXICOLOGICAL SCIENCES LA English DT Article DE apoptosis; cyanide; necrosis; mitochondria; uncoupling protein ID PREVENTS NEURONAL DEATH; INDUCED APOPTOSIS; OXIDATIVE STRESS; DIFFERENT MODES; BRAIN; TRANSLOCATION; INHIBITION; ACTIVATION; EXPRESSION; GENERATION AB Uncoupling protein 2 (UCP-2) is expressed in the inner mitochondrial membrane and modulates mitochondrial function by partially uncoupling oxidative phosphorylation, and it has been reported to modulate cell death. Cyanide is a potent neurotoxin that inhibits complex IV to alter mitochondrial function to induce neuronal death. In primary rat cortical cells KCN produced an apoptotic death at 200-400 mu M. Higher concentrations of potassium cyanide (KCN) (500-600 mu M) switched the mode of death from apoptosis to necrosis. In necrotic cells, ATP levels were severely depleted as compared to cortical cells undergoing apoptosis. To determine if UCP-2 expression could alter KCN-induced cell death, cells were transiently transfected with full-length human UCP-2 cDNA (UCP-2(+)). Overexpression switched the mode of death produced by KCN (400 mu M) from apoptosis to necrosis. The change in cell death was mediated by impaired mitochondrial function as reflected by a marked decrease of ATP levels and reduction in mitochondrial membrane potential. RNA interference or transfection with a dominant interfering mutant blocked the necrotic response observed in UCP-2(+) cells. Additionally, treatment of UCP-2(+) cells with cyclosporin A blocked necrosis, indicating the involvement of mitochondrial permeability pore transition in the necrotic death. These results show that increased expression of UCP-2 alters the response to a potent mitochondrial toxin by switching the mode of cell death from apoptosis to necrosis. It is concluded that UCP-2 levels influence cellular responses to cyanide-induced mitochondrial dysfunction. C1 Purdue Univ, Dept Med Chem & Pharmacognosy, W Lafayette, IN 47907 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Isom, GE (reprint author), Purdue Univ, Dept Med Chem & Pharmacognosy, W Lafayette, IN 47907 USA. EM geisom@purdue.edu FU NIEHS NIH HHS [ES 04140] NR 39 TC 20 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2005 VL 86 IS 1 BP 116 EP 124 DI 10.1093/toxsci/kfi164 PG 9 WC Toxicology SC Toxicology GA 934HI UT WOS:000229699500015 PM 15800031 ER PT J AU Boorman, GA Blackshear, PE Parker, JS Lobenhofer, EK Malarkey, DE Vallant, MK Gerken, DK Irwin, RD AF Boorman, GA Blackshear, PE Parker, JS Lobenhofer, EK Malarkey, DE Vallant, MK Gerken, DK Irwin, RD TI Hepatic gene expression changes throughout the day in the Fischer rat: Implications for toxicogenomic experiments SO TOXICOLOGICAL SCIENCES LA English DT Article DE liver; rat; differential gene expression; microarray; transcriptome; circadian; clock; Per1; Per2; Arntl; Bmal1; Nr1d1 ID CIRCADIAN-RHYTHMS; LIVER; CLOCK; MOUSE; TIME; MICROARRAY; MAMMALS; TRANSCRIPTION; DROSOPHILA; KIDNEY AB There is increasing use of transcriptional profiling in hepatotoxicity studies in the rat. Understanding hepatic gene expression changes over time is critical, since tissue collection may occur throughout the day. Furthermore, when comparing results from different data sets, times of dosing and tissue collection may vary. Circadian effects on the mouse hepatic transcriptome have been well documented. However, limited reports exist for the rat. In one study approximately 7% of the hepatic genes showed a diurnal expression pattern in a comparison of rat liver samples collected during the day versus livers collected at night. The results of a second study comparing rat liver samples collected at multiple time points over a circadian day suggest only minimal variation of the hepatic transcriptome. We studied temporal hepatic gene expression in 48 untreated F344/N rats using both approaches employed in these previous studies. Statistical analysis of microarray (SAM) identified differential expression in day/night comparisons, but was less sensitive for liver samples collected at multiple times of day. However, a Fourier analysis identified numerous periodically expressed genes in these samples including period genes, clock genes, clock-controlled genes, and genes involved in metabolic pathways. Furthermore, rhythms in gene expression were identified for several circadian genes not previously reported in the rat liver. Transcript levels for twenty genes involved in circadian and metabolic pathways were confirmed using quantitative RT-PCR. The results of this study demonstrate a prominent circadian rhythm in gene expression in the rat that is a critical factor in planning toxicogenomic experiments. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Constella Grp Inc, Res Triangle Pk, NC 27709 USA. Paradigm Array Labs, Res Triangle Pk, NC 27709 USA. Battelle Sci & Technol Int, Columbus, OH 43201 USA. RP Boorman, GA (reprint author), NIEHS, Environm Toxicol Program, MD B3-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM boorman@niehs.nih.gov FU NIEHS NIH HHS [N01-ES-25497, NIH-ES-35513] NR 26 TC 26 Z9 28 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2005 VL 86 IS 1 BP 185 EP 193 DI 10.1093/toxsci/kfi166 PG 9 WC Toxicology SC Toxicology GA 934HI UT WOS:000229699500022 PM 15814895 ER PT J AU Kleinman, SH Glynn, SA Higgins, M Triulzi, DJ Smith, JW Nass, CC Garratty, G Murphy, E LeParc, GE Schreiber, GB King, MR Chamberland, ME Nemo, GJ AF Kleinman, SH Glynn, SA Higgins, M Triulzi, DJ Smith, JW Nass, CC Garratty, G Murphy, E LeParc, GE Schreiber, GB King, MR Chamberland, ME Nemo, GJ TI The RADAR repository: a resource for studies of infectious agents and their transmissibility by transfusion SO TRANSFUSION LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; HEPATITIS-C VIRUS; WEST-NILE-VIRUS; BLOOD-TRANSFUSION; UNITED-STATES; RECIPIENTS; DISEASE; DONATIONS; ANTIBODY; SAFETY AB BACKGROUND: An ongoing issue in transfusion medicine is whether newly identified or emerging pathogens can be transmitted by transfusion. One method to study this question is through the use of a contemporary linked donor-recipient repository. STUDY DESIGN AND METHODS: The Retrovirus Epidemiology Donor Study Allogeneic Donor and Recipient (RADAR) repository was established between 2000 and 2003 by seven blood centers and eight collaborating hospitals. Specimens from consented donors were collected, components from their donations were routed to participating hospitals, and recipients of these units gave enrollment and follow-up specimens for long-term storage. The repository was designed to show that zero transmissions to enrolled recipients would indicate with 95 percent confidence that the transfusion transmission rate of an agent with prevalence of 0.05 to 1 percent was lower than 25 percent. RESULTS: The repository contains pre- and posttransfusion specimens from 3,575 cardiac, vascular, and orthopedic surgery patients, linked to 13,201 donation specimens. The mean number of RADAR donation exposures per recipient is 3.85. The distribution of components transfused is 77 percent red cells, 13 percent whole blood-derived platelet concentrates, and 10 percent fresh frozen plasma. A supplementary unlinked donation repository containing 99,906 specimens from 84,339 donors was also established and can be used to evaluate the prevalence of an agent and validate assay(s) performance before accessing the donor-recipient-linked repository. Recipient testing conducted during the establishment of RADAR revealed no transmissions of human immunodeficiency virus, hepatitis C virus, or human T-lymphotropic virus. CONCLUSIONS: RADAR is a contemporary donor-recipient repository that can be accessed to study the transfusion transmissibility of emerging agents. C1 WESTAT Corp, Rockville, MD 20850 USA. Amer Red Cross Blood Serv SE Michigan Reg, Detroit, MI USA. Inst Transfus med, Pittsburgh, PA USA. Oklahoma Blood Inst, Sylvan N Goldman Ctr, Oklahoma City, OK USA. Amer Red Cross Blood Serv, Greater Chesapeake & Potomac Reg, Baltimore, MD USA. Amer Red Cross Blood Serv So Calif Reg, Los Angeles, CA USA. Blood Syst Res Inst, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Florida Blood Serv, St Petersburg, FL USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NHLBI, Blood Resources Branch, Div Blood Dis & Resources, Bethesda, MD 20892 USA. RP Schreiber, GB (reprint author), WESTAT Corp, 1650 Res Blvd, Rockville, MD 20850 USA. EM GeorgeSchreiber@westat.com FU NHLBI NIH HHS [N01-HB-97078, N01-HB-97079, N01-HB-97081, N01-HB-97080, N01-HB-97082, N01-HB-47114, N01-HB-97077] NR 19 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2005 VL 45 IS 7 BP 1073 EP 1083 DI 10.1111/j.1537.2995.00171.x PG 11 WC Hematology SC Hematology GA 942UG UT WOS:000230307800007 PM 15987350 ER PT J AU Akiba, J Umemura, T Alter, HJ Kojiro, M Tabor, E AF Akiba, J Umemura, T Alter, HJ Kojiro, M Tabor, E TI SEN virus: epidemiology and characteristics of a transfusion-transmitted virus SO TRANSFUSION LA English DT Article ID CHRONIC HEPATITIS-C; A-E-HEPATITIS; LIVER-DISEASE; POSTTRANSFUSION HEPATITIS; HEPATOCELLULAR-CARCINOMA; CLINICAL-SIGNIFICANCE; UNKNOWN ETIOLOGY; TT VIRUS; INFECTION; PREVALENCE AB SEN virus (SEN-V) is a blood-borne, single-stranded, nonenveloped DNA virus. Although its prevalence varies by geographic region, it has been detected in as many as 30 percent of postoperative transfusion recipients, compared to 3 percent of postoperative patients who did not receive transfusions. A significant association has been observed between transfusion volume and the occurrence of SEN-V infection. Transmission by transfusion also has been confirmed by the detection of greater than 99 percent homology between SEN-V in donor and recipient sera. Concurrent infections with SEN-V and hepatitis B virus, hepatitis C virus, or human immunodeficiency virus type 1 have been documented, and these observations probably reflect the blood-borne transmission of these viruses as well as SEN-V. Although SEN-V was discovered as part of a search for causes of posttransfusion hepatitis, there is no firm evidence so far that SEN-V infection either causes hepatitis or worsens the course of coexistent liver disease. Nevertheless, SEW V appears to be transmitted by transfusion, and further studies may reveal more about its role in the future. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Kurume Univ, Sch Med, Dept Pathol, Kurume, Fukuoka 830, Japan. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 36 TC 21 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2005 VL 45 IS 7 BP 1084 EP 1088 DI 10.1111/j.1537-2995.00209.x PG 5 WC Hematology SC Hematology GA 942UG UT WOS:000230307800008 PM 15987351 ER PT J AU Patel, HD Byrne, KM Horne, M Leitman, SE Stroncek, DE AF Patel, HD Byrne, KM Horne, M Leitman, SE Stroncek, DE TI Factors affecting the formation of white particulate matter in red blood cell components SO TRANSFUSION LA English DT Article ID PLATELETS AB BACKGROUND: Recently white particulate matter (WPM) in red blood cell (RBC) components has received increased attention. The nature and causes of WPM formation were investigated. STUDY DESIGN AND METHODS: Whole-blood units were collected from 18 healthy subjects with three different types of collection sets. Six units were collected into each type. Units were divided into four equal parts and stored for 4 hours: two parts at room temperature and two at 4 degrees C. RBCs were prepared from each quarter-unit: two by heavy centrifugation (5000 x g) and two by light centrifugation (2000 x g). Whole blood was inspected for WPM over 4 hours and RBCs over 1 hour. RESULTS: No WPM was detected in whole blood, but WPM was detected in at least one RBC component from 9 of the 18 donations. The 36 components prepared by heavy centrifugation were more likely to contain WPM than the 36 prepared by light centrifugation (50% vs. 19%; p < 0.02). The incidence of WPM was similar among RBCs stored at room temperature and 4 degrees C. Donors of RBCs with WPM had higher total cholesterol levels than donors of components without WPM (191 20 mg/dL vs. 163 +/- 32 mg/dL; p < 0.04), but there was no difference in triglyceride levels between the two groups. CONCLUSIONS: WPM is an expected consequence of standard RBC manufacturing methods, but it is more frequent in RBCs prepared by heavy centrifugation and from donors with higher cholesterol levels. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Byrne, KM (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C711,10 Ctr Dr MSC-1184, Bethesda, MD 20892 USA. EM KByrne@mail.cc.nih.gov NR 8 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2005 VL 45 IS 7 BP 1127 EP 1132 DI 10.1111/j.1537-2995.2005.04351.x PG 6 WC Hematology SC Hematology GA 942UG UT WOS:000230307800014 PM 15987357 ER PT J AU Miller, JL AF Miller, JL TI Signaled expression of fetal hemoglobin during development SO TRANSFUSION LA English DT Article ID STEM-CELL FACTOR; GAMMA-GLOBIN GENE; ERYTHROPOIESIS; HYPOXEMIA; DISEASE; GROWTH; BETA; KIT C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDK, Mol Med Branch, NIH, Bethesda, MD 20892 USA. EM jm7f@nih.gov NR 25 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2005 VL 45 IS 7 BP 1229 EP 1232 DI 10.1111/j.1537-2995.2005.00182.x PG 4 WC Hematology SC Hematology GA 942UG UT WOS:000230307800028 PM 15987371 ER PT J AU Franco, R Casado, V Mallol, J Ferre, S Fuxe, K Cortes, A Ciruela, F Lluis, C Canela, EI AF Franco, R Casado, V Mallol, J Ferre, S Fuxe, K Cortes, A Ciruela, F Lluis, C Canela, EI TI Dimer-based model for heptaspanning membrane receptors SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID A(1) ADENOSINE RECEPTORS; PROTEIN-COUPLED RECEPTORS; TERNARY COMPLEX MODEL; OCCUPANCY MODEL; BETA(2)-ADRENERGIC RECEPTOR; MUSCARINIC RECEPTORS; INTRINSIC ACTIVITY; 5-HT1A RECEPTORS; BINDING PROTEINS; 2-STATE MODEL AB The existence of intramembrane receptor-receptor interactions for heptaspanning membrane receptors is now fully accepted, but a model considering dinners as the basic unit that binds to two ligand molecules is lacking. Here, we propose a two-state-dimer model in which the ligand-induced conformational changes from one component of the dimer are communicated to the other. Our model predicts cooperativity in binding, which is relevant because the other current models fail to address this phenomenon satisfactorily. Our two-state-dimer model also predicts the variety of responses elicited by full or partial agonists, neutral antagonists and inverse agonists. This model can aid our understanding of the operation of heptaspanning receptors and receptor channels, and, potentially, be important for improving the treatment of cardiovascular, neurological and neuropsychyatric diseases. C1 Univ Barcelona, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain. NIDA, US Dept HHS, NIH, Baltimore, MD 21224 USA. Karolinska Inst, KF, Div Cellular & Mol Neurochem, Dept Neurosci, S-17177 Stockholm, Sweden. RP Canela, EI (reprint author), Univ Barcelona, Dept Biochem & Mol Biol, A Diagonal,645, E-08028 Barcelona, Spain. EM ecanela@ub.edu RI Canela, Enric I./M-8726-2013; Ferre, Sergi/K-6115-2014; Ciruela, Francisco/A-5096-2013; Franco, Rafael/C-3694-2015; Casado, Vicent/K-1660-2014; OI Canela, Enric I./0000-0003-4992-7440; Ferre, Sergi/0000-0002-1747-1779; Ciruela, Francisco/0000-0003-0832-3739; Franco, Rafael/0000-0003-2549-4919; Fuxe, Kjell/0000-0001-8491-4288; Casado, Vicent/0000-0002-1764-3825 NR 45 TC 49 Z9 49 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD JUL PY 2005 VL 30 IS 7 BP 360 EP 366 DI 10.1016/j.tibs.2005.05.010 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 949IH UT WOS:000230778000003 PM 15951182 ER PT J AU Mazumdar, M Misteli, T AF Mazumdar, M Misteli, T TI Chromokinesins: multitalented players in mitosis SO TRENDS IN CELL BIOLOGY LA English DT Editorial Material ID KINESIN-LIKE PROTEIN; MICROTUBULE-BASED MOTOR; MITOTIC SPINDLE; DNA-BINDING; CHROMOSOME CONDENSATION; CELL-CYCLE; MIDZONE FORMATION; SEGREGATION; KIF4; DROSOPHILA AB Molecular motors generate cellular forces and act in a multitude of intracellular transport processes. The chromokinesins are a subgroup of kinesin motors. Chromokinesins act in various steps of mitosis, including chromosome condensation, metaphase alignment, chromosome segregation, cytokinesis and they help maintain genome stability. The emerging multifunctional nature of the chromokinesins provides insights into the coordination of distinct mitotic steps, and their role in maintenance of genome stability makes them attractive potential targets for therapeutic intervention. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Mazumdar, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mazumdam@mail.nih.gov NR 56 TC 75 Z9 81 U1 1 U2 8 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JUL PY 2005 VL 15 IS 7 BP 349 EP 355 DI 10.1016/j.tcb.2005.05.006 PG 7 WC Cell Biology SC Cell Biology GA 952RN UT WOS:000231023300003 PM 15946846 ER PT J AU Shah, BH AF Shah, BH TI Estrogen stimulation of COX-2-derived PGI(2) confers atheroprotection SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID COX-2 INHIBITION; BREAST-CANCER; PROSTACYCLIN; PHARMACOLOGY; THROMBOXANE; PREVENTION; ROFECOXIB; RISK AB Although selective cyclooxygenase-2 (COX-2) inhibitors provide relief from pain and inflammation, they also reduce the formation of the athero protective prostaglandin I-2 (PGI(2)). They do not reduce the formation of the COX-1-derived thromboxane A(2) (TXA(2)), however, which is both atherogenic and a potent vasoconstrictor. For this reason, the effects of TXA(2) might be exacerbated during extended therapy with COX-2 inhibitors, potentially predisposing patients to heart attack and stroke. Recent studies have demonstrated that the athero-protective effects of estrogen are induced through PGI(2) production, through COX-2 activation. This explains how estrogen production in pre-menopausal females is beneficial for the heart and also raises the possibility that COX-2 inhibitors might be particularly hazardous to females. C1 NICHD, Sect Hormonal Regulat, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHD, Sect Hormonal Regulat, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov NR 16 TC 6 Z9 8 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JUL PY 2005 VL 16 IS 5 BP 199 EP 201 DI 10.1016/j.tem.2005.05.008 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 950AG UT WOS:000230829400001 PM 15950485 ER PT J AU Gottesman, S AF Gottesman, S TI Micros for microbes: non-coding regulatory RNAs in bacteria SO TRENDS IN GENETICS LA English DT Review ID SM-LIKE PROTEIN; ESCHERICHIA-COLI; MESSENGER-RNA; GLUCOSE-TRANSPORTER; RPOS TRANSLATION; POSTTRANSCRIPTIONAL REGULATION; COMPARATIVE GENOMICS; SIGNAL-TRANSDUCTION; ENCODING GENES; HFQ PROTEIN AB Small non-coding RNAs with important regulatory roles are not confined to eukaryotes. Recent studies have led to the identification of numerous small regulatory RNAs in Escherichia coli and in other bacteria. As in eukaryotic cells, a major class of these small RNAs acts by base-pairing with target mRNAs, resulting in changes in the translation and stability of the mRNA. Roles for these non-coding pairing RNAs in bacteria have been demonstrated in several cases. Because these non-coding RNAs act post-transcriptionally, they impose a regulatory step that is independent of and epistatic to any transcriptional signals for their target mRNAs. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 57 TC 287 Z9 309 U1 2 U2 32 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD JUL PY 2005 VL 21 IS 7 BP 399 EP 404 DI 10.1016/j.tig.2005.05.008 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 945LU UT WOS:000230504800009 PM 15913835 ER PT J AU Giniatullin, R Nistri, A Yakel, JL AF Giniatullin, R Nistri, A Yakel, JL TI Desensitization of nicotinic ACh receptors: shaping cholinergic signaling SO TRENDS IN NEUROSCIENCES LA English DT Review ID FRONTAL-LOBE EPILEPSY; FAST SYNAPTIC-TRANSMISSION; RAT CHROMAFFIN CELLS; END-PLATE CURRENTS; ACETYLCHOLINE-RECEPTOR; AGONIST-BINDING; ALPHA-BUNGAROTOXIN; UP-REGULATION; SPINAL-CORD; INTRACELLULAR CALCIUM AB Nicotinic ACh receptors (nAChRs) can undergo desensitization, a reversible reduction in response during sustained agonist application. Although the mechanism of desensitization remains incompletely understood, recent investigations have elucidated new properties underlying desensitization, indicating that it might be important to control synaptic efficacy,, responses to cholinergic agents, and certain nAChR-related disease states. Thus, studying how different nAChR subunits contribute to desensitization might help to explain variations in responsiveness to drugs, and might thus improve their therapeutic applications. Agonist-specific desensitization, desensitization arising from resting receptors, natural mutations dramatically altering desensitization, and the possibility that recovery from desensitization is an important process for modulating receptor function, together provide a new framework for considering desensitization as a target to shape cholinergic signaling. C1 SISSA, Neurobiol Sector, I-34014 Trieste, Italy. SISSA, INFM Unit, I-34014 Trieste, Italy. Kazan Med Univ, Kazan 420012, Russia. NIEHS, Neurobiol Lab, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), SISSA, Neurobiol Sector, Via Beirut 4, I-34014 Trieste, Italy. EM yakel@niehs.nih.gov OI Giniatullin, Rashid/0000-0002-1580-6280 FU Intramural NIH HHS NR 75 TC 190 Z9 196 U1 3 U2 14 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JUL PY 2005 VL 28 IS 7 BP 371 EP 378 DI 10.1016/j.tins.2005.04.009 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 947YQ UT WOS:000230683600007 PM 15979501 ER PT J AU Young, MF AF Young, MF TI Mouse models of osteoarthritis provide new research tools SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Article ID IN-VIVO; MICE; CARTILAGE; GENE; PROTEOGLYCANS; DEFICIENT; BIGLYCAN; DELETION; ADAMTS5; DISEASE AB The options for pharmaceutical intervention of osteoarthritis are limited. There is therefore a crucial need for animal models of osteoarthritis that can be used as research tools for improving our understanding of the disease and for discovering and testing new treatments. Recently, a new mouse model of osteoarthritis was described in which the mice are unable to produce a bone morphogenetic protein (BMP) receptor specifically in joints. A comparison of this model to other models with different etiologies is presented. The findings suggest that all of the models could be linked molecularly. C1 Natl Inst Dent & Craniofacial Res, Mol Biol Bones & Teeth Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Young, MF (reprint author), Natl Inst Dent & Craniofacial Res, Mol Biol Bones & Teeth Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. EM Myoung@dir.nider.nih.gov NR 17 TC 11 Z9 14 U1 3 U2 9 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD JUL PY 2005 VL 26 IS 7 BP 333 EP 335 DI 10.1016/j.tips.2005.05.001 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 950CL UT WOS:000230835100001 PM 15982479 ER PT J AU Lasco, TM Cassone, L Kamohara, H Yoshimura, T McMurray, DN AF Lasco, TM Cassone, L Kamohara, H Yoshimura, T McMurray, DN TI Evaluating the role of tumor necrosis factor-alpha in experimental pulmonary tuberculosis in the guinea pig SO TUBERCULOSIS LA English DT Article DE Mycobacterium tuberculosis; TNF-alpha; guinea pig; granuloma ID MYCOBACTERIUM-BOVIS BCG; EXPERIMENTAL AIRBORNE TUBERCULOSIS; HOST-PARASITE RELATIONSHIPS; T-CELL RESPONSES; CYTOKINE PRODUCTION; FACTOR TNF; IN-VIVO; INFECTION; IMMUNITY; GENE AB Tumor necrosis factor-alpha (TNF-alpha) is suggested to play multiple roles in immune and pathologic responses in tuberculosis. In this study, we have developed a system for the expression of recombinant guinea pig TNF-alpha (rgpTNF-alpha). Using rgpTNF-a along with neutralizing anti-rgpTNF-alpha antiserum, we tested the effect of modulating the levels of TNF-a on antigen-specific Tcell proliferation in splenocytes. By neutralizing TNF-alpha in the supernatant of PPD-pulsed splenocytes with anti-rgpTNF-alpha, we observed hyperproliferation. Conversely, the addition of rgpTNF-alpha resulted in a significant suppression of PPD-induced lymphoproliferation. In addition, when unvaccinated and BCG-vaccinated guinea pigs were treated with polyclonal rgpTNF-a. antiserum throughout the first 3 weeks following low-dose, pulmonary infection with Mycobacterium tuberculosis H37Rv, we observed splenomegaly in BCG-vaccinated guinea pigs. We also detected higher levels of splenic granuloma organization in the non-vaccinated group as well as a significant number of plasma cells associated with granulomata from the BCG-vaccinated group. These results suggest that modulating the availability of TNF-alpha in BCG-vaccinated guinea pigs can lead to immuno-dysregulation and, perhaps, the inappropriate enhancement of humoral immunity. Conversely, abrogating TNF-a activity in the context of a hyperinflammatory response in non-vaccinated guinea pigs may, in fact, rescue them from immunopathological consequences of overproducing TNF-alpha. Published by Elsevier Ltd. C1 Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. Texas A&M Univ, Coll Vet Med, College Stn, TX 77843 USA. Natl Canc Inst Frederick Canc Res & Dev Ctr, Lab Mol Immunoregulat, Ft Detrick, MD 21702 USA. RP Lasco, TM (reprint author), Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. EM tlasco@mycosresearch.com FU NIAID NIH HHS [R01 AI-15495] NR 45 TC 38 Z9 38 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD JUL PY 2005 VL 85 IS 4 BP 245 EP 258 DI 10.1016/j.tube.2005.01.001 PG 14 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 944HF UT WOS:000230417100007 PM 15958260 ER PT J AU Diner, EK Franks, ME Behari, A Linehan, WM Walther, MM AF Diner, EK Franks, ME Behari, A Linehan, WM Walther, MM TI Partial adrenalectomy: The National Cancer Institute experience SO UROLOGY LA English DT Article ID LAPAROSCOPIC PARTIAL ADRENALECTOMY; INTRAOPERATIVE ULTRASOUND; SPARING SURGERY; PHEOCHROMOCYTOMA; MANAGEMENT AB Objectives. To report our experience of partial adrenalectomy and demonstrate whether adrenal function can be preserved in patients with hereditary adrenal pheochromocytoma. Total adrenalectomy has largely been used in the treatment of patients with hereditary adrenal pheochromocytomas. Adrenal cortical-sparing surgery is an alternative approach that aims to balance tumor removal with preservation of adrenocortical function. Methods. From 1995 to 2004, 33 patients with hereditary pheochromocytoma presented with adrenal masses. Partial adrenalectomy (open or laparoscopic) was performed if normal adrenocortical tissue was evident on preoperative imaging or intraoperative ultrasonography. Various operative parameters, as well as postoperative function of the residual adrenal remnants, were determined. Results. Of the 33 patients, 8 underwent open partial adrenalectomy and 25 laparoscopic partial adrenalectomy during a 10-year period. Ten patients underwent simultaneous, bilateral partial adrenalectomy and 8 underwent surgery on a solitary adrenal gland, 4 of whom received postoperative steroid replacement (stopped in 3 after I to 3 months). All other patients had normal catecholamine levels and remained tumor free by imaging at a mean follow-up of 36 months (range 3 to 102). Conclusions. Partial adrenalectomy can preserve adrenal function in patients with adrenal masses. The laparoscopic approach is technically safe and associated with less morbidity without compromising tumor removal. With careful surgical planning, especially in patients with tumors in solitary glands, adrenocortical function may be preserved, thereby avoiding the morbidity associated with medical adrenal replacement. C1 NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 2B-43, Bethesda, MD 20892 USA. EM ericdiner@hotmail.com NR 14 TC 54 Z9 55 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD JUL PY 2005 VL 66 IS 1 BP 19 EP 23 DI 10.1016/j.urology.2005.01.009 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 968JA UT WOS:000232157500005 PM 15961144 ER PT J AU Cesta, MF Baty, CJ Keene, BW Smoak, IW Malarkey, DE AF Cesta, MF Baty, CJ Keene, BW Smoak, IW Malarkey, DE TI Pathology of end-stage remodeling in a family of cats with hypertrophic cardiomyopathy SO VETERINARY PATHOLOGY LA English DT Article DE burned-out phase; dilated phase; end stage; feline; hypertrophic cardiomyopathy; myocardial fibrosis ID DILATED CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY; HUMAN-DISEASE; ANIMAL-MODEL; MUTATION; PROGRESSION; FEATURES; GENE; SPECTRUM; DISARRAY AB End-stage hypertrophic cardiomyopathy (ES-HCM), affecting 5-10% of human hypertrophic cardiomyopathy (HCM) patients, is characterized by relative thinning of the ventricular walls and septum with dilation of the ventricular lumen, decreased fractional shortening, and progression to heart failure. C. J. Baty and others recently documented similar progressive changes to ES-HCM in a family of four cats through serial echocardiograms. At the time of heart failure, these cats exhibited changes similar to those exhibited by human ES-HCM patients. Our objectives were to describe the pathologic alterations associated with ES-HCM and investigate the pathogenesis in three of the four cats, Grossly, there was left atrial dilation with relative thinning of the interventricular septum (IVS) and left ventricular free wall (LVFW). The left atrium contained large thrombi in two of the three cats, and all three cats died following thromboembolization of the aortic bifurcation. Histologically, all three cats had subendocardial and myocardial fibrosis, predominantly of the IVS and LVFW, and one cat had acute, multifocal, myocardial infarcts with mononuclear inflammatory cell infiltrates. The pathogenesis of ES-HCM is uncertain, but theories implicate occlusion of the coronary blood flow by thickening of the coronary vessels, coronary vascular thromboembolism or coronary vessel spasm, apoptosis of myocytes, and myocardial hypertrophy beyond the ability of the vasculature to supply blood. Apoptosis assays did not reveal any apoptotic myocytes. Considering the hypercoagulative state of these cats, coronary vascular thromboembolism could be a major contributing factor. We cannot exclude apoptosis or coronary vessel spasm on the basis of the data presented. C1 Natl Inst Environm Hlth Sci, Lab Expt Pathol, Res Triangle Pk, NC USA. Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA USA. N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC USA. RP Malarkey, DE (reprint author), Natl Inst Environm Hlth Sci, Lab Expt Pathol, Maildrop B3-06, Res Triangle Pk, NC USA. EM malarkey@niehs.nih.gov NR 33 TC 19 Z9 19 U1 0 U2 7 PU AMER COLL VET PATHOLOGIST PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0300-9858 J9 VET PATHOL JI Vet. Pathol. PD JUL PY 2005 VL 42 IS 4 BP 458 EP 467 DI 10.1354/vp.42-4-458 PG 10 WC Pathology; Veterinary Sciences SC Pathology; Veterinary Sciences GA 942KZ UT WOS:000230282600007 PM 16006605 ER PT J AU Powell, LH Meyer, P Weiss, G Matthews, KA Santoro, N Randolph, JF Schocken, M Skurnick, J Ory, MG Sutton-Tyrrell, K AF Powell, LH Meyer, P Weiss, G Matthews, KA Santoro, N Randolph, JF Schocken, M Skurnick, J Ory, MG Sutton-Tyrrell, K TI Ethnic differences in past hysterectomy for benign conditions SO WOMENS HEALTH ISSUES LA English DT Article ID SOCIOECONOMIC VARIATION; UNITED-STATES; WOMEN; PREVALENCE; COHORT; RISK; MENOPAUSE; AUSTRALIA; OUTCOMES; DISEASE AB Background: Hysterectomy for a benign condition is common, particularly in the underserved. The objective was to determine if ethnic differences could be explained by known risk factors. Methods: A phone survey was conducted at random on 15,160 women, ages 40-55, from seven US cities. Subjects were 49.9% Caucasian, 28.1% African American, 12.3% Hispanic, and 9.8% Asian American. Results: Ethnicity was associated with past hysterectomy (odds ratio [OR]: Caucasian = 1.0, African American = 1.66; confidence interval [CI] = 1.46-1.88, Hispanic = 1.64, CI = 1.29-2.07; Asian American = 0.44, CI = 0.34-0.56), after adjustment for age, education, fibroids, body mass index, marital status, smoking, geographic site, and country of education. Conclusion: Because the highest rates occurred in the disadvantaged African American and Hispanic subgroups, and could not be explained by known risk factors, disparity in the form of overuse in these disadvantaged groups may exist. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. Univ Med & Dent New Jersey, Dept Obstet & Gynecol, Sch Med, Newark, NJ 07106 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Albert Einstein Med Sch, Dept Obstet & Gynecol, New York, NY USA. Univ Michigan, Hlth Syst, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA. Univ Calif Los Angeles, Sch Med, Div Geriatr, Los Angeles, CA USA. Univ Med & Dent New Jersey, Dept Prevent Med & Community Hlth, Sch Med, Newark, NJ 07106 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Weiss, G (reprint author), Univ Med & Dent New Jersey, Dept Obstet Gynecol & Womens Hlth, Sch Med, 185 So Orange Ave,MSB-E506, Newark, NJ 07106 USA. EM weissge@umdnj.edu FU NIA NIH HHS [AG12505, AG12495, AG12531, AG12539, AG12546, AG12553, AG12554]; NIAAA NIH HHS [AAG12535]; NINR NIH HHS [NR04061] NR 41 TC 28 Z9 28 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JUL-AUG PY 2005 VL 15 IS 4 BP 179 EP 186 DI 10.1016/j.whi.2005.05.002 PG 8 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 951CU UT WOS:000230907300005 PM 16051109 ER PT J AU Bene, L Szollosi, J Szentesi, G Damjanovich, L Gaspar, R Waldmann, TA Damjanovich, S AF Bene, L Szollosi, J Szentesi, G Damjanovich, L Gaspar, R Waldmann, TA Damjanovich, S TI Detection of receptor trimers on the cell surface by flow cytometric fluorescence energy homotransfer measurements SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE fluorescence anisotropy; receptor clustering; MHCI and MHCII glycoprotein; lL-2R alpha; transferrin receptor; CD45 ID HLA CLASS-I; LIPID RAFTS; SEGMENTAL FLEXIBILITY; PLASMA-MEMBRANE; ANISOTROPY MEASUREMENTS; MONOCLONAL-ANTIBODIES; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; IL-2 RECEPTOR; MOLECULES AB Fluorescence energy homotransfer offers a powerful tool for the investigation of the state of oligomerization of cell surface receptors on a cell-by-cell basis by measuring the polarized components of fluorescence intensity of cells labeled with fluorescently stained antibodies. Here we describe homotransfer-based methods for the flow cytometric detection and analysis of hetero- and homo-associations of cell surface receptors. Homotransfer efficiencies for two- and three-body energy transfer interactions are defined and their frequency distribution curves are computed from the fluorescence anisotropy distributions of multiple-labeled cells. The fractions of receptors involved in homo-clustering is calculated based on the dependence of the fluorescence anisotropy on the surface concentration of the fluorescently stained antibodies. A homotransfer analysis of the homo- and hetero-clustering of the MHCl and MHCII glycoproteins, the cytokine receptor IL-2R alpha, transferrin receptor and the receptor-type tyrosine phosphatase CD45 on JY B and Kit-225-K6 T cells is presented. We investigated how various factors such as the type of dye, rotational mobility of the dye and dye-targeting antibody, as well as the wavelength of the exciting light affect the homotransfer. We show that the homotransfer technique combined with the high statistical resolution of flow cytometry is an effective tool for detecting different oligomeric states of receptors by using fluorophores having restricted rotational mobility on the time scale of fluorescence. (C) 2005 Elsevier B.V All rights reserved. C1 Univ Debrecen, Res Ctr Mol Med, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, Debrecen, Hungary. Univ Debrecen, Med & Hlth Sci Ctr, Dept Surg 1, Debrecen, Hungary. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Hungarian Acad Sci, Cell Biophys Res Grp, H-4012 Debrecen, Hungary. RP Bene, L (reprint author), Univ Debrecen, Res Ctr Mol Med, Med & Hlth Sci Ctr, Dept Biophys & Cell Biol, Debrecen, Hungary. EM bene@jaguar.dote.hu RI Damjanovich, Sandor/A-9284-2011 NR 65 TC 10 Z9 10 U1 0 U2 3 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 JUN 30 PY 2005 VL 1744 IS 2 BP 176 EP 198 DI 10.1016/j.bbamcr.2005.02.002 PG 23 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 944BO UT WOS:000230400100008 PM 15950751 ER PT J AU Phue, JN Noronha, SB Hattacharyya, R Wolfe, AJ Shiloach, J AF Phue, JN Noronha, SB Hattacharyya, R Wolfe, AJ Shiloach, J TI Glucose metabolism at high density growth of E-coli B and E-coli K: Differences in metabolic pathways are responsible for efficient glucose utilization in E-coli B as determined by microarrays and northern blot analyses SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE Escherichia coli; acetate; glucose; Northern blot; gluconeogenesis ID ACETYL-COENZYME-A; GLYOXYLATE BYPASS OPERON; ISOCITRATE DEHYDROGENASE; ACETATE METABOLISM; PHOSPHOENOLPYRUVATE CARBOXYKINASE; REGULATORY PROTEIN; ENTERIC BACTERIA; GENE-EXPRESSION; RPOS; ICLR AB In a series of previous reports it was established by implementing metabolic flux, NMR/MS, and Northern blot analysis that the glyoxylate shunt, the TCA cycle, and acetate uptake by acetyl-CoA synthetase are more active in Escherichia coli BL21 than in Escherichia coli JM109. These differences were accepted as the reason for the differences in the glucose metabolism and acetate excretion of these two strains. Examination of the bacterial metabolism by microarrays and time-course Northern blot showed that in addition to the glyoxylate shunt, the TCA cycle and the acetate uptake, other metabolic pathways are active differently in the two strains. These are gluconeogenesis, sfcA shunt, ppc shunt, glycogen biosynthesis, and fatty acid degradation. It was found that in E. coli JM109, acetate is produced by pyruvate oxidase (poxB) using pyruvate as a substrate rather than by phosphotransacetylase-acetate kinase (Pta-AckA) system which uses acetyl-CoA. The inactivation of the gluconeogenesis enzyme phosphoenolpyruvate synthetase (ppsA), the activation of the anaplerotic sfcA shunt, and low and stable pyruvate dehydrogenase (aceE, aceF) cause pyruvate accumulation which is converted to acetate by pyruvate oxidase B. The behavior of the ppsA, acs, and aceBAK in JM109 was dependent on the glucose supply strategy. When the glucose concentration was high, no transcription of these genes was observed and acetate concentration increased, but at low glucose concentrations these genes were expressed and the acetate concentration decreased. It is possible that there is a major regulatory molecule that controls not only ppsA and aceBAK but also acs. The gluconeogenesis pathway (fbp, pckA, and ppsA) which leads to glycogen accumulation is constitutively active in E. coli BL21 regardless of glucose feeding strategy. Published 2005 Wiley Periodicals, Inc. C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. Indian Inst Technol, Dept Chem Engn, Bombay 400076, Maharashtra, India. Loyola Univ, Dept Microbiol & Immunol, Maywood, IL 60153 USA. RP Phue, JN (reprint author), NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. EM yossi@nih.gov NR 43 TC 78 Z9 82 U1 1 U2 17 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 30 PY 2005 VL 90 IS 7 BP 805 EP 820 DI 10.1002/bit.20478 PG 16 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 931CO UT WOS:000229463600003 PM 15806547 ER PT J AU Wang, J Nguyen, V Glen, J Henderson, B Saul, A Miller, LH AF Wang, J Nguyen, V Glen, J Henderson, B Saul, A Miller, LH TI Improved yield of recombinant merozoite surface protein 3 (MSP3) from Pichia pastoris using chemically defined media SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE malaria; Plasmodium falciparum; merozoite surface protein 3; Pichia pastoris; chemically defined media; nitrogen source ID PLASMODIUM-FALCIPARUM; MALARIA; EXPRESSION; VACCINE; YEAST; FERMENTATION; STRATEGIES; GENE; OPTIMIZATION; MECHANISMS AB Plasmodium falciparum merozoite surface protein 3 (MSP3) is a leading blood-stage malaria vaccine candidate. Vaccination with Pichia pastoris derived recombinant MSP3 protected Aotus nacymai monkeys from the parasite's lethal challenge and the post-challenge antibody titer against MSP3 correlated with protection. In our preliminary attempts to produce this vaccine in fermentors, little or no expression of MSP3 was observed in chemically defined media, although the same P. pastoris strain produced MSP3 in complex media. Our goal is to develop a Phase I/II clinical manufacturing process in completely chemically defined media because of the concern of potential prion contamination in complex media containing animal derived products. Here, we report our investigations into various factors to improve the yield of MSP3 in defined media. We found that an induction pH (pH(i)) 6.8 yielded MSP3 at 434 mg/L whereas there was no product at pH(i) <= 5, though cell growth was the same in all pH(i) levels examined. High levels of NH4+ consumed at pH(i) 6.8 were directly correlated to the enhanced MSP3 production. Furthermore, an additional 3.5-fold increase in the yield of MSP3 was obtained by addition of casamino acids at pH(i) 6.8. No direct correlation was observed between protease activity in the culture supernatants and lack of MSP3 expression. Neither high P. pastoris biomass generated at a high specific growth rate (0.04/h) nor low induction temperatures during induction improved yield. Nitrogen source was the most important factor affecting expression of MSP3 in defined media. Published 2005 Wiley Periodicals, Inc. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Wang, J (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane, Rockville, MD 20852 USA. EM jinwang2@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 36 TC 16 Z9 21 U1 0 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 30 PY 2005 VL 90 IS 7 BP 838 EP 847 DI 10.1002/bit.20491 PG 10 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 931CO UT WOS:000229463600006 PM 15849695 ER PT J AU Cholody, WM Kosakowska-Cholody, T Hollingshead, MG Hariprakasha, HK Michejda, CJ AF Cholody, WM Kosakowska-Cholody, T Hollingshead, MG Hariprakasha, HK Michejda, CJ TI A new synthetic agent with potent but selective cytotoxic activity against cancer SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CHEMOTHERAPY-INDUCED APOPTOSIS; BIFUNCTIONAL INTERCALATORS; DNA-BINDING; CELL-DEATH; PHASE-II; BISIMIDAZOACRIDONES; DIACRIDINES; MITONAFIDE; PATHWAYS; GROWTH AB The synthesis of novel unsymmetrical bifunctional antitumor agents was accomplished by linking an imidazoacridone moiety to another polycyclic heteroaromatic moiety via linkers of various length and rigidity. These compounds bind to cellular DNA, but it is hypothesized that biological effects become manifested when the drug-DNA complexes interact with critical DNA binding proteins that are involved in repair and transcription. The most promising compound of the series, 4ad (WMC79), consists of an imidazoacridone linked to a 3-nitronaph-thalimide moiety via a 1,4-dipropanopiperazine linker. It was found to be potently, but selectively, cytotoxic against colon cancers (GI(50) = 0.5 nM, LC50 = 32 nM) and leukemias (GI(50) = 3.5 nM, LC50 = 33 nM). Compound 4ad, which appears to be a candidate for further development as an anticancer drug, kills sensitive cells by induction of apoptosis. It also showed significant in vivo activity against HCT-116 colon cancer xenografts in nude mice. Other compounds in the series also exhibited antitumor properties, but they were significantly lower than that of 4ad. C1 NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Michejda, CJ (reprint author), NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Canc Res Ctr, Frederick, MD 21702 USA. EM michejda@ncifcrf.gov NR 28 TC 36 Z9 36 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 30 PY 2005 VL 48 IS 13 BP 4474 EP 4481 DI 10.1021/jm048946x PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 940CR UT WOS:000230121800032 PM 15974599 ER PT J AU Mulshine, JL Sullivan, DC AF Mulshine, JL Sullivan, DC TI Lung cancer screening SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HELICAL COMPUTED-TOMOGRAPHY; SMALL PULMONARY NODULES; SPIRAL CT; BASE-LINE; COST-EFFECTIVENESS; SMOKING-CESSATION; ACTION PROJECT; ADULT SMOKERS; CARCINOMA; SURVIVAL C1 NCI, Intervent Sect, Cell & Canc Biol Branch, Lung Canc & Aerodigest Chemoprevent Fac,Ctr Canc, Bethesda, MD 20892 USA. NCI, Canc Imaging Program, Div Canc Treatment & Diag, Rockville, MD USA. RP Mulshine, JL (reprint author), NIH, Ctr Clin, Cell & Canc Biol Branch, Rm 12N226, Bethesda, MD 20892 USA. EM mulshinj@mail.nih.gov NR 52 TC 125 Z9 136 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 JUN 30 PY 2005 VL 352 IS 26 BP 2714 EP 2720 DI 10.1056/NEJMcp042630 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 940HH UT WOS:000230133800008 PM 15987920 ER PT J AU Mambo, E Chatterjee, A de Souza-Pinto, NC Mayard, S Hogue, BA Joque, MO Dizdaroglu, M Bohr, VA Sidransky, D AF Mambo, E Chatterjee, A de Souza-Pinto, NC Mayard, S Hogue, BA Joque, MO Dizdaroglu, M Bohr, VA Sidransky, D TI Oxidized guanine lesions and hOgg1 activity in lung cancer SO ONCOGENE LA English DT Article DE hOGG1; lung cancer; 8-oxoG; mitochondria; DNA repair ID OXIDATIVE DNA-DAMAGE; TRANSCRIPTION-COUPLED REPAIR; BASE EXCISION-REPAIR; ESCHERICHIA-COLI; MAMMALIAN-CELLS; NUCLEAR-DNA; P53 GENE; OGG1; MITOCHONDRIAL; 8-OXOGUANINE AB In humans, the oxidatively induced DNA lesion 8-hydroxyguanine (8-oxoG) is removed from DNA by hOgg1, a DNA glycosylase/AP lyase that specifically incises 8-oxoG opposite cytosine. We analysed the expression of hOGG1 mRNA in 18 lung cancer and three normal cell lines. Although hOGG1 was overexpressed in most cell lines, 2/18 (11.1%) showed a lower hOGG1 mRNA and protein expression (similar to 80% decrease) relative to normal cell lines. Liquid chromatography/mass spectrometry analysis showed increased levels of 8-oxoG in the two cell lines with the lowest hOGG1 mRNA expression. We examined the ability of nuclear and mitochondrial extracts to incise 8-oxoG lesion in cell lines H1650 and H226 expressing lower hOGG1 mRNA and H1915 and H1975 with higher than normal hOGG1 mRNA expression. Both nuclear and mitochondrial extracts from H1915 and H1975 cells were proficient in 8-oxoG removal. However, both cell lines with the lowest hOGG1 mRNA expression exhibited a severe reduction in 8-oxoG incision in both nuclear and mitochondrial extracts. Under-expression of hOGG1 mRNA and hOgg1 protein was associated with a decrease in mitochondrial DNA repair in response to oxidative damaging agents. These results provide evidence for defective incision of 8-oxoG in both nuclear and mitochondria of H1650 and H226 lung cancer cell lines. These results may implicate 8-oxoG repair defects in certain lung cancers. C1 Johns Hopkins Univ, Sch Med, Head & Neck Canc Res Div, Dept Otolaryngol Head & Neck Surg, Baltimore, MD 21205 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Natl Inst Stand & Technol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP Sidransky, D (reprint author), Johns Hopkins Univ, Sch Med, Head & Neck Canc Res Div, Dept Otolaryngol Head & Neck Surg, 720 Rutland Ave,818 Ross Res Bldg, Baltimore, MD 21205 USA. EM dsidrans@jhmi.edu RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X FU NCI NIH HHS [5P50CA096784-03, 5 U01 CA084986-04] NR 51 TC 52 Z9 54 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 30 PY 2005 VL 24 IS 28 BP 4496 EP 4508 DI 10.1038/sj.onc.1208669 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 940PT UT WOS:000230157100003 PM 15856018 ER PT J AU Azran, I Jeang, KT Aboud, M AF Azran, I Jeang, KT Aboud, M TI High levels of cytoplasmic HTLV-1 Tax mutant proteins retain a Tax-NF-kappa B-CBP ternary complex in the cytoplasm SO ONCOGENE LA English DT Article DE HTLV-1; Tax; cytoplasmic Tax mutants; NF-kappa B; CBP; PKAc ID T-CELL LEUKEMIA; VIRUS TYPE-I; LONG TERMINAL REPEAT; CREB BINDING-PROTEIN; TRANSCRIPTIONAL ACTIVATION; TYPE-1 TAX; TRANSACTIVATOR TAX; COACTIVATOR CBP; IKK-ALPHA; NUCLEAR TRANSLOCATION AB The oncogenic potential of HTLV- 1 Tax protein is partially ascribed to its capacity to activate NF-kappa B. The current view is that Tax acts first in the cytoplasm to dissociate NF-kappa B factors from the I kappa B proteins and enable their nuclear translocation, then Tax links p65( RelA), within the nucleus, to CBP/p300 and P/ CAF, which are essential for its optimal transcriptional activity. Our present study challenges the paradigm that Tax-p65( RelA)-CBP/p300 assembly occurs in the nucleus. Using Tax mutants defective for nuclear localization we show that at low levels these mutants induce the nuclear translocation of NF-kappa B factors but not their transcriptional activity, whereas at high levels they trap CBP and free p65( RelA) in the cytoplasm and block, thereby, their transcriptional function. In contrast, wildtype (w.t.) Tax strongly stimulated NF-kappa B-dependent gene expression in all tested experimental settings. These data suggest that the Tax-p65( RelA)-CBP ternary complex is established in the cytoplasm rather than in the nucleus. When this complex is formed with w.t. Tax, the entire moiety translocates into the nucleus and exerts high transcriptional activity. However, if the complex is formed with the cytoplasmic Tax mutants, the resulting moiety is retained in the cytoplasm and is, therefore, devoid of transcriptional activity. C1 Ben Gurion Univ Negev, Fac Hlth Sci, Canc Res Ctr, Dept Microbiol & Immunol, IL-84105 Beer Sheva, Israel. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Aboud, M (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Canc Res Ctr, Dept Microbiol & Immunol, IL-84105 Beer Sheva, Israel. EM aboud@bgu.ac.il RI Jeang, Kuan-Teh/A-2424-2008 NR 78 TC 23 Z9 23 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 30 PY 2005 VL 24 IS 28 BP 4521 EP 4530 DI 10.1038/sj.onc.1208645 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 940PT UT WOS:000230157100005 PM 15806143 ER PT J AU Amundson, SA Do, KT Vinikoor, L Koch-Paiz, CA Bittner, ML Trent, JM Meltzer, P Fornace, AJ AF Amundson, SA Do, KT Vinikoor, L Koch-Paiz, CA Bittner, ML Trent, JM Meltzer, P Fornace, AJ TI Stress-specific signatures: expression profiling of p53 wild-type and -null human cells SO ONCOGENE LA English DT Article DE cDNA microarray; DNA damage; heavy metals; p53 ID THYMIDINE KINASE LOCUS; GENE-EXPRESSION; CDNA MICROARRAY; PROTEIN-KINASE; UV-RADIATION; TK6 CELLS; RESPONSES; APOPTOSIS; IDENTIFICATION; KERATINOCYTES AB Gene expression responses of human cell lines exposed to a diverse set of stress agents were compared by cDNA microarray hybridization. The B-lymphoblastoid cell line TK6 (p53 wild- type) and its p53-null derivative, NH32, were treated in parallel to facilitate investigation of p53-dependent responses. RNA was extracted 4 h after the beginning of treatment when no notable decrease in cell viability was evident in the cultures. Gene expression signatures were defined that discriminated between four broad general mechanisms of stress agents: Non-DNA-damaging stresses ( heat shock, osmotic shock, and 12-O-tetradecanoylphorbol 13-acetate), agents causing mainly oxidative stress ( arsenite and hydrogen peroxide), ionizing radiations ( neutron and gamma-ray exposures), and other DNA-damaging agents ( ultraviolet radiation, methyl methanesulfonate, adriamycin, camptothecin, and cis-Platinum( II) diammine dichloride ( cisplatin)). Within this data set, non-DNA-damaging stresses could be discriminated from all DNA-damaging stresses, and profiles for individual agents were also defined. While DNA-damaging stresses showed a strong p53-dependent element in their responses, no discernible p53-dependent responses were triggered by the non-DNA-damaging stresses. A set of 16 genes did exhibit a robust p53-dependent pattern of induction in response to all nine DNA-damaging agents, however. C1 NCI, Gene Response Sect, Canc Res Ctr, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RP Fornace, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM afornace@hsph.harvard.edu RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [CA-37967]; NIBIB NIH HHS [EB-002033] NR 35 TC 85 Z9 87 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 30 PY 2005 VL 24 IS 28 BP 4572 EP 4579 DI 10.1038/sj.onc.1208653 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 940PT UT WOS:000230157100010 PM 15824734 ER PT J AU Harland, M Taylor, CF Chambers, PA Kukalizch, K Randerson-Moor, JA Gruis, NA de Snoo, FA ter Huurne, JAC Goldstein, AM Tucker, MA Bishop, DT Bishop, JAN AF Harland, M Taylor, CF Chambers, PA Kukalizch, K Randerson-Moor, JA Gruis, NA de Snoo, FA ter Huurne, JAC Goldstein, AM Tucker, MA Bishop, DT Bishop, JAN TI A mutation hotspot at the p14ARF splice site SO ONCOGENE LA English DT Article DE CDKN2A; p14ARF; p16INK4a; melanoma; mutation; splicing ID GERMLINE MUTATIONS; MELANOMA FAMILIES; CDKN2A; SENESCENCE; GENE; LOCUS; RECOMBINATION; FIBROBLASTS; EXPRESSION; PROTEINS AB Germline mutations of CDKN2A that affect the p16INK4a transcript have been identified in numerous melanoma pedigrees worldwide. In the UK, over 50% of pedigrees with three or more cases of melanoma have been found to carry mutations of CDKN2A. Mutations that affect p14ARF exon 1 beta exclusively are very rare. This has led to the suggestion that it is p16INK4a and not p14ARF that plays the critical role in melanoma predisposition. We report the identification of a cluster of five different germline mutations at the p14ARF exon 1 beta splice donor site in melanoma pedigrees. All the five splice site variants showed evidence of being causal mutations. Three of the variants were demonstrated to result in aberrant splicing of the p14ARF mRNA, confirming their role in melanoma predisposition. No other point mutations were identified in the coding region of p14ARF. The p14ARF transcript of CDKN2A is clearly important in disease predisposition in a subset of melanoma pedigrees. Curiously, the only mutations so far reported to affect p14ARF exon 1 beta exclusively have been knockout mutations. Further investigation into the spectrum of mutations observed in this gene may help clarify the exact role of p14ARF in melanoma predisposition. C1 St James Univ Hosp, Canc Res UK Clin Ctr, Genet Epidemiol Div, Leeds LS9 7TF, W Yorkshire, England. St James Univ Hosp, Canc Res UK Clin Ctr, Mutat Detect Facil, Leeds LS9 7TF, W Yorkshire, England. Leiden Univ, Ctr Med, Dept Dermatol, NL-9600 PB Leiden, Netherlands. Leiden Univ, Ctr Med, Ctr Human & Clin Genet, NL-9600 PB Leiden, Netherlands. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Bishop, JAN (reprint author), St James Univ Hosp, Canc Res UK Clin Ctr, Genet Epidemiol Div, Beckett St, Leeds LS9 7TF, W Yorkshire, England. EM j.newton-bishop@cancer.org.uk RI Tucker, Margaret/B-4297-2015; OI Gruis, Nelleke/0000-0002-5210-9150; Bishop, Tim/0000-0002-8752-8785; Newton Bishop, Julia/0000-0001-9147-6802 FU NCI NIH HHS [IR01 CA083115] NR 34 TC 46 Z9 47 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 30 PY 2005 VL 24 IS 28 BP 4604 EP 4608 DI 10.1038/sj.onc.1208678 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 940PT UT WOS:000230157100015 PM 15856016 ER PT J AU Saavedra, JM Ando, H Armando, I Baiardi, G Bregonzio, C Juorio, A Macova, M AF Saavedra, JM Ando, H Armando, I Baiardi, G Bregonzio, C Juorio, A Macova, M TI Anti-stress and anti-anxiety effects of centrally acting angiotensin II AT(1) receptor antagonists SO REGULATORY PEPTIDES LA English DT Article; Proceedings Paper CT Symposium on Molecular Physiology of Vasoactive Peptides CY NOV 19-22, 2003 CL Mar del Plata, ARGENTINA SP Amer Physiol Soc, Latin Amer Initiat, Argentinean Soc Clin Investigat DE stress; brain; inflammation; CRH; catecholamines; anxiety ID INDUCED GASTRIC INJURY; CENTRAL-NERVOUS-SYSTEM; RAT-BRAIN; BINDING-SITES; GENE-EXPRESSION; AUTORADIOGRAPHIC LOCALIZATION; PARAVENTRICULAR NUCLEUS; TYPE-1 RECEPTOR; PHOSPHOINOSITIDE HYDROLYSIS; SUBFORNICAL ORGAN AB The brain and the peripheral (hormonal) angiotensin II systems are stimulated during stress. Activation of brain angiotensin II AT(1) receptors is required for the stress-induced hormone secretion, including CRH, ACTH, corticoids and vasopressin, and for stimulation of the central sympathetic activity. Long-term peripheral administration of the angiotensin II AT(1) antagonist candesartan blocks not only peripheral but also brain AT(1) receptors, prevents the hormonal and sympathoadrenal response to isolation stress and prevents the formation of stress-induced gastric ulcers. The mechanisms responsible for the prevention of stress-induced ulcers by the AT(1) receptor antagonist include protection from the stress-induced ischemia and inflammation (neutrophil infiltration and increase in ICAM-1 and TNF-α) in the gastric mucosa and a partial blockade of the stress-induced sympathoadrenal stimulation, while the protective effect of the glucocorticoid release during stress is maintained. AT(1) receptor antagonism prevents the stress-induced decrease in cortical CRH1 and benzodiazepine binding and is anxiolytic. Blockade of brain angiotensin II AT(1) receptors offers a novel therapeutic opportunity for the treatment of anxiety and other stress-related disorders. © 2005 Elsevier B.V. All rights reserved. C1 NIMH, Pharmacol Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room 2D-57, Bethesda, MD 20892 USA. EM Saavedrj@mail.nih.gov NR 102 TC 55 Z9 58 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUN 30 PY 2005 VL 128 IS 3 BP 227 EP 238 DI 10.1016/j.regpep.2004.12.015 PG 12 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 925PK UT WOS:000229064800009 PM 15837532 ER PT J AU Zhu, PJ Lovinger, DM AF Zhu, PJ Lovinger, DM TI Retrograde endocannabinoid signaling in a postsynaptic neuron/synaptic bouton preparation from basolateral amygdala SO JOURNAL OF NEUROSCIENCE LA English DT Article DE mGluR5; GABAergic transmission; CB1 receptors; depolarization; induced suppression of inhibition; IPSC; basolateral amygdala ID CB1 CANNABINOID RECEPTORS; CEREBELLAR PURKINJE-CELLS; LONG-TERM DEPRESSION; ENDOGENOUS CANNABINOIDS; SYNAPTIC-TRANSMISSION; EXCITATORY SYNAPSES; MAMMALIAN NEURONS; CALCIUM-CHANNELS; RAT AMYGDALA; INHIBITION AB Retrograde synaptic signaling by endogenous cannabinoids (endocannabinoids) is a recently discovered form of neuromodulation in the brain. In the basolateral amygdala (BLA), endocannabinoid signaling has been implicated in learning and memory, specifically in extinction of aversive memories. To examine retrograde endocannabinoid signaling in this brain region, BLA neurons were freshly isolated using an enzyme-free procedure. These isolated neurons retain attached functional excitatory and inhibitory synaptic boutons. Spontaneous GABAergic IPSCs (sIPSCs) were isolated from these freshly isolated neurons and a 4s step of depolarization from -60 to 0 mV produced suppression of sIPSC frequency and amplitude. A similar depolarization-induced suppression of inhibition (DSI) was observed in neurons in BLA slices. DSI in the single-cell preparation was abolished by the CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide, and DSI duration was shortened in the presence of 2-methyl-6-(phenylethynyl) pyridine, an mGluR5 (metabotropic glutamate receptor 5) antagonist. The initial decrease in sIPSCs induced by the DSI procedure was greatly attenuated in recordings with 20mM BAPTA containing postsynaptic internal solution, but a delayed-onset decrease was observed under this recording condition. A CB1 agonist decreased sIPSC frequency and amplitude, whereas CB1 antagonists increased these responses. The antagonist-induced increase was abolished in 20mM BAPTA-filled cells. These data provide solid evidence for retrograde endocannabinoid signaling in the BLA and also indicate that this retrograde signaling requires only a postsynaptic neuron and attached synaptic boutons. C1 NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Fishers TS-13, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov FU Intramural NIH HHS; NIAAA NIH HHS [Z01 AA000407-04] NR 30 TC 68 Z9 74 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 29 PY 2005 VL 25 IS 26 BP 6199 EP 6207 DI 10.1523/JNEUROSCI.1148-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 940SX UT WOS:000230165600019 PM 15987949 ER PT J AU Pletnev, S Magracheva, E Wlodawer, A Zdanov, A AF Pletnev, S Magracheva, E Wlodawer, A Zdanov, A TI A model of the ternary complex of interleukin-10 with its soluble receptors SO BMC STRUCTURAL BIOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; CRYSTAL-STRUCTURE; INTERFERON-GAMMA; ERYTHROPOIETIN RECEPTOR; EXTRACELLULAR DOMAIN; BINDING; IL-10; GROWTH; CELLS; CYTOKINES AB Background: Interleukin-10 (IL-10) is a cytokine whose main biological function is to suppress the immune response by induction of a signal(s) leading to inhibition of synthesis of a number of cytokines and their cellular receptors. Signal transduction is initiated upon formation of a ternary complex of IL-10 with two of its receptor chains, IL-10R1 and IL-10R2, expressed on the cell membrane. The affinity of IL-10R1 toward IL-10 is very high, which allowed determination of the crystal structure of IL-10 complexed with the extracellular/soluble domain of IL-10R1, while the affinity of IL-10R2 toward either IL-10 or IL-10/sIL-10R1 complex is quite low. This so far has prevented any attempts to obtain structural information about the ternary complex of IL-10 with its receptor chains. Results: Structures of the second soluble receptor chain of interleukin-10(sIL-10R2) and the ternary complex of IL-10/sIL-10R1/sIL-10R2 have been generated by homology modeling, which allowed us to identify residues involved in ligand-receptor and receptor- receptor interactions. Conclusion: The previously experimentally determined structure of the intermediate/ binary complex IL-10/sIL-10R1 is the same in the ternary complex. There are two binding sites for the second receptor chain on the surface of the IL-10/sIL-10R1 complex, involving both IL-10 and sIL10R1. Most of the interactions are hydrophilic in nature, although each interface includes two internal hydrophobic clusters. The distance between C-termini of the receptor chains is 25 angstrom, which is common for known structures of ternary complexes of other cytokines. The structure is likely to represent the biologically active signaling complex of IL-10 with its receptor on the surface of the cell membrane. C1 NCI, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Basic Res Program, Sci Applicat Int Corp Frederick, Ft Detrick, MD 21702 USA. RP Zdanov, A (reprint author), NCI, Macromol Crystallog Lab, Canc Res Ctr, Frederick, MD 21702 USA. EM svp@ncifcrf.gov; eugenia@ncifcrf.gov; wlodawer@ncifcrf.gov; zdanov@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 56 TC 23 Z9 24 U1 0 U2 3 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 JUN 28 PY 2005 VL 5 AR 10 DI 10.1186/1472-6807-5-10 PG 15 WC Biophysics SC Biophysics GA 997YB UT WOS:000234283800002 PM 15985167 ER PT J AU Sutton-Tyrrell, K Najjar, SS Boudreau, RM Venkitachalam, L Kupelian, V Simonsick, EM Havlik, R Lakatta, EG Spurgeon, H Kritchevsky, S Pahor, M Bauer, D Newman, A AF Sutton-Tyrrell, K Najjar, SS Boudreau, RM Venkitachalam, L Kupelian, V Simonsick, EM Havlik, R Lakatta, EG Spurgeon, H Kritchevsky, S Pahor, M Bauer, D Newman, A CA Hlth ABC Study TI Elevated aortic pulse wave velocity, a marker of arterial stiffness, predicts cardiovascular events in well-functioning older adults SO CIRCULATION LA English DT Article DE aging; elasticity; epidemiology; mortality; risk factors ID ISOLATED SYSTOLIC HYPERTENSION; STAGE RENAL-DISEASE; HEART-FAILURE; BLOOD-PRESSURE; BRACHIAL-ARTERY; RISK-FACTOR; ALL-CAUSE; MORTALITY; HEALTH; DISTENSIBILITY AB Background - Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity ( aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular ( CV) mortality and CV events in a community- dwelling sample of older adults. Methods and Results - aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition ( Health ABC) study. Vital status, cause of death and coronary heart disease ( CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality ( relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P = 0.019) and cardiovascular mortality ( relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P = 0.004). aPWV quartile was also significantly associated with CHD ( P = 0.007) and stroke ( P = 0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. Conclusions - Among generally healthy, community- dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke. C1 Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. NIA, Gerontol Res Ctr, Bethesda, MD USA. Univ Tennessee, Memphis, TN 38163 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. RP Sutton-Tyrrell, K (reprint author), Univ Pittsburgh, Dept Epidemiol, Grad Sch Publ Hlth, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. EM Tyrrell@edc.pitt.edu RI Venkitachalam, Lakshmi/B-5618-2008; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Boudreau, Robert/0000-0003-0162-5187; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 46 TC 569 Z9 615 U1 3 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 28 PY 2005 VL 111 IS 25 BP 3384 EP 3390 DI 10.1161/CIRCULATIONAHA.104.483628 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 939ZJ UT WOS:000230112400008 PM 15967850 ER PT J AU Libby, P Nathan, DM Abraham, K Brunzell, JD Fradkin, JE Haffner, SM Hsueh, W Rewers, M Roberts, T Savage, PJ Skarlatos, S Wassef, M Rabadan-Diehl, C AF Libby, P Nathan, DM Abraham, K Brunzell, JD Fradkin, JE Haffner, SM Hsueh, W Rewers, M Roberts, T Savage, PJ Skarlatos, S Wassef, M Rabadan-Diehl, C TI Report of the national heart, lung, and blood institute-national institute of diabetes and digestive and kidney diseases working group on cardiovascular complications of type 1 diabetes mellitus SO CIRCULATION LA English DT Article DE atherosclerosis; cardiovascular diseases; diabetes mellitus; insulin ID CORONARY-ARTERY CALCIFICATION; ENDOTHELIUM-DEPENDENT VASODILATION; MYOCARDIAL-INFARCTION; RISK-FACTORS; PITTSBURGH EPIDEMIOLOGY; INSULIN-RESISTANCE; FOLLOW-UP; PROGRESSION; ATHEROSCLEROSIS; MORTALITY AB Cardiovascular disease ( CVD) constitutes the major cause of mortality and morbidity in both type 1 ( T1D) and type 2 ( T2D) diabetes patients. Although the microvascular complications of T1D are well studied, macrovascular CVD, its treatment, and link to diabetes have been investigated primarily in T2D patients. On April 27 and 28, 2003, the National Heart, Lung, and Blood Institute ( NHLBI) and the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK) sponsored a meeting to identify ways to close gaps in our knowledge about CVD in T1D to improve prevention and treatment. Participants were asked to: ( 1) Evaluate opportunities for studying the pathogenesis of CVD in T1D patients. Risk factors unique to these patients were of particular interest, as well as studies of the cause of CVD in T1D with respect to existing databases or cohorts and involving partnerships between basic and clinical investigators. ( 2) Evaluate opportunities for intervention studies to treat or prevent CVD in T1D. Because of practical obstacles ( recruitment, duration, and cost of interventional studies with hard clinical end points), identification of reliable methods and markers that enable efficient intervention were a high priority. The meeting included 3 sessions: ( 1) current understanding of T1D and CVD; ( 2) opportunities to expand our understanding of the pathogenesis and clinical course of CVD in T1D; and ( 3) opportunities for intervention studies to reduce cardiovascular complications in T1D. This report summarizes the presentations made and concludes with recommendations drawn from the presentations and discussion among the participants. C1 NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Colorado, Denver, CO 80202 USA. RP Rabadan-Diehl, C (reprint author), NHLBI, Div Heart & Vasc Dis, NIH, Rockledge 2,Room 10186,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM rabadanc@nhlbi.nih.gov NR 44 TC 143 Z9 146 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 28 PY 2005 VL 111 IS 25 BP 3489 EP 3493 DI 10.1161/CIRCULATIONAHA.104.529651 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 939ZJ UT WOS:000230112400021 PM 15983263 ER PT J AU Mosley, TH Knopman, DS Catellier, DJ Bryan, N Hutchinson, RG Grothues, CA Folsom, AR Cooper, LS Burke, GL Liao, D Szklo, M AF Mosley, TH Knopman, DS Catellier, DJ Bryan, N Hutchinson, RG Grothues, CA Folsom, AR Cooper, LS Burke, GL Liao, D Szklo, M TI Cerebral MRI findings and cognitive functioning - The atherosclerosis risk in communities study SO NEUROLOGY LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Academy-of-Neurology CY APR 05-12, 2001 CL PHILADELPHIA, PA SP Amer Acad Neurol ID WHITE-MATTER LESIONS; MIDDLE-AGED ADULTS; CARDIOVASCULAR HEALTH; ALZHEIMERS-DISEASE; ELDERLY-PEOPLE; OLDER-ADULTS; BRAIN; ROTTERDAM; ABNORMALITIES; PREVALENCE AB Objective: To examine the association between prevalent cerebral abnormalities identified on MRI and cognitive functioning in a predominantly middle-aged, population-based study cohort. Methods: Cerebral MRI was performed on 1,538 individuals (aged 55 to 72) from the Atherosclerosis Risk in Communities (ARIC) cohort, with no history of stroke or TIA, at study sites in Forsyth County, NC, and Jackson, MS. White matter hyperintensities (WMHs), ventricular size, and sulcal size were graded by trained neuroradiologists on a semiquantitative, 10-point scale. Cognitive functioning was assessed using the Delayed Word Recall Test (DWRT), Digit Symbol Substitution Test (DSST), and Word Fluency Test (WFT). Results: High ventricular grade was independently associated with significantly lower scores on the DWRT and DSST and greater risk (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.51 to 3.56) of impaired scores (i.e., <= 10th percentile) on the DWRT. High sulcal grade was associated with a modest decrement in scores on the DWRT. The presence of coexisting high grade WMHs and silent infarcts was independently associated with lower scores on all cognitive tests and greater risk of impaired functioning on the DSST (OR 2.91, 95% CI: 1.23 to 6.89) and WFT (OR 2.28, 95% CI 1.03 to 5.08). The presence of two or more high-grade abnormalities was associated with increased risk of impaired functioning on all cognitive tests (DWRT: OR 2.23, 95% CI 1.40 to 3.55; DSST: OR 2.06, 95% CI 1.13 to 3.76; WFT: OR 2.07, 95% CI 1.23 to 3.49) independent of multiple covariates and silent infarcts. Conclusion: Common changes in brain morphology are associated with diminished cognitive functioning in middle-aged and young-elderly individuals. C1 Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. Hosp Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Penn State Univ, Milton S Hershey Med Ctr, University Pk, PA 16802 USA. Johns Hopkins Med Inst, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. RP Mosley, TH (reprint author), Univ Mississippi, Med Ctr, Dept Geriatr Med, 2500 N State St, Jackson, MS 39216 USA. EM tmosley@medicine.umsmed.edu FU NHLBI NIH HHS [N01-HC-55021, N01-HC-55019, N01-HC-55020, N01-HC-55018, N01-HC-55016, N01-HC-55022, N01-HC-55017, N01-HC-55015] NR 32 TC 88 Z9 90 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 28 PY 2005 VL 64 IS 12 BP 2056 EP 2062 DI 10.1212/01.WNL.0000165985.97397.88 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 939ZI UT WOS:000230112300012 PM 15985571 ER PT J AU Altarescu, G Moore, DF Schiffmann, R AF Altarescu, G Moore, DF Schiffmann, R TI Effect of genetic modifiers on cerebral lesions in Fabry disease SO NEUROLOGY LA English DT Article ID YOUNG; RISK; HYPERPERFUSION; POLYMORPHISMS; MUTATION AB Fabry disease is associated with increased risk of premature stroke and presumptive ischemic cerebral lesions. In 57 consecutive patients, 35% of whom had lesions on brain MRI, the authors found that genotypes of polymorphisms G-174C of interleukin-6, G894T of endothelial nitric oxide synthase, factor V G1691A mutation, and the A-13G and G79A of protein Z were all significantly associated with cerebral lesions. These findings suggest that these proteins modulate Fabry cerebral vasculopathy. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Shaare Zedek Med Ctr, Dept Internal Med, Jerusalem, Israel. Univ Manitoba, Dept Internal Med, Neurol Sect, Winnipeg, MB R3T 2N2, Canada. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D03,9000 Rockville Pike, Bethesda, MD 20892 USA. EM RS4e@nih.gov FU NINDS NIH HHS [NS002984-05] NR 10 TC 49 Z9 51 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 28 PY 2005 VL 64 IS 12 BP 2148 EP 2150 DI 10.1212/01.WNL.0000166000.24321.4F PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 939ZI UT WOS:000230112300035 PM 15985593 ER PT J AU Yewdell, JW AF Yewdell, JW TI Immunoproteasomes: Regulating the regulator SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID 20S PROTEASOME C1 NIAID, Cellular Biol Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yewdell, JW (reprint author), NIAID, Cellular Biol Sect, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. EM jyewdell@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 10 TC 30 Z9 30 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 28 PY 2005 VL 102 IS 26 BP 9089 EP 9090 DI 10.1073/pnas.0504018102 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 941CD UT WOS:000230191400001 PM 15967978 ER PT J AU Fritz, J Mishkin, M Saunders, RC AF Fritz, J Mishkin, M Saunders, RC TI In search of an auditory engram SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE medial temporal lobe; perirhinal cortex; recognition memory ID SHORT-TERM-MEMORY; SUPERIOR TEMPORAL CORTEX; MONKEYS CEBUS-APELLA; RHESUS-MONKEYS; VISUAL RECOGNITION; PERIRHINAL CORTEX; PARAHIPPOCAMPAL CORTICES; SEMANTIC COMMUNICATION; OBJECT RECOGNITION; ENTORHINAL CORTEX AB Monkeys trained preoperatively on a task designed to assess auditory recognition memory were impaired after removal of either the rostral superior temporal gyrus or the medial temporal lobe but were unaffected by lesions of the rhinal cortex. Behavioral analysis indicated that this result occurred because the monkeys did not or could not use long-term auditory recognition, and so depended instead on short-term working memory, which is unaffected by rhinal lesions. The findings suggest that monkeys may be unable to place representations of auditory stimuli into a long-term store and thus question whether the monkey's cerebral memory mechanisms in audition are intrinsically different from those in other sensory modalities. Furthermore, it raises the possibility that language is unique to humans not only because it depends on speech but also because it requires long-term auditory memory. C1 NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Saunders, RC (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM richardsaunders@mail.nih.gov NR 41 TC 68 Z9 69 U1 3 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 28 PY 2005 VL 102 IS 26 BP 9359 EP 9364 DI 10.1073/pnas.0503998102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 941CD UT WOS:000230191400049 PM 15967995 ER PT J AU Zhang, H Zhang, AH Kohan, DE Nelson, RD Gonzalez, FJ Yang, TX AF Zhang, H Zhang, AH Kohan, DE Nelson, RD Gonzalez, FJ Yang, TX TI Collecting duct-specific deletion of peroxisome proliferator-activated receptor gamma blocks thiazolidinedione-induced fluid retention SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE roziglitazone; Cre recombinase; Evans blue technique ID VASCULAR ENDOTHELIAL-CELLS; TYPE-2 DIABETES-MELLITUS; LOWERS BLOOD-PRESSURE; PPAR-GAMMA; ADIPOCYTE DIFFERENTIATION; LIPID-METABOLISM; CONSCIOUS RATS; ALPHA; ROSIGLITAZONE; TROGLITAZONE AB The peroxisome proliferator-activated receptor subtype gamma (PPAR gamma) ligands, namely the synthetic insulin-sensitizing thiazolidinedione (TZD) compounds, have demonstrated great potential in the treatment of type II diabetes. However, their clinical applicability is limited by a common and serious side effect of edema. To address the mechanism of TZD-induced edema, we generated mice with collecting duct (CD)-specific disruption of the PPAR gamma gene. We found that mice with CID knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPAR gamma in the CID. RGZ reduced urinary sodium excretion in control and not in conditional knockout mice. Furthermore, RGZ stimulated sodium transport in primary cultures of CD cells expressing PPAR gamma and not in cells lacking this receptor. These findings demonstrate a PPAR gamma- dependent pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention. C1 Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA. Univ Utah, Dept Pediat, Salt Lake City, UT 84132 USA. Salt Lake Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Yang, TX (reprint author), Univ Utah, Dept Internal Med, Salt Lake City, UT 84132 USA. EM tanxin.yang@hsc.utah.edu FU NHLBI NIH HHS [R0-1 HL079453, R01 HL079453]; NIDDK NIH HHS [K01 DK064981, R0-1 DK066592, R01 DK066592] NR 44 TC 226 Z9 232 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 28 PY 2005 VL 102 IS 26 BP 9406 EP 9411 DI 10.1073/pnas.0501744102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 941CD UT WOS:000230191400057 PM 15956187 ER PT J AU Sumner, AE Finley, KB Genovese, DJ Criqui, MH Boston, RC AF Sumner, AE Finley, KB Genovese, DJ Criqui, MH Boston, RC TI Fasting triglyceride and the triglyceride-HDL cholesterol ratio are not markers of insulin resistance in African Americans SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; IMPAIRED GLUCOSE-TOLERANCE; TREATMENT PANEL-III; METABOLIC SYNDROME; LIPOPROTEIN CHOLESTEROL; ADIPOSE-TISSUE; UNITED-STATES; PREVALENCE; DISTRIBUTIONS AB Background: The "lipid criteria" consist of a triglyceride (TG) level of 130 mg/dL (1.47 mmol/L) or greater and a ratio of TG to high-density lipoprotein cholesterol (HDL-C) of 3 or greater. In Caucasians, the lipid criteria predict insulin resistance in individuals with a body mass index (BMI) of 25 kg/m(2) or greater. Our goal was to determine whether TG levels or TG-HDL-C ratio predicted insulin resistance in African Americans with a BMI of 25 kg/m(2) or more. Methods: Of 125 African Americans, the 98 with a BMI of 25 kg/m(2) or more participated. All subjects had frequently sampled intravenous glucose tolerance tests with insulin resistance determined by the insulin sensitivity index. Subjects were divided into the following tertiles by insulin sensitivity: 12.8 to 4.3, 4.2 to 2.3, and 2.2 to 0.2 mU/L per minute. Insulin resistance was defined as being in the third tertile. Across tertiles, the distribution of variables was compared by 1-way analysis of variance. Areas under the receiver operating characteristic curve were determined to identify variables that predicted insulin resistance. Results: Fasting insulin level, BMI, and waist circumference increased across tertiles (all P<.01), but TG levels and TG-HDL-C ratio did not (all P >=.3). The mean SE areas under the curves for fasting insulin, BMI, and waist circumference were 0.85 +/- 0.04, 0.72 +/- 0.05, and 0.71 +/- 0.05, respectively. For TG level and TG-HDL-C ratio, the areas under the curves were 0.55 +/- 0.06 and 0.56 +/- 0.06, respectively, meaning that the true-positive rate was nearly equal to the false-positive rate. Therefore, they could not be used as markers of insulin resistance. Furthermore, 17 subjects met the lipid criteria but only 7 were in the insulin-resistant tertile, making the sensitivity of these criteria to identify insulin resistance only 17%. Conclusion: In African Americans, TG levels and TG-HDL-C ratio are not reliable markers of insulin resistance. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Univ Penn, Ctr Biostat, Philadelphia, PA 19104 USA. RP Sumner, AE (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 9000 Rockville Pike,Bldg 10-CRC,Room 6W-5940, Bethesda, MD 20892 USA. EM AnneS@intra.niddk.nih.gov NR 25 TC 104 Z9 107 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2005 VL 165 IS 12 BP 1395 EP 1400 DI 10.1001/archinte.165.12.1395 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 940BR UT WOS:000230119200010 PM 15983289 ER PT J AU Whelton, PK Barzilay, J Cushman, WC Davis, BR Iiamathi, E Kostis, JB Leenen, FHH Louis, GT Margolis, KL Mathis, DE Moloo, J Nwachuku, C Panebianco, D Parish, DC Pressel, S Simmons, DL Thadani, U AF Whelton, PK Barzilay, J Cushman, WC Davis, BR Iiamathi, E Kostis, JB Leenen, FHH Louis, GT Margolis, KL Mathis, DE Moloo, J Nwachuku, C Panebianco, D Parish, DC Pressel, S Simmons, DL Thadani, U CA ALLHAT Collaborative Res Grp TI Clinical outcomes in antihypertensive treatment of type 2 diabetes, impaired fasting glucose concentration, and normoglycemia - Antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; CONVERTING-ENZYME-INHIBITION; JOINT NATIONAL COMMITTEE; STAGE RENAL-DISEASE; HIGH BLOOD-PRESSURE; RANDOMIZED-TRIAL; MICROVASCULAR COMPLICATIONS; CARDIOVASCULAR MORBIDITY; OLDER PATIENTS; BETA-BLOCKERS AB Background: Optimal first-step antihypertensive drug therapy in type 2 diabetes mellitus (DM) or impaired fasting glucose levels (IFG) is uncertain. We wished to determine whether treatment with a calcium channel blocker or an angiotensin-converting enzyme inhibitor decreases clinical complications compared with treatment with a thiazide-type diuretic in DM, IFG, and normoglycemia (NG). Methods: Active-controlled trial in 31512 adults, 55 years or older, with hypertension and at least I other risk factor for coronary heart disease, stratified into DM (n = 13 10 1), IFG (n = 1399), and NG (n = 17 012) groups on the basis of national guidelines. Participants were randomly assigned to double-blind first-step treatment with chlorthalidone, 12.5 to 25 mg/d, amlodipine besylate, 2.5 to 10 mg/d, or lisinopril, 10 to 40 mg/d. We conducted an intention-to-treat analysis of fatal coronary heart disease or nonfatal myocardial infarction (primary outcome), total mortality, and other clinical complications. Results: There was no significant difference in relative risk (RR) for the primary outcome in DM or NG participants assigned to amlodipine or lisinopril vs chlorthalidone or in IFG participants assigned to lisinopril vs chlorthalidone. A significantly higher RR (95% confidence interval) was noted for the primary outcome in IFG participants assigned to amlodipine vs chlorthalidone (1.73 [1.10-2.72]). Stroke was more common in NG participants assigned to lisinopril vs chlorthalidone (1.31 [1.10-1.57]). Heart failure was more common in DM and NG participants assigned to amlodipine (1.39 [1.22-1.59] and 1.30 [1.12-1.51], respectively) or lisinopril (1.15 [1.00-1.32] and 1.19 [1.02-1.39], respectively) vs chlorthalidone. Conclusion: Our results provide no evidence of superiority for treatment with calcium channel blockers or angiotensin-converting enzyme inhibitors compared with a thiazide-type diuretic during first-step antihypertensive therapy in DM, IFG, or NG. