FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Birlea, S Birlea, M Cimponeriu, D Apostol, P Cosgarea, R Gavrila, L Tigan, S Costin, G Das, P AF Birlea, S Birlea, M Cimponeriu, D Apostol, P Cosgarea, R Gavrila, L Tigan, S Costin, G Das, P TI Autoimmune diseases and vitamin D receptor Apa-I polymorphism are associated with vitiligo in a small inbred Romanian community SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE vitiligo; autoimmunity; associated diseases; gene polymorphism; vitamin D receptor ID GENERALIZED VITILIGO; RHEUMATOID-ARTHRITIS; SUSCEPTIBILITY; GENE; EPIDEMIOLOGY; MELANOCYTES; FAMILIES; ONSET; SLEV1 AB Vitiligo has been associated with the host's genetic profile, metabolic abnormality and immunostatus. The purpose of this study was to investigate the association of vitiligo with autoimmune diseases for 31 out of 39 subjects with vitiligo and their first-degree relatives living in a small Caucasian inbred rural community. They were compared with healthy individuals. A 2.28% prevalence of vitiligo was calculated and the presence of consanguine marriages (72.3%) was noted for this community. Our results indicate an increased prevalence of thyroidopathies, diabetes mellitus and rheumatoid arthritis in families with vitiligo. We also show that the Apa-I polymorphism of the vitamin D receptor gene is associated with vitiligo. This is the first study of its kind performed in Romania suggesting that the vitamin D receptor gene might play a role in the aetiopathogenesis of skin depigmentation. C1 Zalau Cty Hosp, Dept Dermatol, Zalau 40008, Romania. Zalau Cty Hosp, Dept Neurol, Zalau 40008, Romania. Univ Bucharest, Dept Genet, Bucharest, Romania. Cluj Napoca Univ Med, Dept Dermatol, Cluj Napoca, Romania. Cluj Napoca Univ Med, Dept Biostat & Med Informat, Cluj Napoca, Romania. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Dept Pathol, NL-1105 AZ Amsterdam, Netherlands. RP Birlea, S (reprint author), Zalau Cty Hosp, Dept Dermatol, Corneliu Coposu St 17, Zalau 40008, Romania. EM S_Birlea@yahoo.com NR 35 TC 18 Z9 21 U1 0 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2006 VL 86 IS 3 BP 209 EP 214 DI 10.2340/00015555-0093 PG 6 WC Dermatology SC Dermatology GA 048ZZ UT WOS:000237986400004 PM 16710576 ER PT J AU Peila, R Launer, LJ AF Peila, R. Launer, L. J. TI Inflammation and dementia: epidemiologic evidence SO ACTA NEUROLOGICA SCANDINAVICA LA English DT Article; Proceedings Paper CT Conference on Cholesterol, Alzheimers Disease and Statins (CAS) CY APR 14-15, 2005 CL Stockholm, SWEDEN SP Swedish Fdn Old Servants, Int Task Force Prevent Coronary Heart Dis DE anti-inflammatory medications; cytokines; dementia; inflammation; single nucleotide polymorphism ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; INTERLEUKIN-1 GENE POLYMORPHISMS; SPORADIC ALZHEIMERS-DISEASE; JAPANESE-AMERICAN MEN; COGNITIVE DECLINE; AFRICAN-AMERICAN; RISK; ASSOCIATION; ONSET; ATHEROSCLEROSIS AB Based on experimental and neuropathologic studies, inflammation is postulated to play a central role in processes leading to neurodegeneration as well as vascular injury. To better understand the role of inflammation in cognitive disorders (CD), identify potential biomarkers for CD, and select individuals who may have a genetic susceptibility to CD, several different measures of inflammation have been employed in epidemiologic studies of CD, which are reviewed An inverse association of non-steroidal anti-inflammatory here. medications has been consistently reported. More variable are reports on the associations of various serum markers of cytokines to CD. There are few epidemiologic studies that have examined the association of CD and single nucleotide polymorphisms (SNP) regulating cytokines, although these have been examined in clinical case-control series. Data are summarized on the association of interleukin-I SNPs from the Honolulu Asia Aging Study. There are many outstanding questions about the role of inflammation in CD and how best to measure it in the context of population-based studies. C1 NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Launer, LJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. EM launerl@nia.nih.gov NR 42 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-6314 J9 ACTA NEUROL SCAND JI Acta Neurol. Scand. PY 2006 VL 114 SU 185 BP 102 EP 106 DI 10.1111/j.1600-0404.2006.00693.x PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 069HX UT WOS:000239438100016 ER PT J AU Goransson, M Magnusson, A Heilig, M AF Goransson, M Magnusson, A Heilig, M TI Identifying hazardous alcohol consumption during pregnancy: implementing a research-based model in real life SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE alcohol during pregnancy; screening antenatal care ID DISORDERS IDENTIFICATION TEST; SCREENING INSTRUMENTS; DRINKING; WOMEN; RISK; PREVALENCE AB Aims. It has been repeatedly demonstrated that hazardous alcohol use during pregnancy is rarely detected in regular antenatal care, and that detection can be markedly improved using. systematic screening. A major challenge is to translate research-based strategies into regular antenatal care. Here, we examined whether a screening strategy using the Alcohol Use Disorder Test (AUDIT) and time-line follow-back (TLFB) could be implemented under naturalistic conditions and within available resources, and whether it would improve detection to the extent previously shown in a research context. Methods. Regular midwives at a large antenatal care clinic were randomized to receive brief training and then implement AUDIT and TLFB ("intervention"); or to a waiting-list control group continuing to deliver regular care ("control"). In the intervention condition, AUDIT was used to collect data about alcohol use during the year preceding pregnancy, and TLFB to assess actual consumption during the first trimester. Data were collected from new admissions over 6 months. Results. Drop out was higher among patients of the intervention group than control midwives, 14% (23/162) versus 0% (0/153), and p < 0.0001. A one-day training session combined with continuous expert support was sufficient to implement systematic screening with AUDIT and TLFB largely within resources of regular antenatal care. The use of these instruments identified patients with hazardous consumption during the year preceding pregnancy i.e. AUDIT score 6 or higher (17%, 23/139), and patients with ongoing consumption exceeding 70 g/week and/or binge consumption according to TLFB (17%, 24/139), to a significantly higher degree than regular antenatal screening (0/162). The AUDIT- and TLFB-positive populations overlapped partially, with 36/139 subjects screening positive with either of the instrument and 11/139 were positive for both. Conclusions. We confirm previous findings that alcohol use during pregnancy is more extensive in Sweden than has generally been realized. Systematic screening using AUDIT and TLFB detects hazardous use in a manner which regular antenatal care does not. This remains true under naturalistic conditions, following minimal training of regular antenatal care staff, and can be achieved with minimal resources. The proposed strategy appears attractive for broad implementation. C1 Karolinska Inst, NEUROTEC, Div Psychiat, Stockholm, Sweden. NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. RP Goransson, M (reprint author), Huddinge Univ Hosp, S-14186 Huddinge, Sweden. EM mona.goransson@slpo.sll.se OI Heilig, Markus/0000-0003-2706-2482 NR 31 TC 9 Z9 9 U1 5 U2 7 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PY 2006 VL 85 IS 6 BP 657 EP 662 DI 10.1080/00016340600589677 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 051UV UT WOS:000238188100003 PM 16752255 ER PT J AU Freeman, MP Hibbeln, JR Wisner, KL Brumbach, BH Watchman, M Gelenberg, AJ AF Freeman, MP Hibbeln, JR Wisner, KL Brumbach, BH Watchman, M Gelenberg, AJ TI Randomized dose-ranging pilot trial of omega-3 fatty acids for postpartum depression SO ACTA PSYCHIATRICA SCANDINAVICA LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-College-of-Neuropsychopharmacology CY DEC 12-16, 2004 CL San Juan, PR SP Vanderbilt Univ, Sch Med, Dept Psychiaty, Amer Coll Neuropsychopharmacol DE postpartum period; depression; omega-3 fatty acids ID PLACEBO-CONTROLLED TRIAL; ESSENTIAL FATTY-ACIDS; DOUBLE-BLIND; POSTNATAL DEPRESSION; MAJOR DEPRESSION; FISH-OIL; PREGNANCY; DISORDER; CONSUMPTION; BOOTSTRAP AB Objective: Postpartum depression (PPD) affects 10-15% of mothers. Omega-3 fatty acids are an intriguing potential treatment for PPD. Method: The efficacy of omega-3 fatty acids for PPD was assessed in an 8-week dose-ranging trial. Subjects were randomized to 0.5 g/day (n = 6), 1.4 g/day (n = 3), or 2.8 g/day (n = 7). Results: Across groups, pretreatment Edinburgh Postnatal Depression Scale (EPDS) and Hamilton Rating Scale for Depression (HRSD) mean scores were 18.1 and 19.1 respectively; post-treatment mean scores were 9.3 and 10.0. Percent decreases on the EPDS and HRSD were 51.5% and 48.8%, respectively; changes from baseline were significant within each group and when combining groups. Groups did not significantly differ in pre- or post-test scores, or change in scores. The treatment was well tolerated. Conclusion: This study was limited by small sample size and lack of placebo group. However, these results support further study of omega-3 fatty acids as a treatment for PPD. C1 Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Psychiat, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Obstet & Gynecol, Tucson, AZ 85724 USA. Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Nutr Sci, Tucson, AZ 85724 USA. Univ Pittsburgh, Ctr Med, NIAAA, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Ctr Med, Dept Psychiat Obstet & Gynecol & Reprod Sci & Epi, Pittsburgh, PA 15260 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85724 USA. RP Freeman, MP (reprint author), Univ Arizona, Coll Med, Womens Mental Hlth Program, Dept Psychiat, 1501 N Campbell Ave,POB 245002, Tucson, AZ 85724 USA. EM marienef@email.arizona.edu FU NIMH NIH HHS [R01 MH 60335, 1 K23 MH66265-01] NR 29 TC 110 Z9 113 U1 2 U2 16 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-690X J9 ACTA PSYCHIAT SCAND JI Acta Psychiatr. Scand. PD JAN PY 2006 VL 113 IS 1 BP 31 EP 35 DI 10.1111/j.1600-0447.2005.00660.x PG 5 WC Psychiatry SC Psychiatry GA 008IS UT WOS:000235034600005 PM 16390366 ER PT J AU Flanzer, JP AF Flanzer, Jerry P. BE Liddle, HA Rowe, CL TI Health services with drug-abusing adolescents: the next frontier of research SO ADOLESCENT SUBSTANCE ABUSE: RESEARCH AND CLINICAL ADVANCES LA English DT Article; Book Chapter ID SUBSTANCE-ABUSE; COST-BENEFIT; FOLLOW-UP; OUTCOMES; PREVALENCE; ILLNESS; CARE; INTERVENTIONS; DEPENDENCE; DATOS C1 NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Flanzer, JP (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, 6001 Exec Blvd,Room 4224, Bethesda, MD 20892 USA. NR 58 TC 2 Z9 2 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52182-358-6 PY 2006 BP 204 EP 219 DI 10.1017/CBO9780511543968.011 D2 10.1017/CBO9780511543968 PG 16 WC Substance Abuse SC Substance Abuse GA BXL27 UT WOS:000296285200011 ER PT S AU Bianco, P Kuznetsov, SA Riminucci, M Robey, PG AF Bianco, Paolo Kuznetsov, Sergei A. Riminucci, Mara Robey, Pamela Gehron BE Klimanskaya, I Lanza, R TI Postnatal skeletal stem cells SO ADULT STEM CELLS SE Methods in Enzymology LA English DT Review; Book Chapter ID MARROW STROMAL CELLS; FORMATION IN-VITRO; BONE-MARROW; PROGENITOR CELLS; OSTEOGENESIS IMPERFECTA; HEMATOPOIETIC TISSUES; MONOCLONAL-ANTIBODY; PRECURSOR CELLS; EXPRESSION; DIFFERENTIATION AB Postnatal skeletal stem cells are a subpopulation of the bone marrow stromal cell network. To date, the most straightforward way of assessing the activity of skeletal stem cells within the bone marrow stromal cell (BMSC) population is via analysis of the rapidly adherent, colony-forming unit-fibroblast (CFU-F), and their progeny, BMSCs. Several in vitro methods are employed to determine the differentiation capacity of BMSCs, using osteogenic and adipogenic "cocktails" and staining protocols, and pellet cell culture for chondrogenic differentiation. However, true differentiation potential is best determined by in vivo transplantation in either closed or open systems. By in vivo transplantation, similar to 10% of the clonal strains are able to form bone, stroma, and marrow adipocytes, and are true skeletal stem cells. Furthermore, when derived from patients or animal models with abnormalities in gene expression, they recapitulate the disease phenotype on in vivo transplantation. Although ex vivo expansion of BMSCs inevitably dilutes the skeletal stem cells, when used en masse, they are attractive candidates for reconstruction of segmental bone defects, and as targets for gene therapy. C1 Univ Roma La Sapienza, Dept Expt Med & Pathol, I-00161 Rome, Italy. NIH, Dept Craniofacial & Skeletal Dis, Bethesda, MD 20892 USA. Univ Aquila, I-67100 Laquila, Italy. RP Bianco, P (reprint author), Univ Roma La Sapienza, Dept Expt Med & Pathol, Piazzale Aldo Moro 5, I-00161 Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Intramural NIH HHS NR 58 TC 94 Z9 99 U1 0 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-373650-1 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 419 BP 117 EP 148 DI 10.1016/S0076-6879(06)19006-0 PG 32 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFL62 UT WOS:000242860600006 PM 17141054 ER PT S AU Palena, C Abrams, SI Schlom, J Hodge, JW AF Palena, Claudia Abrams, Scott I. Schlom, Jeffrey Hodge, James W. BE VandeWoude, GF Klein, G TI Cancer vaccines: Preclinical studies and novel strategies SO ADVANCES IN CANCER RESEARCH, VOL 95 SE Advances in Cancer Research LA English DT Review; Book Chapter ID COLONY-STIMULATING FACTOR; T-LYMPHOCYTE EPITOPE; HUMAN CARCINOEMBRYONIC ANTIGEN; MULTIPLE COSTIMULATORY MOLECULES; EXPERIMENTAL MAMMARY-CARCINOMA; ANTITUMOR IMMUNE-RESPONSE; TRANSGENIC MOUSE MODEL; PEPTIDE-BASED VACCINES; HUMAN DENDRITIC CELLS; SINGLE-CHAIN IL-12 AB The development of cancer vaccines, aimed to enhance the immune response against a tumor, is a promising area of research. A better understanding of both the molecular mechanisms that govern the generation of an effective immune response and the biology of a tumor has contributed to substantial progress in the field. Areas of intense investigation in cancer immunotherapy will be discussed here, including: (1) the discovery and characterization of novel tumor antigens to be used as targets for vaccination; (2) the investigation of different vaccine-delivery modalities such as cellular-based vaccines, protein- and peptide-based vaccines, and vector-based vaccines; (3) the characterization of biological adjuvants to further improve the immunogenicity of a vaccine; and (4) the investigation of multimodal therapies where vaccines are being combined with other oncological treatments such as radiation and chemotherapy. A compilation of data from preclinical studies conducted in vitro as well as in animal models is presented here. The results from these studies would certainly support the development of new vaccination strategies toward cancer vaccines with enhanced clinical efficacy. (c) 2006 Elsevier Inc. C1 NCI, Lab Tumor Immunol & Biol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Palena, C (reprint author), NCI, Lab Tumor Immunol & Biol, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 171 TC 30 Z9 32 U1 2 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-230X BN 0-12-006695-5 J9 ADV CANCER RES JI Adv.Cancer Res. PY 2006 VL 95 BP 115 EP 145 DI 10.1016/S0065-230X(06)95004-0 PG 31 WC Oncology SC Oncology GA BEY90 UT WOS:000240180900004 PM 16860657 ER PT B AU Ahmet, I Lakatta, EG Talan, MI AF Ahmet, I. Lakatta, E. G. Talan, M. I. BE Kimchi, A TI Pharmacological stimulation of beta(2)-adrenergic receptors (beta(2)AR) enhances therapeutic effectiveness of beta 1AR blockade in rodent dilated ischemic cardiomyopathy SO ADVANCES IN HEART DISEASE LA English DT Proceedings Paper CT 12th World Congress on Heart Disease CY JUL 16-19, 2005 CL Vancouver, CANADA SP Int Acad Cardiol ID CARDIAC MYOCYTE APOPTOSIS; HEART-FAILURE AB We investigated whether the therapeutic effects of beta(1)AR blockade, most recommended treatment for chronic heart failure (CHF), would be enhanced by addition of chronic pharmacological beta(2)AR stimulation. Metoprolol, a BAR blocker, given alone (beta(1)) or in combination with beta(2)AR agonist, fenoterol (beta(1)beta(2)) were administered to rats via drinking water for 6 weeks, beginning 2 weeks following permanent coronary ligation. The progression of left ventricular (LV) remodeling, infarct expansion, and development of CHF was assessed by repeated echocardiography, pressure-volume loop analyses, and histological evaluation. beta(1)beta(2) prevented LV remodeling, MI expansion and cardiornyocytes hypertrophy to a greater degree than beta(1) due, in large part, to a vasodilatory effect of beta(2)AR stimulation and thus improvement of arterio-ventricular n-fismatch. The abnormal diastolic performance improved only in beta(1)beta(2). beta(1)beta(2) treatment reduced apoptosis throughout myocardium, but beta(1) reduced apoptopsis only in the areas remote from MI. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Ahmet, I (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 978-88-7587-192-5 PY 2006 BP 443 EP 449 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BFP27 UT WOS:000243576100071 ER PT S AU Robyn, J Metcalfe, DD AF Robyn, J Metcalfe, DD BE Alt, FW TI Systemic mastocytosis SO ADVANCES IN IMMUNOLOGY, VOL 89 SE Advances in Immunology LA English DT Review; Book Chapter ID STEM-CELL-FACTOR; HUMAN MAST-CELLS; GASTROINTESTINAL STROMAL TUMORS; C-KIT MUTATION; RECEPTOR TYROSINE KINASE; COLONY-STIMULATING FACTOR; FC-EPSILON-RI; IDIOPATHIC HYPEREOSINOPHILIC SYNDROME; ENDOTHELIAL GROWTH-FACTOR; BLOOD MONONUCLEAR-CELLS AB Systemic mastocytosis is a fascinating disease with diverse clinical features. There have been numerous advances ill understanding the basis of clinical manifestations of this disease and of its molecular pathogenesis in the last If several decades. The development of methods to study mast cell biology using cell culture and murine models has proven invaluable ill this regard. Clarification of the roles of mast cells ill various biological processes has expanded our understanding of their importance ill innate immunity, as well as allergy. New diagnostic methods have allowed the design of detailed criteria to assist ill distinguishing reactive mast cell hyperplasia from systemic mastocytosis. Variants and subvariants of systemic mastocytosis have been defined to assist ill determining prognosis mid ill management of the disease. Elucidation of the roles of the Kit receptor tyrosine kinase and signal transduction pathway activation has contributed to development of potential targeted therapeutic approaches that may prove useful in the future. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Robyn, J (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 391 TC 20 Z9 21 U1 1 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022490-9 J9 ADV IMMUNOL JI Adv.Immunol. PY 2006 VL 89 BP 169 EP 243 DI 10.1016/S0065-2776(05)89005-4 PG 75 WC Immunology SC Immunology GA BEA18 UT WOS:000236402300005 PM 16682275 ER PT S AU Waldmann, TA Morris, JC AF Waldmann, TA Morris, JC BE Allison, JP Franoff, G TI Development of antibodies and chimeric molecules for cancer immunotherapy SO ADVANCES IN IMMUNOLOGY, VOL 90: CANCER IMMUNOTHERAPY SE Advances in Immunology LA English DT Review; Book Chapter ID ACUTE MYELOID-LEUKEMIA; NON-HODGKINS-LYMPHOMA; GROWTH-FACTOR RECEPTOR; ANTI-CD20 MONOCLONAL-ANTIBODY; CHRONIC LYMPHOCYTIC-LEUKEMIA; PHASE-II MULTICENTER; B-CELL LYMPHOMA; IBRITUMOMAB TIUXETAN RADIOIMMUNOTHERAPY; METASTATIC COLORECTAL-CANCER; REGULATORY T-CELLS AB Monoclonal antibodies are among the most rapidly expanding class of therapeutics for cancer treatment. Monoclonal antibodies targeting non-Hodgkin's lymphoma (NHL), Her-2/neu highly expressing metastatic breast cancer, colorectal cancer, acute myelogenous leukemia, and B-cell chronic lymphocytic leukemia (CLL) have received FDA approval. Promising new targets for antibody therapy include cellular growth factor receptors, mediators of tran,or-driven neo-angiogenesis, as well as host negative immunoregulatory checkpoints that impede an effective immune response to neoplasia. Antibody efficacy has been increased by genetic engineering to humanize the antibodies and to increase their effector functions including antibody dependent cellular cytotoxicity. Furthermore, antibodies have been armed with cytokines, chemotherapeutic agents, toxins, and radionuclides to augment their efficacy as tumor cytotoxic agents. As a consequence of these advances, 30 years after their first development, monoclonal antibodies have become an important standard approach for the therapy of neoplasia with 19 therapeutic monoclonal antibodies now approved by the FDA including 8 for the treatment of cancer. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 193 TC 29 Z9 30 U1 0 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022489-5 J9 ADV IMMUNOL JI Adv.Immunol. PY 2006 VL 90 BP 83 EP 131 DI 10.1016/S0065-2776(06)90003-0 PG 49 WC Immunology SC Immunology GA BEC59 UT WOS:000236802500003 PM 16730262 ER PT S AU Goddard, J Gee, T Wang, HL Gorbach, AM AF Goddard, James Gee, Timothy Wang, Hengliang Gorbach, Alexander M. BE Bebis, G Boyle, R Parvin, B Koracin, D Remagnino, P Nefian, A Meenakshisundaram, G Pascucci, V Zara, J Molineros, J Theisel, H Malzbender, T TI Segmentation-based registration of organs in intraoperative video sequences SO Advances in Visual Computing, Pt 2 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Proceedings Paper CT 2nd International Symposium on Visual Computing CY NOV 06-08, 2006 CL Lake Tahoe, NV SP UNR Comp Vis Lab, Desert Res Inst, NASA, Siemens, Intel, DigitalPersona, Equinox Corp, HP, nVIDA, Ford Corp, Mitsubish, UtopiaCompression AB Intraoperative optical imaging of exposed organs in visible, near-infrared, and infrared (IR) wavelengths in the body has the potential to be useful for real-time assessment of organ viability and image guidance during surgical intervention. However, the motion of the internal organs presents significant challenges for fast analysis of recorded 2D video sequences. The movement observed during surgery, due to respiration, cardiac motion, blood flow, and mechanical shift accompanying the surgical intervention, causes organ reflection in the image sequence, making optical measurements for further analysis challenging. Correcting alignment is difficult in that the motion is not uniform over the image. This paper describes a Canny edge-based method for segmentation of the specific organ or region under study, along with a moment-based registration method for the segmented region. Experimental results are provided for a set of intraoperative IR image sequences. C1 Oak Ridge Natl Lab, Image Sci & Machine Vis Grp, Oak Ridge, TN 37831 USA. USN, Med Res Ctr, Silver Spring, MD 20910 USA. NIH, Bethesda, MD 20892 USA. RP Goddard, J (reprint author), Oak Ridge Natl Lab, Image Sci & Machine Vis Grp, Oak Ridge, TN 37831 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 J9 LECT NOTES COMPUT SC PY 2006 VL 4292 BP 835 EP 842 PG 8 WC Computer Science, Artificial Intelligence; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BFN05 UT WOS:000243132300083 ER PT J AU Napravnik, S Eron, JJ McKaig, RG Heine, AD Menezes, P Quinlivan, EB AF Napravnik, Sonia Eron, Joseph J., Jr. McKaig, Rosemary G. Heine, Amy D. Menezes, Prema Quinlivan, E. Byrd TI Factors associated with fewer visits for HIV primary care at a tertiary care center in the Southeastern US SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; UNITED-STATES; INFECTED ADULTS; RURAL-AREAS; HEALTH AB In this study we sought to evaluate sociodemographic and clinical characteristics associated with decreased access to HIV outpatient care in a University-based clinic in the Southeastern U.S. The number of HIV outpatient clinic visits per personyear was estimated among 1,404 HIV infected individuals participating in a large observational clinical cohort study. On average, participants attended 3.38 visits per person-year (95% CI =3.32, 3.44), with 71% attending fewer than 4 visits per year. Younger persons, of Black race/ethnicity, with less advanced HIV disease, and a shorter time from entry to HIV care, had poorer access to care, as did participants without health insurance and residing a greater distance from care. Vulnerable subgroups of HIV infected patients in the South have decreased access to ongoing HIV health care. Interventions including more intensive counseling and active outreach for newly HIV diagnosed individuals and support with obtaining health insurance and transportation may lead to improved outcomes. C1 Univ N Carolina, Div Infect Dis, Sch Med, Chapel Hill, NC 27599 USA. NIAID, Bethesda, MD 20892 USA. RP Napravnik, S (reprint author), Univ N Carolina, Div Infect Dis, Sch Med, 211-A W Cameron Ave, Chapel Hill, NC 27599 USA. EM napravs@med.unc.edu FU NIAID NIH HHS [P30 AI 50410, P30 AI050410] NR 15 TC 25 Z9 25 U1 2 U2 4 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PY 2006 VL 18 SU 1 BP S45 