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Hlth Sci Ctr, Dept Epidemiol, New Orleans, LA 70112 USA. Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70118 USA. Emory Univ, Sch Med, Kaiser Permanente Georgia, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA 30322 USA. Vet Affairs Med Ctr, Med Res Serv, Memphis, TN USA. Univ Texas, Sch Publ Hlth, Coordinating Ctr Clin Trials, Houston, TX USA. Winthrop Univ Hosp, Dept Med, Renal Serv, Nephrol Sect, Stony Brook, NY USA. Winthrop Univ Hosp, Dept Med, Div Nephrol & Hypertens, Stony Brook, NY USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, New Brunswick, NJ 08903 USA. Univ Ottawa, Inst Heart, Div Cardiol, Hypertens Unit, Ottawa, ON, Canada. Hennepin Cty Med Ctr, Div Clin Epidemiol, Minneapolis, MN 55415 USA. Mercer Univ, Sch Med, Med Ctr Cent Georgia, Dept Internal Med, Macon, GA 31207 USA. Univ S Carolina, Sch Med, Dept Internal Med, Columbia, SC 29208 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Hunter Holmes McGuire Vet Affairs Med Ctr, Richmond, VA USA. Univ Arkansas Med Sci, Cent Arkansas Vet Healthcare Syst, Dept Internal Med, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. Univ Oklahoma, Hlth Sci Ctr, Vet Affairs Med Ctr, Dept Med,Cardiovasc Sect, Oklahoma City, OK USA. RP Whelton, PK (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Hlth Sci Ctr, Dept Epidemiol, 1440 Canal St,Suite 2400,TW-5, New Orleans, LA 70112 USA. EM pwhelton@tulane.edu NR 37 TC 151 Z9 160 U1 2 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2005 VL 165 IS 12 BP 1401 EP 1409 DI 10.1001/archinte.165.12.1401 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 940BR UT WOS:000230119200011 PM 15983290 ER PT J AU Emanuel, EJ Emanuel, LL AF Emanuel, EJ Emanuel, LL TI Talking about death, dying, and bereavement with terminally ill patients and their caregivers - Reply SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Emanuel, EJ (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@cc.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUN 27 PY 2005 VL 165 IS 12 BP 1437 EP 1437 DI 10.1001/archinte.165.12.1437-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 940BR UT WOS:000230119200017 ER PT J AU Jeronimo, J Khan, MJ Schiffman, M Solomon, D AF Jeronimo, J Khan, MJ Schiffman, M Solomon, D CA ALTS Grp TI Does the interval between Papanicolaou tests influence the quality of cytology? SO CANCER CYTOPATHOLOGY LA English DT Article DE liquid-based cytology; Papanicolaou (Pap) smear; cervical intraepithelial neoplasia (CIN); cervical carcinoma; repeat cytology ID RANDOMIZED-TRIAL; COLPOSCOPY; TIME; MANAGEMENT; SMEARS AB BACKGROUND. it is commonly believed that the sensitivity of Papanicolaou (Pap) tests decreases with a short interval between cytology samplings. To the authors' knowledge, there is only limited evidence to support this belief. METHODS. For 5055 women in the Atypical Squamous Cells of Undetermined Significance (ASCUS)-Low Grade Squamous Intraepithelial Lesion (LSIL) Triage Study (ALTS), the Pap interval was defined as the number of days between the referral Pap smear demonstrating ASCUS or LSIL ("first cytology") and the enrollment liquid-based ("repeat") cytology. The authors investigated the influence of the interval between Pap smears on repeat cytology by examining percentages of abnormal findings, cellularity, and test sensitivity among women diagnosed with histologic grade 3 cervical intraepithelial neoplasia (CIN3) during the 2-year course of the ALTS. In addition, because human papillomavirus (HPV) DNA adjunct testing is now performed, the authors evaluated HPV viral load, which was assayed using residual liquid cytology specimens, in women with CIN3. RESULTS. The Pap interval ranged from 8-30 days in 763 women, 31-60 days in 2317 women, 61-90 days in 1090 women, 91-120 days in 491 women, and 121-184 days in 394 women (mean of 61.3 days; standard deviation of 34 days). Repeat cytologic interpretations of unsatisfactory findings, ASCUS, and high-grade squamous intraepithelial lesion (HSIL) did not appear to vary among the Pap interval groups. However, low-grade cytologic regression occurred with an increasing Pap interval; negative cytology increased from 28.3% (8-30 days) to 41.6% (121-184 days) (P < 0.0001) whereas LSIL cytology decreased (P trend = 0.002). The approximate cellularity of the samples was slightly better in the interval group of 8-30 days (P Trend = 0.04). Among women with CIN3, the repeat test sensitivity at a threshold of ASCUS or greater and the HPV DNA viral load was not found to vary by Pap interval (P Trend = 0.80 and P Trend = 0.36, respectively). CONCLUSIONS. The authors concluded that a short Pap interval (range, 15-120 days) does not significantly affect the quality of liquid-based repeat cytology, nor the viral load tested from a residual liquid-based specimen. Published 2005 by the American Cancer Society. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, HUMI NIH Res Scholars Program, Chevy Chase, MD USA. RP Jeronimo, J (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. EM guibovij@mail.nih.gov FU NCI NIH HHS [CN-55158, CN-55105, CN-55155, CN-55157, CN-55156, CN-55159, CN-55153, CN-55154] NR 10 TC 4 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD JUN 25 PY 2005 VL 105 IS 3 BP 133 EP 138 DI 10.1002/cncr.21065 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 936RN UT WOS:000229873200004 PM 15822121 ER PT J AU Moaddel, R Price, GB Juteau, JM Leffak, M Wainer, IW AF Moaddel, R Price, GB Juteau, JM Leffak, M Wainer, IW TI The synthesis and initial characterization of an immobilized DNA unwinding element binding (DUE-B) protein chromatographic stationary phase SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE affinity chromatography; immobilized protein; DNA replication; metal complexation chromatography; on-line screening ID HUMAN SERUM-ALBUMIN; IN-VITRO; REPLICATION; COMPLEXES AB The DNA unwinding element binding protein (DUE-B) plays a key role in DNA replication. The DUE-B protein has been immobilized on a liquid chromatography support and the resulting immobilized protein column was used for the on-line screening of a series of steroids. The DUE-B protein was expressed with an added C-terminal sequence of six adjacent histidine residues, a His(6)-tag and immobilized on a chiral ligand exchange support, the CLC-L column, using Ni2+ as the coordinating metal ion. The chromatographic retentions of 12 steroids were determined on the DUE-B/CLC-L column. The magnitudes of the steroid-immobilized DUE-B interactions, reflected by the observed retention times, correlated to the effect of the steroids in the cell-free replication system, i.e. the longer the retention, the greater the increase in DNA replication. The coefficient of determination for the %DNA activities linear relation to retention time was 0.9694. The data suggest that the DUE-B/CLC-L phase can be used for on-line pharmacological studies. The results also indicated that His-tagged proteins can be directly immobilized on the CLC-L stationary phase and the resulting columns used as rapid screens for the isolation and identification of small molecule or protein ligands from complex biological or chemical mixtures. Published by Elsevier B.V. C1 NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Georgetown Univ, Sch Med, Dept Pharmacol, Washington, DC USA. McGill Univ, Dept Oncol, Montreal, PQ, Canada. Replicor Inc, Laval, PQ, Canada. Wright State Univ, Sch Med, Dayton, OH USA. RP Moaddel, R (reprint author), NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moaddelru@grc.nia.nih.gov NR 16 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JUN 25 PY 2005 VL 820 IS 2 BP 197 EP 203 DI 10.1016/j.jchromb.2005.03.030 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 932JY UT WOS:000229551200005 PM 15899373 ER PT J AU Maecker, HT Rinfret, A D'Souza, P Darden, J Roig, E Landry, C Hayes, P Birungi, J Anzala, O Garcia, M Harari, A Frank, I Baydo, R Baker, M Holbrook, J Ottinger, J Lamoreaux, L Epling, CL Sinclair, E Suni, MA Punt, K Calarota, S El-Bahi, S Alter, G Maila, H Kuta, E Cox, J Gray, C Altfeld, M Nougarede, N Boyer, J Tussey, L Tobery, T Bredt, B Roederer, M Koup, R Maino, VC Weinhold, K Pantaleo, G Gilmour, J Horton, H Sekaly, RP AF Maecker, HT Rinfret, A D'Souza, P Darden, J Roig, E Landry, C Hayes, P Birungi, J Anzala, O Garcia, M Harari, A Frank, I Baydo, R Baker, M Holbrook, J Ottinger, J Lamoreaux, L Epling, CL Sinclair, E Suni, MA Punt, K Calarota, S El-Bahi, S Alter, G Maila, H Kuta, E Cox, J Gray, C Altfeld, M Nougarede, N Boyer, J Tussey, L Tobery, T Bredt, B Roederer, M Koup, R Maino, VC Weinhold, K Pantaleo, G Gilmour, J Horton, H Sekaly, RP TI Standardization of cytokine flow cytometry assays SO BMC IMMUNOLOGY LA English DT Article ID T-CELL RESPONSES; IFN-GAMMA; MONONUCLEAR-CELLS; INTERFERON-GAMMA; ELISPOT; CRYOPRESERVATION; QUANTIFICATION; INDIVIDUALS; EXPRESSION; VIABILITY AB Background: Cytokine flow cytometry (CFC) or intracellular cytokine staining (ICS) can quantitate antigen-specific T cell responses in settings such as experimental vaccination. Standardization of ICS among laboratories performing vaccine studies would provide a common platform by which to compare the immunogenicity of different vaccine candidates across multiple international organizations conducting clinical trials. As such, a study was carried out among several laboratories involved in HIV clinical trials, to define the inter-lab precision of ICS using various sample types, and using a common protocol for each experiment ( see additional files online). Results: Three sample types ( activated, fixed, and frozen whole blood; fresh whole blood; and cryopreserved PBMC) were shipped to various sites, where ICS assays using cytomegalovirus (CMV) pp65 peptide mix or control antigens were performed in parallel in 96-well plates. For one experiment, antigens and antibody cocktails were lyophilised into 96-well plates to simplify and standardize the assay setup. Results (CD4(+) cytokine(+) cells and CD8(+) cytokine+ cells) were determined by each site. Raw data were also sent to a central site for batch analysis with a dynamic gating template. Mean inter-laboratory coefficient of variation ( C. V.) ranged from 17 - 44% depending upon the sample type and analysis method. Cryopreserved peripheral blood mononuclear cells ( PBMC) yielded lower inter-lab C. V.' s than whole blood. Centralized analysis ( using a dynamic gating template) reduced the inter-lab C. V. by 5 - 20%, depending upon the experiment. The inter-lab C. V. was lowest ( 18 - 24%) for samples with a mean of > 0.5% IFN gamma + T cells, and highest ( 57 - 82%) for samples with a mean of < 0.1% IFN gamma+ cells. Conclusion: ICS assays can be performed by multiple laboratories using a common protocol with good inter-laboratory precision, which improves as the frequency of responding cells increases. Cryopreserved PBMC may yield slightly more consistent results than shipped whole blood. Analysis, particularly gating, is a significant source of variability, and can be reduced by centralized analysis and/or use of a standardized dynamic gating template. Use of pre-aliquoted lyophilized reagents for stimulation and staining can provide further standardization to these assays. C1 BD Biosci, San Jose, CA USA. Univ Montreal, Montreal, PQ, Canada. Canadian Network Vaccines & Immunotherapeut, CANVAC, Montreal, PQ, Canada. NIAID, NIH, Bethesda, MD 20892 USA. Chelsea & Westminster Hosp, London, England. IAVI, London, England. Uganda Virus Res Inst, Entebbe, Uganda. IAVI, Entebbe, Uganda. Univ Nairobi, Kenya AIDS Vaccine Initiat, Nairobi, Kenya. CHU Vaudois, CH-1011 Lausanne, Switzerland. EUROVAC, Lausanne, Switzerland. Fred Hutchinson Canc Res Ctr, HVTN, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC USA. HVTN, Durham, NC USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Merck & Co Inc, West Point, PA USA. Univ Penn, Philadelphia, PA 19104 USA. Sanofi Pasteur, Lyon, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Natl Inst Communicable Dis, Johannesburg, South Africa. Henry Jackson Fdn, Rockville, MD USA. RP BD Biosci, San Jose, CA USA. EM holden_maecker@bd.com; aline.rinfret@canvac.ca; pdsouza@niaid.nih.gov; jdarden@niaid.nih.gov; roigpatault@videotron.ca; claire.landry@umontreal.ca; p.hayes@ic.ac.uk; jbirungi@iavi.org; oanzala@kaviuon.org; miguel.garcia@chuv.hospvd.ch; alexandre.harari@chuv.hospvd.ch; ifrank@fhcrc.org; rbaydo@fhcrc.org; mcbaker@duke.edu; jaholbro@duke.edu; jotti@duke.edu; llamorea@nih.gov; lepling@medsfgh.ucsf.edu; esinclair@gladstone.ucsf.edu; maria_suni@bd.com; kara_punt@merck.com; calarota@mail.med.upenn.edu; selbahi@free.fr; galter@partners.org; hazelm@nicd.ac.za; ekuta@hivresearch.org; jcox@hivresearch.org; cgray@nicd.ac.za; maltfeld@partners.org; nolwenn.nougarede@aventis.com; boyerj@mail.med.upenn.edu; lynda.tussey@vaxinnate.com; timothy_tobery@merck.com; barryb@itsa.ucsf.edu; roederer@nih.gov; rkoup@mail.nih.gov; smaino@bd.com; kjw@duke.edu; giuseppe.pantaleo@chuv.hospvd.ch; jgilmour@iavi.org; hhorton@fhcrc.org; rafick-pierre.sekaly@umontreal.ca RI Pantaleo, Giuseppe/K-6163-2016; OI Harari, Alexandre/0000-0002-1055-2090 NR 34 TC 117 Z9 124 U1 1 U2 13 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD JUN 24 PY 2005 VL 6 AR UNSP 13 DI 10.1186/1471-2172-6-13 PG 18 WC Immunology SC Immunology GA 017SN UT WOS:000235713700001 PM 15978127 ER PT J AU Sobhany, M Dong, J Negishi, M AF Sobhany, M Dong, J Negishi, M TI Two step mechanism that determines the donor binding specificity of human UDP-N-acetylhexosaminyltransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEPARAN-SULFATE; CRYSTAL-STRUCTURE; ENZYME; EXTL2; GLYCOSYLTRANSFERASES; BIOSYNTHESIS; CATALYSIS; AFFINITY; COMPLEX; WATER AB In its x-ray crystal structures, alpha-1,4-N-acteylhexosaminyltransferase (exostosin-like protein 2 (EXTL2)) forms no direct interaction with the N-acetyl group of the UDP-N-acetylhexosamine. Mutation of the residues that interact with the hydroxyl groups of the donor not only failed to abrogate donor binding but in fact increased binding affinity. Isothermal titration calorimetry is now used to examine the binding nature of various UDP-sugars in H2O and D2O solutions. UDP-N-acetylhexosamines bind to EXTL2 with a high affinity in both solutions, resulting in a relatively large increase of entropy, whereas the weak binding of UDP-galactose and -glucose, which occurred only in D2O solution, only slightly increased entropy. Thus, specific donor binding appears to undergo two distinct steps, beginning with the N-acetyl group expelling water from the donor enzyme complex into the bulk solvent followed by positioning of the donor into the binding site for the subsequent interactions with the enzyme. C1 NIEHS, Lab Reprod & Dev Toxicol, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Lab Reprod & Dev Toxicol, Pharmacogenet Sect, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 21 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2005 VL 280 IS 25 BP 23441 EP 23445 DI 10.1074/jbc.M413379200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000006 PM 15831490 ER PT J AU Xiong, HB Li, HX Kong, HJ Chen, YB Zhao, J Xiong, SD Huang, B Gu, H Mayer, L Ozato, K Unkeless, JC AF Xiong, HB Li, HX Kong, HJ Chen, YB Zhao, J Xiong, SD Huang, B Gu, H Mayer, L Ozato, K Unkeless, JC TI Ubiquitin-dependent degradation of interferon regulatory factor-8 mediated by Cb1 down-regulates interleukin-12 expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEQUENCE-BINDING-PROTEIN; TRANSCRIPTION FACTOR; IFN-GAMMA; PROTEASOME PATHWAY; FACTOR FAMILY; NEGATIVE REGULATOR; GENE-EXPRESSION; P40 EXPRESSION; HOST-DEFENSE; ICSBP GENE AB Interferon regulatory factor (IRF)-8/interferon consensus sequence-binding protein is regulated by both transcription and degradation. IRF-8 induced in peritoneal macrophages by interferon-gamma and lipopolysaccharide was degraded rapidly, and degradation of IRF-8 was blocked by MG132, the proteasome inhibitor, but inhibitors of calpain and lysosomal enzymes had no effect. The ubiquitination of IRF-8 was shown by coimmunoprecipitation from RAW264.7 macrophages retrovirally transduced with IRF-8 and hemagglutinin-ubiquitin. The dominant negative ubiquitin mutants K48R and K29R inhibited IRF-8 degradation in 293T cells, confirming the relationship between ubiquitination of IRF-8 and its degradation. IRF-8 carboxyl-terminal truncation mutants were not ubiquitinated and were consequently stable, indicating that the carboxyl-terminal domain of IRF-8 controls ubiquitination. The ubiquitin-protein isopeptide ligase ( E3) that ubiquitinated IRF-8 was likely to be Cbl, which formed a complex with IRF-8, demonstrable by both immunoprecipitation and gel filtration. Furthermore, IRF-8 stability was increased by dominant negative Cbl, and IRF-8 ubiquitination was significantly attenuated in Cbl-/- cells. Reflecting increased stability and expression, the IRF-8 carboxyl-terminal deletion mutant induced interleukin (IL)-12 p40 promoter activity much more strongly than IRF-8 did. Furthermore, IRF-8-induced IL-12 p40 synthesis in RAW264.7 cells was enhanced by dominant negative Cbl, and peritoneal macrophages from Cbl-/- mice showed increased IL-12 p40 protein production. Taken together, these results suggest that the proteasomal degradation of IRF-8 mediated by the ubiquitin E3 ligase Cbl down-regulates IL-12 expression. C1 CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. Natl Inst Child Hlth & Human Dev, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Fudan Univ, Shanghai Med Univ, Dept Immunol, Shanghai 200025, Peoples R China. Mt Sinai Sch Med, New York, NY 10029 USA. Columbia Univ, Sch Phys & Surg, Dept Microbiol & Immunol, New York, NY 10032 USA. CUNY Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA. RP Xiong, HB (reprint author), CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. EM xionghbl@yahoo.com FU NIAID NIH HHS [AI-24322, AI52325] NR 52 TC 30 Z9 30 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2005 VL 280 IS 25 BP 23531 EP 23539 DI 10.1074/jbc.M414296200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000017 PM 15837792 ER PT J AU Kwon, M Yoon, CS Jeong, W Rhee, SG Waisman, DM AF Kwon, M Yoon, CS Jeong, W Rhee, SG Waisman, DM TI Annexin A2-S100A10 heterotetramer, a novel substrate of thioredoxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UROKINASE PLASMINOGEN-ACTIVATOR; PROTEIN DISULFIDE-ISOMERASE; CELL-ASSOCIATED PLASMINOGEN; SINGLE-CHAIN UROKINASE; II TETRAMER; ALPHA-ENOLASE; PHOSPHOGLYCERATE KINASE; ANGIOGENESIS INHIBITOR; ENZYMATIC-ACTIVITY; NEOPLASTIC-CELLS AB The binding of plasminogen activators and plasminogen to the cell surface results in the rapid generation of the serine protease plasmin. Plasmin is further degraded by an autoproteolytic reaction, resulting in the release of an angiostatin, A(61) (Lys(78)-Lys(468)). Previously, we demonstrated that the annexin A2-S100A10 heterotetramer (AIIt) stimulates the release of A61 from plasmin by promoting the autoproteolytic cleavage of the Lys(468)-Gly(469) bond and reduction of the plasmin Cys(462)-Cys(541) disulfide ( Kwon, M., Caplan, J. F., Filipenko, N. R., Choi, K. S., Fitzpatrick, S. L., Zhang, L., and Waisman, D. M. ( 2002) J. Biol. Chem. 277, 10903-10911). Mechanistically, it was unclear if AIIt promoted a conformational change in plasmin, resulting in contortion of the plasmin disulfide, or directly reduced the plasmin disulfide. In the present study, we show that AIIt thiols are oxidized during the reduction of plasmin disulfides, establishing that AIIt directly participates in the reduction reaction. Incubation of HT1080 cells with plasminogen resulted in the rapid loss of thiol-specific labeling of AIIt by 3-(N-maleimidopropionyl)biocytin. The plasminogen-dependent oxidation of AIIt could be attenuated by thioredoxin. Thioredoxin reductase catalyzed the transfer of electrons from NADPH to the oxidized thioredoxin, thus completing the flow of electrons from NADPH to AIIt. Therefore, we identify AIIt as a substrate of the thioredoxin system and propose a new model for the role of AIIt in the redox-dependent processing of plasminogen and generation of an angiostatin at the cell surface. C1 Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Canc Biol Res Grp, Calgary, AB T2N 4N1, Canada. Ewha Womans Univ, Div Mol Life, Seoul 120750, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Waisman, DM (reprint author), Univ Calgary, Fac Med, Dept Biochem & Mol Biol, Canc Biol Res Grp, 3330 Hosp Dr NW, Calgary, AB T2N 4N1, Canada. EM waisman@ucalgary.ca OI Waisman, David/0000-0002-5097-9662 NR 78 TC 20 Z9 22 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2005 VL 280 IS 25 BP 23584 EP 23592 DI 10.1074/jbc.M504325200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000023 PM 15849182 ER PT J AU Okhrimenko, H Lu, W Xiang, CL Ju, DH Blumberg, PM Gomel, R Kazimirsky, G Brodie, C AF Okhrimenko, H Lu, W Xiang, CL Ju, DH Blumberg, PM Gomel, R Kazimirsky, G Brodie, C TI Roles of tyrosine phosphorylation and cleavage of protein kinase C delta in its protective effect against tumor necrosis factor-related apoptosis inducing ligand-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID N-TERMINAL KINASE; RADIATION-INDUCED APOPTOSIS; DAMAGE-INDUCED APOPTOSIS; PROSTATE-CANCER CELLS; PROTEOLYTIC ACTIVATION; HUMAN KERATINOCYTES; GROWTH-FACTOR; DNA-DAMAGE; PKC-DELTA; ENDOPLASMIC-RETICULUM AB Protein kinase C delta (PKC delta) regulates cell apoptosis in a cell- and stimulus-specific manner. Here, we studied the role of PKC delta in the apoptotic effect of TRAIL in glioma cells. We found that transfection of the cells with a PKC delta kinase-dead mutant (K376R) or with a small interfering RNA targeting the PKC delta mRNA increased the apoptotic effect of tumor necrosis factor-related apoptosis inducing ligand ( TRAIL), whereas overexpression of PKC delta decreased it. PKC delta acted downstream of caspase 8 and upstream of cytochrome c release from the mitochondria. TRAIL induced cleavage of PKC delta within 2-3 h of treatment, which was abolished by caspase 3, 8, and 9 inhibitors. The cleavage of PKC delta was essential for its protective effect because overexpression of a caspase-resistant mutant (PKC delta D327A) did not protect glioma cells from TRAIL-induced apoptosis but rather increased it. TRAIL induced translocation of PKC delta to the perinuclear region and the endoplasmic reticulum and phosphorylation of PKC delta on tyrosine 155. Using a PKC delta Y155F mutant, we found that the phosphorylation of PKC delta on tyrosine 155 was essential for the cleavage of PKC delta in response to TRAIL and for its translocation to the endoplasmic reticulum. In addition, phosphorylation of PKC delta on tyrosine 155 was necessary for the activation of AKT in response to TRAIL. Our results indicate that PKC delta protects glioma cells from the apoptosis induced by TRAIL and implicate the phosphorylation of PKC delta on tyrosine 155 and its cleavage as essential factors in the anti-apoptotic effect of PKC delta. C1 Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurosurg, Detroit, MI 48202 USA. NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnosis Res Ctr, IL-52900 Ramat Gan, Israel. RP Brodie, C (reprint author), Henry Ford Hosp, Hermelin Brain Tumor Ctr, Dept Neurosurg, Detroit, MI 48202 USA. EM chaya@mail.biu.ac.il NR 71 TC 44 Z9 48 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2005 VL 280 IS 25 BP 23643 EP 23652 DI 10.1074/jbc.M501374200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000031 PM 15774464 ER PT J AU Chan, W Calderon, G Swift, AL Moseley, J Li, SH Hosoya, H Arias, IM Ortiz, DF AF Chan, W Calderon, G Swift, AL Moseley, J Li, SH Hosoya, H Arias, IM Ortiz, DF TI Myosin II regulatory light chain is required for trafficking of bile salt export protein to the apical membrane in Madin-Darby canine kidney cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FAMILIAL INTRAHEPATIC CHOLESTASIS; ACTIN-BINDING PROTEINS; GOLGI-DERIVED VESICLES; RAT-LIVER; BLEBBISTATIN INHIBITION; CANALICULAR MEMBRANE; ABC TRANSPORTERS; P-GLYCOPROTEIN; CLAM OOCYTES; IN-VITRO AB BSEP, MDR1, and MDR2 ATP binding cassette transporters are targeted to the apical ( canalicular) membrane of hepatocytes, where they mediate ATP-dependent secretion of bile acids, drugs, and phospholipids, respectively. Sorting to the apical membrane is essential for transporter function; however, little is known regarding cellular proteins that bind ATP binding cassette proteins and regulate their trafficking. A yeast two-hybrid screen of a rat liver cDNA library identified the myosin II regulatory light chain, MLC2, as a binding partner for BSEP, MDR1, and MDR2. The interactions were confirmed by glutathione S-transferase pulldown and co-immunoprecipitation assays. BSEP and MLC2 were overrepresented in a rat liver subcellular fraction enriched in canalicular membrane vesicles, and MLC2 colocalized with BSEP in the apical domain of hepatocytes and polarized WifB, HepG2, and Madin-Darby canine kidney cells. Expression of a dominant negative, non-phosphorylatable MLC2 mutant reduced steady state BSEP levels in the apical domain of polarized Madin-Darby canine kidney cells. Pulse-chase studies revealed that Blebbistatin, a specific myosin II inhibitor, severely impaired delivery of newly synthesized BSEP to the apical surface. These findings indicate that myosin II is required for BSEP trafficking to the apical membrane. C1 Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. Hiroshima Univ, Grad Sch Sci, Dept Sci Biol, Higashihiroshima 7398526, Japan. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Ortiz, DF (reprint author), Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. EM daniel.ortiz@tufts.edu FU NIDDK NIH HHS [P30 DK34928, R01DK060719, R01DK35652, T32DK07542] NR 52 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2005 VL 280 IS 25 BP 23741 EP 23747 DI 10.1074/jbc.M5027200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 936UD UT WOS:000229880000043 PM 15826951 ER PT J AU Lee, JA Moon, HR Kim, HO Kim, KR Lee, KM Kim, BT Hwang, KJ Chun, MW Jacobson, KA Jeong, LS AF Lee, JA Moon, HR Kim, HO Kim, KR Lee, KM Kim, BT Hwang, KJ Chun, MW Jacobson, KA Jeong, LS TI Synthesis of novel apio carbocyclic nucleoside analogues as selective A(3) adenosine receptor agonists SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID S-ADENOSYLHOMOCYSTEINE HYDROLASE; RING-CLOSING METATHESIS; L-HOMOCYSTEINE HYDROLASE; NEPLANOCIN-A; ORGANIC-SYNTHESIS; ANTIVIRAL AGENTS; STEREOSELECTIVE-SYNTHESIS; DESIGN; INHIBITOR; TARGET AB On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a-d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-d, 6, and 7 did not show significant inhibitory activity against S-adenosylhomocysteine hydrolase (SAH) up to 100 mu M, maybe due to the absence of the secondary hydroxyl group at the C3 '-position, which should be oxidized by cofactor-bound NAD+. However, apio-neplanocin A (5a) showed potent and highly selective binding affinity (K-i = 628 +/- 69 nM) at the A(3) adenosine receptor without any binding affinity at the A(1) and A(2)A adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugars using stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A(3) adenosine receptor agonist, which play a great role in developing new A(3) adenosine receptor agonist as well as in identifying the binding site of the receptor. C1 Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. Chonbuk Natl Univ, Dept Chem, Chonju 561756, South Korea. Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Moon, HR (reprint author), Pusan Natl Univ, Coll Pharm, Pusan 609735, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 31 TC 34 Z9 34 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD JUN 24 PY 2005 VL 70 IS 13 BP 5006 EP 5013 DI 10.1021/jo0503207 PG 8 WC Chemistry, Organic SC Chemistry GA 938EO UT WOS:000229982900013 PM 15960499 ER PT J AU Nabel, GJ AF Nabel, GJ TI Close to the edge Neutralizing the HIV-1 envelope SO SCIENCE LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS-INFECTION; B-CELLS; GP41; ANTIBODIES; TOLERANCE C1 NIAID, VRC, NIH, Bethesda, MD 20892 USA. RP Nabel, GJ (reprint author), NIAID, VRC, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gnabel@nih.gov NR 19 TC 29 Z9 31 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 24 PY 2005 VL 308 IS 5730 BP 1878 EP 1879 DI 10.1126/science.1114854 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 940BZ UT WOS:000230120000030 PM 15976295 ER PT J AU Fairhurst, RM Baruch, DI Brittain, NJ Ostera, GR Wallach, JS Hoang, HL Hayton, K Guindo, A Makobongo, MO Schwartz, OM Tounkara, A Doumbo, OK Diallo, DA Fujioka, H Ho, M Wellems, TE AF Fairhurst, RM Baruch, DI Brittain, NJ Ostera, GR Wallach, JS Hoang, HL Hayton, K Guindo, A Makobongo, MO Schwartz, OM Tounkara, A Doumbo, OK Diallo, DA Fujioka, H Ho, M Wellems, TE TI Abnormal display of PfEMP-1 on erythrocytes carrying haemoglobin C may protect against malaria SO NATURE LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; RED-CELLS; SURFACE; ANTIGENS; ANTIBODIES; DISEASE; PATHOGENESIS; POPULATION; RESISTANCE AB Haemoglobin C, which carries a glutamate-to-lysine mutation in the beta-globin chain, protects West African children against Plasmodium falciparum malaria(1,2). Mechanisms of protection are not established for the heterozygous (haemoglobin AC) or homozygous (haemoglobin CC) states. Here we report a marked effect of haemoglobin C on the cell-surface properties of P. falciparum-infected erythrocytes involved in pathogenesis. Relative to parasite-infected normal erythrocytes (haemoglobin AA), parasitized AC and CC erythrocytes show reduced adhesion to endothelial monolayers expressing CD36 and intercellular adhesion molecule-1 (ICAM-1). They also show impaired rosetting interactions with non-parasitized erythrocytes, and reduced agglutination in the presence of pooled sera from malaria-immune adults. Abnormal cell-surface display of the main variable cytoadherence ligand, PfEMP-1 (P. falciparum erythrocyte membrane protein-1), correlates with these findings. The abnormalities in PfEMP-1 display are associated with markers of erythrocyte senescence, and are greater in CC than in AC erythrocytes. Haemoglobin C might protect against malaria by reducing PfEMP-1-mediated adherence of parasitized erythrocytes, thereby mitigating the effects of their sequestration in the microvasculature. C1 NIAID, Lab Malaria & Vestor Res, NIH, Bethesda, MD 20892 USA. NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. NIAID, Biol Imaging Facil, Res Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Calgary, Dept Microbiol & Infect Dis, Calgary, AB T2N 4N1, Canada. Univ Bamako, Fac Med Pharm & Odontostomatol, Dept Parasitol, Malaria Res & Training Ctr, Bamako, Mali. Univ Bamako, Fac Med Pharm & Odontostomatol, Dept Hematol, Malaria Res & Training Ctr, Bamako, Mali. Minist Hlth, Ctr Natl Transfus Sanguine, Bamako, Mali. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vestor Res, NIH, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov NR 30 TC 117 Z9 121 U1 1 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 23 PY 2005 VL 435 IS 7045 BP 1117 EP 1121 DI 10.1038/nature03631 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 937ZT UT WOS:000229970400053 PM 15973412 ER PT J AU Wu, HF Thatcher, LN Bernard, D Parrish, DA Deschamps, JR Rice, KC MacKerell, AD Coop, A AF Wu, HF Thatcher, LN Bernard, D Parrish, DA Deschamps, JR Rice, KC MacKerell, AD Coop, A TI Position of coordination of the lithium ion determines the regioselectivity of demethylations of 3,4-dimethoxymorphinans with L-selectride SO ORGANIC LETTERS LA English DT Article ID BIOLOGICAL EVALUATION; ANALOGS; 14-ALKOXYMORPHINANS; DERIVATIVES; CYPRODIME; AFFINITY; REAGENT AB L-Selectride is an efficient agent for the 3-O-clemethylation of opioids and is known to cleave the least hindered methoxyl group in a molecule. The treatment of a 3,4-dimethoxymorphinan containing a 6-ketal with L-Selectride gave selective 4-O-clemethylation, rather than cleavage of the less hindered 3-methoxyl. In contrast, a 3,4-dimethoxymorphinan lacking a 6-ketal gave selective 3-O-demethylation, suggesting that the regiochemistry of L-Selectride-mediated O-demethylation can be manipulated through altering the position of coordination of the lithium ion. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wu, HF (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, 20 Penn St, Baltimore, MD 21201 USA. EM acoop@rx.umaryland.edu OI Deschamps, Jeffrey/0000-0001-5845-0010; Bernard, Denzil/0000-0001-7529-3336; MacKerell, Alex/0000-0001-8287-6804 FU NIDA NIH HHS [Y1-DA-1002-01, DA-13583, K02 DA019634, K02 DA019634-01] NR 13 TC 12 Z9 12 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUN 23 PY 2005 VL 7 IS 13 BP 2531 EP 2534 DI 10.1021/ol050433c PG 4 WC Chemistry, Organic SC Chemistry GA 937UU UT WOS:000229952100004 PM 15957883 ER PT J AU Pitman, MC Suits, F Gawrisch, K Feller, SE AF Pitman, MC Suits, F Gawrisch, K Feller, SE TI Molecular dynamics investigation of dynamical properties of phosphatidylethanolamine lipid bilayers SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PERIODIC BOUNDARY-CONDITIONS; PHOSPHOLIPID-BILAYERS; CROSS-RELAXATION; BLUE GENE; SIMULATION; CHOLESTEROL; MEMBRANES; NMR; WATER; ORGANIZATION AB We describe the dynamic behavior of a 1-stearoyl-2-oleoyl-phosphatidylethanolamine (SOPE) bilayer from a 20 ns molecular dynamics simulation. The dynamics of individual molecules are characterized in terms of H-2 spin-lattice relaxation rates, nuclear overhauser enhancement spectroscopy (NOESY) cross-relaxation rates, and lateral diffusion coefficients. Additionally, we describe the dynamics of hydrogen bonding through an analysis of hydrogen bond lifetimes and the time evolution of clusters of hydrogen bonded lipids. The simulated trajectory is shown to be consistent with experimental measures of internal, intermolecular, and diffusive motion. Consistent with our analysis of SOPE structure in the companion paper, we see hydrogen bonding dominating the dynamics of the interface region. Comparison of H-2 T-1 relaxation rates for chain methylene segments in phosphatidylcholine and phosphatidylethanolamine bilayers indicates that slower motion resulting from hydrogen bonding extends at least three carbons into the hydrophobic core. NOESY cross-relaxation rates compare well with experimental values, indicating the observed hydrogen bonding dynamics are realistic. Calculated lateral diffusion rates (4 +/- 1 X 10(- 8) cm(2)/s) are comparable, though somewhat lower than, those determined by pulsed field gradient NMR methods. (c) 2005 American Institute of Physics. C1 IBM Corp, TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. RP Pitman, MC (reprint author), IBM Corp, TJ Watson Res Ctr, Yorktown Hts, NY 10598 USA. NR 43 TC 24 Z9 25 U1 1 U2 6 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 JUN 22 PY 2005 VL 122 IS 24 AR 244715 DI 10.1063/1.1899153 PG 10 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 943DN UT WOS:000230332400066 PM 16035801 ER PT J AU Kantorovich, V Pacak, K AF Kantorovich, V Pacak, K TI A new concept of unopposed beta-adrenergic overstimulation in a patient with pheochromocytoma SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kantorovich, V (reprint author), Natl Inst Hlth, Bethesda, MD 20892 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUN 21 PY 2005 VL 142 IS 12 BP 1026 EP 1028 PN 1 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 937IN UT WOS:000229917900018 PM 15968023 ER PT J AU Li, Y Blaszczyk, J Wu, Y Shi, GB Ji, XH Yan, HG AF Li, Y Blaszczyk, J Wu, Y Shi, GB Ji, XH Yan, HG TI Is the critical role of loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase in catalysis due to loop-3 residues arginine-84 and tryptophan-89? Site-directed mutagenesis, biochemical, and crystallographic studies SO BIOCHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; TERNARY COMPLEX; SUBSTRATE; BINDING; PROGRAM; ANALOG; NMR AB Deletion mutagenesis, biochemical, and X-ray crystallographic studies have shown that loop 3 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is required for the assembly of the active center, plays an important role in the stabilization of the ternary complex of HPPK with MgATP and 6-hydroxymethyl-7,8-dihydropterin (HP), and is essential for catalysis. Whether the critical functional importance of loop 3 is due to the interactions between residues R84 and W89 and the two substrates has been addressed by site-directed mutagenesis, biochemical, and X-ray crystallographic studies. Substitution of R84 with alanine causes little changes in the dissociation constants and kinetic constants of the HPPK-catalyzed reaction, indicating that R84 is not important for either substrate binding or catalysis. Substitution of W89 with alanine increases the K-d for the binding of MgATP by a factor of 3, whereas the K-d for HP increases by a factor of 6, which is due to the increase in the dissociation rate constant. The W89A mutation decreases the rate constant for the chemical step of the forward reaction by a factor of 15 and the rate constant for the chemical step of the reverse reaction by a factor of 25. The biochemical results of the W89A mutation indicate that W89 contributes somewhat to the binding of HP and more significantly to the chemical step. The crystal structures of W89A show that W89A has different conformations in loops 2 and 3, but the critical catalytic residues are positioned for catalysis. When these results are taken together, they suggest that the critical functional importance of loop 3 is not due to the interactions of the R84 guanidinium group or the W89 indole ring with the substrates. C1 Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Macromol Crystallog Lab, NCI, Frederick, MD 21702 USA. RP Ji, XH (reprint author), Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. EM jix@ncifcrf.gov; yanh@msu.edu RI Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NIGMS NIH HHS [GM51901] NR 26 TC 9 Z9 9 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 JUN 21 PY 2005 VL 44 IS 24 BP 8590 EP 8599 DI 10.1021/bi0503495 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 938JD UT WOS:000229994900004 PM 15952765 ER PT J AU De Angelis, CD Drazen, JM Frizelle, FA Haug, C Hoey, J Horton, R Kotzin, S Laine, C Marusic, A Overbeke, AJPM Schroeder, TV Sox, HC Van Der Weyden, MB AF De Angelis, CD Drazen, JM Frizelle, FA Haug, C Hoey, J Horton, R Kotzin, S Laine, C Marusic, A Overbeke, AJPM Schroeder, TV Sox, HC Van Der Weyden, MB TI Is this clinical trial fully registered? A statement from the International Committee of Medical Journal Editors SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Editorial Material C1 CMAJ, Ottawa, ON K1G 3Y6, Canada. Natl Lib Med, MEDLINE, Bethesda, MD 20894 USA. RP Hoey, J (reprint author), CMAJ, 1867 Alta Vista Dr, Ottawa, ON K1G 3Y6, Canada. EM john.hoey@cma.ca RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Schroeder, Torben/0000-0002-9827-9438 NR 1 TC 13 Z9 13 U1 0 U2 1 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 21 PY 2005 VL 172 IS 13 BP 1700 EP 1702 DI 10.1503/cmaj.050600 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 934HY UT WOS:000229701100031 PM 15911839 ER PT J AU Moselewski, F O'Donnell, CJ Achenbach, S Ferencik, M Massaro, J Nguyen, A Cury, RC Abbara, S Jang, IK Brady, TJ Hoffmann, U AF Moselewski, F O'Donnell, CJ Achenbach, S Ferencik, M Massaro, J Nguyen, A Cury, RC Abbara, S Jang, IK Brady, TJ Hoffmann, U TI Calcium concentration of individual coronary calcified plaques as measured by multidetector row computed tomography SO CIRCULATION LA English DT Article DE aging; atherosclerosis; calcification; physiologic; coronary disease; tomography ID ELECTRON-BEAM TOMOGRAPHY; HEART-DISEASE EVENTS; ARTERY CALCIUM; ATHEROSCLEROTIC LESIONS; MYOCARDIAL-INFARCTION; CT; QUANTIFICATION; PROGRESSION; CALCIFICATION; DEATH AB Background - Characteristics of individual calcified plaques, especially calcium concentration ( CC), may provide incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and evaluation of therapeutic intervention. In this study, therefore, we assessed the characteristics of individual calcified plaques and their relationship to other parameters derived from CT analysis of coronary calcium in a community- based cross- sectional cohort. Methods and Results - Coronary artery calcium ( CAC) was analyzed in 612 participants of the Framingham Heart Study ( third- generation and offspring cohorts) using prospectively ECG- triggered multidetector CT. We determined the CC, Agatston score, calcified volume, and mineral mass of individual calcified plaques in each subject. Heterogeneity of CC was defined as the standard deviation of CC of all individual calcified plaques in a subject. CAC was detected in 274 of 605 subjects. After excluding 57 subjects ( 21%) because of motion artifacts, we identified a total of 956 calcified coronary plaques in 217 subjects ( 74 women, 143 men; mean age, 57.1 +/- 10.8 years) with detectable CAC and no image artifacts. CC of individual calcified plaques was independent of subject age ( P = 0.76) and sex ( 197.8 +/- 74.8 versus 183.6 +/- 52.8 mg/ cm(3) for men versus women; P = 0.21). Among a subgroup of 125 subjects with multiple ( >= 3) individual calcified plaques, CC was heterogeneous within individual subjects ( mean SD of CC, 43.6 +/- 23.1 mg/ cm3). The degree of heterogeneity of CC in these subjects was independent of age ( P = 0.60), sex ( P = 0.99), and number of plaques ( P = 0.06). Conclusions - The CC of individual calcified plaques is independent of age and sex but heterogeneous within a subject, which may reflect that the pathological process of calcified plaque formation and progression is the same in men and women regardless of age. CC may have incremental value to global calcium scores in the assessment of plaque burden and risk of coronary events and the evaluation of therapeutic intervention. Further studies are warranted to confirm that individual plaque analysis is preferable to global CAC scores to evaluate progression of atherosclerosis and to assess whether individual plaque analysis may be complementary to global CAC measures to assess coronary event risk. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Suite 400, Boston, MA 02114 USA. EM uhoffman@partners.org FU NHLBI NIH HHS [N01-HC-25195] NR 33 TC 30 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 21 PY 2005 VL 111 IS 24 BP 3236 EP 3241 DI 10.1161/CIRCULATIONAHA.104.489781 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 937MX UT WOS:000229930200010 PM 15956133 ER PT J AU Tandle, AT Mazzanti, C Alexander, HR Roberts, DD Libutti, SK AF Tandle, AT Mazzanti, C Alexander, HR Roberts, DD Libutti, SK TI Endothelial monocyte activating polypeptide-II induced gene expression changes in endothelial cells SO CYTOKINE LA English DT Article DE DOC1; EMAP-II; endothelial cells; microarray analysis; SiRNA ID TUMOR-DERIVED CYTOKINE; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE-CELLS; MICROARRAY ANALYSIS; EMAP-II; DNA MICROARRAY; DOWN-REGULATION; HUMAN-MELANOMA; CANCER; ADRENOMEDULLIN AB In the current study we used microarray (MA) analysis to examine gene expression changes in human umbilical vein endothelial cells (HUVEC) exposed to the tumor-derived cytokine, endothelial monocyte-activating polypeptide-II (EMAP-II). HUVEC treated with EMAP-II for 0.5, 1, 2, 4 and 8 It, were analyzed using 10K cDNA arrays. Our results demonstrated that changes in gene expression of < 0.5 and > 2 fold were seen for 69 genes and the majority of gene changes occurred early. Validation of MA analysis for 10 genes by real time RT-PCR, demonstrated the gene changes to be consistent and specific to HUVEC when compared to human fibroblasts treated with EMAP-II. Among these genes, downregulated in ovarian cancer I (DOC1) gene was studied further because of its possible role in EMAP-II induced cytoskeletal remodeling. DOC1 expression was silenced using small interfering RNA. SiRNA to DOC1 completely abolished EMAP-II stimulated gene expression of DOC1 Silencing of DOC1 gene expression reversed the modulatory effect of EMAP-II on 4 other genes, suggesting that DOC1 might play a role in mediating some of the effects of EMAP-II on endothelial cells. Published by Elsevier Ltd. C1 NCI, Surg Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Canc Res Ctr, 10 Ctr Dr,Bldg 10,Room 4W-5940, Bethesda, MD 20892 USA. EM libuttis@mail.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 NR 55 TC 24 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUN 21 PY 2005 VL 30 IS 6 BP 347 EP 358 DI 10.1016/j.cyto.2005.01.020 PG 12 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 937SR UT WOS:000229946300005 PM 15935955 ER PT J AU Lucas, DL Brown, RA Wassef, M Giles, TD AF Lucas, DL Brown, RA Wassef, M Giles, TD TI Alcohol and the cardiovascular system - Research challenges and opportunities SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CORONARY-HEART-DISEASE; K-ATP CHANNELS; MYOCARDIAL-INFARCTION; HDL CHOLESTEROL; BLOOD-PRESSURE; HOST-DEFENSE; IN-VIVO; RISK; ATHEROSCLEROSIS; CONSUMPTION AB Excessive alcohol consumption has long been associated with cardiovascular disorders, including cardiomyopathy, hypertension, coronary artery disease, and stroke. However, recent evidence suggests that moderate alcohol intake can actually provide a measure of cardioprotection, particularly against coronary heart disease and ischemia-reperfusion injury. To explore the various dimensions of these opposing actions of alcohol, the National Institute on Alcohol Abuse and Alcoholism and the National Heart, Lung, and Blood Institute sponsored a state-of-the-art workshop on "Alcohol and the Cardiovascular System: Research Challenges and Opportunities" in Bethesda, Maryland, in May 2003. Speakers discussed the following topics: the epidemiology of alcohol and cardiovascular disease, clinical manifestations of alcohol, genetics of alcohol and cardiovascular disease, mechanisms underlying the molecular and cellular effects of alcohol, the application of new and emerging technology, and translation from discovery to therapeutic modalities of treatment. The panel concluded that future studies are needed to: 1) determine the role of genes and the environment in assessing mechanisms underlying the benefits of alcohol use and cardiovascular disease risk; 2) define the biological mechanisms underlying alcohol-induced peripheral vascular damage; 3) clarify the role of genetic variation in alcohol-metabolizing enzymes, genetic susceptibility, and pharmacogenomics in determining cardiovascular disease risk and effective treatment; 4) determine common mechanisms underlying alcohol-induced cardiovascular disease, such as oxidative stress and inflammation; 5) assess the role of insulin resistance, blood clotting, protein kinase C isoforms, and signal transduction mechanisms mediating alcohol's beneficial effects; and 6) explore the potential of stem cells in myocardial regeneration and repair in hearts damaged by alcohol. (c) 2005 by the American College of Cardiology Foundation. C1 Louisiana State Univ, Sch Med, Hlth Sci Ctr, Cardiovasc Res Sect,Dept Med, New Orleans, LA 70112 USA. NIAAA, Div Metab & Hlth Effect, Bethesda, MD USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Giles, TD (reprint author), Louisiana State Univ, Sch Med, Hlth Sci Ctr, Cardiovasc Res Sect,Dept Med, 1542 Tulane Ave,Room 331E, New Orleans, LA 70112 USA. EM tgiles@lsuhsc.edu NR 51 TC 96 Z9 105 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 21 PY 2005 VL 45 IS 12 BP 1916 EP 1924 DI 10.1016/j.jacc.2005.02.075 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 936IK UT WOS:000229848500002 PM 15963387 ER PT J AU Raman, VK Karmarkar, PV Guttman, MA Dick, AJ Peters, DC Ozturk, C Pessanha, BSS Thompson, RB Raval, AN DeSilva, R Aviles, RJ Atalar, E McVeigh, ER Lederman, RJ AF Raman, VK Karmarkar, PV Guttman, MA Dick, AJ Peters, DC Ozturk, C Pessanha, BSS Thompson, RB Raval, AN DeSilva, R Aviles, RJ Atalar, E McVeigh, ER Lederman, RJ TI Real-time magnetic endovascular repair resonance-guided of experimental abdominal aortic aneurysm in swine SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID TEMPORAL RESOLUTION; MR-ANGIOGRAPHY; CT ANGIOGRAPHY; STENT-GRAFT; FOLLOW-UP; FLUOROSCOPY; PLACEMENT; CATHETERIZATION; VISUALIZATION; FEASIBILITY AB OBJECTIVES This study tested the hypotheses that endografts can be visualized and navigated in vivo solely under real-time magnetic resonance imaging (rtMRI) guidance to repair experimental abdominal aortic aneurysms (AAA) in swine, and that MRI can provide immediate assessment of endograft apposition and aneurysm exclusion. BACKGROUND Endovascular repair for AAA is limited by endoleak caused by inflow or outflow malapposition. The ability of rtMRI to image soft tissue and flow may improve on X-ray guidance of this procedure. METHODS Infrarenal AAA was created in swine by balloon overstretch. We used one passive commercial endograft, imaged based on metal-induced MRI artifacts, and several types of homemade active endografts, incorporating MRI receiver coils (antennae). Custom interactive rtMRI features included color coding the catheter-antenna signals individually, simultaneous multislice imaging, and real-time three-dimensional rendering. RESULTS Eleven repairs were performed solely using rtMRI, simultaneously depicting the device and soft-tissue pathology during endograft deployment. Active devices proved most useful. Intraprocedural MRI provided anatomic confirmation of stent strut apposition and functional corroboration of aneurysm exclusion and restoration of laminar flow in successful cases. In two cases, there was clear evidence of contrast accumulation in the aneurysm sac, denoting endoleak. CONCLUSIONS Endovascular AAA repair is feasible under rtMRI guidance. Active endografts facilitate device visualization and complement the soft tissue contrast afforded by MRI for precise positioning and deployment. Magnetic resonance imaging also permits immediate post-procedural anatomic and functional evaluation of successful aneurysm exclusion. (c) 2005 by the American College of Cardiology Foundation. C1 NHLBI, Cardiovasc Branch, Clin Res Program, Div Intramural Res, Bethesda, MD 20892 USA. NHLBI, Lab Cardiac Energet, Div Intramural Res, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, Clin Res Program, Div Intramural Res, Bldg 10,Room 2c713, Bethesda, MD 20892 USA. EM Lederman@nih.gov RI Thompson, Richard/E-9821-2011; Atalar, Ergin/D-3184-2012; Ozturk, Cengizhan/A-6177-2016 OI Atalar, Ergin/0000-0002-6874-6103; Ozturk, Cengizhan/0000-0002-6966-0774 FU Intramural NIH HHS [Z01 HL004608-08]; NHLBI NIH HHS [Z01 HL 005062-01 CVB] NR 33 TC 34 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUN 21 PY 2005 VL 45 IS 12 BP 2069 EP 2077 DI 10.1016/j.jacc.2005.03.029 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 936IK UT WOS:000229848500026 PM 15963411 ER PT J AU Wang, XP Wang, E Kavanagh, JJ Freedman, RS AF Wang, XP Wang, E Kavanagh, JJ Freedman, RS TI Ovarian cancer, the coagulation pathway, and inflammation SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Review ID PROTEIN-C RECEPTOR; LOW-MOLECULAR-WEIGHT; ENDOTHELIAL GROWTH-FACTOR; HEPARIN-COFACTOR-II; TUMOR-INFILTRATING LYMPHOCYTES; FACTOR CYTOPLASMIC DOMAIN; TISSUE FACTOR EXPRESSION; ACTIVATION-REGULATED CHEMOKINE; FAVORABLE PROGNOSTIC MARKER; PROSTATE-SPECIFIC ANTIGEN AB Epithelial ovarian cancer (EOC) represents the most frequent cause of death in the United States from a cancer involving the female genital tract. Contributing to the overall poor outcome in EOC patients, are the metastases to the peritoneum and stroma that are common in this cancer. In one study, cDNA microarray analysis was performed on fresh tissue to profile gene expression in patients with EOC. This study showed a number of genes with significantly altered expression in the pelvic peritoneum and stroma, and in the vicinity of EOC implants. These genes included those encoding coagulation factors and regulatory proteins in the coagulation cascade and genes encoding proteins associated with inflammatory responses. In addition to promoting the formation of blood clots, coagulation factors exhibit many other biologic functions as well as tumorigenic functions, the later including tumor cell proliferation, angiogenesis, invasion, and metastasis. Coagulation pathway proteins involved in tumorigenesis consist of factor II (thrombin), thrombin receptor (protease-activated receptors), factor III (tissue factor), factor VII, factor X and factor I (fibrinogen), and fibrin and factor XIII. In a recent study we conducted, we found that factor XII, factor XI, and several coagulation regulatory proteins, including heparin cofactor-II and epithelial protein C receptor (EPCR), were also upregulated in the peritoneum of EOC. In this review, we summarize evidence in support of a role for these factors in promoting tumor cell progression and the formation of ascites. We also discuss the different roles of coagulation factor pathways in the tumor and peritumoral microenvironments as they relate to angiogenesis, proliferation, invasion, and metastasis.. Since inflammatory responses are another characteristic of the peritoneum in EOC, we also discuss the linkage between the coagulation cascade and the cytokines/chemokines involved in inflammation. Interleukin-8, which is considered an important chemokine associated with tumor progression, appears to be a linkage point for coagulation and inflammation in malignancy. Lastly, we review findings regarding the inflammatory process yielded by certain clinical trials of agents that target members of the coagulation cascade in the treatment of cancer. Current data suggest that disrupting certain elements of the coagulation and inflammation processes in the tumor microenvironment could be a new biologic approach to cancer therapeutics. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Med Oncol, Houston, TX 77030 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Freedman, RS (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM xipwang@mdanderson.org; ewang@cc.nih.gov; jkavanag@mdanderson.org; rfreedma@mdanderson.org NR 203 TC 3 Z9 3 U1 0 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 21 PY 2005 VL 3 DI 10.1186/1479-5876-3-25 PG 20 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968KM UT WOS:000232161400001 ER PT J AU Chen, ZS Yin, ZQ Chen, S Wang, SJ AF Chen, ZS Yin, ZQ Chen, S Wang, SJ TI Electrophysiological changes of retinal ganglion cells in Royal College of Surgeons rats during retinal degeneration SO NEUROREPORT LA English DT Article DE action potential; electrophysiology; retinal degeneration; retinal ganglion cell; Royal College of Surgeons rats ID INTRINSIC MEMBRANE-PROPERTIES AB Retinitis pigmentosa is one of the main causes of blindness throughout the world and its pathogenesis remains unclear. In this study, patch-clamp recording was performed from ganglion cells in retinal dystrophic Royal College of Surgeons rats and normal rats during development. The three discharge patterns of action potential in ganglion cells of Royal College of Surgeons rats were single, transient, and sustained firing. The main discharge pattern was single firing in PI-2W, then transient and sustained firing. However, during later stages of retinal degeneration, action potential was reduced in amplitude and frequency, and was even lost in Royal College of Surgeons rats. These findings differed dramatically from those of rats without retinal degeneration, suggesting there are functional ganglion cells in Royal College of Surgeons rats early, but lose part function during retinal degeneration, even though morphological differences are not apparent. Understanding the changes of electrophysiological characteristics during retinal degeneration in detail may help explore the optimal time course for treating retinitis pigmentosa. (c) 2005 Lippincott Williams & Wilkins. C1 SW Hosp, SW Eye Hosp, Chongqing 400038, Peoples R China. NEI, NIH, Bethesda, MD 20892 USA. RP Yin, ZQ (reprint author), SW Hosp, SW Eye Hosp, Chongqing 400038, Peoples R China. EM zqyin@mail.tmmu.com.cn NR 18 TC 10 Z9 15 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 21 PY 2005 VL 16 IS 9 BP 971 EP 975 DI 10.1097/00001756-200506210-00018 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 946XW UT WOS:000230607600018 PM 15931071 ER PT J AU Bossert, JM Busch, RF Gray, SM AF Bossert, JM Busch, RF Gray, SM TI The novel mGluR(2/3) agonist LY379268 attenuates cue-induced reinstatement of heroin seeking SO NEUROREPORT LA English DT Article DE drug cues; metabotropic glutamate receptors; opiate self-administration; reinstatement; relapse ID VENTRAL TEGMENTAL AREA; METABOTROPIC GLUTAMATE RECEPTORS; CONDITIONED REWARD; DRUG-SEEKING; RELAPSE; MORPHINE; COCAINE; REINFORCEMENT; SENSITIZATION; NEUROBIOLOGY AB In humans, drug-associated stimuli can provoke heroin relapse during abstinence. In rats, cues paired with heroin self-administration reinstate heroin seeking in a relapse model. The neurobiological mechanisms involved in this reinstatement, however, are largely unknown. Here, we determined the effect of LY379268, an mGluR(2/3) agonist that decreases evoked glutamate release, on cue-induced reinstatement of heroin seeking. Systemic injections of LY379268 attenuated reinstatement of heroin seeking induced by exposure to a discrete tone-light cue that was previously paired with heroin infusions during self-administration training. In contrast, LY379268 had no effect on heroin self-administration. Results indicate that glutamate plays an important role in cue-induced reinstatement of heroin seeking and suggest that mGluR(2/3) agonists should be considered for the treatment of opiate relapse. (c) 2005 Lippincott Williams & Wilkins. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, DHHS,NIH, Baltimore, MD 21224 USA. RP Bossert, JM (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, DHHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jbossert@intra.nida.nih.gov NR 22 TC 62 Z9 62 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 21 PY 2005 VL 16 IS 9 BP 1013 EP 1016 DI 10.1097/00001756-200506210-00026 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 946XW UT WOS:000230607600026 PM 15931079 ER PT J AU Jansen, A Floel, A Menke, R Kanowski, M Knecht, S AF Jansen, A Floel, A Menke, R Kanowski, M Knecht, S TI Dominance for language and spatial processing: limited capacity of a single hemisphere SO NEUROREPORT LA English DT Article DE crowding effect; functional magnetic resonance imaging; language; lateralization; spatial processing ID FUNCTIONAL MRI; LATERALIZATION; HANDEDNESS; ATTENTION; SPEECH; FMRI AB Using functional magnetic resonance imaging during word generation and spatial judgement (Landmark task), we investigated how hemispheric specializations for language and spatial processing interact in healthy individuals. We found individuals with atypical, right-hemispheric dominance for language to have more bilateral activation during spatial judgement than individuals with typical, disjunct hemispheric specialization, that is, left dominance for language and right dominance for spatial tasks. These findings suggest that hemispheric specializations for language and spatial functions interfere to some extent and favour additional recruitment of the opposite hemispheres for spatial functions. (c) 2005 Lippincott Williams & Wilkins. C1 Univ Munster, Dept Neurol, D-4400 Munster, Germany. NIH, Bethesda, MD 20892 USA. Univ Munster, IZKF Munster, D-4400 Munster, Germany. Univ Magdeburg, Dept Neurol 2, D-39106 Magdeburg, Germany. RP Jansen, A (reprint author), Univ Munster, Dept Neurol, D-4400 Munster, Germany. EM anjan@uni-muenster.de RI Floel, Agnes/A-9426-2017; OI Knecht, Stefan/0000-0003-1056-9228 NR 18 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUN 21 PY 2005 VL 16 IS 9 BP 1017 EP 1021 DI 10.1097/00001756-200506210-00027 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 946XW UT WOS:000230607600027 PM 15931080 ER PT J AU Mangold, SL Morgan, JR Strohmeyer, GC Gronenborn, AM Cloninger, MJ AF Mangold, SL Morgan, JR Strohmeyer, GC Gronenborn, AM Cloninger, MJ TI Cyanovirin-N binding to Man alpha 1-2Man functionalized dendrimers SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID HIV-INACTIVATING PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS; CONCANAVALIN-A; LECTIN-BINDING; POLY(AMIDOAMINE) DENDRIMERS; MULTIVALENT INTERACTIONS; ENHANCED BINDING; AFFINITY; GLYCOBIOLOGY; RECOGNITION AB Man alpha 1-2Man functionalized G(3) and G(4)-PAMAM dendrimers have been synthesized and characterized by MALDI-TOF MS and NMR spectroscopy. Precipitation assays to assess the binding of the dimannose-functionalized dendrimers to Cyanovirin-N, a HIV-inactivating protein that blocks virus-to-cell fusion through high mannose mediated interactions, are presented. C1 Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. Montana State Univ, Ctr Bioinspired Nanomat, Bozeman, MT 59717 USA. NIDDK, Phys Chem Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Cloninger, MJ (reprint author), Montana State Univ, Dept Chem & Biochem, 108 Gaines Hall, Bozeman, MT 59717 USA. EM mcloninger@chemistry.montana.edu OI Gronenborn, Angela M/0000-0001-9072-3525 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM62444] NR 53 TC 15 Z9 16 U1 3 U2 4 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 EI 1477-0539 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PD JUN 21 PY 2005 VL 3 IS 12 BP 2354 EP 2358 DI 10.1039/b417789d PG 5 WC Chemistry, Organic SC Chemistry GA 942UP UT WOS:000230308700024 PM 16010372 ER PT J AU Kashuk, CS Stone, EA Grice, EA Portnoy, ME Green, ED Sidow, A Chakravarti, A McCallion, AS AF Kashuk, CS Stone, EA Grice, EA Portnoy, ME Green, ED Sidow, A Chakravarti, A McCallion, AS TI Phenotype-genotype correlation in Hirschsprung disease is illuminated by comparative analysis of the RET protein sequence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE deleterious substitutions; evolutionary conservation; physicochemical properties ID DOMAIN; SEGREGATION; PREDICTION; INFERENCE; ALIGNMENT; MUTATION; RECEPTOR; GENOME; MODEL; RISK AB The ability to discriminate between deleterious and neutral amino acid substitutions in the genes of patients remains a significant challenge in human genetics. The increasing availability of genomic sequence data from multiple vertebrate species allows inclusion of sequence conservation and physicochemical properties of residues to be used for functional prediction. In this study, the RET receptor tyrosine kinase serves as a model disease gene in which a broad spectrum (>= 116) of disease-associated mutations has been identified among patients with Hirschsprung disease and multiple endocrine neoplasia type 2. We report the alignment of the human RET protein sequence with the orthologous sequences of 12 non-human vertebrates (eight mammalian, one avian, and three teleost species), their comparative analysis, the evolutionary topology of the RET protein, and predicted tolerance for all published missense mutations. We show that, although evolutionary conservation alone provides significant information to predict the effect of a RET mutation, a model that combines comparative sequence data with analysis of physiochemical properties in a quantitative framework provides far greater accuracy. Although the ability to discern the impact of a mutation is imperfect, our analyses permit substantial discrimination between predicted functional classes of RET mutations and disease severity even for a multigenic disease such as Hirschsprung disease. C1 Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Comparat Med, Baltimore, MD 21205 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Chakravarti, A (reprint author), Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. EM aravinda@jhmi.edu; amccalli@jhmi.edu RI Stone, Eric/Q-7840-2016; OI Grice, Elizabeth/0000-0003-3939-2200 NR 28 TC 30 Z9 30 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 JUN 21 PY 2005 VL 102 IS 25 BP 8949 EP 8954 DI 10.1073/pnas.0503259102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939CI UT WOS:000230049500031 PM 15956201 ER PT J AU Polack, FP Irusta, PM Hoffman, SJ Schiatti, MP Melendi, GA Delgado, MF Laham, FR Thumar, B Hendry, RM Melero, JA Karron, RA Collins, PL Kleeberger, SR AF Polack, FP Irusta, PM Hoffman, SJ Schiatti, MP Melendi, GA Delgado, MF Laham, FR Thumar, B Hendry, RM Melero, JA Karron, RA Collins, PL Kleeberger, SR TI The cysteine-rich region of respiratory syncytial virus attachment protein inhibits innate immunity elicited by the virus and endotoxin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycoprotein; innate immunity; toll-like receptor 4 ID TOLL-LIKE RECEPTOR-4; NECROSIS-FACTOR RECEPTOR; FACTOR-KAPPA-B; G-GLYCOPROTEIN; IN-VITRO; INFECTION; ACTIVATION; DISEASE; IMMUNIZATION; ASSOCIATION AB The attachment protein (glycoprotein) of respiratory syncytial virus (RSV) has long been associated with disease potentiation and respiratory symptoms. The glycoprotein has a conserved cysteine-rich region (GCRR) whose function is unknown and which is not necessary for efficient viral replication. In this report, we show that the GCRR is a powerful inhibitor of the innate immune response against RSV, and that early secretion of glycoprotein is critical to modulate inflammation after RSV infection. Importantly, the GCRR is also a potent inhibitor of cytokine production mediated by several TLR agonists, indicating that this peptide sequence displays broad antiinflammatory properties. These findings have important implications for RSV pathogenesis and describe an inhibitor of TLR-mediated inflammatory responses that could have clinical applications. C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. INFANT Fdn, RA-1406 Buenos Aires, DF, Argentina. Georgetown Univ, Dept Human Sci, Washington, DC 20057 USA. Wyeth Lederle, Rochester, NY 14623 USA. Inst Salud Carlos III, Madrid 28029, Spain. NIAID, NIH, Bethesda, MD 20892 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Polack, FP (reprint author), Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. EM fpolack@jhsph.edu FU NIAID NIH HHS [R21 AI054952, AI-054952, R01 AI054952] NR 32 TC 68 Z9 69 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 2005 VL 102 IS 25 BP 8996 EP 9001 DI 10.1073/pnas.0409478102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939CI UT WOS:000230049500039 PM 15956195 ER PT J AU Chin, MPS Rhodes, TD Chen, JB Fu, W Hu, WS AF Chin, MPS Rhodes, TD Chen, JB Fu, W Hu, WS TI Identification of a major restriction in HIV-1 intersubtype recombination SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE subtype; RNA dimerization ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 SUBTYPE-C; RETROVIRAL RECOMBINATION; GENETIC-RECOMBINATION; IN-VITRO; VIRAL REPLICATION; TARGET-CELLS; RNA GENOMES; DIMERIZATION; INFECTION AB Genetic recombination increases diversity in HIV-1 populations, thereby allowing variants to escape from host immunity or antiviral therapies. In addition to the currently described nine subtypes of HIV-1, many of the circulating strains are intersubtype recombinants. In this study, we determined the recombination rate between two HIV-1 subtype C viruses and between a subtype B virus and a subtype C virus during a single round of virus replication. Although HIV-1 subtype C recombines at a high rate, similar to that of HIV-1 subtype B, the recombination rate between a subtype B virus and a subtype C virus is much lower than the intrasubtype recombination rate. A 3-nt sequence difference in the dimerization initiation signal (DIS) region between HIV-1 subtypes B and C accounts for most of the reduction of intersubtype recombination. By matching the DIS sequences, the B/C intersubtype recombination rate was elevated 4-fold; by introducing mismatches in the 3-nt sequences, the B/B intrasubtype recombination rate was reduced 4-fold. Further analyses showed that the intermolecular template-switching frequency was unaffected by the sequence identity of the DIS region. These results support the hypothesis that mismatched sequences in the DIS region alter the formation of heterozygous virions, thereby lowering the observable recombination rate. Here, we present the discovery of a major restriction in HIV-1 intersubtype recombination. These results have important implications for virus evolution, the mechanism of HIV-1 RNA packaging, high negative interference in recombination, and the generation of circulating intersubtype recombinants within the infected population. C1 NCI, HIV Drug Discovery Program, Frederick, MD 21702 USA. W Virginia Univ, Dept Microbiol Immunol & Cell Biol, Morgantown, WV 26505 USA. RP Hu, WS (reprint author), NCI, HIV Drug Discovery Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 NR 42 TC 77 Z9 81 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 JUN 21 PY 2005 VL 102 IS 25 BP 9002 EP 9007 DI 10.1073/pnas.0502522102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939CI UT WOS:000230049500040 PM 15956186 ER PT J AU Virtaneva, K Porcella, SF Graham, MR Ireland, RM Johnson, CA Ricklefs, SM Babar, I Parkins, LD Romero, RA Corn, GJ Gardner, DJ Bailey, JR Parnell, MJ Musser, JM AF Virtaneva, K Porcella, SF Graham, MR Ireland, RM Johnson, CA Ricklefs, SM Babar, I Parkins, LD Romero, RA Corn, GJ Gardner, DJ Bailey, JR Parnell, MJ Musser, JM TI Longitudinal analysis of the group A Streptococcus transcriptome in experimental pharyngitis in cynomolgus macaques SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Affymetrix GeneChip; clinical correlation; colonization; carriage ID COMPLETE GENOME SEQUENCE; ACUTE RHEUMATIC-FEVER; GENE-EXPRESSION; IMMUNE-RESPONSE; VIBRIO-CHOLERAE; M3 STRAIN; IN-VIVO; INFECTION; PYOGENES; HOST AB Identification of the genetic events that contribute to host-pathogen interactions is important for understanding the natural history of infectious diseases and developing therapeutics. Transcriptome studies conducted on pathogens have been central to this goal in recent years. However, most of these investigations have focused on specific end points or disease phases, rather than analysis of the entire time course of infection. To gain a more complete understanding of how bacterial gene expression changes over time in a primate host, the transcriptome of group A Streptococcus (GAS) was analyzed during an 86-day infection protocol in 20 cynomolgus macaques with experimental pharyngitis. The study used 260 custom Affymetrix (Santa Clara, CA) chips, and data were confirmed by TaqMan analysis. Colonization, acute, and asymptomatic phases of disease were identified. Successful colonization and severe inflammation were significantly correlated with an early onset of superantigen gene expression. The differential expression of two-component regulators covR and spy0680 (M1_spy0874) was significantly associated with GAS colony-forming units, inflammation, and phases of disease. Prophage virulence gene expression and prophage induction occurred predominantly during high pathogen cell densities and acute inflammation. We discovered that temporal changes in the GAS transcriptome were integrally linked to the phase of clinical disease and host-defense response. Knowledge of the gene expression patterns characterizing each phase of pathogen-host interaction provides avenues for targeted investigation of proven and putative virulence factors and genes of unknown function and will assist vaccine research. C1 NIAID, Rocky Mt Lab, Lab Human Bacteriol Pathogenesis, NIH, Hamilton, MT 59840 USA. NIAID, Rocky Mt Lab, Vet Branch, NIH, Hamilton, MT 59840 USA. Baylor Coll Med, Ctr Human Bacteriol Pathogenesis Res, Dept Pathol, Houston, TX 77030 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Lab, Lab Human Bacteriol Pathogenesis, NIH, Hamilton, MT 59840 USA. EM musser@bcm.tmc.edu FU NIAID NIH HHS [U01 AI060595, UO1-AI-060595] NR 33 TC 130 Z9 134 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 21 PY 2005 VL 102 IS 25 BP 9014 EP 9019 DI 10.1073/pnas.0503671102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 939CI UT WOS:000230049500042 PM 15956184 ER PT J AU Bleckwenn, NA Golding, H Bentley, WE Shiloach, J AF Bleckwenn, NA Golding, H Bentley, WE Shiloach, J TI Production of recombinant proteins by vaccinia virus in a microcarrier based mammalian cell perfusion bioreactor SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE vaccinia; bioreactor; microcarrier; ATF; EGFP; gp120 ID BACULOVIRUS EXPRESSION SYSTEM; SF-9 INSECT CELLS; HIV ENVELOPE; MONOCLONAL-ANTIBODY; SUSPENSION-CULTURES; GENE-EXPRESSION; CLINICAL-TRIAL; GROWTH-FACTOR; HELA-CELLS; GLYCOPROTEIN AB The HeLa cell-vaccinia virus expression system was evaluated for the production of recombinant proteins (enhanced green fluorescent protein (EGFP) and HIV envelope coat protein, gp120) using microcarriers in 1.5 L perfused bioreactor cultures. Perfusion was achieved by use of an alternating tangential flow device (ATF), increasing the length of the exponential phase by 50 h compared to batch culture and increasing the maximum cell density from 1.5 x 10(6) to 4.4 x 10(6) cell/mL. A seed train expansion method using cells harvested from microcarrier culture and reseeding onto fresh carriers was developed. EGFP was first used as a model protein to study process parameters affecting protein yield, specifically dissolved oxygen (DO) and temperature during the production phase. The highest level of EGFP, 12 +/- 1.5 mu g/10(6) infected cells, was obtained at 50% DO and 31 degrees C. These setpoints were then used to produce glycoprotein, gp120, which was purified and deglycosylated, revealing a significant amount of N-linked glycosylation. Also, biological activity was assayed, resulting in an ID50 of 3.1 mu g/mL, which is comparable to previous reports. Published 2005 Wiley Periodicals, Inc.(dagger) C1 NIDDK, Biotechnol Unit, DHHS, NIH, Bethesda, MD USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD USA. RP Bleckwenn, NA (reprint author), NIDDK, Biotechnol Unit, DHHS, NIH, Bldg 14A Rm 173,MSC 5522,9000 Rockville Pike, Bethesda, MD USA. EM yossic@nih.gov FU Intramural NIH HHS NR 55 TC 17 Z9 17 U1 2 U2 13 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUN 20 PY 2005 VL 90 IS 6 BP 663 EP 674 DI 10.1002/bit.20423 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 931CM UT WOS:000229463400001 PM 15858791 ER PT J AU Clarimon, J Xiromerisiou, G Eerola, J Gourbali, V Hellstrom, O Dardiotis, E Peuralinna, T Papadimitriou, A Hadjigeorgiou, GM Tienari, PJ Singleton, AB AF Clarimon, J Xiromerisiou, G Eerola, J Gourbali, V Hellstrom, O Dardiotis, E Peuralinna, T Papadimitriou, A Hadjigeorgiou, GM Tienari, PJ Singleton, AB TI Lack of evidence for a genetic association between FGF20 and Parkinson's disease in Finnish and Greek patients SO BMC NEUROLOGY LA English DT Article ID FAMILIAL AGGREGATION; CLONING AB Background: Fibroblast growth factor 20 (FGF20) is a neurotrophic factor preferentially expressed in the substantia nigra of rat brain and could be involved in dopaminergic neurons survival. Recently, a strong genetic association has been found between FGF20 gene and the risk of suffering from Parkinson's disease (PD). Our aim was to replicate this association in two independent populations. Methods: Allelic, genotypic, and haplotype frequencies of four biallelic polymorphisms were assessed in 151 sporadic PD cases and 186 controls from Greece, and 144 sporadic PD patients and 135 controls from Finland. Results: No association was found in any of the populations studied. Conclusion: Taken together, these findings suggest that common genetic variants in FGF20 are not a risk factor for PD in, at least, some European populations. C1 NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Univ Thessaly, Sch Med, Dept Neurol, Neurogenet Unit, Larisa, Greece. Univ Helsinki, Cent Hosp, Dept Neurol, FIN-00014 Helsinki, Finland. Univ Helsinki, Biomedicum, Neurosci Programme, FIN-00014 Helsinki, Finland. RP Clarimon, J (reprint author), NIA, Mol Genet Unit, Neurogenet Lab, NIH, Bldg 35 Room 1A1000, Bethesda, MD 20892 USA. EM clarimon@mail.nih.gov; xiromerisiouge@mail.nih.gov; Johanna.eerola@helsinki.fi; geocl83x@hotmail.com; olli.hellstrom@epshp.fi; edar@med.uth.gr; terhi.peuralinna@helsinki.fi; alexpapadimitriou@yahoo.com; gmhadji@yahoo.com; pentti.tienari@hus.fi; singleta@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Tienari, Pentti/A-4893-2012 NR 12 TC 33 Z9 35 U1 2 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2377 J9 BMC NEUROL JI BMC Neurol. PD JUN 20 PY 2005 VL 5 AR 11 DI 10.1186/1471-2377-5-11 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 024IE UT WOS:000236187900001 PM 15967032 ER PT J AU Kino, T Tiulpakov, A Ichijo, T Chheng, L Kozasa, T Chrousos, GP AF Kino, T Tiulpakov, A Ichijo, T Chheng, L Kozasa, T Chrousos, GP TI G protein beta interacts with the glucocorticoid receptor and suppresses its transcriptional activity in the nucleus SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PITUITARY-ADRENAL AXIS; STEROID-HORMONES; SOMATOSTATIN; LOCALIZATION; COMPLEX; GAMMA; ACTIVATION; AFFINITY; RACK1; STIMULATION AB Extracellular stimuli that activate cell surface receptors modulate glucocorticoid actions via as yet unclear mechanisms. Here, we report that the guanine nucleotide-binding protein (G protein)-coupled receptor-activated WD-repeat G beta interacts with the glucocorticoid receptor (GR), comigrates with it into the nucleus and suppresses GR-induced transactivation of the glucocorticoid-responsive genes. Association of G gamma with G beta is necessary for this action of G beta. Both endogenous and enhanced green fluorescent protein (EGFP)-fused G beta 2 and G gamma 2 proteins were detected in the nucleus at baseline, whereas E a fraction of EGFP-G beta 2 and DsRed2-GR comigrated to the nucleus or the plasma membrane, depending on the exposure of cells to dexamethasone or somatostatin, respectively. G beta 2 was associated with GR/glucocorticoid response elements (GREs) in vivo and suppressed activation function-2-directed transcriptional activity of the GR. We conclude that the G beta gamma complex interacts with the GR and suppresses its transcriptional activity by associating with the transcriptional complex formed on GR-responsive promoters. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Illinois, Coll Med, Dept Pharmacol, Chicago, IL 60612 USA. RP Kino, T (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. EM kinot@mail.nih.gov NR 42 TC 76 Z9 78 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 20 PY 2005 VL 169 IS 6 BP 885 EP 896 DI 10.1083/jcb.200409150 PG 12 WC Cell Biology SC Cell Biology GA 937MY UT WOS:000229930300006 PM 15955845 ER PT J AU Shen, TL Park, AYJ Alcaraz, A Peng, X Jang, I Koni, P Flavell, RA Gu, H Guan, JL AF Shen, TL Park, AYJ Alcaraz, A Peng, X Jang, I Koni, P Flavell, RA Gu, H Guan, JL TI Conditional knockout of focal adhesion kinase in endothelial cells reveals its role in angiogenesis and vascular development in late embryogenesis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID TYROSINE PHOSPHORYLATION; TRANSGENIC MICE; BLOOD-VESSELS; IN-VIVO; MIGRATION; FAK; SRC; PAXILLIN; ACTIVATION; MOTILITY AB Focal adhesion kinase (FAK) is a critical mediator of signal transduction by integrins and growth factor receptors in a variety of cells including endothelial cells (ECs). Here, we describe EC-specific knockout of FAK using a Cre-lox approach. In contrast to the total FAK knockout, deletion of FAK specifically in ECs did not affect early embryonic development including normal vasculogenesis. However, in late embryogenesis, FAK deletion in the ECs led to defective angiogenesis in the embryos, yolk sac, and placenta, impaired vasculature and F associated hemorrhage, edema, and developmental delay, and late embryonic lethal phenotype. Histologically, ECs and blood vessels in the mutant embryos present a disorganized, detached, and apoptotic appearance. Consistent with these phenotypes, deletion of FAK in ECs isolated from the floxed FAK mice led to reduced tubulogenesis, cell survival, proliferation, and migration in vitro. Together, these results strongly suggest a role of FAK in angiogenesis and vascular development due to its essential function in the regulation of multiple EC activities. C1 Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. Cornell Univ, Coll Vet Med, Dept Biomed Sci, Ithaca, NY 14853 USA. NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. Columbia Univ Coll Phys & Surg, Dept Microbiol, New York, NY 10032 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Immunobiol Sect, New Haven, CT 06520 USA. RP Guan, JL (reprint author), Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA. EM jg19@cornell.edu RI Koni, Pandelakis/A-3349-2008; Shen, Tang-Long/C-7460-2011; OI Shen, Tang-Long/0000-0001-6264-3608 FU Intramural NIH HHS; NHLBI NIH HHS [HL73394, R01 HL073394] NR 43 TC 181 Z9 188 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 20 PY 2005 VL 169 IS 6 BP 941 EP 952 DI 10.1083/jcb.200411155 PG 12 WC Cell Biology SC Cell Biology GA 937MY UT WOS:000229930300011 PM 15967814 ER PT J AU Hess, ST Kumar, M Verma, A Farrington, J Kenworthy, A Zimmerberg, J AF Hess, ST Kumar, M Verma, A Farrington, J Kenworthy, A Zimmerberg, J TI Quantitative electron microscopy and fluorescence spectroscopy of the membrane distribution of influenza hemagglutinin SO JOURNAL OF CELL BIOLOGY LA English DT Article ID RESONANCE ENERGY-TRANSFER; LIPID RAFT MICRODOMAINS; GPI-ANCHORED PROTEINS; MAST-CELL MEMBRANE; PLASMA-MEMBRANE; GLUCOSYLCERAMIDE SYNTHASE; VIRUS HEMAGGLUTININ; CYTOPLASMIC DOMAINS; BETA-CYCLODEXTRIN; PORE FORMATION AB Although lipid-dependent protein clustering in biomembranes mediates numerous functions, there is little consensus among membrane models on cluster organization or size. Here, we use influenza viral envelope protein hemagglutinin ( HA(0)) to test the hypothesis that clustering results from proteins partitioning into preexisting, fluid-ordered "raft" domains, wherein they have a random distribution. Japan HA(0) expressed in fibroblasts was visualized by electron microscopy using immunogold labeling and probed by fluorescence resonance energy transfer (FRET). Labeled HA coincided with electron-dense, often noncircular membrane patches. Poisson and K-test (Ripley, B. D. A 1977. J. R. Stat. Soc. Ser. B. 39: 172-212) analyses reveal clustering on accessible length scales (20-900 nm). Membrane treatments with methyl-beta-cyclodextrin and glycosphingolipid synthesis inhibitors did not abolish clusters but did alter their pattern, especially at the shortest lengths, as was corroborated by changes in FRET efficiency. The magnitude and density dependence of the measured FRET efficiency also indicated a non-random distribution on molecular length scales (similar to 6-7 nm). This work rules out the tested hypothesis for HA over the accessible length scales, yet shows clearly how the spatial distribution of HA depends on lipid composition. C1 NICHHD, Lab Celllular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA. RP Zimmerberg, J (reprint author), NICHHD, Lab Celllular & Mol Biophys, NIH, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov NR 58 TC 73 Z9 74 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 20 PY 2005 VL 169 IS 6 BP 965 EP 976 DI 10.1083/jcb.200412058 PG 12 WC Cell Biology SC Cell Biology GA 937MY UT WOS:000229930300013 PM 15967815 ER PT J AU Curino, AC Engelholm, LH Yamada, SS Holmbeck, K Lund, LR Molinolo, AA Behrendt, N Nielsen, BS Bugge, TH AF Curino, AC Engelholm, LH Yamada, SS Holmbeck, K Lund, LR Molinolo, AA Behrendt, N Nielsen, BS Bugge, TH TI Intracellular collagen degradation mediated by uPARAP/Endo 180 is a major pathway of extracellular matrix turnover during malignancy SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROTEIN UPARAP/ENDO180; DEFICIENT MICE; BREAST-CANCER; RECEPTOR; METALLOPROTEINASES; DISEASE; PHAGOCYTOSIS; ENDO180; CELLS; MODEL AB We recently reported that uPARAP/Endo180 can mediate the cellular uptake and lysosomal degradation of collagen by cultured fibroblasts. Here, we show that uPARAP/Endo180 has a key role in the degradation of collagen during mammary carcinoma progression. In the normal murine mammary gland, uPARAP/Endo180 is widely expressed in periductal fibroblast-like mesenchymal cells that line mammary epithelial cells. This pattern of uPARAP/Endo180 expression is preserved during polyomavirus middle T-induced mammary carcinogenesis, with strong uPARAP/Endo180 expression by mesenchymal cells embedded within the collagenous stroma surrounding nests of uPARAP/ Endo180-negative tumor cells. Genetic ablation of uPARAP/ Endo180 impaired collagen turnover that is critical to tumor expansion, as evidenced by the abrogation of cellular collagen uptake, tumor fibrosis, and blunted tumor growth. These studies identify uPARAP/Endo180 as a key mediator of collagen turnover in a pathophysiological context. C1 NIDCR, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. NIDCR, Mol Carcinogenesis Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIDCR, Craniofacial & Skeletal Dis Branch, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. RP Bugge, TH (reprint author), NIDCR, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov OI Engelholm, Lars/0000-0002-6616-1232 NR 46 TC 80 Z9 88 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 20 PY 2005 VL 169 IS 6 BP 977 EP 985 DI 10.1083/jcb.200411153 PG 9 WC Cell Biology SC Cell Biology GA 937MY UT WOS:000229930300014 PM 15967816 ER PT J AU Badros, A Goloubeva, O Rapoport, AP Ratterree, B Gahres, N Meisenberg, B Takebe, N Heyman, M Zwiebel, J Streicher, H Gocke, CD Tomic, D Flaws, JA Zhang, B Fenton, RG AF Badros, A Goloubeva, O Rapoport, AP Ratterree, B Gahres, N Meisenberg, B Takebe, N Heyman, M Zwiebel, J Streicher, H Gocke, CD Tomic, D Flaws, JA Zhang, B Fenton, RG TI Phase II study of G3139, a Bcl-2 antisense oligonucleotide, in combination with dexamethasone and thalidomide in relapsed multiple myeloma patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID REFRACTORY PROSTATE-CANCER; B-CELL ACTIVATION; PLASMA-CELLS; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE; BACTERIAL-DNA; CPG MOTIFS; EXPRESSION; CHEMOTHERAPY; APOPTOSIS; SURVIVAL AB Purpose Bcl-2 regulates the mitochondrial apoptosis pathway that promotes chemotherapy resistance. Bcl-2 antisense oligonucleotide, G3139, targets Bcl-2 mRNA. Patients and Methods G3139 was administered (3 to 7 mg/kg/d for 7 days) by continuous intravenous infusion. On day 4, patients started thaliclomide (100 to 400 mg as tolerated) and dexamethasone (40 mg daily for 4 days) on 21-day cycles for three cycles. Stable and responding patients continued on 35-day cycles for 2 years. Results Thirty-three patients (median age, 60 years; range, 28 to 76 years) received 220 cycles. Patients received a median of three prior regimens including thaliclomide (n = 15) and stem-cell transplantation (n = 31). The regimen was well tolerated; the median number of cycles per patient was eight (range, one to 16+ cycles). Toxicities included reversible increase in creatinine, thrombocytopenia, neutropenia, fatigue, anorexia, constipation, fever, neuropathy, edema, electrolyte disturbances, and hyperglycemia. Fifty-five percent of patients had objective responses, including two complete responses (CRs), four near CRs (positive immunofixation), and 12 partial responses; six patients had minimal responses (MRs). Of patients who received prior thalidomide, seven had objective responses, and three had MRs. The median duration of response was 13 months, and estimated progression-free and overall survival times were 12 and 17.4 months, respectively. Responding patients had significant increase in polyclonal immunoglobulin M (P = .005), indicating innate immune system activation. Western blot analysis of Bcl-2 protein isolated from myeloma cells before and after G3139 demonstrated a decrease of Bcl-2 levels in three of seven patients compared with six of nine patients using reverse transcriptase polymerase chain reaction. Conclusion G3139, dexamethasone, and thalidomide are well tolerated and result in encouraging clinical responses in relapsed multiple myeloma patients. C1 Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Badros, A (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM abadros@umm.edu FU NCI NIH HHS [UO1 CA69854] NR 46 TC 68 Z9 80 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2005 VL 23 IS 18 BP 4089 EP 4099 DI 10.1200/JCO.2005.14.381 PG 11 WC Oncology SC Oncology GA 936WR UT WOS:000229886700013 PM 15867202 ER PT J AU Weil, RJ Lonser, RR Quezado, MM AF Weil, RJ Lonser, RR Quezado, MM TI Skull and brain metastasis from tibial osteosarcoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID DIAGNOSIS; SARCOMA C1 NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Weil, RJ (reprint author), NINDS, Surg Neurol Branch, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 20 PY 2005 VL 23 IS 18 BP 4226 EP 4229 DI 10.1200/JCO.2005.05.055 PG 4 WC Oncology SC Oncology GA 936WR UT WOS:000229886700028 PM 15961770 ER PT J AU Lore, K Smed-Sorensen, A Vasudevan, J Mascola, JR Koup, RA AF Lore, K Smed-Sorensen, A Vasudevan, J Mascola, JR Koup, RA TI Myeloid and plasmacytoid dendritic cells transfer HIV-1 preferentially to antigen-specific CD4(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CLASS-II TRANSPORT; PRODUCTIVE INFECTION; LANGERHANS CELLS; DC-SIGN; INTRAVAGINAL INOCULATION; TRANSMISSION; REPLICATION; MATURATION; SURFACE AB Dendritic cells (DCs) are essential antigen-presenting cells for the induction of T cell immunity against pathogens such as human immunodeficiency virus (HIV)-1. At the same time, HIV-1 replication is strongly enhanced in DC-T cell clusters, potentially undermining this process. We found that immature CD123(+) plasmacytoid DCs (PDCs) and CD11c(+) myeloid DCs (MDCs) were susceptible to both a CCR5- and a CXCR4-using HIV-1 isolate in vitro and were able to efficiently transfer that infection to autologous CD4(+) T cells. Soon after HIV-1 exposure, both PDCs and MDCs were able to transfer the virus to T cells in the absence of a productive infection. However, once a productive infection was established in the DCs, newly synthesized virus was predominantly spread to T cells. HIV-1 exposure of the MDCs and PDCs did not inhibit their ability to present cytomegalovirus (CMV) antigens and activate CMV-specific memory T cells. As a result, both PDCs and MDCs preferentially transmitted HIV-1 to the responding CMV antigen-specific CD4(+) T cells rather than to nonresponding T cells. This suggests that the induction of antigen-specific T cell responses by DCs, a process crucial to immune defense, can lead to preferential HIV-1 infection and the deletion of responding CD4(+) T cells. C1 NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Core Virol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Karolinska Inst, Dept Med, Ctr Infect Med, S-14186 Huddinge, Sweden. RP Lore, K (reprint author), NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA. EM klore@mail.nih.gov NR 42 TC 133 Z9 133 U1 0 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 JUN 20 PY 2005 VL 201 IS 12 BP 2023 EP 2033 DI 10.1084/jem.20042413 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 937MZ UT WOS:000229930400017 PM 15967828 ER PT J AU De Angelis, CD Drazen, JM Frizelle, FA Haug, C Hoey, J Kotzin, S Laine, C Marusic, A Overbeke, AJPM Schroeder, TV Sox, HC Van der Weyden, MB Horton, R AF De Angelis, CD Drazen, JM Frizelle, FA Haug, C Hoey, J Kotzin, S Laine, C Marusic, A Overbeke, AJPM Schroeder, TV Sox, HC Van der Weyden, MB Horton, R TI Is this clinical trial fully registered? SO MEDICAL JOURNAL OF AUSTRALIA LA English DT Editorial Material C1 Natl Lib Med, Bethesda, MD 20894 USA. RI Marusic, Ana/E-7683-2013; OI Marusic, Ana/0000-0001-6272-0917; Schroeder, Torben/0000-0002-9827-9438 NR 1 TC 3 Z9 3 U1 0 U2 1 PU AUSTRALASIAN MED PUBL CO LTD PI SYDNEY PA LEVEL 1, 76 BERRY ST, SYDNEY, NSW 2060, AUSTRALIA SN 0025-729X J9 MED J AUSTRALIA JI Med. J. Aust. PD JUN 20 PY 2005 VL 182 IS 12 BP 609 EP 610 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 951SP UT WOS:000230951500005 PM 15963015 ER PT J AU Feder, N AF Feder, N TI Consulting by NIH scientists SO SCIENTIST LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Feder, N (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM federn@extra.niddk.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD JUN 20 PY 2005 VL 19 IS 12 BP 8 EP 8 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 937BY UT WOS:000229900800002 ER PT J AU Schiffman, M Herrero, R DeSalle, R Hildesheim, A Wacholder, S Rodriguez, AC Bratti, MC Sherman, ME Morales, J Guillen, D Alfaro, M Hutchinson, M Wright, TC Solomon, D Chen, ZG Schussler, J Castle, PE Burk, RD AF Schiffman, M Herrero, R DeSalle, R Hildesheim, A Wacholder, S Rodriguez, AC Bratti, MC Sherman, ME Morales, J Guillen, D Alfaro, M Hutchinson, M Wright, TC Solomon, D Chen, ZG Schussler, J Castle, PE Burk, RD TI The carcinogenicity of human papillornavirus types reflects viral evolution SO VIROLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS INFECTION; CERVICAL INTRAEPITHELIAL NEOPLASIA; NATURAL-HISTORY; YOUNG-WOMEN; CANCER; CLASSIFICATION; TRANSFORMATION AB Persistent infections with carcinogenic human papillomaviruses (HPV) cause virtually all cervical cancers. Cervical HPV types (n > 40) also represent the most common sexually transmitted agents, and most infections clear in 1-2 years. The risks of persistence and neoplastic progression to cancer and its histologic precursor, cervical intraepithelial neoplasia grade 3 (CIN3), differ markedly by HPV type. To study type-specific HPV natural history, we conducted a 10,000-woman, population-based prospective study of HPV infections and CIN3/cancer in Guanacaste, Costa Rica. By studying large numbers of women, we wished to separate viral persistence from neoplastic progression. We observed a strong concordance of newly-revised HPV evolutionary groupings with the separate risks of persistence and progression to CIN3/cancer. HPV16 was uniquely likely both to persist and to cause neoplastic progression when it persisted, making it a remarkably powerful human carcinogen that merits separate clinical consideration. Specifically, 19.9% of HPV16-infected women were diagnosed with CIN3/cancer at enrollment or during the five-year follow-up. Other carcinogenic types, many related to HPV16, were not particularly persistent but could cause neoplastic progression, at lower rates than HPV16, if they did persist. Some low-risk types were persistent but, nevertheless, virtually never caused CIN3. Therefore, carcinogenicity is not strictly a function of persistence. Separately, we noted that the carcinogenic HPV types code for an E5 protein, whereas most low-risk types either lack a definable homologous E5 ORF and/or a translation start codon for E5. These results present several clear clues and research directions in our ongoing efforts to understand HPV carcinogenesis. Published by Elsevier Inc. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, US Dept Hlth & Human Serv, Rockville, MD 20852 USA. Natl Canc Inst, Div Canc Prevent, NIH, US Dept Hlth & Human Serv, Rockville, MD 20852 USA. Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Amer Museum Nat Hist, Div Invertebrate Zool, New York, NY USA. Women & Infants Hosp Rhode Isl, Providence, RI 02905 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Bronx, NY 10467 USA. Informat Managament Serv, Silver Spring, MA USA. RP Schiffman, M (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, US Dept Hlth & Human Serv, Room 7066,6120 Exec Blvd, Rockville, MD 20852 USA. EM schiffmm@mail.nih.gov RI Chen, Zigui/E-8490-2017 FU NCI NIH HHS [CA78527] NR 35 TC 314 Z9 328 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUN 20 PY 2005 VL 337 IS 1 BP 76 EP 84 DI 10.1016/j.virol.2005.04.002 PG 9 WC Virology SC Virology GA 933ZD UT WOS:000229670700008 PM 15914222 ER PT J AU Merke, DP Bornstein, SR AF Merke, DP Bornstein, SR TI Congenital adrenal hyperplasia SO LANCET LA English DT Review ID STEROID 21-HYDROXYLASE DEFICIENCY; FOR-PEDIATRIC-ENDOCRINOLOGY; POLYCYSTIC-OVARY-SYNDROME; HIGH-INTENSITY EXERCISE; GENDER-RELATED BEHAVIOR; GLUCOCORTICOID TREATMENT; HORMONE ANALOG; FINAL HEIGHT; ADRENOMEDULLARY FUNCTION; DEXAMETHASONE TREATMENT AB Congenital adrenal hyperplasia (CAH) due to deficiency of 21-hydroxylase is a disorder of the adrenal cortex characterised by cortisol deficiency, with or without aldosterone deficiency, and androgen excess. Patients with the most severe form also have abnormalities of the adrenal medulla and epinephrine deficiency. The severe classic form occurs in one in 15 000 births worldwide, and the mild non-classic form is a common cause of hyperandrogenism. Neonatal screening for CAH and gene-specific prenatal diagnosis are now possible. Standard hormone replacement fails to achieve normal growth and development for many children with CAH, and adults can experience iatrogenic Cushing's syndrome, hyperandrogenism, infertility, or the development of the metabolic syndrome. This Seminar reviews the epidemiology, genetics, pathophysiology, diagnosis, and management of CAH, and provides an overview of clinical challenges and future therapies. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Dresden, Dept Internal Med 3, Dresden, Germany. RP Merke, DP (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bldg 10,Room 1-2740,10 Ctr Dr MSC 1932, Bethesda, MD 20892 USA. EM dmerke@nih.gov NR 154 TC 290 Z9 318 U1 4 U2 32 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 18 PY 2005 VL 365 IS 9477 BP 2125 EP 2136 DI 10.1016/S0140-6736(05)66736-0 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 936LZ UT WOS:000229858800030 PM 15964450 ER PT J AU Kim, KY Kovacs, M Kawamoto, S Sellers, JR Adelstein, RS AF Kim, KY Kovacs, M Kawamoto, S Sellers, JR Adelstein, RS TI Disease-associated mutations and alternative splicing alter the enzymatic and motile activity of nonmuscle myosins II-B and II-C SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAVY-CHAIN GENE; MOTOR DOMAIN; MECHANISM; ABLATION; LOCALIZATION; MIGRATION; ISOFORMS; FECHTNER; ADHESION; CELLS AB Human families with single amino acid mutations in nonmuscle myosin heavy chain (NMHC) II-A (MYH9) and II-C (MYH14) have been described as have mice generated with a point mutation in NMHC II-B (MYH10). These mutations (R702C and N93K in human NMHC II-A, R709C in murine NMHC II-B, and R726S in human NMHC II-C) result in phenotypes affecting kidneys, platelets, and leukocytes (II-A), heart and brain (II-B), and the inner ear (II-C). To better understand the mechanisms underlying these defects, we characterized the in vitro activity of mutated and wild-type baculovirus-expressed heavy meromyosin (HMM) II-B and II-C. We also expressed two alternatively spliced isoforms of NMHC II-C which differ by inclusion/ exclusion of eight amino acids in loop 1, with and without mutations. Comparison of the actin-activated MgATPase activity and in vitro motility shows that mutation of residues Asn-97 and Arg-709 in HMM II-B and the homologous residue Arg-722 (Arg-730 in the alternatively spliced isoform) in HMM II-C decreases both parameters but affects in vitro motility more severely. Analysis of the transient kinetics of the HMM II-B R709C mutant shows an extremely tight affinity of HMM for ADP and a very slow release of ADP from acto-HMM. Although mutations generally decreased HMM activity, the R730S mutation in HMM II-C, unlike the R730C mutation, had no effect on actin-activated MgATPase activity but decreased the rate of in vitro motility by 75% compared with wild type. Insertion of eight amino acids into the HMM II-C heavy chain increases both actin-activated MgATPase activity and in vitro motility. C1 NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Adelstein, RS (reprint author), NHLBI, Mol Cardiol Lab, NIH, Bldg 10,Rm 8N202,10 Ctr Dr MSC 1762, Bethesda, MD 20892 USA. EM AdelsteR@NHLBI.NIH.gov RI Kovacs, Mihaly/A-6841-2011; OI Adelstein, Robert/0000-0002-8683-2144 NR 37 TC 60 Z9 63 U1 0 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 22769 EP 22775 DI 10.1074/jbc.M503488200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800027 PM 15845534 ER PT J AU Pullmann, R Juhaszova, M de Silanes, IL Kawai, T Mazan-Mamczarz, K Halushka, MK Gorospe, M AF Pullmann, R Juhaszova, M de Silanes, IL Kawai, T Mazan-Mamczarz, K Halushka, MK Gorospe, M TI Enhanced proliferation of cultured human vascular smooth muscle cells linked to increased function of RNA-binding protein HuR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR MESSENGER-RNA; GROWTH-FACTOR; GENE-EXPRESSION; GLOBAL ANALYSIS; DOWN-REGULATION; ANGIOTENSIN-II; ALPHA-ACTIN; TNF-ALPHA; CYCLIN-A; KINASE AB In dividing cells, the RNA-binding protein HuR associates with and stabilizes labile mRNAs encoding proliferative proteins, events that are linked to the increased cytoplasmic presence of HuR. Here, assessment of HuR levels in various vascular pathologies (intimal hyperplasia, atherosclerosis and neointimal proliferation, sclerosis of arterialized saphenous venous graft, and fibromuscular dysplasia) revealed a distinct increase in HuR expression and cytoplasmic abundance within the intima and neointima layers. On the basis of these observations, we postulated a role for HuR in promoting the proliferation of vascular smooth muscle cells. To test this hypothesis directly, we investigated the expression, subcellular localization, and proliferative influence of HuR in human vascular smooth muscle cells (hVSMCs). Treatment of hVSMCs with platelet-derived growth factor increased HuR levels in the cytoplasm, thereby influencing the expression of metabolic, proliferative, and structural genes. Importantly, knockdown of HuR expression by using RNA interference caused a reduction of hVSMC proliferation, both basally and following platelet-derived growth factor treatment. We propose that HuR contributes to regulating hVSMC growth and homeostasis in pathologies associated with vascular smooth muscle proliferation. C1 NIA IRP, LCMB, NIH, Baltimore, MD 21224 USA. NIA IRP, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21231 USA. RP Gorospe, M (reprint author), NIA IRP, LCMB, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov RI Lopez de Silanes, Isabel/K-4962-2015; OI Lopez de Silanes, Isabel/0000-0001-6762-9792; Halushka, Marc/0000-0002-7112-7389 FU NIA NIH HHS [Z01 AG000511-08] NR 46 TC 42 Z9 42 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 22819 EP 22826 DI 10.1074/jbc.M501106200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800033 PM 15824116 ER PT J AU Kim, JA Yeh, DC Ver, M Li, YH Carranza, A Conrads, TP Veenstra, TD Harrington, MA Quon, MJ AF Kim, JA Yeh, DC Ver, M Li, YH Carranza, A Conrads, TP Veenstra, TD Harrington, MA Quon, MJ TI Phosphorylation of Ser(24) in the pleckstrin homology domain of insulin receptor substrate-1 by mouse Pelle-like kinase/interleukin-1 receptor-associated kinase - Cross-talk between inflammatory signaling and insulin signaling that may contribute to insulin resistance SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; RAT ADIPOSE-CELLS; NF-KAPPA-B; PROTEIN-KINASE; FACTOR-ALPHA; TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; SERINE PHOSPHORYLATION; TARGETED DISRUPTION; PLASMA-MEMBRANE AB Inflammation contributes to insulin resistance in diabetes and obesity. Mouse Pelle-like kinase (mPLK, homolog of human IL-1 receptor-associated kinase (IRAK)) participates in inflammatory signaling. We evaluated IRS-1 as a novel substrate for mPLK that may contribute to linking inflammation with insulin resistance. Wildtype mPLK, but not a kinase-inactive mutant (mPLK-KD), directly phosphorylated full-length IRS-1 in vitro. This in vitro phosphorylation was increased when mPLK was immunoprecipitated from tumor necrosis factor (TNF)-alpha- treated cells. In NIH-3T3(IR) cells, wild-type mPLK (but not mPLK-KD) co-immunoprecipitated with IRS-1. This association was increased by treatment of cells with TNF-alpha. Using mass spectrometry, we identified Ser(24) in the pleckstrin homology (PH) domain of IRS-1 as a specific phosphorylation site for mPLK. IRS-1 mutants S24D or S24E (mimicking phosphorylation at Ser(24)) had impaired ability to associate with insulin receptors resulting in diminished tyrosine phosphorylation of IRS-1 and impaired ability of IRS-1 to bind and activate PI-3 kinase in response to insulin. IRS-1-S24D also had an impaired ability to mediate insulin-stimulated translocation of GLUT4 in rat adipose cells. Importantly, endogenous mPLK/IRAK was activated in response to TNF-alpha or interleukin 1 treatment of primary adipose cells. In addition, using a phospho-specific antibody against IRS-1 phosphorylated at Ser(24), we found that interleukin-1 or TNF-alpha treatment of Fao cells stimulated increased phosphorylation of endogenous IRS-1 at Ser(24). We conclude that IRS-1 is a novel physiological substrate for mPLK. TNF-alpha-regulated phosphorylation at Ser(24) in the pleckstrin homology domain of IRS-1 by mPLK/IRAK represents an additional mechanism for cross-talk between inflammatory signaling and insulin signaling that may contribute to metabolic insulin resistance. C1 NCCAM, Diabet Unit, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Mass Spectrometry Ctr, NCI,NIH, Frederick, MD 21702 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Walther Canc Inst, Indianapolis, IN 46202 USA. RP Quon, MJ (reprint author), NCCAM, Diabet Unit, NIH, Bldg 10,Rm 6C-205,10 Ctr Dr,MSC 1632, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008 FU NCI NIH HHS [N01-CA-12400] NR 84 TC 54 Z9 58 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 23173 EP 23183 DI 10.1074/jbc.M501439200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800075 PM 15849359 ER PT J AU Morinaga, N Iwamaru, Y Yahiro, K Tagashira, M Moss, J Noda, M AF Morinaga, N Iwamaru, Y Yahiro, K Tagashira, M Moss, J Noda, M TI Differential activities of plant polyphenols on the binding and internalization of cholera toxin in vero cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLTRANSFERASE ACTIVITY; INDUCED FLUID ACCUMULATION; ENDOPLASMIC-RETICULUM; ADENYLATE-CYCLASE; MEMBRANE; IDENTIFICATION; GANGLIOSIDES; INHIBITION; ACTIVATION; MECHANISM AB Plant polyphenols, RG-tannin, and applephenon had been reported to inhibit cholera toxin (CT) ADP-ribosyltransferase activity and CT-induced fluid accumulation in mouse ileal loops. A high molecular weight fraction of hop bract extract (HBT) also inhibited CT ADP-ribosyltransferase activity. We report here the effect of those polyphenols on the binding and entry of CT into Vero cells. Binding of CT to Vero cells or to ganglioside GM1, a CT receptor, was inhibited in a concentration-dependent manner by HBT and applephenon but not RG-tannin. These observations were confirmed by fluorescence microscopy using Cy3-labeled CT. Following toxin binding to cells, applephenon, HBT, and RG-tannin suppressed its internalization. HBT or applephenon precipitated CT, CTA, and CTB from solution, creating aggregates larger than 250 kDa. In contrast, RG-tannin precipitated CT poorly; it formed complexes with CT, CTA, or CTB, which were demonstrated with sucrose density gradient centrifugation and molecular weight exclusion filters. In agreement, CTA blocked the inhibition of CT internalization by RG-tannin. These data suggest that some plant polyphenols, similar to applephenon and HBT, bind CT, forming large aggregates in solution or, perhaps, on the cell surface and thereby suppress CT binding and internalization. In contrast, RG-tannin binding to CT did not interfere with its binding to Vero cells or GM1, but it did inhibit internalization. C1 Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, Chiba 2608670, Japan. Asahi Brewery Co Ltd, Fundamental Res Labs, Moriya, Ibaraki 3020106, Japan. NHLBI, NIH, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. RP Morinaga, N (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM nmorinaga@faculty.chiba-u.jp NR 24 TC 36 Z9 39 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 23303 EP 23309 DI 10.1074/JBC.M502093200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800089 PM 15814610 ER PT J AU Wang, J Liu, H Lin, CM Aladjem, MI Epner, EM AF Wang, J Liu, H Lin, CM Aladjem, MI Epner, EM TI Targeted deletion of the chicken beta-globin regulatory elements reveals a cooperative gene silencing activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOCUS-CONTROL REGION; RNA-POLYMERASE-II; OPEN CHROMATIN-STRUCTURE; HUMAN-LEUKEMIA-CELLS; ERYTHROID-CELLS; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; HYPERSENSITIVE SITES; HISTONE ACETYLATION; DNA METHYLATION AB The chicken beta-globin locus represents a well characterized system to study the role of both proximal and distal regulatory elements in a eukaryotic multigene domain. The function of the chicken beta(A)/epsilon-intergenic enhancer and upstream regulatory elements 5'-HS1 and 5'-HS2 were studied using a gene targeting approach in chicken DT40 cells followed by microcell-mediated chromosome transfer into human erythroleukemia cells ( K562). These regulatory elements all repressed expression of the rho- and beta(H)-chicken globin genes in the chromosome transfer assay. No rho- or beta(H)-globin gene expression was detected in K562 cells containing the chicken chromosome without deletions, whereas rho- and beta(H)-mRNA was activated in K562 cells containing chicken chromosomes with deletions of the intergenic enhancers, 5'-HS1 and 5'-HS2. Transcriptional activation of the rho- and beta(H)-globin genes correlated with hyperacetylation of histones H3 and H4, loss of histone H3 lysine 9 methylation, and binding of RNA polymerase II to the gene promoters. Surprisingly, the status of CpG dinucleotide methylation at the promoters did not correlate with the transcriptional status of the genes. Our results using a chromosomal transfer assay demonstrate an identical silencing function for these regulatory elements, which suggests they function as part of a common silencing pathway or complex. C1 Oregon Hlth Sci Univ, Dept Med, Oregon Canc Inst, Ctr Hematol Malignancies, Portland, OR 97239 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Epner, EM (reprint author), Oregon Hlth Sci Univ, Dept Med, Oregon Canc Inst, Ctr Hematol Malignancies, Portland, OR 97239 USA. EM epnere@ohsu.edu RI Aladjem, Mirit/G-2169-2010 OI Aladjem, Mirit/0000-0002-1875-3110 FU NIDDK NIH HHS [DK56798] NR 58 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 17 PY 2005 VL 280 IS 24 BP 23340 EP 23348 DI 10.1074/jbc.M501161200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934XB UT WOS:000229741800093 PM 15824098 ER PT J AU Kang, SU Shi, ZD Worthy, KM Bindu, LK Dharmawardana, PG Choyke, SJ Bottaro, DP Fisher, RJ Burke, TR AF Kang, SU Shi, ZD Worthy, KM Bindu, LK Dharmawardana, PG Choyke, SJ Bottaro, DP Fisher, RJ Burke, TR TI Examination of phosphoryl-mimicking functionalities within a macrocyclic Grb2 SH2 domain-binding platform SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PHOSPHOTYROSYL MIMETICS; SIGNAL-TRANSDUCTION; OLEFIN METATHESIS; PHOSPHINIC ACIDS; DESIGN; AFFINITY; LIGANDS; INHIBITORS; KINASE AB Reported herein are the design, synthesis, and Grb2 SH2 domain-binding affinities of several phosphoryl-mimicking groups displayed within the context of a conformationally constrained macrocyclic platform. With use of surface plasmon resonance techniques, single-digit nanomolar affinities were exhibited by phosphonic acid and malonyl-containing diacidic phosphoryl mimetics (for 4h and 4g, K-D = 1.47 and 3.62 nM, respectively). Analogues containing monoacidic phosphoryl mimetics provided affinities of K-D = 16-67 nM. Neutral phosphoryl-mimicking groups did not show appreciable binding. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014 OI Bottaro, Donald/0000-0002-5057-5334; NR 29 TC 22 Z9 22 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 16 PY 2005 VL 48 IS 12 BP 3945 EP 3948 DI 10.1021/jm050059m PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 935SZ UT WOS:000229805000003 PM 15943469 ER PT J AU Pettit, GR Rhodes, MR Herald, DL Hamel, E Schmidt, JM Pettitt, RK AF Pettit, GR Rhodes, MR Herald, DL Hamel, E Schmidt, JM Pettitt, RK TI Antineoplastic agents. 445. Synthesis and evaluation of structural modifications of (Z)- and (E)-combretastatin A-4 SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID BASIC SIDE-CHAIN; ANTIMITOTIC NATURAL-PRODUCTS; DNA TOPOISOMERASE-II; COMBRETASTATIN A-4; BIOLOGICAL EVALUATION; COMBRETUM-CAFFRUM; ANTITUMOR AGENTS; CELL-GROWTH; TUBULIN POLYMERIZATION; IN-VITRO AB A series of cis- and trans-stilbenes related to combretastatin A-4 (1a), with a variety of substituents at the X-position of the aryl B-ring, were synthesized and evaluated for inhibitory activity employing six human cancer cell lines (NCI-H460 lung carcinoma, BXPC-3 pancreas, SK-N-SH neuroblastoma, SW1736 thyroid, DU-145 prostate, and FADU pharynx-squamous sarcoma) as well as the P-388 murine lymphocyte leukemia cell line. Several of the cis-stilbene derivatives were significantly inhibitory against all cell lines used, with potencies comparable to that of the parent la. All were potent inhibitors of tubulin polymerization. The corresponding trans-stilbenes had little or no activity as tubulin polymerization inhibitors and were relatively inactive against the seven cancer cell lines. In terms of inhibition of both cancer cell growth and tubulin polymerization, the dimethylamino and bromo cis-stilbenes were the most potent of the new derivatives, the latter having biological activity approaching that of la. As part of the present study, the X-ray crystal structure of the 3'-O-phosphate of combretastatin A-4 (1b) was successfully elucidated. Compound 1b has been termed the "combretastatin A-4 prodrug", and it is currently undergoing clinical trials for the treatment of human cancer patients. C1 Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA. RP Pettit, GR (reprint author), Arizona State Univ, Canc Res Inst, POB 872404, Tempe, AZ 85287 USA. EM bpettit@asu.edu FU NCI NIH HHS [CA44344-06-12, R01CA90441-01] NR 98 TC 104 Z9 106 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 16 PY 2005 VL 48 IS 12 BP 4087 EP 4099 DI 10.1021/jm0205797 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 935SZ UT WOS:000229805000016 PM 15943482 ER PT J AU Agol, VI Chumakov, K Ehrenfeld, E Wimmer, E AF Agol, VI Chumakov, K Ehrenfeld, E Wimmer, E TI Don't drop current vaccine until we have new ones SO NATURE LA English DT Letter C1 Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIAID, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Sch Med, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. RP Agol, VI (reprint author), Russian Acad Med Sci, MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow 142782, Russia. RI Agol, Vadim/E-1941-2013 NR 1 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 16 PY 2005 VL 435 IS 7044 BP 881 EP 881 DI 10.1038/435881b PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935RN UT WOS:000229799700018 PM 15959489 ER PT J AU Dasso, M AF Dasso, M TI Cell biology - New cog for a familiar machine SO NATURE LA English DT Editorial Material ID MITOTIC SPINDLE; COMPLEX C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 18,Room 106, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 NR 8 TC 6 Z9 6 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 16 PY 2005 VL 435 IS 7044 BP 899 EP 900 DI 10.1038/435899a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935RN UT WOS:000229799700031 PM 15959504 ER PT J AU Turner, MJ Kleeberger, SR Lightfoot, JT AF Turner, MJ Kleeberger, SR Lightfoot, JT TI Influence of genetic background on daily running-wheel activity differs with aging SO PHYSIOLOGICAL GENOMICS LA English DT Article DE average daily activity; body weight; broad-sense heritability; inbred mice ID IN-HOUSE MICE; INBRED MOUSE STRAINS; PHYSICAL-ACTIVITY; VOLUNTARY ACTIVITY; MUS-DOMESTICUS; EXERCISE; PERFORMANCE; AGE; LONGEVITY; SELECTION AB In humans, physical activity declines with age. We tested the hypothesis that genetic background and age interact to determine daily wheel-running physical activity patterns in mice. Five female mice from ten inbred strains (A/J, AKR/J, Balb/cJ, CBA/J, C3H/HeJ, C3Heb/FeJ, C57B1/6J, C57L/J, DBA/2J, and SWR/J) were studied for 26 wk starting at 10 wk of age. All mice were housed in separate cages, each with a running wheel and magnetic sensor. Throughout the 26-wk period, age-related change in daily duration ( P < 0.0001), daily distance ( P < 0.0001), and average velocity (P = 0.0003) differed between the inbred strains. Unlike the other strains, SWR/J mice increased their running-wheel activity throughout the 6-mo time period. Broad-sense heritability estimations for the strains across the 26-wk period ranged between 0.410 and 0.855 for the three physical activity phenotypes. Furthermore, the broad-sense heritability estimates for daily running-wheel distance differed across time and suggested an interaction between genetic background and age on physical activity in these inbred mice. C1 Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA. NIEHS, Lab Resp Biol, Durham, NC USA. RP Turner, MJ (reprint author), Univ N Carolina, Dept Kinesiol, Charlotte, NC 28223 USA. EM miturner@uncc.edu FU NIA NIH HHS [AG-022417]; NIDDK NIH HHS [DK-61635] NR 35 TC 53 Z9 54 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN 16 PY 2005 VL 22 IS 1 BP 76 EP 85 DI 10.1152/physiolgenomics.00243.2004 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 952FC UT WOS:000230987700009 PM 15855385 ER PT J AU Ghorbel, MT Becker, KG Henley, JM AF Ghorbel, MT Becker, KG Henley, JM TI Profile of changes in gene expression in cultured hippocampal neurones evoked by the GABA(B) receptor agonist baclofen SO PHYSIOLOGICAL GENOMICS LA English DT Article DE cDNA microarrays; G protein-coupled receptor; hippocampus; gamma-aminobutyric acid ID GAMMA-AMINOBUTYRIC-ACID; LONG-TERM-MEMORY; NEUROTROPHIC FACTOR; TRANSCRIPTION FACTORS; CDNA MICROARRAYS; NERVOUS-SYSTEM; B-RECEPTORS; DNA ARRAYS; BRAIN; INHIBITION AB Metabotropic gamma-aminobutyric acid receptors (GABA(B)Rs) play a critical role in inhibitory synaptic transmission in the hippocampus. However, little is known about a possible long-term effect requiring transcriptional changes. Here, using microarray technology and RT-PCR of RNA from cultured rat embryonic hippocampal neurones, we report the profile of genes that are up- or downregulated by activation of GABABRs by baclofen but are not changed by baclofen in the presence of the GABA(B)R antagonist CGP-55845A. Our data show, for the first time, regulation of transcription of defined mRNAs after specific GABA(B) receptor activation. The identified genes can be grouped into those encoding signal transduction, endocytosis/trafficking, and structural classes of proteins. For example, butyrylcholinesterase, brain-derived neurotrophic factor, and COPS5 (Jab1) genes were upregulated, whereas Rab8 interacting protein and Rho GTPase-activating protein 4 were downregulated. These results provide important baseline genomic data for future studies aimed at investigating the long-term effects of GABA(B)R activation in neurones such as their roles in neuronal growth, pathway formation and stabilization, and synaptic plasticity. C1 Univ Bristol, Sch Med Sci, Dept Anat, Med Res Council Ctr Synapt Plastic, Bristol BS8 1TD, Avon, England. NIA, DNA Array Unit, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Henley, JM (reprint author), Univ Bristol, Sch Med Sci, Dept Anat, Med Res Council Ctr Synapt Plastic, Bristol BS8 1TD, Avon, England. EM j.m.henley@bris.ac.uk RI Henley, Jeremy/A-2776-2009; OI Becker, Kevin/0000-0002-6794-6656; Henley, Jeremy/0000-0003-3589-8335 FU Intramural NIH HHS; Medical Research Council [G9629038]; Wellcome Trust [, 074017] NR 48 TC 18 Z9 19 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN 16 PY 2005 VL 22 IS 1 BP 93 EP 98 DI 10.1152/physiolgenomics.00202.2004 PG 6 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 952FC UT WOS:000230987700011 PM 15784695 ER PT J AU Cho, HY Jedlicka, AE Clarke, R Kleeberger, SR AF Cho, HY Jedlicka, AE Clarke, R Kleeberger, SR TI Role of Toll-like receptor-4 in genetic susceptibility to lung injury induced by residual oil fly ash SO PHYSIOLOGICAL GENOMICS LA English DT Article DE particle; inbred mice; heritability; nuclear factor-kappa B; activator protein-1 ID ENHANCED ALLERGIC SENSITIZATION; DIESEL EXHAUST PARTICLES; NF-KAPPA-B; AIR-POLLUTION; PARTICULATE MATTER; EPITHELIAL-CELLS; INNATE IMMUNITY; LIPOPOLYSACCHARIDE; MICE; EXPOSURE AB The mechanisms of susceptibility to particle-induced lung injury are not clearly understood. To evaluate the contribution of genetic background to pulmonary pathogenesis, we compared the lung injury responses to residual oil fly ash ( ROFA) in inbred mouse strains and calculated heritability estimates. Significant interstrain ( genetic) variation was observed in ROFA-induced lung inflammation and hyperpermeability phenotypes; broad-sense heritability ranged from similar to 0.43 to 0.62, and the coefficient of genetic determination ranged from 0.28 to 0.45. C3H/HeJ (HeJ) mice were most resistant to the ROFA-induced injury responses. This was particularly important, as HeJ mice contain a dominant negative mutation in Toll-like receptor-4 (Tlr4). We then characterized ROFA-induced injury and TLR4 signaling in HeJ mice and its coisogenic strain C3H/HeOuJ (OuJ; Tlr4 normal) to understand the potential role of Tlr4 in this model. ROFA-induced lung injury was significantly greater in OuJ mice compared with HeJ mice. ROFA also significantly enhanced transcript and protein levels of lung TLR4 in OuJ but not in HeJ mice. Greater activation of downstream signal molecules (i.e., MYD88, TRAF6, IRAK-1, NF-kappa B, MAPK, AP-1) was observed in OuJ mice than in HeJ mice before the development of ROFA-induced pulmonary injury. Putative TLR4-dependent inflammatory genes that were differentially induced by ROFA in the two strains include interleukin-1 beta and tumor necrosis factor-alpha. Results support an important contribution of genetic background to particle-mediated lung injury, and Tlr4 is a candidate susceptibility gene. C1 NIEHS, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Pulmatrix Inc, Cambridge, MA 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 NIEHS NIH HHS [ES-09609, P30ES-00002] NR 46 TC 22 Z9 27 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD JUN 16 PY 2005 VL 22 IS 1 BP 108 EP 117 DI 10.1152/physiolgenomics.00037.2005 PG 10 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 952FC UT WOS:000230987700013 PM 15784698 ER PT J AU Harris-Love, MO AF Harris-Love, MO TI Safety and efficacy of submaximal eccentric strength training for a subject with polymyositis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID MUSCLE STRENGTH; EXERCISE; DERMATOMYOSITIS; CONTRACTIONS; ADAPTATION C1 NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Harris-Love, MO (reprint author), NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Dept Hlth & Human Serv, 10 Ctr Dr,Bldg 10,Room 1-1469, Bethesda, MD 20892 USA. EM mlove@nih.gov RI Harris-Love, Michael/J-1359-2014 OI Harris-Love, Michael/0000-0002-1842-3269 NR 15 TC 24 Z9 25 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD JUN 15 PY 2005 VL 53 IS 3 BP 471 EP 474 DI 10.1002/art.21185 PG 4 WC Rheumatology SC Rheumatology GA 933RV UT WOS:000229651500025 PM 15934111 ER PT J AU Dobbin, KK Shih, JH Simon, RM AF Dobbin, KK Shih, JH Simon, RM TI Comment on 'Evaluation of the gene-specific dye bias in cDNA microarray experiments SO BIOINFORMATICS LA English DT Letter ID DESIGNS C1 NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. RP Dobbin, KK (reprint author), NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NR 7 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 15 PY 2005 VL 21 IS 12 BP 2803 EP 2804 DI 10.1093/bioinformatics/bti428 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 937OE UT WOS:000229934600001 PM 15817695 ER PT J AU Anantharaman, V Aravind, L AF Anantharaman, V Aravind, L TI MEDS and PocR are novel domains with a predicted role in sensing simple hydrocarbon derivatives in prokaryotic signal transduction systems SO BIOINFORMATICS LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; PROTEIN SECONDARY STRUCTURE; SALMONELLA-TYPHIMURIUM; REGULATORY PROTEIN; RECEPTORS; BACTERIAL; DATABASE; EVOLUTION; COMMON; ANCIENT AB We identify two conserved domains in diverse bacterial and archaeal signaling proteins. One of them, the MEDS domain, is typified by the DmcR protein from Methylococcus and the other by the PocR protein of Salmonella typhi. We provide evidence that both these domains are likely to sense simple hydrocarbon derivatives and transduce downstream signals on binding these ligands. The PocR ligand-binding domain is shown to contain a novel variant of the fold found in PAS and GAF domains. The MEDS domain is present in both methylotrophs and complex methanogens, and both the MEDS and PocR domains show a lineage-specific expansion in the latter organisms, suggesting a role in sensing their principle growth substrates. The MEDS domain is also found in the negative regulators of the sigma factor SigB in actinomycetes, including pathogens like Mycobacterium tuberculosis. Hence it is possible that these sigma factors, involved in aerial mycelium development and stress response in the actinomycetes, might be under the regulation of as yet uncharacterized small molecules. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM aravind@ncbi.nlm.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 NR 32 TC 13 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN 15 PY 2005 VL 21 IS 12 BP 2805 EP 2811 DI 10.1093/bioinformatics/bti418 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 937OE UT WOS:000229934600002 PM 15814558 ER PT J AU Bertolino, A Arciero, G Rubino, V Latorre, V De Candia, M Mazzola, V Blasi, G Caforio, G Hariri, A Kolachana, B Nardini, M Weinberger, DR Scarabino, T AF Bertolino, A Arciero, G Rubino, V Latorre, V De Candia, M Mazzola, V Blasi, G Caforio, G Hariri, A Kolachana, B Nardini, M Weinberger, DR Scarabino, T TI Variation of human amygdala response during threatening stimuli as a function of 5'HTTLPR genotype and personality style SO BIOLOGICAL PSYCHIATRY LA English DT Article DE fear; amygdala; fMRI; genetic factors; personality style; serotonin transporter genotype ID FACIAL EXPRESSIONS; FEAR; POLYMORPHISM; GENE; FMRI; ANXIETY; BRAIN; ATTACHMENT; DISORDERS; KNOWLEDGE AB Background: In the brain, processing of fearful stimuli engages the amygdala, and the variability of its activity is associated with genetic factors as well as with emotional salience. The objective of this study was to explore the relevance of personality style for variability of amygdala response. Methods. We studied two groups (n = 14 in each group) of healthy subjects categorized by contrasting cognitive styles with which they attribute salience to fearful stimuli: so-called phobic prone subjects who exaggerate potential environmental threat versus so-called eating disorders prone subjects who tend to be much, less centered around fear. The two groups underwent functional magnetic resonance imaging (fMRI) at 3T during performance of a perceptual task of threatening stimuli and they were also matched for the genotype of the 5'variable number tandem repeat (VNTR) polymorphism in the serotonin transporter Results. The fMRI results indicated that phobic prone results indicated that phobic prone subjects selectively recruit the amygdala to a larger extent than eating disorders prone subjects. Activity in the amygdala was also independently predicted by personality style and genotype of the serotonin transporter. Moreover, brain activity during a working memory task did not differentiate the two groups. Conclusions. The results of the present study suggest that aspects of personality style are rooted in biological responses of the fear circuitry associated with processing of environmental information. C1 Univ Bari, Dipartimento Sci Neurol & Psichiatriche, Sect Mental Disorders, I-70124 Bari, Italy. Univ Bari, Psychiat Neurosci Grp, I-70124 Bari, Italy. Ist Psicoterapia & Postrazionalista, Rome, Italy. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. IRCCS Casa Sollievo Sofferenza, Dept Neuroradiol, San Giovanni Rotondo, Italy. Univ Pittsburgh, Sch Med, Dept Psychiat, Dev Imaging Genom Program, Pittsburgh, PA USA. RP Bertolino, A (reprint author), Univ Bari, Dipartimento Sci Neurol & Psichiatriche, Sect Mental Disorders, Piazza Giulio Cesare,9, I-70124 Bari, Italy. EM bertolia@psichiat.uniba.it RI Hariri, Ahmad/D-5761-2011; Bertolino, Alessandro/O-6352-2016 OI Bertolino, Alessandro/0000-0002-1251-1380 NR 58 TC 143 Z9 148 U1 3 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2005 VL 57 IS 12 BP 1517 EP 1525 DI 10.1016/j.biopsych.2005.02.031 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 938MO UT WOS:000230007700007 PM 15953488 ER PT J AU Gorelick, DA Kim, YK Bencherif, B Boyd, SJ Nelson, R Copersino, M Endres, CJ Dannals, RF Frost, JJ AF Gorelick, DA Kim, YK Bencherif, B Boyd, SJ Nelson, R Copersino, M Endres, CJ Dannals, RF Frost, JJ TI Imaging brain mu-opioid receptors in abstinent cocaine users: Time course and relation to cocaine craving SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 23rd Collegium-Internationale-Neuro-Psychopharmacologium Congress (CINP) CY JUN 23, 2002 CL MONTREAL, CANADA DE cocaine; craving; mu-opioid receptor; PETscan; carfentanil; abstinence ID MESSENGER-RNA LEVELS; NUCLEUS-ACCUMBENS; DIFFERENTIAL REGULATION; GENE-EXPRESSION; REWARD REGIONS; RAT CNS; STRIATUM; BINDING; PROENKEPHALIN; DEPENDENCE AB Background: Cocaine treatment upregulates brain mu-opioid receptors (mOR) in animals. Human data regarding this phenomenon are limited. We previously used positron emission tomography (PET) with [C-11]-carfentanil to show increased mOR binding in brain regions of 10 cocaine-dependent men after 1 and 28 days of abstinence. Methods: Regional brain mOR binding potential (BP) was measured with [C-11]carfentanil PET scanning in 17 cocaine users over 12 weeks of abstinence on a research ward and in 16 healthy control subjects. Results. Mu-opioid receptor BP was increased in the frontal, anterior cingulate, anti lateral temporal cortex after 1 day of abstinence. Mu-opioid receptor BP remained elevated in the first two regions after I week and in the anterior cingulate and anterior frontal cortex after 12 weeks. Increased binding in some regions at 1 day and 1 week was positively correlated with self-reported cocaine craving. Mu-opioid receptor BP was significantly correlated with percentage of days with cocaine use and amount of cocaine used per day of use during the 2 weeks before admission and with urine benzoylecgonine concentration at the first PET scan. Conclusions. These results suggest that chronic cocaine use influences endogenous opioid systems in the human brain and might explain mechanisms of cocaine craving and reinforcement. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Radiol Sci, Baltimore, MD 21205 USA. RP Gorelick, DA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS; NIDA NIH HHS [R01 DA-09479] NR 57 TC 86 Z9 91 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 15 PY 2005 VL 57 IS 12 BP 1573 EP 1582 DI 10.1016/j.biopsych.2005.02.026 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 938MO UT WOS:000230007700014 PM 15953495 ER PT J AU Gilbert, DL Sallee, FR Zhang, J Lipps, TD Wassermann, EM AF Gilbert, DL Sallee, FR Zhang, J Lipps, TD Wassermann, EM TI Transcranial magnetic stimulation-evoked cortical inhibition: A consistent marker of attention-deficit/hyperactivity disorder scores in Tourette syndrome SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Advancing the Neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD) CY FEB 28, 2004 CL Boston, MA DE motor evoked potential; transcranial magnetic stimulation; biological marker; ADHD; children ID DEFICIT-HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE SCALE; MOTOR CORTEX; TIC DISORDER; CHILDREN; EXCITABILITY; RELIABILITY; SEVERITY AB Background: Prior case-control studies using Transcranial Magnetic Stimulation (TMS) to probe the neural inhibitory circuitry of Attention Deficit Hyperactivity Disorder (ADHD), Tourette Syndrome (TS), and Obsessive Compulsive Disorder (OCD), have yielded conflicting results. Using regression analysis in TS patients with tics, ADHD, and/or OCD symptoms, all ranging from none to severe, we previously found that TMS-evoked short interval intracortical inhibition (SICI) correlated inversely with ADHD scores. We sought to validate this observation. Methods. We used regression to estimate the consistency of the association between ADHD symptom scores and TMS-evoked SICI at two separate visits in 28 children and adults with TS. Results. ADHD scores correlated significantly and consistently with SICI, particularly in patients not taking dopamine receptor blockers (r =.60 and r =.58). Hyperactivity, not inattention, scores accounted for ADHD-related variance in SICI. Conclusions. SICI reliably reflects the severity of hyperactivity in children and adults with TS. C1 Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. Univ Cincinnati, Div Psychiat, Cincinnati, OH USA. NINDS, Brain Stimulat Unit, Bethesda, MD 20892 USA. RP Gilbert, DL (reprint author), Childrens Hosp, Med Ctr, Div Neurol, ML 11006,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM d.gilbert@cchmc.org RI Gilbert, Donald/D-6443-2016 OI Gilbert, Donald/0000-0002-9245-6878 FU NINDS NIH HHS [K23 NS41920] NR 16 TC 51 Z9 54 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 JUN 15 PY 2005 VL 57 IS 12 BP 1597 EP 1600 DI 10.1016/j.biopsych.2005.02.022 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 938MO UT WOS:000230007700018 PM 15953499 ER PT J AU Davis, DA Singer, KE Sierra, MD Narazaki, M Yang, FQ Fales, HM Yarchoan, R Tosato, G AF Davis, DA Singer, KE Sierra, MD Narazaki, M Yang, FQ Fales, HM Yarchoan, R Tosato, G TI Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1 alpha in the circulation SO BLOOD LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; FACTOR-I; BONE-MARROW; LYMPHOCYTE CHEMOATTRACTANT; BRADYKININ RECEPTORS; HUMAN-PLASMA; SDF-1; HIV-1; CLONING; MOBILIZATION AB The chemokine stromal-derived factor-1 alpha (SDF-1 alpha) is an essential regulator of hematopoiesis, lymphocyte homing, pre-B-cell growth, and angiogenesis. As SDF-1 alpha is constitutively expressed in many tissues, chemokine function is mostly regulated by proteolytic degradation. Human serum cleaves the 68-amino acid chemokine, SDF-1 alpha, at both termini. The enzyme or enzymes responsible for the removal of the carboxy-terminal lysine from SDF-1 alpha, leading to significant reduction in biologic activity, have not been identified. Using a new biochemical assay for measuring the carboxy-terminal cleavage activity, we purified from serum and plasma a peptidase that specifically removes the carboxy-terminal lysine from SDF-1 alpha and identified it as carboxypeptidase N (CPN, also known as kininase 1, arginine carboxypeptidase, and anaphylotoxin inactivator). We demonstrate that SDF-1 alpha in serum and plasma lacks the carboxy terminal lysine, and depletion of CPN from serum and plasma significantly reduces the SDF-1 alpha carboxylpeptidase activity. Purified CPN effectively and specifically removes the carboxy-terminal lysine from SDF-1 alpha and significantly reduces the chemokine's biologic activity as a pre-B-cell growth factor and chemoattractant. Thus, in addition to its role as a regulator of the biologic activity of kinins and anaphylatoxins, CPN is an important regulator of the biologic activity of SDF-1 alpha, by reducing the chemokine-specific activity. (c) 2005 by The American Society of Hematology. C1 NCI, HIV & AIDS Malignancy Branch, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, HIV & AIDS Malignancy Branch, Expt Transplantat & Immunol Branch, NIH, Bldg 10,Rm 105255,9000 Rockville Pl, Bethesda, MD 20892 USA. EM dd162w@nih.gov NR 55 TC 68 Z9 68 U1 2 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2005 VL 105 IS 12 BP 4561 EP 4568 DI 10.1182/blood-2004-12-4618 PG 8 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300013 PM 15718415 ER PT J AU Erdmann, AA Gao, ZG Jung, U Foley, J Borenstein, T Jacobson, KA Fowler, DH AF Erdmann, AA Gao, ZG Jung, U Foley, J Borenstein, T Jacobson, KA Fowler, DH TI Activation of Th1 and Tc1 cell adenosine A(2A) receptors directly inhibits IL-2 secretion in vitro and IL-2-driven expansion in vivo SO BLOOD LA English DT Article ID VERSUS-HOST DISEASE; T-CELLS; INFLAMMATION; LYMPHOCYTES; RAT; INTERLEUKIN-2; CYTOTOXICITY; PROTECTION; ADHESION; SUBSETS AB To evaluate the direct effect of adenosine on cytokine-polarized effector T cells, murine type 1 helper T cells (Th1) and type 1 cytotoxic T lymphocytes (Tc1) and Th2/Tc2 cells were generated using an antigen-presenting cell (APC)-free method. Tc1 and Tc2 cells had similar adenosine signaling, as measured by intracellular cyclic AMP (cAMP) increase upon adenosine A(2A) receptor agonism by CGS21680 (CGS). CGS greatly reduced Tc1 and Tc2 cell interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-alpha) secretion, with nominal effect on interferon gamma (IFN-gamma) secretion. Tc2 cell IL-4 and IL-5 secretion was not reduced by CGS, and IL-10 secretion was moderately reduced. Agonist-mediated inhibition of IL-2 and TNF-alpha secretion occurred via A(2A) receptors, with no involvement of A(1), A(2B), or A(3) receptors. Adenosine agonist concentrations that abrogated cytokine secretion did not inhibit Tc1 or Tc2 cell cytolytic function. Adenosine modulated effector T cells in vivo, as CGS administration reduced CD4(+)Th1 and CD8(+)Tc1 cell expansion to alloantigen and, in a separate model, reduced antigen-specific CD4(+)Th1 cell numbers. Remarkably, agonist-mediated T-cell inhibition was abrogated by in vivo IL-2 therapy. Adenosine receptor activation therefore preferentially inhibits type I cytokine secretion, most notably IL-2. Modulation of adenosine receptors may thus represent a suitable target primarily for inflammatory conditions mediated by Th1 and Tc1 cells. (c) 2005 by The American Society of Hematology. C1 NCI, NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NCI, NIH, Expt Transplantat & Immunol Branch, 9000 Rockville Pike,Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 33 TC 71 Z9 78 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2005 VL 105 IS 12 BP 4707 EP 4714 DI 10.1182/blood-2004-04-1407 PG 8 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300035 PM 15746085 ER PT J AU Eissmann, P Beauchamp, L Wooters, J Tilton, JC Long, EO Watzl, C AF Eissmann, P Beauchamp, L Wooters, J Tilton, JC Long, EO Watzl, C TI Molecular basis for positive and negative signaling by the natural killer cell receptor 2B4 (CD244) SO BLOOD LA English DT Article ID LINKED LYMPHOPROLIFERATIVE-DISEASE; PROTEIN-TYROSINE-PHOSPHATASE; GENE-PRODUCT SAP/SH2D1A; CUTTING EDGE; T-CELLS; HOMOPHILIC INTERACTION; IMMUNE RECEPTORS; SURFACE-MOLECULE; ENCODING GENE; SLAM FAMILY AB Triggering of 2B4 (CD244) can induce natural killer (NK)-cell activation, costimulation, or even inhibition of NK-cell activity. Here, we investigate the molecular basis for the different signals generated by 2B4. We show that the first immunoreceptor tyrosine-based switch motif (ITSM) within the cytoplasmic tail of 2B4 is sufficient for 2B4-mediated NK-cell activation, whereas the third ITSM can negatively influence 2B4 signaling. We further identify signaling molecules that associate with 2B4. Signaling lymphocyte activation molecule-associated protein (SAP) can bind to all 4 ITSMs of 2B4 in a phosphorylation-dependent manner. The phosphorylated third ITSM can additionally recruit the phosphatases SHP-1, SHP-2, SHIP, and the inhibitory kinase Csk. SAP acts as an inhibitor of interactions between 2B4 and these negative regulatory molecules, explaining how 2B4 inhibits NK-cell activation in the absence of functional SAP, as occurs in cells from patients with X-linked lymphoproliferative syndrome (XLP). Recently, another function for SAP was proposed: SAP can recruit the kinase Fyn to the SLAM (CD150) immune receptor. We now show that Fyn can also associate with phosphorylated 2B4. Finally, we demonstrate that Fyn and Csk can both phosphorylate 2B4, suggesting a possible mechanism of 2B4 phosphorylation. (c) 2005 by The American Society of Hematology. C1 Univ Heidelberg, Inst Immunol, D-69120 Heidelberg, Germany. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Wyeth Res, Cambridge, England. RP Watzl, C (reprint author), Univ Heidelberg, Inst Immunol, INF 305, D-69120 Heidelberg, Germany. EM carsten.watzl@urz.uni-heidelberg.de RI Watzl, Carsten/B-4911-2013; Long, Eric/G-5475-2011 OI Watzl, Carsten/0000-0001-5195-0995; Long, Eric/0000-0002-7793-3728 NR 52 TC 118 Z9 121 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2005 VL 105 IS 12 BP 4722 EP 4729 DI 10.1182/blood-2004-09-3796 PG 8 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300037 PM 15713798 ER PT J AU Jolly, PS Bektas, M Watterson, KR Sankala, H Payne, SG Milstien, S Spiegel, S AF Jolly, PS Bektas, M Watterson, KR Sankala, H Payne, SG Milstien, S Spiegel, S TI Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors SO BLOOD LA English DT Article ID PROTEIN-COUPLED RECEPTORS; SPHINGOSINE 1-PHOSPHATE RECEPTORS; SPHINGOSINE-1-PHOSPHATE RECEPTORS; LYMPHOID ORGANS; SMOOTH-MUSCLE; KINASE; ACTIVATION; GROWTH; PDGF; MIGRATION AB Mast cells play a central role in inflammatory and immediate-type allergic reactions by secreting a variety of biologically active substances, including sphingosine-1 phosphate (S1P). Sphingosine kinase 1 (SphK1) and formation of S1P, which leads to transactivation of S1P receptors and their downstream signaling pathways, regulates mast-cell functions initiated by cross-linking of the high-affinity immunoglobulin E (IgE) receptor FC epsilon RI. Surprisingly, overexpression of SphK1 in rat basophilic leukemia (RBL)-2H3 mast cells impaired degranulation as well as migration toward antigen. These effects were reversed by serum withdrawal, yet the increased formation and secretion of S1P were the same as in the presence of serum. Nonetheless, serum increased localization of SphK1 at the plasma membrane. This restricted formation of S1P induced internalization and desensitization of S1P receptors on the surface of mast cells as determined by confocal immunofluorescence microscopy, aberrant S1P receptor signaling, and lack of S1P receptor coupling to G proteins. Serum starvation, which significantly reduced membrane-associated SphK1 activity, restored S1P receptor functions. Our results have important implications for mast-cell migration and degranulation as well as for the biologic functions of the S1P receptors on cells that are circulating in the bloodstream. (c) 2005 by The American Society of Hematology. C1 Virginia Commonwealth Univ, Ctr Med, Dept Biochem, Richmond, VA 23298 USA. Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Ctr Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu FU NCI NIH HHS [P30 CA16059]; NIAID NIH HHS [AIS0094] NR 36 TC 48 Z9 51 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2005 VL 105 IS 12 BP 4736 EP 4742 DI 10.1182/blood-2004-12-4686 PG 7 WC Hematology SC Hematology GA 935CQ UT WOS:000229757300039 PM 15741218 ER PT J AU Shuangshoti, S Rushing, EJ Mena, H Olsen, C Sandberg, GD AF Shuangshoti, S Rushing, EJ Mena, H Olsen, C Sandberg, GD TI Supratentorial extraventricular ependymal neoplasms - A clinicopathologic study of 32 patients SO CANCER LA English DT Article DE supratentorial; ependymoma; Ki-67; p53; ploidy; prognosis ID CLEAR-CELL EPENDYMOMA; P53 GENE-MUTATIONS; INTRACRANIAL EPENDYMOMAS; PROGNOSTIC RELEVANCE; ASTROCYTIC TUMORS; EXPRESSION; SURVIVAL; GRADE; PROLIFERATION; ASTROBLASTOMA AB BACKGROUND. Published research on the clinicopathologic features of extraventricular ependymal neoplasms of the cerebral hemispheres has been scant. METHODS. Thirty-two archival cases were studied to investigate the prognostic impact of clinicopathologic parameters including flow cytometry, the proliferation (Ki-67) labeling index, and p53 expression. RESULTS. Among these 32 cases were 2 subependymornas, 19 ependymomas, and 11 anaplastic ependymomas. No significant gender predilection was observed, and 45% of patients were in their second or third decade of life. The left cerebral hemisphere was 1.5 times more commonly involved. On available imaging studies, lesions were often cystic, with or without a mural nodule. Tumors expressed glial fibrillary acidic protein (87%), S-100 protein (77%), cytokeratin (43%), and epithelial membrane antigen (17%). Ki-67 proliferation index paralleled tumor grade. Immunoreactivity for p53 protein was observed in the 2 cases of subependymoma, in 10 of 11 anaplastic ependymomas, and in 6 of 17 ependymomas. Flow cytometry performed in 27 tumors revealed diploidy in 20 cases and aneuploidy in 4 cases (3 anaplastic and I classic ependymomas), with S-phase fraction ranging from 0.29.7. Eleven subjects were additionally treated with radiotherapy, and 3 with chemotherapy. Follow up was available in 25 (78%) patients. CONCLUSIONS. The results of the current study suggest that there is no significant relation between histopathology, Ki-67 proliferation index, p53 immunolabeling, tumor ploidy, and biologic behavior. Published 2005 by the American Cancer Society. C1 Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. Clin Brain Disorders Branch, Sect Neuropathol, NIH, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. RP Sandberg, GD (reprint author), Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, 16th St & Alaska Ave NW,Bldg 54, Washington, DC 20306 USA. EM sandberg@afip.osd.mil NR 35 TC 30 Z9 36 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 15 PY 2005 VL 103 IS 12 BP 2598 EP 2605 DI 10.1002/cncr.21111 PG 8 WC Oncology SC Oncology GA 933IT UT WOS:000229622800021 PM 15861411 ER PT J AU Risinger, JI Maxwell, GL Chandramouli, GVR Aprelikova, O Litzi, T Umar, A Berchuck, A Barrett, JC AF Risinger, JI Maxwell, GL Chandramouli, GVR Aprelikova, O Litzi, T Umar, A Berchuck, A Barrett, JC TI Gene expression profiling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling SO CANCER RESEARCH LA English DT Article ID DNA MISMATCH REPAIR; RECEPTOR-TYPE-II; COLORECTAL-CANCER; PROMOTER HYPERMETHYLATION; INSTABILITY PHENOTYPE; CARCINOMA; MLH1; TUMORS; CONSEQUENCES; METHYLATION AB Microsatellite instability (NISI) is a molecular phenotype present in similar to 25% of endometrial cancers. We examined the global gene expression profiles of early-stage endometrioid endometrial cancers with and without the MSI phenotype to test the hypothesis that MSI phenotype may determine a unique molecular signature among otherwise similar cancers. Unsupervised principal component analysis of the expression data from these cases indicated two distinct groupings of cancers based on MSI phenotype. A relatively small number of array features (392) at high statistical value (P < 0.001) were identified that drive the instability signature in these cancers; 109 of these transcripts differed by at least 2-fold. These data identify distinct gene expression profiles for MSI and micro-satellite stable (MSS) cancers, which suggest that cancers with MSI develop in part by different mechanisms from their similar stable counterparts. In particular, we found evidence that two members of the secreted frizzled related protein family (SFRP1 and SFRP4) were more frequently down-regulated in MSI cancers as compared with MSS cancers. Down-regulation was accompanied by promoter hypermethylation for SFRP1. SFRP1 was hypermethylated in 8 of 12 MSI cancers whereas only 3 of 16 MSS cancers were methylated. The WNT target fibroblast growth factor 18 was found to be up-regulated in MSI cancers. These data classify histologically similar endometrioid endometrial cancers into two distinct groupings with implications affecting therapy and prevention. C1 NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Duke Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Durham, NC USA. RP Risinger, JI (reprint author), NCI, Lab Biosyst & Canc, NIH, Room 5046,Bldg 37,9000 Rockville Pike,MSC 4264, Bethesda, MD 20892 USA. EM risingej@mail.nih.gov NR 41 TC 34 Z9 36 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 JUN 15 PY 2005 VL 65 IS 12 BP 5031 EP 5037 DI 10.1158/0008-5472.CAN-04-0850 PG 7 WC Oncology SC Oncology GA 934UN UT WOS:000229734300012 PM 15958545 ER PT J AU Docquier, F Farrar, D D'Arcy, V Chernukhin, I Robinson, AF Loukinov, D Vatolin, S Pack, S Mackay, A Harris, RA Dorricott, H O'Hare, MJ Lobanenkov, V Klenova, E AF Docquier, F Farrar, D D'Arcy, V Chernukhin, I Robinson, AF Loukinov, D Vatolin, S Pack, S Mackay, A Harris, RA Dorricott, H O'Hare, MJ Lobanenkov, V Klenova, E TI Heightened expression of CTCF in breast cancer cells is associated with resistance to apoptosis SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; ZINC-FINGER FACTOR; C-MYC; DIFFERENTIAL EXPRESSION; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTOR; MEDIATED APOPTOSIS; BCL-2 EXPRESSION; MAMMALIAN-CELLS; GENE FAMILY AB CTCF is a candidate tumor suppressor gene encoding a multifunctional transcription factor. Surprisingly for a tumor suppressor, the levels of CTCF in breast cancer cell lines and tumors were found elevated compared with breast cell lines with finite life span and normal breast tissues. In this study, we aimed to investigate the possible cause for this increase in CTCF content and in particular to test the hypothesis that up-regulation of CTCF may be linked to resistance of breast cancer cells to apoptosis. For this purpose, apoptotic cell death was monitored following alterations of CTCF levels induced by transient transfection and conditional knockdown of CTCF in various cell lines. We observed apoptotic cell death in all breast cancer cell lines examined following CTCF down-regulation. In addition, overexpression of CTCF partially protected cells from apoptosis induced by overexpression of Bax or treatment with sodium butyrate. To elucidate possible mechanisms of this phenomenon, we used a proteomics approach and observed that levels of the proapoptotic protein, Bax, were increased following CTCF down-regulation in MCF7 cells. Taken together, these results suggest that in some cellular contexts CTCF shows antiapoptotic characteristics, most likely exerting its functions through regulation of apoptotic genes. We hypothesize that CTCF overexpression may have evolved as a compensatory mechanism to protect breast cancer cells from apoptosis, thus providing selective survival advantages to these cells. The observations reported in this study may lead to development of therapies based on selective reduction of CTCF in breast cancer cells. C1 Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. Univ Oxford, Dept Biochem, Genet Unit, Oxford OX1 2JD, England. UCL, LICR, Breast Canc Lab, London, England. UCL, Dept Physiol, London, England. NIAID, Mol Pathol Sect, Immunopathol Lab, NIH, Rockville, MD 20852 USA. RP Klenova, E (reprint author), Univ Essex, Dept Biol Sci, Wivenhoe Pk,Cent Campus, Colchester CO4 3SQ, Essex, England. EM klenovae@essex.ac.uk RI Pack, Svetlana/C-2020-2014 FU Worldwide Cancer Research [99-0514] NR 51 TC 52 Z9 57 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2005 VL 65 IS 12 BP 5112 EP 5122 DI 10.1158/0008-5472.CAN-03-3498 PG 11 WC Oncology SC Oncology GA 934UN UT WOS:000229734300022 PM 15958555 ER PT J AU Filleur, S Volz, K Nelius, T Mirochnik, Y Huang, HH Zaichuk, TA Aymerich, MS Becerra, SP Yap, R Veliceasa, D Shroff, EH Volpert, OV AF Filleur, S Volz, K Nelius, T Mirochnik, Y Huang, HH Zaichuk, TA Aymerich, MS Becerra, SP Yap, R Veliceasa, D Shroff, EH Volpert, OV TI Two functional epitopes of pigment epithelial-derived factor block angiogenesis and induce differentiation in prostate cancer SO CANCER RESEARCH LA English DT Article ID CEREBELLAR GRANULE NEURONS; ENDOTHELIAL GROWTH-FACTOR; FACTOR PEDF; NEUROENDOCRINE DIFFERENTIATION; TUMOR-GROWTH; IN-VIVO; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; DIABETIC-RETINOPATHY; GENE-TRANSFER AB Pigment epithelial-derived factor (PEDF), an angiogenesis inhibitor with neurotrophic properties, balances angiogenesis in the eye and blocks tumor progression. Its neurotrophic function and the ability to block vascular leakage is replicated by the PEDF 44-mer peptide (residues 58-101). We analyzed PEDFs' three-dimensional structure and identified a potential receptor-binding surface. Seeking PEDF-based antiangiogenic agents we generated and tested peptides representing the middle and lower regions of this surface. We identified previously unknown antiangiogenic epitopes consisting of the 34-mer (residues 24-57) and a shorter proximal peptide (TGA, residues 16-26) with the critical stretch L19VEEED24 an a fragment within the 44-mer (ERT, residues 78-94), which retained neurotrophic activity. The 34-mer and TGA, but not the 44-mer reproduced PEDF angioinhibitory signals hinged on c-jun-NH2-kinase-dependent nuclear factor of activate T cell deactivation and caused apoptosis. Conversely, the FAT, but not the 34-mer/TGA induced neuronal differentiation. For the 44-mer/ERT, we showed a novel ability to cause neuroendocrine differentiation in prostate cancer cells. PEDF and the peptides bound endothelial and PC-3 prostate cancer cells. Bound peptides were displaced by PEDF, but not by each other, suggesting multiple receptors. PEDF and its active fragments blocked tumor formation when conditionally expressed by PC-3 cells. The 34- and 44-mer used distinct mechanisms: the 34-mer acted on endothelial cells, blocked angiogenesis, and induced apoptosis whereas 44-mer prompted neuroendocrine differentiation in cancer cells. Our results map active regions for the two PEDF functions, signaling via distinct receptors, identify candidate peptides, and provide their mechanism of action for future development of PEDF-based tumor therapies. C1 Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, RH Lurie Comprehens Canc Ctr, Chicago, IL 60611 USA. Univ Illinois, Dept Microbiol & Immunol, Chicago, IL 60680 USA. Otto Von Guericke Univ, Dept Urol, Magdeburg, Germany. NEI, Sect Prot Struct Funct, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD USA. RP Volpert, OV (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, Tarry Res Bldg,Ste 16-761,300 E Superior St, Chicago, IL 60611 USA. EM olgavolp@northwestern.edu FU NHLBI NIH HHS [HL 068033-04]; NIDDK NIH HHS [T32 DK 62716-02]; NIGMS NIH HHS [GM47522] NR 57 TC 120 Z9 124 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 JUN 15 PY 2005 VL 65 IS 12 BP 5144 EP 5152 DI 10.1158/0008-5472.CAN-04-3744 PG 9 WC Oncology SC Oncology GA 934UN UT WOS:000229734300025 PM 15958558 ER PT J AU Meng, LH Kohlhagen, G Liao, ZY Antony, S Sausville, E Pommier, Y AF Meng, LH Kohlhagen, G Liao, ZY Antony, S Sausville, E Pommier, Y TI DNA-protein cross-links and replication-dependent histone H2AX phosphorylation induced by aminoflavone (NSC 686288), a novel anticancer agent active against human breast cancer cells SO CANCER RESEARCH LA English DT Article ID TOPOISOMERASE-I; S-PHASE; CLEAVAGE COMPLEXES; MAMMALIAN-CELLS; ANTITUMOR AGENT; CAMPTOTHECIN; ACTIVATION; DAMAGE; DERIVATIVES; INDUCTION AB Aminoflavone (5-amino-2,3-fluorophenyl)-6,8-difluoro-7-methyl-4H-1-benzopyran-4-one) (NSC 686288) is a candidate for possible advancement to phase I clinical trial. Aminoflavone has a unique activity profile in the NCI 60 cell lines (COMPARE analysis; http://www.dtp.nci.nih.gov/docs/ dtp_search.html), and exhibits potent cellular and animal antitumor activity. To elucidate the mechanism of action of aminoflavone, we studied DNA damage in MCF-7 cells. Aminoflavone induced DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB). Aminoflavone induced high levels of DPC and much lower level of SSB than camptothecin, which induces equal levels of DPC and SSB due to the trapping topoisomerase I-DNA complexes. Accordingly, neither topoisomerase I nor topoisomerase II were detectable in the aminoflavone-induced DPC. Aminoflavone also induced dose- and time-dependent histone H2AX phosphorylation (gamma-H2AX). gamma-H2AX foci occurred with DPC formation, and like DPC, persisted after aminoflavone removal. Aphidicolin prevented gamma-H2AX formation, suggesting that gamma-H2AX foci correspond to replication-associated DNA double-strand breaks. Accordingly, no gamma-H2AX foci were found in proliferating cell nuclear antigen-negative or in mitotic cells. Bromodeoxyuridine incorporation and fluorescence-activated cell sorting analyses showed DNA synthesis inhibition uniformly throughout the S phase after exposure to aminoflavone. Aminoflavone also induced RPA2 and p53 phosphorylation, and induced p21(Waf1/Cip1) and MDM2, demonstrating S-phase checkpoint activation. These studies suggest that aminoflavone produces replication-dependent DNA lesions and S-phase checkpoint activation following DPC formation. gamma-H2AX may be a useful clinical marker for monitoring the efficacy of aminoflavone in tumor therapies. C1 Natl Canc Inst, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Pommier, Y (reprint author), Natl Canc Inst, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37,Room 5068,37 Convent Dr, Bethesda, MD 20892 USA. EM pommier@nih.gov NR 33 TC 35 Z9 37 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 15 PY 2005 VL 65 IS 12 BP 5337 EP 5343 DI 10.1158/0008-5472.CAN-05-0003 PG 7 WC Oncology SC Oncology GA 934UN UT WOS:000229734300048 PM 15958581 ER PT J AU Fujiwara, H Melenhorst, JJ El Ouriaghli, F Kajigaya, S Grube, M Sconocchia, G Rezvani, K Price, DA Hensel, NF Douek, DC Barrett, AJ AF Fujiwara, H Melenhorst, JJ El Ouriaghli, F Kajigaya, S Grube, M Sconocchia, G Rezvani, K Price, DA Hensel, NF Douek, DC Barrett, AJ TI In vitro induction of myeloid leukemia-specific CD4 and CD8 T cells by CD40 ligand-activated B cells gene modified to express primary granule proteins SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; ANTIGEN-PRESENTING CELLS; HLA CLASS-I; NEUTROPHIL ELASTASE; DENDRITIC CELLS; HEALTHY-INDIVIDUALS; CANCER VACCINES; TUMOR-ANTIGEN; LYMPHOCYTES; IMMUNOTHERAPY AB The primary granule proteins (PGP) of myeloid cells are a source of multiple antigens with immunotherapeutic potential for myeloid leukemias. Therefore, we developed a method to induceT-cell responses to PGP protein sequences. We found that gene-transfected antigen-presenting cells efficiently expand functionally competent PGP-specific CD4 and CD8 T cells. The system was optimized using T-cell responses to autologous CD40-activated B cells (CD40-B) transfected with a cytomegalovirus pp65-encoding expression vector. To generate leukemia-specific T cells, expression vectors encoding the PGP proteinase 3 (PR3) human neutrophil elastase, and cathepsin-G were transfected into CD40-B cells to stimulate postallogeneic stem cell transplantation T cells from five patients with myeloid and three with lymphoid leukemias. T-cell responses to PGP proteinase 3 and human neutrophil elastase were observed in CD8(+) and CD4(+) T cells only in patients with myeloid leukemias. T-cell responses against cathepsin-G occurred in both myeloid and lymphoblastic leukemias. T cells from a patient with chronic myelogenous leukemia (CML) and from a posttransplant CML patient, expanded against PGP, produced IFN-gamma or were cytotoxic to the patient's CML cells, demonstrating specific antileukemic efficacy. This study emphasizes the clinical potential of PGP for expansion and adoptive transfer of polyclonal leukemia antigen-specific T cells to treat leukemia. C1 NHLBI, Hematol Branch, Stem Cell Allotransplant Sect, NIH, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, Stem Cell Allotransplant Sect, NIH, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Intramural NIH HHS [Z99 AI999999]; Medical Research Council [G108/441] NR 33 TC 21 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2005 VL 11 IS 12 BP 4495 EP 4503 DI 10.1158/1078-0432.CCR-04-2363 PG 9 WC Oncology SC Oncology GA 934RM UT WOS:000229725900030 PM 15958635 ER PT J AU Kudo-Saito, C Schlom, J Camphausen, K Coleman, CN Hodge, JW AF Kudo-Saito, C Schlom, J Camphausen, K Coleman, CN Hodge, JW TI The requirement of multimodal therapy (vaccine, local tumor radiation, and reduction of suppressor cells) to eliminate established tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID REGULATORY T-CELLS; CARCINOEMBRYONIC ANTIGEN GENE; ANTITUMOR-ACTIVITY; IMMUNE-RESPONSES; CANCER-PATIENTS; COLORECTAL-CARCINOMA; DENDRITIC CELLS; CUTTING EDGE; HELPER CELLS; SELF-ANTIGEN AB Purpose: Numerous immune-based strategies are currently being evaluated for cancer therapy in preclinical models and clinical trials. Whereas many strategies look promising in preclinical models, they are often evaluated before or shortly following tumor implantation. The elimination of well-established tumors often proves elusive. Here we show that a multimodal immune-based therapy can be successfully employed to eliminate established tumors. Experimental Design: This therapy consists of vaccines directed against a self-tumor-associated antigen, the use of external beam radiation of tumors to up-regulate Fas on tumor cells, and the use of a monoclonal antibody (mAb) to reduce levels of CD4(+)CD25(+) suppressor cells. Results: We show here for the first time that (a) antigen-specific immune responses induced by vaccines were optimally augmented when anti-CD25 mAb was given at the same time as vaccination; (b) anti-CD25 mAb administration in combination with vaccines equally augmented T-cell immune responses specific for a self-antigen as well as those specific for a non-self antigen; (c) whereas the combined use of vaccines and anti-CD25 mAb enhanced antigen-specific immune responses, it was not sufficient to eliminate established tumors; (d) the addition of external beam radiation of tumors to the vaccine/anti-CD25 mAb regimen was required for the elimination of established tumors; and (e) Tcells from mice receiving the combination therapy showed significantly higher T-cell responses specific not only for the antigen in the vaccine but also for additional tumor-derived antigens (p53 and gp70). Conclusions: These studies reported here support the rationale for clinical trials employing multimodal immune-based therapies. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 55 TC 61 Z9 64 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 JUN 15 PY 2005 VL 11 IS 12 BP 4533 EP 4544 DI 10.1158/1078-0432.CCR-04-2237 PG 12 WC Oncology SC Oncology GA 934RM UT WOS:000229725900034 PM 15958639 ER PT J AU Dote, H Cerna, D Burgan, WE Carter, DJ Cerra, MA Hollingshead, MG Camphausen, K Tofilon, PJ AF Dote, H Cerna, D Burgan, WE Carter, DJ Cerra, MA Hollingshead, MG Camphausen, K Tofilon, PJ TI Enhancement of in vitro and in vivo tumor cell radiosensitivity by the DNA methylation inhibitor zebularine SO CLINICAL CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; SUPPRESSOR GENE; EPIGENETIC INACTIVATION; HISTONE DEACETYLASE; CANCER-CELLS; IONIZING IRRADIATION; CPG ISLAND; HYPERMETHYLATION; EXPRESSION; CHROMATIN AB Aberrant DNA hypermethylation is a frequent finding in tumor cells, which has suggested that inhibition of DNA methylation may be an effective cancer treatment strategy. Because DNA methylation affects gene expression and chromatin structure, parameters considered to influence radioresponse, we investigated the effects of the DNA methylation inhibitor zebularine on the radiosensitivity of human tumor cells. Three human tumor cell lines were used in this study (MiaPaCa, DU145, and U251) and the methylation status of three genes frequently hypermethylated in tumor cells (RASSF1A, HIC-1, and 14-3-3 sigma) was determined as a function of zebularine exposure. Zebularine resulted in DNA demethylation in a time-dependent manner, with the maximum loss of methylation detected by 48 hours. Treatment of cells with zebularine for 48 hours also resulted in an increase in radiosensitivity with dose enhancement factors of > 1.5. As a measure of radiation-induced DNA damage, gamma H2AX expression was determined. Whereas zebularine had no effect on radiation-induced gamma H2AX foci at 1 hour, the number of gamma H2AX foci per cell was significantly greater in the zebularine-treated cells at 24 hours after irradiation, suggesting the presence of unrepaired DNA damage. Zebularine administration to mice reactivated gene expression in U251 xenografts; irradiation of U251 tumors in micetreated with zebularine resulted in an increase in radiation -induced tumor growth delay.These results indicate that zebularine can enhance tumor cell radiosensitivity in vitro and in vivo and suggest that this effect may involve an inhibition of DNA repair. C1 NCI, Mol Radiat Therapeut Branch, Radiat Res Program, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. RP Tofilon, PJ (reprint author), NCI, Mol Radiat Therapeut Branch, Radiat Res Program, Div Canc Treatment & Diagnosis, EPN-6015A,6130 Execut Blvd,MSC 7440, Bethesda, MD 20892 USA. EM tofilonp@mail.nih.gov NR 48 TC 64 Z9 68 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2005 VL 11 IS 12 BP 4571 EP 4579 DI 10.1158/1078-0432.CCR-05-0050 PG 9 WC Oncology SC Oncology GA 934RM UT WOS:000229725900038 PM 15958643 ER PT J AU Chow, HHS Hakim, IA Vining, DR Crowel, JA Ranger-Moore, J Chew, WM Celaya, CA Rodney, SR Hara, Y Alberts, DS AF Chow, HHS Hakim, IA Vining, DR Crowel, JA Ranger-Moore, J Chew, WM Celaya, CA Rodney, SR Hara, Y Alberts, DS TI Effects of dosing condition on the oral bioavailability of green tea catechins after single-dose administration of Polyphenon E in healthy individuals SO CLINICAL CANCER RESEARCH LA English DT Article ID ACETAMINOPHEN GLUCURONIDATION; EPIGALLOCATECHIN GALLATE; DRUG ABSORPTION; CANCER; RATS; FOOD; (-)-EPIGALLOCATECHIN-3-GALLATE; PHARMACOKINETICS; CONSUMPTION; INHIBITION AB Purpose: Green tea has been shown to exhibit cancer-preventive activities in preclinical studies. Its consumption has been associated with decreased risk of certain types of cancers in humans. The oral bioavailability of the major green tea constituents, green tea catechins, is low, resulting in systemic catechin levels in humans many fold less than the effective concentrations determined in in vitro systems. We conducted this clinical study to test the hypothesis that the oral bioavailability of green tea catechins can be enhanced when consumed in the absence of food. Experimental Designs: Thirty healthy volunteers were randomly assigned to one of the following doses of Polyphenon E (a clecaffeinated and defined green tea catechin mixture): 400, 800, or 1,200 mg, based on the epigallocatechin gallate content (10 subjects per dose group). After an overnight fast, study participants took a single dose of Polyphenon E with or without a light breakfast, which consisted of one or two 4-oz muffins and a glass of water. Following a 1 -week washout period, subjects were crossed over to take the same dose of Polyphenon E under the opposite fasting/fed condition. Tea catechin concentrations in plasma and urine samples collected after dosing were determined by high-pressure liquid chromatography analysis. Results: Consistent with previous reports, epigallocatechin gallate and epicatechin gallate were present in plasma mostly as the free form, whereas epicatechin and epigallocatechin were mostly present as the glucuronicle and sulfate conjugates. There was > 3.5-fold increase in the average maximum plasma concentration of free epigallocatechin gallate when Polyphenon E was taken in the fasting condition than when taken with food. The dosing condition led to a similar change in plasma-free epigallocatechin and epicatechin gallate levels. Taking Polyphenon E in the fasting state did not have a significant effect on the plasma levels of total (free and conjugated) epigallocatechin, but resulted in lower plasma levels of total epicatechin. Urinary epigallocatechin gallate and epicatechin gallate levels were very low or undetectable following Polyphenon E administration with either dosing condition. Taking Polyphenon E under the fasting state resulted in a significant decrease in the urinary recovery of total epigallocatechin and epicatechin. Polyphenon E administered as a single dose over the dose range studied was generally well-tolerated by the study participants. Mild and transient nausea was noted in some of the study participants and was seen most often at the highest study agent dose (1,200 mg epigallocatechin gallate) and in the fasting condition. Conclusions: We conclude that greater oral bioavailability of free catechins can beachieved bytaking the Polyphenon E capsules on an empty stomach after an overnight fast. Polyphenon E up to a dose that contains 800 mg epigallocatechin gallate is well-tolerated when taken under the fasting conclition.This dosing condition is also expected to optimize the biological effects of tea catechins. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Mitsui Norin Co Ltd, Shizuoka, Japan. RP Chow, HHS (reprint author), Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. EM schow@azcc.arizona.edu FU NCI NIH HHS [N01-CN-25119] NR 30 TC 206 Z9 210 U1 0 U2 11 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 15 PY 2005 VL 11 IS 12 BP 4627 EP 4633 DI 10.1158/1078-0432.CCR-04-2549 PG 7 WC Oncology SC Oncology GA 934RM UT WOS:000229725900044 PM 15958649 ER PT J AU Azuma, Y Arnaoutov, A Anan, T Dasso, M AF Azuma, Y Arnaoutov, A Anan, T Dasso, M TI PIASy mediates SUMO-2 conjugation of Topoisomerase-II on mitotic chromosomes SO EMBO JOURNAL LA English DT Article DE chromatin; mitosis; PIASy; SUMO; Topoisomerase-II ID E3 LIGASE; COMPLEX; ORGANIZATION; MOTIF AB Here we show that the PIASy protein is specifically required for mitotic modification of Topoisomerase-II by SUMO-2 conjugation in Xenopus egg extracts. PIASy was unique among the PIAS family members in its capacity to bind mitotic chromosomes and recruit Ubc9 onto chromatin. These properties were essential, since PIASy mutants that did not bind chromatin or failed to recruit Ubc9 were functionally inactive. We observed that PIASy depletion eliminated essentially all chromosomal accumulation of EGFP-SUMO-2-conjugated species, suggesting that it is the primary E3-like factor for mitotic chromosomal substrates of SUMO-2. PIASy-dependent SUMO-2-conjugated species were highly concentrated on the inner centromere, and inhibition of PIASy blocked anaphase sister chromatid segregation in egg extracts. Taken together, our observations suggest that PIASy is a critical regulator of mitotic SUMO-2 conjugation for Topoisomerase-II and other chromosomal substrates, and that its activity may have particular relevance for centromeric functions required for proper chromosome segregation. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 18,Room 106,18 Lib Dr,MSC 5431, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD001902-13] NR 25 TC 85 Z9 87 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 2005 VL 24 IS 12 BP 2172 EP 2182 DI 10.1038/sj.emboj.7600700 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 945OE UT WOS:000230511000012 PM 15933717 ER PT J AU Asano, S Park, JE Sakchaisri, K Yu, LR Song, S Supavilai, P Veenstra, TD Lee, KS AF Asano, S Park, JE Sakchaisri, K Yu, LR Song, S Supavilai, P Veenstra, TD Lee, KS TI Concerted mechanism of Swe1/Wee1 regulation by multiple kinases in budding yeast SO EMBO JOURNAL LA English DT Article DE budding yeast; Cdc5; Cdc28; G2/M transition; Swe1 ID SACCHAROMYCES-CEREVISIAE; MORPHOGENESIS CHECKPOINT; SWE1P DEGRADATION; CELL-CYCLE; PROTEIN-KINASE; POLO KINASE; PHOSPHORYLATION; CYTOKINESIS; CDC5; BOX AB In eukaryotes, entry into mitosis is induced by cyclin B-bound Cdk1 which is held in check by the protein kinase, Wee1. In budding yeast, Swe1 (Wee1 ortholog) is targeted to the bud neck through Hsl1 (Nim1-related kinase) and its adaptor Hsl7, and is hyperphosphorylated prior to ubiquitin-mediated degradation. Here, we show that Hsl1 and Hsl7 are required for proper localization of Cdc5 (Polo-like kinase homolog) to the bud neck and Cdc5-dependent Swe1 phosphorylation. Mitotic cyclin (Clb2)-bound Cdc28 (Cdk1 homolog) directly phosphorylated Swe1 and this modification served as a priming step to promote subsequent Cdc5-dependent Swe1 hyperphosphorylation and degradation. Clb2-Cdc28 also facilitated Cdc5 localization to the bud neck through the enhanced interaction between the Clb2-Cdc28-phosphorylated Swe1 and the polo-box domain of Cdc5. We propose that the concerted action of Cdc28/Cdk1 and Cdc5/Polo on their common substrates is an evolutionarily conserved mechanism that is crucial for effectively triggering mitotic entry and other critical mitotic events. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Mahidol Univ, Fac Sci, Dept Pharmacol, Bangkok 10400, Thailand. NCI, Lab Proteom & Analyt Technol, Frederick, MD 21701 USA. Chungbuk Natl Univ, Coll Pharm, Chungbuk, South Korea. RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Room 3118, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov FU Intramural NIH HHS NR 26 TC 71 Z9 73 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 15 PY 2005 VL 24 IS 12 BP 2194 EP 2204 DI 10.1038/sj.emboj.7600683 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 945OE UT WOS:000230511000014 PM 15920482 ER PT J AU Rhee, SG Chae, HZ Kim, K AF Rhee, SG Chae, HZ Kim, K TI Peroxiredoxins: A historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE peroxiredoxin; thiol-specific antioxidant; thioredoxin peroxidase; hydrogen peroxide; peroxinitrite; cysteine sulfinic acid; sulfiredoxin ID THIOL-SPECIFIC ANTIOXIDANT; ALKYL HYDROPEROXIDE REDUCTASE; CYSTEINE-SULFINIC ACID; NECROSIS-FACTOR-ALPHA; MAMMALIAN PEROXIREDOXIN; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; THIOREDOXIN PEROXIDASE; SALMONELLA-TYPHIMURIUM; 2-CYS PEROXIREDOXIN AB The observation that purified yeast glutamine synthetase is rapidly inactivated in a thiol-containing buffer yet retains activity in crude extracts containing the same thiol led to our discovery of an enzyme that protects against oxidation in a thiol-containing system. This novel antioxidant enzyme was shown to reduce hydroperoxides and, more recently, peroxynitrite with the use of electrons provided by a physiological thiol like thioredoxin. It defined a family of proteins, present in organisms from all kingdoms, that was named peroxiredoxin (Prx). All Prx enzymes contain a conserved Cys residue that undergoes a cycle of peroxide-dependent oxidation and thiol-dependent reduction during catalysis. Mammalian cells express six isoforms of Prx (Prx I to VI), which are classified into three subgroups (2-Cys, atypical 2-Cys, and 1-Cys) based on the number and position of Cys residues that participate in catalysis. The relative abundance of Prx enzymes in mammalian cells appears to protect cellular components by removing the low levels of peroxides produced as a result of normal cellular metabolism. During catalysis, the active site cysteine is occasionally overoxidized to cysteine sulfinic acid. Contrary to the general belief that oxidation to the sulfinic state is an irreversible process in cells, studies on the fate of the overoxidized Prx species revealed a mechanism by which the catalytically active thiol form is recovered. This sulfinic reduction is a slow, ATP-dependent process that is specific to 2-Cys Prx isoforms. This reversible overoxidation may represent an adaptation unique to eukaryotic cells that accommodates the intracellular messenger function of H2O2, but experimental validation of such speculation is yet to come. Published by Elsevier Inc. C1 Natl Heart Lung & Blood Inst, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. Chonnam Natl Univ, Coll Nat Sci, Dept Biol Sci, Kwangju 500757, South Korea. RP Rhee, SG (reprint author), Natl Heart Lung & Blood Inst, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 77 TC 818 Z9 867 U1 3 U2 73 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN 15 PY 2005 VL 38 IS 12 BP 1543 EP 1552 DI 10.1016/j.freeadbiomed.2005.02.026 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 933XL UT WOS:000229666100001 PM 15917183 ER PT J AU Pidasheva, S Canaff, L Simonds, WF Marx, SJ Hendy, GN AF Pidasheva, S Canaff, L Simonds, WF Marx, SJ Hendy, GN TI Impaired cotranslational processing of the calcium-sensing receptor due to signal peptide missense mutations in familial hypocalciuric hypercalcemia SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEONATAL SEVERE HYPERPARATHYROIDISM; AUTOSOMAL-DOMINANT HYPOCALCEMIA; EXTRACELLULAR CA2+-SENSING RECEPTOR; ENDOPLASMIC-RETICULUM MEMBRANE; BENIGN HYPERCALCEMIA; FUNCTIONAL-CHARACTERIZATION; GENE; EXPRESSION; PROTEIN; KINDREDS AB The CASR, a cell surface glycoprotein expressed in parathyroid gland and kidney, is critical for maintaining extracellular calcium homeostasis. The inherited disorders, familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT), are caused by inactivating mutations in the CASR gene. The CASR has an N-terminal, 19 amino acid signal peptide that is predicted to direct the nascent polypeptide chain, as it emerges from the ribosome, into the endoplasmic reticulum (ER). Here, we report the functional characterization of three CASR mutations identified in hypercalcemic/hyperparathyroid patients. The mutations, L11S, L13P and T14A, lie within the signal peptide hydrophobic core. When transiently transfected into kidney cells, L11S and L13P mutants demonstrated reduced intracellular and plasma membrane expression and signaling to the mitogen-activated protein kinase pathway in response to extracellular calcium relative to wild-type CASR and the T14A mutant. All mutant CASR RNAs translated into protein normally. In cotranslational processing assays, which test the functionality of the signal peptide in the early secretory pathway, the wild-type CASR and mutant T14A nascent polypeptides were targeted to microsomal vesicles, representing the ER, translocated into the vesicular lumen and underwent core N-glycosylation. In contrast, the L11S and L13P mutants failed to be inserted in the microsomes and undergo glycosylation. This is the first study examining the function of the CASR signal sequence and reveals that both L11S and L13P mutants are markedly impaired with respect to cotranslational processing, accounting for the observed parathyroid dysfunction. C1 McGill Univ, Royal Victoria Hosp, Calcium Res Lab, Montreal, PQ H3A 1A1, Canada. McGill Univ, Royal Victoria Hosp, Hormones & Canc Res Unit, Montreal, PQ H3A 1A1, Canada. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Physiol, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. RP Hendy, GN (reprint author), McGill Univ, Royal Victoria Hosp, Calcium Res Lab, Room H4-67,687 Pine Ave W, Montreal, PQ H3A 1A1, Canada. EM geoffrey.hendy@mcgill.ca NR 47 TC 44 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUN 15 PY 2005 VL 14 IS 12 BP 1679 EP 1690 DI 10.1093/hmg/ddi176 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 934HL UT WOS:000229699800011 PM 15879434 ER PT J AU Erker, L Schubert, R Yakushiji, H Barlow, C Larson, D Mitchell, JB Wynshaw-Boris, A AF Erker, L Schubert, R Yakushiji, H Barlow, C Larson, D Mitchell, JB Wynshaw-Boris, A TI Cancer chemoprevention by the antioxidant tempol acts partially via the p53 tumor suppressor SO HUMAN MOLECULAR GENETICS LA English DT Article ID ATM-DEFICIENT MICE; DEPENDENT PROTEIN-KINASE; RNA SURVEILLANCE PROTEIN; DNA STRAND BREAKS; ATAXIA-TELANGIECTASIA; OXIDATIVE STRESS; INDUCED PHOSPHORYLATION; CALORIE RESTRICTION; IONIZING-RADIATION; CELL-PROLIFERATION AB We previously demonstrated that the nitroxide antioxidant tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) increased latency to tumorigenesis and doubled (100%) the lifespan of Atm-deficient mice, a mouse model of ataxia telangiectasia, which displays accelerated oxidative damage and stress. Tempol treatment of cancer-prone p53-deficient mice resulted in a small but significant (25%) increase in lifespan by prolonging latency to tumorigenesis, demonstrating that existing oxidative stress and damage are not necessary for the chemopreventative effects of tempol. However, the relatively small effect on latency in p53-deficient mice and the finding that tempol-mediated resistance to oxidative insult was p53-dependent suggested a more direct role of p53 in the chemopreventative effects of tempol. Surprisingly, tempol treatment specifically increased serine 18 phosphorylation of p53 (but not gamma-H2AX) and p21 expression in primary thymocytes in vitro in a p53-dependent fashion. Inhibition of phosphoinositide 3-kinase (PI3K) family members suggested that SMG-1 was responsible for the tempol-mediated enhancement of p53 serine 18 phosphorylation. These data suggest that the chemopreventative effect of tempol is not solely due to the reduction of oxidative stress and damage but may also be related to redox-mediated signaling functions that include p53 pathway activation. C1 Univ Calif San Diego, Sch Med, Dept Pediat, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Ctr Comprehens Canc, La Jolla, CA 92093 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Wynshaw-Boris, A (reprint author), Univ Calif San Diego, Sch Med, Dept Pediat, 9500 Gilman Dr,Mailstop 0627, La Jolla, CA 92093 USA. EM awynshawboris@ucsd.edu NR 67 TC 37 Z9 37 U1 0 U2 2 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 JUN 15 PY 2005 VL 14 IS 12 BP 1699 EP 1708 DI 10.1093/hmg/ddi181 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 934HL UT WOS:000229699800013 PM 15888486 ER PT J AU Sobolski, GK AF Sobolski, GK TI Biotechnology products and university-based science SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Sobolski, GK (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. EM sobolskig@cc.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUN 15 PY 2005 VL 293 IS 23 BP 2862 EP 2862 DI 10.1001/jama.293.23.2862-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 935MD UT WOS:000229785500016 PM 15956629 ER PT J AU Johnson, PF AF Johnson, PF TI Molecular stop signs: regulation of cell-cycle arrest by C/EBP transcription factors SO JOURNAL OF CELL SCIENCE LA English DT Article DE C/EBP; cell cycle; proliferation arrest ID ENHANCER-BINDING-PROTEIN; STIMULATING FACTOR-RECEPTOR; MAMMARY EPITHELIAL-CELLS; ACUTE MYELOID LEUKEMIAS; ALPHA GENE-EXPRESSION; SERUM-ALBUMIN GENE; GROWTH ARREST; DEFICIENT MICE; ONCOGENIC RAS; GRANULOCYTIC DIFFERENTIATION AB The CCAAT/enhancer-binding protein (C/EBP) family of transcription factors plays an important role in controlling cell proliferation and differentiation. C/EBP alpha is a particularly potent regulator of cell-cycle exit and is induced in terminally differentiating adipocytes and myeloid cells, where it also activates differentiation-specific genes. The growth-inhibiting activity of C/EBP alpha suppresses tumorigenesis in myeloid cells and possibly other tissues. In addition, recent work has identified C/EBP alpha as a component of the p53-regulated growth arrest response elicited by DNA damage in epidermal keratinocytes. Several studies have explored the mechanism by which C/EBP alpha blocks cell-cycle progression at the G1-S boundary, and several models have been proposed but no universally accepted mechanism has emerged. Controversial issues include whether C/EBP alpha acts through an 'off-DNA' mechanism to inhibit cyclin-dependent kinases, and whether and how it functions with the RB-E2F system to repress transcription of S-phase genes. Other C/EBP-family members have also been implicated in positive and negative control of cell proliferation, and the mechanisms underlying their growth-regulatory activities are beginning to be elucidated. C1 NCI, Ctr Canc Res, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Johnson, PF (reprint author), NCI, Ctr Canc Res, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 91 TC 169 Z9 174 U1 0 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD JUN 15 PY 2005 VL 118 IS 12 BP 2545 EP 2555 DI 10.1242/jcs.02459 PG 11 WC Cell Biology SC Cell Biology GA 943LQ UT WOS:000230355700001 PM 15944395 ER PT J AU Makhnovskii, YA Berezhkovskii, AM Zitserman, VY AF Makhnovskii, YA Berezhkovskii, AM Zitserman, VY TI Homogenization of boundary conditions on surfaces randomly covered by patches of different sizes and shapes SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID LIGAND-BINDING; DIFFUSION; RECEPTORS C1 Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Moscow 119991, Russia. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. Russian Acad Sci, Inst High Temp, Thermophys Ctr, Moscow 125412, Russia. LY Karpov Phys Chem Res Inst, Moscow 103064, Russia. RP Makhnovskii, YA (reprint author), Russian Acad Sci, AV Topchiev Petrochem Synth Inst, Leninsky Prospekt 29, Moscow 119991, Russia. EM Yuam@ips.ac.ru RI Makhnovskii, Yurii/B-1223-2014 OI Makhnovskii, Yurii/0000-0002-1517-536X NR 6 TC 28 Z9 29 U1 0 U2 2 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 JUN 15 PY 2005 VL 122 IS 23 AR 236102 DI 10.1063/1.1930827 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 939RZ UT WOS:000230091400074 PM 16008497 ER PT J AU Feeney, ME Tang, YH Pfafferott, K Roosevelt, KA Draenert, R Trocha, A Yu, XG Verrill, C Allen, T Moore, C Mallal, S Burchett, S McIntosh, K Pelton, SI St John, AA Hazra, R Klenerman, P Altfeld, M Walker, BD Goulder, PJR AF Feeney, ME Tang, YH Pfafferott, K Roosevelt, KA Draenert, R Trocha, A Yu, XG Verrill, C Allen, T Moore, C Mallal, S Burchett, S McIntosh, K Pelton, SI St John, AA Hazra, R Klenerman, P Altfeld, M Walker, BD Goulder, PJR TI HIV-R viral escape in infancy followed by emergence of a variant-specific CTL response SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYTOTOXIC T-LYMPHOCYTES; LONG-TERM NONPROGRESSORS; ORIGINAL ANTIGENIC SIN; INFECTED CHILDREN; IMMUNE-RESPONSES; TYPE-1 INFECTION; IN-VIVO; REPLICATION; SELECTION AB Mutational escape from the CTL response represents a major driving force for viral diversification in HIV-1-infected adults, but escape during infancy has not been described previously. We studied the immune response of perinatally infected children to an epitope (B57-TW10) that is targeted early during acute HIV-1 infection in adults expressing HLA-B57 and rapidly mutates under this selection pressure. Viral sequencing revealed the universal presence of escape mutations within TW10 among B57- and B5801-positive children. Mutations in TW10 and other B57-restricted epitopes arose early following perinatal infection of B57-positive children born to B57-negative mothers. Surprisingly, the majority of B57/5801-positive children exhibited a robust response to the TW10 escape variant while recognizing the wild-type epitope weakly or not at all. These data demonstrate that children, even during the first years of life, are able to mount functional immune responses of sufficient potency to drive immune escape. Moreover, our data suggest that the consequences of immune escape may differ during infancy because most children mount a strong variant-specific immune response following escape, which is rarely seen in adults. Taken together, these findings indicate that the developing immune system of children may exhibit greater plasticity in responding to a continually evolving chronic viral infection. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Infect Dis Div, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. John Radcliffe Hosp, Nuffield Dept Med, Oxford OX3 9DU, England. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Royal Perth Hosp, Ctr Clin Immunol & Biomed Stat, Perth, WA, Australia. Boston Med Ctr, Boston, MA 02118 USA. Queen Elizabeth Hosp, Bridgetown, Barbados. NCI, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Feeney, ME (reprint author), 149 13th St,5th Floor, Charlestown, MA 02129 USA. EM mnfeeney@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [K23-AI52078] NR 26 TC 83 Z9 88 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7524 EP 7530 PG 7 WC Immunology SC Immunology GA 935OK UT WOS:000229791400009 PM 15944251 ER PT J AU Wille-Reece, U Wu, CY Flynn, BJ Kedl, RM Seder, RA AF Wille-Reece, U Wu, CY Flynn, BJ Kedl, RM Seder, RA TI Immunization with HIV-1 Gag protein conjugated to a TLR7/8 agonist results in the generation of HIV-1 Gag-specific Th1 and CD8(+) T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; ADAPTIVE IMMUNE-RESPONSES; AIDED CROSS-PRESENTATION; DENDRITIC CELLS; CPG-DNA; IN-VIVO; BOOST VACCINATION; SOLUBLE-PROTEINS; RHESUS MACAQUES; BACTERIAL-DNA AB One strategy to induce optimal cellular and humoral immune responses following immunization is to use vaccines or adjuvants that target dendritic cells and B cells. Activation of both cell types can be achieved using specific TLR ligands or agonists directed against their cognate receptor. In this study, we compared the ability of the TLR7/8 agonist R-848, which signals only via TLR7 in mice, with CpG oligodeoxynucleotides for their capacity to induce HIV-1 Gag-specific T cell and Ab responses when used as vaccine adjuvants with HIV-1 Gag protein in mice. Injection of R-848 and CpG oligodeoxynucleotides alone enhanced the innate immune responses in vivo as demonstrated by high serum levels of inflammatory cytokines, including IL-12p70 and IFN-alpha, and increased expression of CD80, CD86, and CD40 on CD11c(+) dendritic cells. By contrast, R-848 was a relatively poor adjuvant for inducing primary Th1 or CD8(+) T cell responses when administered with HIV-1 Gag protein. However, when a TLR7/8 agonist structurally and functionally similar to R-848 was conjugated to HIV-1 Gag protein both Th1 and CD8(+) T cells responses were elicited as determined by intracellular cytokine and tetramer staining. Moreover, within the population of HIV-1 Gag-specific CD8(+) CD62(low) cells, similar to 50% of cells expressed CD127, a marker shown to correlate with the capacity to develop into long-term memory cells. Overall, these data provide evidence that TLR7/8 agonists can be effective vaccine adjuvants for eliciting strong primary immune responses with a viral protein in vivo, provided vaccine delivery is optimized. C1 NIAID, Vaccine Res Ctr, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. 3M Pharmaceut, St Paul, MN 55144 USA. RP Seder, RA (reprint author), NIAID, Vaccine Res Ctr, Cellular Immunol Sect, NIH, 40 Convent Dr,Bldg 40, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov NR 44 TC 123 Z9 128 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7676 EP 7683 PG 8 WC Immunology SC Immunology GA 935OK UT WOS:000229791400026 PM 15944268 ER PT J AU Mayorov, VI Rogozin, IB Adkison, LR Gearhart, PJ AF Mayorov, VI Rogozin, IB Adkison, LR Gearhart, PJ TI DNA polymerase eta contributes to strand bias of mutations of A versus T in immunoglobulin genes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; XERODERMA-PIGMENTOSUM VARIANT; STIMULATED B-CELLS; SOMATIC HYPERMUTATION; ANTIBODY DIVERSIFICATION; MISMATCH REPAIR; CUTTING EDGE; MICE; AID AB DNA polymerase (pol) eta participates in hypermutation of A:T bases in Ig genes because humans deficient for the polymerase have fewer substitutions of these bases. To determine whether polymerase eta is also responsible for the well-known preference for mutations of A vs T on the nontranscribed strand, we sequenced variable regions from three patients with xeroderma pigmentosum variant (XP-V) disease, who lack polymerase eta. The frequency of mutations in the intronic region downstream of rearranged J(H)4 gene segments was similar between XP-V and control clones; however, there were fewer mutations of A:T bases and correspondingly more substitutions of C:G bases in the XP-V clones (p < 10(-7)). There was significantly less of a bias for mutations of A compared with T nucleotides in the XP-V clones compared with control clones, whereas the frequencies for mutations of C and G were identical in both groups. An analysis of mutations in the WA sequence motif suggests that polymerase eta generates more mutations of A than T on the nontranscribed strand. This in vivo data from polymerase eta-deficient B cells correlates well with the in vitro specificity of the enzyme. Because polymerase eta inserts more mutations opposite template T than template A, it would generate more substitutions of A on the newly synthesized strand. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Mercer Univ, Sch Med, Dept Basic Med Sci, Macon, GA 31207 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Russian Acad Sci, Inst Cytol & Genet, Novosibirsk 630090, Russia. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov FU Intramural NIH HHS NR 57 TC 50 Z9 50 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7781 EP 7786 PG 6 WC Immunology SC Immunology GA 935OK UT WOS:000229791400039 PM 15944281 ER PT J AU Martomo, SA Fu, DT Yang, WW Joshi, NS Gearhart, PJ AF Martomo, SA Fu, DT Yang, WW Joshi, NS Gearhart, PJ TI Deoxyuridine is generated preferentially in the nontranscribed strand of DNA from cells expressing activation-induced cytidine deaminase SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-SWITCH RECOMBINATION; SOMATIC HYPERMUTATION; ANTIBODY DIVERSIFICATION; IMMUNOGLOBULIN GENES; DHFR GENE; AID; ENZYME; URACIL; REPAIR; GLYCOSYLASE AB Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and class switch recombination of Ig genes in B cells. Although AID has been shown to deaminate deoxycytidine to deoxyuridine in DNA in vitro, there is no physical evidence for increased uracils in DNA from cells expressing AID in vivo. We used several techniques to detect uracil bases in a gene that was actively transcribed in Escherichia coli cells expressing AID. Plasmid DNA containing the gene was digested with uracil-DNA glycosylase to remove uracil, and apurinic/apryimidinic endonuclease to nick the abasic site. The nicked DNA was first analyzed using alkaline gel electrophoresis, in which there was a 2-fold increase in the linear form of the plasmid after AID induction compared with plasmid from noninduced bacteria. Second, using a quantitative denaturing Southern blot technique, the gene was predominantly nicked in the nontranscribed strand compared with the transcribed strand. Third, using ligation-mediated PCR, the nicks were mapped on the nontranscribed strand and were located primarily at cytosine bases. These data present direct evidence for the presence of uracils in DNA from cells that are induced to express AID, and they are preferentially generated at cytosines in the nontranscribed strand during transcription. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov OI Joshi, Nikhil/0000-0002-7045-7837 NR 35 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7787 EP 7791 PG 5 WC Immunology SC Immunology GA 935OK UT WOS:000229791400040 PM 15944282 ER PT J AU Wojciechowski, W Li, HF Marshall, S Dell'Agnola, C Espinoza-Delgado, I AF Wojciechowski, W Li, HF Marshall, S Dell'Agnola, C Espinoza-Delgado, I TI Enhanced expression of CD20 in human tumor B cells is controlled through ERK-dependent mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; CHRONIC LYMPHOCYTIC-LEUKEMIA; NON-HODGKINS-LYMPHOMA; MONOCLONAL-ANTIBODY THERAPY; STAGE-SPECIFIC EXPRESSION; RITUXIMAB IN-VITRO; LOW-GRADE; T-CELLS; PHASE-I; ANTIGEN-EXPRESSION AB Rituximab, a chimeric Ab directed against CD20, induces apoptosis in targeted cells. Although the majority of B cell malignancies express the CD20 Ag, only similar to 50% of patients will respond to single-agent rituximab. The available data suggest that a decreased CD20 expression could account for the lack of response observed in some patients treated with rituximab. Despite the potential critical role of CD20 in the biology of B cell malignancies, the mechanisms controlling its expression are poorly understood. We evaluated the effect of the immune modulator agent bryostatin-1 on the expression of CD20 in non-Hodgkin's lymphoma cells. Using the B cell lines, DB and RAMOS, as well as tumor cells derived from a chronic lymphocytic leukemia patient, we demonstrated that bryostatin-1 enhanced the expression of both CD20 mRNA and protein. The enhanced expression of CD20 was associated with increased transcriptional activity of the CD20 gene, whereas the stability of CD20 mRNA was not affected. The effect of bryostatin-1 on CD20 expression in non-Hodgkin's lymphoma cells was mediated through the MAPK kinase/ERK signal transduction pathway and involved protein kinase C, but was independent of p38 MAPK and was insensitive to dexamethasone. Cells pretreated with bryostatin-1 were more susceptible to the proapoptotic effect of anti-CD20 Ab. Overall, these data demonstrate for the first time that ERK phosphorylation is required for the up-regulated expression of CD20 on B cell malignancies. The findings also suggest that bryostatin-1 and rituximab could be a valuable combined therapy for B cell malignancies. C1 NIA, Hematol Oncol Sect, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. RP Espinoza-Delgado, I (reprint author), 5600 Nathan Shock Dr,Room 4C10, Baltimore, MD 21224 USA. EM espinozaig@grc.nia.nih.gov NR 85 TC 23 Z9 25 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 JUN 15 PY 2005 VL 174 IS 12 BP 7859 EP 7868 PG 10 WC Immunology SC Immunology GA 935OK UT WOS:000229791400049 PM 15944291 ER PT J AU Brenner, M Meng, HC Yarlett, NC Joe, B Griffiths, MM Remmers, EF Wilder, RL Gulko, PS AF Brenner, M Meng, HC Yarlett, NC Joe, B Griffiths, MM Remmers, EF Wilder, RL Gulko, PS TI The non-MHC quantitative trait locus Cia5 contains three major arthritis genes that differentially regulate disease severity, pannus formation, and joint damage in collagen-and pristane-induced arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; ADJUVANT-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY LOCI; HISTOCOMPATIBILITY COMPLEX; LINKAGE ANALYSIS; TYROSINE-PHOSPHATASE; MULTIPLE-SCLEROSIS; FUSION PROTEIN; RAT MODELS AB Cia5 is a locus on rat chromosome 10 which regulates the severity of collagen- and pristane-induced arthritis (CIA and PIA). To refine the region toward positional identification, Cia5 subcongenic strains were generated and studied in PIA and CIA. The protective effect of the telomeric locus Cia5a was confirmed in both models. A second arthritis severity locus (Cia5d) was identified within the most centromeric portion of Cia5. DA.F344(Cia5d) rats had a significantly lower median arthritis severity index in PIA, but not in CIA, compared with DA. On histologic analyses DA.F344(Cia5a) and DA.F344(Cia5d) congenics with PIA preserved a nearly normal joint architecture compared with DA, including significant reduction in synovial hyperplasia, pannus, angiogenesis, inflammatory infiltration, bone and cartilage erosions. Cia5 and Cia5a synovial levels of IL-1 beta mRNA were reduced. Although both DA.F344(Cia5) and DA.F344(Cia5a) rats were protected in CIA, the arthritis scores of DA.F344(Cia5) were significantly higher than those of DA.F344(Cia5a), suggesting the existence of a third locus where F344-derived alleles centromeric from Cia5a contribute to increased arthritis severity. The existence of the third locus was further supported by higher levels of autoantibodies against rat type II collagen in DA.F344(Cia5) congenics compared with DA.F344(Cia5a). Our results determined that Cia5 contains three major arthritis severity regulatory loci regulating central events in the pathogenesis of arthritis, and differentially influencing CIA and PIA. These loci are syntenic to regions on human chromosomes 17q and 5q implicated in the susceptibility to rheumatoid arthritis, suggesting that the identification of these genes will be relevant to human disease. C1 N Shore Long Isl Jewish Res Inst, Robert S Boas Ctr Genom & Human Genet, Lab Expt Rheumatol, Manhasset, NY 11030 USA. NIAMS, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Utah, Vet Affairs Med Ctr, NIAMS, Salt Lake City, UT 84132 USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT 84132 USA. NYU, Sch Med, Dept Med, New York, NY USA. RP Gulko, PS (reprint author), N Shore Long Isl Jewish Res Inst, Robert S Boas Ctr Genom & Human Genet, Lab Expt Rheumatol, 330 Community Dr Room 139, Manhasset, NY 11030 USA. EM pgulko@nshs.edu OI Brenner, Max/0000-0002-8010-148X FU NIAID NIH HHS [R01-AI54348]; NIAMS NIH HHS [R01 AR052439, R01-AR46213] NR 69 TC 38 Z9 38 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7894 EP 7903 PG 10 WC Immunology SC Immunology GA 935OK UT WOS:000229791400053 PM 15944295 ER PT J AU Zhang, JZ Li, GL Bafica, A Pantelic, M Zhang, P Broxmeyer, H Liu, Y Wetzler, L He, JJ Chen, T AF Zhang, JZ Li, GL Bafica, A Pantelic, M Zhang, P Broxmeyer, H Liu, Y Wetzler, L He, JJ Chen, T TI Neisseria gonorrhoeae enhances infection of dendritic cells by HIV type 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED-DISEASES; TOLL-LIKE RECEPTOR-2; CARCINOEMBRYONIC ANTIGENS CD66; IMMUNODEFICIENCY-VIRUS TYPE-1; GONOCOCCAL OPACITY PROTEINS; EPITHELIAL-CELLS; T-LYMPHOCYTES; CUTTING EDGE; DC-SIGN; CYTOKINE RELEASE AB Clinical studies indicate that Neisseria gonorrhoeae (gonococci (GC)) has the capacity to enhance HIV type 1 (HIV-1) infection. We studied whether GC enhances HIV infection of activated dendritic cells (DCs). The results show that GC can dramatically enhance HIV replication in human DCs during coinfection. The GC component responsible for HIV infection enhancement may be peptidoglycan, which activates TLR2. TLR2 involvement is suggested by bacterial lipoprotein, a TLR2-specific inducer, which stimulates a strong enhancement of HIV infection by human DCs. Moreover, participation of TLR2 is further implicated because GC is unable to stimulate expression of HIV in DCs of TLR2-deficient HIV-1-transgenic mice. These results provide one potential mechanism through which GC infection increases HIV replication in patients infected with both GC and HIV. C1 Indiana Univ, Sch Med, Walther Oncol Ctr,Walther Oncol Inst, Dept Microbiol & Immunol,Div Infect Dis, Indianapolis, IN 46202 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Oswaldo Cruz Fdn, Lab Imunorregulacao & Microbiol, Salvador, BA, Brazil. Boston Univ, Sch Med, Evans Biomed Res Ctr, Dept Med,Div Infect Dis, Boston, MA 02118 USA. RP Chen, T (reprint author), Indiana Univ, Sch Med, Walther Oncol Ctr,Walther Oncol Inst, Dept Microbiol & Immunol,Div Infect Dis, MS415E,635 Barnhill Dr, Indianapolis, IN 46202 USA. EM tiechen@iupui.edu FU NIAID NIH HHS [R01AI47736]; NINDS NIH HHS [R01NS39804] NR 65 TC 39 Z9 39 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2005 VL 174 IS 12 BP 7995 EP 8002 PG 8 WC Immunology SC Immunology GA 935OK UT WOS:000229791400064 PM 15944306 ER PT J AU Stapleton, JT Chaloner, K Williams, CF AF Stapleton, JT Chaloner, K Williams, CF TI GB virus C infection and survival in the Amsterdam Cohort study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID COINFECTION; MORTALITY C1 Iowa City VA Med Ctr, Med Serv, Iowa City, IA USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Biostat, Iowa City, IA 52242 USA. Univ Iowa, Dept Stat & Actuarial Sci, Iowa City, IA 52242 USA. NIAID, Epidemiol Branch, Div AIDS, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Stapleton, JT (reprint author), UIHC, Dept Internal Med, SW34-P,GH,200 Hawkins, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu RI Chaloner, Kathryn/B-5090-2013 NR 10 TC 7 Z9 7 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 JUN 15 PY 2005 VL 191 IS 12 BP 2157 EP 2158 DI 10.1086/430505 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 927OT UT WOS:000229203900026 PM 15898008 ER PT J AU Hasegawa, T Ukai, W Jo, DG Xu, XR Mattson, MP Nakagawa, M Araki, W Saito, T Yamada, T AF Hasegawa, T Ukai, W Jo, DG Xu, XR Mattson, MP Nakagawa, M Araki, W Saito, T Yamada, T TI Homocysteic acid induces intraneuronal accumulation of neurotoxic A beta 42: Implications for the pathogenesis of Alzheimer's disease SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE amyloid plaques; apoptosis; cerebrospinal fluid; gamma secretase; hippocampus; homocysteine ID GAMMA-SECRETASE ACTIVITY; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; AMYLOID PRECURSOR PROTEIN; OXIDATIVE STRESS; NEUROFIBRILLARY TANGLES; CORTICAL-NEURONS; TRANSGENIC MODEL; A-BETA; CELLS; BRAIN AB The causes of neuronal dysfunction and degeneration in Alzheimer's disease (AD) are not fully understood, but increased production of neurotoxic forms of amyloid beta-peptide-42 (A beta 42) seems of major importance. Large extracellular deposits of aggregated A beta 42 (plaques) is a diagnostic feature of AD, but A beta 42 may be particularly cytotoxic when it accumulates inside neurons. The factors that may promote the intracellular accumulation of A beta 42 in AD are unknown, but recent findings suggest that individuals with elevated homocysteine levels are at increased risk for AD. We show that homocysteic acid (HA), an oxidized metabolite of homocysteine, induces intraneuronal accumulation of a A beta 42 that is associated with cytotoxicity. The neurotoxicity of HA can be attenuated by an inhibitor of gamma-secretase, the enzyme activity that generates A beta 42, suggesting a key role for intracellular A beta 42 accumulation in the neurotoxic action of HA. Concentrations of HA in cerebrospinal fluid (CSF) were similar in AD and control subjects. CSF homocysteine levels were elevated significantly in AD patients, however, and homocysteine exacerbated HA-induced neurotoxicity, suggesting a role for HA in the pathogenic action of elevated homocysteine levels in AD. These findings suggest that the intracellular accumulation of A beta 42 plays a role in the neurotoxic action of HA, and suggest a potential therapeutic benefit of agents that modify the production and neurotoxic actions of HA and homocysteine. (c) 2005 Wiley-Liss, Inc. C1 Saga Womens Junior Coll, Saga 8408550, Japan. Toyama Chem Co, Toyama, Japan. Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD USA. Natl Inst Neurosci, NCNP, Tokyo, Japan. Fukuoka Univ Hosp, Fukuoka, Japan. RP Hasegawa, T (reprint author), Saga Womens Junior Coll, 1313 Honjyou Honjyou Town, Saga 8408550, Japan. EM hasegawa@saga-wjc.ac.jp RI Mattson, Mark/F-6038-2012; Araki, Wataru/G-7913-2014 OI Araki, Wataru/0000-0001-8467-6937 NR 46 TC 42 Z9 46 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 15 PY 2005 VL 80 IS 6 BP 869 EP 876 DI 10.1002/jnr.20514 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 931KT UT WOS:000229484900015 PM 15898106 ER PT J AU Simon, R AF Simon, R TI Development and validation of therapeutically relevant multi-gene biomarker classifiers SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENE-EXPRESSION PROFILES; BREAST-CANCER; MICROARRAY DATA; TAMOXIFEN; CLASSIFICATION C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 10 TC 57 Z9 61 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 15 PY 2005 VL 97 IS 12 BP 866 EP 867 DI 10.1093/jnci/dji168 PG 2 WC Oncology SC Oncology GA 937FA UT WOS:000229908800001 PM 15956642 ER PT J AU Vocke, CD Yang, YF Pavlovich, CP Schmidt, LS Nickerson, ML Torres-Cabala, CA Merino, MJ Walther, MM Zbar, B Linehan, WM AF Vocke, CD Yang, YF Pavlovich, CP Schmidt, LS Nickerson, ML Torres-Cabala, CA Merino, MJ Walther, MM Zbar, B Linehan, WM TI High frequency of somatic frameshift BHD gene mutations in Birt-Hogg-Dube-associated renal tumors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SPONTANEOUS PNEUMOTHORAX; CELL CARCINOMA; MET PROTOONCOGENE; KIDNEY NEOPLASIA; CANCER; GERMLINE; APC; CLASSIFICATION; POLYPOSIS; MODEL AB The Birt-Rogg-Dube (BHD) syndrome is an inherited genodermatosis characterized by a predisposition to hamartomatous skin lesions, pulmonary cysts, and renal carcinoma. Seventy-seven renal tumors from 12 patients with germline BHD mutations were examined by DNA sequencing to identify somatic mutations in the second copy of BHD. Sequence alterations were detected in the majority of renal tumors (41 of 77, 53%), with loss of heterozygosity at the BHD focus in a minority of additional tumors (14 of 77, 17%). The somatic mutations were distributed across the entire gene, and the majority resulted in frameshifts that are predicted to truncate the BHD protein. These results support a role for BHD as a tumor suppressor gene that predisposes to the development of renal tumors when both copies are inactivated. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. Natl Canc Inst, Immunobiol Lab, Frederick, MD USA. RP Vocke, CD (reprint author), NCI, Urol Oncol Branch, Bldg 10,CRC,Rm 1W-5888, Bethesda, MD 20892 USA. EM vockec@mail.nih.gov FU PHS HHS [N01-C0-12400] NR 26 TC 119 Z9 122 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 15 PY 2005 VL 97 IS 12 BP 931 EP 935 DI 10.1093/jnci/dji154 PG 5 WC Oncology SC Oncology GA 937FA UT WOS:000229908800015 PM 15956655 ER PT J AU Manrow, RE AF Manrow, RE TI Re: Clinical trials registration efforts gain some ground SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 Natl Canc Inst, Int Canc Res Databank Branck, Off Canc Informat Prod & Syst, Off Commun,NIH,Dept Hlth Human Serv, Rockville, MD 20852 USA. RP Manrow, RE (reprint author), Natl Canc Inst, Int Canc Res Databank Branck, Off Canc Informat Prod & Syst, Off Commun,NIH,Dept Hlth Human Serv, Suite 300A,6116 Execut Blvd, Rockville, MD 20852 USA. EM rmanrow@mail.nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 15 PY 2005 VL 97 IS 12 BP 936 EP 936 DI 10.1093/jnci/dji155 PG 1 WC Oncology SC Oncology GA 937FA UT WOS:000229908800016 PM 15956658 ER PT J AU Umar, A AF Umar, A TI Re: Revised Bethesda guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Umar, A (reprint author), NCI, Natl Inst Hlth, 6130 Execut Blvd,EPN 2141, Bethesda, MD 20892 USA. EM asad.umar@nih.gov NR 4 TC 0 Z9 0 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 JUN 15 PY 2005 VL 97 IS 12 BP 937 EP 938 DI 10.1093/jnci/dji158 PG 2 WC Oncology SC Oncology GA 937FA UT WOS:000229908800019 ER PT J AU Schiffman, M Castle, PE Solomon, D Stoler, M Wheeler, CM AF Schiffman, M Castle, PE Solomon, D Stoler, M Wheeler, CM TI Re: A study of the impact of adding HPV types to cervical cancer screening and triage tests - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID DNA C1 NCI, Hormonal & Reprod Epidemiol Branch, NIH, Dept Hlth, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, NIH, Dept Human Serv, Bethesda, MD 20892 USA. Univ Virginia, Dept Pathol, Charlottesville, VA 22903 USA. Univ New Mexico, Dept Mol Genet, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Schiffman, M (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, NIH, Dept Hlth, Bethesda, MD 20892 USA. EM schiffmm@exchange.nih.gov NR 7 TC 0 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUN 15 PY 2005 VL 97 IS 12 BP 939 EP 941 DI 10.1093/jnci/dji160 PG 3 WC Oncology SC Oncology GA 937FA UT WOS:000229908800021 ER PT J AU Crain, BJ Tran, SD Mezey, E AF Crain, BJ Tran, SD Mezey, E TI Transplanted human bone marrow cells generate new brain cells SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Symposium of the European-Charcot-Foundation on Preserve the Neuron CY DEC 11-13, 2003 CL Lisbon, PORTUGAL SP European Charcot Fdn DE human; bone marrow transplantation; neurons; glia; buccal epithelium; cell fusion; transdifferentiation ID STEM-CELLS; IN-VIVO; EPITHELIAL-CELLS; ADULT MICE; HEPATOCYTES; FUSION; DIFFERENTIATION; EXPRESSION; MUSCLE; BLOOD AB Multiple studies have reported that adult cells of bone marrow origin can differentiate into muscle, skin, liver, lung, epithelial cells, and neurons. To determine whether such cells might produce neurons and other cells in the human brain, we examined paraffin sections from female patients who had received bone marrow transplants from male donors. Y-chromosomes were labeled using autoradiography and fluorescent in situ hybridization. Neurons and astrocytes were identified histologically and immunohistochemically in neocortex, hippocampus, striatum, and cerebellum. However, most labeled cells in both gray and white matter appeared to be glia. Others have suggested that such Y-labeling represents fusion between host and donor cells, rather than true transdifferentiation. The possibilities of fusion and microchimerism were therefore examined using buccal epithelial cells as a model system. The female patients in this study had received either bone marrow or stem cell (CD34+ enriched) transplants from their brothers. Double labeling for X- and Y-chromosomes showed that Y-labeled buccal cells could not be explained by fusion. Genotyping studies of one patient, her brother, and her son ruled out the possibility of microchimerism. Whether, and under what circumstances, some form of bone marrow transplantation might provide adequate number of cells capable of replacing lost brain cells or enhancing their function will require additional studies. (c) 2005 Elsevier B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Natl Inst Dental & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD USA. NINDS, Basic Neurosci Program, NIH, Bethesda, MD USA. RP Crain, BJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, 720 Rutland Ave, Baltimore, MD 21205 USA. EM bcrain@jhmi.edu NR 23 TC 51 Z9 60 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUN 15 PY 2005 VL 233 IS 1-2 BP 121 EP 123 DI 10.1016/j.jns.2005.03.017 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 939GM UT WOS:000230060500020 PM 15949500 ER PT J AU Anderson, B AF Anderson, B TI Dexrazoxane for the prevention of cardiomyopathy in anthracycline treated pediatric cancer patients SO PEDIATRIC BLOOD & CANCER LA English DT Article; Proceedings Paper CT 8th International Conference on Long-Term Complications of Treatment of Children and Adolescents with Cancer CY JUN 25-26, 2004 CL Ontario, CANADA SP Natl Canc Inst, Roswell Pk Canc Inst ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DOXORUBICIN-CONTAINING THERAPY; ADVANCED BREAST-CANCER; LATE CARDIOTOXICITY; CHILDHOOD-CANCER; CHILDREN; ICRF-187; INFUSION; CARDIOPROTECTION; TOXICITY AB Anthracyclines play a major role in chemotherapeutic regimens for a variety of childhood cancers, but produce dose-related cardiotoxicity. Dexrazoxane, a chelating agent that binds iron intracellularly, has been cautiously included in anthracycline-based regimens. Our understanding of anthracycline and dexrazoxane pharmacokinetics in children is very limited. In addition, the administration schedule used for adults (bolus dexrazoxane prior to bolus anthracycline) may not be the best to attain both short- and long-term cardioprotection. Dexrazoxane could diminish the anti-tumor activity of and/or increase toxicities from anthracyclines. Pediatric oncologists must be assured this intervention does not diminish the success, in curing children with cancer. (c) 2005 Wiley-Liss, Inc. C1 NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Pediat Sect, Rockville, MD 20852 USA. RP Anderson, B (reprint author), NCI, Canc Therapy Evaluat Program, Clin Invest Branch, Pediat Sect, 6130 Execut Blvd,Execut Plaza N, Rockville, MD 20852 USA. EM andersonb@ctep.nci.nih.gov NR 23 TC 13 Z9 13 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 15 PY 2005 VL 44 IS 7 BP 584 EP 588 DI 10.1002/pbc.20358 PG 5 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 921TZ UT WOS:000228789300002 PM 15700251 ER PT J AU Hasler, G LaSalle-Ricci, VH Ronquillo, JG Crawley, SA Cochran, LW Kazuba, D Greenberg, BD Murphy, DL AF Hasler, G LaSalle-Ricci, VH Ronquillo, JG Crawley, SA Cochran, LW Kazuba, D Greenberg, BD Murphy, DL TI Obsessive-compulsive disorder symptom dimensions show specific relationships to psychiatric comorbidity SO PSYCHIATRY RESEARCH LA English DT Article DE OCD; comorbidity; factor analysis; cluster analysis ID ANOREXIA-NERVOSA; TIC DISORDERS; SUBTYPES; PREVALENCE; FAMILY; SCALE; ONSET; OCD; DEPRESSION; SPECTRUM AB The goals of this study were to examine relationships among symptom categories in obsessive-compulsive disorder (OCD), to establish OCD symptom dimensions by factor- and cluster-analytic analyses, and to explore associations between OCD symptom dimensions and comorbid neuropsychiatric conditions. A total of 3 17 OCD participants underwent a systematic diagnostic interview using the Structured Clinical Interview for DSM-IV OCD symptoms assessed by the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (N= 169) and by the Thoughts and Behaviors Inventory (N=275) were Subjected to factor and cluster analyses. An identical four-factor solution emerged in two different data sets from overlapping samples, ill agreement with most smaller factor-analytic studies employing the YBOCS checklist alone. The cluster analysis confirmed the four-factor solution and provided additional information on the similarity among OCD symptom categories at five different levels. OCD symptom dimensions showed specific relationships to comorbid psychiatric disorders: Factor I (aggressive, sexual, religious and somatic obsessions, and checking compulsions) was broadly associated with comorbid anxiety disorders and depression; FactorII (obsessions of symmetry, and repeating, counting and ordering/arranging compulsions) with bipolar disorders and panic disorder/agoraphobia; and Factor III (contamination obsessions and cleaning compulsions) with eating disorders. Factors I and II were associated with early onset OCD. This study encourages the use of cluster analyses as a supplementary method to factor analyses to establish psychiatric symptom dimensions. The frequent co-occurrence of OCD with other psychiatric disorders and the relatively specific association patterns between OCD symptom dimensions and comorbid disorders support the importance of OCD subtyping for treatment, genetic, and other research studies of this heterogeneous disorder. (c) 2005 Published by Elsevier Ireland Ltd. C1 NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Butler Hosp, Brown Med Sch, Dept Psychiat & Human Behav, Providence, RI 02906 USA. RP Hasler, G (reprint author), NIMH, Intramural Res Program, Mood & Anxiety Disorders Program, NIH, 15K North Dr,Room 200,MSC 2670, Bethesda, MD 20892 USA. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 FU Intramural NIH HHS NR 42 TC 133 Z9 135 U1 5 U2 19 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 JUN 15 PY 2005 VL 135 IS 2 BP 121 EP 132 DI 10.1016/j.psychres.2005.03.003 PG 12 WC Psychiatry SC Psychiatry GA 941DB UT WOS:000230193800005 PM 15893825 ER PT J AU Freidlin, B Korn, EL AF Freidlin, B Korn, EL TI Testing treatment effects in the presence of competing risks SO STATISTICS IN MEDICINE LA English DT Article DE competing risks; cause-specific hazard; cumulative incidence; latent failure time model ID CAUSE-SPECIFIC FAILURE; BREAST-CANCER; CONCURRENT CHEMOTHERAPY; CUMULATIVE INCIDENCE; ADJUVANT THERAPY; RADIATION; RADIOTHERAPY; PROBABILITY; RECURRENCE; CURVES AB Competing risks are often encountered in clinical research. In the presence of multiple failure types, the time to the first failure of any type is typically used as an overall measure of the clinical impact for the patients. On the other hand, use of endpoints based on the type of failure directly related to the treatment mechanism of action allows one to focus on the aspect of the disease targeted by treatment. We review the methodology commonly used for testing failure specific treatment effects. Simulation results demonstrate that the cause-specific log-rank test is robust (in the sense of preserving the nominal level of the test) and has good power properties for testing for differences in the marginal latent failure-time distributions, whereas the use of a popular cumulative incidence based approach may be problematic for this aim. Published in 2005 by John Wiley & Sons, Ltd. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Freidlin, B (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, 6130 Execut Blvd,EPN 8122,MSC 7434, Bethesda, MD 20892 USA. EM freidlinb@ctep.nci.nih.gov NR 40 TC 26 Z9 26 U1 1 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2005 VL 24 IS 11 BP 1703 EP 1712 DI 10.1002/sim.2054 PG 10 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 929VN UT WOS:000229374800007 PM 15706579 ER PT J AU Boyce-Rustay, JM Holmes, A AF Boyce-Rustay, JM Holmes, A TI Functional roles of NMDA receptor NR2A and NR2B subunits in the acute intoxicating effects of ethanol in mice SO SYNAPSE LA English DT Article ID NUCLEUS-ACCUMBENS; FYN-KINASE; SENSITIVITY; ANTAGONISTS; NEURONS; INHIBITION; IFENPRODIL; DOPAMINE; REWARD AB The present study examined the roles of NR2A and NR2B subunit-containing NMDA receptors in the mediation of the sedative/hypnotic effects of ethanol in mice. The ability of the competitive NMDA antagonist, CGP-37849 (0, 1, or 3 mg/kg), and the NR2B-selective antagonist, Ro 25-6981 (0, 3, or 10 mg/kg), to alter (3 g/kg) ethanol-induced sleep time was measured in C57BL/6J mice and NR2A knockout (KO) mice. The results show that pretreatment with either antagonist significantly potentiated the sedative/hypnotic effects of ethanol in C57BL/6J mice. These effects were not significantly altered in NR2A KO mice. Basal sleep time responses to ethanol were also normal in NR2A KO mice. These findings confirm a major role for NMDA receptors in the acute intoxicating actions of ethanol and provide tentative support for a prepotent role of the NR2B subunit in these effects. (c) Published 2005 Wiley-Liss, Inc. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Boyce-Rustay, JM (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Bldg 10,Room 3C216, Bethesda, MD 20892 USA. EM boycej@mail.nih.gov NR 19 TC 32 Z9 33 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JUN 15 PY 2005 VL 56 IS 4 BP 222 EP 225 DI 10.1002/syn.20143 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 923CT UT WOS:000228887200006 PM 15803501 ER PT J AU Shiao, YH Crawford, EB Anderson, LM Patel, P Ko, K AF Shiao, YH Crawford, EB Anderson, LM Patel, P Ko, K TI Allele-specific germ cell epimutation in the spacer promoter of the 45S ribosomal RNA gene after Cr(III) exposure SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE gene methylation; sperm DNA; Chromium(III); rRNA spacer promoter; paternal exposure ID INTERGENIC SPACER; MALE-MICE; MOUSE; TRANSCRIPTION; SEQUENCE; CANCER; REGION AB Paternal exposure of mice to Cr(III) causes increased tumor risk in offspring; an epigenetic mechanism has been hypothesized. Representational difference analysis of gene methylation in sperm revealed hypomethylation in the 45S ribosomal RNA (rRNA) gene after Cr(III) exposure, compared with controls. The most striking effects were seen in the rRNA spacer promoter, a region in the intergenic region of rRNA gene clusters that can influence transcription. Methylation of the rRNA spacer promoter has not been studied heretofore. Sperm DNAs from Cr(III)-treated and control mice were modified by the bisulfite method followed by PCR amplification of the spacer promoter, including 27 CpG sites. Cloning and dideoxy sequencing identified sequence variants (T or G at base -2214) in the spacer promoter. The T allele had less DNA methylation than the G allele in control mice (17 of 17 clones vs. 42 of 72 clones, P = 0.0004). In spite of diversity of sperm DNA methylation patterns, the DNA clones from Cr(III)-exposed mice had fewer methylated CpG sites, by an average of 19% (P < 0.0001). This difference was limited to the G allele. The pyrosequencing technique was applied to quantify the percentage of methylation directly from amplified PCR products. Strikingly, for nine CpG sites including the spacer promoter core region, hypomethylation was highly significant in the Cr(III)-treated group (paired T test, P < 0.0001). Thus, one allele of the 45S rRNA spacer promoter is hypomethylated in sperm germ cells after Cr(III) exposure. This epimutation may lead to increase of tumor risk in the offspring. Published by Elsevier Inc. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Thomas Jefferson Univ, Ctr Translat Med, Philadelphia, PA 19107 USA. RP Shiao, YH (reprint author), NCI, Comparat Carcinogenesis Lab, W 7th St,Bldg 538,Room 205, Frederick, MD 21702 USA. EM shiao@mail.ncifrcf.gov NR 20 TC 29 Z9 32 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 15 PY 2005 VL 205 IS 3 BP 290 EP 296 DI 10.1016/j.taap.2004.10.017 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 933HC UT WOS:000229618500009 PM 15922014 ER PT J AU Takafuji, VA Howard, RD Ward, DL Sharova, LV Crisman, MV AF Takafuji, VA Howard, RD Ward, DL Sharova, LV Crisman, MV TI Modulation of equine articular chondrocyte messenger RNA levels following brief exposures to recombinant equine interleukin-1 beta SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE interleukin-1 beta; osteoarthritis; chondrocytes; gene expression ID FIBROBLAST GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; GENE-EXPRESSION; NITRIC-OXIDE; IN-VITRO; OSTEOARTHRITIC CARTILAGE; PROTEOGLYCAN METABOLISM; SIGNAL-TRANSDUCTION; FACTOR-BETA; ARTHRITIS AB The effect of recombinant equine IL-1 beta (EqIL-1 beta) on steady-state mRNA levels of equine articular chondrocytes in high-density monolayer culture was investigated using a customized cDNA array analysis. Total RNA samples isolated from chondrocytes cultured in media alone or with the addition of 1 ng/ml EqIL-1 beta for 1-, 3-, and 6-h durations of exposure were reverse transcribed, radiolabeled, and hybridized to a customized 380-target cDNA array. Means of duplicate log base 2 transformed hybridization signals were normalized to equine glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mean signal intensities. Differentially expressed transcripts were identified using a two-stage mixed linear analysis of variance model (Statistical Analysis Software, Cary, NC). A time-dependent pattern was observed in the number of transcripts increased >= twofold in response to EqIL-1 beta after 1, 3 and 6 h (1, 2 and 109 transcripts, respectively). At 6 h of EqIL-1 beta stimulation, signal intensities for 88 cDNA targets with purported function in processes related to cell cycle, intracellular signaling, transcription, translation, extracellular matrix turnover, and inflammation, as well as a number of cDNAs lacking homology to previously reported cDNA sequences, were increased > two-fold and were associated with p < 0.05. Principal component analysis identified a vector component (similar to 10% of the total variation) corresponding to a potential EqIL-1P co-regulation of cell cycle associated gene transcription. These results support and expand our existing comprehension of the complex role of IL-1 in modulated chondrocyte gene expression and suggest the involvement of specific target gene up-regulation and activation of downstream inflammatory cascade mediators. This study adds to the current understanding of the molecular events associated with an IL-1 induced inflammation and pathobiologic processes that may be associated with the development of equine osteoarthritis. (c) 2005 Elsevier B.V. All rights reserved. C1 VA MD Reg Coll Vet Med, Orthoped Res Lab, Blacksburg, VA 24061 USA. VA MD Reg Coll Vet Med, Mol Diagnost Lab, Blacksburg, VA 24061 USA. VA MD Reg Coll Vet Med, Stat Serv Lab, Blacksburg, VA 24061 USA. NIA, NIH, Baltimore, MD 21224 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Howard, RD (reprint author), Univ Missouri, 379 E Campus Dr,Clydesdale Hall, Columbia, MO 65211 USA. EM howardrd@missouri.edu NR 48 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JUN 15 PY 2005 VL 106 IS 1-2 BP 23 EP 38 DI 10.1016/j.vetimm.2005.01.003 PG 16 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 934VT UT WOS:000229737800003 PM 15910990 ER PT J AU Golovko, MY Faergeman, NJ Cole, NB Castagnet, PI Nussbaum, RL Murphy, EJ AF Golovko, MY Faergeman, NJ Cole, NB Castagnet, PI Nussbaum, RL Murphy, EJ TI alpha-Synuclein gene deletion decreases brain palmitate uptake and alters the palmitate metabolism in the absence of alpha-synuclein palmitate binding SO BIOCHEMISTRY LA English DT Article ID FATTY-ACID UPTAKE; STEROL CARRIER PROTEIN-2; LEWY BODY DEMENTIA; L-CELL FIBROBLASTS; PARKINSONS-DISEASE; RAT-LIVER; SUBCELLULAR-LOCALIZATION; TITRATION CALORIMETRY; ALZHEIMERS-DISEASE; PHOSPHOLIPASE-D AB alpha-Synuclein is an abundant protein in the central nervous system that is associated with a number of neurodegenerative disorders, including Parkinson's disease. Its physiological function is poorly understood, although recently it was proposed to function as a fatty acid binding protein. To better define a role for alpha-synuclein in brain fatty acid uptake and metabolism, we infused awake, wild-type, or alpha-synuclein gene-ablated mice with [1-C-14]palmitic acid (16:0) and assessed fatty acid uptake and turnover kinetics in brain phospholipids. alpha-Synuclein deficiency decreased brain 16:0 uptake 35% and reduced its targeting to the organic fraction. The incorporation coefficient for 16:0 entering the brain acyl-CoA pool was significantly decreased 36% in alpha-synuclein gene-ablated mice. Because incorporation coefficients alone are not predictive of fatty acid turnover in individual phospholipid classes, we calculated kinetic values for 16:0 entering brain phospholipid pools. alpha-Synuclein deficiency decreased the incorporation rate and fractional turnover of 16:0 in a number of phospholipid classes, but also increased the incorporation rate and fractional turnover of 16:0 in the choline glycerophospholipids. No differences in incorporation rate or turnover were observed in liver phospholipids, confirming that these changes in lipid metabolism were brain specific. Using titration microcalorimetry, we observed no binding of 16:0 or oleic acid to alpha-synuclein in vitro. Thus, alpha-synuclein has effects on 16:0 uptake and metabolism similar to those of an FABP, but unlike FABP, it does not directly bind 16:0; hence, the mechanism underlying these effects is different from that of a classical FABP. C1 Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Sch Med & Hlth Sci, Grand Forks, ND 58202 USA. Univ N Dakota, Dept Chem, Grand Forks, ND 58202 USA. Odense Univ, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Murphy, EJ (reprint author), Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Sch Med & Hlth Sci, 501 N Columbia Rd, Grand Forks, ND 58202 USA. EM emurphy@medicine.nodak.edu FU NINDS NIH HHS [1R21 NS043697-01A]; PHS HHS [5P20 R017699-02] NR 80 TC 58 Z9 58 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 14 PY 2005 VL 44 IS 23 BP 8251 EP 8259 DI 10.1021/bi0502137 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934RI UT WOS:000229725500005 PM 15938614 ER PT J AU Yikilmaz, E Rouault, TA Schuck, P AF Yikilmaz, E Rouault, TA Schuck, P TI Self-association and ligand-induced conformational changes of iron regulatory proteins 1 and 2 SO BIOCHEMISTRY LA English DT Article ID RESPONSIVE ELEMENT; CIRCULAR-DICHROISM; MESSENGER-RNA; SEDIMENTATION ANALYSIS; SECONDARY STRUCTURE; PICHIA-PASTORIS; BINDING PROTEIN; LAMM EQUATION; DEGRADATION; IRP2 AB Iron regulatory proteins (IRPs) regulate iron metabolism in mammalian cells. We used biophysical techniques to examine the solution properties of apo-IRP1 and apo-IRP2 and the interaction with their RNA ligand, the iron regulatory element (IRE). Sedimentation velocity and equilibrium experiments have shown that apo-IRP1 exists as an equilibrium mixture of monomers and dimers in solution, with an equilibrium dissociation constant in the low micromolar range and slow kinetic exchange between the two forms. However, only monomeric IRP1 is observed in complex with IRE, In contrast, IRP2 exists as monomer in both the apo-IRP2 form and in the IRP2/IRE complex. For both IRPs, sedimentation velocity and dynamic light-scattering experiments show a decrease of the Stokes radius upon binding of IRE. This conformational change was also observed by circular dichroism. Studies with an RNA molecule complementary to IRE indicate that, although specific base interactions can increase the stability of the protein/RNA complex, they are not essential for inducing this conformational change. The dynamic change of the IRP between different oligomeric and conformational states induced by interaction with IRE may play a role in the iron regulatory functions of IRPs. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Bioengn & Phys Sci, ORS, OD, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bldg 13,Room 3N17,13 South Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 43 TC 15 Z9 15 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 14 PY 2005 VL 44 IS 23 BP 8470 EP 8478 DI 10.1021/bi0500325 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 934RI UT WOS:000229725500027 PM 15938636 ER PT J AU Galperin, MY AF Galperin, MY TI A census of membrane-bound and intracellular signal transduction proteins in bacteria: Bacterial IQ, extroverts and introverts SO BMC MICROBIOLOGY LA English DT Review ID COMPLETE GENOME SEQUENCE; 2-COMPONENT REGULATORY SYSTEM; ESCHERICHIA-COLI K-12; SP STRAIN PCC-7120; ADENYLYL CYCLASES; SALMONELLA-ENTERICA; BACILLUS-SUBTILIS; DEHYDROGENASE SYNTHESIS; NUCLEOTIDE CYCLASES; TOPOLOGY PREDICTION AB Background: Analysis of complete microbial genomes showed that intracellular parasites and other microorganisms that inhabit stable ecological niches encode relatively primitive signaling systems, whereas environmental microorganisms typically have sophisticated systems of environmental sensing and signal transduction. Results: This paper presents results of a comprehensive census of signal transduction proteins histidine kinases, methyl-accepting chemotaxis receptors, Ser/Thr/Tyr protein kinases, adenylate and diguanylate cyclases and c-di-GMP phosphodiesterases-encoded in 167 bacterial and archaeal genomes, sequenced by the end of 2004. The data have been manually checked to avoid false-negative and false-positive hits that commonly arise during large-scale automated analyses and compared against other available resources. The census data show uneven distribution of most signaling proteins among bacterial and archaeal phyla. The total number of signal transduction proteins grows approximately as a square of genome size. While histidine kinases are found in representatives of all phyla and are distributed according to the power law, other signal transducers are abundant in certain phylogenetic groups but virtually absent in others. Conclusion: The complexity of signaling systems differs even among closely related organisms. Still, it usually can be correlated with the phylogenetic position of the organism, its lifestyle, and typical environmental challenges it encounters. The number of encoded signal transducers (or their fraction in the total protein set) can be used as a measure of the organism's ability to adapt to diverse conditions, the 'bacterial IQ', while the ratio of transmembrane receptors to intracellular sensors can be used to define whether the organism is an 'extrovert', actively sensing the environmental parameters, or an 'introvert', more concerned about its internal homeostasis. Some of the microorganisms with the highest IQ, including the current leader Wolinella succinogenes, are found among the poorly studied beta-, delta- and epsilon-proteobacteria. Among all bacterial phyla, only cyanobacteria appear to be true introverts, probably due to their capacity to conduct oxygenic photosynthesis, using a complex system of intracellular membranes. The census data, available at http://www.ncbi.nlm.nih.gov/Complete_Genomes/SignalCensus.html, can be used to get an insight into metabolic and behavioral propensities of each given organism and improve prediction of the organism's properties based solely on its genome sequence. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 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 [Z99 LM999999] NR 121 TC 226 Z9 240 U1 4 U2 37 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD JUN 14 PY 2005 VL 5 AR 35 DI 10.1186/1471-2180-5-35 PG 19 WC Microbiology SC Microbiology GA 953IV UT WOS:000231070700001 PM 15955239 ER PT J AU Ameli, R Snow, J Rakocevic, G Dalakas, MC AF Ameli, R Snow, J Rakocevic, G Dalakas, MC TI A neuropsychological assessment of phobias in patients with stiff person syndrome SO NEUROLOGY LA English DT Article AB A neuropsychological assessment was performed in 10 patients with stiff person syndrome (SPS) to determine whether their anxiety and phobic symptoms precede stiffness and spasms or represent a reaction to disability. No neurocognitive dysfunction was noted. Patients perceived fears and anxiety as realistic and caused by SPS rather than due to an inherent phobic neurosis. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disordrs Program, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, 10 Ctr Dr,Bldg 10,Rm 4N248, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 10 TC 22 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 14 PY 2005 VL 64 IS 11 BP 1961 EP 1963 DI 10.1212/01.WNL.0000163984.71993.FE PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 935IJ UT WOS:000229774000030 PM 15955955 ER PT J AU Kelley, K Theodore, WH AF Kelley, K Theodore, WH TI Prognosis 30 years after temporal lobectomy SO NEUROLOGY LA English DT Article ID EPILEPSY SURGERY; LOBE EPILEPSY; SEIZURE CONTROL; MORTALITY AB To assess the long-term outcome after temporal lobectomy, the authors obtained information from 48 patients and families traced though the NIH Medical Records Department, Social Security, National Death Indices, and other sources. Preoperative evaluation, limited by current standards, was based mainly on interictal surface EEG. After a mean 29.9-year follow-up, 24 were seizure free, and 10 had died. Early seizure recurrence and invasive EEG studies predicted worse long-term outcome. C1 NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NINDS, Clin Epilepsy Sect, NIH, NIH Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 10 TC 13 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 14 PY 2005 VL 64 IS 11 BP 1974 EP 1976 DI 10.1212/01.WNL.0000163998.01543.CF PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 935IJ UT WOS:000229774000034 PM 15955959 ER PT J AU Chalela, JA Dunn, B Todd, JW Warach, S AF Chalela, JA Dunn, B Todd, JW Warach, S TI Induced hypertension improves cerebral blood flow in acute ischemic stroke SO NEUROLOGY LA English DT Editorial Material C1 NINDS, Stroke Diagnost & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Chalela, JA (reprint author), NINDS, Stroke Diagnost & Therapeut Sect, NIH, 10 Ctr Dr,Room B1D733,MSC 1063, Bethesda, MD 20892 USA. EM chalelaj@ninds.nih.gov NR 2 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUN 14 PY 2005 VL 64 IS 11 BP 1979 EP 1979 DI 10.1212/01.WNL.0000156360.70336.18 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 935IJ UT WOS:000229774000036 PM 15955961 ER PT J AU Callicott, JH Straub, RE Pezawas, L Egan, MF Mattay, VS Hariri, AR Verchinski, BA Meyer-Lindenberg, A Balkissoon, R Kolachana, B Goldberg, TE Weinberger, DR AF Callicott, JH Straub, RE Pezawas, L Egan, MF Mattay, VS Hariri, AR Verchinski, BA Meyer-Lindenberg, A Balkissoon, R Kolachana, B Goldberg, TE Weinberger, DR TI Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-for-Neuroscience CY NOV 08-12, 2003 CL NEW ORLEANS, LA SP Soc Neurosci DE association; hippocampus; morphometry ID WORKING-MEMORY; TRANSMISSION/DISEQUILIBRIUM TEST; HAPLOTYPE TRANSMISSION; VAL66MET POLYMORPHISM; NEURITE OUTGROWTH; RELATIVE RISK; ASSOCIATION; BRAIN; DISRUPTED-IN-SCHIZOPHRENIA-1; LINKAGE AB Disrupted-in-schizophrenia 1 (DISC1) is a promising schizophrenia candidate gene expressed predominantly within the hippocampus. We typed 12 single-nucleotide polymorphisms (SNPs) that covered the DISC1 gene. A three-SNP haplotype [hCV219779 (C)-rs821597 (G)-rs821616 (A)] spanning 83 kb of the gene was associated with schizophrenia in a family-based sample (P = 0.002). A common nonconservative SNP (Ser704Cys) (rs821616) within this haplotype was associated with schizophrenia (P = 0.004). Based on primary expression of DISC1 in hippocampus, we hypothesized that allelic variation at Ser704Cys would have a measurable impact on hippocampal structure and function as assayed via specific hippocampus-related intermediate phenotypes. In addition to overtransmission in schizophrenia, the Ser allele was associated with altered hippocampal structure and function in healthy subjects, including reduced hippocampal gray matter volume and altered engagement of the hippocampus during several cognitive tasks assayed with functional magnetic resonance imaging. These convergent data suggest that allelic variation within DISC1, either at Ser704Cys or haplotypes monitored by it, increases the risk for schizophrenia and that the mechanism of this effect involves structural and functional alterations in the hippocampal formation. C1 NIMH, Div Intramural Res, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program,NIH, Bethesda, MD 20892 USA. US Dept HHS, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), Bldg 10,Ctr Dr,Room 4C-216,MSC 1364, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Hariri, Ahmad/D-5761-2011; Callicott, Joseph/C-9102-2009; OI Callicott, Joseph/0000-0003-1298-3334; Pezawas, Lukas/0000-0002-1329-6352; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 NR 49 TC 341 Z9 360 U1 2 U2 15 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2005 VL 102 IS 24 BP 8627 EP 8632 DI 10.1073/pnas.0500515102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200042 PM 15939883 ER PT J AU Cook, JD Davis, BJ Cai, SL Barrett, JC Conti, CJ Walker, CL AF Cook, JD Davis, BJ Cai, SL Barrett, JC Conti, CJ Walker, CL TI Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE developmental programming; gene-environment interaction; Eker rat; uterine leiomyoma; Tsc-2 ID NEONATAL DIETHYLSTILBESTROL EXPOSURE; ESTROGEN-RECEPTOR-ALPHA; CORONARY HEART-DISEASE; RENAL-CELL CARCINOMA; EKER RAT; MOUSE UTERUS; UTERINE ADENOCARCINOMA; TUBEROUS SCLEROSIS; BIRTH-WEIGHT; TSC2 GENE AB Gene-environment interactions are important determinants of cancer risk. Traditionally, gene-environment interactions are thought to contribute to tumor-suppressor-gene penetrance by facilitating or inhibiting the acquisition of additional somatic mutations required for tumorigenesis. Here, we demonstrate that a distinctive type of gene-environment interaction can occur during development to enhance the penetrance of a tumor-suppressor-gene defect in the adult. Using rats carrying a germ-line defect in the tuberous sclerosis complex 2 (Tsc-2) tumor-suppressor gene predisposed to uterine leiomyomas, we show that an early-life exposure to diethylstilbestrol during development of the uterus increased tumor-suppressor-gene penetrance from 65% to > 90% and tumor multiplicity and size in genetically predisposed animals, but it failed to induce tumors in wild-type rats. This exposure was shown to impart a hormonal imprint on the developing uterine myometrium, causing an increase in expression of estrogen-responsive genes before the onset of tumors. Loss of function of the normal Tsc-2 allele remained the rate-limiting event for tumorigenesis; however, tumors that developed in exposed animals displayed an enhanced proliferative response to steroid hormones relative to tumors that developed in unexposed animals. These data suggest that exposure to environmental factors during development can permanently reprogram normal physiological tissue responses and thus lead to increased tumor-suppressor-gene penetrance in genetically susceptible individuals. C1 Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, Smithville, TX 78957 USA. Univ Texas, Grad Sch Biomed Sci, Houston, TX 77030 USA. AstraZeneca, Waltham, MA 02451 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Walker, CL (reprint author), Univ Texas, MD Anderson Canc Ctr, Sci Pk Res Div, POB 389, Smithville, TX 78957 USA. EM cwalker@odin.mdacc.tmc.edu FU NCI NIH HHS [CA16672, P30 CA016672]; NICHD NIH HHS [HD46282, R01 HD046282]; NIEHS NIH HHS [ES07784, ES08263, P30 ES007784, R01 ES008263] NR 42 TC 59 Z9 61 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2005 VL 102 IS 24 BP 8644 EP 8649 DI 10.1073/pnas.0503218102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200045 PM 15937110 ER PT J AU Martomo, SA Yang, WW Wersto, RP Ohkumo, T Kondo, Y Yokoi, M Masutani, C Hanaoka, F Gearhart, PJ AF Martomo, SA Yang, WW Wersto, RP Ohkumo, T Kondo, Y Yokoi, M Masutani, C Hanaoka, F Gearhart, PJ TI Different mutation signatures in DNA polymerase eta(-) and MSH6-deficient mice suggest separate roles in antibody diversification SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE class switch recombination; somatic hypermutation; low-fidelity DNA polymerase; mismatch repair ID CLASS-SWITCH RECOMBINATION; IMMUNOGLOBULIN VARIABLE GENES; AFFECT SOMATIC HYPERMUTATION; CYTIDINE DEAMINASE AID; STIMULATED B-CELLS; MISMATCH REPAIR; DEFICIENT MICE; REGIONS; IG; REVEALS AB Hypermutation in immunoglobulin genes produces a high frequency of substitutions of all four bases, which are likely generated by low-fidelity DNA polymerases. Indeed, humans deficient for DNA polymerase (pol) eta have decreased substitutions of A-T base pairs in variable and switch regions. To study the role of pol eta in a genetically tractable system, we created mice lacking pol eta. B cells from Polh(-/-) mice produced normal amounts of IgG, indicating that pol eta does not affect class switch recombination. Similar to their human counterparts, variable and switch regions from Polh(-/-) mice had fewer substitutions of A-T base pairs and correspondingly more mutations of C-G base pairs, which firmly establishes a central role for pol eta in hypermutation. Notably, the location and types of substitutions differ markedly from those in Msh6(-/-) clones, which also have fewer A-T mutations. The data suggest that pol eta preferentially synthesizes a repair patch on the nontranscribed strand, whereas MSH6 functions to generate the patch. C1 NIA, Lab Mol Gerontol, NIH, Res Resources Branch, Baltimore, MD 21224 USA. Osaka Univ, Grad Sch Frontier Biosci, Osaka 5650871, Japan. RIKEN, Discovery Res Inst, Wako, Saitama 3510198, Japan. Japan Sci & Technol Agcy, Solut Oriented Res Sci & Technol, Wako, Saitama 3510198, Japan. RP Gearhart, PJ (reprint author), NIA, Lab Mol Gerontol, NIH, Res Resources Branch, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gearhartp@grc.nia.nih.gov RI Masutani, Chikahide/I-6160-2014 NR 46 TC 92 Z9 92 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2005 VL 102 IS 24 BP 8656 EP 8661 DI 10.1073/pnas.0501852102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200047 PM 15939880 ER PT J AU Dubois, SP Waldmann, TA Muller, JR AF Dubois, SP Waldmann, TA Muller, JR TI Survival adjustment of mature dendritic cells by IL-15 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; cytokine; antigen-presenting cells; memory phenotype CD8 T cell ID CD8(+) T-CELLS; NATURAL-KILLER-CELLS; KAPPA-B SITE; CUTTING EDGE; GENE-EXPRESSION; IN-VIVO; MEMORY; INTERLEUKIN-15; IL-15R-ALPHA; APOPTOSIS AB The survival of CD8(+)/CD44(hi) memory phenotype T cells depends on an IL-15 activity on nonlymphoid cells. Here, we report that IL-15 and its receptor were induced on dendritic cells (DCs) by a combination of IFN-gamma and NF-kappa B relA inducers. IL-15 conferred in an autocrine loop resistance to apoptosis that accompanied the maturation process in DCs in vitro. As an apparent result in vivo, mice deficient in IL-15 or its receptor harbor few DCs. Injecting DCs into IL-15(-/-) mice was associated with the appearance of CD8(+)/CD44(hi) T cells that depended on IL-15 expression but also correlated with the longevity of the DCs. These findings support the hypothesis that DCs mediate the effect of IL-15 on CD8(+)/CD44(hi) memory phenotype T cells. C1 NCI, Metab Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov NR 33 TC 57 Z9 60 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2005 VL 102 IS 24 BP 8662 EP 8667 DI 10.1073/pnas.0503360102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200048 PM 15932944 ER PT J AU Harashima, S Clarke, A Christie, MR Notkins, AL AF Harashima, S Clarke, A Christie, MR Notkins, AL TI The dense core transmembrane vesicle protein IA-2 is a regulator of vesicle number and insulin secretion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE beta cells; MIN-6 cells; short interfering RNA; glucose ID DEPENDENT DIABETES-MELLITUS; PHOSPHATASE-LIKE MOLECULE; TYROSINE-PHOSPHATASE; PANCREATIC-ISLETS; BETA-CELLS; EXPRESSION; AUTOANTIGEN; GLUCOSE; PREDICTION; FAMILY AB IA-2 is an enzymatically inactive member of the transmembrane protein tyrosine phosphate family located in dense core secretory vesicles and a major autoantigen in type 1 diabetes. Recent studies showed that targeted disruption of the IA-2 gene in mice resulted in impairment of insulin secretion and glucose intolerance. Insulin homeostasis, however, is a complex process involving a cascade of regulatory factors, and IA-2 is widely expressed in neuroendocrine cells throughout the body. Consequently, it is uncertain whether the impairment of insulin secretion in IA-2 knockout mice is a direct result of the knockout of IA-2 in beta cells or to counter regulatory alterations resulting from IA-2 knockout in other neuroendocrine cells. To define the function of IA-2, we studied the secretion of insulin in a single cell type, MIN-6, by overexpressing and knocking down IA-2. Our experiments showed that overexpression of IA-2 resulted in a 6-fold increase in glucose- or K+-induced insulin secretion and a approximate to 3-fold increase in the number of secretory vesicles and the insulin content of cells. in contrast, knockdown of endogenous IA-2 by short interfering RNA resulted in nearly a complete loss of glucose-induced insulin secretion and a 50% decrease in basal insulin release. The half-life of insulin in cells overexpressing IA-2 was nearly twice as great as that in mock-transfected cells, suggesting that IA-2 was stabilizing the insulin-containing vesicles. From these results we conclude that in beta cells, IA-2 is an important regulator of dense core vesicle number and glucose-induced and basal insulin secretion. C1 Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Churchill Hosp, Diabet Res Labs, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England. Univ London Kings Coll, Guys Kings Coll, Dept Med, London SE5 9PJ, England. Univ London Kings Coll, St Thomas Sch Med, London SE5 9PJ, England. RP Notkins, AL (reprint author), Natl Inst Dent & Craniofacial Res, Expt Med Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. EM anotkins@mail.nih.gov NR 28 TC 46 Z9 47 U1 1 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 JUN 14 PY 2005 VL 102 IS 24 BP 8704 EP 8709 DI 10.1073/pnas.0408887102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200055 PM 15939893 ER PT J AU Shannon, JG Howe, D Heinzen, RA AF Shannon, JG Howe, D Heinzen, RA TI Virulent Coxiella burnetii does not activate human dendritic cells: Role of lipopolysaccharide as a shielding molecule SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE immune evasion; Q fever; toll-like receptor; persistence; phase variation ID TOLL-LIKE RECEPTOR-2; Q FEVER INFECTIONS; PHASE-I LIPOPOLYSACCHARIDE; LONG-TERM PERSISTENCE; CELLULAR-IMMUNITY; GUINEA PIGS; WHITE MICE; MATURATION; INTERLEUKIN-10; CYTOKINES AB Coxiella, burnetii is an obligate intracellular bacterium and the etiological agent of the zoonotic disease Q fever. Acute human Q fever is characterized by flu-like symptoms that, in some cases, can result in a persistent infection that may reactivate months or years after initial exposure. Mechanisms by which this obligate parasite evades clearance by the host immune response during persistent infection are unknown. Here, we characterized the interaction of C burnetii with dendritic cells (DC), critical components of both innate and adaptive immunity. Human DC were infected with two isogenic C. burnetti strains that differ in LPS length. Infection by the Nine Mile phase I (NMI) strain, which is fully virulent and produces full-length LPS, did not result in DC maturation. In contrast, infection by the avirulent Nine Mile phase 11 strain, producing a severely truncated LPS, resulted in toll-like receptor 4-independent DC maturation and approximate to 10-fold more IL-12 and TNF production. NMI did not actively inhibit DC maturation as NMI-infected DC subsequently matured if treated with Escherichia coli LPS or Nine Mile phase II. Furthermore, removal of LPS from NMI dramatically increased its ability to stimulate DC. We propose a model whereby LIPS of virulent C. burnetii masks toll-like receptor ligands from innate immune recognition by DC, thereby allowing replication without significant maturation or inflammatory cytokine production. This immune evasion strategy may allow C. burnetii to, persist in an immunocompetent host. C1 NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Heinzen, RA (reprint author), NIAID, Coxiella Pathogenesis Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, 903 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov RI Shannon, Jeffrey/A-5735-2009 OI Shannon, Jeffrey/0000-0003-4211-4308 NR 45 TC 67 Z9 70 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 14 PY 2005 VL 102 IS 24 BP 8722 EP 8727 DI 10.1073/pnas.0501863102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 935TV UT WOS:000229807200058 PM 15939879 ER PT J AU Stroncek, DF Basil, C Nagorsen, D Deola, S Arico, E Smith, K Wang, E Marincola, FM Panelli, MC AF Stroncek, DF Basil, C Nagorsen, D Deola, S Arico, E Smith, K Wang, E Marincola, FM Panelli, MC TI Delayed polarization of mononuclear phagocyte transcriptional program by type I interferon isoforms SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTORS; STIMULATED GENES; EXPRESSION PATTERNS; INDUCIBLE GENE; RETINOIC ACID; IFN-ALPHA; PROTEIN; ACTIVATION AB Background: Interferon ( IFN)-alpha is considered a key modulator of immunopathological processes through a signature-specific activation of mononuclear phagocytes (MPs). This study utilized global transcript analysis to characterize the effects of the entire type I IFN family in comparison to a broad panel of other cytokines on MP previously exposed to Lipopolysaccharide ( LPS) stimulation in vitro. Results: Immature peripheral blood CD14+ MPs were stimulated with LPS and 1 hour later with 42 separate soluble factors including cytokines, chemokines, interleukins, growth factors and IFNs. Gene expression profiling of MPs was analyzed 4 and 9 hours after cytokine stimulation. Four hours after stimulation, the transcriptional analysis of MPs revealed two main classes of cytokines: one associated with the alternative and the other with the classical pathway of MP activation without a clear polarization of type I IFNs effects. In contrast, after 9 hours of stimulation most type I IFN isoforms induced a characteristic and unique transcriptional pattern separate from other cytokines. These "signature" IFNs included; IFN-beta, IFN-alpha 2b/alpha 2, IFN-alpha 1, IFN-alpha 2, IFN-alpha C, IFN-alpha J1, IFN-alpha H2, and INF-alpha 4B and induced the over-expression of 44 genes, all of which had known functional relationships with IFN such as myxovirus resistance (Mx)-1, Mx-2, and interferon-induced hepatitis C-associated microtubular aggregation protein. A second group of type I IFNs segregated separately and in closer association with the type II IFN-gamma. The phylogenetic relationship of amino acid sequences among type I IFNs did not explain their subclassification, although differences at positions 94 through 109 and 175 through 189 were present between the signature and other IFNs. Conclusion: Seven IFN-alpha isoforms and IFN-beta participate in the late phase polarization of MPs conditioned by LPS. This information broadens the previous view of the central role played by IFN-alpha in autoimmunity and tumor rejection by including and/ or excluding an array of related factors likely to be heterogeneously expressed by distinct sub-populations of individuals in sickness or in response to biological therapy. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Med Berlin, Med Klin 2, Charite, Berlin, Germany. RP Stroncek, DF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov; chris.basil@gmail.com; dirk.nagorsen@charite.de; sdeola@cc.nih.gov; earico@cc.nih.gov; KSmith2@cc.nih.gov; EWang@cc.nih.gov; FMarincola@cc.nih.gov; MPanelli@cc.nih.gov NR 70 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD JUN 13 PY 2005 VL 3 DI 10.1186/1479-5876-3-24 PG 21 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 968KJ UT WOS:000232161100001 ER PT J AU Glasgow, E Ryu, SL Yamashita, M Zhang, BJ Mutsuga, N Gainer, H AF Glasgow, E Ryu, SL Yamashita, M Zhang, BJ Mutsuga, N Gainer, H TI APeg3, a novel paternally expressed gene 3 antisense RNA transcript specifically expressed in vasopressinergic magnocellular neurons in the rat supraoptic nucleus SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Peg 3; antisense; imprinted genes; Supraoptic nucleus; hypothalamus; vasopressin; non-coding RNA ID ZINC-FINGER GENE; HUMAN-CHROMOSOME 19Q13.4; IMPRINTED GENE; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; PROXIMAL CHROMOSOME-7; OXYTOCIN; PEG3; METHYLATION; REGION; BRAIN AB Vasopressin (VP) and oxytocin (OT) play critical roles in the regulation of salt and water balance, lactation, and various behaviors and are expressed at very high levels in specific magnocellular neurons (MCNs) in the hypothalamo-neurohypophysial system (HNS). In addition to the cell-specific expression of the VP and OT genes in these cells, there are other transcripts that are preferentially expressed in the VP or OT MCNs. One such gene, paternally expressed gene 3 (Peg3), is an imprinted gene expressed exclusively from the paternal allele that encodes a Kruppel-type zinc finger-containing protein involved in maternal behavior and is abundantly expressed in the VP-MCNs. We report here the robust expression in the VP-MCNs of an RNA, which we designate APeg3 that is transcribed in the antisense direction to the 3' untranslated region of the Peg3 gene. The APeg3 mRNA is about 1 kb in size, and the full-length sequence of APeg3, as determined by 5' and 3' RACE, contains an open reading frame that predicts a protein of 93 amino acids and is predominantly expressed in VP-MCNs. Both Peg3 and APeg3 gene expression in the VP-MCNs increase during systemic hyperosmolality in vivo, demonstrating that both of these genes are osmoregulated. Published by Elsevier B.V. C1 Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Northeastern Ohio Univ Coll Med & Pharm, Coll Med, Dept Neurobiol, Rootstown, OH 44272 USA. RP Gainer, H (reprint author), Natl Inst Neurol Disorders & Stroke, Neurochem Lab, NIH, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov OI Glasgow, Eric/0000-0001-7729-3954 NR 50 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD JUN 13 PY 2005 VL 137 IS 1-2 BP 143 EP 151 DI 10.1016/j.molbrainres.2005.02.030 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 939AB UT WOS:000230043400018 ER PT J AU Hubbs, A Greskevitch, M Kuempel, E Suarez, F Toraason, M AF Hubbs, A Greskevitch, M Kuempel, E Suarez, F Toraason, M TI Abrasive blasting agents: Designing studies to evaluate relative risk SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article; Proceedings Paper CT 38th Annual Conference on Toxicology and Risk Assessment CY APR 26-30, 2004 CL West Chester, OH SP Tri -Serv Toxicol, US Environm Protect Agency, Nat Ctr Environm Assessment, Agency Toxic Substances Dis Registry, Div Toxicol, Nat Inst Occupational Safety Hlth ID COMPARATIVE PULMONARY TOXICITY; FERRIC-OXIDE PARTICLES; LUNG-CANCER; AUTOIMMUNE-DISEASE; CRYSTALLINE SILICA; EXPOSURE-RESPONSE; SURFACE-AREA; LYMPH-NODES; IRON-OXIDES; INHALATION AB Workers exposed to respirable crystalline silica used in abrasive blasting are at increased risk of developing a debilitating and often fatal fibrotic lung disease called silicosis. The National Institute for Occupational Safety and Health (NIOSH) recommends that silica sand be prohibited as abrasive blasting material and that less hazardous materials be used in blasting operations. However, data arc, needed on the relative risks associated with exposure to abrasive blasting materials other than silica. NIOSH has completed acute studies in rats (Hubbs et al., 2001; Porter et al., 2002). To provide dose-response data applicable to making recommendation for occupational exposure limits, NIOSH has collaborated with the National Toxicology Program (NTP) to design longer term studies with silica substitutes. For risk assessment purposes, selected doses will include concentrations that are relevant to human exposures. Rat lung burdens achieved should be comparable to those estimated in humans with working lifetime exposures, even if this results in "overloading" doses in rats. To quantify both (lose and response, retained particle burdens in the lungs and lung-associated lymph nodes will be measured, as well as biochemical and pathological indices of pulmonary response. This design will facilitate assessment of the pulmonary fibrogenic potential of inhaled abrasive blasting agents at occupationally relevant concentrations. C1 NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA. NIOSH, Cincinnati, OH 45226 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hubbs, A (reprint author), NIOSH, Hlth Effects Lab Div, Ctr Dis Control & Prevent, Mailstop L2015,1095 Willowdale Rd, Morgantown, WV 26505 USA. EM AHuhbs@cdc.gov NR 80 TC 8 Z9 8 U1 3 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD JUN 11 PY 2005 VL 68 IS 11-12 BP 999 EP 1016 DI 10.1080/15287390590912612 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 946OP UT WOS:000230582100010 PM 16020188 ER PT J AU Sigurdson, AJ Ronckers, CM Mertens, AC Stovall, M Smith, SA Liu, Y Berkow, RL Hammond, S Neglia, JP Meadows, AT Sklar, CA Robison, LL Inskip, PD AF Sigurdson, AJ Ronckers, CM Mertens, AC Stovall, M Smith, SA Liu, Y Berkow, RL Hammond, S Neglia, JP Meadows, AT Sklar, CA Robison, LL Inskip, PD TI Primary thyroid cancer after a first tumour in childhood (the Childhood Cancer Survivor Study): a nested case-control study SO LANCET LA English DT Article ID 2ND MALIGNANT NEOPLASMS; BONE-MARROW-TRANSPLANTATION; HODGKINS-DISEASE; EPIDEMIOLOGIC EVIDENCE; THERAPEUTIC RADIATION; RISK; RADIOTHERAPY; ADOLESCENCE; IRRADIATION; NEUROBLASTOMA AB Background Survivors of malignant disease in childhood who have had radiotherapy to the head, neck, or upper thorax have an increased risk of subsequent primary thyroid cancer, but the magnitude of risk over the therapeutic dose range has not been well established. We aimed to quantify the long-term risk of thyroid cancer after radiotherapy and chemotherapy. Methods In a nested case-control study, 69 cases with pathologically confirmed thyroid cancer and 265 matched controls without thyroid cancer were identified from 14 054 5-year survivors of cancer during childhood from the Childhood Cancer Survivor Study cohort. Childhood cancers were diagnosed between 1970 and 1986 with cohort follow-up to 2000. Findings Risk of thyroid cancer increased with radiation doses up to 20-29 Gy (odds ratio 9.8 [95% Cl 3.2-34.8]). At doses greater than 30 Gy, a fall in the dose-response relation was seen. Both the increased and decreased risks were more pronounced in those diagnosed with a first primary malignant disease before age 10 years than in those older than 10 years. Furthermore, the fall in risk remained when those diagnosed with Hodgkin's lymphoma were excluded. Chemotherapy for the first cancer was not associated with thyroid-cancer risk, and it did not modify the effect of radiotherapy. 29 (42%) cases had a first diagnosis of Hodgkin's lymphoma compared with 49 (19%) controls. 11 (42%) of those who had Hodgkin's lymphoma had subsequent thyroid cancers smaller than 1 cm compared with six (17%) of those who had other types of childhood cancer (p=0.07). Interpretation The reduction in radiation dose-response for risk of thyroid cancer after childhood exposure to thyroid doses higher than 30 Gy is consistent with a cell-killing effect. Standard long-term follow-up of patients who have had Hodgkin's lymphoma for detection of thyroid cancer should also be undertaken for survivors of any cancer during childhood who received radiotherapy to the thorax or head and neck region. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. Univ Alabama, Birmingham, AL USA. Childrens Hosp, Dept Lab Med & Pathol, Columbus, OH 43205 USA. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7092,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov FU NCI NIH HHS [CA 55727] NR 49 TC 192 Z9 199 U1 0 U2 6 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 11 PY 2005 VL 365 IS 9476 BP 2014 EP 2023 DI 10.1016/S0140-6736(05)66695-0 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 934IB UT WOS:000229701400023 PM 15950715 ER PT J AU Currier, JS Kendall, MA Zackin, R Henry, WK Alston-Smith, B Torriani, FJ Schouten, J Mickelberg, K Li, YJ Hodis, HN AF Currier, JS Kendall, MA Zackin, R Henry, WK Alston-Smith, B Torriani, FJ Schouten, J Mickelberg, K Li, YJ Hodis, HN CA AACTG 5078 Study Team TI Carotid artery intima-media thickness and HIV infection: traditional risk factors overshadow impact of protease inhibitor exposure SO AIDS LA English DT Article DE atherosclerosis; HIV infection; carotid intima-media thickness; protease inhibitors ID INSULIN-RESISTANCE; ANTIRETROVIRAL THERAPY; MYOCARDIAL-INFARCTION; HYPERLIPIDEMIA; ATHEROSCLEROSIS; LIPODYSTROPHY; METABOLISM; INDINAVIR; COHORT AB Context: The impact of HIV infection and exposure to antiretroviral therapy on the development of subclinical atherosclerosis is incompletely understood. Objective: To compare intima-media thickness (IMT) of the carotid artery between HIV-infected subjects receiving protease inhibitor-containing regimens and subjects not receiving these regimens and to compare differences in the IMT of the carotid artery between HIV-infected subjects and HIV-uninfected subjects. Methods: A prospective matched cohort study in university-based outpatient clinics. Groups of three individuals (triads) matched on the following characteristics were enrolled: age, sex, race/ethnicity, smoking status, blood pressure and menopausal status. Group 1, HIV-infected subjects with continuous use of protease inhibitor (PI) therapy for >= 2 years; group 2, HIV-infected subjects without prior PI use; and group 3: HIV-uninfected. Ultrasonographers at six sites sent standardized ultrasound images to a central reading site for carotid IMT measurements. Carotid IMT was compared within the HIV-infected groups (1 and 2) and between the HIV-infected and uninfected groups in a matched analysis. Results: One hundred and thirty-four individuals were enrolled in 45 triads. The median IMT in groups 1, 2 and 3 was 0.690, 0.712 and 0.698 mm, respectively. There were no statistically significant differences in IMT between groups 1 and 2, or in the combined HIV groups compared with the HIV uninfected group. Significant predictors of carotid IMT in a multivariate model included high-density lipoprotein (HDL) cholesterol, the interaction of HDL cholesterol and triglycerides, age and body mass index. Conclusions: We found no association between PI inhibitor exposure or HIV infection and carotid IMT. (c) 2005 Lippincott Williams & Wilkins. C1 Univ Calif Los Angeles, David Geffen Sch Med, Ctr Clin AIDS Res & Educ, Dept Med,Div Infect Dis, Los Angeles, CA USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Minnesota, Hennepin Cty Med Ctr, HIV Program, Minneapolis, MN USA. NIAID, Div Aids, Bethesda, MD USA. Univ Calif San Diego, Dept Med, Div Infect Dis, San Diego, CA 92103 USA. Univ Washington, Dept Gen Surg, Seattle, WA 98195 USA. Univ Penn, AIDS Clin Trials Unit, Philadelphia, PA 19104 USA. Univ So Calif, Keck Sch Med, Div Cardiovasc Med, Atherosclerosis Res Unit, Los Angeles, CA 90089 USA. RP Currier, JS (reprint author), Univ Calif Los Angeles, CARE Ctr, CHS, BH-412,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM jscurrier@mednet.ucla.edu RI Kendall, Michelle/B-7665-2016 OI Kendall, Michelle/0000-0001-9160-4544 FU NIAID NIH HHS [U01 AI27660, U01 AI027660, K24 AI056933, AI-3885, K24 AI56933] NR 22 TC 125 Z9 128 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 10 PY 2005 VL 19 IS 9 BP 927 EP 933 DI 10.1097/01.aids.0000171406.53737.f9 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 943QA UT WOS:000230367700009 PM 15905673 ER PT J AU Seaberg, EC Munoz, A Lu, M Detels, R Margolick, JB Riddler, SA Williams, CM Phair, JP AF Seaberg, EC Munoz, A Lu, M Detels, R Margolick, JB Riddler, SA Williams, CM Phair, JP CA Multictr AIDS Cohort Study TI Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003 SO AIDS LA English DT Article DE HIV; antiretroviral therapy; highly active antiretroviral therapy; hypertension; isolated systolic hypertension ID ISOLATED SYSTOLIC HYPERTENSION; CARDIOVASCULAR RISK-FACTOR; MULTICENTER AIDS COHORT; INTIMA-MEDIA THICKNESS; HIV-POSITIVE PATIENTS; BLOOD-PRESSURE; INSULIN-RESISTANCE; INFECTION; ATHEROSCLEROSIS; HYPERLIPIDEMIA AB Objective: To examine the impact of HIV infection and highly active antiretroviral therapy on systolic and diastolic hypertension. Design: Cohort study with semi-annual assessment of the outcome. Methods: We studied 5578 participants of the Multicenter AIDS Cohort Study with blood pressure measurements obtained between 1984 and 2003. The primary outcomes were systolic hypertension (SH; systolic blood pressure > 140 mmHg) and diastolic hypertension (DH; diastolic blood pressure > 90 mmHg). Statistical analyses were performed using multiple logistic regression with robust variance estimation. Results: Of the 84 813 person-visits available for analysis, 7.3 and 8.0% showed SH and DH, respectively. Controlling for age, race, body mass index, and smoking, HIV positive men not taking antiretroviral therapy were significantly less likely than HIV negative men to have SH [odds ratio (OR), 0.79; 95% confidence interval (CI), 0.700.89], as were men taking mono/combination therapy (OR, 0.69; 95% CI, 0.59-0.80). The prevalence of SH among men taking highly active antiretroviral therapy (HAART) for less than 2 years was similar to that among HIV negative men (OR, 1.06; 95% Cl, 0.87-1.30), but was significantly higher thereafter; for 2 to 5 years of HAART (OR, 1.51; 95% CI, 1.25-1.82) and for more than 5 years of HAART (OR, 1.70; 95% CI, 1.34-2.16). In contrast, DH was not significantly higher among men with prolonged HAART use compared to that among HIV negative controls. Conclusions: Prolonged HAART use was significantly associated with a higher prevalence of SH. This finding suggests that individuals taking HAART may be at increased risk of developing hypertension-related conditions and underscores the importance of blood pressure monitoring among these individuals. (c) 2005 Lippincott Williams & Wilkins C1 Johns Hopkins Univ, Blooomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Blooomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NIAID, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL 60611 USA. Northwestern Univ, Dept Med, Chicago, IL 60611 USA. RP Seaberg, EC (reprint author), Johns Hopkins Univ, Blooomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,Room E-7634, Baltimore, MD 21205 USA. EM eseaberg@jhsph.edu FU NCRR NIH HHS [5-M01-RR-00052]; NIAID NIH HHS [UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35042, UO1-AI-35043, UO1-AI-37613, UO1-AI-37984] NR 40 TC 159 Z9 165 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 10 PY 2005 VL 19 IS 9 BP 953 EP 960 DI 10.1097/01.aids.0000171410.76607.f8 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 943QA UT WOS:000230367700013 PM 15905677 ER PT J AU Culmsee, C Mattson, MP AF Culmsee, C Mattson, MP TI p53 in neuronal apoptosis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE p53; MDM-2; BH3-only proteins; DNA damage; glutamate; neurodegeneration ID FACTOR-KAPPA-B; CYCLIN-DEPENDENT KINASES; TUMOR-SUPPRESSOR GENE; CEREBRAL-ARTERY OCCLUSION; PROGRAMMED CELL-DEATH; AMYLOID-BETA-PEPTIDE; N-TERMINAL KINASE; TELANGIECTASIA-MUTATED PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; RADIATION-INDUCED APOPTOSIS AB The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and activation of p53 can trigger apoptosis in many cell types including neurons. Apoptosis is a form of programmed cell death that occurs in neurons during development of the nervous system and may also be responsible for neuronal deaths that occur in neurological disorders such as stroke, and Alzheimer's and Parkinson's diseases. p53 production is rapidly increased in neurons in response to a range of insults including DNA damage, oxidative stress, metabolic compromise, and cellular calcium overload. Target genes induced by p53 in neurons include those encoding the pro-apoptotic proteins Bax and the BH3-only proteins PUMA and Noxa. In addition to such transcriptional control of the cell death machinery, p53 may more directly trigger apoptosis by acting at the level of mitochondria, a process that can occur in synapses (synaptic apoptosis). Preclinical data suggest that agents that inhibit p53 may be effective therapeutics for several neurodegenerative conditions. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Munich, Dept Pharm Pharmazeut Biol Biotechnol, Munich, Germany. NIA, Res Program, Neurosci Lab, Baltimore, MD 21224 USA. RP Culmsee, C (reprint author), Univ Munich, Dept Pharm Pharmazeut Biol Biotechnol, Marchioninistr 15, Munich, Germany. EM ccuph@cup.uni-muenchen.de RI Mattson, Mark/F-6038-2012 NR 210 TC 232 Z9 243 U1 1 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 10 PY 2005 VL 331 IS 3 BP 761 EP 777 DI 10.1016/j.bbrc.2005.03.149 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 926PU UT WOS:000229135900011 PM 15865932 ER PT J AU Kohn, KW Pommier, Y AF Kohn, KW Pommier, Y TI Molecular interaction map of the p53 and Mdm2 logic elements, which control the Off-On switch of p53 in response to DNA damage SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE DNA damage; p300 acetyltransferase; apoptosis; Chk2; ATM ID PROLYL ISOMERASE PIN1; UBIQUITIN LIGASE; DEPENDENT ACETYLATION; NEGATIVE REGULATOR; COACTIVATOR P300; PROTEIN-KINASE; PHOSPHORYLATION; NETWORKS; DOMAIN; HAUSP AB The molecular network that controls responses to genotoxic stress is centered at p53 and Mdm2. Recent findings have shown this network to be more complex than previously envisioned. Using a notation specifically designed for circuit diagram-like representations of bioregulatory networks, we have prepared an updated molecular interaction map of the immediate connections of p53 and Mdm2, which are described as logic elements of the network. We use the map as the basis for a comprehensive review of current concepts of signal processing by these logic elements (ail interactive version of the maps-eMIMs can be examined at http://discover.nci.nih.gov/mim). We also used molecular interaction maps to propose a p53 Off On switch in response to DNA damage. Published by Elsevier Inc. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kohn, KW (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM kohnk@dc37a.nci.nih.gov; pommier@nih.gov NR 42 TC 78 Z9 81 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 10 PY 2005 VL 331 IS 3 BP 816 EP 827 DI 10.1016/j.bbrc.2005.03.186 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 926PU UT WOS:000229135900016 PM 15865937 ER PT J AU Mayorov, VI Rogozin, IB Adkison, LR Frahm, C Kunkel, TA Pavlov, YI AF Mayorov, VI Rogozin, IB Adkison, LR Frahm, C Kunkel, TA Pavlov, YI TI Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes SO BMC IMMUNOLOGY LA English DT Article ID INDUCED CYTIDINE DEAMINASE; CLASS-SWITCH RECOMBINATION; DNA-POLYMERASE-ETA; SINGLE-STRANDED-DNA; ACTIVATION-INDUCED DEAMINASE; ERROR-PRONE POLYMERASES; RNA EDITING ENZYME; HYPER-IGM SYNDROME; SACCHAROMYCES-CEREVISIAE; ANTIBODY DIVERSIFICATION AB Background: Antibody genes are diversified by somatic hypermutation (SHM), gene conversion and class-switch recombination. All three processes are initiated by the activation-induced deaminase ( AID). According to a DNA deamination model of SHM, AID converts cytosine to uracil in DNA sequences. The initial deamination of cytosine leads to mutation and recombination in pathways involving replication, DNA mismatch repair and possibly base excision repair. The DNA sequence context of mutation hotspots at G-C pairs during SHM is DGYW/WRCH (G-C is a hotspot position, R = A/G, Y = T/C, W = A/T, D = A/ G/T). Results: To investigate the mechanisms of AID-induced mutagenesis in a model system, we studied the genetic consequences of AID expression in yeast. We constructed a yeast vector with an artificially synthesized human AID gene insert using codons common to highly expressed yeast genes. We found that expression of the artificial hAIDSc gene was moderately mutagenic in a wild-type strain and highly mutagenic in an ung1 uracil-DNA glycosylase-deficient strain. A majority of mutations were at G-C pairs. In the ung1 strain, C-G to T-A transitions were found almost exclusively, while a mixture of transitions with 12% transversions was characteristic in the wild-type strain. In the ung1 strain mutations that could have originated from deamination of the transcribed stand were found more frequently. In the wild-type strain, the strand bias was reversed. DGYW/WRCH motifs were preferential sites of mutations. Conclusion: The results are consistent with the hypothesis that AID-mediated deamination of DNA is a major cause of mutations at G-C base pairs in immunoglobulin genes during SHM. The sequence contexts of mutations in yeast induced by AID and those of somatic mutations at G-C pairs in immunoglobulin genes are significantly similar. This indicates that the intrinsic substrate specificity of AID itself is a primary determinant of mutational hotspots at G-C base pairs during SHM. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc, Omaha, NE 68198 USA. Mercer Univ, Sch Med, Macon, GA 31207 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. SD RAS, Inst Cytol & Genet, Novosibirsk 630090, Russia. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Pavlov, YI (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA. EM mayorov_vi@mercer.edu; rogozin@ncbi.nlm.nih.gov; adkison_lr@mercer.edu; cfrahm@unmc.edu; kunkel@niehs.nih.gov; ypavlov@unmc.edu NR 100 TC 25 Z9 27 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2172 J9 BMC IMMUNOL JI BMC Immunol. PD JUN 10 PY 2005 VL 6 AR UNSP 10 DI 10.1186/1471-2172-6-10 PG 12 WC Immunology SC Immunology GA 017SL UT WOS:000235713500001 PM 15949042 ER PT J AU Sharp, GB Lagarde, F Mizuno, T Sauvaget, C Fukuhara, T Allen, N Suzuki, G Tokuoka, S AF Sharp, GB Lagarde, F Mizuno, T Sauvaget, C Fukuhara, T Allen, N Suzuki, G Tokuoka, S TI Relationship of hepatocellular carcinoma to soya food consumption: A cohort-based, case-control study in Japan SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE soya; isoflavone; hepatitis b virus; hepatitis c virus; hepatocellular carcinoma ID ATOMIC-BOMB SURVIVORS; PRIMARY LIVER-CANCER; HEPATITIS-B; PREMENOPAUSAL WOMEN; TESTOSTERONE LEVELS; SERUM TESTOSTERONE; BREAST-CANCER; RISK; ISOFLAVONES; GENISTEIN AB To determine if the risk of hepatocellular carcinoma (HCC) is reduced by consumption of soya foods, we conducted a case-control study within a cohort of Japanese A-bomb survivors. We compared the prediagnosis consumption of isoflavone-rich miso soup and tofu to HCC risk, adjusting for hepatitis B (HBV) and C (HCV) viral infections, the major HCC risk factors in this population. The study included 176 pathologist-confirmed cases of HCC diagnosed in 1964-1988 and 560 controls who died of diseases other than liver cancer. We examined dietary information collected at least 2 years before diagnosis or death and tissue-based measures of viral hepatitis. Using logistic regression, crude ORs were 0.5 (95% CI 0.29-0.95) and 0.5 (95% CI 0.20-0.99) for high vs. low miso soup and tofu intake, respectively. Adjusting for year of birth, sex, HBV, HCV and other factors, the OR for miso soup was unchanged at 0.5 (95% CI 0.14-1.55), and miso results were similar when ORs were recalculated separately for earlier and later birth cohorts to assess consistency of results. The adjusted OR for tofu was 0.9 (95% CI 0.20-3.51). We also found a statistically significant (p < 0.0001) interaction between sex and HCV, with risk of HCC being substantially higher for women. We conclude that consumption of miso soup and other soya foods may reduce HCC risk. (c) 2005 Wiley-Liss, Inc. C1 Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan. Natl Acad Sci, Washington, DC 20418 USA. Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Radiobiol & Mol Epidemiol, Hiroshima, Japan. Hiroshima Prefectural Hosp, Dept Pathol, Hiroshima, Japan. Univ Oxford, Canc Res UK, Epidemiol Unit, Oxford, England. Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima, Japan. RP Sharp, GB (reprint author), NIAID, Epidemiol Branch, Basic Sci Program, Div AIDS,NIH, 3700-B Rockledge Dr,Rm 4103, Bethesda, MD 20892 USA. EM gsharp@niaid.nih.gov OI Sauvaget, Catherine/0000-0002-8053-4963 FU NCPDCID CDC HHS [NCI-4893-8-001] NR 46 TC 25 Z9 25 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 JUN 10 PY 2005 VL 115 IS 2 BP 290 EP 295 DI 10.1002/ijc.20897 PG 6 WC Oncology SC Oncology GA 920ZJ UT WOS:000228733700016 PM 15688396 ER PT J AU Nawar, E Mbulaiteye, SM Gallant, JE Wohl, DA Ardini, M Hendershot, T Goedert, JJ Rabkin, CS AF Nawar, E Mbulaiteye, SM Gallant, JE Wohl, DA Ardini, M Hendershot, T Goedert, JJ Rabkin, CS CA ACC Study Collaborators TI Risk factors for Kaposi's sarcoma among HHV-8 seropositive homosexual men with AIDS SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE Kaposi's sarcoma; human herpesvirus; AIDS-related malignancy ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-HERPESVIRUS-8 INFECTION; SEXUAL TRANSMISSION; HERPESVIRUS; COHORT; MALIGNANCIES; TYPE-1; TRANSFUSION; PERSPECTIVE AB Kaposi's sarcoma (KS) is a frequent complication of the acquired immunodeficiency syndrome (AIDS) in homosexual men. Risk factors for developing this malignancy are uncertain, other than immunosuppression and coinfection with human herpesvirus 8 (HHV-8). We therefore examined factors associated with KS in a cross-sectional analysis of 99 cases among 503 HHV-8 seropositive homosexual men with AIDS. Data were collected by computer-assisted personal interviews and medical chart reviews. HHV-8 seroreactivity was determined by enzyme-linked immunosorbent assay for antibodies against HHV-8 K8.1 glycoprotein. KS was significanty less common in blacks compared to whites [risk ratio (RR) = 0.4; 95% CI = 0.2=0.8] and more common in subjects who had completed college (RR = 1.7; 95% CI = 1.1-2.7) or had annual income greater than $30,000 (RR = 1.5; 95% CI = 1.1-2.2). KS was less common in cigarette smokers (RR = 0.6; 95% CI = 0.50.9) and users of crack cocaine (RR = 0.4; 95% CI = 0.1-0.8). KS was less common in bisexual men compared to men who were exclusively homosexual (estimated RR = 0.6; 95% CI = 0.4-0.9) and inversely associated with number of female partners. KS was also less common in men who had received pay for sex (RR = 0.6; 95% CI = 0.4-1.0). These cross-sectional associations could be biased by potential differences in relative timing of HHV-8 and HIV infection, a postulated determinant of KS risk. Alternatively, our findings may reflect factors protective against KS in individuals infected with HHV-8. Future research should focus on identifying practical measures for countering KS that do not increase the risk of other diseases. published 2005 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA. Res Triangle Inst, Washington, DC USA. RP Rabkin, CS (reprint author), 6120 Execut Blvd,Execut Plaza S Rm 8016,MSC 7248, Rockville, MD 20852 USA. EM rabkinc@mail.nih.gov FU NCI NIH HHS [N01-CP-81017, N01-CO-12400] NR 30 TC 26 Z9 29 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 10 PY 2005 VL 115 IS 2 BP 296 EP 300 DI 10.1002/ijc.20887 PG 5 WC Oncology SC Oncology GA 920ZJ UT WOS:000228733700017 PM 15688390 ER PT J AU Kreimer, AR Clifford, GM Snijders, PJF Castellsague, X Meijer, CJLM Pawlita, M Viscidi, R Herrero, R Franceschi, S AF Kreimer, AR Clifford, GM Snijders, PJF Castellsague, X Meijer, CJLM Pawlita, M Viscidi, R Herrero, R Franceschi, S CA IARC Multicenter Oral Canc Study G TI HPV16 semiquantitative viral load and serologic biomarkers in oral and oropharyngeal squamous cell carcinomas SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE human papillomavirus; HPV16 viral load; oral cancer; oropharyngeal cancer ID HUMAN-PAPILLOMAVIRUS TYPE-16; VIRUS-LIKE PARTICLES; CERVICAL-CARCINOMA; NECK CANCERS; NATURAL-HISTORY; SEXUAL-BEHAVIOR; IN-SITU; WOMEN; HEAD; ANTIBODIES AB A considerable subset of oropharyngeal squamous cell carcinomas (SCCs) are positive for human papillomavirus (HPV); however, delineating etiologically-associated HPV infections from SCCs with concurrent HPV infection unrelated to tumorigenesis is challenging. Viral load assessment in biopsy specimens may help facilitate such differentiation. HPV16 viral load and serologic markers were assessed among oral and oropharyngeal cases from a multinational study conducted by the International Agency for Research on Cancer (IARC). HPV16 viral load, measured semi-quantitatively by PCR-enzyme immunnassay, was dichotomized as high or low based on the median optical density value. Serologic antibodies to HPV16 virus-like particles (VLPs) and to HPV16 E6 and E7 proteins were measured by ELISA. Compared to HPV DNA-negative cases (n = 852), HPV16 DNA-positive cases with high viral load (n = 26) were significantly more likely to originate in the oropharynx (odds ratio [OR], 12.0; 95% confidence interval [CI], 5.2-27.5) and, after adjustment for tumor site (AdjOR), have antibodies against HPV16 VLPs (AdjOR, 14.6; 95% Cl, 6.0-35.6), E6 (AdjOR, 57.6; 95% CI, 21.4-155.3) and E7 (AdjOR, 25.6; 95% CI, 9.3-70.8). HPV16 DNA-positive cases with low viral load (n = 27) were more commonly oropharyngeal (OR, 2.7; 95% CI, 1.1-6.2) and seropositive for HPV16 VI Ps (AdjOR, 2.7; 95% CI, 1.1-6.9), E6 (AdjOR, 3.0; 95% CI, 0.7-14.0) and E7 (AdjOR, 3.5; 95% CI, 0.7-16.3), compared to HPV DNA-negative cases; the associations, however, were neither as strong nor as significant as the associations for high viral load. As there appears to be a strong association between HPV16 serologic markers and viral load, in the absence of data on serologic markers, HPV16 viral load may be used to help delineate the subset of HPV16 DNA-positive oral and oropharyngeal cancers that may be the consequence of HPV infection. (c) 2005 Wiley-Liss, Inc. C1 Int Agcy Res Canc, F-69372 Lyon, France. NCI, NIH, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. ICO, IDIBELL, Lhospitalet De Llobregat, Spain. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div Dev Neurovirol, Baltimore, MD USA. Inst Costarricense Invest & Ensenanza Nutr & Salu, San Jose, Costa Rica. RP Kreimer, AR (reprint author), NCI, NIH, Canc Prevent Fellowship Program, 6120 Execut Blvd,Suite T-41, Bethesda, MD 20892 USA. EM kreimera@mail.nih.gov RI Pawlita, Labor/C-9720-2011; BOSCH JOSE, FRANCESC XAVIER/J-6339-2012; Kreimer, Aimee/H-1687-2015; Castellsague Pique, Xavier/N-5795-2014; Waterboer, Tim/G-1252-2010; OI BOSCH JOSE, FRANCESC XAVIER/0000-0002-7172-3412; Castellsague Pique, Xavier/0000-0002-0802-3595; Pawlita, Michael/0000-0002-4720-8306 NR 29 TC 33 Z9 35 U1 0 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 JUN 10 PY 2005 VL 115 IS 2 BP 329 EP 332 DI 10.1002/ijc.20872 PG 4 WC Oncology SC Oncology GA 920ZJ UT WOS:000228733700022 PM 15688391 ER PT J AU Camandola, S Cutler, RG Gary, DS Milhavet, O Mattson, MP AF Camandola, S Cutler, RG Gary, DS Milhavet, O Mattson, MP TI Suppression of calcium release from inositol 1,4,5-trisphosphate-sensitive stores mediates the anti-apoptotic function of nuclear factor-kappa B SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTRACELLULAR CA2+ STORES; ENDOPLASMIC-RETICULUM; HIPPOCAMPAL-NEURONS; OXIDATIVE STRESS; BCL-2 EXPRESSION; IP3 RECEPTOR; CELL-DEATH; NEURODEGENERATIVE DISORDERS; PRESENILIN-1 MUTATIONS AB The activation of the transcription factor nuclear factor-κ B (NF-κ B) by growth factors, cytokines, and cellular stress can prevent apoptosis, but the underlying mechanism is unknown. Here we provide evidence for an action of NF-κ B on calcium signaling that accounts for its anti-apoptotic function. Embryonic fibroblasts lacking the transactivating subunit of NF-κ B RelA (p65) exhibit enhanced inositol 1,4,5- trisphosphate (IP3) receptor-mediated calcium release and increased sensitivity to apoptosis, which are restored upon re-expression of RelA. The size of the endoplasmic reticulum (ER) calcium pool and the number of IP3 receptors per cell are decreased in response to stimuli that activate NF-κ B and are increased when NF-κ B activity is suppressed. The selective antagonism of IP3 receptors blocks apoptosis in RelA-deficient cells, whereas activation of NF-κ B in normal cells leads to decreased levels of the type 1 IP3 receptor and decreased calcium release. Overexpression of Bcl-2 normalizes ER calcium homeostasis and prevents calcium-mediated apoptosis in RelA-deficient cells. These findings establish an ER calcium channel as a pivotal target for NF-κ B-mediated cell survival signaling. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Camandola, S (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, GRC 4F01,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM camandolasi@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 71 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 2005 VL 280 IS 23 BP 22287 EP 22296 DI 10.1074/jbc.M410923200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932MN UT WOS:000229557900074 PM 15814613 ER PT J AU Chen, B Colgrave, ML Daly, NL Rosengren, KJ Gustafson, KR Craik, DJ AF Chen, B Colgrave, ML Daly, NL Rosengren, KJ Gustafson, KR Craik, DJ TI Isolation and characterization of novel cyclotides from Viola hederaceae - Solution structure and anti-HIV activity of vhl-1, a leaf-specific expressed cyclotide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METHIONINE SULFOXIDE REDUCTASE; NMR STRUCTURE CALCULATION; SPIN COUPLING-CONSTANTS; CYSTINE KNOT MOTIF; KALATA B1; MACROCYCLIC PEPTIDES; PLANT CYCLOTIDES; CIRCULAR PROTEINS; DRUG DESIGN; SPECTROSCOPY AB Based on a newly established sequencing strategy featured by its efficiency, simplicity, and easy manipulation, the sequences of four novel cyclotides (macrocyclic knotted proteins) isolated from an Australian plant Viola hederaceae were determined. The three-dimensional solution structure of V. hederaceae leaf cyclotide-1 ( vhl-1), a leaf-specific expressed 31-residue cyclotide, has been determined using two-dimensional H-1 NMR spectroscopy. vhl-1 adopts a compact and well defined structure including a distorted triple-stranded β- sheet, a short 310 helical segment and several turns. It is stabilized by three disulfide bonds, which, together with backbone segments, form a cyclic cystine knot motif. The three-disulfide bonds are almost completely buried into the protein core, and the six cysteines contribute only 3.8% to the molecular surface. A pH titration experiment revealed that the folding of vhl-1 shows little pH dependence and allowed the pK(a) of 3.0 for Glu(3) and &SIM; 5.0 for Glu(14) to be determined. Met(7) was found to be oxidized in the native form, consistent with the fact that its side chain protrudes into the solvent, occupying 7.5% of the molecular surface. vhl-1 shows anti-HIV activity with an EC50 value of 0.87 μ m. C1 Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. Chinese Acad Sci, Chengdu Inst Biol, Ctr Nat Prod, Chengdu 610041, Peoples R China. NCI, Mol Targets Dev Program, Ctr Canc Res, NIH, Ft Detrick, MD 21702 USA. RP Chen, B (reprint author), Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. EM d.craik@imb.uq.edu.au RI Daly, Norelle/D-4302-2013; Craik, David/B-1695-2010; Colgrave, Michelle/A-5710-2012; Rosengren, K. Johan/P-4450-2016 OI Craik, David/0000-0003-0007-6796; Colgrave, Michelle/0000-0001-8463-805X; Rosengren, K. Johan/0000-0002-5007-8434 NR 53 TC 75 Z9 81 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 10 PY 2005 VL 280 IS 23 BP 22395 EP 22405 DI 10.1074/jbc.M501737200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 932MN UT WOS:000229557900085 PM 15824119 ER PT J AU Ryan, QC Headlee, D Acharya, M Sparreboom, A Trepel, JB Ye, J Figg, WD Hwang, K Chung, EJ Murgo, A Melillo, G Elsayed, Y Monga, M Kalnitskiy, M Zwiebel, J Sausville, EA AF Ryan, QC Headlee, D Acharya, M Sparreboom, A Trepel, JB Ye, J Figg, WD Hwang, K Chung, EJ Murgo, A Melillo, G Elsayed, Y Monga, M Kalnitskiy, M Zwiebel, J Sausville, EA TI Phase I and pharmacokinetic study of MS-275, a histone deacetylase inhibitor, in patients with advanced and refractory solid tumors or lymphoma SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID VIVO ANTITUMOR-ACTIVITY; BREAST-CANCER CELLS; SODIUM PHENYLBUTYRATE; REPRESS TRANSCRIPTION; BUTYRATE PRODRUG; TRICHOSTATIN-A; ACETYLATION; DIFFERENTIATION; TRIBUTYRIN; EXPRESSION AB Purpose The objective of this study was to define the maximum-tolerated dose (MTD), the recommended phase 11 dose, the dose-limiting toxicity, and determine the pharmacokinetic (PK) and pharmacodynamic profiles of MS-275. Patients and Methods Patients with advanced solid tumors or lymphoma were treated with MS-275 orally initially on a once daily X 28 every 6 weeks (daily) and later on once every-14-days (q14-day) schedules. The starting dose was 2 mg/m(2) and the dose was escalated in three- to six-patient cohorts based on toxicity assessments. Results With the daily schedule, the MTD was exceeded at the first dose level. Preliminary PK analysis suggested the half-life of MS-275 in humans was 39 to 80 hours, substantially longer than predicted by preclinical studies. With the q14-day schedule, 28 patients were treated. The MTD was 10 mg/m(2) and dose-limiting toxicities were nausea, vomiting, anorexia, and fatigue. Exposure to MS-275 was dose dependent, suggesting linear PK. Increased histone H3 acetylation in peripheral-blood mononuclear-cells was apparent at all dose levels by immunofluorescence analysis. Ten of 29 patients remained on treatment for >= 3 months. Conclusion The MS-275 oral formulation on the daily schedule was intolerable at a dose and schedule explored. The q14-day schedule is reasonably well tolerated. Histone deacetylase inhibition was observed in peripheral-blood mononuclear-cells. Based on PK data from the q14-day schedule, a more frequent dosing schedule, weekly X 4, repeated every 6 weeks is presently being evaluated. C1 NCI, Clin Trials Unit, Dev Therapeut Program, Div Canc Treatment & Diagnosis, Bethesda, MD USA. NCI, Clin Pharmacol Res Core Med Oncol Clin Res Unit, Bethesda, MD USA. NCI, Ctr Canc Res, Invest Drug Branch, Div Canc Treatment & Diagnosis, Bethesda, MD USA. NCI, SAIC Frederick Inc, Dev Therapeut Program, Frederick, MD USA. RP Sausville, EA (reprint author), Univ Maryland, Greenebaum Canc Ctr, 22 S Greene St, Baltimore, MD 21201 USA. EM esausville@umm.edu RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 59 TC 259 Z9 275 U1 0 U2 9 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 10 PY 2005 VL 23 IS 17 BP 3912 EP 3922 DI 10.1200/JCO.2005.02.188 PG 11 WC Oncology SC Oncology GA 934RU UT WOS:000229726800006 PM 15851766 ER PT J AU Quinn, TC Overbaugh, J AF Quinn, TC Overbaugh, J TI HIV/AIDS in women: An expanding epidemic SO SCIENCE LA English DT Review ID HIV-1 INFECTION; TRANSMISSION; POPULATION AB More than 20 years into the human immunodeficiency virus-type 1 (HIV-1) epidemic, women account for nearly half of the 40 million people living with HIV-1 worldwide, with an even higher proportion existing in developing countries. Social determinants of female vulnerability to HIV-1 include gender disparities, poverty, cultural and sexual norms, lack of education, and violence. Women ire also more susceptible to HIV-1 because of hormonal changes, vaginal microbial ecology and physiology, and a higher prevalence of sexually transmitted diseases. Prevention strategies must address the wide range of gender inequalities that promote the dissemination of HIV-1. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Int Hlth, Baltimore, MD 21205 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA. RP Quinn, TC (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tquinn@jhmi.edu NR 12 TC 220 Z9 230 U1 2 U2 17 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 10 PY 2005 VL 308 IS 5728 BP 1582 EP 1583 DI 10.1126/science.1112489 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 936BH UT WOS:000229827000041 PM 15947174 ER PT J AU Yarovinsky, F Zhang, DK Andersen, JF Bannenberg, GL Serhan, CN Hayden, MS Hieny, S Sutterwala, FS Flavell, RA Ghosh, S Sher, A AF Yarovinsky, F Zhang, DK Andersen, JF Bannenberg, GL Serhan, CN Hayden, MS Hieny, S Sutterwala, FS Flavell, RA Ghosh, S Sher, A TI TLR11 activation of dendritic cells by a protozoan profilin-like protein SO SCIENCE LA English DT Article ID TOXOPLASMA-GONDII INFECTION; TOLL-LIKE RECEPTOR-5; CUTTING EDGE; STRANDED-RNA; IL-12; RECOGNITION; RESISTANCE; PARASITE; IMMUNITY; GENE AB Mammalian Toll-like receptors (TLRs) play an important role in the innate recognition of pathogens by dendritic cells (DCs). Although TLRs are clearly involved in the detection of bacteria and viruses, relatively little is known about. their function in the innate response to eukaryotic microorganisms. Here we identify a profilin-like molecule from the protozoan parasite Toxoplasma gondii that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88. T. gondii profilin activates DCs through TLR11 and is the first chemically defined ligand for this TLR. Moreover, TLR11 is required in vivo for parasite-induced IL-12 production and optimal resistance to infection, thereby establishing a role for the receptor in host recognition of protozoan pathogens. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Med Entomol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Yarovinsky, F (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM fyarovinsky@niaid.nih.gov; asher@niaid.nih.gov RI Hayden, Matthew/C-1263-2008 FU Intramural NIH HHS; NIAID NIH HHS [R01-AI59440, 1R01AI045806-01A1, AI05093]; NIGMS NIH HHS [R01-GM38765]; Wellcome Trust NR 28 TC 551 Z9 605 U1 5 U2 40 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 10 PY 2005 VL 308 IS 5728 BP 1626 EP 1629 DI 10.1126/science.1109893 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 936BH UT WOS:000229827000057 PM 15860593 ER PT J AU Chandran, K Sullivan, NJ Felbor, U Whelan, SP Cunningham, JM AF Chandran, K Sullivan, NJ Felbor, U Whelan, SP Cunningham, JM TI Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection SO SCIENCE LA English DT Article ID ENVELOPE GLYCOPROTEIN; CATHEPSIN-B; INFLUENZA HEMAGGLUTININ; MEMBRANE-FUSION; INHIBITORS; CYSTEINE; ENTRY; PROTEINASES; CELLS; MICE AB Ebola virus (EboV) causes rapidly fatal hemorrhagic fever in humans and there is currently no effective treatment. We found that the infection of African green monkey kidney (Vero) cells by vesicular stornatitis viruses bearing the EboV gtycoprotein (GP) requires the activity of endosomal cysteine proteases. Using selective protease inhibitors and protease-deficient cell lines, we identified an essential role for cathepsin B (CatB) and an accessory role for cathepsin L (CatL) in EboV GP-dependent entry. Biochemical studies demonstrate that CatB and CatL mediate entry by carrying out proteolysis of the EboV GP subunit GP1 and support a multistep mechanism that explains the relative contributions of these enzymes to infection. CatB and CatB/CatL inhibitors diminish the multiplication of infectious EboV-Zaire in cultured cells and may merit investigation as anti-EboV drugs. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Biozentrum, Inst Human Genet, D-97074 Wurzburg, Germany. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Cunningham, JM (reprint author), Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM jcunningham@rics.bwh.harvard.edu FU NIAID NIH HHS [R01 AI059371, R01 AI059371-01A1] NR 25 TC 401 Z9 417 U1 11 U2 159 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 10 PY 2005 VL 308 IS 5728 BP 1643 EP 1645 DI 10.1126/science.1110656 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 936BH UT WOS:000229827000062 PM 15831716 ER PT J AU Meltzer, PS AF Meltzer, PS TI Cancer genomics - Small RNAs with big impacts SO NATURE LA English DT Editorial Material ID IDENTIFICATION C1 NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, 50 South Dr, Bethesda, MD 20892 USA. EM pmeltzer@nhgri.nih.gov NR 9 TC 192 Z9 218 U1 3 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUN 9 PY 2005 VL 435 IS 7043 BP 745 EP 746 DI 10.1038/435745a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933NK UT WOS:000229638700029 PM 15944682 ER PT J AU Horstmann, E Emanuel, EJ Grady, C AF Horstmann, E Emanuel, EJ Grady, C TI Phase 1 clinical trials in oncology - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID METASTATIC BREAST-CANCER; TUMOR RESPONSE; CHEMOTHERAPY; SURVIVAL C1 NIH, Bethesda, MD 20892 USA. RP Horstmann, E (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM cgrady@nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 9 PY 2005 VL 352 IS 23 BP 2452 EP 2453 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 933NL UT WOS:000229638900025 ER PT J AU Wechselberger, C Strizzi, L Kenney, N Hirota, M Sun, YP Ebert, A Orozco, O Bianco, C Khan, NI Wallace-Jones, B Normanno, N Adkins, H Sanicola, M Salomon, DS AF Wechselberger, C Strizzi, L Kenney, N Hirota, M Sun, YP Ebert, A Orozco, O Bianco, C Khan, NI Wallace-Jones, B Normanno, N Adkins, H Sanicola, M Salomon, DS TI Human Cripto-1 overexpression in the mouse mammary gland results in the development of hyperplasia and adenocarcinoma SO ONCOGENE LA English DT Article DE Cripto-1; transgenic mice; mammary development; mammary tumorigenesis; MMTV-LTR ID INTEGRIN-LINKED KINASE; COLON-CANCER CELLS; HUMAN BREAST CARCINOMAS; FACTOR-RELATED PROTEINS; GROWTH-FACTOR-ALPHA; TRANSGENIC MICE; SIGNALING PATHWAY; EPITHELIAL-CELLS; ANTISENSE OLIGONUCLEOTIDES; BRANCHING MORPHOGENESIS AB Human Cripto-1 (CR-1) is overexpressed in approximately 80% of human breast, colon and lung carcinomas. Mouse Cr-1 upregulation is also observed in a number of transgenic (Tg) mouse mammary tumors. To determine whether CR-1 can alter mammary gland development and/or may contribute to tumorigenesis in vivo, we have generated Tg mouse lines that express human CR-1 under the transcriptional control of the mouse mammary tumor virus ( MMTV). Stable Tg MMTV/CR-1 FVB/N lines expressing different levels of CR-1 were analysed. Virgin female MMTV/CR-1 Tg mice exhibited enhanced ductal branching, dilated ducts, intraductal hyperplasia, hyperplastic alveolar nodules and condensation of the mammary stroma. Virgin aged MMTV/CR-1 Tg mice also possessed persistent end buds. In aged multiparous MMTV/ CR-1 mice, the hyperplastic phenotype was most pronounced with multifocal hyperplasias. In the highest CR1-expressing subline, G4,38% (12/31) of the multiparous animals aged 12 - 20 months developed hyperplasias and approximately 33% (11/31) developed papillary adenocarcinomas. The long latency period suggests that additional genetic alterations are required to facilitate mammary tumor formation in conjunction with CR-1. This is the first in vivo study that shows hyperplasia and tumor growth in CR-1-overexpressing animals. C1 NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. Hampton Univ, Dept Biol Sci, Hampton, VA 23668 USA. Free Univ Berlin, Med Ctr Benjamin Franklin, Dept Obstet & Gynecol, D-12200 Berlin, Germany. Biogen Idec Inc, Cambridge, MA 02142 USA. IT Fdn, Div Haematol Oncol, I-80131 Naples, Italy. IT Fdn, Dept Expt Oncol, I-80131 Naples, Italy. RP Salomon, DS (reprint author), NCI, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Bldg 10,Room 5B39,10 Ctr Dr, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov OI Normanno, Nicola/0000-0002-7158-2605 NR 71 TC 58 Z9 59 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JUN 9 PY 2005 VL 24 IS 25 BP 4094 EP 4105 DI 10.1038/sj.onc.1208417 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 934BA UT WOS:000229680300008 PM 15897912 ER PT J AU Martinez, A Zudaire, E Julian, M Moody, TW Cuttitta, F AF Martinez, A Zudaire, E Julian, M Moody, TW Cuttitta, F TI Gastrin-releasing peptide (GRP) induces angiogenesis and the specific GRP blocker 77427 inhibits tumor growth in vitro and in vivo SO ONCOGENE LA English DT Article DE GRP; lung cancer; angiogenesis; nonpeptidic antagonist; tumor growth ID MICROVASCULAR ENDOTHELIAL-CELLS; LUNG-CANCER CELLS; BOMBESIN-LIKE PEPTIDES; AUTOCRINE GROWTH; GENE-EXPRESSION; POTENTIAL ROLE; NUDE-MICE; RECEPTOR; HYPOXIA; ANTAGONISTS AB Angiogenesis is becoming a major target for antitumor therapies, and identifying new angiogenic factors and their specific inhibitors may provide new avenues for tumor management. Here we identify gastrin-releasing peptide (GRP) as a new angiogenic molecule that is secreted by tumors and acts directly upon GRP receptors in the endothelial cells. Addition of GRP increases endothelial cell migration and cord formation in vitro, and induces angiogenesis in an in vivo assay. We have recently identified a small molecule GRP blocker, compound 77427. This inhibitor significantly reduced endothelial cell cord formation in vitro and angiogenesis in vivo. Conversely, when applied to VEGF-induced angiogenesis, the small molecule did not have any effect, demonstrating its specificity. Furthermore, this GRP blocker was able to reduce lung tumor cell growth in vitro as demonstrated by MTT and clonogenic assays. When applied to a xenograft model with lung cancer cells, compound 77427 reduced tumor volume to undetectable sizes, although when the treatment was suspended, tumors began to grow again at normal rates. Our collective observations indicate that GRP is a new angiogenic peptide and that its inhibition offers an attractive tool to reduce tumor burden. C1 NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Vasc Biol Fac, NIH, Bethesda, MD 20892 USA. San Pablo CEU Univ, Dept Chem Sci, Madrid 28668, Spain. RP Martinez, A (reprint author), CSIC, Inst Cajal, Dept Cell Biol & Neuroanat, Av Doctor Arce 37, E-28002 Madrid, Spain. EM amartinez@cajal.csic.es RI Martinez, Alfredo/A-3077-2013; Cuttitta, Frank/B-4758-2016 OI Martinez, Alfredo/0000-0003-4882-4044; NR 44 TC 28 Z9 29 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 JUN 9 PY 2005 VL 24 IS 25 BP 4106 EP 4113 DI 10.1038/sj.onc.1208581 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 934BA UT WOS:000229680300009 PM 15750618 ER PT J AU Justinova, Z Solinas, M Tanda, G Redhi, GH Goldberg, SR AF Justinova, Z Solinas, M Tanda, G Redhi, GH Goldberg, SR TI The endogenous cannabinoid anandamide and its synthetic analog R(+)-methanandamide are intravenously self-administered by squirrel monkeys SO JOURNAL OF NEUROSCIENCE LA English DT Article DE anandamide; cannabinoids; methanandamide; reinforcing effects; self-administration; squirrel monkey ID RECEPTOR KNOCKOUT MICE; ENDOCANNABINOID CONTENTS; PHARMACOLOGICAL-ACTIVITY; MOUSE-BRAIN; FIXED-RATIO; SR 141716A; ANTAGONIST; REWARD; DELTA(9)-TETRAHYDROCANNABINOL; DEPENDENCE AB Anandamide, an endogenous ligand for brain cannabinoid CB1 receptors, produces many behavioral effects similar to those of Delta(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana. Reinforcing effects of THC have been demonstrated in experimental animals, but there is only indirect evidence that endogenous cannabinoids such as anandamide participate in brain reward processes. We now show that anandamide serves as an effective reinforcer of drug-taking behavior when self-administered intravenously by squirrel monkeys. We also show that methanandamide, a synthetic long-lasting anandamide analog, similarly serves as a reinforcer of drug-taking behavior. Finally, we show that the reinforcing effects of both anandamide and methanandamide are blocked by pretreatment with the cannabinoid CB1 receptor antagonist rimonabant (SR141716). These findings strongly suggest that release of endogenous cannabinoids is involved in brain reward processes and that activation of cannabinoid CB1 receptors by anandamide could be part of the signaling of natural rewarding events. C1 Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Univ Poitiers, Lab Biol & Physiol Cellulaire, F-86022 Poitiers, France. RP Goldberg, SR (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011; Solinas, Marcello/M-3500-2016 OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484; Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS [Z01 DA000001-23, Z99 DA999999] NR 38 TC 62 Z9 64 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 JUN 8 PY 2005 VL 25 IS 23 BP 5645 EP 5650 DI 10.1523/JNEUROSCI.0951-05.2005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 933OO UT WOS:000229643000021 PM 15944392 ER PT J AU Jha, P Brown, D Nagelkerke, N Slutsky, AS Jamison, DT AF Jha, P Brown, D Nagelkerke, N Slutsky, AS Jamison, DT TI Global IDEA - Response SO CANADIAN MEDICAL ASSOCIATION JOURNAL LA English DT Letter ID MORTALITY; DECLINE; INDIA C1 Univ Toronto, St Michaels Hosp, Ctr Global Hlth Res, Toronto, ON M5B 1W8, Canada. United Arab Emirates Univ, Al Ain, U Arab Emirates. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Canadian Imperial Bank Commerce, Toronto, ON, Canada. RP Jha, P (reprint author), Univ Toronto, St Michaels Hosp, Ctr Global Hlth Res, Toronto, ON M5B 1W8, Canada. RI Slutsky, Arthur/A-6013-2008 OI Slutsky, Arthur/0000-0002-6063-3876 NR 8 TC 2 Z9 2 U1 0 U2 0 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0820-3946 J9 CAN MED ASSOC J JI Can. Med. Assoc. J. PD JUN 7 PY 2005 VL 172 IS 12 BP 1538 EP 1539 DI 10.1503/cmaj.1050072 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 930EE UT WOS:000229397800005 ER PT J AU Baumgartner, WA Burrows, S del Nido, PJ Gardner, TJ Goldberg, S Gorman, RC Letsou, GV Mascette, A Michler, RE Puskas, JD Rose, EA Rosengart, TK Sellke, FW Shumway, SJ Wilke, N AF Baumgartner, WA Burrows, S del Nido, PJ Gardner, TJ Goldberg, S Gorman, RC Letsou, GV Mascette, A Michler, RE Puskas, JD Rose, EA Rosengart, TK Sellke, FW Shumway, SJ Wilke, N TI Recommendations of the national heart, lung, and Blood Institute Working Group on future direction in cardiac surgery SO CIRCULATION LA English DT Article DE surgery; heart diseases; research ID ISCHEMIC MITRAL REGURGITATION; CORONARY-ARTERY-DISEASE; DYSFUNCTION; REPAIR AB New surgical procedures, imaging modalities, and medical devices have improved therapy for many patients and made treatment possible for others who have had few options in the past. In February 2004, the National Heart, Lung, and Blood Institute's (NHLBI) Advisory Council proposed that the institute evaluate the status and future directions in cardiac surgery. In response to this recommendation, the NHLBI convened a working group of cardiac surgeons on May 7 and 8, 2004, to assess the state of cardiac surgery research, identify critical gaps in current knowledge, determine areas of opportunity, and obtain specific recommendations for future research activities. The working group discussed surgical revascularization, novel surgical approaches, valvular research directions, biotechnology and cell-based therapy, heart failure, imaging modalities, and barriers to clinical research and presents its recommendations here. C1 NHLBI, NIH, Bethesda, MD USA. RP Baumgartner, WA (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Blalock 618, Baltimore, MD 21287 USA. EM wbaumgar@csurg.jhmi.jhu.edu FU NHLBI NIH HHS [R01 HL071137, R01 HL063954] NR 19 TC 21 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 7 PY 2005 VL 111 IS 22 BP 3007 EP 3013 DI 10.1161/CIRCULATIONAHA.104.530154 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 933CD UT WOS:000229600700021 PM 15939834 ER PT J AU Tsai, HH Reches, M Tsai, CJ Gunasekaran, K Gazit, E Nussinov, R AF Tsai, HH Reches, M Tsai, CJ Gunasekaran, K Gazit, E Nussinov, R TI Energy landscape of amyloidogenic peptide oligomerization by parallel-tempering molecular dynamics simulation: Significant role of Asn ladder SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid oligomerization; bottleneck channel; beta-helix; human calcitonin; mutagenesis ID YEAST PRION SUP35; SOLID-STATE NMR; HUMAN CALCITONIN; FIBRIL FORMATION; FOLDING SIMULATIONS; FORMING PEPTIDE; EXPLICIT WATER; BETA-HAIRPIN; TRP-CAGE; PROTEIN AB Recent evidence suggests that amyloidogenic oligomers may be the toxic species in cell cultures. Thus, it is crucial to understand their structure and oligomerization mechanism in atomistic detail. By employing tens of fast central processing units and an advanced phase-space sampling algorithm, parallel-tempering molecular dynamics, we have explored the energy landscape of amyloidogenic peptide oligomerization in explicit water. A pentapeptide, DFNKF, derived from human calcitonin and its mutant, DFAKF, was simulated with a total simulation time of approximate to 500 Ins. The detailed oligomerization process of a DFNKF parallel beta-sheet formation at 300 K has been characterized. The assembly of a parallel beta-sheet from the amorphous state mainly occurs via a "bottleneck" channel where the interstrand Asn-Asn stacking is the major interaction. The interactions of Asn-Asn stacking include both backbone and side-chain hydrogen bonds. The Asn-Asn interactions work like "glue" by sticking the DFNKF strands together and assist the "on-pathway" oligomerization. The Asn-Asn stacking observed here is similar to the Asn ladder commonly found in globular p-helix proteins. A control run shows that when Asn is mutated to Ala, the stability and population of the DFAKF parallel beta-sheet is decreased. Furthermore, our in vitro mutagenesis experiments show that the ability of DFAKF peptides to form amyloid fibrils is significantly reduced, in agreement with the simulations. Knowledge of the energy landscape of oligomerization may provide hints for rational drug design, preventing amyloid-associated diseases. C1 Natl Canc Inst, Lab Expt & Computat Biol, Basic Res Program, Frederick, MD 21702 USA. George S Wise Fac Life Sci, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Natl Canc Inst, Lab Expt & Computat Biol, Basic Res Program, Bldg 469,Room 145, Frederick, MD 21702 USA. EM tsaih@ncifcrf.gov; ruthn@ncifcrf.gov RI Gazit, Ehud/C-3715-2011; Reches, Meital/B-2348-2013 OI Gazit, Ehud/0000-0001-5764-1720; Reches, Meital/0000-0001-5652-9868 FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 50 TC 85 Z9 88 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 2005 VL 102 IS 23 BP 8174 EP 8179 DI 10.1073/pnas.0408653102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500020 PM 15923262 ER PT J AU Tesar, PJ AF Tesar, PJ TI Derivation of germ-line-competent embryonic stem cell lines from preblastocyst mouse embryos SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE morula ID ES CELLS; EXPRESSION; METHYLATION; NANOG; STAGE; MICE; DIFFERENTIATION; PLURIPOTENCY; TROPHOBLAST; MEMBRANES AB The first differentiation event of the mammalian embryo is thought to occur during blastulation and results in two populations of cells, the inner cell mass (ICM) and the trophectoderm. Most embryonic stem (ES) cell lines have been derived from the ICM or a further subset of ICM cells known as the epiblast. There appears to be a limited period of embryonic development during which pluripotent ES cells can be adapted from the cells of the blastocyst to culture. A method is presented here that allows ES cell lines to be isolated from preblastocyst mouse embryos. These lines were derived from 129S2/SvHsd mouse morulae and earlier cleavage stages with high efficiency. The lines expressed genes and antigens characteristic of pluripotent ES cells. XY cell lines remained karyotypically stable through extensive passaging and produced germ-line-competent chimeras upon blastocyst injection. These results suggest that true ES cells can be derived from embryos explanted at any stage of preimplantation development in the mouse. This finding raises the interesting question of whether ES cell lines derived from embryos at different stages of preimplantation development possess the same potential. C1 Univ Oxford, Dept Zool, Mammalian Dev Lab, Oxford OX1 3PS, England. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Tesar, PJ (reprint author), Univ Oxford, Dept Zool, Mammalian Dev Lab, S Parks Rd, Oxford OX1 3PS, England. EM paul.tesar@zoo.ox.ac.uk RI Tesar, Paul/C-9848-2014 OI Tesar, Paul/0000-0003-1532-3155 NR 32 TC 68 Z9 75 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 2005 VL 102 IS 23 BP 8239 EP 8244 DI 10.1073/pnas.0503231102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500031 PM 15917331 ER PT J AU Camphausen, K Purow, B Sproull, M Scott, T Ozawa, T Deen, DF Tofilon, PJ AF Camphausen, K Purow, B Sproull, M Scott, T Ozawa, T Deen, DF Tofilon, PJ TI Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microarray; intracerebral; brain tumor ID BREAST-CANCER; INHIBITOR AB Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. C1 NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Brain Tumor Res Ctr, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Tofilon, PJ (reprint author), NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. EM tofilonp@mail.nih.gov NR 15 TC 69 Z9 71 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 2005 VL 102 IS 23 BP 8287 EP 8292 DI 10.1073/pnas.0502887102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500039 PM 15928080 ER PT J AU Jendreyko, N Popkov, M Rader, C Barbas, CF AF Jendreyko, N Popkov, M Rader, C Barbas, CF TI Phenotypic knockout of VEGF-R2 and Tie-2 with an intradiabody reduces tumor growth and angiogenesis in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE intrabody; protein engineering; therapeutic; gene transfer; combination therapy ID RECEPTOR TYROSINE KINASE; INTRACELLULAR IMMUNIZATION; ANTIBODIES; INHIBITION; EXPRESSION; VASCULOGENESIS; ANGIOPOIETINS; MECHANISMS; REGRESSION; SYSTEM AB The endothelial cell receptor-tyrosine kinases, VEGF receptor 2 (VEGF-R2) and Tie-2, and their ligands, vascular endothelial growth factor (VEGF) and angiopoietins I and 2, respectively, play key roles in tumor angiogenesis. Several studies suggest that the VEGF receptor pathway and the Tie-2 pathway are independent and essential mediators of angiogenesis, leading to the hypothesis that simultaneous interference with both pathways should result in additive effects on tumor growth. In this study, a human melanoma xenograft model (M21) was used to analyze the effects of simultaneous intradiabody depletion of vascular endothelial growth receptor-R2 and Tie-2 on tumor angiogenesis and tumor xenograft growth. The intradiabodies were expressed from recombinant adenovirus delivered through subtumoral injection. Blockade of both VEGF-R2 and Tie-2 pathways simultaneously or the VEGF receptor pathway alone resulted in a significant inhibition of tumor growth and tumor angiogenesis (92.2% and 74.4%, respectively). In addition, immunohistochemical staining of intradiabodytreated tumors demonstrated a decreased number of tumor-associated blood vessels versus control treatment. Previous studies with intrabodies had demonstrated that the Tie-2 receptor pathway was essential for tumor growth. The simultaneous blockade of the VEGF and Tie-2 pathways resulted in effective inhibition of tumor growth and demonstrated the potential of simultaneous targeting of multiple pathways as a therapeutic strategy. C1 Scripps Res Inst, Dept Biol Mol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Barbas, CF (reprint author), Scripps Res Inst, Dept Biol Mol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM carlos@scripps.edu FU NCI NIH HHS [CA 86258, R01 CA086258] NR 33 TC 55 Z9 58 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 JUN 7 PY 2005 VL 102 IS 23 BP 8293 EP 8298 DI 10.1073/pnas.0503168102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500040 PM 15928093 ER PT J AU Gold, PW Wong, ML Goldstein, DS Gold, HK Ronsaville, DS Esler, M Alesci, S Masood, A Licinio, J Geracioti, TD Perini, G Debellis, MD Holmes, C Vgontzas, AN Charney, DS Chrousos, GP McCann, SM Kling, MA AF Gold, PW Wong, ML Goldstein, DS Gold, HK Ronsaville, DS Esler, M Alesci, S Masood, A Licinio, J Geracioti, TD Perini, G Debellis, MD Holmes, C Vgontzas, AN Charney, DS Chrousos, GP McCann, SM Kling, MA TI Cardiac implications of increased arterial entry and reversible 24-h central and peripheral norepinephrine levels in melancholia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebrospinal fluid; epinephrine; major depression; cardiovascular disease; chronic heart failure ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; PLASMA NOREPINEPHRINE; SYMPATHETIC ACTIVITY; MAJOR DEPRESSION; SYSTEM; ACTIVATION; MORTALITY; SYMPTOMS; KINETICS AB The mortality of chronic heart failure (CHIF) doubles either when CHIF patients are depressed or when their plasma norepinephrine (NE) level exceeds those of controls by approximate to 40%. We hypothesized that patients with major depression had centrally driven, sustained, stress-related, and treatment-reversible increases in plasma NE capable of increasing mortality in CHIF patients with depression. We studied 23 controls and 22 medication-free patients with melancholic depression. In severely depressed patients before and after electroconvulsive therapy (ECT), we measured cerebrospinal fluid (CSF) NE, plasma NE, plasma epinephrine (EPI), and plasma cortisol hourly for 30 h. In mildly-to-moderately depressed melancholic patients, we assessed basal and stress-mediated arterial NE appearance. Severely depressed patients had significant increases in mean around-the-clock levels of CSIF NE (P < 0.02), plasma NE (P < 0.02), plasma EPI (P < 0.02), and plasma cortisol (P < 0.02). CSF NE, plasma NE, and cortisol all rose together throughout the night and peaked in the morning. Each fell to control values after ECT. Mildly-to-moderately melancholic patients also had increased basal (P < 0.05) and stress-related (P < 0.03) arterial NE-appearance rates. Severely melancholic depressed, medication-free patients had around-the-clock increases in plasma NE levels capable of increasing mortality in CHF. Twenty-four-hour indices of central noradrenergic, adrenomedullary, and adrenocortical secretion were also elevated. Concurrent diurnal rhythms of these secretions could potentiate their cardiotoxicity. Even mildly-to-moderately depressed melancholic patients had clinically relevant increases in the arterial NE-appearance rate. These findings will not apply to all clinical subtypes of major depression. C1 NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat, Inst Neuropsychiat, Los Angeles, CA 90095 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Baker Heart Res Inst, Melbourne, Vic 8008, Australia. Univ Cincinnati, Sch Med, Dept Psychiat, Cincinnati, OH 45267 USA. Univ Padua, Dept Neurol & Psychiat Sci, I-35122 Padua, Italy. Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27708 USA. Penn State Univ, Dept Psychiat, Hershey, PA 17033 USA. CUNY Mt Sinai Sch Med, Deans Off, New York, NY 10029 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. RP Gold, PW (reprint author), NIMH, Clin Neuroendocrinol Branch, NIH, Bldg 10-2D46,10 Ctr Dr,MSC 1284, Bethesda, MD 20892 USA. EM philipgold@mail.nih.gov RI Kling, Mitchel/F-4152-2010; Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013; OI Kling, Mitchel/0000-0002-2232-1409; Licinio, Julio/0000-0001-6905-5884; PERINI, GIULIA/0000-0003-3261-1984 NR 25 TC 55 Z9 57 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUN 7 PY 2005 VL 102 IS 23 BP 8303 EP 8308 DI 10.1073/pnas.0503069102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933RL UT WOS:000229650500042 PM 15919819 ER PT J AU Sung, KS Go, YY Ahn, JH Kim, YH Kim, Y Choi, CY AF Sung, KS Go, YY Ahn, JH Kim, YH Kim, Y Choi, CY TI Differential interactions of the homeodomain-interacting protein kinase 2 (HIPK2) by phosphorylation-dependent sumoylation SO FEBS LETTERS LA English DT Article DE homeodomain-interacting protein kinase 2; small ubiquitin-like modifier 1; phosphorylation; differential interaction ID PROTEIN KINASE-2; TRANSCRIPTION FACTORS; COVALENT MODIFICATION; P53 PHOSPHORYLATION; SUMO-1 MODIFICATION; MEDIATED APOPTOSIS; GENE-EXPRESSION; UBIQUITIN; NUCLEAR; PROTEIN-KINASE-2 AB Homeodomain-interacting protein kinase 2 (HIPK2) interacts with and phosphorylates various transcription factors that are critical regulators of cell fate decisions and apoptosis during development. Here we show that lysine 25 of HIPK2 is the major sumoylation site, both in vitro and in vivo, and that the sumoylation of this site occurs in a phosphorylation-dependent manner. This became clear with the finding that kinase-dead HIPK2 (K221R) could not be efficiently sumoylated in vitro. The sumoylation of HIPK2 resulted in the disruption of its interaction with a Groucho corepressor. Consequently, sumoylation inhibited the regulatory activity of HIPK2 on the Groucho-mediated repression of transcription, whereas not on p53-mediated transactivation. These results suggest that phosphorylation-dependent sumoylation enables HIPK2 to drive different target gene transcription by means of differential interactions with its binding partners. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. Sungkyunkwan Univ, Sch Med, Dept Mol Cell Biol, Samsung Biomed Res Inst, Suwon 440746, South Korea. Digital Biotech, Ansan 425839, South Korea. Natl Heart Lung & Blood Inst, Lab Res Program, NIH, Bethesda, MD 20892 USA. RP Choi, CY (reprint author), Sungkyunkwan Univ, Dept Biol Sci, 300 Chunchundong, Suwon 440746, South Korea. EM choicy@skku.ac.kr NR 29 TC 27 Z9 27 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUN 6 PY 2005 VL 579 IS 14 BP 3001 EP 3008 DI 10.1016/j.febslet.2005.04.053 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 935ZR UT WOS:000229822500006 PM 15896780 ER PT J AU Nitto, T Lin, C Dyer, KD Wagner, RA Rosenberg, HF AF Nitto, T Lin, C Dyer, KD Wagner, RA Rosenberg, HF TI Characterization of a ribonuclease gene and encoded protein from the reptile, Iguana iguana SO GENE LA English DT Article DE ribonuclease; reptile; evolution; enzyme; ribonucleic acid ID EOSINOPHIL CATIONIC PROTEIN; AMINO-ACID-SEQUENCE; PANCREATIC RIBONUCLEASE; RANA-CATESBEIANA; A SUPERFAMILY; RNASE; INHIBITOR; CYTOTOXICITY; PURIFICATION; EVOLUTION AB In this work we identify an intronless open reading frame encoding an RNase A ribonuclease from genomic DNA from the Iguana iguana IgH2 cell line. The iguana RNase is expressed primarily in pancreas, and represents the majority of the specific enzymatic activity in this tissue. The encoded sequence shares many features with its better-known mammalian counterparts including the crucial His(12), LyS(40) and His(114) catalytic residues and efficient hydrolytic activity against yeast tRNA substrate (k(cat)/K-m, - 6 x 10(4) M-1 s(-1)), albeit at a reduced pH optimum (pH 6.0). Although the catalytic activity of the iguana RNase is not diminished by human placental RI, iguana RNase is not bactericidal nor is it cytotoxic even at micromolar concentrations. Phylogenetic analysis indicates moderate (46%) amino acid sequence similarity to a pancreatic RNase isolated from Chelydra serpentina (snapping turtle) although no specific relationship could be determined between these RNases and the pancreatic ribonucleases characterized among mammalian species. Further analysis of ribonucleases from nonmammalian vertebrate species is needed in order to define relationships and lineages within the larger RNase A gene superfamily. (c) 2005 Elsevier B.V. All rights reserved. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Div Lab Anim Resources, Pittsburgh, PA 15261 USA. RP Nitto, T (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM tnitto@niaid.nih.gov NR 28 TC 8 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 6 PY 2005 VL 352 BP 36 EP 44 DI 10.1016/j.gene.2005.03.002 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 941YE UT WOS:000230249300005 PM 15893436 ER PT J AU Khaled, AR Bulavin, DV Kittipatarin, C Li, WQ Alvarez, M Kim, K Young, HA Fornace, AJ Durum, SK AF Khaled, AR Bulavin, DV Kittipatarin, C Li, WQ Alvarez, M Kim, K Young, HA Fornace, AJ Durum, SK TI Cytokine-driven cell cycling is mediated through Cdc25A SO JOURNAL OF CELL BIOLOGY LA English DT Article ID S-PHASE CHECKPOINT; NF-KAPPA-B; INTRACELLULAR PH; MEMORY CELLS; T-CELLS; SURVIVAL; INTERLEUKIN-7; IL-7; PHOSPHORYLATION; PHOSPHATASE AB Lymphocytes are the central mediators of the immune response, requiring cytokines for survival and proliferation. Survival signaling targets the Bcl-2 family of apoptotic mediators, however, the pathway for the cytokine-driven proliferation of lymphocytes is poorly understood. Here we show that cytokine-induced cell cycle progression is not solely dependent on the synthesis of cyclin-dependent kinases (Cdks) or cyclins. Rather, we observe that in lymphocyte cell lines dependent on interleukin-3 or interleukin-7, or primary lymphocytes dependent on interleukin 7, the phosphatase Cdc25A is the critical mediator of proliferation. Withdrawal of IL-7 or IL-3 from dependent lymphocytes activates the stress kinase, p38 MAPK, which phosphorylates Cdc25A, inducing its degradation. As a result, Cdk/cyclin complexes remain phosphorylated and inactive and cells arrest before the induction of apoptosis. Inhibiting p38 MAPK or expressing a mutant Cdc25A, in which the two p38 MAPK target sites, S75 and S123, are altered, renders cells resistant to cytokine withdrawal, restoring the activity of Cdk/cyclin complexes and driving the cell cycle independent of a growth stimulus. C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32628 USA. NCI, Div Basic Sci, Bethesda, MD 20892 USA. NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Sahm Yook Univ, Dept Pharm, Seoul 139742, South Korea. RP Khaled, AR (reprint author), Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32628 USA. EM akhaled@mail.ucf.edu; durums@mail.ncifcrf.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [N01-CO-12400, K22 CA097984, K22 CA097984-01, N01CO12400] NR 46 TC 50 Z9 50 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 6 PY 2005 VL 169 IS 5 BP 755 EP 763 DI 10.1083/jcb.200409099 PG 9 WC Cell Biology SC Cell Biology GA 933BY UT WOS:000229600100010 PM 15928203 ER PT J AU Bektas, M Payne, SG Liu, H Goparaju, S Milstien, S Spiegel, S AF Bektas, M Payne, SG Liu, H Goparaju, S Milstien, S Spiegel, S TI A novel acylglycerol kinase that produces lysophosphatidic acid modulates cross talk with EGFR in prostate cancer cells SO JOURNAL OF CELL BIOLOGY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; MOLECULAR-CLONING; PHOSPHATIDIC-ACID; FUNCTIONAL-CHARACTERIZATION; PHOSPHOLIPASE-D; LIPID KINASES; HUMAN BREAST; NUDE-MICE; GROWTH; FAMILY AB The bioactive phospholipids, lysophosphatidic acid (LPA) and phosphatidic acid (PA), regulate pivotal processes related to the pathogenesis of cancer. Here, we report characterization of a novel lipid kinase, designated acylglycerol kinase (AGK), that phosphorylates monoacylglycerol and diacylglycerol to form LPA and PA, respectively. Confocal microscopy and subcellular fractionation suggest that AGK is localized to the mitochondria. AGK expression was up-regulated in prostate cancers compared with normal prostate tissues from the same patient. Expression of AGK in PC-3 prostate cancer cells markedly increased formation and secretion of LPA. This increase resulted in concomitant transactivation of the EGF receptor and sustained activation of extracellular signal related kinase (ERK) 1/2, culminating in enhanced cell proliferation. AGK expression also increased migratory responses. Conversely, down-regulating expression of endogenous AGK inhibited EGF- but not LPA-induced ERK1/2 activation and progression through the S phase of the cell cycle. Hence, AGK can amplify EGF signaling pathways and may play an important role in the pathophysiology of prostate cancer. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Sch Med, Massey Canc Ctr, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Goparaju, Sravan/H-3422-2011 FU NCI NIH HHS [R01 CA061774, R01CA61774] NR 42 TC 91 Z9 95 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD JUN 6 PY 2005 VL 169 IS 5 BP 801 EP 811 DI 10.1083/jcb.200407123 PG 11 WC Cell Biology SC Cell Biology GA 933BY UT WOS:000229600100014 PM 15939762 ER PT J AU Rao, VK Knutsen, T Ried, T Wangsa, D Flynnb, BM Langham, G Egorin, MJ Cole, D Balis, F Steinberg, SM Bates, S Fojo, T AF Rao, VK Knutsen, T Ried, T Wangsa, D Flynnb, BM Langham, G Egorin, MJ Cole, D Balis, F Steinberg, SM Bates, S Fojo, T TI The extent of chromosomal aberrations induced by chemotherapy in non-human primates depends on the schedule of administration SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE drug resistance; chromosomal damaged; genotoxicity; secondary malignancies; CIV chemotherapy ID ACUTE MYELOID-LEUKEMIA; BONE-MARROW TRANSPLANT; HIGH-DOSE CHEMOTHERAPY; STEM-CELL SUPPORT; BREAST-CANCER; MICROSATELLITE INSTABILITY; ALKYLATING-AGENTS; PERIPHERAL-BLOOD; BODY IRRADIATION; DRUG-RESISTANCE AB We utilized a non-human primate model, the rhesus monkey (Macaca mulatta), to quantitate the extent of chromosomal damage in bone marrow cells following chemotherapy. Thiotepa, etoposide, and paclitaxel were chosen as the chemotherapy agents due to their distinct mechanisms of action. Chromosomal aberrations were quantitated using traditional Giemsa stain. We sought to evaluate the extent to which genotoxicity was dependent on the schedule of administration by giving chemotherapy as either a bolus or a 96 h continuous infusion. Neutropenia and areas under the concentration curve (AUCs) were monitored to ensure comparable cytotoxicity and dose administered. At least 100 metaphases were scored in each marrow sample by an investigator unaware of the treatment history of the animals. All three drugs produced a statistically significant higher percentage of abnormal metaphases following bolus chemotherapy (p < 0.0001, p = 0.0015 and p < 0.0001 for thiotepa, etoposide and paclitaxel, respectively). We conclude that infusional administration of thiotepa, etoposide and paclitaxel is less genotoxic to normal bone marrow cells than is bolus administration. These results suggest infusional regimens may be considered where there are concerns about long-term genotoxic sequelae, including secondary cancer, teratogenicity, or possibly the development of drug resistance. We believe this approach provides a reproducible model in which drugs and eventually, regimens can be compared. (c) 2005 Published by Elsevier B.V. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIMH, Vet Med & Resource Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Lab Anim, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA 15213 USA. RP Fojo, T (reprint author), NCI, Canc Res Ctr, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 58 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 6 PY 2005 VL 583 IS 2 BP 105 EP 119 DI 10.1016/j.mrgentox.2005.01.013 PG 15 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 937FC UT WOS:000229909000001 PM 15927870 ER PT J AU Mattson, MP AF Mattson, MP TI The need for controlled studies of the effects of meal frequency on health SO LANCET LA English DT Editorial Material ID DIETARY RESTRICTION; GLUCOSE-METABOLISM; RATS; DISEASE; MICE; OBESITY; TERM C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 26 TC 30 Z9 30 U1 0 U2 11 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 4 PY 2005 VL 365 IS 9475 BP 1978 EP 1980 DI 10.1016/S0140-6736(05)66667-6 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 932XJ UT WOS:000229587800035 PM 15936428 ER PT J AU Myers, DA Gibson, M Schulkin, J Van-Meerveld, BG AF Myers, DA Gibson, M Schulkin, J Van-Meerveld, BG TI Corticosterone implants to the amygdala and type 1 CRH receptor regulation: Effects on behavior and colonic sensitivity SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE amygdala; corticosterone (CORT); CRH ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; MESSENGER-RNA; PARAVENTRICULAR NUCLEUS; CONDITIONED FEAR; STRESS; HORMONE; RESPONSES; RAT; ANTAGONIST AB Corticosterone (CORT) micropellets were stereotaxically placed bilaterally at the dorsal margin of the central nucleus of the amygala (CeA). Both behavioral and physiological responses were recorded (plus maze and colonic discomfort) at 7 days post-implantation. Corticosterone reduced the exploration of the plus maze and increased colonic distress. The ability of a CRH type 1 receptor antagonist, antalarmin, to block behavioral and colonic effects of central placement of CORT was also examined. The diminished exploration in the plus maze and colon distress observed in response to CORT placement at the CeA were averted by the administration of antalarmin. These results provide further evidence for the role of the CRH type I receptor to ameliorate both behavioral and physiological functions. © 2005 Elsevier B.V. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73014 USA. Georgetown Univ, Dept Physiol & Biophys, Clin Neuroendocrinol Branch, NIMH, Washington, DC USA. Univ Oklahoma, Hlth Sci Ctr, Dept Physiol, Norman, OK 73019 USA. RP Myers, DA (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73014 USA. EM dean-myers@ouhsc.edu NR 29 TC 50 Z9 51 U1 1 U2 4 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 JUN 3 PY 2005 VL 161 IS 1 BP 39 EP 44 DI 10.1016/j.bbr.2005.03.001 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 932QM UT WOS:000229568400005 PM 15904708 ER PT J AU Krauss, J Arndt, MAE Vu, BK Newton, DL Seeber, S Rybak, SM AF Krauss, J Arndt, MAE Vu, BK Newton, DL Seeber, S Rybak, SM TI Efficient killing of CD22(+) tumor cells by a humanized diabody-RNase fusion protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE CD22; ribonuclease; fusion protein; cytotoxicity; humanized diabody ID SINGLE-CHAIN FV; MONOCLONAL-ANTIBODY; PHASE-I; CYTOTOXIC RIBONUCLEASE; ANTI-CD22 IMMUNOTOXIN; PSEUDOMONAS EXOTOXIN; SCID MICE; LYMPHOMA; RECOMBINANT; THERAPY AB We report on the generation of a dimeric immunoenzyme capable of simultaneously delivering two ribonuclease (RNase) effector domains on one molecule to CD22(+) tumor cells. As targeting moiety a diabody derived from the previously humanized scFv SGIII with grafted specificity of the murine anti-CD22 mAb RFB4 was constructed. Further engineering the interface of this construct (V(L)36(Leu&RARR; Tyr)) resulted in a highly robust bivalent molecule that retained the same high affinity as the murine mAb RFB4 (K-D = 0.2 nM). A dimeric immunoenzyme comprising this diabody and Rana pipiens liver ribonuclease I (rapLRI) was generated, expressed as soluble protein in bacteria, and purified to homogeneity. The dimeric fusion protein killed several CD22(+) tumor cell lines with high efficacy (IC50 = 3-20 nM) and exhibited 9- to 48-fold stronger cytotoxicity than a monovalent rapLRI-scFv counterpart. Our results demonstrate that engineering of dimeric antibody ribonuclease fusion proteins can markedly enhance their biological efficacy. © 2005 Elsevier Inc. All rights reserved. C1 Univ Essen Gesamthsch, Dept Med Oncol & Canc Res, D-45122 Essen, Germany. Univ Essen Gesamthsch, Inst Immunol, D-45122 Essen, Germany. NCI, SAIC, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21702 USA. RP Krauss, J (reprint author), Univ Essen Gesamthsch, Dept Med Oncol & Canc Res, D-45122 Essen, Germany. EM juergen.krauss@uni-essen.de FU NCI NIH HHS [N01-CO-12400] NR 40 TC 27 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 3 PY 2005 VL 331 IS 2 BP 595 EP 602 DI 10.1016/j.bbrc.2005.03.215 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 924EG UT WOS:000228961000034 PM 15850802 ER PT J AU Gao, ZG Chiao, P Zhang, X Zhang, XH Lazar, MA Seto, E Young, HA Ye, JP AF Gao, ZG Chiao, P Zhang, X Zhang, XH Lazar, MA Seto, E Young, HA Ye, JP TI Coactivators and corepressors of NF-kappa B in I kappa Beta alpha gene promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEROID-RECEPTOR COACTIVATOR-1; HISTONE ACETYLTRANSFERASE ACTIVITY; THYROID-HORMONE RECEPTOR; NUCLEAR RECEPTORS; TRANSCRIPTIONAL COACTIVATOR; TRANSACTIVATION DOMAIN; COR COREPRESSORS; PHOSPHORYLATION; ACTIVATION; P65 AB In this study, we investigated recruitment of coactivators (SRC-1, SRC-2, and SRC-3) and corepressors (HDAC1, HDAC2, HDAC3, SMRT, and NCoR) to the I kappa B alpha gene promoter after NF-kappa B activation by tumor necrosis factor-alpha. Our data from chromatin immunoprecipitation assay suggest that coactivators and corepressors are simultaneously recruited to the promoter, and their binding to the promoter DNA is oscillated in HEK293 cells. SRC-1, SRC-2, and SRC-3 all enhanced I kappa B alpha transcription. However, the interaction of each coactivator with the promoter exhibited different patterns. After tumor necrosis factor-alpha treatment, SRC-1 signal was increased gradually, but SRC-2 signal was reduced immediately, suggesting replacement of SRC-2 by SRC-1. SRC-3 signal was increased at 30 min, reduced at 60 min, and then increased again at 120 min, suggesting an oscillation of SRC-3. The corepressors were recruited to the promoter together with the coactivators. The binding pattern suggests that the corepressor proteins formed two types of corepressor complexes, SMRT-HDAC1 and NCoR- HDAC3. The two complexes exhibited a switch at 30 and 60 min. The functions of cofactors were confirmed by gene overexpression and RNA interference-mediated gene knockdown. These data suggest that gene transactivation by the transcription factor NF-kappa B is subject to the regulation of a dynamic balance between the coactivators and corepressors. This model may represent a mechanism for integration of extracellular signals into a precise control of gene transcription. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Cellular & Mol Immunol Sect, Expt Immunol Lab, NIH, Ft Detrick, MD 21702 USA. Univ S Florida, H Lee Moffit Canc Ctr & Res Inst, Tampa, FL 33612 USA. Univ Penn, Div Endocrinol Diab & Metab, Philadelphia, PA 19104 USA. RP Ye, JP (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. EM yej@pbrc.edu RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 FU NIDDK NIH HHS [DK068036, R01 DK068036, R56 DK068036] NR 53 TC 83 Z9 89 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2005 VL 280 IS 22 BP 21091 EP 21098 DI 10.1074/jbc.M500754200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800024 PM 15811852 ER PT J AU Sakamoto, A Chen, M Nakamura, T Xie, T Karsenty, G Weinstein, LS AF Sakamoto, A Chen, M Nakamura, T Xie, T Karsenty, G Weinstein, LS TI Deficiency of the G-protein alpha-subunit G(s)alpha in osteoblasts leads to differential effects on trabecular and cortical bone SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PARATHYROID-HORMONE; IN-VITRO; ALPHA-SUBUNIT; GROWTH-PLATE; OSTEOPROGENITOR CELLS; PTH/PTHRP RECEPTOR; PROSTAGLANDIN E-2; MC3T3-E1 CELLS; KNOCKOUT MICE; EXPRESSION AB The G-protein alpha-subunit G(s)alpha is required for the intracellular cAMP responses to hormones and other agonists. G(s)alpha is known to mediate the cAMP response to parathyroid hormone and other hormones and cytokines in bone and cartilage. To analyze the in vivo role of G(s)alpha signaling in osteoblasts, we developed mice with osteoblast/osteocyte-specific G(s)alpha deficiency (BGsKO) by mating G(s)alpha-floxed mice with collagen I alpha 1 promoter-Cre recombinase transgenic mice. Early skeletal development was normal in BGsKO mice, because formation of the initial cartilage template and bone collar was unaffected. The chondrocytic zones of the growth plates also appeared normal in BGsKO mice. BGsKO mice had a defect in the formation of the primary spongiosa with reduced immature osteoid (new bone formation) and overall length, which led to reduced trabecular bone volume. In contrast, cortical bone was thickened with narrowing of the bone marrow cavity. This was probably due to decreased cortical bone resorption, because osteoclasts were markedly reduced on the endosteal surface of cortical bone. In addition, the expression of alkaline phosphatase, an early osteoblastic differentiation marker, was normal, whereas the expression of the late osteoblast differentiation markers osteopontin and osteocalcin was reduced, suggesting that the number of mature osteoblasts in bone is reduced. Expression of the osteoclast- stimulating factor receptor activator of NF-kappa B ligand was also reduced. Overall, our findings have similarities to parathyroid hormone null mice and confirm that the differential effects of parathyroid hormone on trabecular and cortical bone are primarily mediated via G(s)alpha in osteoblasts. Osteoblast-specific G(s)alpha deficiency leads to reduced bone turnover. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Rm 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov RI Nakamura, Takashi/P-7796-2016 OI Nakamura, Takashi/0000-0001-9904-1037 NR 40 TC 50 Z9 51 U1 1 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 JUN 3 PY 2005 VL 280 IS 22 BP 21369 EP 21375 DI 10.1074/jbc.M500346200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800056 PM 15797856 ER PT J AU Ledee, DR Gao, CY Seth, R Fariss, RN Tripathi, BK Zelenka, PS AF Ledee, DR Gao, CY Seth, R Fariss, RN Tripathi, BK Zelenka, PS TI A specific interaction between muskelin and the cyclin-dependent kinase 5 activator p39 promotes peripheral localization of muskelin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KELCH-REPEAT SUPERFAMILY; DIRECTED PROTEIN-KINASE; LENS FIBER CELLS; NEURONAL DIFFERENTIATION; EPITHELIAL-CELLS; P35/CDK5 KINASE; BOVINE BRAIN; CDK5; PHOSPHORYLATION; EXPRESSION AB Previous studies implicate cyclin-dependent kinase 5 in cell adhesion and migration of epithelial cells of the cornea and lens. To explore molecular interactions underlying these functions, we performed yeast two-hybrid screening of an embryonic rat lens library for proteins that interact with cyclin-dependent kinase 5 and its regulators, p35 and p39. This screen identified a specific interaction between p39 and muskelin, an intracellular protein known to affect cytoskeletal organization in adherent cells. Immunohistochemistry detected muskelin in the developing lens and in other tissues, including brain and muscle. Glutathione S-transferase pull-down experiments and co-immunoprecipitations confirmed the specificity of the p39-muskelin interaction. Deletion analysis of p39 showed that muskelin binds to the p39 C terminus, which contains a short insertion ( amino acids 329-366) absent from p35. Similar analysis of muskelin mapped the interaction with p39 to the fifth kelch repeat. Co-expression of p39 and muskelin in COS1 cells or lens epithelial cells altered the intracellular localization of muskelin, recruiting it to the cell periphery. These findings demonstrate a novel interaction between muskelin and the cyclin-dependent kinase 5 activator p39 and suggest that p39 may regulate the subcellular localization of muskelin. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NEI, NIH, Bldg 7,Rm 102,7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. EM zelenkap@nei.nih.gov NR 38 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2005 VL 280 IS 22 BP 21376 EP 21383 DI 10.1074/jbc.M501215200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800057 PM 15797862 ER PT J AU Choi, CY Kim, YH Kim, YO Park, SJ Kim, EA Riemenschneider, W Gajewski, K Schulz, RA Kim, Y AF Choi, CY Kim, YH Kim, YO Park, SJ Kim, EA Riemenschneider, W Gajewski, K Schulz, RA Kim, Y TI Phosphorylation by the DHIPK2 protein kinase modulates the corepressor activity of groucho SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR TCF; EYE-SPECIFIC ENHANCER; EYELESS GENE; VISCERAL MESODERM; DROSOPHILA EMBRYO; CO-REPRESSORS; EXPRESSION; INTERACTS; HIPK2; DIFFERENTIATION AB Groucho function is essential for Drosophila development, acting as a corepressor for specific transcription factors that are downstream targets of various signaling pathways. Here we provide evidence that Groucho is phosphorylated by the DHIPK2 protein kinase. Phosphorylation modulates Groucho corepressor activity by attenuating its protein-protein interaction with a DNA-bound transcription factor. During eye development, DHIPK2 modifies Groucho activity, and eye phenotypes generated by overexpression of Groucho differ depending on its phosphorylation state. Moreover, analysis of nuclear extracts fractionated by column chromatography further shows that phospho- Groucho associates poorly with the corepressor complex, whereas the unphosphorylated form binds tightly. We propose that Groucho phosphorylation by DHIPK2 and its subsequent dissociation from the corepressor complex play a key role in relieving the transcriptional repression of target genes regulated by Groucho, thereby controlling cell fate determination during development. C1 NHLBI, Lab Res Program, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Dept Sci Biol, Suwon 440746, South Korea. Digital Biotech, Ansan 425839, South Korea. Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Choi, CY (reprint author), NHLBI, Lab Res Program, NIH, Bldg 10, Bethesda, MD 20892 USA. EM choicy@skku.ac.kr; yongsok@helix.nih.gov FU Intramural NIH HHS NR 62 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2005 VL 280 IS 22 BP 21427 EP 21436 DI 10.1074/jbc.M500496200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800063 PM 15802274 ER PT J AU Suzuki, M Neutzner, A Tjandra, N Youle, RJ AF Suzuki, M Neutzner, A Tjandra, N Youle, RJ TI Novel structure of the N terminus in yeast Fis1 correlates with a specialized function in mitochondrial fission SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYNAMIN-RELATED GTPASE; DOMINANT OPTIC ATROPHY; TRIPLE-RESONANCE NMR; WD REPEAT PROTEIN; C-13-ENRICHED PROTEINS; OUTER-MEMBRANE; CHEMICAL-SHIFT; DNM1P; SPECTROSCOPY; SENSITIVITY AB Mitochondrial fission is facilitated by a multiprotein complex assembled at the division site. The required components of the fission machinery in Saccharomyces cerevisiae include Dnm1, Fis1, and Mdv1. In the present study, we determined the protein structure of yeast Fis1 using NMR spectroscopy. Although the six alpha-helices, as well as their folding, in the yeast Fis1 structure are similar to those of the tetratricopeptide repeat (TPR) domains of the human Fis1 structure, the two structures differ in their N termini. The N-terminal tail of human Fis1 is flexible and unstructured, whereas a major segment of the longer N terminus of yeast Fis1 is fixed to the concave face formed by the six alpha- helices in the TPR domains. To investigate the role of the fixed N terminus, exogenous Fis1 was expressed in yeast lacking the endogenous protein. Expression of yeast Fis1 protein rescued mitochondrial fission in Delta fis1 yeast only when the N-terminal TPR binding segment was left intact. The presence of this segment is also correlated to the recruitment of Mdv1 to mitochondria. The conformation of the N- terminal segment embedded in the TPR pocket indicates an intra-molecular regulation of Fis1 bioactivity. Although the TPR-like helix bundle of Fis1 mediates the interaction with Dnm1 and Mdv1, the N terminus of Fis1 is a prerequisite to recruit Mdv1 to facilitate mitochondrial fission. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. NINDS, Biochem Sect, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3503,50 Ctr Dr,MSC 8013, Bethesda, MD 20892 USA. EM nico@helix.nih.gov; youler@ninds.nih.gov OI Neutzner, Albert/0000-0001-9254-5558 NR 49 TC 45 Z9 51 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2005 VL 280 IS 22 BP 21444 EP 21452 DI 10.1074/jbc.M414092200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800065 PM 15809300 ER PT J AU Liu, XB Bandyopadhyay, BC Singh, BB Groschner, K Ambudkar, IS AF Liu, XB Bandyopadhyay, BC Singh, BB Groschner, K Ambudkar, IS TI Molecular analysis of a store-operated and 2-acetyl-sn-glycerol-sensitive non-selective cation channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR POTENTIAL CHANNELS; SALIVARY-GLAND CELLS; CA2+ INFLUX; CALCIUM-ENTRY; TRP PROTEINS; SUBUNIT; BRAIN; DIACYLGLYCEROL; ASSOCIATION; DEPLETION AB We have reported that internal Ca2+ store depletion in HSY cells stimulates a nonselective cation current which is distinct from I-CRAC in RBL cells and TRPC1-dependent I-SOC in HSG cells (Liu, X., Groschner, K., and Ambudkar, I. S. ( 2004) J. Membr. Biol. 200, 93 - 104). Here we have analyzed the molecular composition of this channel. Both thapsigargin (Tg) and 2-acetyl-sn-glycerol (OAG) stimulated similar non-selective cation currents and Ca2+ entry in HSY cells. The effects of Tg and OAG were not additive. HSY cells endogenously expressed TRPC1, TRPC3, and TRPC4 but not TRPC5 or TRPC6. Immunoprecipitation of TRPC1 pulled down TRPC3 but not TRPC4. Conversely, TRPC1 co-immunoprecipitated with TRPC3. Expression of antisense TRPC1 decreased (i) Tg- and OAG-stimulated currents and Ca2+ entry and (ii) the level of endogenous TRPC1 but not TRPC4. Antisense TRPC3 similarly reduced Ca2+ entry and endogenous TRPC3. Yeast two-hybrid analysis revealed an interaction between NTRPC1 and NTRPC3 (CTRPC1-CTRPC3, CTRPC3-CTRPC1, or CTRPC1-NTRPC3 did not interact), which was confirmed by glutathione S-transferase (GST) pull-down assays (GST-NTRPC3 pulled down TRPC1 and vice versa). Expression of NTRPC1 or NTRPC3 induced similar dominant suppression of Tg- and OAG-stimulated Ca2+ entry. NTRPC3 did not alter surface expression of TRPC1 or TRPC3 but disrupted TRPC1-TRPC3 association. In aggregate, our data demonstrate that TRPC1 and TRPC3 co-assemble, via N-terminal interactions, to form a heteromeric storeoperated non-selective cation channel in HSY cells. Thus selective association between TRPCs generate distinct store-operated channels. Diversity of store-operated channels might be related to the physiology of the different cell types. C1 NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH,DHHS, Bethesda, MD 20892 USA. Univ N Dakota, Sch Med, Dept Biochem & Mol Biol, Grand Forks, ND 58203 USA. Graz Univ, Dept Pharmacol & Toxikol, A-8010 Graz, Austria. RP Ambudkar, IS (reprint author), NIDCR, Secretory Physiol Sect, Gene Therapy & Therapeut Branch, NIH,DHHS, Bldg 10,Rm 1N-113, Bethesda, MD 20892 USA. EM indu.ambudkar@nih.gov RI Groschner, Klaus/A-2550-2010 NR 30 TC 107 Z9 112 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 3 PY 2005 VL 280 IS 22 BP 21600 EP 21606 DI 10.1074/jbc.c400492200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930TA UT WOS:000229438800084 PM 15834157 ER PT J AU Inbar, Y Benyamini, H Nussinov, R Wolfson, HJ AF Inbar, Y Benyamini, H Nussinov, R Wolfson, HJ TI Prediction of multimolecular assemblies by multiple docking SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE multimolecular assembly; docking; combinatorial assembly ID PROTEIN-PROTEIN DOCKING; T-CELL-RECEPTOR; GENETIC ALGORITHM; SHAPE COMPLEMENTARITY; GLOBULAR-PROTEINS; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; RESOLUTION; COMPLEX; RECOGNITION AB The majority of proteins function when associated in multimolecular assemblies. Yet, prediction of the structures of multimolecular complexes has largely not been addressed, probably due to the magnitude of the combinatorial complexity of the problem. Docking applications have traditionally been used to predict pairwise interactions between molecules. We have developed an algorithm that extends the application of docking to multimolecular assemblies. We apply it to predict quaternary structures of both oligomers and multi-protein complexes. The algorithm predicted well a near-native arrangement of the input subunits for all cases in our data set, where the number of the subunits of the different target complexes varied from three to ten. In order to simulate a more realistic scenario, unbound cases were tested. In these cases the input conformations of the subunits are either unbound conformations of the subunits or a model obtained by a homology modeling technique. The successful predictions of the unbound cases, where the input conformations of the subunits are different from their conformations within the target complex, suggest that the algorithm is robust. We expect that this type of algorithm should be particularly useful to predict the structures of large macromolecular assemblies, which are difficult to solve by experimental structure determination. (c) 2005 Elsevier Ltd. All rights reserved. C1 Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Inst Mol Med, Sackler Sch Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, NCI Frederick, Ft Detrick, MD 21702 USA. RP Inbar, Y (reprint author), Tel Aviv Univ, Sch Comp Sci, Raymond & Beverly Sackler Fac Exact Sci, IL-69978 Tel Aviv, Israel. EM inbaryuv@tau.ac.il RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-12400] NR 54 TC 50 Z9 50 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 3 PY 2005 VL 349 IS 2 BP 435 EP 447 DI 10.1016/j.jmb.2005.03.039 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930BR UT WOS:000229391300016 PM 15890207 ER PT J AU Newton-Cheh, C Hirschhorn, JN AF Newton-Cheh, C Hirschhorn, JN TI Genetic association studies of complex traits: design and analysis issues SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE association study; complex trait; genetics; genomics; single nucleotide polymorphism; review ID DIETARY-FAT INTAKE; HUMAN-GENOME; CROHNS-DISEASE; LINKAGE DISEQUILIBRIUM; POPULATION STRATIFICATION; TRANSMISSION/DISEQUILIBRIUM TEST; QUANTITATIVE TRAITS; HAPLOTYPE STRUCTURE; COMMON DISEASE; INSULIN GENE AB Most common diseases and many important quantitative traits are complex genetic traits, with multiple genetic and environmental variables contributing to the observed phenotype. Because of the multi-factorial nature of complex traits, each individual genetic variant generally has only a modest effect, and the interaction of genetic variants with each other or with environmental factors can potentially be quite important in determining the observed phenotype. It remains largely unknown what sort of genetic variants explain inherited variation in complex traits, but recent evidence suggests that common genetic variants will explain at least some of the inherited variation in susceptibility to common disease. Genetic association studies, in which the allele or genotype frequencies at markers are determined in affected individuals and compared with those of controls (either population- or family-based), may be an effective approach to detecting the effects of common variants with modest effects. With the explosion in single nucleotide polymorphism (SNP) discovery and genotyping technologies, large-scale association studies have become feasible, and small-scale association studies have become plentiful. We review the different types of association studies and discuss issues that are important to consider when performing and interpreting association studies of complex genetic traits. Heritable and accurately measured phenotypes, carefully matched large samples, well-chosen genetic markers, and adequate standards in genotyping, analysis, and interpretation are all integral parts of a high-quality association study. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Genet, Boston, MA 02115 USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), Harvard Univ, Broad Inst, 1 Kendall Sq,Bldg 300, Cambridge, MA 02139 USA. EM joel.hirschhorn@childrens.harvard.edu NR 84 TC 162 Z9 172 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN 3 PY 2005 VL 573 IS 1-2 BP 54 EP 69 DI 10.1016/j.mrfmmm.2005.01.006 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 923CX UT WOS:000228887700005 PM 15829237 ER PT J AU Kaiser, J Zerhouni, E AF Kaiser, J Zerhouni, E TI Elias Zerhouni: Taking stock SO SCIENCE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. NR 1 TC 1 Z9 1 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 JUN 3 PY 2005 VL 308 IS 5727 BP 1398 EP 1399 DI 10.1126/science.308.5727.1398 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933HK UT WOS:000229619300013 ER PT J AU Chesebro, B Trifilo, M Race, R Meade-White, K Teng, C LaCasse, R Raymond, L Favara, C Baron, G Priola, S Caughey, B Masliah, E Oldstone, M AF Chesebro, B Trifilo, M Race, R Meade-White, K Teng, C LaCasse, R Raymond, L Favara, C Baron, G Priola, S Caughey, B Masliah, E Oldstone, M TI Anchorless prion protein results in infectious amyloid disease without clinical scrapie SO SCIENCE LA English DT Article ID CELL-FREE FORMATION; SPONGIFORM ENCEPHALOPATHIES; PRECURSOR PROTEIN; NEURONAL PRP; MICE; RESISTANT; BRAIN; CONVERSION; PATHOLOGY; PLAQUES AB In prion and Alzheimer's diseases, the roles played by amyloid versus nonamyloid deposits in brain damage remain unresolved. In scrapie-infected transgenic mice expressing prion protein (PrP) lacking the glycosylphosphatidylinositol (GPI) membrane anchor, abnormal protease-resistant PrPres was deposited as amyloid plaques, rather than the usual nonamyloid form of PrPres. Although PrPres amyloid plaques induced brain damage reminiscent of Alzheimer's disease, clinical manifestations were minimal. In contrast, combined expression of anchorless and wild-type PrP produced accelerated clinical scrapie. Thus, the PrP GPI anchor may play a role in the pathogenesis of prion diseases. C1 NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, Hamilton, MT 59840 USA. Scripps Res Inst, Dept Neuropharmacol, Div Virol, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. RP Chesebro, B (reprint author), NIAID, Rocky Mt Labs, Lab Persistent Viral Dis, Hamilton, MT 59840 USA. EM bchesebro@niaid.nih.gov FU NIA NIH HHS [AG004342] NR 40 TC 391 Z9 405 U1 1 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 3 PY 2005 VL 308 IS 5727 BP 1435 EP 1439 DI 10.1126/science.1110837 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 933HK UT WOS:000229619300044 PM 15933194 ER PT J AU Xiao, XS Miao, ZH Antony, S Pommier, Y Cushman, M AF Xiao, XS Miao, ZH Antony, S Pommier, Y Cushman, M TI Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE indenoisoquinoline; dihydroindenoisoquinoline; antitumor; topoisomerase 1; prodrug ID TOPOISOMERASE-I INHIBITORS; BIOLOGICAL EVALUATION; MJ-III-65 NSC-706744; CAMPTOTHECIN; CHLORIDE; DESIGN; COMPLEXES; POISON AB Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase 1 (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top 1. Through COMPARE analysis, cytotoxicity studies in Top 1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells. (c) 2005 Elsevier Ltd. All rights reserved. C1 Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Sch Pharm & Pharmaceut Sci, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Cushman, M (reprint author), Purdue Univ, Sch Pharm & Pharmaceut Sci, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. EM cushman@pharmacy.purdue.edu FU NCI NIH HHS [U01 CA89566]; PHS HHS [N01-C0-56000] NR 23 TC 21 Z9 22 U1 0 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 JUN 2 PY 2005 VL 15 IS 11 BP 2795 EP 2798 DI 10.1016/j.bmcl.2005.03.101 PG 4 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 933XG UT WOS:000229665600020 PM 15911256 ER PT J AU Stepchenkova, EI Kozmin, SG Alenin, VV Pavlov, YI AF Stepchenkova, EI Kozmin, SG Alenin, VV Pavlov, YI TI Genome-wide screening for genes whose deletions confer sensitivity to mutagenic purine base analogs in yeast SO BMC GENETICS LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; IONIZING-RADIATION; 6-N-HYDROXYLAMINOPURINE; MUTANTS; 2-AMINO-N6-HYDROXYADENINE; FRAGMENTATION; SPECIFICITY; PROGRESSION; RESISTANCE AB Background: N-hydroxylated base analogs, such as 6-hydroxylaminopurine (HAP) and 2-amino-6- hydroxylaminopurine (AHA), are strong mutagens in various organisms due to their ambiguous base-pairing properties. The systems protecting cells from HAP and related noncanonical purines in Escherichia coli include specialized deoxyribonucleoside triphosphatase RdgB, DNA repair endonuclease V, and a molybdenum cofactor-dependent system. Fewer HAP-detoxification systems have been identified in yeast Saccharomyces cerevisiae and other eukaryotes. Cellular systems protecting from AHA are unknown. In the present study, we performed a genome-wide search for genes whose deletions confer sensitivity to HAP and AHA in yeast. Results: We screened the library of yeast deletion mutants for sensitivity to the toxic and mutagenic action of HAP and AHA. We identified novel genes involved in the genetic control of base analogs sensitivity, including genes controlling purine metabolism, cytoskeleton organization, and amino acid metabolism. Conclusion: We developed a method for screening the yeast deletion library for sensitivity to the mutagenic and toxic action of base analogs and identified 16 novel genes controlling pathways of protection from HAP. Three of them also protect from AHA. C1 St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. RP Pavlov, YI (reprint author), St Petersburg State Univ, Dept Genet, St Petersburg 199034, Russia. EM stepchenkova@yahoo.com; kozmin@niehs.nih.gov; alenin@alenin.usr.pu.ru; ypavlov@unmc.edu RI Kozmin, Stanislav/J-6849-2012; Stepchenkova, Elena/F-9931-2014 OI Kozmin, Stanislav/0000-0002-4128-4447; Stepchenkova, Elena/0000-0002-5854-8701 NR 38 TC 9 Z9 10 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2156 J9 BMC GENET JI BMC Genet. PD JUN 2 PY 2005 VL 6 AR 31 DI 10.1186/1471-2156-6-31 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 942WQ UT WOS:000230314000002 PM 15932646 ER PT J AU Newman, AH Grundt, P Nader, MA AF Newman, AH Grundt, P Nader, MA TI Dopamine D3 receptor partial agonists and antagonists as potential drug abuse therapeutic agents SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Review ID COCAINE-SEEKING BEHAVIOR; CONDITIONED PLACE PREFERENCE; D-3 RECEPTOR; HIGH-AFFINITY; RHESUS-MONKEYS; COMPETITIVE ANTAGONIST; MEDICATION DEVELOPMENT; D-3/D-2 RECEPTORS; BRAIN REWARD; MUTANT MICE C1 NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Wake Forest Univ, Sch Med, Dept Physiol Pharmacol & Radiol, Winston Salem, NC 27157 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM anewman@intra.nida.nih.gov FU NIDA NIH HHS [DA14637, N01DA-1-8816, DA12460] NR 110 TC 133 Z9 135 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 2 PY 2005 VL 48 IS 11 BP 3663 EP 3679 DI 10.1021/jm040190e PG 17 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 930UX UT WOS:000229443700001 PM 15916415 ER PT J AU Tarasova, NI Seth, R Tarasov, SG Kosakowska-Cholody, T Hrycyna, CA Gottesman, MM Michejda, CJ AF Tarasova, NI Seth, R Tarasov, SG Kosakowska-Cholody, T Hrycyna, CA Gottesman, MM Michejda, CJ TI Transmembrane inhibitors of P-glycoprotein, an ABC transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANT CELLS; ESCHERICHIA-COLI; CONFORMATIONAL-CHANGES; POLAR INTERACTIONS; MEMBRANE-PROTEINS; RECEPTOR FUNCTION; DRUG-RESISTANCE; IN-VIVO; PEPTIDE; BINDING AB Drug resistance mediated by ABC transporters such as P-glycoprotein (P-gp) continues to be a major impediment to effective cancer chemotherapy. We have developed a panel of highly specific peptide inhibitors of P-gp based on the structure of the transmembrane domains of the transporter. These peptides are thought to exert their inhibitory action by disrupting the proper assembly of P-gp. A novel 96-well-plate assay based on the efflux of fluorescent P-gp substrate DiOC(2) (3-ethyl-2-[3-(3-ethyl-2(3H)-benzoxazolylidene)-1-propenyl]benzoxazolium iodide) was developed and used for structure-functional characterization of transporter inhibitors. The studies strongly suggest that potent and selective inhibitors of ABC transporters can now be developed solely on the basis of the primary structures of the target proteins. The inhibition of P-gp with transmembrane peptides was shown to be chirality-independent. A 25-residue long retroinverso D-analogue of transmembrane domain 5 inhibited the efflux of the fluorescent P-gp substrate with an IC50 of 500 nM. Transmembrane peptides effectively sensitized resistant cancer cells to doxorubicin in vitro without demonstrating any cell toxicity of their own. The newly synthesized P-gp antagonists appear to be promising nontoxic drug resistance inhibitors that merit further development. C1 NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, Frederick, MD 21702 USA. NCI, Cell Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Tarasova, NI (reprint author), NCI, Mol Aspects Drug Design Sect, Struct Biophys Lab, POB B, Frederick, MD 21702 USA. EM tarasova@ncifcrf.gov NR 36 TC 33 Z9 34 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD JUN 2 PY 2005 VL 48 IS 11 BP 3768 EP 3775 DI 10.1021/jm049065t PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 930UX UT WOS:000229443700014 PM 15916428 ER PT J AU Oxman, MN Levin, MJ Johnson, GR Schmader, KE Straus, SE Gelb, LD Arbeit, RD Simberkoff, MS Gershon, AA Davis, LE Weinberg, A Boardman, KD Williams, HM Zhang, JHY Peduzzi, PN Beisel, CE Morrison, VA Guatelli, JC Brooks, PA Kauffman, CA Pachucki, CT Neuzil, KM Betts, RF Wright, PF Griffin, MR Brunell, P Soto, NE Marques, AR Keay, SK Goodman, RP Cotton, DJ Gnann, JW Loutit, J Holodniy, M Keitel, WA Crawford, GE Yeh, SS Lobo, Z Toney, JF Greenberg, RN Keller, PM Harbecke, R Hayward, AR Irwin, MR Kyriakides, TC Chan, CY Chan, ISF Wang, WWB Annunziato, PW Silber, JL AF Oxman, MN Levin, MJ Johnson, GR Schmader, KE Straus, SE Gelb, LD Arbeit, RD Simberkoff, MS Gershon, AA Davis, LE Weinberg, A Boardman, KD Williams, HM Zhang, JHY Peduzzi, PN Beisel, CE Morrison, VA Guatelli, JC Brooks, PA Kauffman, CA Pachucki, CT Neuzil, KM Betts, RF Wright, PF Griffin, MR Brunell, P Soto, NE Marques, AR Keay, SK Goodman, RP Cotton, DJ Gnann, JW Loutit, J Holodniy, M Keitel, WA Crawford, GE Yeh, SS Lobo, Z Toney, JF Greenberg, RN Keller, PM Harbecke, R Hayward, AR Irwin, MR Kyriakides, TC Chan, CY Chan, ISF Wang, WWB Annunziato, PW Silber, JL CA Shingles Prevention Study Grp TI A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID INACTIVATED VARICELLA VACCINE; IMMUNE-RESPONSES; NATURAL-HISTORY; HEALTH SURVEY; VIRUS; PAIN; QUESTIONNAIRE; RECIPIENTS; SEVERITY; VALIDITY AB BACKGROUND The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster ( 315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia ( 27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent ( P< 0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent ( P< 0.001), and reduced the incidence of herpes zoster by 51.3 percent ( P< 0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults. C1 VA San Diego Healthcare Syst, Shingles Prevent Study, La Jolla, CA 92161 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. VA Cooperat Studies Program Coordinating Ctr, West Haven, CT USA. Durham VA Med Ctr, Ctr Geriatr Res Educ & Clin, Durham, NC USA. Duke Univ, Med Ctr, Ctr Aging, Durham, NC USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. St Louis VA Med Ctr, St Louis, MO USA. Washington Univ, Dept Med, St Louis, MO USA. VA Boston Healthcare Syst, Boston, MA USA. VA New York Harbor Healthcare Syst, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. Columbia Univ, New York, NY USA. New Mexico VA Healthcare Syst, Albuquerque, NM USA. VA Cooperat Studies Program Clin Res Pharm Coordi, Albuquerque, NM USA. Minneapolis VA Med Ctr, Minneapolis, MN USA. VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA. Vet Affairs Edward Hines Jr Hosp, Chicago, IL USA. VA Puget Sound Healthcare Syst, Seattle, WA USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Baltimore VA Med Ctr, Baltimore, MD 21218 USA. Birmingham VA Med Ctr, Birmingham, AL USA. VA Palo Alto Healthcare Syst, Palo Alto, CA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Vet Adm Med Ctr, Northport, NY 11768 USA. James A Haley Vet Hosp, Tampa, FL 33612 USA. Lexington VA Med Ctr, Lexington, KY 40511 USA. Merck Res Labs, W Point, PA USA. Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90024 USA. RP Oxman, MN (reprint author), VA San Diego Healthcare Syst, Shingles Prevent Study, Mail Code 111F-1,3350 La Jolla Village Dr, La Jolla, CA 92161 USA. EM mnoxman@ucsd.edu RI Irwin, Michael/H-4870-2013 OI Irwin, Michael/0000-0002-1502-8431 NR 38 TC 997 Z9 1041 U1 2 U2 51 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 2 PY 2005 VL 352 IS 22 BP 2271 EP 2284 DI 10.1056/NEJMoa051016 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 930VY UT WOS:000229446400004 PM 15930418 ER PT J AU Perez, ZN Musingarimi, P Craig, NL Dyda, F Burgess, A Hickman, AB AF Perez, ZN Musingarimi, P Craig, NL Dyda, F Burgess, A Hickman, AB TI Purification, crystallization and preliminary crystallographic analysis of the Hermes transposase SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID DNA-BINDING DOMAIN; ELEMENT; COMMON; HOBO; PROTEIN; PLANTS; FAMILY; TAM3; AC C1 NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RP Hickman, AB (reprint author), NIDDK, Mol Biol Lab, Bethesda, MD 20892 USA. EM ahickman@helix.nih.gov NR 20 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD JUN PY 2005 VL 61 BP 587 EP 590 DI 10.1107/S1744309105015721 PN 6 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 970OJ UT WOS:000232319200013 PM 16511103 ER PT J AU Schmittner, J Schroeder, JR Epstein, DH Preston, KL AF Schmittner, J Schroeder, JR Epstein, DH Preston, KL TI Menstrual cycle length during methadone maintenance SO ADDICTION LA English DT Article DE amenorrhea; heroin; menstruation; methadone ID FOLLOW-UP; HEROIN-ADDICTS; WOMEN; NARCOTICS; MECHANISM; DEATH AB Aims While the menstrual disruption of heroin has been demonstrated, there are few published data concerning methadone maintenance and menstrual function. This study was conducted to evaluate whether cycle length was more regular during methadone maintenance. Settings An out-patient research treatment program in Baltimore, Maryland, USA. Participants A total of 19 1 heroin and cocaine-using women from two clinical trials, lasting 25-29 weeks; each woman was maintained on 70-100 mg of methadone. Measurements Start/end dates of each menses were collected. Design Menstrual patterns were classified as regular, irregular, transient amenorrhea, persistent amenorrhea or cycle restart. Repeated-measures regression modeling determined correlates of cycle length and predictors of long cycles (> 40 days) and short cycles (< 20 days). Bleeding episodes were defined as I or more bleeding days, bound by at least 2 non-bleeding days. Correlates/predictors examined were body mass index, drug use, methadone dose and race. Findings In the 133 women for whom menstrual patterns could be determined, cycle-length irregularity was common: irregular, 62 (46.7%); regular, 37 (27.81%); cycle restart, 16 (12%); persistent amenorrhea, 11 (8.3%); transient amenorrhea, seven (5.3%,). Each additional week on methadone maintenance was associated with decreased risk of long (OR=0.96, P<0.01 and short (OR=0.92, P<0.01) cycles. Of 27 women with secondary amenorrhea pre-study, 16 (59%) restarted menses. Positivity for opioids or cocaine was not significantly associated with short or long cycles. Conclusions Cycle length begins to normalize during methadone maintenance. Menses resumption may occur. Methadone maintenance, despite interfering with menstrual function in an absolute sense, may interfere less than illicit heroin abuse. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Schmittner, J (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jschmitt@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS NR 27 TC 21 Z9 22 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 2005 VL 100 IS 6 BP 829 EP 836 DI 10.1111/j.1360-0443.2005.01091.x PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 932VZ UT WOS:000229583900016 PM 15918813 ER PT J AU Abroms, L Simons-Morton, B Haynie, DL Chen, RS AF Abroms, L Simons-Morton, B Haynie, DL Chen, RS TI Psychosocial predictors of smoking trajectories during middle and high school SO ADDICTION LA English DT Article DE middle school; smoking; trajectories ID CIGARETTE-SMOKING; ADOLESCENT SMOKING; NATURAL-HISTORY; OUTCOMES; ADULTHOOD; PATTERNS; CHILDREN AB Aims Little is known about the heterogeneity in and risk factors associated With trajectories of smoking during adolescence. This study aimed to (1) identify smoking trajectories empirically and (2) identify risk factors for trajectory group membership. Design Latent growth mixture models were used to identify population smoking trajectories. and logistic regression was used to estimate risk factors for group membership. Setting The participants were drawn from seven middle schools in a Maryland school district. Participants Participants consisted of 1320 6th graders who Were followed to the 9th grade. Measurements Measurements of smoking risk factors were made in the fall of 6th grade and smoking stage was assessed on five different occasions between the fall of 6th and 9th grades. Findings Five distinct smoking trajectories were identified. Overall, being female. having friends who smoked. deviance acceptance and outcome expectations were associated with an increased likelihood of being an intender, delayed escalator, early experimenter and early user compared to a never smoker. Additionally, comparisons with never smokers revealed unique identifiers for intenders, early experimenters and early users, but not delayed escalators. Conclusions There is much heterogeneity in the manner in which middle-schoolers progress from having no intention of smoking to becoming smokers. Implications for prevention programs are discussed. C1 George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, Washington, DC 20037 USA. NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Ctr New Designs Learning & Scholarship, Washington, DC USA. RP Abroms, L (reprint author), George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Serv, Dept Prevent & Community Hlth, 2175 K St NW,Room 7015, Washington, DC 20037 USA. EM sphlca@gwumc.edu OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 30 TC 53 Z9 55 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD JUN PY 2005 VL 100 IS 6 BP 852 EP 861 DI 10.1111/j.1360-0443.2005.01090.x PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 932VZ UT WOS:000229583900018 PM 15918815 ER PT J AU de Cabo, RC Navas, P AF de Cabo, Rafael C. Navas, Placido TI Guest editorial SO AGE LA English DT Editorial Material C1 NIA, Lab Expt Gerontol, NIH, Geront Res Ctr, Baltimore, MD 21224 USA. Univ Pablo Olavide, Ctr Andaluz Biol Desarrollo, Seville 41013, Spain. RP de Cabo, RC (reprint author), NIA, Lab Expt Gerontol, NIH, Geront Res Ctr, Box 10,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD JUN PY 2005 VL 27 IS 2 BP 127 EP 127 DI 10.1007/s11357-005-4294-y PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 121PJ UT WOS:000243169200004 PM 23598618 ER PT J AU Lopez-Lluch, G Rios, M Lane, MA Navas, P de Cabo, R AF Lopez-Lluch, G. Rios, M. Lane, M. A. Navas, P. de Cabo, R. TI Mouse liver plasma membrane redox system activity is altered by aging and modulated by calorie restriction SO AGE LA English DT Article DE cytochrome b5 reductase; plasma membrane redox system; quinone reductase; ubiquinone ID OXIDATIVE DNA-DAMAGE; VITAMIN-E-DEFICIENCY; ELECTRON-TRANSPORT; COENZYME-Q; LIFE-SPAN; SKELETAL-MUSCLE; HL-60 CELLS; RAT-LIVER; ASCORBATE; STRESS AB Caloric restriction (CR) is known as the only non-genetic method proven to slow the rate of aging and extend lifespan in animals. Free radical production emerges from normal metabolic activity and generates the accumulation of oxidized macromolecules, one of the main characteristics of aging. Due to its central role in cell bioenergetics, a great interest has been paid to CR-induced modifications in mitochondria, where CR has been suggested to decrease reactive oxygen species production. The plasma membrane contains a trans-membrane redox system (PMRS) that provides electrons to recycle lipophilic antioxidants, such as alpha-tocopherol and coenzyme Q (CoQ), and to modulate cytosolic redox homeostasis. In the present study, we have investigated age differences in the PMRS in mouse liver and their modulation by CR. Aging induced a decrease in the ratio of CoQ(10)/CoQ(9) and alpha-tocopherol in liver PM from AL-fed mice that was attenuated by CR. CoQ-dependent NAD(P)H dehydrogenases highly increased in CR old mice liver PMs. On the other hand, the CoQ-independent NADH-FCN reductase activity increased in AL-fed animals; whereas, in mice under CR this activity did not change during aging. Our results suggest that liver PMRS activity changes during aging and that CR modulates these changes. By this mechanism CR maintains a higher antioxidant capacity in liver PM of old animals by increasing the activity of CoQ-dependent reductases. Also, the putative role of PMRS in the modulation of redox homeostasis of cytosol is implicated. C1 NIA, Lab Expt Gerontol, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Pablo Olavide, Lab Andaluz Biol, Seville 41013, Spain. RP de Cabo, R (reprint author), NIA, Lab Expt Gerontol, NIH, Gerontol Res Ctr, Box 10,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Lopez-Lluch, Guillermo/N-4742-2014; OI Lopez-Lluch, Guillermo/0000-0001-9830-8502; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 50 TC 17 Z9 17 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0161-9152 J9 AGE JI Age PD JUN PY 2005 VL 27 IS 2 BP 153 EP 160 DI 10.1007/s11357-005-2726-3 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 121PJ UT WOS:000243169200008 PM 23598622 ER PT J AU Guralnik, JM AF Guralnik, JM TI The evolution of research on disability in old age SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material DE aging; disability; physical function C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Guralnik, JM (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. EM jg48s@nih.gov NR 13 TC 6 Z9 6 U1 2 U2 7 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD JUN PY 2005 VL 17 IS 3 BP 165 EP 167 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 949PD UT WOS:000230799700001 PM 16110726 ER PT J AU Russo, DA AF Russo, DA TI Mechanisms for training and career development at NIAAA and the NIH SO ALCOHOL LA English DT Meeting Abstract CT Meeting of the Alcohol-and-Immunology-Research-Interest-Group CY NOV 18, 2005 CL Loyola Univ Med Ctr, Maywood, IL SP Alcohol & Immunol Res Interest Grp HO Loyola Univ Med Ctr C1 NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0741-8329 J9 ALCOHOL JI Alcohol PD JUN PY 2005 VL 36 IS 2 BP 134 EP 134 PG 1 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 003DQ UT WOS:000234662200032 ER PT J AU Bergeson, SE Berman, AE Dodd, PR Edenberg, HJ Hitzemann, RJ Lewohl, JM Lodowski, KH Sommer, WH AF Bergeson, SE Berman, AE Dodd, PR Edenberg, HJ Hitzemann, RJ Lewohl, JM Lodowski, KH Sommer, WH TI Expression profiling in alcoholism research SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article ID GENE-EXPRESSION; MICROARRAY ANALYSIS; BRAIN; ETHANOL; MOUSE; QTL; CONSUMPTION; GENOMEWIDE; PREFERENCE; EXPOSURE AB This article represents the proceedings of a symposium at the 2004 International Society for Biomedical Research on Alcoholism in Mannheim, Germany, organized and co-chaired by Susan E. Bergeson and Wolfgang Sommer. The presentations and presenter were (1) Gene Expression in Brains of AlcoholPreferring and Non-Preferring Rats, by Howard J. Edenberg (2) Candidate Treatment Targets for Alcoholism: Leads from Functional Genomics Approaches, by Wolfgang Sommer (3) Microarray Analysis of Acute and Chronic Alcohol Response in Brain, by Susan E. Bergeson (4) On the Integration of QTL and Gene Expression Analysis, by Robert J. Hitzemann (5) Microarray and Proteomic Analysis of the Human Alcoholic Brain, by Peter R. Dodd. C1 Univ Texas, Waggoner Ctr Alcohol & Addict Res, Neurobiol Sect, Austin, TX 78712 USA. Univ Queensland, SMMS, Brisbane, Qld, Australia. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46204 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. NIAAA, Lab Clin & Translat Sci, NIH, Bethesda, MD USA. Karolinska Inst, NEUROTEC, Div Psychiat, Stockholm, Sweden. RP Bergeson, SE (reprint author), Univ Texas, Waggoner Ctr Alcohol & Addict Res, Neurobiol Sect, A4800,MBB1-138AA,1 Univ Stn, Austin, TX 78712 USA. EM bergeson@mail.utexas.edu RI Dodd, Peter/A-4865-2010; Lewohl, Joanne/D-6163-2011; OI Dodd, Peter/0000-0001-5970-0181; Sommer, Wolfgang/0000-0002-5903-6521; Edenberg, Howard/0000-0003-0344-9690 FU NIAAA NIH HHS [R21 AA013182, K01 AA013403, K01 AA013403-01, L30 AA015308, L30 AA015308-02, P50 AA007611, R01 AA012404, R01 AA012725, R21 AA013182-01, R24 AA012725, R28 AA012725, T32 AA007471, U01 AA013475, U01 AA013475-02, U01 AA013484, U01 AA013518, U01 AA013521] NR 35 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2005 VL 29 IS 6 BP 1066 EP 1073 DI 10.1097/01.ALC.0000171043.29384.3E PG 8 WC Substance Abuse SC Substance Abuse GA 941KE UT WOS:000230212900018 PM 21512613 ER PT J AU Stromland, K Mattson, SN Adnams, CM Autti-Ramo, I Riley, EP Warren, KR AF Stromland, K Mattson, SN Adnams, CM Autti-Ramo, I Riley, EP Warren, KR TI Fetal alcohol spectrum disorders: An international perspective SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE fetal alcohol syndrome; fetal alcohol spectrum disorders; birth defects ID CORPUS-CALLOSUM; OPTIC-NERVE; CHILDREN; BRAIN; EXPOSURE; ABNORMALITIES; ANOMALIES; COMMUNITY; PATTERNS; ETHANOL AB This article presents the proceedings of a symposium presented at the 2004 annual meeting of the International Society for Biomedical Research on Alcoholism, held in Mannheim, Germany. The organizers and chairpersons were Kerstin Stromland and Kenneth R. Warren. The presentations were as follows: 1) "Comparison of FASD in Moscow, Russia, and San Diego, California," by Sarah N. Mattson; 2) "Neurobehavior and Interventions in FASD in South Africa," presented by Colleen M. Adnams; 3) "Ophthalmologic Involvement in the Fetal Alcohol Syndrome" presented by Kerstin Stromland; and 4) "Brain Imaging in Children With Fetal Alcohol Spectrum Disorders," by Ilona Autti-Ramo. C1 NIAAA, Off Sci Affairs, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Inst Clin Neurosci, Dept Pediat Ophthalmol, Gothenburg, Sweden. San Diego State Univ, Ctr Behav Teratol, Dept Psychol, San Diego, CA 92182 USA. Univ Cape Town, ZA-7925 Cape Town, South Africa. Univ Helsinki, Cent Hosp, Dept Child Neurol, Helsinki, Finland. RP Warren, KR (reprint author), NIAAA, Off Sci Affairs, NIH, 5635 Fishers Ln, Bethesda, MD 20892 USA. EM kwarren@mail.nih.gov RI Riley, Edward/E-6369-2013; Mattson, Sarah/G-5344-2011 OI Riley, Edward/0000-0001-8747-891X; Mattson, Sarah/0000-0001-8499-9605 NR 34 TC 9 Z9 9 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JUN PY 2005 VL 29 IS 6 BP 1121 EP 1126 DI 10.1097/01.ALC.0000168172.62481.07 PG 6 WC Substance Abuse SC Substance Abuse GA 941KE UT WOS:000230212900025 ER PT J AU Bertoni, AG Bonds, DE Thom, T Chen, GJ Goff, DC AF Bertoni, AG Bonds, DE Thom, T Chen, GJ Goff, DC TI Acute coronary syndrome national statistics: Challenges in definitions SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; PAIN OBSERVATION UNIT; SAME-DAY-DISCHARGE; CHEST-PAIN; HEART-DISEASE; EMERGENCY-DEPARTMENT; UNSTABLE ANGINA; EUROPEAN-SOCIETY; OUTPATIENT PTCA; MEDICAL-CARE AB Background Increasing convergence in the management of acute myocardial infarction (AMI) and unstable angina (UA) has led some to consider whether these 2 diagnoses should be consolidated into acute coronary syndrome (ACS) for the purpose of coronary heart disease surveillance. Methods We used the 1988-2001 Nationwide Inpatient Sample, which has demographic and diagnosis data on 6 to 7 million discharges per year from a sample of US nonfederal hospitals. We identified discharges with a first- or all-listed diagnosis of AMI (international Classification of Diseases, Ninth Revision, Clinical Modification 4 7 0) or UA (International Classification of Diseases, Ninth Revision, Clinical Modification 411) and defined ACS-first as a primary diagnosis of either condition and all-listed ACS as codes 410 or 411 among any diagnoses. Sampling weights were applied to produce yearly national discharge estimates; annual population estimates were used to calculate yearly hospital discharge rates; rates were then adjusted to the 2000 standard population. Results Rates of first- and all-listed AMIs changed little. Rates of first-listed UA fell 87% from 29.7/10000 in 1988 to 3.9/10000 in 2001. This sharp decline was seen among all age and sex groups. Consequently, rates of ACS as a primary diagnosis declined 44%. In contrast, discharge rates for all-listed UA and ACS declined only modestly. Conclusions As a primary diagnosis, UA is disappearing. Rates of first-listed ACS are quite sensitive to the decline in UA. Although discharge data based on first-listed diagnoses have been used to estimate the national incidence of AMI, they may not provide accurate data regarding current trends for ACS. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. Natl Heart Blood & Lung Inst, NIH, Bethesda, MD USA. RP Bertoni, AG (reprint author), Wake Forest Univ, Baptist Med Ctr, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM abertoni@wfubmc.edu NR 35 TC 18 Z9 18 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2005 VL 149 IS 6 BP 1055 EP 1061 DI 10.1016/j.ahj.2004.10.040 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 947CZ UT WOS:000230622100028 PM 15976788 ER PT J AU Ekelund, U Brage, S Sardhina, LB Anderssen, SA Andersen, LB Harro, M Franks, PW Cooper, AR Riddoch, C Froberg, K AF Ekelund, U Brage, S Sardhina, LB Anderssen, SA Andersen, LB Harro, M Franks, PW Cooper, AR Riddoch, C Froberg, K TI Level of physical activity and adiposity in children: relevance of sedentary behaviors - Reply to C Maffeis SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID ENERGY-EXPENDITURE C1 MRC, Epidemiol Unit, Elsie Widdowson Lab, Cambridge CB1 9NL, England. Univ Tecn Lisboa, Fac Human Movement, P-1100 Lisbon, Portugal. Norwegian Univ Sport & Phys Educ, Dept Sports Med, Oslo, Norway. Univ Tartu, Dept Publ Hlth, Tartu, Estonia. NIDDK, Diabet & Arthrit Epidemiol Sect, NIH, Phoenix, AZ USA. Univ Bristol, Dept Exercise & Hlth Sci, Bristol, Avon, England. Middlesex Univ, London Sport Inst, London N17 8HR, England. Univ So Denmark, Inst Sport Sci & Clin Biomech, Odense, Denmark. RP Ekelund, U (reprint author), MRC, Epidemiol Unit, Elsie Widdowson Lab, Fulbourn Rd, Cambridge CB1 9NL, England. EM ulf.ekelund@mrc-epid.cam.ac.uk RI Brage, Soren/C-6415-2013; Cooper, Ashley/D-9956-2014 OI Brage, Soren/0000-0002-1265-7355; Cooper, Ashley/0000-0001-8644-3870 NR 6 TC 0 Z9 0 U1 0 U2 14 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUN PY 2005 VL 81 IS 6 BP 1449 EP 1450 PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 934LH UT WOS:000229709800031 ER PT J AU Jatoi, I Proschan, MA AF Jatoi, I Proschan, MA TI Randomized trials of breast-conserving therapy versus mastectomy for primary breast cancer - A pooled analysis of updated results SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE breast cancer; breast-conserving therapy; mastectomy; randomized trials; metaanalysis ID COMPARING TOTAL MASTECTOMY; 20-YEAR FOLLOW-UP; CONSERVATIVE TREATMENT; CLINICAL-TRIALS; TUMOR RECURRENCE; SURGERY; LUMPECTOMY; RADIOTHERAPY; IRRADIATION; CARCINOMA AB We have undertaken a pooled analysis of the 6 major randomized trials comparing mastectomy (NIT) and breast-conserving therapy (BCT) in the treatment of primary breast cancer. Specifically, these trials compared the 2 most widely used options in local treatment: mastectomy and axillary dissection (MT) versus breast-conserving surgery, axillary dissection, and breast radiotherapy (BCT). The early results of these 6 trials formed the basis for a 1990 National Institutes of Health Consensus statement. However, most of these trials have recently published long-term follow-up results, and this pooled analysis incorporates the updated results of these 6 trials. For each of these trials, the observed number of treatment events was compared with that expected under the null hypothesis, given the number of patients per arm and the total number of events. Approximate odds ratios were computed using the observed and expected number of events, and the variance of the observed number of events. These were then pooled across trials to give overall odds ratios for the risk of locoregional recurrence, total recurrence, and death. Four of the 6 trials show that NIT significantly reduces the risk of locoregional recurrence when compared with BCT, and the pooled odds ratio also shows a significant benefit for NIT (odds ratio [OR], 1.561; 95% confidence interval [CI], 1.289-1.890; P < 0.001). However, only I trial shows a statistically significant benefit for NIT in reducing mortality, and the pooled odds ratio shows no significant difference between NIT and BCT (OR, 1.070; 95% CI, 0.935-1.224; P = 0.33). This pooled analysis confirms that NIT and BCT have comparable effects on mortality, even after long-term follow up. However, BCT is associated with a significantly greater risk of locoregional recurrence. C1 Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Natl Naval Med Res Inst, Dept Surg, Bethesda, MD USA. NHLBI, Dept Biostat, NIH, Bethesda, MD 20892 USA. RP Jatoi, I (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM ismail.jatoi@us.army.mil NR 31 TC 109 Z9 120 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD JUN PY 2005 VL 28 IS 3 BP 289 EP 294 DI 10.1097/01.coc.0000156922.58631.d7 PG 6 WC Oncology SC Oncology GA 934EL UT WOS:000229689600013 PM 15923803 ER PT J AU Kirrane, EF Hoppin, JA Kamel, F Umbach, DM Boyes, WK DeRoos, AJ Alavanja, M Sandler, DP AF Kirrane, EF Hoppin, JA Kamel, F Umbach, DM Boyes, WK DeRoos, AJ Alavanja, M Sandler, DP TI Retinal degeneration and other eye disorders in wives of farmer pesticide applicators enrolled in the agricultural health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE agriculture; eye diseases; occupational exposure; pesticides; retinal degeneration; spouses ID AGE-RELATED MACULOPATHY; VISUAL-SYSTEM; MACULAR DEGENERATION; EPIDEMIOLOGY; RAT; ORGANOPHOSPHATES; TOXICITY; PATTERNS; WORKERS AB Retinal degeneration is the leading cause of visual impairment in older adults. An association between retinal degeneration and fungicide use was observed previously among farmer pesticide applicators in the Agricultural Health Study, a large study of farm families from Iowa and North Carolina. The objective of this investigation was to determine whether wives of these farmer pesticide applicators were at increased risk of retinal degeneration. Self-reported cross-sectional data obtained via questionnaire between 1993 and 1997 from 31,173 wives were used. Associations of specific pesticides and groups of pesticides based on function (fungicides, herbicides, insecticides, and fumigants) or chemical structure (organophosphates, organochlorines, and carbamates) with eye disorders were evaluated using logistic and hierarchical logistic regression analyses. Self-reported retinal degeneration was associated with the wife's fungicide use (odds ratio = 1.9, 95% confidence interval: 1.2, 3.1) after adjustment for age and state of residence. Specific fungicides that appeared to drive this association were maneb or mancozeb and ziram. No associations between pesticide use and other eye disorders were found. Although these findings for retinal degeneration are based solely on self-reported disease, they are consistent with those reported for farmer pesticide applicators. These findings suggest that exposure to some fungicides and other pesticides may increase the risk of retinal degeneration and warrant further investigation. C1 NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Coda Inc, Durham, NC USA. US EPA, Res Triangle Pk, NC 27711 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA. NCI, NIH, US Dept HHS, Rockville, MD USA. RP Hoppin, JA (reprint author), NIEHS, Epidemiol Branch, NIH, US Dept HHS, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM hoppin1@niehs.nih.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 32 TC 16 Z9 17 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 JUN 1 PY 2005 VL 161 IS 11 BP 1020 EP 1029 DI 10.1093/aje/kwi140 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 928PZ UT WOS:000229285500004 PM 15901622 ER PT J AU Hauptmann, M Lubin, JH Stewart, PA Hayes, RB Blair, A AF Hauptmann, M Lubin, JH Stewart, PA Hayes, RB Blair, A TI Re: "Mortality from solid cancers among workers in formaldehyde industries" - Reply SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID NASOPHARYNGEAL CARCINOMA; OCCUPATIONAL EXPOSURES; RISK; WOOD C1 NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Hauptmann, M (reprint author), NCI, NIH, US Dept HHS, Bethesda, MD 20892 USA. NR 11 TC 3 Z9 3 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 BP 1090 EP 1091 DI 10.1093/aje/kwi156 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 928PZ UT WOS:000229285500013 ER PT J AU Adams, KF Leitzmann, MF Kipnis, V Midthune, D Subar, A Thompson, F Hollenbeck, A Campbell, D Mouw, T Hurwitz, P Schatzkin, A AF Adams, KF Leitzmann, MF Kipnis, V Midthune, D Subar, A Thompson, F Hollenbeck, A Campbell, D Mouw, T Hurwitz, P Schatzkin, A CA NIL AARP Diet Hlth Study TI Association between body mass and colon cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S80 EP S80 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100315 ER PT J AU Bonner, MR Coble, J Blair, A Hoppin, JA Sandler, DP Alavanja, MCR AF Bonner, MR Coble, J Blair, A Hoppin, JA Sandler, DP Alavanja, MCR TI Malathion exposure and cancer incidence in the Agricultural Health Study (AHS) SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S84 EP S84 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100332 ER PT J AU Brinton, L Sakoda, L Frederiksen, K Graubard, B Kjaer, S Sherman, M Olsen, J Mellemkjaer, L AF Brinton, L Sakoda, L Frederiksen, K Graubard, B Kjaer, S Sherman, M Olsen, J Mellemkjaer, L TI Relationship of benign gynecologic diseases to subsequent risk of ovarian and uterine cancers. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Rockville, MD 20852 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S146 EP S146 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100581 ER PT J AU Chen, H Schernhammer, E Schwarzschild, MA Ascherio, A AF Chen, H Schernhammer, E Schwarzschild, MA Ascherio, A TI Night shift work and risk of Parkinson's Disease. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S90 EP S90 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100355 ER PT J AU Chen, J Wacholder, S Morton, LM Bhatti, P Hartge, P AF Chen, J Wacholder, S Morton, LM Bhatti, P Hartge, P TI Quantifying selection bias in epidemiologic studies. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 7 Z9 7 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 JUN 1 PY 2005 VL 161 IS 11 SU S BP S145 EP S145 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100574 ER PT J AU Daugherty, SE Platz, EA Fallin, MD Welch, R Reding, D Huang, WY Chatterjee, N Hayes, RB AF Daugherty, SE Platz, EA Fallin, MD Welch, R Reding, D Huang, WY Chatterjee, N Hayes, RB TI Alpha-methylacyl-coa racemase (AMACR) variants and prostate cancer in plco. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S150 EP S150 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100597 ER PT J AU Freeman, LEB Bonner, MR Blair, A Hoppin, JA Sandler, DP Lynch, C Knott, C Alavanja, MCR AF Freeman, LEB Bonner, MR Blair, A Hoppin, JA Sandler, DP Lynch, C Knott, C Alavanja, MCR TI Cancer incidence among pesticide applicators exposed to diazinon in the agricultural health study cohort. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S103 EP S103 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100408 ER PT J AU Hartge, P Cahill, JI Bernstein, L Gallagher, R Savitz, D AF Hartge, P Cahill, JI Bernstein, L Gallagher, R Savitz, D TI Declining rates of participation in population-based research: How bad is the problem, and what is the solution? SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S147 EP S147 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100583 ER PT J AU Hartmuller, V McEligot, A Balbuena, R West, D Giles, G Boyd, N Senie, R John, E Daly, M Seminara, D AF Hartmuller, V McEligot, A Balbuena, R West, D Giles, G Boyd, N Senie, R John, E Daly, M Seminara, D CA Breast Cancer Family Registry TI The breast cancer family registry: Diet collection methodology for studies of the genetic epidemiology of breast cancer. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Breast Canc Family Registry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S14 EP S14 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100056 ER PT J AU Herrell, R Merikangas, K Gamma, A Ajdacic, V Eich, D Rossler, W Angst, J AF Herrell, R Merikangas, K Gamma, A Ajdacic, V Eich, D Rossler, W Angst, J TI Drug use trajectories in a 20-year prospective study of a probability sample of young adults. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NIMH, NIH, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S124 EP S124 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100491 ER PT J AU Hoppin, JA Umbach, DM London, SJ Lynch, CF Alavanja, MCR Sandler, DP AF Hoppin, JA Umbach, DM London, SJ Lynch, CF Alavanja, MCR Sandler, DP TI Pesticides associated with wheeze among commercial pesticide applicators in the agricultural health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NIEHS, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S85 EP S85 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100337 ER PT J AU Kirkland, S Harris, TB AF Kirkland, S Harris, TB TI What's new with the old: Aging as the future of population epidemiology. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 Dalhousie Univ, Dept Epidemiol & Community Hlth, Halifax, NS, Canada. Dalhousie Univ, Dept Med, Halifax, NS, Canada. NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Dalhousie Univ, Div Geriatr Med, Halifax, NS B3H 3J5, Canada. Calif Pacific Med Ctr, Inst Res, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S97 EP S97 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100384 ER PT J AU Law, DCG Klebanoff, MA Brock, JW Longnecker, MP AF Law, DCG Klebanoff, MA Brock, JW Longnecker, MP TI Maternal serum PCB and DDE levels and time to pregnancy. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S125 EP S125 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100497 ER PT J AU Leitzmann, MF Calton, B Chang, SC Wright, ME Subar, A Thompson, F Kipnis, V Midthune, D Mouw, T Hurwitz, P Campbell, D Hollenbeck, A Schatzkin, A AF Leitzmann, MF Calton, B Chang, SC Wright, ME Subar, A Thompson, F Kipnis, V Midthune, D Mouw, T Hurwitz, P Campbell, D Hollenbeck, A Schatzkin, A TI History of diabetes and subsequent prostate cancer risk in the NIH-AARP diet and health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S20 EP S20 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100081 ER PT J AU Lim, U Solomon, RS Morton, LM Leitzmann, M Subar, AF Kipnis, V Midthune, D Thompson, FE Mouw, T Hurwitz, P Campbell, DS Hartge, P Hollenbeck, A Schatzkin, A AF Lim, U Solomon, RS Morton, LM Leitzmann, M Subar, AF Kipnis, V Midthune, D Thompson, FE Mouw, T Hurwitz, P Campbell, DS Hartge, P Hollenbeck, A Schatzkin, A TI Anthropometric indicators and risk of lymphoid malignancies in the prospective NIH-AARP diet and health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 US Dept HHS, NCI, DCEG, NEB,NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S22 EP S22 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100087 ER PT J AU Louis, GMB Lynch, CD Weiner, J McGuinness, B Vena, J AF Louis, GMB Lynch, CD Weiner, J McGuinness, B Vena, J TI Polychlorinated biphenyl (PCBs) exposure and menstrual cycle characteristics. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NICHD, DESPR, NIH, DHHS, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S127 EP S127 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100502 ER PT J AU Marcus, PM Miedzinksi, M AF Marcus, PM Miedzinksi, M TI Measuring the impact of hipaxs privacy rule in the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S151 EP S151 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100598 ER PT J AU McGlynn, KA Graubard, BI Nam, JM Stanczyk, FZ Longnecker, MP Klebanoff, MA AF McGlynn, KA Graubard, BI Nam, JM Stanczyk, FZ Longnecker, MP Klebanoff, MA TI Maternal hormone levels and cryptorchism SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S49 EP S49 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100196 ER PT J AU Morton, LM Cahill, J Hartge, P AF Morton, LM Cahill, J Hartge, P TI Participation in epidemiologic studies: Survey of practice. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 US Dept HHS, NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S69 EP S69 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100272 ER PT J AU Nguyen, RHN Wilcox, AJ Moen, BE McConnaughey, DR Lie, RT AF Nguyen, RHN Wilcox, AJ Moen, BE McConnaughey, DR Lie, RT TI Maternal occupation and oral clefts in Norway. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 Univ Bergen, Bergen, Norway. NIEHS, NIH, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S82 EP S82 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100323 ER PT J AU Perkins, N Schisterman, EF AF Perkins, N Schisterman, EF TI The use and misuse of "optimal" cut-points SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NICHD, DESPR, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S66 EP S66 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100260 ER PT J AU Purdue, MP Mink, PJ Hartge, P Huang, WY Weissfeld, J Buys, S Hayes, RB AF Purdue, MP Mink, PJ Hartge, P Huang, WY Weissfeld, J Buys, S Hayes, RB TI Hormone replacement therapy and colorectal adenoma: Data from the prostate, lung, colorectal and ovarian (PLCO) cancer screening trial. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S10 EP S10 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100040 ER PT J AU Ronckers, C Sigurdson, A Stovall, M Smith, S Sklar, C Land, C Neglia, J Mertens, A Hammond, S Meadows, A Robison, L Inskip, P AF Ronckers, C Sigurdson, A Stovall, M Smith, S Sklar, C Land, C Neglia, J Mertens, A Hammond, S Meadows, A Robison, L Inskip, P TI Radiation and thyroid cancer in the childhood cancer survivor study: A detailed evaluation of dose-response and its modifiers. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S11 EP S11 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100044 ER PT J AU Schisterman, EF Perkins, N AF Schisterman, EF Perkins, N TI Confidence intervals for the Youden index and corresponding optimal cut-point. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NICHD, DESPR, NIH, Rockville, MD 20854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S9 EP S9 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100034 ER PT J AU Stolzenberg-Solomon, RZ Graubard, B Chari, S Limburg, P Taylor, PR Virtamo, J Albanes, D AF Stolzenberg-Solomon, RZ Graubard, B Chari, S Limburg, P Taylor, PR Virtamo, J Albanes, D TI Insulin, glucose, insulin resistance, and pancreatic cancer in male smokers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, NEB, DCEG, NIH, Rockville, MD 20852 USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S93 EP S93 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100368 ER PT J AU Wilcox, AJ Lie, RT Solvoll, K Drevon, CA Aabyholm, F Vindenes, H AF Wilcox, AJ Lie, RT Solvoll, K Drevon, CA Aabyholm, F Vindenes, H TI Folic acid deficiency as a cause of facial clefts SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S95 EP S95 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100374 ER PT J AU Wright, ME Weinstein, SJ Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Wright, ME Weinstein, SJ Pietinen, P Taylor, PR Virtamo, J Albanes, D TI Serum vitamin E and all-cause, cancer, and cardiovascular disease mortality in a cohort of male smokers. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT Joint Meeting of the Society-for-Epidemiologic-Research/Canadian-Society-for-Epidemiology-and -Biostatistics CY JUN 27-30, 2005 CL Toronto, CANADA SP Soc Epidemiol Res, Canadian Soc Epidemiol & Biostat C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2005 VL 161 IS 11 SU S BP S151 EP S151 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 932ZS UT WOS:000229594100600 ER PT J AU Schmidt, LS Nickerson, ML Warren, MB Glenn, GM Toro, JR Merino, MJ Turner, ML Choyke, PL Sharma, N Peterson, J Morrison, P Maher, ER Walther, MM Zbar, B Linehan, WM AF Schmidt, LS Nickerson, ML Warren, MB Glenn, GM Toro, JR Merino, MJ Turner, ML Choyke, PL Sharma, N Peterson, J Morrison, P Maher, ER Walther, MM Zbar, B Linehan, WM TI Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dube syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RENAL-CELL CARCINOMA; GERMAN-SHEPHERD DOG; NIHON RAT MODEL; SPONTANEOUS PNEUMOTHORAX; INTESTINAL POLYPOSIS; NODULAR DERMATOFIBROSIS; PERIFOLLICULAR FIBROMAS; KIDNEY NEOPLASIA; MESSENGER-RNA; GENE AB Birt-Hogg-Dube syndrome (BHD), a genodermatosis characterized by multiple hamartomas of the hair follicle (fibrofolliculoma), predisposes individuals to an increased risk of developing renal neoplasms and spontaneous pneumothorax. Previously, we localized the BHD locus (also known as FLCN) to chromosome 17p11.2 by linkage analysis and subsequently identified germline mutations in a novel gene in probands from eight of the nine families with BHD in our screening panel. Affected members of five of the families inherited an insertion/deletion of a cytosine in a C-8 tract in exon 11. This mutation was also identified by exon 11 screening in probands from 22 of 52 additional families with BHD and therefore represents a hypermutable "hotspot" for mutation in BHD. Here, we screened the remaining 30 families from this large BHD cohort by direct sequence analysis and identified germline BHD mutations in 84% (51/61) of all families with BHD recruited to our study. Mutations were located along the entire length of the coding region, including 16 insertion/deletion, 3 nonsense, and 3 splice-site mutations. The majority of BHD mutations were predicted to truncate the BHD protein, folliculin. Among patients with a mutation in the exon 11 hotspot, significantly fewer renal tumors were observed in patients with the C-deletion than those with the C-insertion mutation. Coding-sequence mutations were not found, however, in probands from two large families with BHD whose affected members shared their family's BHD-affected haplotype. Of the 53 families with BHD whose members inherited either a germline mutation or the affected haplotype, 24 (45%) had at least one member with renal neoplasms. Three families classified with familial renal oncocytoma were identified with BHD mutations, which represents the first disease gene associated with this rare form of renal neoplasm. This study expands the BHD-mutation spectrum and evaluates genotype-phenotype correlations among families with BHD. C1 NCI, Immunobiol Lab, Ctr Canc Res, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick Inc, Basic Res Program, Frederick, MD USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Belfast City Hosp Trust, Belfast, Antrim, North Ireland. Univ Birmingham, Inst Biomed Res, Sect Med & Mol Genet, Birmingham, W Midlands, England. RP Schmidt, LS (reprint author), NCI, Immunobiol Lab, Ctr Canc Res, Bldg 560,Room 12-69, Frederick, MD 21702 USA. EM schmidtl@ncifcrf.gov RI MAHER, EAMONN/A-9507-2008 OI MAHER, EAMONN/0000-0002-6226-6918 FU PHS HHS [N01-C0-12400] NR 29 TC 178 Z9 184 U1 0 U2 7 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 JUN PY 2005 VL 76 IS 6 BP 1023 EP 1033 DI 10.1086/430842 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 925IX UT WOS:000229047900008 PM 15852235 ER PT J AU Edison, RJ Muenke, M AF Edison, RJ Muenke, M TI Reply to "Statin drugs and congenital anomalies" by Gibb and Scialli SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID A REDUCTASE INHIBITORS; SONIC HEDGEHOG; CELL-DEATH; RETINOIC-ACID; LIMB; EXPRESSION; MALFORMATIONS; LOVASTATIN; DEFECTS; SIMVASTATIN C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr, Bethesda, MD 20892 USA. EM mmuenke@nhgri.NIH.gov NR 34 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUN 1 PY 2005 VL 135A IS 2 BP 232 EP 234 DI 10.1002/ajmg.a.30686 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 931LY UT WOS:000229488000028 ER PT J AU Cusick, M SanGiovanni, JP Chew, EY Csaky, KG Hall-Shimel, K Reed, GF Caruso, RC Ferris, FL AF Cusick, M SanGiovanni, JP Chew, EY Csaky, KG Hall-Shimel, K Reed, GF Caruso, RC Ferris, FL TI Central visual function and the NEI-VFQ-25 near and distance activities subscale scores in people with type 1 and 2 diabetes SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 29-MAY 04, 2001 CL FT LAUDERDALE, FL SP Assoc Res Vis & Ophthalmol ID QUALITY-OF-LIFE; FUNCTION QUESTIONNAIRE; GENERAL HEALTH; EYE DISEASE; RETINOPATHY; VISION; ACUITY; AREDS AB PURPOSE: To investigate relationships between clinical measures of central visual function and NEI-VFQ-25 Near and Distance Activities subscales in patients with diabetic retinopathy. DESIGN: Clinic-based, cross-sectional, observational study. METHODS: The NEI-VFQ-25 was administered to 170 people with type 1 or 2 diabetes before an ocular examination that included visual acuity, contrast sensitivity, and central visual fields. Multiple linear regression and exact multiple logistic regression were used to assess the relationship between poor acuity (< 69 letters), poor contrast sensitivity (< 1.5 log units), and abnormal visual fields (mean deviation <= -5dB) and NEI-VFQ-25 sub, scale scores. RESULTS: Final multivariable linear models explained a beta = 4.7 letter difference (P <= .001) for each 25-point Near Activities subscale score difference. Similar effects were observed for the Distance Activities subscale, although the magnitudes of regression and partial correlation coefficients were lower (beta = 3.3 letters, P <= .01). Final logistic regression models on abnormal clinical categories of central visual function demonstrated relationships only with the Near Activities subscale. For a 1,point change in Near Activities subscale score, the odds of obtaining a poor score for visual acuity, central visual fields, and contrast sensitivity changed by 0.08 (P <= .001), 0.07 (P <= .05), and 0.12 (P <= .001), respectively. CONCLUSIONS: NEI-VFQ-25 Near and Distance Activities subscales demonstrate utility as measures of central visual function in persons with type 1 or 2 diabetes. Low scores on the NEI-VFQ-25 may reflect poor central visual fields and contrast sensitivity in addition to poor visual acuity. (c) 2005 by Elsevier Inc. All rights reserved. C1 Howard Hughes Med Inst, Natl Inst Hlth, Res Scholars Program, Div Epidemiol & Clin Res, Bethesda, MD 20817 USA. Howard Hughes Med Inst, Natl Inst Hlth, Res Scholars Program, NEI, Bethesda, MD 20817 USA. Off Sci Director, Bethesda, MD USA. Ophthalm Genet & Vis Funct Branch, Bethesda, MD USA. RP Chew, EY (reprint author), Howard Hughes Med Inst, Natl Inst Hlth, Res Scholars Program, Div Epidemiol & Clin Res, Bethesda, MD 20817 USA. EM eyc@nei.nih.gov RI SanGiovanni, John Paul/A-7605-2008 FU Intramural NIH HHS [Z99 EY999999] NR 23 TC 33 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JUN PY 2005 VL 139 IS 6 BP 1042 EP 1050 DI 10.1016/j.ajo.2005.01.008 PG 9 WC Ophthalmology SC Ophthalmology GA 939BC UT WOS:000230046100011 PM 15953434 ER PT J AU Ashikaga, H Covell, JW Omens, JH AF Ashikaga, H Covell, JW Omens, JH TI Diastolic dysfunction in volume-overload hypertrophy is associated with abnormal shearing of myolaminar sheets SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE finite deformation; strain; fiber; sheet; diastolic function ID CANINE LEFT-VENTRICLE; HEART-FAILURE; MYOCARDIAL DEFORMATION; PASSIVE STIFFNESS; CROSS-LINKING; MECHANICS; DETERMINANTS; ARCHITECTURE; RELAXATION; PROGNOSIS AB Diastolic dysfunction in volume-overload hypertrophy by aortocaval fistula is characterized by increased passive stiffness of the left ventricle (LV). We hypothesized that changes in passive properties are associated with abnormal myolaminar sheet mechanics during diastolic filling. We determined three-dimensional finite deformation of myofiber and myolaminar sheets in the LV free wall of six dogs with cineradiography of implanted markers during development of volume-overload hypertrophy by aortocaval fistula. After 9 +/- 2 wk of volume overload, all dogs developed edema of extremities, pulmonary congestion, elevated LV end-diastolic pressure (5 +/- 2 vs. 21 +/- 4 mmHg, P < 0.05), and increased LV volume. There was no significant change in systolic function [dP/dt(max): 2,476 +/- 203 vs. 2,330 +/- 216 mmHg/s, P = not significant (NS)]. Diastolic relaxation was significantly reduced (dP/dt(min): -2,466 +/- 190 vs. -2,076 +/- 166 mmHg/s, P < 0.05; time constant of LV pressure decline: 32 +/- 2 vs. 43 +/- 1 ms, P < 0.05), whereas duration of diastolic filling was unchanged (304 +/- 33 vs. 244 +/- 42 ms, P = NS). Fiber stretch and sheet shear occur predominantly in the first third of diastolic filling, and chronic volume overload induced remodeling in lengthening of the fiber and reorientation of the laminar sheet architecture. Sheet shear was significantly increased and delayed at the subendocardial layer (P < 0.05), whereas magnitude of fiber stretch was not altered in volume overload (P = NS). These findings indicate that enhanced filling in volume-overload hypertrophy is achieved by enhanced sheet shear early in diastole. These results provide the first evidence that changes in motion of radially oriented laminar sheets may play an important functional role in pathology of diastolic dysfunction in this model. C1 Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Ashikaga, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, 10 Ctr Dr,MSC 1061,Bldg 10,B1D416, Bethesda, MD 20892 USA. EM ashikagah@nhlbi.nih.gov OI Ashikaga, Hiroshi/0000-0003-3689-6892 FU NHLBI NIH HHS [R01 HL032583, HL-32583, R01 HL032583-17] NR 47 TC 15 Z9 15 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2005 VL 288 IS 6 BP H2603 EP H2610 DI 10.1152/ajpheart.01276.2004 PG 8 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 926RI UT WOS:000229139900009 PM 15708954 ER PT J AU Patrick, CB McHowat, J Rosenberger, TA Rapoport, SI Murphy, EJ AF Patrick, CB McHowat, J Rosenberger, TA Rapoport, SI Murphy, EJ TI Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE palmitic acid; signal transduction; phospholipase A(2); catecholamines; phospholipids ID PHOSPHOLIPASE A(2) ACTIVITY; CHRONIC LITHIUM TREATMENT; FATTY-ACIDS; BRAIN PHOSPHOLIPIDS; PARKINSONS-DISEASE; CHEMICAL SYMPATHECTOMY; CARDIAC MYOCYTES; BINDING PROTEIN; ACYL-COENZYME; METABOLISM AB Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 mu Ci/kg of either [1-C-14]palmitic acid ([1-C-14]16: 0) or [1-C-14]arachidonic acid ([1-C-14]20: 4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-C-14]20: 4 n-6-infused rats, which indicates that less 20: 4 n-6 was recycled in denervated rats. In [1-C-14]16:0-infused rats, incorporation rate and turnover values of 16: 0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-C-14]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20: 4 n-6 turnover. These results demonstrate marked reductions in 20: 4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity. C1 Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, Grand Forks, ND 58202 USA. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. St Louis Univ, Dept Pathol, St Louis, MO 63103 USA. Univ N Dakota, Dept Chem, Grand Forks, ND 58202 USA. RP Murphy, EJ (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Pharmacol Physiol & Therapeut, 501 N Columbia Rd,Rm 3700, Grand Forks, ND 58202 USA. EM emurphy@medicine.nodak.edu NR 52 TC 4 Z9 4 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2005 VL 288 IS 6 BP H2611 EP H2619 DI 10.1152/ajpheart.00549.2004 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 926RI UT WOS:000229139900010 PM 15681700 ER PT J AU Shneyvays, V Leshem, D Zinman, T Mamedova, LK Jacobson, KA Shainberg, A AF Shneyvays, V Leshem, D Zinman, T Mamedova, LK Jacobson, KA Shainberg, A TI Role of adenosine A(1) and A(3) receptors in regulation of cardiomyocyte homeostasis after mitochondrial respiratory chain injury SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE Ca2+ transience; hypoxia; ATP-sensitive K+ channel; sodium azide; heart disease; ischemia ID K-ATP CHANNEL; RAT CARDIAC MYOCYTES; RABBIT HEART; METABOLIC INHIBITION; POTASSIUM CHANNELS; CALCIUM OVERLOAD; CA2+ OVERLOAD; SODIUM-AZIDE; CELL-DEATH; CARDIOPROTECTION AB Activation of either the A(1) or the A(3) adenosine receptor (A(1)R or A(3)R, respectively) elicits delayed cardioprotection against infarction, ischemia, and hypoxia. Mitochondrial contribution to the progression of cardiomyocyte injury is well known; however, the protective effects of adenosine receptor activation in cardiac cells with a respiratory chain deficiency are poorly elucidated. The aim of our study was to further define the role of A1R and A3R activation on functional tolerance after inhibition of the terminal link of the mitochondrial respiratory chain with sodium azide, in a state of normoxia or hypoxia, compared with the effects of the mitochondrial ATP-sensitive K+ channel opener diazoxide. Treatment with 10 mM sodium azide for 2 h in normoxia caused a considerable decrease in the total ATP level; however, activation of adenosine receptors significantly attenuated this decrease. Diazoxide ( 100 mu M) was less effective in protection. During treatment of cultured cardiomyocytes with hypoxia in the presence of 1 mM sodium azide, the A(1)R agonist 2-chloro-N-6-cyclopentyladenosine was ineffective, whereas the A3R agonist 2-chloro-N-6-iodobenzyl-5'-N-methylcarboxamidoadenosine (Cl-IB-MECA) attenuated the decrease in ATP level and prevented cell injury. Cl-IB-MECA delayed the dissipation in the mitochondrial membrane potential during hypoxia in cells impaired in the mitochondrial respiratory chain. In cells with elevated intracellular Ca2+ concentration after hypoxia and treatment with NaN3 or after application of high doses of NaN3, Cl-IB-MECA immediately decreased the elevated intracellular Ca2+ concentration toward the diastolic control level. The A(1)R agonist was ineffective. This may be especially important for the development of effective pharmacological agents, because mitochondrial dysfunction is a leading factor in the pathophysiological cascade of heart disease. C1 Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, IL-52900 Ramat Gan, Israel. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Shainberg, A (reprint author), Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, IL-52900 Ramat Gan, Israel. EM shaina@mail.biu.ac.il RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 49 TC 34 Z9 36 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD JUN PY 2005 VL 288 IS 6 BP H2792 EP H2801 DI 10.1152/ajpheart.01157.2004 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 926RI UT WOS:000229139900033 PM 15681707 ER PT J AU Buckley, CA Rouhani, FN Kaler, M Adamik, B Hawari, FI Levine, SJ AF Buckley, CA Rouhani, FN Kaler, M Adamik, B Hawari, FI Levine, SJ TI Amino-terminal TACE prodomain attenuates TNFR2 cleavage independently of the cysteine switch SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE tumor necrosis factor-alpha-converting enzyme; 1,10-phenanthroline; a disintegrin and metalloprotease; 55-kDa type I tumor necrosis factor receptor; 75-kDa type II tumor necrosis factor receptor ID TUMOR-NECROSIS-FACTOR; ALPHA-CONVERTING-ENZYME; FACTOR-RECEPTOR; METALLOPROTEASE-DISINTEGRINS; INTRACELLULAR MATURATION; PROTEIN; CELLS; EXPRESSION; LOCALIZATION; STIMULATION AB TNF-α-converting enzyme (TACE, ADAM17) cleaves membrane- associated cytokines and receptors and thereby regulates inflammatory and immune events, as well as lung development and mucin production. For example, the TACE- mediated cleavage of the type II75-kDa TNF receptor (TNFR2) generates a soluble TNF-binding protein that modulates TNF bioactivity. TACE is synthesized as a latent proenzyme that is retained in an inactive state via an interaction between its prodomain and catalytic domain. Although the formation of an intramolecular bond between a cysteine in the prodomain and a zinc atom in the catalytic site had been thought to mediate this inhibitory activity, it was recently reported that the cysteine- switch motif is not required. Here, we hypothesized that the amino terminus of the TACE prodomain might contribute to the ability of the prodomain to maintain TACE in an inactive state independently of a cysteine- switch mechanism. We synthesized a 37- amino acid peptide corresponding to TACE amino acids 18-54 (N-TACE(18-54)) and assessed whether it possessed TACE inhibitory activity. In an in vitro model assay system, N- TACE(18-54) attenuated TACE- catalyzed cleavage of a TNFR2: Fc substrate. Furthermore, N-TACE(18-54) inhibited constitutive TNFR2 shedding from a human monocytic cell line by 42%. A 19-amino acid, leucine- rich domain, corresponding to TACE amino acids 30-48, demonstrated partial inhibitory activity. In summary, we have identified a subdomain within the amino terminus of the TACE prodomain that attenuates TACE catalytic activity independently of a cysteine- switch mechanism, which provides new insight into the regulation of TACE enzymatic activity. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Levine, SJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Rm 6D03,MSC 1590, Bethesda, MD 20892 USA. EM levines@nhlbi.nih.gov NR 49 TC 25 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUN PY 2005 VL 288 IS 6 BP L1132 EP L1138 DI 10.1152/ajplung.00429.2004 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 924XB UT WOS:000229013200016 PM 15749738 ER PT J AU Yang, TX Huang, YG Ye, WL Hansen, P Schnermann, JB Briggs, JP AF Yang, TX Huang, YG Ye, WL Hansen, P Schnermann, JB Briggs, JP TI Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article ID RENIN EXPRESSION; CYCLOOXYGENASE-2; DISEASE; SUSCEPTIBILITY; PROGRESSION; INHIBITION; IMPAIRMENT; DISRUPTION; KIDNEY; MOUSE AB The present study was undertaken to determine whether the severity of renal failure or hypertension in homozygous cyclooxygenase (COX)-2-deficient (COX-2-/-) mice affected by genetic background or gender. COX-2 deletion was introduced into three congenic genetic backgrounds, 129/Sv (129/COX-2-/-), C57/BL6 (C57/COX2-/-), and BALB/c (BALB/COX-2-/-), by backcrossing the original mixed-background knockout mice with the respective inbred strains for 9 or 10 generations. Evaluation of the severity of hypertension and renal failure was performed in knockout and wild-type mice at the age of 2.5-3.5 mo. Blood pressure measured by tail-cuff plethysmography was significantly elevated in the male 129/COX2-/- mice (165.8 +/- 9.2 vs. 116 +/- 5.1 mmHg, P < 0.05), and to a much lesser extent in the female 129/COX-2-/- mice (127.4 +/- 3.3 vs. 102.4 +/- 3.3), whereas it was unchanged in the C57- or BALB/COX-2-/- mice regardless of gender. Urinary excretion of albumin, determined by EIA, was remarkably increased in the 129/COX-2-/- (16.4 +/- 4.1 vs. 0.16 +/- 0.043 mg albumin/mg creatinine, P < 0.001), and to a lesser extent in the male C57/COX-2-/- mice (0.595 +/- 0.416 vs. 0.068 +/- 0.019). Albumin excretion was not elevated in the male BALB/COX-2-/- or in female COX-2-/- mice on any of the three genetic backgrounds. Histological analysis showed abundant protein casts, dilated tubules, and infiltration of inflammatory cells in the male 129/COX-2-/- mice, but not in COX-2-/- mice in other strains or gender. However, the presence of small glomeruli in the nephrogenic zone was observed in all strains of COX-2 knockout mice, regardless of genetic background and gender. Therefore, we conclude that the severity of hypertension and renal failure in COX-2-deficient mice is influenced by genetic background and gender, whereas the incomplete maturation of outer cortical nephrons appears to be independent of genetic background effects. C1 Univ Utah, Div Nephrol, Salt Lake City, UT 84148 USA. NIDDKD, NIH, Bethesda, MD USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. RP Yang, TX (reprint author), Univ Utah, Div Nephrol, Bldg 2,Res Serv 151 E,500 Foothill Dr, Salt Lake City, UT 84148 USA. EM tianxin.yang@hsc.utah.edu RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NHLBI NIH HHS [HL-079453]; NIDDK NIH HHS [DK-064981, DK-066592] NR 40 TC 65 Z9 65 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUN PY 2005 VL 288 IS 6 BP F1125 EP F1132 DI 10.1152/ajprenal.00219.2004 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 924QR UT WOS:000228995500008 PM 15613621 ER PT J AU Krieger, S Lis, S Cetin, T Gallhofer, B Meyer-Lindenberg, A AF Krieger, S Lis, S Cetin, T Gallhofer, B Meyer-Lindenberg, A TI Executive function and cognitive subprocesses in first-episode, drug-naive schizophrenia: An analysis of N-back performance SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID WORKING-MEMORY; DYSFUNCTION AB Objective: This study investigated changes in the cognitive architecture of N-back performance in schizophrenia. Method: N-back performance of 12 patients with first-episode, drug-naive schizophrenia and matched healthy comparison subjects was studied in a reaction-time decomposition paradigm. Results: Imposition of a working memory load led to a significant drop in response accuracy in patients. Reaction-time decomposition suggested slowing of visuomotor and choice reaction processing as well as an inability of parallel processing directed by working memory. Discussion: Although N-back tasks validly access working memory function as a neurocognitive trait in the illness, several additional subprocesses and the ability for cognitive parallel processing are altered and require further study in schizophrenia. C1 NIMH, Neuroimaging Core Facil, Bethesda, MD 20892 USA. Univ Giessen, Sch Med, Dept Psychiat, Giessen, Germany. NIMH, Unit Syst Neurosci Psychiat, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Meyer-Lindenberg, A (reprint author), NIMH, Neuroimaging Core Facil, 10 4C101,9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov OI Meyer-Lindenberg, Andreas/0000-0001-5619-1123; Lis, Stefanie/0000-0002-8051-2756 NR 10 TC 42 Z9 44 U1 1 U2 3 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 JUN PY 2005 VL 162 IS 6 BP 1206 EP 1208 DI 10.1176/appi.ajp.162.6.1206 PG 3 WC Psychiatry SC Psychiatry GA 931SA UT WOS:000229504300026 PM 15930072 ER PT J AU Stillman, FA Wipfli, HL Lando, HA Leischow, S Samet, JM AF Stillman, FA Wipfli, HL Lando, HA Leischow, S Samet, JM TI Building capacity for international tobacco control research: The global tobacco research network SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article AB The Global Tobacco Research Network (GTRN) was developed to enhance global tobacco control research through information sharing and collaboration among researchers. The formation of the GTRN is timely because of the need to ratify, implement, and track the Framework Convention on Tobacco Control. While the spectrum of international tobacco control research continues to expand, resources to support these efforts are still quite limited. As an issue-specific network focused on information sharing and capacity building associated with tobacco control research, the GTRN will provide an opportunity for enhancing the effectiveness of tobacco control initiatives. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, Baltimore, MD 21205 USA. Univ Minnesota, Dept Epidemiol, Minneapolis, MN USA. NCI, Rockville, MD USA. RP Stillman, FA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Inst Global Tobacco Control, 615 N Wolfe St,Rm W6027, Baltimore, MD 21205 USA. EM jstillma@jhsph.edu FU NHLBI NIH HHS [R01 HL073699, R01-HL-73699]; PHS HHS [282980019] NR 8 TC 18 Z9 18 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUN PY 2005 VL 95 IS 6 BP 965 EP 968 DI 10.2105/AJPH.2004.047183 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 929YF UT WOS:000229381800017 PM 15914817 ER PT J AU Hasler, G Gergen, PJ Kleinbaum, DG Ajdacic, V Gamma, A Eich, D Rossler, W Angst, J AF Hasler, G Gergen, PJ Kleinbaum, DG Ajdacic, V Gamma, A Eich, D Rossler, W Angst, J TI Asthma and panic in young adults - A 20-year prospective community study SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE anxiety; child development; respiratory tract disease; sex; smoking ID EXERCISE-INDUCED ASTHMA; RESPIRATORY SYMPTOMS; ANXIETY DISORDERS; CIGARETTE-SMOKING; ZURICH COHORT; MAJOR DEPRESSION; BIRTH-COHORT; ATTACKS; PREVALENCE; RISK AB Rationale: Psychologic factors are increasingly recognized to influence the onset and course of asthma. Previous cross-sectional community-based studies have provided evidence for a relatively specific association between asthma and panic. Objectives: To examine concurrent and longitudinal associations between asthma and panic in young adults. Measurements and Main Results: Prospective communitybased cohort study of young adults (n = 591) followed between ages 19 and 40. Information was derived from six subsequent semi-structured diagnostic interviews conducted by professionals. Cross-sectionally (over the whole study period), asthma was more strongly associated with panic disorder (odds ratio [OR] = 4.0; 95% confidence interval [CI], 1.7, 9.3) than with any panic, which included panic disorder and panic attacks (OR = 2.1; 95% CI, 1.1, 4.5). Longitudinally, after adjusting for potentially confounding variables, active asthma predicted subsequent panic disorder (OR = 4.5; 95% CI, 1.1, 20.1), and the presence of panic disorder predicted subsequent asthma activity (OR = 6.3; 95% CI, 2.8, 14.0). Asthma predicted any panic (OR = 2.7; 95% CI, 1.1, 7.1), whereas any panic did not predict subsequent asthma activity. Associations were stronger in smokers than in nonsmokers, and stronger in women than in men. Smoking, early-childhood anxiety, and a family history of allergy were important confounders of the asthma-panic association. Conclusions: This is the first long-term follow-up study on asthma and panic. It showed close-response-type relationships between panic and asthma, and bidirectional longitudinal associations between the two conditions. It provided evidence for familial factors and smoking as possible shared etiologic explanations. C1 NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. NIAID, Asthma Allergy Inflammat Branch, Div Allergy, NIH, Bethesda, MD 20892 USA. Psychiat Univ Hosp, Zurich, Switzerland. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. RP Hasler, G (reprint author), NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, NIH, 15K N Dr,Room 200,MSC 2670, Bethesda, MD 20892 USA. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Ajdacic-Gross, Vladeta/0000-0002-7032-9237 NR 61 TC 138 Z9 140 U1 3 U2 8 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 JUN 1 PY 2005 VL 171 IS 11 BP 1224 EP 1230 DI 10.1164/rccm.200412-1669OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 930JB UT WOS:000229410800006 PM 15764721 ER PT J AU Kirk, AD Pinto, PA AF Kirk, AD Pinto, PA TI Laparoscopic kidney donation: Looking more than skin deep SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material ID LIVE-DONOR NEPHRECTOMY; RECIPIENTS; IMPACT; TRIAL C1 NIDDKD, Transplantat Branch, NIH, Bethesda, MD USA. NCI, Urol Oncol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Kirk, AD (reprint author), NIDDKD, Transplantat Branch, NIH, Bethesda, MD USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 12 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUN PY 2005 VL 5 IS 6 BP 1177 EP 1178 DI 10.1111/j.1600-6143.2005.00956.x PG 2 WC Surgery; Transplantation SC Surgery; Transplantation GA 925DJ UT WOS:000229031400002 PM 15888020 ER PT J AU Bower, JE Meyerowitz, BE Desmond, KA Bernaards, CA Rowland, JH Ganz, PA AF Bower, JE Meyerowitz, BE Desmond, KA Bernaards, CA Rowland, JH Ganz, PA TI Perceptions of positive meaning and vulnerability following breast cancer: Predictors and outcomes among long-term breast cancer survivors SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID QUALITY-OF-LIFE; BONE-MARROW TRANSPLANTATION; POSTTRAUMATIC GROWTH; MULTIETHNIC SAMPLE; DEPRESSION SCALE; WOMEN; ADJUSTMENT; BENEFIT; EVENTS; STRESS AB Background: Survival rates for women with early-stage breast cancer have increased significantly in recent years. However, little is known about the long-term impact of the cancer experience on women's psychological functioning. Theoretical and descriptive accounts suggest that cancer may evoke both perceptions of vulnerability and positive meaning, with potentially different effects on mental health. Purpose: This study was designed to evaluate the prevalence and stability of these perceptions in a large sample of breast cancer survivors, to identify their antecedents, and to determine their impact on long-term adjustment. Methods: Breast cancer survivors (N = 763) were assessed longitudinally at 1 to 5 years and 5 to 10 years postdiagnosis. Participants completed surveys assessing perceptions of positive meaning and vulnerability and standard measures of psychological adjustment of and quality of life. Results: The majority of women reported positive changes in outlook and priorities as well as feelings of vulnerability at both assessment points. Consistent with hypotheses, results showed that perceptions of positive meaning and vulnerability were positively correlated and were both associated with factors that increased the disruptiveness of the cancer experience. Vulnerability was strongly associated with negative affect, whereas meaning was associated with positive affect in cross-sectional and longitudinal analyses. Conclusions: Results suggest that a cancer diagnosis may lead to enduring feelings of vulnerability as well as positive changes in meaning; however, these perceptions have very different mental health correlates. C1 Univ Calif Los Angeles, Neuropsychiat Inst, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA. Stat Consultant, Culver City, CA USA. NCI, Div Canc Control & Populat Sci, Off Canc Survivorship, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Bower, JE (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst, Cousins Ctr Psychoneuroimmunol, Room 3306,Box 957076, Los Angeles, CA 90095 USA. EM jbower@ucla.edu FU NCI NIH HHS [R01CA63028] NR 50 TC 128 Z9 133 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD JUN PY 2005 VL 29 IS 3 BP 236 EP 245 DI 10.1207/s15324796abm2903_10 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 938OP UT WOS:000230013000010 PM 15946118 ER PT J AU Hopenfeld, B Stinstra, JG MacLeod, RS AF Hopenfeld, B Stinstra, JG MacLeod, RS TI The effect of conductivity on ST-sSegment epicardial potentials arising from subendocardial ischemia SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE ischemia; ST depression; conductivity; computer model AB We quantify and provide biophysical explanations for some aspects of the relationship between the bidomain conductivities and ST-segment epicardial potentials that result from subendocardial ischemia. We performed computer simulations of ischemia with a realistic whole heart model. The model included a patch of subendocardial ischemic tissue of variable transmural thickness with reduced action potential amplitude. We also varied both intracellular and extracellular conductivities of the heart and the conductivity of ventricular blood in the simulations. At medium or high thicknesses of transmural ischemia (i.e., at least 40% thickness through the heart wall), a consistent pattern of two minima of the epicardial potential over opposite sides of the boundary between healthy and ischemic tissue appeared on the epicardium over a wide range of conductivity values. The magnitude of the net epicardial potential difference, the epicardial maximum minus the epicardial minimum, was strongly correlated to the intracellular to extracellular conductivity ratios both along and across fibers. Anisotropy of the ischemic source region was critical in predicting epicardial potentials, whereas anisotropy of the heart away from the ischemic region had a less significant impact on epicardial potentials. Subendocardial ischemia that extends through at least 40% of the heart wall is manifest on the epicardium by at least one area of ST-segment depression located over a boundary between ischemic and healthy tissue. The magnitude of the depression is a function of the bidomain conductivity values. C1 Univ Utah, Nora Eccles Harrison Cardiovasc Res & Training In, Salt Lake City, UT 84112 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT 84112 USA. Univ Utah, Comp & Imaging Inst, Salt Lake City, UT 84112 USA. RP Hopenfeld, B (reprint author), NHLBI, NIH, 10 Ctr Dr,MSC 1061, Bethesda, MD 20892 USA. EM brhopenfeld@yahoo.com NR 10 TC 22 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD JUN PY 2005 VL 33 IS 6 BP 751 EP 763 DI 10.1007/s10439-005-3236-2 PG 13 WC Engineering, Biomedical SC Engineering GA 939LU UT WOS:000230075100004 PM 16078615 ER PT J AU Bergsagel, P Robbiani, D Affer, M Kuehl, W Chesi, M AF Bergsagel, P Robbiani, D Affer, M Kuehl, W Chesi, M TI Biology of multiple myeloma: Oncogene activation in the germinal center, and a critical role for cyclin D dysregulation SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 Mayo Clin, Dept Med, Scottsdale, AZ USA. Cornell Univ, Program Immunol, New York, NY USA. NCI, Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 008 BP 30 EP 30 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100009 ER PT J AU Robbiani, DF Colon, K Szabo, P Affer, M Nickerson, H Qi, C Morse, HC Chesi, M Bergsagel, PL AF Robbiani, DF Colon, K Szabo, P Affer, M Nickerson, H Qi, C Morse, HC Chesi, M Bergsagel, PL TI Somatic activation of MYC and BCL6 induces multiple myeloma and diffuse lymphoma in mice SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 Cornell Univ, Weill Med Coll, Program Immunol, New York, NY USA. Mayo Clin, Scottsdale, AZ USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 021 BP 35 EP 35 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100022 ER PT J AU Staudt, L AF Staudt, L TI Molecular diagnosis yields molecular targets in lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 NCI, Metab Branch, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 026 BP 36 EP 36 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100027 ER PT J AU Wilson, W AF Wilson, W TI New treatments for mantle cell lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 055 BP 49 EP 49 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100056 ER PT J AU Hagenbeek, A Van Glabbeke, M Teodorovic, I Rozewicz, C Klasa, R Marcus, RE Wolf, M Kimby, E van Oers, MHJ AF Hagenbeek, A Van Glabbeke, M Teodorovic, I Rozewicz, C Klasa, R Marcus, RE Wolf, M Kimby, E van Oers, MHJ TI The role of rituximab maintenance treatment in relapsed follicular NHL: An interim analysis of the EORTC randomized intergroup trial SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 Univ Med Ctr Utrecht, EORTC Lymphoma Grp, Utrecht, Netherlands. EORTC Data Ctr, Brussels, Belgium. NCI, CTG Hematol Grp, Vancouver, BC, Canada. BNLI, Cambridge, England. Australasian Leukemia & Lymphoma Grp, Melbourne, Vic, Australia. Nord Lymphoma Grp, Stockholm, Sweden. HOVON, Utrecht, Netherlands. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 061 BP 52 EP 52 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100062 ER PT J AU Dunleavy, K Janik, J Cohen, J Grant, N Steinberg, S Jaffe, E Wilson, W AF Dunleavy, K Janik, J Cohen, J Grant, N Steinberg, S Jaffe, E Wilson, W TI Study of the treatment and biology of lymphomatoid granulomatosis (LYG); A rare EBV lymphoproliferative disorder SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 NIAID, Cellular Immunol Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Jaffe, Elaine/G-8984-2014 OI Jaffe, Elaine/0000-0003-4632-0301 NR 0 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 079 BP 59 EP 59 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100080 ER PT J AU Lin, T Blum, K Dalton, J Wu, D Fischer, B Moran, M Johnson, A Lucas, D Heerema, N Lozanski, G Suarez, J Colevas, A Byrd, J Grever, M AF Lin, T Blum, K Dalton, J Wu, D Fischer, B Moran, M Johnson, A Lucas, D Heerema, N Lozanski, G Suarez, J Colevas, A Byrd, J Grever, M TI Flavopiridol given as a 30-min intravenous (IV) bolus followed by 4-HR continuous IV infusion (CIVI) results in clinical activity and tumor lysis in refractory chronic lymphocytic leukemia (CLL) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Aventis Pharmaceut, Sci & Med Affairs, Bridgewater, NJ USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RI Blum, Kristie/E-2768-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 096 BP 65 EP 65 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100097 ER PT J AU Pro, B Leber, B Smith, M Younes, A Fayad, L Hagemeister, F McLaughlin, P Rodriguez, M Kwak, LW Caddick, Y Zwiebel, J AF Pro, B Leber, B Smith, M Younes, A Fayad, L Hagemeister, F McLaughlin, P Rodriguez, M Kwak, LW Caddick, Y Zwiebel, J TI A phase II trial of oblimersen sodium (G3139) plus rituximab for treatment of patients with recurrent B-cell non-Hodgkin's lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. McMaster Univ, Med Ctr, Hamilton, ON, Canada. NCI, Invest Drug Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 103 BP 68 EP 68 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100104 ER PT J AU Wilson, W Dunleavy, K Pittaluga, S Grant, N Steinberg, S Raffeld, M Jaffe, E Staudt, L Janik, J AF Wilson, W Dunleavy, K Pittaluga, S Grant, N Steinberg, S Raffeld, M Jaffe, E Staudt, L Janik, J TI Dose-adjusted EPOCH-rituximab: A novel pharmacodynamic regimen with high efficacy in all clinical risk groups, and GCB and ABC subtypes of untreated diffuse large B-cell lymphoma SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th International Conference on Malignant Lymphoma CY JUN 09-11, 2005 CL Lugano, SWITZERLAND C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 SU 5 MA 108 BP 69 EP 69 PG 1 WC Oncology SC Oncology GA 989JY UT WOS:000233670100109 ER PT J AU Manegold, C Symanowski, J Gatzemeier, U Reck, M von Pawel, J Kortsik, C Nackaerts, K Lianes, P Vogelzang, NJ AF Manegold, C Symanowski, J Gatzemeier, U Reck, M von Pawel, J Kortsik, C Nackaerts, K Lianes, P Vogelzang, NJ TI Second-line (post-study) chemotherapy received by patients treated in the phase III trial of pemetrexed plus cisplatin versus cisplatin alone in malignant pleural mesothelioma SO ANNALS OF ONCOLOGY LA English DT Article DE malignant pleural mesothelioma; pemetrexed; second-line chemotherapy ID LEUKEMIA GROUP-B; GEMCITABINE; CARBOPLATIN; CANCER; CYCLOPHOSPHAMIDE; COMBINATION; DOXORUBICIN AB Background: A phase III trial in patients with malignant pleural mesothelioma demonstrated a survival advantage for pemetrexed plus cisplatin compared with single-agent cisplatin. Because post-study chemotherapy (PSC) may have influenced the outcome of the trial, we examined its use and association with survival. Patients and methods: Eighty-four patients from the pemetrexed plus cisplatin arm and 105 patients from the single-agent cisplatin arm received PSC. Kaplan-Meier survival estimates were compared by treatment groups, and by PSC and non-PSC subgroups. Results: The percentage of patients receiving PSC was imbalanced between the treatment arms. Fewer pemetrexed plus cisplatin treated patients received PSC (37.2% versus 47.3%). A multiple regression analysis performed in this trial showed that PSC had a statistically significant correlation with prolonged survival (P < 0.01), adjusting for baseline prognostic factors and treatment intervention. The adjusted hazard ratio for PSC over non-PSC subgroups was 0.56 (confidence interval 0.44-0.72). Conclusions: PSC in malignant pleural mesothelioma. was significantly associated with prolonged survival. It is not known whether the reduced risk of death was associated with PSC or whether patients who had prolonged survival tended to receive more PSC. The pemetrexed plus cisplatin treatment group had a statistically significant survival advantage even though fewer patients from that arm of the trial received PSC. The potentially beneficial role of PSC should be assessed in prospective trials. C1 Univ Heidelberg, Med Ctr, Dept Surg, D-68167 Mannheim, Germany. Eli Lilly & Co, Indianapolis, IN 46285 USA. Hosp Grosshansdorf, Grosshansdorf, Germany. Asklepios Fachklin, Munich, Germany. St Hildegardis Krankenhaus, Mainz, Germany. Univ Hosp Gasthuisberg, Louvain, Belgium. Hosp Mataro, Barcelona, Spain. NCI, Las Vegas, NV USA. RP Manegold, C (reprint author), Univ Heidelberg, Med Ctr, Dept Surg, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany. EM Prof.Manegold@t-online.de RI Nackaerts, Kristiaan/B-6596-2015 NR 23 TC 80 Z9 82 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JUN PY 2005 VL 16 IS 6 BP 923 EP 927 DI 10.1093/annonc/mdi187 PG 5 WC Oncology SC Oncology GA 936PM UT WOS:000229867900011 PM 15824080 ER PT J AU Alexander, HR AF Alexander, HR TI A motion for cautious optimism with ocular melanoma: In the treatment of patients the ayes have it SO ANNALS OF SURGICAL ONCOLOGY LA English DT Editorial Material ID PROGNOSTIC-FACTORS; UVEAL MELANOMA; LIVER; SURVIVAL C1 NCI, Surg Metab Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, Ctr Canc Res, 10 Ctr Dr,Bldg 10,4W-5940, Bethesda, MD 20892 USA. EM richard_alexander@nih.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JUN PY 2005 VL 12 IS 6 BP 417 EP 419 DI 10.1245/ASO.2005.03.905 PG 3 WC Oncology; Surgery SC Oncology; Surgery GA 932KV UT WOS:000229553500001 PM 15886901 ER PT J AU Vance, BA Harley, PH Backlund, PS Ward, Y Phelps, TL Gress, RE AF Vance, BA Harley, PH Backlund, PS Ward, Y Phelps, TL Gress, RE TI Human CD69 associates with an N-terminal fragment of calreticulin at the cell surface SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE CD69; calreticulin; LC/MS/MS; leukocyte activation; cell signaling ID ACTIVATION ANTIGEN; T-LYMPHOCYTES; MASS-SPECTROMETRY; HUMAN NEUTROPHILS; GENE-COMPLEX; EXPRESSION; PROTEIN; RECEPTOR; IDENTIFICATION; PEPTIDE AB CD69 is thought to be a pluripotent signaling molecule expressed on the surface of a number of activated leukocytes including B, T, and NK cells, monocytes, neutrophils, and platelets. While some advances have been made regarding the mechanisms by which CD69 may participate in such diverse functions as cell aggregation, cellular cytotoxicity, and release of cytokines and inflammatory mediators, the most proximal links of signal initiation have not been identified. Our study has identified, by immunoprecipitation and direct protein sequencing (LC/MS/MS), binding of CD69 to an N-terminal protein fragment of calreticulin expressed on the cell surface of human PBMCs. Given the recently identified roles calreticulin plays in cell adhesion and angiogensis, the identification of CD69 binding directly to calreticulin may provide insights into mechanism(s) by which CD69 or other CD69 family members, i.e., LLT1 and AICL participates in such diverse functions. Published by Elsevier Inc. C1 NCI, NIH, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NICHHD, NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NCI, NIH, Canc Res Ctr, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. RP Vance, BA (reprint author), Univ Penn, Abramson Family Res Inst & Canc Ctr, 546 BRBII-III,421 Curie Blvd, Philadelphia, PA 19014 USA. EM vanceb@mail.med.upenn.edu NR 39 TC 14 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 2005 VL 438 IS 1 BP 11 EP 20 DI 10.1016/j.abb.2005.04.009 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 932JR UT WOS:000229550500002 PM 15893733 ER PT J AU Bauer, I Hohl, M Al-Sarraj, A Vinson, C Thiel, G AF Bauer, I Hohl, M Al-Sarraj, A Vinson, C Thiel, G TI Transcriptional activation of the Egr-1 gene mediated by tetradecanoylphorbol acetate and extracellular signal-regulated protein kinase SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE CRE; CREB; Egr-1; Elk-1; MAP kinase phosphatase 1; phorbol ester; serum response element; transcription ID SERUM RESPONSE ELEMENT; EPIDERMAL GROWTH-FACTOR; TERNARY COMPLEX FACTORS; TRANSDUCTION PATHWAYS; BIOLOGICAL-ACTIVITY; C-FOS; CELLS; EXPRESSION; INDUCTION; BINDING AB Activation of extracellular signal-regulated protein kinase (ERK) triggers the biosynthesis of Egr-1, a zinc finger transcription factor. Likewise, the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) strongly upregulates Egr-1 biosynthesis. Here, we have analyzed the genetic elements involved in the regulation of Egr-1 gene transcription by ERK and TPA in human hepatoma cells. Expression experiments using mitogen-activated protein kinase phosphatase-1 or a dominant-negative mutant of the ternary complex factor Elk-1 revealed that the distal cluster of serum response elements is essential in the TPA-induced enhancement of Egr-1 promoter activity, encompassing two independent TPA-responsive elements. The CRE in the proximal Egr-1 promoter plays, if anything, only a marginal role in TPA-induced stimulus-transcription coupling of the Egr-1 gene. The fact that Egr-1 promoter/reporter gene transcription is upregulated by a constitutively active CREB mutant indicates that the CRE couples other signaling cascades via CREB to the Egr-1 gene. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Saarland, Ctr Med, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. Univ Saarland, Ctr Med, Dept Anesthesiol & Crit Care Med, D-66421 Homburg, Germany. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Thiel, G (reprint author), Univ Saarland, Ctr Med, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. EM gerald.thiel@uniklinik-saarland.de NR 54 TC 23 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 2005 VL 438 IS 1 BP 36 EP 52 DI 10.1016/j.abb.2005.03.016 PG 17 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 932JR UT WOS:000229550500005 PM 15910736 ER PT J AU Burt, RK Cohen, B Rose, J Petersen, F Oyama, Y Stefoski, D Katsamakis, G Carrier, E Kozak, T Muraro, PA Martin, R Hintzen, R Slavin, S Karussis, D Haggiag, S Voltarelli, JC Ellison, GW Jovanovic, B Popat, U McGuirk, J Statkute, L Verda, L Haas, J Arnold, R AF Burt, RK Cohen, B Rose, J Petersen, F Oyama, Y Stefoski, D Katsamakis, G Carrier, E Kozak, T Muraro, PA Martin, R Hintzen, R Slavin, S Karussis, D Haggiag, S Voltarelli, JC Ellison, GW Jovanovic, B Popat, U McGuirk, J Statkute, L Verda, L Haas, J Arnold, R TI Hematopoietic stem cell transplantation for multiple sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Review ID BONE-MARROW-TRANSPLANTATION; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; TOTAL-BODY IRRADIATION; DISEASE; MS; MULTICENTER; PREVENTION; THERAPY; MRI AB Hematopoietic stern cell transplantation. (HSCT) was proposed as a treatment for muliple sclerosis (MS) in 1905 based on favorable results in,ani,mal models including, experimental autoimmune encephalomyelitis. These initial or first-generation trials were developed by medical oncology subspecialists, used malignancy-specific my eloablative transplantation regimens, and selected patients with secondary progressive MS with rapid progression of disability. In general, these trials suffered from higher than anticipated toxic reactions including A related and disease-related mortality, continued loss of brain volume as seen on magnetic resonance imagmg (MRI), and, at least in some patients, continued progressive disability despite marked attenuation or absences of gadolinium-enhancing lesions on MRI. Learning from these experiences, second-generation transplantation trials for MS are using MS-specific nonmyeloablative transplantation regimens and selecting for active relapses despite the use of interferon treatment in patients with less accumulated disability. While still preliminary, results using second-generation, nonmyeloablative HSCT re miens are encouraging with minimal treatment-related morbidity, and improvement in Expanded Disability Status Scale (EDSS) scores. The following 3 variables seem important in predicting the benefit and minimizing the toxic effects from an autologous stem cell transplantation in patients with MS: the selection of patients who still have inflammatory disease (ie, gadolinium enhancement on MRI and/or frequent active relapses), treatment early in the course before the. onset of significant irreversibly progressive disability, and the use of a safer lymphoablative but nonmyeloablative HSCT conditioning regimen. C1 Northwestern Univ Feinberg, Sch Med, Dept Med, Div Immunotherapy, Chicago, IL 60611 USA. Northwestern Univ Feinberg, Sch Med, Dept Neurol, Div Immunotherapy, Chicago, IL 60611 USA. Northwestern Univ Feinberg, Sch Med, Dept Prevent Med, Div Immunotherapy, Chicago, IL 60611 USA. Univ Utah, Dept Neurol, Salt Lake City, UT USA. Univ Utah, Dept Med, Salt Lake City, UT 84112 USA. Rush Univ, Med Ctr, Dept Neurol, Chicago, IL 60612 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Charles Univ, Dept Med, Prague, Czech Republic. NINDS, NIH, Bethesda, MD 20892 USA. Erasmus Med Ctr, Dept Neurol, Rotterdam, Netherlands. Hadassah Univ Hosp, Dept Bone Marrow Transplant, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Dept Neurol, IL-91120 Jerusalem, Israel. Univ Sao Paulo, Dept Med, Sao Paulo, Ribeiro Preto, Brazil. MD Anderson Canc Ctr, Houston, TX USA. Kansas City Canc Ctr, Kansas City, MO USA. Charite Hosp, Dept Hematol & Oncol, Berlin, Germany. RP Burt, RK (reprint author), Northwestern Univ Feinberg, Sch Med, Dept Med, Div Immunotherapy, 750 N Lake Shore Dr,ABA Bldg,Room 649, Chicago, IL 60611 USA. EM rburt@northwestern.edu RI Kozak, Tomas/K-3561-2012 NR 25 TC 42 Z9 47 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2005 VL 62 IS 6 BP 860 EP 864 DI 10.1001/archneur.62.6.860 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 933AK UT WOS:000229596000003 PM 15956156 ER PT J AU Levy, LM Levy-Reis, I Fujii, M Dalakas, MC AF Levy, LM Levy-Reis, I Fujii, M Dalakas, MC TI Brain gamma-aminobutyric acid changes in stiff-person syndrome SO ARCHIVES OF NEUROLOGY LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; INTRATHECAL BACLOFEN THERAPY; H-1 MR SPECTROSCOPY; IN-VIVO; DECARBOXYLASE AUTOANTIBODIES; N-ACETYLASPARTATE; NMR-SPECTROSCOPY; RAT-BRAIN; GLUTAMATE; GABA AB Background: Patients with stiff-person syndrome (SPS) have circulating antibodies against glutamic acid decarboxylase, the rate-limiting enzyme responsible for the synthesis of γ-aminobutyric acid (GABA). Although the patients' symptoms of stiffness and unexpected spasms can be explained on the basis of reduced or impaired inhibitory neuro transmitters, such as GABA, it is unclear whether the level of GABA in the brains of these patients is reduced and, if so, whether the reduction is due to anti-glutamic acid decarboxylase antibodies. Objective: To measure GABA levels in the brains of patients with SPS. Design: Prospective case-control study. Setting: National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md. Patients: Eight patients with SPS with high titers of circulating anti-glutamic acid decarboxylase antibodies and typical clinical symptoms of SPS and 16 control subjects. Main Outcome Measures: Results of brain magnetic resonance imaging and magnetic resonance spectroscopy, which measures GABA levels in specific brain regions. Results: No abnormalities were noted on brain magnetic resonance images. A prominent and significant decrease in GABA level was, however, observed in the sensorimotor cortex and a smaller decrease in the posterior occipital cortex but not in the cingulate cortex or pons. Conclusions: The reduction of brain GABA in patients with SPS supports the clinical symptoms and indicates that the inhibitory GABAergic pathways are involved in the disease. Regardless of the responsible autoantigens, in SPS autoantibodies block the function of GABAergic neurons and interfere with the synthesis of GABA but do not cause structural changes in the brain. C1 NINDS, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. Washington Univ, Med Ctr, Neuroradiol Sect, Washington, DC USA. RP Levy, LM (reprint author), NINDS, Neuroimaging Branch, NIH, Bldg 10,5N226, Bethesda, MD 20892 USA. EM llevy@mfa.gwu.edu NR 43 TC 51 Z9 52 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2005 VL 62 IS 6 BP 970 EP 974 DI 10.1001/archneur.62.6.970 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 933AK UT WOS:000229596000015 PM 15956168 ER PT J AU Lindahl, V Pearson, JL Colpe, L AF Lindahl, V Pearson, JL Colpe, L TI Prevalence of suicidality during pregnancy and the postpartum SO ARCHIVES OF WOMENS MENTAL HEALTH LA English DT Review DE suicidality; postpartum; pregnancy; maternal mortality ID NEW-YORK-CITY; MENTAL-HEALTH; POSTNATAL DEPRESSION; MATERNAL DEATH; FOLLOW-UP; MORTALITY; INJURIES; HOMICIDE; SYMPTOMS; SUICIDES AB This review examined the available prevalence estimates of suicidality (suicide deaths, attempts, and ideation including thoughts of self harm) in pregnancy and the postpartum. Studies that used defined community or clinic samples were identified through multiple electronic databases and contacts with primary authors. Definitions of and measurement of suicide deaths, intentional self-harming behavior, suicide attempts. and thoughts of death and self-harm were varied and are described with each study. While suicide deaths and attempts are lower during pregnancy and the postpartum than in the general population of women. when deaths do occur, suicides account for up to 20% of postpartum deaths. Self-harm ideation is more common than attempts or deaths., with thoughts of self-harm during pregnancy and the postpartum ranging front 5 to 14%. The risk for suicidality is significantly elevated among depressed women during the perinatal period, and suicide has been found to be the second or leading cause of death in this depressed population. C1 NIMH, Bethesda, MD 20892 USA. RP Pearson, JL (reprint author), NIMH, Bethesda, MD 20892 USA. EM jp36u@nih.gov NR 49 TC 155 Z9 158 U1 0 U2 16 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 1434-1816 J9 ARCH WOMEN MENT HLTH JI Arch. Womens Ment. Health PD JUN PY 2005 VL 8 IS 2 BP 77 EP 87 DI 10.1007/s00737-005-0080-1 PG 11 WC Psychiatry SC Psychiatry GA 016VZ UT WOS:000235650500002 PM 15883651 ER PT J AU Ward, MM AF Ward, MM TI Prospects for disease modification in ankylosing spondylitis: Do nonsteroidal antiinflammatory drugs do more than treat symptoms? SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material C1 NIAMS, NIH, IRP, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, NIH, IRP, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 10 TC 11 Z9 12 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 JUN PY 2005 VL 52 IS 6 BP 1634 EP 1636 DI 10.1002/art.21055 PG 3 WC Rheumatology SC Rheumatology GA 934PW UT WOS:000229721700004 PM 15934065 ER PT J AU Ward, MM AF Ward, MM TI Association between physician volume and in-hospital mortality in patients with systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CORONARY ANGIOPLASTY VOLUME; ACUTE MYOCARDIAL-INFARCTION; HEALTH-CARE; EXPERIENCE; OUTCOMES; CARDIOLOGISTS; SURVIVAL; DISEASE; DEATHS; COSTS AB Objective. Systemic lupus erythematosus (SLE) is an uncommon, clinically complex disease for which prior experience treating similar patients may be particularly important. This study was undertaken to determine if physician volume is associated with the outcome of hospitalization of patients with SLE. Methods. Data on in-hospital mortality in a population-based sample of 15,509 patients with SLE ages 18 years or older who were hospitalized in 2000, 2001, or 2002 in New York or Pennsylvania were obtained from state health planning agencies. Risks of in-hospital mortality were examined in relation to the average annual number of patients with SLE hospitalized by the admitting physician. Results. Physician volume was inversely associated with mortality. Mortality was 4.1% among patients of physicians who treated < 1 hospitalized patient with SLE per year, 3.5% among patients of physicians who treated 1-3 patients per year, and 2.5% among patients of physicians who treated > 3 patients per year. After adjustment for demographic characteristics, severity of illness, and hospital characteristics, the mortality risk was 20% lower among patients in the middle category of physician volume (odds ratio 0.80, 95% confidence interval 0.66-0.96, P =0.02), and 42% lower among patients in the highest category of physician volume (odds ratio 0.58, 95% confidence interval 0.42-0.82, P = 0.002), compared with patients in the lowest category. The association was stronger among patients with nephritis (n = 2,673), for whom the adjusted odds of mortality were similar to 60% lower among those in the highest category of physician volume. Conclusion. Our findings indicate that higher disease-specific physician volume is associated with lower risks of in-hospital mortality in patients with SLE. C1 NIAMS, NIH, IRP, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, NIH, IRP, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 28 TC 21 Z9 21 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 JUN PY 2005 VL 52 IS 6 BP 1646 EP 1654 DI 10.1002/art.21053 PG 9 WC Rheumatology SC Rheumatology GA 934PW UT WOS:000229721700007 PM 15934091 ER PT J AU Nagaraju, K Casciola-Rosen, L Lundberg, I Rawat, R Cutting, S Thapliyal, R Chang, J Dwivedi, S Mitsak, M Chen, YW Plotz, P Rosen, A Hoffman, E Raben, N AF Nagaraju, K Casciola-Rosen, L Lundberg, I Rawat, R Cutting, S Thapliyal, R Chang, J Dwivedi, S Mitsak, M Chen, YW Plotz, P Rosen, A Hoffman, E Raben, N TI Activation of the endoplasmic reticulum stress response in autoimmune myositis - Potential role in muscle fiber damage and dysfunction SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; UNFOLDED PROTEIN RESPONSE; MHC CLASS-I; NF-KAPPA-B; SKELETAL-MUSCLE; HEAVY-CHAINS; EXPRESSION; POLYMYOSITIS; DERMATOMYOSITIS; INTERLEUKIN-1-ALPHA AB Objective. The etiology and pathogenesis of human inflammatory myopathies remain unclear. Findings of several studies suggest that the degree of inflammation does not correlate consistently with the severity of clinical disease or of structural changes in the muscle fibers, indicating that nonimmune pathways may contribute to the pathogenesis of myositis. This study was undertaken to investigate these pathways in myositis patients and in a class I major histocompatibility complex (MHC)-transgenic mouse model of myositis. Methods. We examined muscle tissue from human myositis patients and from class I MHC-transgenic mice for nonimmune pathways, using biochemical, immunohistochemical, and gene expression profiling assays. Results. Up-regulation of class I MHC in skeletal muscle fibers was an early and consistent feature of human inflammatory myopathies. Class I MHC staining in muscle fibers of myositis patients showed both cell surface and a reticular pattern of internal reactivity. The pathways of endoplasmic reticulum (ER) stress response, the unfolded protein response (glucose-regulated protein 78 pathway), and the ER overload response (NF-kappa B pathway) were significantly activated in muscle tissue of human myositis patients and in the mouse model. Ectopic expression of wild-type mouse class I MHC (H-2K(b)) but not degradable glycosylation mutants of H-2K(b) induced ER stress response in C2C12 skeletal muscle cells. Conclusion. These results indicate that the ER stress response may be a major nonimmune mechanism responsible for skeletal muscle damage and dysfunction in autoimmune myositis. Strategies to interfere with this pathway may have therapeutic value in patients with this disease. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Baltimore, MD 21224 USA. Karolinska Univ Hosp, Solna, Sweden. Karolinska Inst, Stockholm, Sweden. NIAMSD, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Nagaraju, K (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Rheumatol, Mason F Lord Bldg,Ctr Tower,Suite 5300,Room 608, Baltimore, MD 21224 USA. EM knagaraj@jhmi.edu OI Cutting, Shawna/0000-0002-0072-7248 FU NIAMS NIH HHS [AR-44684]; NIDCR NIH HHS [DE-12354] NR 50 TC 168 Z9 177 U1 2 U2 9 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 JUN PY 2005 VL 52 IS 6 BP 1824 EP 1835 DI 10.1002/art.21103 PG 12 WC Rheumatology SC Rheumatology GA 934PW UT WOS:000229721700027 PM 15934115 ER PT J AU Coecke, S Balls, M Bowe, G Davis, J Gstraunthaler, G Hartung, T Hay, R Merten, OW Price, A Schechtman, L Stacey, G Stokes, W AF Coecke, S Balls, M Bowe, G Davis, J Gstraunthaler, G Hartung, T Hay, R Merten, OW Price, A Schechtman, L Stacey, G Stokes, W TI Guidance on Good Cell Culture Practice - A report of the second ECVAM task force on Good Cell Culture Practice SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID FETAL BOVINE SERUM; MONOCLONAL-ANTIBODY PRODUCTION; CROSS-CONTAMINATION; TISSUE-CULTURE; ORGAN-CULTURE; LINES; RECOMMENDATIONS; ALTERNATIVES; TERMINOLOGY; MYCOPLASMA AB The maintenance of high standards is fundamental to all good scientific practice, and is essential for maximising the reproducibility, reliability, credibility, acceptance and proper application of any results produced. The aim of this Guidance on Good Cell Culture Practice (GCCP) is to promote the maintenance of these standards and to reduce uncertainty in the development and application of animal and human cell and tissue culture procedures and products, by encouraging greater international harmonisation, rationalisation and standardisation of laboratory practices, quality control systems, safety procedures, recording and reporting, and compliance with laws, regulations and ethical principles. The scope of the document has deliberately been broadly defined, to include systems based on cells and tissues obtained from humans and animals, and issues related to the characterisation and maintenance of essential characteristics, as well as quality assurance, recording and reporting, safety, education and training, and ethics. C1 Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. Bio Prod Lab, Dept Res & Dev, Elstree, Herts, England. FRAME, Nottingham, England. ATCC, Manassas, VA USA. Innsbruck Med Univ, Dept Physiol, A-6010 Innsbruck, Austria. Genethon, Evry, France. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Natl Inst Biol Stand & Controls, Div Cell Biol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, UK Stem Cell Bank, Potters Bar EN6 3QG, Herts, England. Natl Inst Environm Hlth Sci, Evaluat Alternat Toxicol Methods Environm Toxicol, Natl Toxicol Program Interagcy Ctr, Res Triangle Pk, NC USA. RP Coecke, S (reprint author), Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, Via Fermi 1, I-21020 Ispra, VA, Italy. EM sandra.coecke@jrc.it NR 94 TC 123 Z9 126 U1 6 U2 21 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD JUN PY 2005 VL 33 IS 3 BP 261 EP 287 PG 27 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 940XZ UT WOS:000230180500011 PM 16180980 ER PT J AU Wood, J Schmidt, L Lugg, D Ayton, J Phillips, T Shepanek, M AF Wood, J Schmidt, L Lugg, D Ayton, J Phillips, T Shepanek, M TI Life, survival, and behavioral health in small closed communities: 10 years of studying isolated antarctic groups SO AVIATION SPACE AND ENVIRONMENTAL MEDICINE LA English DT Article; Proceedings Paper CT Workshop on New Directions in Spaceflight Behavioral Health CY DEC 02-03, 2003 CL Davis, CA DE behavioral health; Antarctica; extreme environments; closed communities; social environments; pooled time-series regressions; hierarchical statistical models; content analysis AB In the late 1980s the Australian Antarctic Division collaborated with NASA to use the Australian National Antarctic Research Expeditions' (ANARE) stations to pursue research of benefit to both programs. This article outlines the data collection efforts, the development of analyses, and selected results, and describes some of the benefits for the aerospace, health, and environmental psychology communities. The Behavior and Performance Laboratory at Johnson Space Center developed a questionnaire to sample broadly the many aspects of life in extreme environments analogous to space missions. Data were collected from volunteers involved in various ANAREs conducted from 1994 to 2003. Pool-timed series regression, hierarchical models, and content analysis have all enhanced the understanding of the kinds of psychosocial variables relevant in extreme environments, and how these variables relate to each other; examples are given. Observations gathered over the last 10 yr comprise a unique, comprehensive, and advanced representation of psychosocial factors in this extreme environment and provide a strong base for future research and application. C1 NASA HQ, Off Chief Hlth & Med Officer, Washington, DC 20546 USA. Wyle Labs, Houston, TX USA. Baylor Coll Med, NSBRI, JSC, Houston, TX 77030 USA. Australian Antarctic Div, Kingston, Tas, Australia. NIH, Bethesda, MD 20892 USA. RP Lugg, D (reprint author), NASA HQ, Off Chief Hlth & Med Officer, 300 E St SW, Washington, DC 20546 USA. EM desmond.j.lugg@nasa.gov NR 13 TC 9 Z9 11 U1 1 U2 3 PU AEROSPACE MEDICAL ASSOC PI ALEXANDRIA PA 320 S HENRY ST, ALEXANDRIA, VA 22314-3579 USA SN 0095-6562 J9 AVIAT SPACE ENVIR MD JI Aviat. Space Environ. Med. PD JUN PY 2005 VL 76 IS 6 SU S BP B89 EP B93 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Sport Sciences SC Public, Environmental & Occupational Health; General & Internal Medicine; Sport Sciences GA 933GJ UT WOS:000229616600014 PM 15943201 ER PT J AU Brasted, PJ Bussey, TJ Murray, EA Wise, SP AF Brasted, PJ Bussey, TJ Murray, EA Wise, SP TI Conditional motor learning in the nonspatial domain: Effects of errorless learning and the contribution of the fornix to one-trial learning SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE associative learning; arbitrary mapping; learning curve; hippocampus; medial temporal lobe ID CROSSED UNILATERAL LESIONS; INFERIOR TEMPORAL CORTEX; IN-PLACE MEMORY; RHESUS-MONKEYS; RECOGNITION MEMORY; ALZHEIMERS-DISEASE; REWARD ASSOCIATION; HIPPOCAMPAL SYSTEM; PREFRONTAL CORTEX; NEURONAL-ACTIVITY AB Conditional motor learning contributes importantly to behavioral flexibility. In previous work, the authors found that fornix transections impaired the ability of macaque monkeys (Macaca mulatto) to learn conditional motor associations between the nonspatial features of visual stimuli and nonspatially differentiated responses. In the present study, they found that significant 1-trial learning of such associations also depended on the fornix. Furthermore, removal of the hippocampus, subiculum, and subjacent parahippocampal cortex, added to fornix transection, had no effect, thus demonstrating that fornix transections eliminated the contribution of the hippocampal system. In addition, the authors examined the effect of errorless learning and found, in control monkeys, that errors made prior to the 1st correct response retarded 1-trial learning. C1 NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Wise, SP (reprint author), NIMH, Lab Syst Neurosci, NIH, 49 Convent Dr,Bldg 49,Room B1EE17, Bethesda, MD 20892 USA. EM stevenwise@mail.nih.gov RI Bussey, Timothy/M-2758-2016; OI Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 NR 59 TC 13 Z9 13 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD JUN PY 2005 VL 119 IS 3 BP 662 EP 676 DI 10.1037/0735-7044.119.3.662 PG 15 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 942BT UT WOS:000230258600003 PM 15998187 ER PT J AU Ueda, A Matsui, K Yamamoto, Y Pedersen, LC Sueyoshi, T Negishi, M AF Ueda, A Matsui, K Yamamoto, Y Pedersen, LC Sueyoshi, T Negishi, M TI Thr(176) regulates the activity of the mouse nuclear receptor CAR and is conserved in the NR1I subfamily members PXR and VDR SO BIOCHEMICAL JOURNAL LA English DT Article DE activation function 2 (AF2) domain; constitutively active receptor (CAR); nuclear receptor; pregnane X receptor; xenobiotic; vitamin D-3 receptor ID ENHANCER MODULE; TRANSCRIPTIONAL ACTIVATION; GENE-EXPRESSION; CYP2B GENE; INDUCTION; METABOLISM; CYP3A4; GAMMA AB The mouse nuclear receptor CAR (constitutively active receptor) is a transcription factor that is activated by phenobarbital-type inducers such as TCPOBOP {1,4 bis[2-(3,5-dichloropyridyloxy)] benzene} in liver in vivo. However, CAR is constitutively active in cell-based transfection assays, the molecular mechanism for which has not been elucidated yet. In the model structure of CAR, Thr(176) constitutes a part of the ligand-binding surface, but its side chain is not directed toward the surface, instead it forms a hydrogen bond with Thr(350) in the AF2 (activation function 2) domain of CAR. Thr(350) is known to regulate CAR activity [Ueda, Kakizaki, Negishi, and Sueyoshi (2002) Mol. Pharmacol. 61, 1284-1288]. Thr(176) was mutated to various amino acids to examine whether this interaction played a role in conferring the constitutive activity. Hydrophobic and positively charged amino acids at position 176 abrogated the constitutive activity, whereas polar and negatively charged amino acids retained it. When one of the small hydrophobic amino acids, such as alanine or valine, was substituted for threonine, the mutants were fully activated by TCPOBOP. The co-activator SRC-1 (steroid receptor co-activator-1) regulated the activity changes associated with the mutations. Thr(248) and Ser(230) are the Thr(176)-corresponding residues in human pregnane X receptor and mouse vitamin D-3 receptor respectively, interacting directly with the conserved threonine in the AF2 domains. Thr(248) and Ser(230) also regulated the ligand-dependent activity of these receptors by augmenting binding of the receptors to SRC-1. Thr(176), Thr(248) and Ser230 are conserved residues in the NR1I (nuclear receptor 1I) subfamily members and determine their activity. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 24 TC 13 Z9 13 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD JUN 1 PY 2005 VL 388 BP 623 EP 630 PN 2 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 937JD UT WOS:000229919500025 PM 15610065 ER PT J AU Hahn, Y Lee, B AF Hahn, Y Lee, B TI Identification of nine human-specific frameshift mutations by comparative analysis of the human and the chimpanzee genome sequences SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 13th International Conference on Intelligent Systems for Molecular Biology CY JUN 25-29, 2005 CL Detroit, MI SP Int Soc Computat Biol ID PAN-HOMO DIVERGENCE; MOLECULAR-CLONING; PROTEIN FAMILY; DNA-SEQUENCE; GENE; EVOLUTION; INACTIVATION; NEUROTENSIN; EXPRESSION; MOUSE AB Motivation: The recent release of the draft sequence of the chimpanzee genome is an invaluable resource for finding genome-wide genetic differences that might explain phenotypic differences between humans and chimpanzees. Results: In this paper, we describe a simple procedure to identify potential human-specific frameshift mutations that occurred after the divergence of human and chimpanzee. The procedure involves collecting human coding exons bearing insertions or deletions compared with the chimpanzee genome and identification of homologs from other species, in support of the mutations being human-specific. Using this procedure, we identified nine genes, BASE, DNAJB3, FLJ33674, HEJ1, NTSR2, RPL13AP, SCGB1D4, WBSCR27 and ZCCHC13, that show human-specific alterations including truncations of the C-terminus. In some cases, the frameshift mutation results in gene inactivation or decay. In other cases, the altered protein seems to be functional. This study demonstrates that even the unfinished chimpanzee genome sequence can be useful in identifying modification of genes that are specific to the human lineage and, therefore, could potentially be relevant to the study of the acquisition of human-specific traits. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 35 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN PY 2005 VL 21 SU 1 BP I186 EP I194 DI 10.1093/bioinformatics/bti1000 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 942HH UT WOS:000230273000021 PM 15961456 ER PT J AU Jothi, R Kann, MG Przytycka, TM AF Jothi, R Kann, MG Przytycka, TM TI Predicting protein-protein interaction by searching evolutionary tree automorphism space SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 13th International Conference on Intelligent Systems for Molecular Biology CY JUN 25-29, 2005 CL Detroit, MI SP Int Soc Computat Biol ID MULTIPLE SEQUENCE ALIGNMENT; COEVOLUTION AB Motivation: Uncovering the protein-protein interaction network is a fundamental step in the quest to understand the molecular machinery of a cell. This motivates the search for efficient computational methods for predicting such interactions. Among the available predictors are those that are based on the co-evolution hypothesis "evolutionary trees of protein families (that are known to interact) are expected to have similar topologies". Many of these methods are limited by the fact that they can handle only a small number of protein sequences. Also, details on evolutionary tree topology are missing as they use similarity matrices in lieu of the trees. Results: We introduce MORPH, a new algorithm for predicting protein interaction partners between members of two protein families that are known to interact. Our approach can also be seen as a new method for searching the best superposition of the corresponding evolutionary trees based on tree automorphism group. We discuss relevant facts related to the predictability of protein-protein interaction based on their co-evolution. When compared with related computational approaches, our method reduces the search space by similar to 3 x 10(5)-fold and at the same time increases the accuracy of predicting correct binding partners. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Jothi, R (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RI Kann, Maricel/E-5701-2012; Jothi, Raja/G-3780-2015 FU Intramural NIH HHS NR 22 TC 27 Z9 29 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN PY 2005 VL 21 SU 1 BP I241 EP I250 DI 10.1093/bioinformatics/bti1009 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 942HH UT WOS:000230273000027 PM 15961463 ER PT J AU Tharakaraman, K Marino-Ramirez, L Sheetlin, S Landsman, D Spouge, JL AF Tharakaraman, K Marino-Ramirez, L Sheetlin, S Landsman, D Spouge, JL TI Alignments anchored on genomic landmarks can aid in the identification of regulatory elements SO BIOINFORMATICS LA English DT Article; Proceedings Paper CT 13th International Conference on Intelligent Systems for Molecular Biology CY JUN 25-29, 2005 CL Detroit, MI SP Int Soc Computat Biol ID FACTOR-BINDING SITES; PSI-BLAST; STATISTICAL SIGNIFICANCE; REPRESENTED WORDS; LOCAL ALIGNMENT; DNA-SEQUENCES; MOTIFS; PROMOTERS; DISCOVERY; PATTERNS AB The transcription start site (TSS) has been located for an increasing number of genes across several organisms. Statistical tests have shown that some cis-acting regulatory elements have positional preferences with respect to the TSS, but few strategies have emerged for locating elements by their positional preferences. This paper elaborates such a strategy. First, we align promoter regions without gaps, anchoring the alignment on each promoter's TSS. Second, we apply a novel word-specific mask. Third, we apply a clustering test related to gapless BLAST statistics. The test examines whether any specific word is placed unusually consistently with respect to the TSS. Finally, our program A-GLAM, an extension of the GLAM program, uses significant word positions as new 'anchors' to realign the sequences. A Gibbs sampling algorithm then locates putative cis-acting regulatory elements. Usually, Gibbs sampling requires a preliminary masking step, to avoid convergence onto a dominant but uninteresting signal from a DNA repeat. However, since the positional anchors focus A-GLAM on the motif of interest, masking DNA repeats during Gibbs sampling becomes unnecessary. Results: In a set of human DNA sequences with experimentally characterized TSSs, the placement of 791 octonucleotide words was unusually consistent ( multiple test corrected P < 0.05). Alignments anchored on these words sometimes located statistically significant motifs inaccessible to GLAM or AlignACF. C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Spouge, JL (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM spouge@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 30 TC 13 Z9 14 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JUN PY 2005 VL 21 SU 1 BP I440 EP I448 DI 10.1093/bioinformatics/bti1028 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 942HH UT WOS:000230273000050 PM 15961489 ER PT J AU Liang, HL Bressler, SL Buffalo, EA Desimone, R Fries, P AF Liang, HL Bressler, SL Buffalo, EA Desimone, R Fries, P TI Empirical mode decomposition of field potentials from macaque V4 in visual spatial attention SO BIOLOGICAL CYBERNETICS LA English DT Article; Proceedings Paper CT Workshop on Nonlinear Spatio-Temporal Neural Dynamics CY JUL 21, 2004 CL Baltimore, MD ID BACKGROUND EEG ACTIVITY; SIGNAL; ORIGIN AB Empirical mode decomposition (EMD) has recently been introduced as a local and fully data-driven technique for the analysis of non-stationary time-series. It allows the frequency and amplitude of a time-series to be evaluated with excellent time resolution. In this article we consider the application of EMD to the analysis of neuronal activity in visual cortical area V4 of a macaque monkey performing a visual spatial attention task. We show that, by virtue of EMD, field potentials can be resolved into a sum of intrinsic components with different degrees of oscillatory content. Low-frequency components in single-trial recordings contribute to the average visual evoked potential (AVEP), whereas high-frequency components do not, but are identified as gamma-band (30-90 Hz) oscillations. The magnitude of time-varying gamma activity is shown to be enhanced when the monkey attends to a visual stimulus as compared to when it is not attending to the same stimulus. Comparison with Fourier analysis shows that EMD may offer better temporal and frequency resolution. These results support the idea that the magnitude of gamma activity reflects the modulation of V4 neurons by visual spatial attention. EMD, coupled with instantaneous frequency analysis, is demonstrated to be a useful technique for the analysis of neurobiological time-series. C1 Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Houston, TX 77030 USA. Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Univ Nijmegen, FC Donders Ctr Cognit Neuroimaging, NL-6525 EK Nijmegen, Netherlands. MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. 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 Fries, Pascal/E-3196-2010 OI Fries, Pascal/0000-0002-4270-1468 FU PHS HHS [64204, 67776] NR 23 TC 43 Z9 46 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-1200 J9 BIOL CYBERN JI Biol. Cybern. PD JUN PY 2005 VL 92 IS 6 BP 380 EP 392 DI 10.1007/s00422-005-0566-y PG 13 WC Computer Science, Cybernetics; Neurosciences SC Computer Science; Neurosciences & Neurology GA 938AM UT WOS:000229972300005 PM 15906081 ER PT J AU Shaywitz, SE Shaywitz, BA AF Shaywitz, SE Shaywitz, BA TI Dyslexia (specific reading disability) SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Advancing the Neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD) CY FEB 28, 2004 CL Boston, MA DE reading; dyslexia; brain imaging; functional magnetic resonance imaging (fMRI) ID WORD FORM AREA; DEVELOPMENTAL DYSLEXIA; FUNCTIONAL CONNECTIVITY; COGNITIVE PROFILES; PHONOLOGICAL-CORE; BRAIN ACTIVATION; ADULT DYSLEXICS; EPISODIC MEMORY; VISUAL-MOTION; CHILDREN AB Converging evidence from a number of lines of investigation indicates that dyslexia represents a disorder within the language system and more specifically within a particular subcomponent of that system, phonological processing. Recent advances in imaging technology. particularly the development of functional magnetic resonance imaging, provide evidence of a, neurobiological signature for dyslaxia, specifically a disruption of two left hemisphere posterior brain systems, one parieto-lemporal, the other occipito-temporal, with compensatory engagement of anterior systems around the inferior frontal gyrus and a posterior (right occipito-temporal) system. Furthermore, good evidence indicates a computational role for the left occipito-temporal system the development of fluent (automatic) reading. The brain systems for reading are malleable and their disruption in dyslexic children may be remediated by provision of an evidence-based. effective reading intervention. In addition, functional magnetic resonance imaging studies of young adults with, reading difficulties and longitudinally from age 5 through their mid twenties suggests that their may be two types of reading difficulties, one primarily on a genetic basis, the other, and far more common, reflecting environmental influences. These studies offer the promise for more precise identification and effective management of dyslexia in children, adolescents and adults. C1 NICHHD, Yale Ctr Study Learning & Attent, New Haven, CT USA. RP Shaywitz, SE (reprint author), Yale Univ, Sch Med, Dept Pediat, POB 333, New Haven, CT 06510 USA. EM sally.shaywitz@yale.edu FU NICHD NIH HHS [P50 HD25802, P01 HD 21888] NR 94 TC 312 Z9 331 U1 14 U2 106 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2005 VL 57 IS 11 BP 1301 EP 1309 DI 10.1016/j.biopsych.2005.01.043 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 932RH UT WOS:000229570500013 PM 15950002 ER PT J AU Volkow, ND Wang, GJ Fowler, JS Ding, YS AF Volkow, ND Wang, GJ Fowler, JS Ding, YS TI Imaging the effect of methylphenidate on brain dopamine: New model on its therapeutic actions for attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Advancing the Neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD) CY FEB 28, 2004 CL Boston, MA DE methylphenidate; attention-deficit/hyperactivity disorder; dopamine; dopamine transporter; saliency ID DEFICIT HYPERACTIVITY DISORDER; NUCLEUS-ACCUMBENS; THREO-METHYLPHENIDATE; STIMULANT MEDICATION; INCENTIVE SALIENCE; TRANSPORTER GENE; CHILDREN; ASSOCIATION; ADHD; POLYMORPHISM AB Methylphenidate hydrochloride (MP) is an effective treatment for attention-deficit/hyperactivity disorder (ADHD), a common neurobehavioral disorder of childhood onset characterized by inattention, hyperactivity, and distractibility. Methylphenidate hydrochloride blocks the dopamine transporters (DAT), the main mechanism for removing dopamine (DA) from the synapse, is believed to be involved in its therapeutic properties. However, the mechanism(s) by which increases in DA improve symptomatology in ADHD are not completely understood. Our studies of the dopaminergic of effects of MP in the human brain using positron emission tomography (PET) have shown that MP blocks DAT, and that extracellular DA increases in proportion to the level of blockade and the rate of DA release (modulated by DA cell firing). These DA increases are greater when MP is given concomitantly with a salient effects. Additionally, MP stimulus than with a neutral stimulus, documenting the context dependency of MP MP-induced increases in DA are due in part to its are associated with an enhanced perception of the stimulus as salient. We postulate the MPs therapeutic of ability to enhance the magnitude of DA increases induced by stimuli that by themselves generate weak responses, enhancing their saliency and the attention and interest they elicit. We postulate that these effects would improve school performance. C1 NIDA, NIAAA, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, NIAAA, NIH, 6001 Execut Blvd,Suite 5274,Mail Drop Code 9581, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov NR 56 TC 181 Z9 188 U1 6 U2 26 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2005 VL 57 IS 11 BP 1410 EP 1415 DI 10.1016/j.biopsych.2004.11.006 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 932RH UT WOS:000229570500026 PM 15950015 ER PT J AU Castellanos, FX Sonuga-Barke, EJS Scheres, A Di Martino, A Hyde, C Walters, JR AF Castellanos, FX Sonuga-Barke, EJS Scheres, A Di Martino, A Hyde, C Walters, JR TI Varieties of attention-deficit/hyperactivity disorder-related intra-individual variability SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Advancing the Neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD) CY FEB 28, 2004 CL Boston, MA DE attention-cleficit/hyperactivity disorder; time-series analyses; fast Fourier transform; endophenotypes; reaction time; variability; Morlet wavelet ID DEFICIT-HYPERACTIVITY DISORDER; HEART-RATE-VARIABILITY; DUAL PATHWAY MODEL; ECHO-PLANAR MRI; BASAL GANGLIA; FUNCTIONAL CONNECTIVITY; SUSTAINED ATTENTION; RESPONSE-INHIBITION; WAVELET NETWORKS; FIRING RATE AB Intra-individual variability in behavior and functioning is ubiquitous among children with attention-deficit/hyperactivity disorder (ADHD), but it has not been systematically examined or integrated within causal models. This article seeks to provide a conceptual, methodologic, and analytic framework as a foundation for future research. We first identify five key-research questions and methodologic issues. For illustration, we examine the periodic structure of Eriksen Flanker task reaction nine (RT) data obtained from 24 boys with ADHD and 18 age-matched comparison boys. Reaction the variability in ADHD differed quantitatively from control subjects, particularly at a modal frequency around .05 Hz (cycle length approximately 20 sec). These oscillations in RT were unaffected by double-blind placebo and were suppressed by double-blind methylphenidate. Together with converging lines of basic and clinical evidence, these secondary data analyses support the speculative hypothesis that the increased power of multisecond oscillations in ADHD RT data, and by inference, in attentional performance, represents a catecholaminergic deficit in the ability to appropriately, modulate such oscillations in neuronal activity. These results highlight the importance of retaining time-series data and quantitatively examining intra-subject measures of variability as a putative endophenotype for ADHD. C1 NYU, Ctr Child Study, Inst Pediat Neurosci, New York, NY 10016 USA. Univ Southampton, Dept Psychol, Southampton SO9 5NH, Hants, England. NINDS, Neurophysiol Pharmacol Sect, Bethesda, MD USA. BioAssessments LLC, Elkton, MD USA. RP Castellanos, FX (reprint author), NYU, Ctr Child Study, Inst Pediat Neurosci, 215 Lexington Ave, New York, NY 10016 USA. EM castef01@med.nyu.edu RI Sonuga-Barke, Edmund/D-9137-2011; Di Martino, Adriana/L-2497-2014; OI Di Martino, Adriana/0000-0001-6927-290X; Castellanos, Francisco/0000-0001-9192-9437 FU NIMH NIH HHS [R21 MH066393, MH0660393] NR 90 TC 276 Z9 279 U1 2 U2 45 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUN 1 PY 2005 VL 57 IS 11 BP 1416 EP 1423 DI 10.1016/j.biopsych.2004.12.005 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 932RH UT WOS:000229570500027 PM 15950016 ER PT J AU Sportes, C McCarthy, NJ Hakim, F Steinberg, SM Liewebe, DJ Weng, D Kummar, S Gea-Banacloche, Y Chow, CK Dean, RM Castro, KM Marchigiani, D Bishop, MR Fowler, DH Gress, RE AF Sportes, C McCarthy, NJ Hakim, F Steinberg, SM Liewebe, DJ Weng, D Kummar, S Gea-Banacloche, Y Chow, CK Dean, RM Castro, KM Marchigiani, D Bishop, MR Fowler, DH Gress, RE TI Establishing a platform for immunotherapy: Clinical outcome and study of immune reconstitution after high-dose chemotherapy with progenitor cell support in breast cancer patients SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE high-dose chemotherapy; autologous stem cell transplantation; immune reconstitution; brest cancer ID BONE-MARROW-TRANSPLANTATION; COLONY-STIMULATING FACTOR; LYMPH-NODE INVOLVEMENT; INTENSIVE CHEMOTHERAPY; RANDOMIZED-TRIAL; PHASE-I; REGENERATION; PATHWAYS AB Tumor vaccine after high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) aims at directing immune recovery toward tumor responses after optimizing minimal residual disease. We have characterized T-cell recovery and tumor response after a regimen devised as a platform for such immunotherapy. One hundred patients with high-risk or metastatic breast cancer received 3 to 7 cycles of paclitaxel and cyclophosphamide (overall response rate, 78%)and then HDC with melphalan and etoposide. Seventy-one patients received HDC and ASCT (no mortality at 100 days). At 24 months after transplantation, progression-free and overall survival probabilities for patients with stage IIIA, IIIB, and IV disease were 82%, 81%, and 42% and 100%, 94%, and 68%, respectively. The median progression-free and overall survivals from entry on study for stage IV patients were 15.3 and 38.1 months, respectively. CD3(+), CD8(+), and CD4(+) cells were severely depleted after ASCT. Although total CD8(+) T-cell numbers approached the normal range by 3 months, most of these cells were CD28(-). Naive CD45RA(+)CD4(+) T cells approached the normal range only 18 months after ASCT and only in younger patients. The described observations provide the basis for devising a strategy for cancer vaccine administration after ASCT. Incorporating immune reconstitution enhancement after ASCT may be advantageous. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Auckland, Div Oncol, Auckland 1, New Zealand. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Med Hematol Oncol, Taussig Canc Ctr, Cleveland, OH 44195 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NIAID, Div Aids, Clin Res Management Branch, NIH, Bethesda, MD 20892 USA. RP Sportes, C (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, 10 Ctr Dr,CRC Room 43142, Bethesda, MD 20892 USA. EM kastensc@mail.nih.gov RI McCarthy, Nicole/A-3468-2013 NR 34 TC 12 Z9 14 U1 0 U2 3 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUN PY 2005 VL 11 IS 6 BP 472 EP 483 DI 10.1016/j.bbmt.2005.03.010 PG 12 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 939GF UT WOS:000230059800008 PM 15931636 ER PT J AU Qin, J Leung, DHY AF Qin, J Leung, DHY TI A semiparametric two-component "compound" mixture model and its application to estimating malaria attributable fractions SO BIOMETRICS LA English DT Article DE attributable fraction; density ratio model; empirical likelihood; malaria; mixture methods ID NONPARAMETRIC-ESTIMATION; EMPIRICAL LIKELIHOOD; DISTRIBUTIONS; PROPORTIONS; BIAS AB Malaria remains a major epidemiologic problem in many developing countries. Malaria is defined as the presence of parasites and symptoms (usually fever) due to the parasites. In endemic areas, an individual may have symptoms attributable either to malaria or to other causes. From a clinical viewpoint, it is important to correctly diagnose an individual who has developed symptoms so that the appropriate treatments can be given. From an epidemiologic and economic viewpoint, it is important to determine the proportion of malaria-affected cases in individuals who have symptoms so that policies on intervention program can be developed. Once symptoms have developed in an individual., the diagnosis of malaria can be based on the analysis of the parasite levels in blood samples. However, even a blood test is not conclusive as in endemic areas many healthy individuals can have parasites in their blood slides. Therefore, data from this type of study can be viewed as coming from a mixture distribution, with the components corresponding to malaria and nonmalaria cases. A unique feature in this type of data, however, is the fact that a proportion of the nonmalaria cases have zero parasite levels. Therefore, one of the component distributions is itself a mixture distribution. In this article, we propose a semiparametric likelihood approach for estimating the proportion of clinical malaria using parasite-level data from a group of individuals with symptoms. Our approach assumes the density ratio for the parasite levels in clinical malaria and nonclinical malaria cases can be modeled using a logistic model. We use empirical likelihood to combine the zero and nonzero data. The maximum semiparametric likelihood estimate is more efficient than existing nonparametric estimates using only the frequencies of zero and nonzero data. On the other hand, it is more robust than a fully parametric maximum likelihood estimate that assumes a parametric model for the nonzero data. Simulation results show that the performance of the proposed method is satisfactory. The proposed method is used to analyze data from a malaria survey carried out in Tanzania. C1 NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Singapore Management Univ, Sch Econ & Social Sci, Singapore 259756, Singapore. RP Qin, J (reprint author), NIAID, Biostat Res Branch, NIH, 6700B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM jingqin@niaid.nih.gov; denisleung@smu.edu.sg RI LEUNG, Denis Heng Yan/D-1439-2009 NR 18 TC 8 Z9 8 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2005 VL 61 IS 2 BP 456 EP 464 DI 10.1111/j.1541-0420.2005.00330.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 936ZI UT WOS:000229893900015 PM 16011692 ER PT J AU Pfeiffer, RM Chatterjee, N AF Pfeiffer, RM Chatterjee, N TI On a supplemented case-control design SO BIOMETRICS LA English DT Article DE logistic regression; pseudo-likelihood; stratified sampling; two-phase design ID 2-PHASE AB The supplemented case-control design consists of a case-control sample and of an additional sample of disease-free subjects who arise from a given stratum of one of the measured exposures in the case-control study. The supplemental data might, for example, arise from a population survey conducted independently of the case-control study. This design improves precision of estimates of main effects and especially of joint exposures, particularly when joint exposures are uncommon and the prevalence of one of the exposures is low. We first present a pseudo-likelihood estimator (PLE) that is easy to compute. We further adapt two-phase design methods to find maximum likelihood estimates (MLEs) for the log odds ratios for this design and derive asymptotic variance estimators that appropriately account for the differences in sampling schemes of this design from that of the traditional two-phase design. As an illustration of our design we present a study that was conducted to assess the influence to joint exposure of hepatitis-B virus (HBV) and hepatitis-C virus (HCV) infection on the risk of hepatocellular carcinoma in data from Qidong County, Jiangsu Province, China. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd,EPS 8030, Bethesda, MD 20892 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 3 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2005 VL 61 IS 2 BP 584 EP 590 DI 10.1111/j.1541-0420.2005.00319.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 936ZI UT WOS:000229893900031 PM 16011708 ER PT J AU Qin, J Zhang, B AF Qin, J Zhang, B TI Marginal likelihood, conditional likelihood and empirical likelihood: Connections and applications SO BIOMETRIKA LA English DT Article DE case-control study; conditional likelihood; empirical likelihood; exponential-tilt model; linkage analysis; marginal likelihood; serniparametric mixture model; unordered-paired data ID LOGISTIC-REGRESSION MODELS; SELECTION BIAS MODELS; CONFIDENCE-INTERVALS; ESTIMATING EQUATIONS; NONPARAMETRIC-TESTS; MIXTURE MODEL; LINKAGE MAPS; DISCRIMINATION; DISTRIBUTIONS AB Marginal likelihood and conditional likelihood are often used for eliminating nuisance parameters. For a parametric model, it is well known that the full likelihood can be decomposed into the product of a conditional likelihood and a marginal likelihood. This property is less transparent in a nonparametric or semiparametric likelihood setting. In this paper we show that this nice parametric likelihood property can be carried over to the empirical likelihood world. We discuss applications in case-control studies, genetical linkage analysis, genetical quantitative traits analysis, tuberculosis infection data and unordered-paired data, all of which can be treated as semiparametric finite mixture models. We consider the estimation problem in detail in the simplest case of unordered-paired data where we can only observe the minimum and maximum values of two random variables; the identities of the minimum and maximum values are lost. The profile empirical likelihood approach is used for maximum semiparametric likelihood estimation. We present some large-sample results along with a simulation study. C1 NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. Univ Toledo, Dept Math, Toledo, OH 43606 USA. RP Qin, J (reprint author), NIAID, Biostat Res Branch, 6700B Rockledge Dr,MSC 7609, Bethesda, MD 20892 USA. EM jingqin@niaid.nih.gov; bzhang@utnet.utoledo.edu NR 45 TC 6 Z9 7 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 2005 VL 92 IS 2 BP 251 EP 270 DI 10.1093/biomet/92.2.251 PG 20 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 942OZ UT WOS:000230293000001 ER PT J AU Chatterjee, N Carroll, RJ AF Chatterjee, N Carroll, RJ TI Serniparametric maximum likelihood estimation exploiting gene-environment independence in case-control studies SO BIOMETRIKA LA English DT Article DE case-control study; gene-environment interaction; genetic epidemiology; logistic regression; population stratification; profile likelihood; retrospective study; serniparametric method ID MODELS; REGRESSION AB We consider the problem of maximum-likelihood estimation in case-control studies of gene-environment associations with disease when genetic and environmental exposures can be assumed to be independent in the underlying population. Traditional logistic regression analysis may not be efficient in this setting. We study the semiparametric maximum likelihood estimates of logistic regression parameters that exploit the gene-environment independence assumption and leave the distribution of the environmental exposures to be nonparametric. We use a profile-likelihood technique to derive a simple algorithm for obtaining the estimator and we study the asymptotic theory. The results are extended to situations where genetic and environmental factors are independent conditional on some other factors. Simulation studies investigate small-sample properties. The method is illustrated using data from a case-control study designed to investigate the interplay of BRCA1/2 mutations and oral contraceptive use in the aetiology of ovarian cancer. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Texas A&M Univ, College Stn, TX 77843 USA. RP Chatterjee, N (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. EM chattern@mail.nih.gov; carroll@stat.tamu.edu NR 15 TC 126 Z9 127 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD JUN PY 2005 VL 92 IS 2 BP 399 EP 418 DI 10.1093/biomet/92.2.399 PG 20 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 942OZ UT WOS:000230293000010 ER PT J AU Burnett, CA Xie, JW Quijano, J Shen, ZM Hunter, F Bur, M Li, KCP Danthi, SN AF Burnett, CA Xie, JW Quijano, J Shen, ZM Hunter, F Bur, M Li, KCP Danthi, SN TI Synthesis, in vitro, and in vivo characterization of an integrin alpha(V)beta 3-targeted molecular probe for optical imaging of tumor SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE integrin alpha(V)beta 3; tumor; molecular probe; imaging ID NONPEPTIDE ALPHA(V)BETA(3) ANTAGONISTS; CYCLIC RGD PEPTIDE; CELL-ADHESION; CLINICAL DEVELOPMENT; RECEPTOR ANTAGONIST; ANGIOGENESIS; POTENT; CANCER; OSTEOPOROSIS; ATTACHMENT AB Integrin 043 is a widely-recognized target for the development of targeted molecular probes for imaging pathological conditions. alpha(v)beta(3) is a cell-surface receptor protein that is upregulated in various pathological conditions including osteoporosis, rheumatoid arthritis, macular degeneration, and cancer. The synthesis of an a(v)beta(3)-targeted optical probe 7 from compound 1, and its in vitro and in vivo characterization is described. A series of aliphatic carbamate derivatives of the potent non-peptide integrin antagonist 1 was synthesized and the binding affinity to 003 was determined in both enzyme linked immunosorbent assay (ELISA) and cell adhesion inhibition assays. The hydrophobic carbamate-linked appendages improved the binding affinity of the parent compound for alpha(v)beta(3) by 2-20 times. A Boc-protected neopentyl derivative in the series is shown to have the best binding affinity to a(v)beta(3) (IC50 = 0.72 nM) when compared to compound 1 as well as to c-RGDfV. Optical probe 7 utilizes the neopentyl linker and demonstrates increased binding affinity and significant tumor cell uptake in vitro as well as specific tumor accumulation and retention in vivo. These results illustrate the potential of employing integrin-targeted molecular probes based on 1 to image a multitude of diseases associated with a(v)beta(3) overexpression. Published by Elsevier Ltd. C1 NIAID, Mol Imaging Lab, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Danthi, SN (reprint author), NIAID, Mol Imaging Lab, Ctr Clin, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM ndanthi@cc.nih.gov RI Danthi, Simhan/B-7639-2014 NR 39 TC 30 Z9 37 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUN 1 PY 2005 VL 13 IS 11 BP 3763 EP 3771 DI 10.1016/j.bmc.2005.03.024 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 930CV UT WOS:000229394300015 PM 15863003 ER PT J AU Young, HA AF Young, HA TI Untitled SO BIOPHARM INTERNATIONAL LA English DT Letter C1 NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21701 USA. EM Youngh@ncifcrf.gov NR 0 TC 9 Z9 9 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD JUN PY 2005 VL 18 IS 6 BP 16 EP 16 PG 1 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 934RE UT WOS:000229725100003 ER PT J AU Flomenbom, O Klafter, J Szabo, A AF Flomenbom, O Klafter, J Szabo, A TI What can one learn from two-state single-molecule trajectories? SO BIOPHYSICAL JOURNAL LA English DT Article ID FLUORESCENCE SPECTROSCOPY; CONFORMATIONAL DYNAMICS; ENZYMATIC DYNAMICS; KINETICS; CHANNEL; MEMBRANE; TIME AB A time trajectory of an observable that fluctuates between two values ( say, on and off), stemming from some unknown multisubstate kinetic scheme, is the output of many single-molecule experiments. Here we show that when all successive waiting times along the trajectory are uncorrelated the on and the off waiting time probability density functions contain all the information. By relating the lack of correlation in the trajectory to the topology of kinetic schemes, we can immediately specify those kinetic schemes that are equally consistent with experiment, and cannot be differentiated by any sophisticated analyses of the trajectory. Correlated trajectories, however, contain additional information about the underlying kinetic scheme, and we consider the strategy that one should use to extract it. C1 Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Flomenbom, O (reprint author), Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Chem, IL-69978 Tel Aviv, Israel. EM flomenbo@post.tau.ac.il RI Szabo, Attila/H-3867-2012; Flomenbom, Ophir/B-8443-2014 OI Flomenbom, Ophir/0000-0003-3498-9059 NR 27 TC 59 Z9 63 U1 1 U2 13 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUN PY 2005 VL 88 IS 6 BP 3780 EP 3783 DI 10.1529/biophysj.104.055905 PG 4 WC Biophysics SC Biophysics GA 931RO UT WOS:000229503000009 PM 15764653 ER PT J AU Bleckwenn, NA Bentley, WE Shiloach, J AF Bleckwenn, NA Bentley, WE Shiloach, J TI Production of recombinant protein using the HeLaS3-vaccinia virus expression system: Bioreactor perfusion and effects of post-infection temperature SO BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY LA English DT Article DE vaccinia; enhanced green fluorescent protein (EGFP); perfusion; hollow fiber; HeLaS3 ID HIGH-DENSITY CULTURE; VACCINIA VIRUS; HELA-CELLS; MAMMALIAN-CELLS; GENE-EXPRESSION; CLINICAL-TRIAL; HIV ENVELOPE; PHASE-I; GLYCOPROTEIN; VACCINATION AB Adaptation of the vaccinia virus expression system to HeLa S3 suspension bioreactor culture for the production of recombinant protein was conducted. Evaluation of hollow fiber perfusion of suspension culture demonstrated its potential for increased cell density prior to infection. The hollow fiber was also used for medium manipulations prior to infection. Two process parameters, multiplicity of infection (MOI) and temperature during the protein production phase, were evaluated to determine their effect on expression of the reporter protein, enhanced green fluorescent protein (EGFP). An MOI of 1.0 was sufficient for infection and led to the highest level of intracellular EGFP expression. Reducing the temperature to WC during the protein production phase increased production of the protein two-fold compared to 37 degrees C in spinner flask culture. Scaling up the process to a 1.5-liter bioreactor with hollow fiber perfusion led to an overall production level of 9.9 mu g EGFP/10(6) infected cells, or 27mg EGFP per liter. C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, NIH, DHHS Bldg,14A Rm 173,MSC 5522,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yossi@nih.gov FU Intramural NIH HHS NR 30 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0916-8451 EI 1347-6947 J9 BIOSCI BIOTECH BIOCH JI Biosci. Biotechnol. Biochem. PD JUN PY 2005 VL 69 IS 6 BP 1065 EP 1072 DI 10.1271/bbb.69.1065 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Applied; Food Science & Technology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry; Food Science & Technology GA 943FC UT WOS:000230336900001 PM 15973036 ER PT J AU Manji, HK AF Manji, HK TI Combined genomic and proteomic studies identify novel targets in the treatment of severe mood disorders SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 16 EP 17 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500008 ER PT J AU Angst, J Gamma, A Ajdacic, V Eich, D Rossler, W Merikangas, KR AF Angst, J Gamma, A Ajdacic, V Eich, D Rossler, W Merikangas, KR TI The bipolar spectrum: epidemiology and clinical perspectives SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA C1 Univ Zurich, Psychiat Hosp, Zurich, Switzerland. NIMH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 18 EP 18 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500010 ER PT J AU Insel, TR AF Insel, TR TI Report from the National Institute of Mental Health SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 21 EP 21 DI 10.1111/j.1399-5618.2005.00225_6.x PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500020 ER PT J AU Nugent, AC Milham, M Bain, EE Mah, L Cannon, D Marrett, S Zarate, C Pine, D Drevets, WC AF Nugent, AC Milham, M Bain, EE Mah, L Cannon, D Marrett, S Zarate, C Pine, D Drevets, WC TI Cortical abnormalities in treated and untreated bipolar disorder as investigated with voxel based morphometry SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE morphometry; gray matter; medication effects C1 NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD USA. Univ Illinois, Beckman Inst, Urbana, IL 61801 USA. NIMH, Funct MRI Facil, NIH, Bethesda, MD USA. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 24 EP 24 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500027 ER PT J AU Zarate, CA Duan, YF Mah, L Nugent, AC Quiroz, JA Singh, J Manji, HK Drevets, WC AF Zarate, CA Duan, YF Mah, L Nugent, AC Quiroz, JA Singh, J Manji, HK Drevets, WC TI Cerebral metabolic changes in bipolar depressed patients treated with the D-2/D-3 receptor agonist pramipexole SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar depression; pramipexole; Positron Emission Tomography (PET) C1 NIMH, Sect Neuroimaging, Bethesda, MD USA. NIMH, Lab Mol Pathophysiol, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 25 EP 26 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500031 ER PT J AU Altshuler, LL Post, R Black, DO Denicoff, KD Frye, MA Grunze, H Keck, PE Kupka, R Leverich, G McElroy, SL Nolen, WA Suppes, T Walden, J AF Altshuler, LL Post, R Black, DO Denicoff, KD Frye, MA Grunze, H Keck, PE Kupka, R Leverich, G McElroy, SL Nolen, WA Suppes, T Walden, J TI Subsyndromal depression and impaired life functioning in bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar disorder; subsyndromal depression; subthreshold depression C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. W Los Angeles Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Dept Psychiat, Los Angeles, CA USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Cincinnati Vet Affairs Med Ctr, Mental Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH USA. Altrech Inst Mental Hlth Care, Utrecht, Netherlands. Univ Groningen Hosp, Dept Psychiat, Groningen, Netherlands. Ludwig Maximilians Univ Munchen, Dept Psychiat, Munich, Germany. Univ Freiburg, Dept Psychiat, D-7800 Freiburg, Germany. Univ Munster, Dept Psychiat, Munster, Germany. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-5647 EI 1399-5618 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 28 EP 28 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500038 ER PT J AU Ameli, R Holmes, MK Luckenbaugh, DA Manji, HK Zarate, CA AF Ameli, R Holmes, MK Luckenbaugh, DA Manji, HK Zarate, CA TI Assessment of anhedonia in unipolar and bipolar depression and healthy subjects: examining the validity of the Snaith Hamilton Pleasure Scale SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE anhedonia; affective disorders; psychometrics C1 NIMH, Mood & Anxiety Disorders Program, Mol Pathophysiol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 28 EP 29 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500039 ER PT J AU Ameli, R Holmes, MK Zarate, CA Luckenbaugh, DA Manji, HK AF Ameli, R Holmes, MK Zarate, CA Luckenbaugh, DA Manji, HK TI The clinician administered scale of anhedonia (CASA) in unipolar & bipolar depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE anhedonia; depression; clinician-administered C1 NIMH, Mood & Anxiety Disorders Program, Mol Pathophysiol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 29 EP 29 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500040 ER PT J AU Denicoff, KD Singh, J Sporn, J Zarate, CA Quiroz, JA Brutsche, NE Luckenbaugh, DA Jolkovsky, LA Manji, HK Charney, DS AF Denicoff, KD Singh, J Sporn, J Zarate, CA Quiroz, JA Brutsche, NE Luckenbaugh, DA Jolkovsky, LA Manji, HK Charney, DS TI Antiglucocorticoid therapy in bipolar depression with mifepristone SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar depression; treatment study; anti-glucocorticoid C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 47 EP 47 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500097 ER PT J AU Gandhi, SK Cannon, DM Erickson, K Taylor-Tavares, JV Wood, S Bain, EE Zarate, C Sahakian, BJ Manji, HK Drevets, WC AF Gandhi, SK Cannon, DM Erickson, K Taylor-Tavares, JV Wood, S Bain, EE Zarate, C Sahakian, BJ Manji, HK Drevets, WC TI Decreased latency to response in unmedicated bipolar subjects: not associated with impaired accuracy SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar disorder; memory; probabilistic reversal C1 NIMH, Mood & Anxiety Disorder Program, NIH, Bethesda, MD USA. Univ Cambridge, Dept Psychiat, Cambridge, England. RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 57 EP 57 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500117 ER PT J AU Gould, NF Holmes, MK Pine, DS Burgess, N Manji, HK Zarate, CA AF Gould, NF Holmes, MK Pine, DS Burgess, N Manji, HK Zarate, CA TI Duke nukem 3-D: video games, virtual reality and spatial memory in patients with mood disorders SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE memory; spatial; neuropsychology C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 61 EP 62 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500132 ER PT J AU Post, RM Leverich, GS Altshuler, LL Frye, MS Nolen, WA Kupka, RW Suppes, T McElroy, S Keck, P Denicoff, KD Grunze, H AF Post, RM Leverich, GS Altshuler, LL Frye, MS Nolen, WA Kupka, RW Suppes, T McElroy, S Keck, P Denicoff, KD Grunze, H TI Antidepressant switch rates and poor sustained antidepressant efficacy in adjunctive treatment of bipolar depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE depression; antidepressants; hypomania C1 NIMH, Biol Psychiat Branch, NIH, DHHS, Bethesda, MD USA. RI Nolen, Willem/E-9006-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 87 EP 88 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500220 ER PT J AU Quiroz, JA Zarate, CA Singh, J Denicoff, KD Charney, DS Manji, HK AF Quiroz, JA Zarate, CA Singh, J Denicoff, KD Charney, DS Manji, HK TI N-acetyl-aspartate (NAA) and NAA-Glutamate (NAAG) levels differs across brain regions in acutely depressed bipolar patients: a proton magnetic resonance spectroscopy study SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar depression; magnetic resonance spectroscopy; N-acetyl-aspartate (NAA) C1 NIMH, Mol Pathophysiol Lab, NIH, HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 88 EP 89 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500224 ER PT J AU Quiroz, JA Zarate, CA Singh, J de Jesus, G Denicoff, K Luckenbaugh, D Charney, DS Manji, HK AF Quiroz, JA Zarate, CA Singh, J de Jesus, G Denicoff, K Luckenbaugh, D Charney, DS Manji, HK TI The efficacy of the glutamate modulating agent riluzole in bipolar depression SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE bipolar depression; riluzole; glutamate C1 NIMH, Mood & Anxiety Disorders Program, NIH, HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 88 EP 88 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500223 ER PT J AU Rich, BA Vinton, D Hommer, R Dickstein, D McClure, E Monk, C Ernst, M Pine, D Leibenluft, E AF Rich, BA Vinton, D Hommer, R Dickstein, D McClure, E Monk, C Ernst, M Pine, D Leibenluft, E TI The pathophysiology of social cognition deficits in pediatric bipolar disorder SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE pediatric bipolar disorder; attention; faces; IMRI; amygdala; striatum C1 NIMH, NIH, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 90 EP 90 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500230 ER PT J AU Szabo, ST Einat, H Chen, W Falke, C Du, J Manji, HK AF Szabo, ST Einat, H Chen, W Falke, C Du, J Manji, HK TI Neurogranin: a critical molecule at the nexus of 3 major signaling pathways and mood modulation SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE carbamazepine; bipolar; polypharmacy C1 NIMH, Mol Pathophysiol Lab, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Einat, Haim/A-7203-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 105 EP 106 PG 2 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500273 ER PT J AU Young, RC Beyer, J Gyulai, L Marangell, LB Mulsant, B Sajatovic, M Evans, J AF Young, RC Beyer, J Gyulai, L Marangell, LB Mulsant, B Sajatovic, M Evans, J TI A randomized controlled trial of acute treatments in late-life mania SO BIPOLAR DISORDERS LA English DT Meeting Abstract CT 6th International Conference on Bipolar Disorder CY JUN 16-18, 2005 CL Pittsburgh, PA DE mania; bipolar; geriatric C1 Cornell Univ, Weill Med Coll, White Plains, NY USA. Duke Univ, Durham, NC USA. Univ Penn, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NIMH, Rockville, MD 20857 USA. RI Sajatovic, Martha/I-8001-2014 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 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 SU 2 BP 114 EP 114 PG 1 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 929TO UT WOS:000229369500302 ER PT J AU Rasgon, NL Altshuler, LL Fairbanks, L Elman, S Bitran, J Labarca, R Saad, M Kupka, R Nolen, WA Frye, MA Suppes, T McElroy, SL Keck, PE Leverich, G Grunze, H Walden, J Post, R Mintz, J AF Rasgon, NL Altshuler, LL Fairbanks, L Elman, S Bitran, J Labarca, R Saad, M Kupka, R Nolen, WA Frye, MA Suppes, T McElroy, SL Keck, PE Leverich, G Grunze, H Walden, J Post, R Mintz, J TI Reproductive function and risk for PCOS in women treated for bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; hirsutism; menstrual abnormalities; polycystic ovary syndrome; weight gain; women ID POLYCYSTIC-OVARY-SYNDROME; ENDOCRINE DISORDERS; EPILEPSY; VALPROATE; LAMOTRIGINE; OBESITY; ABNORMALITIES; PREVALENCE; OVERWEIGHT; THERAPY AB Introduction: This study examined the reproductive function and prevalence of polycystic ovary syndrome (PCOS) in women with bipolar disorder taking antimanic medications. Method: Women aged 18-45 treated for bipolar disorder and not taking steroid contraceptives were recruited to complete questionnaires about their menstrual cycle and to provide blood samples for measurement of a range of reproductive endocrine and metabolic hormone levels. Eighty women participated in completing the questionnaires and 72 of them provided blood samples. Results: Fifty-two of the 80 women (65%) reported current menstrual abnormalities, 40 of which (50%) reported one or more menstrual abnormalities that preceded the diagnosis of bipolar disorder. Fifteen women (38%) reported developing menstrual abnormalities since treatment for bipolar disorder, 14 of which developed abnormalities since treatment with valproate (p = 0.04). Of the 15 patients reporting menstrual abnormalities since starting medication, 12 (80%) reported changes in menstrual flow (heavy or prolonged bleeding) and five (33%) reported changes in cycle frequency. No significant differences were observed between women receiving or not receiving valproate in mean levels of free or total serum testosterone levels. This was true for the total sample and for the sub-group without preexisting menstrual problems. However, within the valproate group, duration of use was significantly correlated with free testosterone levels (r = 0.33, p = 0.02). Three of the 50 women (6%) taking VPA, and 0% of the 22 taking other antimanic medications, met criteria for PCOS (p = 0.20). Other reproductive and metabolic values outside the normal range across treatment groups included elevated 17 alpha-OH progesterone levels, luteinizing hormone: follicle-stimulating hormone ratios, homeostatic model assessment (HOMA) values, and low estrogen and dehydroepiandrosterone sulfate (DHEAS) levels. Preexisting menstrual abnormalities predicted higher levels of 17 alpha-OH progesterone, free testosterone, and estrone as well as development of new menstrual abnormalities. Body mass index (BMI) was significantly positively correlated with free testosterone levels and insulin resistance (HOMA) across all subjects, regardless of medication used. Conclusions: Rates of menstrual disturbances are high in women with bipolar disorder and, in many cases, precede the diagnosis and treatment for the disorder. Treatment with valproate additionally contributes significantly to the development of menstrual abnormalities and an increase in testosterone levels over time. A number of bipolar women, regardless of type of medication treatment received, have reproductive and metabolic hormonal abnormalities, yet the etiology of such abnormalities requires further study. Women with preexisting menstrual abnormalities may represent a group at risk for development of reproductive dysfunction while being treated for bipolar disorder. C1 Stanford Sch Med, Dept Psychiat, Palo Alto, CA 94305 USA. VA Greater Los Angeles Healthcare Syst, Dept Psychiat, W Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Inst Neuropsiquiat Chile, Santiago, Chile. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Altrech Inst Mental Hlth Care, Utrecht, Netherlands. Univ Groningen, Med Ctr, Dept Psychiat, Groningen, Netherlands. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Cincinnati Vet Affairs Med Ctr, Mental Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH USA. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. LMU Munich, Dept Psychiat, Munich, Germany. Univ Freiburg, Dept Psychiat, Freiburg, Germany. Univ Munster, Dept Psychiat, D-4400 Munster, Germany. RP Rasgon, NL (reprint author), Stanford Sch Med, Dept Psychiat & Behav Sci, 401 Quarry Rd,Room 2360, Palo Alto, CA 94305 USA. EM nrasgon@stanford.edu RI Nolen, Willem/E-9006-2014 FU NIMH NIH HHS [R01 MH079261] NR 36 TC 79 Z9 81 U1 0 U2 5 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD JUN PY 2005 VL 7 IS 3 BP 246 EP 259 DI 10.1111/j.1399-5618.2005.00201.x PG 14 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 925VJ UT WOS:000229081100004 PM 15898962 ER PT J AU Carruthers, CM Foster, PMD AF Carruthers, CM Foster, PMD TI Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE phthalate; DBP; testes; epididymis; anogenital distance; development; malformations ID ALTERS SEXUAL-DIFFERENTIATION; FALLING SPERM QUALITY; DI(N-BUTYL) PHTHALATE; SEMEN QUALITY; INSL3 GENE; TESTICULAR CANCER; CRYPTORCHIDISM; TESTIS; MALFORMATIONS; ANTIANDROGENS AB BACKGROUND: Gestational exposure to di-n-butyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to interfere with the development of the male reproductive tract by acting as an antiandrogen. This study was conducted to identify the critical days for the abnormal development of the male reproductive tract, specifically the testis and epididymis. METHODS: Timed-pregnant Sprague-Dawley rats were dosed with DBP at 500 mg/kg/day on gestation day (GD) 14 and 15, 15 and 16, 16 and 17,17 and 18, 18 and 19, or 19 and 20 (GD 0 = plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and 13, while areloa number was recorded on PND 13 only. After weaning, males were allowed to mature to PND 90 at which time they were necropsied. Areloa number and AGD were recorded and testes, epididymides, seminal vesicles, prostate gland, kidneys, and liver weighed. Blood serum was collected and assayed for total testosterone concentration. RESULTS: There were no observable effects on litter size, sex ratio, serum testosterone concentration, or mortality of pups. Statistically significant permanent reductions in AGD were seen in males exposed prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20. However, permanent retention occurred only ill males after DBP exposure on GD 16 and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal weights; while exposure on only GD 16 and 17 caused a significant increase in the weights of the testes due to edema. In this study, epididymal and testicular malformations were most prevalent after exposure to DBP on any gestational day. Epididymal malformations, characterized by agenesis of various regions and small or flaccid testes were significantly increased in DBP-exposed males only on GD 16 and 17. CONCLUSIONS: These findings suggest that 2-day DBP exposure is highly detrimental to the developing reproductive tract of the male fetus and the critical window for abnormal development is GD 16-18. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Carruthers, CM (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM carruth1@niehs.nih.gov NR 35 TC 67 Z9 70 U1 1 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2005 VL 74 IS 3 BP 277 EP 285 DI 10.1002/bdrb.20050 PG 9 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 942BF UT WOS:000230257200008 PM 15954088 ER PT J AU Seggewiss, R Dunbar, CE AF Seggewiss, R Dunbar, CE TI Old before its time: age-related thymic dysfunction may preclude efficacy of gene therapy in older SCID-X1 patients SO BLOOD LA English DT Editorial Material ID SEVERE COMBINED IMMUNODEFICIENCY AB Guzman and collegues demonstrate that it is possible to specifically target leukemic stem/progenitor cells with the naturally occurring small molecule parthenolide. These findings open new avenues for the treatment of hematological malignancies. C1 NHLBI, Bethesda, MD 20892 USA. RP Seggewiss, R (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2005 VL 105 IS 11 BP 4160 EP 4161 DI 10.1182/blood-2005-03-1008 PG 2 WC Hematology SC Hematology GA 928SR UT WOS:000229292500009 ER PT J AU Howard, OMZ Dong, HF Su, SB Caspi, RR Chen, X Plotz, P Oppenheim, JJ AF Howard, OMZ Dong, HF Su, SB Caspi, RR Chen, X Plotz, P Oppenheim, JJ TI Autoantigens signal through chemokine receptors: uveitis antigens induce CXCR3- and CXCR5-expressing lymphocytes and immature dendritic cells to migrate SO BLOOD LA English DT Article ID RETINOID-BINDING-PROTEIN; EXPERIMENTAL AUTOIMMUNE UVEITIS; HEMATOPOIETIC PROGENITOR CELLS; S-ANTIGEN; BEHCETS-DISEASE; T-LYMPHOCYTES; HUMAN IRBP; IN-VITRO; RAT EYE; EXPRESSION AB We tested the hypothesis that interaction between autoantigens and chemoattractant receptors may be an important step in the development of autoimmunity. The retinal autoantigens S-antigen (S-Ag) and interphotoreceptor retinoid binding protein (IRBP) can induce autoimmune uveitis in rodent models. We evaluated the chemotactic activity of S-Ag and IRBP and found that both induced migration of human and mouse immature dendritic cells (iDCs) and lymphocytes, but not neutrophils, monocytes, or mature DCs. Cross-desensitization studies and single-receptor transfected cells revealed that subfamily of alpha chemokine receptors CXCR5 and CXCR3 mediated the chemotactic effect of IRBP, while only CXCR3 was required for the chemotactic response to S-Ag. Examination of the relationships between chemoattraction and the ability to elicit pathology at the protein or peptide levels in the mouse uveitis model revealed dissociation of the capacity to induce uveitis, lymphocyte proliferation, and chemoattraction. These studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs and T and B cells expressing CXCR3 and CXCR5. C1 NCI, Ctr Canc Res, Mol Immunoregulat Lab, Basic Res Program,Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. NIAMSD, NEI, Immunol Lab, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. RP Howard, OMZ (reprint author), POB B, Frederick, MD 21702 USA. EM howardz@mail.ncifcrf.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015; OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027; Caspi, Rachel/0000-0002-7140-7671 FU NCI NIH HHS [N01 CO012400, N01-CO-012400] NR 49 TC 25 Z9 29 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2005 VL 105 IS 11 BP 4207 EP 4214 DI 10.1182/blood-2004-07-2697 PG 8 WC Hematology SC Hematology GA 928SR UT WOS:000229292500017 PM 15713799 ER PT J AU Jamur, MC Grodzki, ACG Berenstein, EH Hamawy, MM Siraganian, RP Oliver, C AF Jamur, MC Grodzki, ACG Berenstein, EH Hamawy, MM Siraganian, RP Oliver, C TI Identification and characterization of undifferentiated mast cells in mouse bone marrow SO BLOOD LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the American-Society-for-Cell-Biology CY DEC 08-12, 2001 CL WASHINGTON, D.C. SP Amer Soc Cell Biol ID BASOPHILIC LEUKEMIA-CELLS; FC-EPSILON-RI; ALPHA-GALACTOSYL DERIVATIVES; MONOCLONAL-ANTIBODY AA4; C-KIT LIGAND; HISTAMINE-RELEASE; SPLEEN COLONIES; IGE; PROGENITORS; DIFFERENTIATION AB Sequential immunomagnetic isolation with 2 monoclonal antibodies was used to purify and characterize an undifferentiated mast cell in adult mouse bone marrow that had not been previously recognized. This cell represents 0.02% of the cells in the bone marrow, is CD34(+), CD13(+), and c-kit(+), and does not express FC epsilon RI. However, by polymerase chain reaction (PCR) the cell contains message for the alpha and beta subunits of FC epsilon RI, mast cell-specific proteases, and carboxypeptidase A. Morphologically, this cell has a large nucleus, little cytoplasm, few cytoplasmic organelles, and no cytoplasmic granules. In vitro, in the presence of interleukin-3 (IL-3) and stem cell factor (SCF) these cells differentiate only into a granulated mast cell that now expresses CD13, c-kit, mast cell-specific gangliosides, Fc epsilon RI, and binds immunoglobulin E (IgE). When injected into lethally irradiated mice, these cells are able to reconstitute the mast cell population in the spleen. C1 Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, BR-14049900 Ribeirao Preto, SP, Brazil. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. RP Oliver, C (reprint author), Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biol Celular & Mol & Bioagentes Patogen, Avenida Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP, Brazil. EM coliver@rbp.fmrp.usp.br RI Jamur, Maria Celia/L-5520-2016 OI Jamur, Maria Celia/0000-0001-7065-8543 NR 44 TC 53 Z9 54 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2005 VL 105 IS 11 BP 4282 EP 4289 DI 10.1182/blood-2004-02-0756 PG 8 WC Hematology SC Hematology GA 928SR UT WOS:000229292500027 PM 15718418 ER PT J AU Sims, GP Ettinger, R Shirota, Y Yarboro, CH Illei, GG Lipsky, PE AF Sims, GP Ettinger, R Shirota, Y Yarboro, CH Illei, GG Lipsky, PE TI Identification and characterization of circulating human transitional B cells SO BLOOD LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RECEPTOR-INDUCED APOPTOSIS; HEAT-STABLE ANTIGEN(HI); VARIABLE REGION GENES; CENTER FOUNDER CELLS; PERIPHERAL-BLOOD; T-CELL; ACTIVATING FACTOR; LYMPHOCYTE-B; BONE-MARROW AB Murine B-cell development begins in bone marrow and results in the generation of immature transitional B cells that transit to the spleen to complete their maturation. it remains unclear whether the same developmental pathway takes place in humans. Using markers characteristic of human bone marrow immature B cells, we have identified a population of circulating human B cells with a phenotype most similar to mouse transitional type I (T1) B cells, although these human counter-parts express CD5. These cells die rapidly in culture, and B-cell activation factor member of the tumor necrosis factor (TNF) family (BAFF) does not effect their survival regardless of B-cell receptor (BCR) stimulation. In contrast, bone marrow stromal cells or interleukin-4 (IL-4) significantly enhanced their survival. In the presence of T-cell signals provided by IL-4 or CD40 ligation, BCR stimulation can induce progression into cell cycle. Interestingly, circulating B cells that phenotypically and functionally resemble murine T2 B cells are found in cord blood and adult peripheral blood, suggesting that B-cell maturation may not be restricted to the spleen. Notably, increased proportions of T1 B cells were found in blood of patients with systemic lupus erythematosus (SLE), although bone marrow production and selection appeared to be normal. C1 NIAMSD, Intramural Res Program, Autoimmun Branch, Bethesda, MD 20892 USA. NIAMSD, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Intramural Res Program, Autoimmun Branch, 9000 Rockville Pike,Bldg 10,Room 6D47C, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov NR 68 TC 296 Z9 302 U1 0 U2 18 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2005 VL 105 IS 11 BP 4390 EP 4398 DI 10.1182/blood-2004-11-4284 PG 9 WC Hematology SC Hematology GA 928SR UT WOS:000229292500041 PM 15701725 ER PT J AU Chan, EM Comer, EM Brown, FC Richkind, KE Holmes, ML Chong, BH Shiffman, R Zhang, DE Slovak, ML Willman, CL Noguchi, CT Li, YJ Heiber, DJ Kwan, L Chan, RJ Vance, GH Ramsey, HC Hromas, RA AF Chan, EM Comer, EM Brown, FC Richkind, KE Holmes, ML Chong, BH Shiffman, R Zhang, DE Slovak, ML Willman, CL Noguchi, CT Li, YJ Heiber, DJ Kwan, L Chan, RJ Vance, GH Ramsey, HC Hromas, RA TI AML1-FOG2 fusion protein in myelodysplasia SO BLOOD LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-of-Hematology CY DEC 04-07, 2004 CL San Diego, CA SP Amer Soc Hematol ID ACUTE MYELOID-LEUKEMIA; CO-REPRESSOR; HEMATOPOIETIC-CELLS; AML1; GENE; DIFFERENTIATION; CLONING; MCTBP2; REGION; CTBP AB Core binding factor (CBF) participates in specification of the hematopoietic stem cell and functions as a critical regulator of hematopoiesis. Translocation or point mutation of acute myeloid leukemia 1 (AML1)/RUNX1, which encodes the DNA-binding subunit of CBF, plays a central role in the pathogenesis of acute myeloid leukemia and myelodysplasia. We characterized the t(X;21)(p22.3;q22.1) in a patient with myelodysplasia that fuses AML1 in-frame to the novel partner gene FOG2/ ZFPM2. The reciprocal gene fusions AMLl-FOG2 and FOG2-AML1 are both expressed. AMLI-FOG2, which fuses the DNA-binding domain of AML1 to most of FOG2, represses the transcriptional activity of both CBF and GATA1. AML1-FOG2 retains a motif that recruits the corepressor C-terminal binding protein (CtBP) and these proteins associate in a protein complex. These results suggest a central role for CtBP in AML1-FOG2 transcriptional repression and implicate coordinated disruption of the AML1 and GATA developmental programs in the pathogenesis of myelodysplasia. C1 Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Pediat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA. Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. Genzyme Genet, Santa Fe, NM USA. Univ New S Wales, Dept Med, Sydney, NSW, Australia. Monterey Bay Oncol Ctr, Monterey, CA USA. Scripps Res Inst, La Jolla, CA 92037 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NIDDK, NIH, Bethesda, MD USA. Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Pathol, Albuquerque, NM 87131 USA. Univ New Mexico, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. RP Chan, EM (reprint author), Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol, 1044 W Walnut St,R4-202, Indianapolis, IN 46202 USA. EM echan@iupui.edu NR 21 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 1 PY 2005 VL 105 IS 11 BP 4523 EP 4526 DI 10.1182/blood-2004-07-2762 PG 4 WC Hematology SC Hematology GA 928SR UT WOS:000229292500058 PM 15705784 ER PT J AU Ashok, A Barnes, AM Marini, JC AF Ashok, A Barnes, AM Marini, JC TI Chaperone-procollagen interactions differ with mutation location in osteogenesis imperfecta SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY JUN 25-29, 2005 CL Geneva, SWITZERLAND SP European Calcified Tissue Soc, Int Bone & Mineral Soc, Eli Lilly, Elsevier, Merck, Novartis, Nycomed, Roche & GlaxoSmithKline, Servier, Alliance Better Bone Hlth C1 NICHD, NIH, BEMB, 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 8756-3282 J9 BONE JI Bone PD JUN PY 2005 VL 36 SU 2 BP S224 EP S225 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 938DK UT WOS:000229979900267 ER PT J AU Black, DM Rosen, CJ Palermo, L Hue, T Ensrud, KE Greenspan, SL Lang, TF McGowan, JA Bilezikian, JP AF Black, DM Rosen, CJ Palermo, L Hue, T Ensrud, KE Greenspan, SL Lang, TF McGowan, JA Bilezikian, JP TI The effect of 1 year of alendronate following 1 year of PTH 1-84: Second year results from the PTH and alendronate (PATH) trial SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY JUN 25-29, 2005 CL Geneva, SWITZERLAND SP European Calcified Tissue Soc, Int Bone & Mineral Soc, Eli Lilly, Elsevier, Merck, Novartis, Nycomed, Roche & GlaxoSmithKline, Servier, Alliance Better Bone Hlth C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. ME Ctr Osteo Res, Bangor, ME USA. Univ Minnesota, Minneapolis, MN 55455 USA. MVAMC, Minneapolis, MN USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIAMS, NIH, Bethesda, MD USA. Columbia Univ, New York, NY 10027 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2005 VL 36 SU 2 BP S448 EP S449 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 938DK UT WOS:000229979900754 ER PT J AU Sigurdsson, G Aspelund, T Chang, M Jonsdottir, B Sigurdsson, S Eiriksdottir, G Gudmundsson, A Harris, TB Gudnason, V Lang, TF AF Sigurdsson, G Aspelund, T Chang, M Jonsdottir, B Sigurdsson, S Eiriksdottir, G Gudmundsson, A Harris, TB Gudnason, V Lang, TF TI The gender difference in bone strength continues to increase into old age SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY JUN 25-29, 2005 CL Geneva, SWITZERLAND SP European Calcified Tissue Soc, Int Bone & Mineral Soc, Eli Lilly, Elsevier, Merck, Novartis, Nycomed, Roche & GlaxoSmithKline, Servier, Alliance Better Bone Hlth C1 Iceland Heart Assoc, Kopavogur, Iceland. Univ Hosp, Landspitali, Reykjavik, Iceland. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 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 8756-3282 J9 BONE JI Bone PD JUN PY 2005 VL 36 SU 2 BP S156 EP S156 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 938DK UT WOS:000229979900116 ER PT J AU Uveges, TE Bergwitz, C Kozloff, KM Forlino, A Kuznetsova, NV Gronowitz, G Goldstein, SA Leikin, S Marini, JC AF Uveges, TE Bergwitz, C Kozloff, KM Forlino, A Kuznetsova, NV Gronowitz, G Goldstein, SA Leikin, S Marini, JC TI Homozygosity for a dominant-negative type I collagen mutation attenuates the type IVOI phenotype of the heterozygous Brtl mouse: Insight into disease mechanism SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY JUN 25-29, 2005 CL Geneva, SWITZERLAND SP European Calcified Tissue Soc, Int Bone & Mineral Soc, Eli Lilly, Elsevier, Merck, Novartis, Nycomed, Roche & GlaxoSmithKline, Servier, Alliance Better Bone Hlth C1 NICHD, NIH, BEMB, Bethesda, MD USA. Univ Michigan, Ortho Res Labs, Ann Arbor, MI 48109 USA. NICHD, NIH, Sect Phys Biochem, Bethesda, MD USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD JUN PY 2005 VL 36 SU 2 BP S128 EP S129 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 938DK UT WOS:000229979900059 ER PT J AU Yaccoby, S Zhan, F Qiang, Y Tian, E Zangari, M Tricot, G Barlogie, B Rudikoff, S Shaughnessy, J AF Yaccoby, S Zhan, F Qiang, Y Tian, E Zangari, M Tricot, G Barlogie, B Rudikoff, S Shaughnessy, J TI Toward elucidation of the role of altered Wnt signaling in myeloma and development of corresponding therapeutic interventions SO BONE LA English DT Meeting Abstract CT 2nd Joint Meeting of the European-Calcified-Tissue-Society/International-Bone-and-Mineral-Society CY JUN 25-29, 2005 CL Geneva, SWITZERLAND SP European Calcified Tissue Soc, Int Bone & Mineral Soc, Eli Lilly, Elsevier, Merck, Novartis, Nycomed, Roche & GlaxoSmithKline, Servier, Alliance Better Bone Hlth C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Natl Canc Inst, Cellular & Mol Biol 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 8756-3282 J9 BONE JI Bone PD JUN PY 2005 VL 36 SU 2 BP S114 EP S114 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 938DK UT WOS:000229979900029 ER PT J AU Rogozin, IB Sverdlov, AV Babenko, VN Koonin, EV AF Rogozin, IB Sverdlov, AV Babenko, VN Koonin, EV TI Analysis of evolution of exon-intron structure of eukaryotic genes SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE intron evolution; intron gain; intron loss; protosplice site; exon shuffling; early eukaryotes ID PROTO-SPLICE SITES; PHYLOGENETIC ANALYSIS; ANIMAL DIVERGENCE; ISOMERASE GENE; SNRNP PROTEIN; POSITIONS; SEQUENCES; ORIGIN; GAIN; CONSERVATION AB The availability of multiple, complete eukaryotic genome sequences allows one to address many fundamental evolutionary questions on genome scale. One such important, long-standing problem is evolution of exon-intron structure of eukaryotic genes. Analysis of orthologous genes from completely sequenced genomes revealed numerous shared intron positions in orthologous genes from animals and plants and even between animals, plants and protists. The data on shared and lineage-specific intron positions were used as the starting point for evolutionary reconstruction with parsimony and maximum-likelihood approaches. Parsimony methods produce reconstructions with intron-rich ancestors but also infer lineage-specific, in many cases, high levels of intron loss and gain. Different probabilistic models gave opposite results, apparently depending on model parameters and assumptions, from domination of intron loss, with extremely intron-rich ancestors, to dramatic excess of gains, to the point of denying any true conservation of intron positions among deep eukaryotic lineages. Development of models with adequate, realistic parameters and assumptions seems to be crucial for obtaining more definitive estimates of intron gain and loss in different eukaryotic lineages. Many shared intron positions were detected in ancestral eukaryotic paralogues which evolved by duplication prior to the divergence of extant eukarycitic lineages. These findings indicate that numerous introns were present in eukaryotic genes already at the earliest stages of evolution of eukaryotes and are compatible with the hypothesis that the original, catastrophic intron invasion accompanied the emergence of the eukaryotic cells. Comparison of various features of old and younger introns starts shedding light on probable mechanisms of intron insertion, indicating that propagation of old introns is unlikely to be a major mechanism for origin of new ones. The existence and structure of ancestral protosplice sites were addressed by examining the context of introns inserted within codons that encode amino acids conserved in all eukaryotes and, accordingly, are not subject to selection for splicing efficiency. It was shown that introns indeed predominantly insert into or are fixed in specific protosplice sites which have the consensus sequence (A/C)AG]Gt. C1 Natl Lib Med, NCBI, NIH, Bethesda, MD 20894 USA. RP Rogozin, IB (reprint author), Natl Lib Med, NCBI, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM rogozin@ncbi.nlm.nih.gov RI Babenko, Vladimir/K-5609-2014; OI Babenko, Vladimir/0000-0002-3077-9559 NR 83 TC 114 Z9 117 U1 3 U2 22 PU HENRY STEWART PUBLICATIONS PI LONDON PA RUSSELL HOUSE, 28/30 LITTLE RUSSELL ST, LONDON WC1A 2HN, ENGLAND SN 1467-5463 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD JUN PY 2005 VL 6 IS 2 BP 118 EP 134 DI 10.1093/bib/6.2.118 PG 17 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 939PV UT WOS:000230085800002 PM 15975222 ER PT J AU Baerlocher, MO Collingwood, P Becker, GJ AF Baerlocher, Mark O. Collingwood, Peter Becker, Gary J. TI Enhancing Interventional Radiology Training in Canada: Creating New Choices for Medical Students and Residents. Current Training Options in the United States SO CANADIAN ASSOCIATION OF RADIOLOGISTS JOURNAL-JOURNAL DE L ASSOCIATION CANADIENNE DES RADIOLOGISTES LA English DT Article C1 [Becker, Gary J.] NIH, Canc Imaging Program, Bethesda, MD 20892 USA. [Collingwood, Peter] Mem Univ Newfoundland, Dept Radiol, St John, NF, Canada. [Baerlocher, Mark O.] Univ Toronto, Sch Med, Toronto, ON, Canada. RP Baerlocher, MO (reprint author), 146 Brunswick Ave, Toronto, ON M5S 2M2, Canada. EM mark.baerlocher@utoronto.ca NR 15 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0846-5371 J9 CAN ASSOC RADIOL J JI Can. Assoc. Radiol. J.-J. Assoc. Can. Radiol. PD JUN PY 2005 VL 56 IS 3 BP 163 EP 169 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA V10TU UT WOS:000207487100006 PM 16144276 ER PT J AU Gulcelik, MA Dinc, S Bir, F Elitok, O Alagol, H Oz, M AF Gulcelik, MA Dinc, S Bir, F Elitok, O Alagol, H Oz, M TI Locally applied molgramostim improves wound healing at colonic anastomoses in rats after ligation of the common bile duct SO CANADIAN JOURNAL OF SURGERY LA English DT Article ID EXPERIMENTAL OBSTRUCTIVE-JAUNDICE; STIMULATING FACTOR; GRANULOCYTE-COLONY; INTESTINAL ANASTOMOSES; KERATINOCYTE GROWTH; SODIUM TAUROCHOLATE; BOWEL ANASTOMOSES; CELLS; CHEMOTHERAPY; ULCERS AB Background: Several systemic factors, including jaundice, long-term corticosteroid therapy, diabetes and malnutrition, increase the risk of anastomotic dehiscence. The local application of molgramostim (recombinant human granulocyte-macrophage colony stimulating factor) has been reported to improve impaired dermal wound healing. Since jaundice, one of the systemic risk factors for anastomotic dehiscence, causes significant impairment of anastomotic healing, we hypothesized that locally injected molgramostim could improve the healing of bowel anastomoses in bile-duct-ligated rats used as an experimental model for jaundice. Methods: Eighty-six Sprague-Dawley rats were randomized into 4 groups of 20-22 animals each as follows: group 1 - colonic anastomosis only; group 2 - laparotomy followed 7 days later by colonic anastomosis; group 3 - common-bile-duct ligation (CBDL) followed 7 days later by colonic anastomosis ( control group); group 4 - CBDL followed by colonic anastomosis with locally applied molgramostim. Laparotomy was performed under anesthesia in group 2 rats. In groups 3 and 4, laparotomy was followed by ligation and dissection of the common bile duct. After 7 days, colonic anastomosis was performed; in group 4 rats, molgramostim (50 mu g) was injected into the perianastomotic area. On postoperative day 3, rats were killed, and the bursting pressures and hydroxyproline levels measured. Two rats from each group were selected for histopathological examination. Results: The mean bursting pressure in group 4 was significantly higher than that in group 3 (37.8 v. 30.5 mm Hg [p < 0.01]). The mean hydroxyproline level in group 3 was significantly lower than that of the other groups (2.7 v. 3.1-3.5 mg/g tissue [p < 0.01]). On histopathological examination, specimens from group 4 rats showed an increased mononuclear cell population and a smaller gap on the anastomotic line than those from group 3. Conclusion: The local injection of molgramostim improves healing of the impaired wound in rats subjected to CBDL. C1 NIDA, Intramural Res Program, Cellular Neurobiol Sect, Baltimore, MD 21224 USA. Pamukkale Univ, Dept Pathol, Denizli, Turkey. Ankara Oncol Training & Res Hosp, Dept Gen Surg, Ankara, Turkey. RP Oz, M (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 38 TC 7 Z9 7 U1 2 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 0008-428X J9 CAN J SURG JI Can. J. Surg. PD JUN PY 2005 VL 48 IS 3 BP 213 EP 218 PG 6 WC Surgery SC Surgery GA 933NJ UT WOS:000229637600007 PM 16013625 ER PT J AU Ramirez, AG Gallion, KJ Suarez, L Giachello, AL Marti, JR Medrano, MA Perez-Stable, EJ Talavera, GA Trapido, EJ AF Ramirez, AG Gallion, KJ Suarez, L Giachello, AL Marti, JR Medrano, MA Perez-Stable, EJ Talavera, GA Trapido, EJ TI A National Agenda for Latino Cancer Prevention and Control SO CANCER LA English DT Editorial Material DE Latinos; Hispanics; cancer priorities; research; professional training; public education ID REGIONAL HISPANIC POPULATIONS AB Although cancer is a leading cause of morbidity and premature death among Latinos, there is limited knowledge of cancer-related issues and priorities of greatest significance to the Latino population, the largest minority group in the nation. This information is vital in helping to guide Latino cancer research, training, and awareness efforts at national, regional, and local levels. To help identify cancer issues of greatest relevance to Latinos, Redes En Accion, The National Hispanic/Latino Cancer Network, a major network among the National Cancer Institute's Special Populations Networks, conducted a survey of 624 key opinion leaders from around the country. Respondents were asked to rank the three cancer sites most important to Latinos in their region and the five issues of greatest significance for this population's cancer prevention and control. Recommendations were prioritized for three specific areas: 1) research, 2) training and/or professional education, and 3) awareness and/or public education. Among cancers, breast carcinoma was ranked number one, followed in order by cervical and lung carcinomas. The issues of greatest significance to Latinos were 1) access to cancer screening and care, 2) tobacco use, 3) patient-doctor communication, 4) nutrition, and 5) risk communication. This survey solicited information from scientists, health care professionals, leaders of government agencies, professional and community-based organizations, and other stakeholders in Latino health. The results laid the foundation for a national Redes En Accion Latino cancer agenda, thus providing a useful tool for individuals and organizations engaged in cancer prevention and control efforts among the Hispanic-Latino population. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. San Antonio Canc Inst, Baylor Coll Med, Ctr Canc, San Antonio, TX USA. Texas Dept Hlth, Epidemiol Res Serv, Austin, TX 78756 USA. Univ Illinois, Jane Addams Coll Social Work, Chicago, IL USA. Brooklyn Hosp Ctr, Dept Surg, New York, NY USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Diego State Univ, Grad Sch Publ Hlth, San Diego, CA 92182 USA. Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Ramirez, AG (reprint author), Baylor Coll Med, Chron Dis Prevet & Control Res Ctr, 8207 Callaghan Rd,Suite 110, San Antonio, TX 78230 USA. EM aramirez@bcm.tmc.edu FU NCI NIH HHS [U01-CA86117] NR 13 TC 16 Z9 16 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 JUN 1 PY 2005 VL 103 IS 11 BP 2209 EP 2215 DI 10.1002/cncr.21053 PG 7 WC Oncology SC Oncology GA 928OS UT WOS:000229282000001 PM 15822119 ER PT J AU Stevens, EV Raffeld, M Espina, V Kristensen, GB Trope, CG Kohn, EC Davidson, B AF Stevens, EV Raffeld, M Espina, V Kristensen, GB Trope, CG Kohn, EC Davidson, B TI Expression of xeroderma pigmentosum A protein predicts improved outcome in metastatic ovarian carcinoma SO CANCER LA English DT Article DE xeroderma pigmentosum A; nucleotide excision repair; ovarian carcinoma; immunocytochemistry ID NUCLEOTIDE EXCISION-REPAIR; MESSENGER-RNA LEVELS; INDUCED DNA-DAMAGE; GERM-CELL TUMORS; CANCER PATIENTS; CISPLATIN SENSITIVITY; EFFUSION CYTOLOGY; CHEMOTHERAPY; ERCC1; XPA AB BACKGROUND. The nucleotide excision repair (NER) proteins repair DNA adducts due to xenobiotics and cancer chemotherapy. The authors hypothesized that expression of the NER protein xeroderma pigmentosum A (XPA) would be reduced in a clinically significant fashion in metastatic ovarian carcinoma. METHODS. Malignant effusion specimens were studied so that there was a uniform metastatic ovarian carcinoma population for study. XPA protein expression was analyzed by immunocytochemistry in 142 effusion specimens (109 peritoneal specimens, 33 pleural specimens) from 125 patients. Specimens were obtained at diagnosis (n = 76), and at disease recurrence (n = 66). Patients in the latter group received platinum-based chemotherapy. RESULTS. XPA was expressed in cancer cells in 136 of the 142 (96%) effusion specimens. Strongest expression occurred in leukocytes and reactive mesothelial cells. XPA expression did not correlate with treatment status, effusion site, International Federation of Gynecology and Obstetrics stage, histologic grade, or the extent of residual disease. More effusion tumor cells from patients with a complete response to chemotherapy expressed XPA compared with those with a partial or no response (P = 0.03, chi(2) test). Patients with recurrent disease with XPA expressed > 25% of tumor cells had better progression-free survival (PFS) by univariate analysis (median = 0 vs. 11 months, P < 0.001; 95% confidence interval [CI], 1-5, 8-14) and overall survival (OS; median = 24 vs. 34 months, P = 0.04; 95% CI, 17-31, 24-44). XPA was the only predictor of PFS outcome by multivariate analysis (P = 0.03). CONCLUSIONS. The results of the current study showed that XPA was widely expressed in metastatic ovarian carcinoma effusion specimens and in the cells of the effusion microenvironment. Paradoxically, XPA expression was associated with better response to chemotherapy and predicted better PFS and OS. C1 Univ Oslo, Dept Pathol, Norwegian Radium Hosp, N-0310 Oslo, Norway. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD USA. NCI, Food & Drug Adm Clin Proteom Program, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Oslo, Dept Gynecol Oncol, Norwegian Radium Hosp, Oslo, Norway. RP Davidson, B (reprint author), Univ Oslo, Dept Pathol, Norwegian Radium Hosp, N-0310 Oslo, Norway. EM bend@ulrik.uio.no OI Espina, Virginia/0000-0001-5080-5972 NR 31 TC 20 Z9 21 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2005 VL 103 IS 11 BP 2313 EP 2319 DI 10.1002/cncr.21031 PG 7 WC Oncology SC Oncology GA 928OS UT WOS:000229282000014 PM 15844177 ER PT J AU Cohen, RJ Curtis, RE Inskip, PD Fraumeni, JF AF Cohen, RJ Curtis, RE Inskip, PD Fraumeni, JF TI The risk of developing second cancers among survivors of childhood soft tissue sarcoma SO CANCER LA English DT Article DE second cancers; soft tissue sarcoma; rhabdomyosarcoma; fibrosarcoma; childhood cancer ID 2ND MALIGNANT NEOPLASMS; LONG-TERM SURVIVORS; CANCER; MELANOMA; RHABDOMYOSARCOMA; RADIOTHERAPY; CHILDREN; CHEMOTHERAPY; ADOLESCENCE; LEUKEMIA AB BACKGROUND. Previous studies have shown that children who are treated for soft tissue sarcoma (STS) are at increased risk for developing second cancers. However, the risk for specific cancer sites and variations in risk by treatment and STS histology remain unclear. METHODS. The study evaluated 1499 children (age < 18 years) who survived for >= 1 year after they were diagnosed with STS and who were reported to the Surveillance, Epidemiology, and End Results (SEER) population-based cancer registries from 1973 to 2000. RESULTS. Twenty-seven children developed 28 subsequent primary malignancies, compared with 4.5 expected malignances based on general population rates (observed-to-expected [O/E] ratio = 6.3 (95% confidence interval [95% CI], 4.2-9.1). The risk of developing a subsequent malignancy was increased among children with rhabdomyosarcoma (observed = 11 malignancies; O/E ratio = 7.7), fibromatons neoplasms (observed = 9 malignancies; O/E ratio = 5.8), and other specified STS (observed = 7 malignancies; O/E ratio = 6.5). Initial therapy with radiation and chemotherapeutic agents was associated with a significantly higher risk of second malignancies compared with surgery alone (O/E ratio = 15.2 vs. 1.4; P < 0.0001). Elevated risks were observed for acute myeloid leukemia, cutaneous melanoma, female breast cancer, and sarcomas of the bone and soft tissue, with generally higher risks among patients who initially received combined modality therapy. Excess cancers of the oral cavity were prominent among long-term survivors. For several children, the pattern of multiple malignancies was consistent with a genetic syndrome, particularly neurofibromatosis type 1 and Li-Fraumeni syndrome. CONCLUSIONS. The risk of second malignancies was increased for all histologic types of childhood STS and was particularly high among patients who received combined modality therapy. Published 2005 by the American Cancer Society. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Natl Hlth Res Scholars Program, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Curtis, RE (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, 6120 Execut Blvd,Room 7042, Bethesda, MD 20892 USA. EM rcurtis@mail.nih.gov NR 24 TC 52 Z9 55 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUN 1 PY 2005 VL 103 IS 11 BP 2391 EP 2396 DI 10.1002/cncr.21040 PG 6 WC Oncology SC Oncology GA 928OS UT WOS:000229282000025 PM 15852362 ER PT J AU Weeraratna, AT AF Weeraratna, AT TI A wnt-er wonderland - The complexity of wnt signaling in melanoma SO CANCER AND METASTASIS REVIEWS LA English DT Review DE Wnt; melanoma; frizzled; beta-catenin; Wnt5a; Jnk ID PLANAR CELL-POLARITY; PROTEIN-KINASE-C; CONVERGENT EXTENSION MOVEMENTS; VERTEBRATE AXIS FORMATION; STABILIZE BETA-CATENIN; NEURAL CREST FORMATION; MALIGNANT-MELANOMA; ENDOPLASMIC-RETICULUM; TRANSCRIPTION FACTOR; FRIZZLED HOMOLOGS AB Wnt signaling is a complex process that requires the interplay of several different proteins. In addition to a large cohort of Wnt ligands, and frizzled receptors, some Wnt pathways also require the presence of co-receptors. Wnt ligands may activate one of three pathways, the canonical pathway, involving beta-catenin, the planar cell polarity pathway and the Wnt/calcium pathway. All three pathways have different results for the cells in which they signal. Aberrant activation of these pathways can lead to the development and progression of several cancers. In this review we will discuss the different Wnt pathways, and their contribution to melanoma progression. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. EM weerarat@grc.nia.nih.gov NR 120 TC 51 Z9 53 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD JUN PY 2005 VL 24 IS 2 BP 237 EP 250 DI 10.1007/s10555-005-1574-z PG 14 WC Oncology SC Oncology GA 940VQ UT WOS:000230174400004 PM 15986134 ER PT J AU Sparreboom, A Loos, WJ Burger, H Sissung, TM Verweij, J Figg, WD Nooter, K Gelderblom, H AF Sparreboom, A Loos, WJ Burger, H Sissung, TM Verweij, J Figg, WD Nooter, K Gelderblom, H TI Effect of ABCG2 genotype on the oral Bioavailability of topotecan SO CANCER BIOLOGY & THERAPY LA English DT Article DE topotecan; ABCG2; pharmacokinetics; pharmacogenetics; accumulation; mutant; in vitro ID CANCER RESISTANCE PROTEIN; BREAST-CANCER; HALF-TRANSPORTER; P-GLYCOPROTEIN; OVARIAN-CANCER; PHARMACOKINETICS; EXPRESSION; PHARMACOGENOMICS; POLYMORPHISMS; LOCALIZATION AB ABCG2 ( BCRP/MXR/ABCP) functions as an efflux transporter for many agents, including topotecan, and the protein is expressed at high levels in the human intestine. Some individuals possess a nonsynonymous variant in the ABCG2 gene at nucleotide 421, substituting Lysine for Glutamine on position 141 at exon 5. The present pilot study indicates that this genotype results in a 30% reduced efflux transport of topotecan in vitro compared to the wild-type. In a preliminary fashion, the heterozygous CA allele observed in two patients was associated with a 1.34-fold increased oral bioavailability of topotecan compared to the bioavailability in ten patients with the wild-type allele (42.0% versus 31.4%; P = 0.037). It is suggested that the high frequency of the A allele in certain ethnic groups may have therapeutic implications for individuals treated with topotecan or other ABCG2 substrates. C1 Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Josephine Nefkens Inst, NL-3075 EA Rotterdam, Netherlands. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. RP Loos, WJ (reprint author), Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Josephine Nefkens Inst, Groene Hilledijk 301, NL-3075 EA Rotterdam, Netherlands. EM w.loos@erasmusmc.nl RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 23 TC 106 Z9 117 U1 0 U2 5 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUN PY 2005 VL 4 IS 6 BP 650 EP 653 PG 4 WC Oncology SC Oncology GA 022GE UT WOS:000236042600022 PM 15908806 ER PT J AU Shi, MQ Hao, S Quereshi, M Guo, WL Zheng, CY Xiang, J AF Shi, MQ Hao, S Quereshi, M Guo, WL Zheng, CY Xiang, J TI Significant tumor regression induced by microencapsulation of recombinant tumor cells secreting fusion protein SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE microencapsulation; recombinant cells; RM4-TNF-alpha; antitumor ID NECROSIS-FACTOR-ALPHA; PHASE-I; MURINE; CANCER; GAMMA; MICE; TNF; INVOLVEMENT; INHIBITION; INTERFERON AB Implantation of microencapsulated engineered cells secreting molecules with antineoplastic properties into tumors is a novel approach to cancer gene therapy. In this study, we constructed an engineered tumor cell line, VkCk/RM4-TNF-alpha, which secreted RM4/TNF-alpha fusion protein containing the chimeric antitumor antibody, F(ab')(2) (RM4), recognizing the tumor antigen TAG72, as well as the TNF-alpha moiety. The engineered cells were encapsulated into microencapsules. The RM4/TNF-alpha fusion protein secreted by encapsulated VkCk/RM4-TNF-alpha cells could be diffused through the microencapsule membrane into the supernatant and exert a cytotoxic effect on L929 cells in vitro. The antigen-specific binding-reactivity of RM4/TNF-alpha for the TAG72 antigen was confirmed by immunohistochemical staining of rat LMCR tumor cells which expressed TAG72 antigen. Implantation of microencapsules containing VkCk/RM4-TNF-alpha cells into LMCR tumors in rats induced tumor regression as a result of tumor necrosis formation. Taken together, these data suggest that microencapsulation of recombinant tumor cells secreting antibody/cytokine fusion protein might be an alternative approach in the treatment of cancers. C1 Univ Saskatchewan, Saskachewan Canc Agcy, Dept Oncol, Res Unit, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Saskachewan Canc Agcy, Dept Microbiol, Res Unit, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Saskachewan Canc Agcy, Dept Immunol, Res Unit, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Saskachewan Canc Agcy, Dept Pathol, Saskatoon, SK S7N 4H4, Canada. Univ Saskatchewan, Saskachewan Canc Agcy, Dept Geog, Saskatoon, SK S7N 4H4, Canada. Natl Inst Dental Res, Gene Therapy Branch, NIH, Bethesda, MD USA. RP Xiang, J (reprint author), Univ Saskatchewan, Saskachewan Canc Agcy, Dept Oncol, Res Unit, 20 Campus Dr, Saskatoon, SK S7N 4H4, Canada. EM jxiang@scf.sk.ca RI Shi, Meiqing/K-3665-2016 NR 30 TC 6 Z9 6 U1 1 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD JUN PY 2005 VL 20 IS 3 BP 260 EP 266 DI 10.1089/cbr.2005.20.260 PG 7 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 948DO UT WOS:000230696400003 PM 15989471 ER PT J AU Yang, YL Ludwig, RL Jensen, JP Pierre, SA Medaglia, MV Davydov, IV Safiran, YJ Oberoi, P Kenten, JH Phillips, AC Weissman, AM Vousden, KH AF Yang, YL Ludwig, RL Jensen, JP Pierre, SA Medaglia, MV Davydov, IV Safiran, YJ Oberoi, P Kenten, JH Phillips, AC Weissman, AM Vousden, KH TI Small molecule inhibitors of HDM2 ubiquitin ligase activity stabilize and activate p53 in cells SO CANCER CELL LA English DT Article ID RIBOSOMAL-PROTEIN L23; TUMOR-SUPPRESSOR; IN-VIVO; TERMINAL UBIQUITINATION; CONJUGATING ENZYME; NUCLEAR EXPORT; CANCER-THERAPY; MDM2; DEGRADATION; APOPTOSIS AB The p53 tumor suppressor protein is regulated by its interaction with Ill which serves as a ubiquitin ligase (E3) to target p53 for degradation. We have identified a family of small molecules (HL198) that inhibits HDM2's E3 activity. These compounds show some specificity for HDM2 in vitro, although at higher concentrations effects on unrelated RING and HECT domain E3s are detectable, which could be due, at least in part, to effects on E2-ubiquitin thiol-ester levels. In cells, the compounds allow the stabilization of p53 and HDM2 and activation of p53-dependent transcription and apoptosis, although other p53-independent toxicity was also observed. C1 NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, NIH, Frederick, MD 21702 USA. Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. MesoScale Diagnost LLC, MesoScale Discovery, Gaithersburg, MD 20877 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Weissman, AM (reprint author), NCI, Lab Prot Dynam & Signaling, Canc Res Ctr, NIH, 1050 Boyles St, Frederick, MD 21702 USA. EM amw@nih.gov NR 65 TC 246 Z9 258 U1 0 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JUN PY 2005 VL 7 IS 6 BP 547 EP 559 DI 10.1016/j.ccr.2005.04.029 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 937WX UT WOS:000229958000008 PM 15950904 ER PT J AU Wacholder, S AF Wacholder, S TI Publication environment and broad investigation of the genome SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID ASSOCIATION; FALSE C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 4 TC 12 Z9 12 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 JUN PY 2005 VL 14 IS 6 BP 1361 EP 1361 DI 10.1158/1055-9965.EPI-05-0404 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935GB UT WOS:000229766600004 PM 15941938 ER EF