EP S50 DI 10.1080/09540120600838928 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 090MU UT WOS:000240956200007 PM 16938674 ER PT J AU Herbeuval, JP Shearer, GM AF Herbeuval, JP Shearer, GM TI Are Blockers of gp120/CD4 interaction effective inhibitors of HIV-1 lmmunopathogenesis? SO AIDS REVIEWS LA English DT Article DE HIV-1 immunopathogenesis; interferon-alpha; plasmacytoid dendritic cells; CD4(+) T-cell apoptosis; TRAIL/DR5; sCD4-IgG therapy ID APOPTOSIS-INDUCING LIGAND; TUMOR-NECROSIS-FACTOR; CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; TRAIL-INDUCED APOPTOSIS; DENDRITIC CELLS; HIV-1-INFECTED PATIENTS; DISEASE PROGRESSION; DEATH DOMAIN AB Objective: The immunopathogenic mechanisms that result in the depletion of CD4(+) T-cells after HIM infection remain controversial. We consider here mechanisms that have been suggested, and propose a data-supported model in which CD4(+) T-cells undergo apoptosis that is signaled by the binding of viral gp120 to cellular CD4. Procedures: Blood leucocytes from HIV-1-uninfected donors, including CD4(+) and CD8(+) T-cells, monocytes, myeloid and plasmacytoid dendritic cells (pDC) were cultured with either infectious or noninfectious HIV-1. The cultures were tested for expression of interferon-alpha, TRAIL, DR5 and apoptosis. Inhibitors of IFN alpha, TRAIL, DR5 and gp120/CD4 binding were added to the cultures. Ex vivo studies were performed using peripheral blood mononuclear cells (PBMC) from HIV-1-infected patients to test the validity of our in vitro findings. Findings: Both infectious and noninfectious HIM induced pDC to produce IFN alpha, which induced expression of TRAIL by CD4(+) but not CD8(+) T-cells. CD4(+) T-cells expressed the TRAIL death receptor 5 (DR5), upon HIM binding to CD4. Antibodies against TRAIL and DR5 partly inhibited apoptosis. However, soluble CD4 (sCD4-IgG) efficiently blocked IFNa production, TRAIL and DR5 expression and apoptosis of T helper cells. Studies of HIV-1-infected patients' PBMC indicated increased plasma TRAIL production and CD4(+) T-cell DR5 expression, which correlated directly with viral load and inversely with CD4 count. Conclusion: Noninfectious interactions between HIM and CD4 are major contributors to CD4+ T-cell death via IFN alpha-induced TRAIL expression and HIV-1-induced DR5 expression on CD4(+) T-cells. Since noninfectious as well as infectious HIM induces the death cascade resulting in selective apoptosis of CD4(+) T-cells, these HIV-1/CD4-dependent binding events would not necessarily be reflected in HIM RNA and DNA expression by the CD4(+) target T-cells. Because each step of this model leading to apoptosis requires the binding of gp120 to CD4, we suggest that molecules which block this very early event in virus/target cell interaction will be effective in preventing or reducing the depletion of CD4(+) T-cells during progression to AIDS. The above mechanisms and the effect of sCD4-IgG are summarized in our proposed Model. C1 NCI, NIH, Expt Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Shearer, GM (reprint author), NCI, NIH, Expt Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. EM shearerg@mail.nih.gov NR 59 TC 10 Z9 11 U1 0 U2 1 PU PERMANYER PUBLICATIONS PI BARCELONA PA MALLORCA, 310, BARCELONA, SPAIN SN 1139-6121 J9 AIDS REV JI Aids Rev. PD JAN-MAR PY 2006 VL 8 IS 1 BP 3 EP 8 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 029AI UT WOS:000236529800001 PM 16736946 ER PT J AU Grant, BF Dawson, DA AF Grant, Bridget F. Dawson, Deborah A. TI Introduction to the National Epidemiologic Survey on Alcohol and Related Conditions SO ALCOHOL RESEARCH & HEALTH LA English DT Editorial Material C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Bethesda, MD USA. NR 0 TC 80 Z9 80 U1 0 U2 4 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2006 VL 29 IS 2 BP 74 EP 78 PG 5 WC Substance Abuse SC Substance Abuse GA 101ZO UT WOS:000241780600001 ER PT J AU Falk, DE Yi, HY Hiller-Sturmhofel, S AF Falk, Daniel E. Yi, Hsiao-Ye Hiller-Sturmhofel, Susanne TI An epidemiologic analysis of co-occurring alcohol and tobacco use and disorders - Findings from the National Epidemiologic Survey on Alcohol and Related Conditions SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE age differences; epidemiology; alcohol and other drug use disorders (AODD); racial differences; tobacco; nicotine; comorbidity; ethnic differences; gender differences ID NICOTINE DEPENDENCE; UNITED-STATES; SMOKING; DRINKING AB The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) sought to determine the prevalence of drinking, smoking, and associated disorders in the general population. This survey, which includes a large representative sample of the adult population of the United States, found that drinking rates were highest among young adults and declined with increasing age. Rates of smoking and co-use of alcohol and tobacco were highest among the youngest respondents and declined thereafter. Similar patterns existed for the presence of alcohol use disorders (AUDs), nicotine dependence, and comorbidity between AUDs and nicotine dependence. Among ethnic/racial groups evaluated, Whites were most likely to drink and Native Americans/Alaskan Natives were most likely to smoke and to have an AUD, nicotine dependence, or comorbid AUD and nicotine dependence. Finally, the rates of tobacco use, daily tobacco use, and nicotine dependence increased with increasing levels of alcohol consumption and the presence of an AUD. These,findings have important implications for the development of prevention and intervention approaches. C1 CSR Inc, NIAAA, Alcohol Epidemiol Data Syst, Arlington, VA USA. RP Falk, DE (reprint author), CSR Inc, NIAAA, Alcohol Epidemiol Data Syst, Arlington, VA USA. NR 19 TC 202 Z9 207 U1 2 U2 12 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2006 VL 29 IS 3 BP 162 EP 171 PG 10 WC Substance Abuse SC Substance Abuse GA 146NE UT WOS:000244940400001 PM 17373404 ER PT J AU Zakhari, S AF Zakhari, Samir TI Overview: How is alcohol metabolized by the body? SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE ethanol-to-acetaldehyde metabolism; alcohol dehydrogenase (ADH); aldehyde dehydrogenase (ALDH); acetaldehyde; acetate; cytochrome P450 2E1 (CYP2E1); catalase; reactive oxygen species (ROS); blood alcohol concentration (BAC); liver; stomach; brain; fetal alcohol effects; genetics and heredity; ethnic group; hypoxia ID FIRST-PASS METABOLISM; LIVER-DISEASE; GENETIC POLYMORPHISMS; ETHANOL-METABOLISM; ALDEHYDE DEHYDROGENASE; ACETALDEHYDE ADDUCTS; HEPATIC INFLAMMATION; 1ST-PASS METABOLISM; REACTIVE OXYGEN; PROTEIN ADDUCTS AB Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2EI), and catalase. Variations in the genes for these enzymes have been found to influence alcohol consumption, alcohol-related tissue damage, and alcohol dependence. The consequences of alcohol metabolism include oxygen deficits (i.e., hypoxia) in the liver; interaction between alcohol metabolism byproducts and other cell components, resulting in the formation of harmful compounds (i.e., adducts); formation of highly reactive oxygen-containing molecules (i.e., reactive oxygen species [ROS]) that can damage other cell components; changes in the ratio of NADH to NAD(+) (i.e., the cell's redox state); tissue damage; fetal damage, impairment of other metabolic processes; cancer; and medication interactions. Several issues related to alcohol metabolism require further research. C1 NIAAA, Div Metab & Hlth Effects, Bethesda, MD USA. RP Zakhari, S (reprint author), NIAAA, Div Metab & Hlth Effects, Bethesda, MD USA. NR 62 TC 187 Z9 198 U1 12 U2 61 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2006 VL 29 IS 4 BP 245 EP 254 PG 10 WC Substance Abuse SC Substance Abuse GA 194RW UT WOS:000248362500001 PM 17718403 ER PT J AU Ramchandani, VA O'Connor, S AF Ramchandani, Vijay A. O'Connor, Sean TI Studying alcohol elimination using the alcohol clamp method SO ALCOHOL RESEARCH & HEALTH LA English DT Article DE alcohol absorption; ethanol metabolism; alcohol clamp method; alcohol elimination; alcohol elimination rate (AER); breath alcohol concentration (BrAC); intravenous infusion; pharmacokinetics; pharmacodynamics; Michaelis-Menten kinetics; alcohol dehydrogenase (ADH); acetaldehyde dehydrogenase (ALDH); genetic polymorphisms; liver; food intake ID FAMILY HISTORY; JEWISH POPULATION; MG-PERCENT; METABOLISM; PHARMACOKINETICS; POLYMORPHISM; ASSOCIATION; ABSORPTION; PHENOTYPES; DEPENDENCE AB Researchers studying alcohol absorption and metabolism in humans have been aided by the alcohol clamp method, in which alcohol is administered intravenously, allowing study participants to achieve and maintain a target breath alcohol concentration (BrAC) for an extended period of time. This tool minimizes the variability in BrACs that occurs after alcohol consumption by administering alcohol at a dose and rate that is computed for each person individually. The alcohol clamp can be used to evaluate several influences on alcohol elimination, including gender, ethnicity, genetic variations in alcohol-metabolizing enzymes, and food consumption. C1 NIAAA, Unit Human Physiol & Pharmacokinet, Lab Clin & Translat Studies, Div Intramural Clin & Biol Res, Bethesda, MD USA. Indiana Univ, Sch Med, Indiana, PA USA. Indiana Alcohol Res Ctr, Indiana, PA USA. Richard L Roudebush Vet Affairs Med Ctr, Substance Abuse Treatment Sect, Indianapolis, IN USA. RP Ramchandani, VA (reprint author), NIAAA, Unit Human Physiol & Pharmacokinet, Lab Clin & Translat Studies, Div Intramural Clin & Biol Res, Bethesda, MD USA. NR 28 TC 17 Z9 17 U1 0 U2 2 PU NATL INST ALCOHOL ABUSE ALCOHOLISM PI ROCKVILLE PA 6000 EXECUTIVE BLVD, ROCKVILLE, MD 20892-7003 USA SN 1535-7414 J9 ALCOHOL RES HEALTH JI Alcohol Res. Health PY 2006 VL 29 IS 4 BP 286 EP 290 PG 5 WC Substance Abuse SC Substance Abuse GA 194RW UT WOS:000248362500006 PM 17718408 ER PT J AU Ramchandani, VA O'Connor, S Neumark, Y Zimmermann, US Morzorati, SL de Wit, H AF Ramchandani, VA O'Connor, S Neumark, Y Zimmermann, US Morzorati, SL de Wit, H TI The alcohol clamp: Applications, challenges, and new directions - An RSA 2004 symposium summary SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol clamp; alcohol elimination rate; ADH; family history of alcoholism; neuroendocrine effects; auditory event-related potentials ID PITUITARY-ADRENAL AXIS; EVENT-RELATED POTENTIALS; AUDITORY-EVOKED-POTENTIALS; FAMILY HISTORY; LUTEINIZING-HORMONE; ACUTE TOLERANCE; STEADY-STATE; JEWISH POPULATION; GONADAL-HORMONES; AMINO-ACIDS AB This article summarizes the proceedings of a symposium organized and cochaired by Vijay Ramchandani and Sean O'Connor and presented at the 2004 Research Society on Alcoholism meeting in Vancouver, BC, Canada. The objectives of this symposium were: (1) to provide a rationale for the development and use of the alcohol clamp and the requirements for its use in alcohol challenge studies; (2) to highlight recent studies conducted using the alcohol clamp to identify sources of variation in the pharmacokinetics and pharmacodynamics of alcohol, as well as to address important research questions related to the relationship between the response to alcohol and the risk for alcoholism; and (3) to provide a perspective on progress, address limitations of the clamp, and identify new directions for alcohol challenge research. The symposium began with an introduction and overview of the alcohol clamp, by Vijay Ramchandani. This was followed by 4 presentations that highlighted recent studies conducted using the clamp including: (1) determination of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in a male Jewish population, by Yehuda Neumark; (2) examination of family history of alcoholism, recent drinking history, and levels and rates of administration as determinants of the response to alcohol and risk for alcoholism, by Sean O'Connor; (3) evaluation of the time course of ethanol intoxication on neuroendocrine function in humans, by Ulrich Zimmermann; and (4) a study of the effects of steady-state blood alcohol levels on auditory event-related potentials in rats, by Sandra Morzorati. Harriet de Wit summarized and discussed the research presented at the symposium and provided her perspective on future directions for research using the alcohol clamp. C1 NIAAA, Div Intramural Clin & Biol Res, Lab Clin & Translat Studies, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46204 USA. RL Roudeboush VA Med Ctr, Indianapolis, IN USA. Hebrew Univ Jerusalem, Braun Sch Publ Hlth, Jerusalem, Israel. Max Planck Inst Psychiat, D-80804 Munich, Germany. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. RP Ramchandani, VA (reprint author), NIAAA, Div Intramural Clin & Biol Res, Lab Clin & Translat Studies, 10 Ctr Dr,MSC 1108, Bethesda, MD 20892 USA. EM vijayr@mail.nih.gov RI Zimmermann, Ulrich/B-9357-2011; OI de Wit, Harriet/0000-0002-7211-8994 NR 62 TC 22 Z9 23 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD JAN PY 2006 VL 30 IS 1 BP 155 EP 164 DI 10.1111/j.1530-0277.2006.00017.x PG 10 WC Substance Abuse SC Substance Abuse GA 003ZL UT WOS:000234721700020 PM 16433744 ER PT J AU Zotenko, E Guimaraes, KS Jothi, R Przytycka, TM AF Zotenko, Elena Guimaraes, Katia S. Jothi, Raja Przytycka, Teresa M. TI Decomposition of overlapping protein complexes: A graph theoretical method for analyzing static and dynamic protein associations SO ALGORITHMS FOR MOLECULAR BIOLOGY LA English DT Article ID SACCHAROMYCES-CEREVISIAE; INTERACTION NETWORKS; FUNCTIONAL MODULES; SCALE-FREE; YEAST; INTERACTOME; PATHWAY AB Background: Most cellular processes are carried out by multi-protein complexes, groups of proteins that bind together to perform a specific task. Some proteins form stable complexes, while other proteins form transient associations and are part of several complexes at different stages of a cellular process. A better understanding of this higher-order organization of proteins into overlapping complexes is an important step towards unveiling functional and evolutionary mechanisms behind biological networks. Results: We propose a new method for identifying and representing overlapping protein complexes (or larger units called functional groups) within a protein interaction network. We develop a graph-theoretical framework that enables automatic construction of such representation. We illustrate the effectiveness of our method by applying it to TNF alpha/NF-kappa B and pheromone signaling pathways. Conclusion: The proposed representation helps in understanding the transitions between functional groups and allows for tracking a protein's path through a cascade of functional groups. Therefore, depending on the nature of the network, our representation is capable of elucidating temporal relations between functional groups. Our results show that the proposed method opens a new avenue for the analysis of protein interaction networks. C1 [Zotenko, Elena; Guimaraes, Katia S.; Jothi, Raja; Przytycka, Teresa M.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. [Zotenko, Elena] Univ Maryland, Dept Comp Sci, College Pk, MD 20742 USA. [Guimaraes, Katia S.] Univ Fed Pernambuco, Ctr Informat, Recife, PE, Brazil. RP Przytycka, TM (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bldg 10, Bethesda, MD 20892 USA. EM zotenko@mail.nih.gov; guimarak@mail.nih.gov; jothi@mail.nih.gov; przytyck@mail.nih.gov RI Guimaraes, Katia/C-5577-2008; Jothi, Raja/G-3780-2015; OI Zotenko, Elena/0000-0002-0256-3195 NR 27 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-7188 J9 ALGORITHM MOL BIOL JI Algorithms. Mol. Biol. PY 2006 VL 1 AR 7 DI 10.1186/1748-7188-1-7 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 255ZP UT WOS:000252697600019 PM 16722537 ER PT S AU Hardy, J AF Hardy, John BE Jucker, M Beyreuther, K Haass, C Nitsch, RM Christen, Y TI The Amyloid Hypothesis: history and alternatives SO Alzheimer: 100 Years and Beyond SE RESEARCH AND PERSPECTIVES IN ALZHEIMERS DISEASE LA English DT Proceedings Paper CT Conference on Alzheimer - 100 Years and Beyond CY NOV 02-05, 2006 CL Univ Tubingen, Inst Psychiat, Tubingen, GERMANY HO Univ Tubingen, Inst Psychiat C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Porter Neurosci Bldg,Main Campus, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 3-540-37651-8 J9 RES PER ALZ PY 2006 BP 151 EP 154 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA BFO03 UT WOS:000243382000015 ER PT S AU Mattson, MR AF Mattson, Mark R. BE Jucker, M Beyreuther, K Haass, C Nitsch, RM Christen, Y TI Molecular and cellular pathways towards and away from Alzheimer's disease SO Alzheimer: 100 Years and Beyond SE RESEARCH AND PERSPECTIVES IN ALZHEIMERS DISEASE LA English DT Proceedings Paper CT Conference on Alzheimer - 100 Years and Beyond CY NOV 02-05, 2006 CL Univ Tubingen, Inst Psychiat, Tubingen, GERMANY HO Univ Tubingen, Inst Psychiat C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MR (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 3 Z9 3 U1 1 U2 8 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0945-6066 BN 3-540-37651-8 J9 RES PER ALZ PY 2006 BP 371 EP 375 DI 10.1007/978-3-540-37652-1_47 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA BFO03 UT WOS:000243382000047 ER PT J AU Hardy, J Pittman, A Myers, A Fung, HC de Silva, R Duckworth, J AF Hardy, J Pittman, A Myers, A Fung, HC de Silva, R Duckworth, J TI Tangle diseases and the tau haplotypes SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE neurofibrillary tangles; tangle diseases; tau haplotypes ID PROGRESSIVE SUPRANUCLEAR PALSY; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; FRONTOTEMPORAL DEMENTIA; GENE; ASSOCIATION; POLYMORPHISMS; POPULATION; PATHOLOGY; COMPLEX AB Neurofibrillary tangles are found in many neurologic diseases. Here we review the unusual characteristics of the MAPT locus, which shows genetic association with many of these diseases and in Caucasian populations, is the largest stretch of linkage disequilibrium in the genome. We discuss the reason for this disequilibrium, its evolutionary history, and the role of genetic variability at MAPT in the etiology of tauopathies. C1 NIA, Neurogenet Lab, Porter Neurosci Ctr, Rockville, MD 20852 USA. NINDS, NIH, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Studies, London, England. Chang Gung Mem Hosp, Dept Neurol 2, Taipei 10591, Taiwan. Chang Gung Univ, Coll Med, Taipei, Taiwan. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Ctr, 35 Convent Dr, Rockville, MD 20852 USA. EM hardyj@mail.nih.gov RI de Silva, Rohan/C-1734-2008; Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009; Pittman, Alan/D-6231-2012 OI de Silva, Rohan/0000-0002-5052-5775; Myers, Amanda/0000-0002-3100-9396; FU Medical Research Council [G0501560, G0701075] NR 24 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD JAN-MAR PY 2006 VL 20 IS 1 BP 60 EP 62 DI 10.1097/01.wad.0000201853.54493.d8 PG 3 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 020OX UT WOS:000235920300011 PM 16493238 ER PT J AU Hardy, J AF Hardy, John BE Perry, G Avila, J Kinoshita, J Smith, MA TI Alzheimer's disease: The amyloid cascade hypothesis: An update and reappraisal SO ALZHEIMER'S DISEASE: A CENTURY OF SCIENTIFIC AND CLINICAL RESEARCH LA English DT Article; Book Chapter ID CORE PROTEIN; MUTATION; GENE AB Here I recap the scientific and personal background of the delineation of the amyloid cascade hypothesis for Alzheimer's disease that I wrote with Gerry Higgins and the events leading to the writing of that influential review. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hardy, J (reprint author), NIA, Neurogenet Lab, Porter Neurosci Bldg,35 Convent Dr, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov NR 16 TC 10 Z9 10 U1 0 U2 16 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS BN 978-1-58603-619-5 PY 2006 BP 151 EP 153 PG 3 WC Biochemistry & Molecular Biology; Clinical Neurology; Neurosciences; Pathology SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Pathology GA BMB04 UT WOS:000271716100017 ER PT J AU Barasch, E Gottdiener, JS Larsen, EKM Chaves, PHM Newman, AB Manolio, TA AF Barasch, E Gottdiener, JS Larsen, EKM Chaves, PHM Newman, AB Manolio, TA TI Clinical significance of calcification of the fibrous skeleton of the heart and aortosclerosis in community dwelling elderly. The Cardiovascular Health Study (CHS) SO AMERICAN HEART JOURNAL LA English DT Article ID MITRAL ANNULAR CALCIFICATION; C-REACTIVE PROTEIN; AORTIC-VALVE SCLEROSIS; OLDER-ADULTS; ATHEROSCLEROTIC DISEASE; MYOCARDIAL-INFARCTION; INFLAMMATORY MARKERS; ANULAR CALCIUM; ASSOCIATION; STROKE AB Background Mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVS) are associated with aging, and MAC and AVS are markers of advanced atherosclerosis. No studies have examined the prevalence and the clinical relevance of all 3 forms of calcification in a single free-living elderly population. Methods We used 2-climensional echocardiography to evaluate MAC, AAC, AVS and all 3 combined in 3929 participants, mean age 76 +/- 5 years, 60% women, in the Cardiovascular Health Study, a prospective community-based observational study designed to assess cardiovascular disease (CVD) risk factors and outcomes in elderly persons. Results Mitral annular calcification was found in 1640 (42%) subjects, AAC in 1710 (44%), AVS in 2114 (54%), and all 3 combined in 662(17%). The participants with these findings were older than those without them, and those with MAC had worse cardiovascular, renal, metabolic, and functional profile than those with AAC and AVS. Age-, sex-, and race-adjusted logistic regression analysis found a significant association between the 3 calcification categories and CVD, the strongest being between the combined group with congestive heart failure (odds ratio 2.04, 95% CI 1.34-3.09). In highly adjusted models, only MAC was associated with CVD, and the strength of association was related to the severity of MAC. Conclusions In free-living elderly, MAC, AAC, and AVS are highly prevalent and are associated with CVD. Mitral annular calcification in particular has strong association with CVD, and with an adverse biomedical profile. C1 SUNY Stony Brook, St Francis Hosp, Dept Res & Educ, Roslyn, NY 11576 USA. Univ Maryland, Sch Med, Div Cardiol, Baltimore, MD 21201 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Johns Hopkins Univ, Dept Med & Epidemiol, Baltimore, MD USA. Univ Pittsburgh, Hlth Aging Res Program, Pittsburgh, PA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Barasch, E (reprint author), SUNY Stony Brook, St Francis Hosp, Dept Res & Educ, 100 Port Washington Blvd, Roslyn, NY 11576 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01-HC-15103, N01-HC-85079-85086] NR 38 TC 40 Z9 43 U1 0 U2 0 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 JAN PY 2006 VL 151 IS 1 BP 39 EP + DI 10.1016/j.ahj.2005.03.052 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 000TK UT WOS:000234485100006 PM 16368289 ER PT J AU Gottdiener, JS Kitzman, DW Aurigemma, GP Arnold, AM Manolio, TA AF Gottdiener, JS Kitzman, DW Aurigemma, GP Arnold, AM Manolio, TA TI Left atrial volume, geometry, and function in systolic and diastolic heart failure of persons >= 65 years of age (The Cardiovascular Health Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID OLDER-ADULTS; RISK-FACTORS; ECHOCARDIOGRAPHY; SIZE; FIBRILLATION; POPULATION; DIMENSIONS; PREDICTORS; COHORT AB The left atrium enlarges in association with many factors, including aging, atrial fibrillation, hypertension, diastolic dysfunction, and heart failure (HF) with low ejection fraction. However, left atrial (LA) volume, geometry, and emptying have not been compared between diastolic and systolic HF, nor has the association of LA volume for new HF been determined in older subjects, many of whom have normal ejection fraction. We used echocardiography to measure the LA volume, geometry, and emptying in 851 community-dwelling subjects >= 65 years of age, including 180 with HF at baseline and 255 participants who subsequently developed HF. The LA volume, area, and linear dimensions were higher in the prevalent and incident HF groups than in controls and did not differ between those with systolic versus diastolic HF, independent of co-morbidities and Doppler measures of diastolic function. The fractional area change was associated with prevalent, but not incident, HF. In conclusion, in population-based older subjects, the LA size is increased and LA emptying decreased in patients with either systolic or diastolic HF. LA size is associated with the new development of HF. These findings highlight the important role of the left atrium in HF, with or without a decreased ejection fraction. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Maryland, Div Cardiol, Ctr Med, Baltimore, MD 21201 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Massachusetts, Med Ctr, Worcester, MA 01605 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Gottdiener, JS (reprint author), Univ Maryland, Div Cardiol, Ctr Med, Baltimore, MD 21201 USA. EM jgottdie@medicine.umaryland.edu FU NHLBI NIH HHS [N01-HC-85079, N01-HC-15103, N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084, N01-HC-85085, N01-HC-85086]; NIA NIH HHS [R01 AG018915, R37 AG018915] NR 20 TC 151 Z9 160 U1 1 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JAN 1 PY 2006 VL 97 IS 1 BP 83 EP 89 DI 10.1016/j.amjcard.2005.07.126 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 002BU UT WOS:000234587200018 PM 16377289 ER PT J AU Walston, J Xue, Q Semba, RD Ferrucci, L Cappola, AR Ricks, M Guralnik, J Fried, LP AF Walston, J Xue, Q Semba, RD Ferrucci, L Cappola, AR Ricks, M Guralnik, J Fried, LP TI Serum antioxidants, inflammation, and total mortality in older women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE aging; antioxidants; carotenoids; inflammation; interleukin-6; mortality; selenium ID CU/ZN-SUPEROXIDE DISMUTASE; CORONARY-ARTERY-DISEASE; NF-KAPPA-B; GLUTATHIONE-PEROXIDASE; HYDROGEN-PEROXIDE; GENE-EXPRESSION; ALPHA-CAROTENE; INTERLEUKIN-6; HEALTH; FRAILTY AB The inflammatory cytokine interleukin-6 (IL-6) has been linked to poor health outcomes in older adults. Oxidative stress triggers the production of IL-6, and antioxidant micronutrients play a critical role in decreasing this inflammatory response. The authors sought to identify the relations between serum levels of antioxidant nutrients and IL-6 and mortality in older women. Levels of alpha- and beta-carotene, lycopene, lutein/zeaxanthin, alpha-cryptoxanthin, total carotenoids, retinol, alpha-tocopherol, zinc, and selenium were measured at baseline in 619 participants in Women's Health and Aging Study I (Baltimore, Maryland, 1992-1998). IL-6 was measured at baseline and at follow-up 1 and 2 years later, and all-cause mortality was determined over a 5-year period. Participants with the highest serum levels of alpha-carotene, total carotenoids, and selenium were significantly less likely to be in the highest tertile of serum IL-6 at baseline (p < 0.0001). Those with the lowest levels of alpha- and beta-carotene, lutein/zeaxanthin, and total carotenoids were significantly more likely to have increasing IL-6 levels over a period of 2 years. Those with the lowest selenium levels had a significantly higher risk of total mortality over a period of 5 years (hazard ratio = 1.54, 95% confidence interval: 1.03, 2.32). These findings suggest that specific antioxidant nutrients may play an important role in suppressing IL-6 levels in disabled older women. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA. NIA, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Walston, J (reprint author), Johns Hopkins Univ, Sch Med, John R Burton Pavil,5505 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM jwalston@jhmi.edu FU NCRR NIH HHS [M01-RR0000052]; NIA NIH HHS [N01-AG12112, P30 AG021334, R01 AG027012, R37 AG19905] NR 34 TC 99 Z9 102 U1 1 U2 6 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 JAN 1 PY 2006 VL 163 IS 1 BP 18 EP 26 DI 10.1093/aje/kwj007 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 997CS UT WOS:000234223200003 PM 16306311 ER PT J AU Kaufman, DW Kelly, JP Issaragrisil, S Laporte, JR Anderson, T Levy, M Shapiro, S Young, NS AF Kaufman, DW Kelly, JP Issaragrisil, S Laporte, JR Anderson, T Levy, M Shapiro, S Young, NS TI Relative incidence of agranulocytosis and aplastic anemia SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article DE epidemiology; international; bone marrow failure; hematopoiesis ID THAILAND AB Agranulocytosis and aplastic anemia are both rare, life-threatening blood dyscrasias. Agranulocytosis is mainly caused by medicines, whereas the etiology of aplastic anemia is largely unexplained. In two epidemiologic studies using the same methods, we observed a striking inverse relationship between the incidence of the two diseases in different regions, including five countries in Europe, and Israel and Thailand. The annual incidence of agranulocytosis ranged from 1.1 to 4.9 cases per million, and that of aplastic anemia, from 0.7 to 4.1 per million; the inverse correlation was consistent among the regions (R-2 = 0.74). There is no clear explanation for this previously unreported pattern, but it seems unlikely to be due to methodology. C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Mahidol Univ, Siriraj Hosp, Fac Med, Div Hematol,Dept Med, Bangkok 10700, Thailand. Univ Autonoma Barcelona, Hosp Vall Hebron, Fundacio Inst Catala Farmacol, E-08193 Barcelona, Spain. Hadassah Univ Hosp, Div Med, Clin Pharmacol Unit, IL-91120 Jerusalem, Israel. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Kaufman, DW (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM dkaufman@slone.bu.edu RI Laporte, Joan-Ramon/A-1302-2011; OI Issaragrisil, Surapol/0000-0002-8924-0646 NR 8 TC 16 Z9 16 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD JAN PY 2006 VL 81 IS 1 BP 65 EP 67 DI 10.1002/ajh.20489 PG 3 WC Hematology SC Hematology GA 000PS UT WOS:000234474900011 PM 16369972 ER PT J AU Grupe, A Li, YH Rowland, C Nowotny, P Hinrichs, AL Smemo, S Kauwe, JSK Maxwell, TJ Cherny, S Doil, L Tacey, K van Luchene, R Myers, A Vrieze, FW Kaleem, M Hollingworth, P Jehu, L Foy, C Archer, N Hamilton, G Holmans, P Morris, CM Catanese, J Sninsky, J White, TJ Powell, J Hardy, J O'Donovan, M Lovestone, S Jones, L Morris, JC Thal, L Owen, M Williams, J Goate, A AF Grupe, A Li, YH Rowland, C Nowotny, P Hinrichs, AL Smemo, S Kauwe, JSK Maxwell, TJ Cherny, S Doil, L Tacey, K van Luchene, R Myers, A Vrieze, FW Kaleem, M Hollingworth, P Jehu, L Foy, C Archer, N Hamilton, G Holmans, P Morris, CM Catanese, J Sninsky, J White, TJ Powell, J Hardy, J O'Donovan, M Lovestone, S Jones, L Morris, JC Thal, L Owen, M Williams, J Goate, A TI A scan of chromosome 10 identifies a novel locus showing strong association with late-onset Alzheimer disease SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RIBOSOMAL-PROTEIN S3A; HAPLOTYPE RECONSTRUCTION; SUSCEPTIBILITY LOCUS; GENOME SCREEN; HUMAN BRAIN; GENE; POPULATION; LINKAGE; GENOTYPE; FAMILIES AB Strong evidence of linkage to late-onset Alzheimer disease ( LOAD) has been observed on chromosome 10, which implicates a wide region and at least one disease-susceptibility locus. Although significant associations with several biological candidate genes on chromosome 10 have been reported, these findings have not been consistently replicated, and they remain controversial. We performed a chromosome 10-specific association study with 1,412 genebased single-nucleotide polymorphisms ( SNPs), to identify susceptibility genes for developing LOAD. The scan included SNPs in 677 of 1,270 known or predicted genes; each gene contained one or more markers, about half (48%) of which represented putative functional mutations. In general, the initial testing was performed in a white case-control sample from the St. Louis area, with 419 LOAD cases and 377 age-matched controls. Markers that showed significant association in the exploratory analysis were followed up in several other white case-control sample sets to confirm the initial association. Of the 1,397 markers tested in the exploratory sample, 69 reached significance (P < .05). Five of these markers replicated at P < .05 in the validation sample sets. One marker, rs498055, located in a gene homologous to RPS3A ( LOC439999), was significantly associated with Alzheimer disease in four of six case-control series, with an allelic P value of .0001 for a meta-analysis of all six samples. One of the case-control samples with significant association to rs498055 was derived from the linkage sample (P = .0165). These results indicate that variants in the RPS3A homologue are associated with LOAD and implicate this gene, adjacent genes, or other functional variants ( e. g., noncoding RNAs) in the pathogenesis of this disorder. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Dept Biol, St Louis, MO 63110 USA. Washington Univ, Dept Genet, St Louis, MO 63110 USA. Celera Diagnost, Alameda, CA USA. NIA, Bethesda, MD 20892 USA. Cardiff Univ, Dept Psychol Med, Wales Coll Med, Cardiff, Wales. Cardiff Univ, Biostat & Bioinformat Unit, Wales Coll Med, Cardiff, Wales. Univ London Kings Coll, Dept Neurosci, Inst Psychiat, London WC2R 2LS, England. Newcastle Gen Hosp, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Goate, A (reprint author), Washington Univ, Sch Med, Dept Psychiat, B8134,660 S Euclid Ave, St Louis, MO 63110 USA. EM goate@icarus.wustl.edu RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Powell, John/G-4412-2011; Kauwe, John/B-2034-2009; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; Hunter, Gillian/A-1952-2015; Holmans, Peter/F-4518-2015; OI Myers, Amanda/0000-0002-3100-9396; Powell, John/0000-0001-6124-439X; Kauwe, John/0000-0001-8641-2468; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379 FU Intramural NIH HHS; Medical Research Council [G0300429, G0701075, G9810900]; NHGRI NIH HHS [T32 HG000045]; NIA NIH HHS [AG 05146, AG05128, P01 AG003991, P01 AG03991, P50 AG005128, P50 AG005131, P50 AG005146, P50 AG005681, P50 AG008671, P50 AG016570, P50 AG05131, P50 AG05681, P50 AG16570, P50-AG08671, R01 AG016208, R01 AG16208, U24 AG021886]; NIGMS NIH HHS [GM065509, P50 GM065509]; NIMH NIH HHS [MH60451, P50 MH060451, U01 MH046281, U01 MH046290, U01 MH046373]; NINDS NIH HHS [NS39764, P50 NS039764] NR 38 TC 92 Z9 93 U1 3 U2 4 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 JAN PY 2006 VL 78 IS 1 BP 78 EP 88 DI 10.1086/498851 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 993CN UT WOS:000233930400008 PM 16385451 ER PT J AU Hinrichs, AL Wang, JC Bufe, B Kwon, JM Budde, J Allen, R Bertelsen, S Evans, W Dick, D Rice, J Foroud, T Nurnberger, J Tischfield, JA Kuperman, S Crowe, R Hesselbrock, V Schuckit, M Almasy, L Porjesz, B Edenberg, HJ Begleiter, H Meyerhof, W Bierut, LJ Goate, AM AF Hinrichs, AL Wang, JC Bufe, B Kwon, JM Budde, J Allen, R Bertelsen, S Evans, W Dick, D Rice, J Foroud, T Nurnberger, J Tischfield, JA Kuperman, S Crowe, R Hesselbrock, V Schuckit, M Almasy, L Porjesz, B Edenberg, HJ Begleiter, H Meyerhof, W Bierut, LJ Goate, AM TI Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID LINKAGE DISEQUILIBRIUM; SUSCEPTIBILITY LOCI; GENETIC-LINKAGE; FAMILY; ALLELE; 6-N-PROPYLTHIOURACIL; PHENYLTHIOCARBAMIDE; IDENTIFICATION; POLYMORPHISMS; ASSOCIATION AB A coding single-nucleotide polymorphism (cSNP), K172N, in hTAS2R16, a gene encoding a taste receptor for bitter beta-glucopyranosides, shows significant association with alcohol dependence (P = .00018). This gene is located on chromosome 7q in a region reported elsewhere to exhibit linkage with alcohol dependence. The SNP is located in the putative ligand-binding domain and is associated with an increased sensitivity to many bitter beta-glucopyranosides in the presence of the N172 allele. Individuals with the ancestral allele K172 are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is uncommon in European Americans ( minor-allele frequency [MAF] 0.6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. German Inst Human Nutr Potsdam Rehbruecke, Nuthetal, Germany. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Rutgers State Univ, Piscataway, NJ USA. Univ Iowa, Sch Med, Iowa City, IA 52242 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Southwest Fdn, San Antonio, TX USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Goate, AM (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid Ave, St Louis, MO 63110 USA. EM goate@icarus.wustl.edu OI Nurnberger, John/0000-0002-7674-1767; Tischfield, Jay/0000-0003-3217-8287; Edenberg, Howard/0000-0003-0344-9690 FU NIAAA NIH HHS [U10AA08401, U10 AA008401] NR 37 TC 80 Z9 84 U1 4 U2 26 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 JAN PY 2006 VL 78 IS 1 BP 103 EP 111 DI 10.1086/499253 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 993CN UT WOS:000233930400010 PM 16385453 ER PT J AU Riazuddin, S Khan, SN Ahmed, ZM Ghosh, M Caution, K Nazli, S Kabra, M Zafar, AU Chen, K Naz, S Antonellis, A Pavan, WJ Green, ED Wilcox, ER Friedman, PL Morell, RJ Riazuddin, S Friedman, TB AF Riazuddin, S Khan, SN Ahmed, ZM Ghosh, M Caution, K Nazli, S Kabra, M Zafar, AU Chen, K Naz, S Antonellis, A Pavan, WJ Green, ED Wilcox, ER Friedman, PL Morell, RJ Riazuddin, S Friedman, TB TI Mutations in TRIOBP, which encodes a putative cytoskeletal-organizing protein, are associated with nonsyndromic recessive deafness SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID ALLELIC MUTATIONS; PCDH15; EAR AB In seven families, six different mutant alleles of TRIOBP on chromosome 22q13 cosegregate with autosomal recessive nonsyndromic deafness. These alleles include four nonsense (Q297X, R788X, R1068X, and R1117X) and two frameshift (D1069fsX1082 and R1078fsX1083) mutations, all located in exon 6 of TRIOBP. There are several alternative splice isoforms of this gene, the longest of which, TRIOBP-6, comprises 23 exons. The linkage interval for the deafness segregating in these families includes DFNB28. Genetic heterogeneity at this locus is suggested by three additional families that show significant evidence of linkage of deafness to markers on chromosome 22q13 but that apparently have no mutations in the TRIOBP gene. C1 Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD 20850 USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. All India Inst Med Sci, Dept Pediat, Genet Unit, New Delhi, India. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. NIH, Internal Med Consult Serv, Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. RP Friedman, TB (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mol Genet Lab, NIH, 5 Res Court,Room 2A-19, Rockville, MD 20850 USA. EM friedman@nidcd.nih.gov; friedman@nidcd.nih.gov RI Nasim Khan, Shaheen/F-2135-2015; naz, sadaf/F-4406-2015; SHEIKH, RIAZUDDIN/L-2406-2015; OI Morell, Robert/0000-0003-1537-7356; Naz, Sadaf/0000-0002-1912-0235 FU Intramural NIH HHS; NIDCD NIH HHS [T32 DC000035, Z01 DC000039, ZO1 DC000035-07, ZO1 DC000039-07] NR 14 TC 40 Z9 44 U1 0 U2 3 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 JAN PY 2006 VL 78 IS 1 BP 137 EP 143 DI 10.1086/499164 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 993CN UT WOS:000233930400014 PM 16385457 ER PT J AU Zhang, MD Ardlie, K Wacholder, S Welch, R Chanock, S O'Brien, TR AF Zhang, MD Ardlie, K Wacholder, S Welch, R Chanock, S O'Brien, TR TI Genetic variations in CC chemokine receptors and hypertension SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE CCR5-Delta 32; CCR2-641; chemokine; epidemiology; genetics; human immunodeficiency virus type 1; hypertension ID HEART-DISEASE; PROGRESSION; PREVALENCE; RISK; AIDS AB Background: CC-chemokine receptor 5 (CCR5) is a co-receptor for human immunodeficiency virus type 1 (HIV-1) infection. Homozycrosity for a 32-base pair (bp) deletion (Delta 32) in the CCR5 gene confers resistance to HIV-1. Previous studies found an increased prevalence of hypertension among CCR5-Delta 32 homozygotes and among carriers of a polymorphism (CCR2-64I) found on the gene that codes a closely related chemokine receptor. The present study was carried out to verify these associations. Methods: Subjects in this cross-sectional study were selected from the Global Repository at Genomics Collaborative, which includes patients and healthy control subjects enrolled at multiple clinical sites in the United States and other nations. The current study includes 2842 subjects with hypertension and 2893 nonhypertensive control subjects from white populations in the United States and Poland. Case and control subjects were frequency matched by age, gender, and birthplace. All subjects were genotyped for CCR5-Delta 32 and CCR2-641 polymorphisms by established Taqman assays. Results: The CCR5-Delta 32 genotype was not found to be associated with hypertension (CCR5-A32 heterozygosity: odds ratio [OR] 0.99, 95% confidence interval [CI] 0.87 to 1.14; CCR5-Delta 32 homozygosity: OR 1.07, 95% CI 0.68 to 1.67) among these subjects. There was also no association between CCR2-641 genotype and hypertension (CCR2-64I heterozygosity: OR 0.96 95% CI 0.83 to 1.10: CCR2-641 homozygosity: OR 1.18, 95% CI 0.73 to 1.92). These results changed little after adjustment for potential confounding variables. Conclusion: The results of the present study, which is much larger than previously published studies, provide no evidence that either CCR5-Delta 32 or CCR2-641 is associated with hypertension. C1 NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Dept Hlth & Human Serv,NIH, Rockville, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Dept Hlth & Human Serv,NIH, Rockville, MD USA. NCI, Div Canc Epidemiol & Genet, Core Genotyping Facil, Dept Hlth & Human Serv,NIH, Rockville, MD USA. Genom Collaborat Inc, Cambridge, MA USA. NCI, SAIC Frederick, Frederick, MD USA. RP O'Brien, TR (reprint author), NCI, Div Canc Epidemiol & Genet, Viral Epidemiol Branch, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,Room 7082,MSC 7234, Rockville, MD 20852 USA. EM obrient@exchange.nih.gov NR 16 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD JAN PY 2006 VL 19 IS 1 BP 67 EP 72 DI 10.1016/j.amjhyper.2005.06.025 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 005VH UT WOS:000234851700013 PM 16461193 ER PT J AU Lea, JP McClellan, WM Melcher, C Gladstone, E Hostetter, T AF Lea, JP McClellan, WM Melcher, C Gladstone, E Hostetter, T TI CKD risk factors reported by primary care physicians: Do guidelines make a difference? SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE kidney disease; hypertension; diabetes; African Americans; family history; primary care providers ID STAGE RENAL-DISEASE; KIDNEY-DISEASE; DIALYSIS AB Background: End-stage renal disease is epidemic within the United States among certain high-risk groups. The National Kidney Disease Education Program examined the awareness of chronic kidney disease (CKD) risk factors among primary care physicians who treat high-risk populations, such as African Americans, persons with diabetes, persons with hypertension, and family members of dialysis patients. Methods: We conducted a survey of 465 primary care physicians in 4 communities with high-risk populations. Respondents were asked to score 9 potential CKD risk factors on a 4-point scale graded from "Does not increase risk at all" to "Increases risk greatly." Potential risk factors included African-American race, diabetes, hypertension, and family history of CKD. Results: Respondents saw a mean of 414 +/- 222 (SD) patients/mo. Primary care physicians were more likely to report that diabetes and hypertension were significant risk factors for CKD. Conversely, 34.4% did not consider family history of kidney disease to increase the risk for CKD, and 22% of respondents did not consider African-American race a CKD risk factor. Conclusion: Primary care physicians need targeted education to increase awareness of populations at high risk for CKD. C1 Emory Univ, Dept Med, Div Renal, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. NIH, Bethesda, MD 20892 USA. RP Lea, JP (reprint author), Emory Univ, Dept Med, Div Renal, Rollins Sch Publ Hlth, 101 Woodruff Circle,WMB Rm 338, Atlanta, GA 30322 USA. EM jlea@emory.edu NR 13 TC 51 Z9 52 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2006 VL 47 IS 1 BP 72 EP 77 DI 10.1053/j.ajkd.2005.09.027 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 008JG UT WOS:000235036000009 PM 16377387 ER PT J AU Palm, WM Walchenbach, R Bruinsma, B Admiraal-Behloul, F Middelkoop, HAM Launer, LJ van der Grond, J van Buchern, MA AF Palm, WM Walchenbach, R Bruinsma, B Admiraal-Behloul, F Middelkoop, HAM Launer, LJ van der Grond, J van Buchern, MA TI Intracranial compartment volumes in normal pressure hydrocephalus: Volumetric assessment versus outcome SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID CEREBROSPINAL-FLUID DISTRIBUTION; PREDICTIVE VALUE; LUMBAR DRAINAGE; BRAIN ATROPHY; TAP-TEST; CSF; DIAGNOSIS; TEMPORARY; TOMOGRAPHY; RESISTANCE AB BACKGROUND AND PURPOSE: Although enlargement of the cerebral ventricles plays a central role in the diagnosis of normal pressure hydrocephalus (NPH), there are no reports on the use of volumetric assessment to distinguish between patients who respond to ventriculoperitoneal shunt surgery and those who do not. The purpose of this study is to explore the association between preoperative intracranial compartment volumes and postoperative improvement. METHODS: Twenty-six patients (17 men; mean age, 75 years [range, 54-87 years]) with a clinical or radiologic suspicion of NPH were included in the study. Gait, cognition, and bladder function were evaluated by clinical rating. MR imaging of the brain was acquired at 0.5T and 1.5T. Total intracranial volume, ventricular volume, brain volume, and pericerebral CSF volume were determined by volumetric assessment. Four imaging variables were determined: ventricular volume ratio, brain volume ratio, pericerebral CSF volume ratio, and the ratio of ventricular volume to pericerebral CSF volume. All patients underwent ventriculoperitoneal shunt surgery. RESULTS: Clinical follow-up was assessed 1 year after shunt surgery. No difference in the mean ventricular volume ratio, the mean brain volume ratio, the mean pericerebral CSF volume ratio, and the mean ratio between ventricular and pericerebral CSF volume was found between subjects who improved on gait or cognition or bladder function and those who did not. CONCLUSION: Volumetric assessment has no predictive value in differentiating between NPH patients who respond to ventriculoperitoneal shunt surgery and those who do not. C1 Leiden Univ, Med Ctr, Dept Radiol, NL-2300 RC Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Neurosurg, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. NIA, Neuroepidemiol Sect, Bethesda, MD 20892 USA. RP Palm, WM (reprint author), Leiden Univ, Med Ctr, Dept Radiol, C2-S,POB 9600, NL-2300 RC Leiden, Netherlands. NR 32 TC 21 Z9 22 U1 0 U2 2 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD JAN PY 2006 VL 27 IS 1 BP 76 EP 79 PG 4 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 004VC UT WOS:000234779600027 PM 16418361 ER PT J AU Bingham, RJ AF Bingham, RJ TI Watching over you SO AMERICAN JOURNAL OF NURSING LA English DT Editorial Material C1 NINR, Bethesda, MD 20892 USA. RP Bingham, RJ (reprint author), NINR, Bethesda, MD 20892 USA. EM masson@erols.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD JAN PY 2006 VL 106 IS 1 BP 39 EP 39 PG 1 WC Nursing SC Nursing GA 000NA UT WOS:000234467700031 PM 16481778 ER PT J AU Romero, R Espinoza, J Erez, O Hassan, S AF Romero, R Espinoza, J Erez, O Hassan, S TI The role of cervical cerclage in obstetric practice: Can the patient who could benefit from this procedure be identified? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material DE cervical cerclage; incompetent cervix; preterm delivery; prematurity; cervical insufficiency ID SPONTANEOUS PRETERM DELIVERY; RANDOMIZED CONTROLLED-TRIAL; HIGH-RISK PREGNANCIES; UTERINE CERVIX; INCOMPETENT CERVIX; BED REST; TRANSFUNDAL PRESSURE; EMERGENCY CERCLAGE; MICROBIAL INVASION; TRANSVAGINAL ULTRASONOGRAPHY AB This editorial critically examines the definition of "cervical insufficiency." The definition, the clinical ascertainment, efforts to develop an objective method of diagnosis, as well as the nature of cervical disease leading to spontaneous mid-trimester spontaneous abortion and preterm delivery are reviewed. The value and limitations of cervical sonography as a risk assessment tool for spontaneous preterm delivery are appraised. The main focus is on the role of cervical cerclage to prevent an adverse pregnancy outcome. The value of assessing the presence or absence of endocervical inflammation in the Outcome of cerclage placement is discussed. (c) 2006 Mosby, Inc. All rights reserved. C1 NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, DHHS,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS NR 133 TC 78 Z9 80 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2006 VL 194 IS 1 BP 1 EP 9 DI 10.1016/j.ajog.2005.12.002 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 999JS UT WOS:000234386200001 PM 16389003 ER PT J AU Bdolah, Y Palomaki, GE Yaron, Y Bdolah-Abram, T Goldman, M Levine, RJ Sachs, BP Haddow, JE Karumanchi, SA AF Bdolah, Y Palomaki, GE Yaron, Y Bdolah-Abram, T Goldman, M Levine, RJ Sachs, BP Haddow, JE Karumanchi, SA TI Circulating angiogenic proteins in trisomy 13 SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preeclampsia; trisomy 13; soluble fms-like tyrosine kinase-1 (sFlt-1); placental growth factor; angiogenesis factor ID ENDOTHELIAL GROWTH-FACTOR; MATERNAL SUSCEPTIBILITY LOCUS; GENOME-WIDE SCAN; SEVERE PREECLAMPSIA; TYROSINE KINASE-1; FACTOR RECEPTOR; DOWN-SYNDROME; SERUM; RISK; PREGNANCY AB Objective: Women who are carrying a trisomy 13 fetus are more prone to develop preeclampsia. Excess circulating soluble fms-like tyrosine kinase-1 has been implicated recently in the pathogenesis of preeclampsia. Since the fms-like tyrosine kinase-1/soluble fins-like tyrosine kinase-1 gene is located on chromosome 13q 12, we hypothesized that the extra copy of this gene in trisomy 13 may lead to excess circulating soluble fms-like tyrosine kinase-1, reduced free placental growth factor level, and increased soluble fms-like tyrosine kinase-1/placental growth factor ratio. This may then contribute to the increased risk of preeclampsia that has been observed in these patients. Our objective was to characterize the maternal circulating angiogenic proteins in trisomy 13 pregnancies. Study design: Maternal serum samples of trisomy 13, 18, 21 and normal karyotype pregnancies were obtained from first and second trimester screening programs. We chose 17 cases of trisomy 13 that were matched for maternal age, freezer storage time, and parity with 85 normal karyotype control samples. Additionally, 20 cases of trisomy 18 and 17 cases of trisomy 21 were included. Cases and control samples were assayed for levels of soluble fins-like tyrosine kinase-1 and placental growth factor by enzyme-linked immunosorbent assay in a blinded fashion. Because of the skewed distributions of soluble fins-like tyrosine kinase-1 and placental growth factor, nonparametric analytic techniques were used, and the results are reported as median and ranges. Results: In early pregnancy trisomy 13 cases and control samples, the median circulating soluble fins-like tyrosine kinase-1/placental growth factor ratios were 17.0 (range, 1.2-61.3) and 6.7 (range, 0.8-62.9), respectively (P =.003). The median soluble fins-like tyrosine kinase-1/placental growth factor ratios in trisomy 18 and 21 were 4.8 (range, 0.9-53.9) and 5.1 (range, 1.0-18.1), which were not significantly different than the control samples. Furthermore, the differences between trisomy 13 and control samples were more pronounced in the second trimester specimens than in the specimens from the first trimester. Conclusion: These data suggest that alterations in circulating angiogenic factors may be involved intimately in the pathogenesis of preeclampsia in trisomy 13. A larger clinical study that measures these factors longitudinally and correlates them with pregnancy outcomes is needed to further establish the link between trisomy 13, altered angiogenic factors, and preeclampsia. (c) 2006 Mosby, Inc. All rights reserved. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Obstet & Gynecol, Boston, MA USA. Fdn Blood Res, Scarborough, ME 04074 USA. Women & Infants Hosp Rhode Isl, Dept Pathol, Div Med Screening, Providence, RI USA. Tel Aviv Sourasky Med Ctr, Inst Genet, Prenatal Diag Unit, Tel Aviv, Israel. NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD USA. RP Karumanchi, SA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave,RW 663B, Boston, MA 02215 USA. EM sananth@bidmc.harvard.edu FU NHLBI NIH HHS [HL 079594] NR 42 TC 33 Z9 38 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2006 VL 194 IS 1 BP 239 EP 245 DI 10.1016/j.ajog.2005.06.031 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 999JS UT WOS:000234386200036 PM 16389038 ER PT J AU Garfield, RE Irani, AM Schwartz, LB Bytautiene, E Romero, R AF Garfield, RE Irani, AM Schwartz, LB Bytautiene, E Romero, R TI Structural and functional comparison of mast cells in the pregnant versus nonpregnant human uterus SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE pregnancy; uterine contractility; mast cells; ragweed; allergy; myometrium ID HUMAN MYOMETRIUM; HISTAMINE; CONTRACTILITY; HETEROGENEITY; LABOR; MEDIATORS; DENSITY; WOMEN AB Objective: To characterize uterine mast cells and investigate uterine muscle strips contractile responses to challenge with an allergen in nonpregnant and pregnant women. Study design: A double-antibody labeling technique was used to identify tryptase positive or chymase-tryptase-positive mast cells in uterine samples from term pregnant and nonpregnant women. Longitudinal myometrial strips were prepared from biopsies of hysterectomy specimens from patients undergoing procedures for benign indications and women who had elective cesarean sections. Responses to ragweed antigen were compared in uterine tissues from allergic and nonallergic patients and with passively sensitized tissues in the absence or presence of H-1 receptor antagonist and a cyclooxygenase inhibitor. Results: Tryptase-chymase-positive mast cells were predominant in nonpregnant myometrium, whereas tryptase-positive cells were dominant in pregnant myotnetrium. Mast cell density was significantly higher in tissue from pregnant women than those of nonpregnant women. Studies in tissues from patients with known allergy to ragweed, as well as in passively sensitized tissues, showed an immediate and substantial increase in the frequency and force of myometrial contraction after a challenge with ragweed antigen. A similar response was observed to histamine. There was no contractile response to antigen challenge in tissues from nonallergic patients. An H, receptor antagonist partially inhibited the response to antigen, whereas a cyclooxygenase inhibitor had no effect. Conclusion: Sensitized isolated pregnant and nonpregnant human uterine tissue is capable of responding to antigen challenge with strong myometrial contractions. This ability, along with the increased density of mast cells in pregnant tissues as compared with nonpregnant tissues, indicates a possible role for mast cells in mediating uterine contractility in pregnancy. (c) 2006 Mosby, Inc. All rights reserved. C1 Univ Texas, Med Branch, Dept Obstet & Gynecol, Div Reprod Sci, Galveston, TX 77555 USA. Virginia Commonwealth Univ, Hlth Syst, Dept Pediat, Richmond, VA USA. Virginia Commonwealth Univ, Hlth Syst, Dept Internal Med, Richmond, VA USA. NICHHD, Perinatol Res Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. RP Garfield, RE (reprint author), Univ Texas, Med Branch, Dept Obstet & Gynecol, Div Reprod Sci, 301 Univ Blvd,Rt J-62, Galveston, TX 77555 USA. EM rgarfiel@utmb.edu NR 29 TC 30 Z9 31 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2006 VL 194 IS 1 BP 261 EP 267 DI 10.1016/j.ajog.2005.05.011 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 999JS UT WOS:000234386200039 PM 16389041 ER PT J AU Grossniklaus, HE Wilson, DJ Bressler, SB Bressler, NM Toth, CA Green, WR Miskala, P AF Grossniklaus, HE Wilson, DJ Bressler, SB Bressler, NM Toth, CA Green, WR Miskala, P CA Submacular Surgery Trials Res Grp TI Clinicopathologic studies of eyes that were obtained postmortem from four patients who were enrolled in the submacular surgery trials: SST report no. 16 SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID INDOCYANINE GREEN ANGIOGRAPHY; CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; OPHTHALMIC FINDINGS; GOOD VISION; PHOTOCOAGULATION; MEMBRANECTOMY; RETENTION; LESIONS AB PURPOSE: To compare the fundus photographic and fluorescein angiographic features with the histologic findings in eyes from patients enrolled in the Submacular Surgery Trials (SST). DESIGN: Clinical trials with clinicopathologic correlation. METHODS: Eyes that were obtained postmortem from patients who participated in the donor program were processed at the SST Pathology Center and examined histologically; the macular regions were reconstructed topographically with two,dimensional cartography. Fundus photographic and fluorescein angiographic features were correlated with the histopathologic and two-dimensional cartographic findings. RESULTS: The eyes from two patients each from the SST Group N and B Trials were studied. The study eye of one patient that had been assigned randomly to observation contained a subretinal fibrovascular scar that corresponded to a histologic growth pattern of a thick, collagenized subretinal component combined with a sub, retinal pigment epithelium (subRPE) fibrovascular component. The study eye of the other patient who was assigned randomly to observation showed angiographic occult without classic choroidal neovascularization (CNV) that corresponded to subRPE CNV. The study eye of one patient who was assigned randomly to surgery showed an angiographic surgical defect without CNV and histologic retinal pigment epithelium (RPE)/photoreceptor atrophy that was associated with a thin layer of subRPE CNV. The study eye of the other patient who was assigned randomly to surgery showed an angio, graphic surgical defect with classic CNV that corresponded to histologic RPE/photoreceptor atrophy that was associated with subRPE fibrovascular tissue and subretinal CNV. Both surgical eyes contained linear breaks in Bruch's membrane that included chevron-shaped breaks. CONCLUSION: Four SST study eyes that were examined postmortem contained CNV. The angiographic patterns and histologic features of the CNV support previous correlations of surgically excised CNV. C1 Emory Univ, Sch Med, Emory Eye Ctr, Dept Ophthalmol, Atlanta, GA USA. Casey Eye Inst, Portland, OR USA. Wilmer Ophthalmol Inst, Baltimore, MD USA. Duke Univ, Ctr Eye, Durham, NC USA. NEI, NIH, Bethesda, MD USA. RP Grossniklaus, HE (reprint author), Emory Eye Ctr, Montgomery Ophthalm Pathol Lab, BT 428,1365 Clifton Rd, Atlanta, GA 30322 USA. EM ophtheg@emory.edu FU NEI NIH HHS [U10 EY 11547, U10 EY 11558, U10 EY 11557, U10 EY 12662] NR 19 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD JAN PY 2006 VL 141 IS 1 BP 93 EP 104 DI 10.1016/j.ajo.2005.07.076 PG 12 WC Ophthalmology SC Ophthalmology GA 000FQ UT WOS:000234446700014 PM 16386982 ER PT J AU Nussenblatt, RB Kim, J Thompson, DJS Davis, MD Chew, E Ferris, FL Buggage, R AF Nussenblatt, RB Kim, J Thompson, DJS Davis, MD Chew, E Ferris, FL Buggage, R TI Vitamin E in the treatment of uveitis-associated macular edema SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR AB PURPOSE: To investigate whether high-dose alpha-tocopherol (vitamin E) could reduce vision loss and retinal thickening associated with uveitis,associated cystoid macular edema. DESIGN: A double-masked, randomized study. METHODS: Uveitis patients with macular edema seen at the NIH were randomized and received either 1600IU/day of vitamin E or placebo for 4 months. Visual acuity and retinal thickening were collected for the efficacy and the safety of the high dose of vitamin E. RESULTS: Changes in visual acuity and retinal thickening. CONCLUSIONS: Four,month oral supplementation with 1600 IU/d of vitamin E had no apparent effect on uveitis,associated macular edema or visual acuity in this small study. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. EMMES Corp, Rockville, MD USA. Univ Wisconsin, Fundus Photograph Reading Ctr, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10S219,10 Ctr Dr, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999] NR 6 TC 7 Z9 8 U1 0 U2 0 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 JAN PY 2006 VL 141 IS 1 BP 193 EP 194 DI 10.1016/j.ajo.2005.07.036 PG 2 WC Ophthalmology SC Ophthalmology GA 000FQ UT WOS:000234446700031 PM 16386999 ER PT J AU Zudaire, E Martinez, A Garayoa, M Pio, R Kaur, G Woolhiser, MR Metcalfe, DD Hook, WA Siraganian, RP Guise, TA Chirgwin, JM Cuttitta, F AF Zudaire, E Martinez, A Garayoa, M Pio, R Kaur, G Woolhiser, MR Metcalfe, DD Hook, WA Siraganian, RP Guise, TA Chirgwin, JM Cuttitta, F TI Adrenomedullin is a cross-talk molecule that regulates tumor and mast cell function during human carcinogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID POSSIBLE PROMOTION MECHANISM; POOR-PROGNOSIS; AUTOCRINE GROWTH; IN-VIVO; ANGIOGENESIS; EXPRESSION; CANCER; PEPTIDE; LINES; DEGRANULATION AB We have previously demonstrated that adrenomedullin (AM) plays a critical role as an autocrine/paracrine tumor cell survival factor. We now present evidence that AM is an important regulator of mast cell (MC) function and that this modulation is potentially involved in tumor promotion. AM induced histamine or P-hexosaminidase release from rat and human MCs through a receptor-independent pathway. AM was chemotactic for human MCs and stimulated mRNA expression of vascular endothelial growth factor, monocyte chemoattractant protein-1, and basic fibroblast growth factor in this cell type. Differentiated but not undifferentiated human MCs responded to hypoxic insult with elevated AM mRNA/protein expression. Using confocal microscopy, we identified AM-producing MCs in tumor infiltrates of human breast and lung cancer patients. in mixed culture assays both anchorage-dependent and -independent growth of human lung cancer A549 cells, an effect that was suppressed by MC-targeted siRNA AM knockdown. Finally, HMC-1 cells induced in vivo angiogenesis as assessed by directed in vivo angiogenesis assay analysis; neutralizing anti-AM monoclonal antibody blocked this ability. Our collective data suggest a new role for AM as a cross-talk molecule that integrates tumor and MC communication, underlying a unique promotion mechanism of human cancers. C1 NCI, CCBB, CCR, Bethesda, MD 20892 USA. CSIC, Dept Cell Biol & Neuroanat, Inst Cajal, Madrid, Spain. Univ Navarra, Dept Cellular & Pathol, E-31080 Pamplona, Spain. Univ Navarra, Dept Biochem, E-31080 Pamplona, Spain. NCI, Biol Testing Branch, Div Canc Treatment & Diag, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Receptor & Signal Transduct Sect, Oral Infect & Immunol Branch, Bethesda, MD USA. Univ Virginia Hlth Syst, Dept Internal Med, Div Endocrinol, Charlottesville, VA USA. RP Zudaire, E (reprint author), NCI, CCBB, CCR, Bldg 10,Rm 12N226, Bethesda, MD 20892 USA. EM zudairee@mail.nih.gov RI Martinez, Alfredo/A-3077-2013; Cuttitta, Frank/B-4758-2016; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 FU Intramural NIH HHS NR 54 TC 49 Z9 54 U1 2 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2006 VL 168 IS 1 BP 280 EP 291 DI 10.2353/ajpath.2006.050291 PG 12 WC Pathology SC Pathology GA 000GP UT WOS:000234449400030 PM 16400030 ER PT J AU Newman, TK Barr, CS Holston, RE Davis, NY Goldman, D Higley, JD AF Newman, TK Barr, CS Holston, RE Davis, NY Goldman, D Higley, JD TI Multiple, novel polymorphisms in the rhesus macaque (Macaca mulatta) DRD4 promoter are associated with impulsive behavior. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 NIAAA, Lab Clin & Translat Studies, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2006 SU 42 BP 138 EP 138 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 016YQ UT WOS:000235661100343 ER PT J AU North, KE Cole, SA Goring, HHH Almasy, L Diego, VP Laston, S Comuzzie, AG Howard, B Lee, ET Best, LG Fabsitz, RR Ebbesson, SOE MacCluer, JW AF North, KE Cole, SA Goring, HHH Almasy, L Diego, VP Laston, S Comuzzie, AG Howard, B Lee, ET Best, LG Fabsitz, RR Ebbesson, SOE MacCluer, JW TI The genetics of cardiovascular disease risk factors in American Indians and Alaska natives: The Strong Heart and GOCADAN Studies. SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX USA. MedStar Res Inst, Washington, DC USA. Univ Oklahoma, Hlth Sci Ctr, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Missouri Breaks Ind Res Inc, Timber Lake, SD USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2006 SU 42 BP 139 EP 139 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 016YQ UT WOS:000235661100346 ER PT J AU Saika, S Ikeda, K Yamanaka, O Flanders, KC Ohnishi, Y Nakajima, Y Muragaki, Y Ooshima, A AF Saika, S Ikeda, K Yamanaka, O Flanders, KC Ohnishi, Y Nakajima, Y Muragaki, Y Ooshima, A TI Adenoviral gene transfer of BMP-7, Id2, or Id3 suppresses injury-induced epithelial-to-mesenchymal transition of lens epithelium in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE lens epithelial cell; bone morphogenic protein-7; inhibitor of differentiation; Smad ID GROWTH-FACTOR-BETA; SMAD PROTEINS; CELL-PROLIFERATION; MESANGIAL CELLS; RENAL FIBROSIS; EXPRESSION; TRANSDIFFERENTIATION; DIFFERENTIATION; VECTOR; OPACIFICATION AB We have examined the effect of adenovirus-mediated expression of bone morphogenic protein-7 (BMP-7) and inhibitors of differentiation 2 and 3 (Id2 and Id3) on injury-induced epithelial-to-mesenchymal transition (EMT) of lens epithelium in mice. Id2 and Id3 are known to be upregulated by BMP-7 and to antagonize Smad2/3 signaling. The Cre-LoxP system adenoviral gene transfer was used. Three microliters of adenoviral solution (2 X 10(7) PFU/mu l) were injected into the right lens of adult male C57BL/6 mice (n = 144) at the time of capsular injury induced using a hypodermic needle under both general and topical anesthesia. A mixture of Cre-adenovirus (Cre-Ad) and vector encoding mBMP-7, mId2, or mId3 was administered in a test group. Control lenses were treated with Cre-Ad alone. After healing intervals of 5 or 10 days, the animals were killed and then we performed histological processes or RNA extraction from the lens. RT-PCR, real-time RT-PCR, and immunohistochemistry showed expression of each introduced gene in the lens. Exogenous BMP-7 upregulated expression of Id2 and Id3 in injured lenses, and gene introduction of Id2 or Id3 also upregulated BMP-7 expression. Gene transfer of BMP-7, Id2, or Id3 delayed injury-induced EMT of the lens epithelial cells as evaluated by histology and expression patterns of alpha-smooth muscle actin and collagens in association with reduction of Smad2 COOH- terminal phosphorylation. Gene transfer of BMP-7, Id2, or Id3 delayed injury-induced EMT of lens epithelial cells and subsequent sealing of the capsular break with fibrous tissue in mice. C1 Wakayama Med Coll, Dept Ophthalmol, Wakayama 6410012, Japan. Wakayama Med Coll, Dept Pathol, Wakayama 6410012, Japan. Osaka City Univ, Grad Sch Med, Dept Anat, Osaka, Japan. NCI, Lab Cell Regulat a& Carcinogenesis, NIH, Bethesda, MD USA. RP Saika, S (reprint author), Wakayama Med Coll, Dept Ophthalmol, 811-1 Kimiidera 2, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp NR 50 TC 40 Z9 51 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD JAN PY 2006 VL 290 IS 1 BP C282 EP C289 DI 10.1152/ajpcell.00306.2005 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 991JM UT WOS:000233809600031 PM 16120655 ER PT J AU Chen, H Karne, RJ Hall, G Campia, U Panza, JA Cannon, RO Wang, YH Katz, A Levine, M Quon, MJ AF Chen, H Karne, RJ Hall, G Campia, U Panza, JA Cannon, RO Wang, YH Katz, A Levine, M Quon, MJ TI High-dose oral vitamin C partially replenishes vitamin C levels in patients with Type 2 diabetes and low vitamin C levels but does not improve endothelial dysfunction or insulin resistance SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE hypertension; hyperglycemia; hypercholesterolemia; insulin sensitivity; sodium nitroprusside ID DEPENDENT DIABETES-MELLITUS; RECOMMENDED DIETARY ALLOWANCE; SKELETAL-MUSCLE VASODILATION; NITRIC-OXIDE RELEASE; ASCORBIC-ACID; OXIDATIVE STRESS; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; DEHYDROASCORBATE TRANSPORT; CARDIOVASCULAR-DISEASE AB Endothelial dysfunction is a hallmark of Type 2 diabetes related to hyperglycemia and oxidative stress. Nitric oxide-dependent vasodilator actions of insulin may augment glucose disposal. Thus endothelial dysfunction may worsen insulin resistance. Intra-arterial administration of vitamin C improves endothelial dysfunction in diabetes. In the present study, we investigated effects of high- dose oral vitamin C to alter endothelial dysfunction and insulin resistance in Type 2 diabetes. Plasma vitamin C levels in 109 diabetic subjects were lower than healthy (36 +/- 2 mu M) levels. Thirty-two diabetic subjects with low plasma vitamin C (< 40 mu M) were subsequently enrolled in a randomized, double-blind, placebo-controlled study of vitamin C (800 mg/day for 4 wk). Insulin sensitivity (determined by glucose clamp) and forearm blood flow in response to ACh, sodium nitroprusside (SNP), or insulin (determined by plethysmography) were assessed before and after 4 wk of treatment. In the placebo group (n = 17 subjects), plasma vitamin C (22 +/- 3 mu M), fasting glucose (159 +/- 12 mg/dl), insulin (19 +/- 7 mu U/ml), and SIClamp [2.06 +/- 0.29 X 10(-4) dl(.)kg(-1.)min(-1)/(mu U/ml)] did not change significantly after placebo treatment. In the vitamin C group (n = 15 subjects), basal plasma vitamin C (23 +/- 2 mu M) increased to 48 +/- 6 mu M ( P < 0.01) after treatment, but this was significantly less than that expected for healthy subjects (> 80 mu M). No significant changes in fasting glucose (156 +/- 11 mg/dl), insulin (14 +/- 2 mu U/ ml), SIClamp 2.71 +/- 0.46 X 10(-4) dl(.)kg(-1.)min(-1)/(mu U/ml)], or forearm blood flow in response to ACh, SNP, or insulin were observed after vitamin C treatment. We conclude that high-dose oral vitamin C therapy, resulting in incomplete replenishment of vitamin C levels, is ineffective at improving endothelial dysfunction and insulin resistance in Type 2 diabetes. C1 NCCAM, Diabet Unit, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 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; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 FU Intramural NIH HHS NR 83 TC 66 Z9 66 U1 1 U2 4 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 JAN PY 2006 VL 290 IS 1 BP H137 EP H145 DI 10.1152/ajpheart.00768.2005 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 996BA UT WOS:000234148200017 PM 16126809 ER PT J AU Patel, K Chen, YF Dennehy, K Blau, J Connors, S Mendonca, M Tarpey, M Krishna, M Mitchell, JB Welch, WJ Wilcox, CS AF Patel, K Chen, YF Dennehy, K Blau, J Connors, S Mendonca, M Tarpey, M Krishna, M Mitchell, JB Welch, WJ Wilcox, CS TI Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT 8th Meeting on Cardiovascular-Kidney Interactions in Health and Disease CY MAY 27-30, 2005 CL Amelia Isl, FL DE tempol; superoxide dismutase; blood pressure; nitric oxide; hypertension ID EXTRACELLULAR-SUPEROXIDE DISMUTASE; SYMPATHETIC-NERVE ACTIVITY; THICK ASCENDING LIMB; NITRIC-OXIDE; BLOOD-PRESSURE; OXIDATIVE STRESS; ANGIOTENSIN-II; AFFERENT ARTERIOLES; IN-VIVO; TEMPOL AB Patel, Kinjal, Yifan Chen, Kathryn Dennehy, Jonathan Blau, Stephanie Connors, Margarida Mendonca, Margaret Tarpey, Murali Krishna, James B. Mitchell, William J. Welch, and Christopher S. Wilcox. Acute antihypertensive action of nitroxides in the spontaneously hypertensive rat. Am J Physiol Regul Integr Comp Physiol 290: R37-R43, 2006. First published September 22, 2005; doi:10.1152/ajpregu.00469.2005.-Tempol is an amphipathic radical nitroxide (N) that acutely reduces blood pressure (BP) and heart rate (HR) in the spontaneously hypertensive rat (SHR). We investigated the hypothesis that the response to nitroxides is determined by SOD mimetic activity or lipophilicity. Groups (n = 6 - 10) of anesthetized SHRs received graded intravenous doses of Ns: tempol (T), 4-amino-tempo (AT), 4-oxo-tempo (OT), 4-trimethylammonium-2,2,6,6-tetramethylpiperidine-1-oxyl iodide (CAT-1), 3-carbamoyl-proxyl (3-CP), or 3-carboxyproxyl (3-CTPY). Others received native or liposomal (L) Cu/Zn SOD. T and OT are uncharged, AT is positively charged and cell-permeable, and CAT-1 is positively charged and cell-impermeable. 3-CP and 3-CTPY have five-member pyrrolidine rings, whereas T, AT, OT, and CAT- 1 have six-member piperidine rings. T and AT reduced mean arterial pressure (MAP) similarly (- 48 +/- 2 mmHg and - 55 +/- 8 mmHg) but more (P < 0.05) than OT and CAT-1. 3-CP and 3-CTPY were ineffective. The group mean change in MAP with piperidine Ns correlated with SOD activity (r = -0.94), whereas their ED50 correlated with lipophilicity (r = 0.89). SOD and L-SOD did not lower BP acutely but reduced it after 90 min (-32 +/- 5 and -31 +/- 6 mmHg; P < 0.05 vs. vehicle). Pyrrolidine nitroxides are ineffective antihypertensive agents. The antihypertensive response to piperidine Ns is predicted by SOD mimetic action, and the sensitivity of response is by hydrophilicity. SOD exerts a delayed hypotensive action that is not enhanced by liposome encapsulation, suggesting it must diffuse to an extravascular site. C1 Georgetown Univ, Div Nephrol & Hypertens, Washington, DC 20007 USA. Univ Alabama, Anesthesiol Res Div, Birmingham, AL USA. NCI, Radiat Oncol Branch, Clin Oncol Program, Div Canc Treatment,NIH, Bethesda, MD 20892 USA. RP Wilcox, CS (reprint author), Georgetown Univ, Div Nephrol & Hypertens, 3800 Reservoir Rd,NW,PHC F6003, Washington, DC 20007 USA. EM wilcoxch@georgetown.edu FU NHLBI NIH HHS [HL-68686]; NIDDK NIH HHS [DK-49870, DK-59274, DK-36079] NR 35 TC 28 Z9 28 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN PY 2006 VL 290 IS 1 BP R37 EP R43 DI 10.1152/ajpregu.00469.2005 PG 7 WC Physiology SC Physiology GA 993CS UT WOS:000233930900005 PM 16179488 ER PT J AU Yang, ZW Asico, LD Yu, PY Wang, Z Jones, JE Escano, CS Wang, XY Quinn, MT Sibley, DR Romero, GG Felder, RA Jose, PA AF Yang, ZW Asico, LD Yu, PY Wang, Z Jones, JE Escano, CS Wang, XY Quinn, MT Sibley, DR Romero, GG Felder, RA Jose, PA TI D-5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article; Proceedings Paper CT 8th Meeting on Cardiovascular-Kidney Interactions in Health and Disease CY MAY 27-30, 2005 CL Amelia Isl, FL DE hypertension ID PROTEIN-KINASE-A; SPONTANEOUSLY HYPERTENSIVE RATS; SMOOTH-MUSCLE-CELLS; OXIDATIVE STRESS; NAD(P)H OXIDASE; PHOSPHOLIPASE-D; ANGIOTENSIN-II; SUPEROXIDE PRODUCTION; GENOME SCAN; ACTIVATION AB D-5 dopamine receptor regulation of reactive oxygen species production, NADPH oxidase, and blood pressure. Am J Physiol Regul Integr Comp Physiol 290: R96 - R104, 2006; doi: 10.1152/ ajpregu. 00434.2005. - Activation of D-1- like receptors (D-1 and/or D-5) induces antioxidant responses; however, the mechanism(s) involved in their antioxidant actions are not known. We hypothesized that stimulation of the D-5 receptor inhibits NADPH oxidase activity, and thus the production of reactive oxygen species (ROS). We investigated this issue in D-5 receptor-deficient (D-5(-/-)) and wild-type (D-5(-/-)) mice. NADPH oxidase protein expression (gp91(phox), p47(phox), and Nox 4) and activity in kidney and brain, as well as plasma thiobarbituric acid-reactive substances (TBARS) were higher in D-5(-/-) than in D-5(-/-) mice. Furthermore, apocynin, an NADPH oxidase inhibitor, normalized blood pressure, renal NADPH oxidase activity, and plasma TBARS in D-5(-/-) mice. In HEK-293 cells that heterologously expressed human D5 receptor, its agonist fenoldopam decreased NADPH oxidase activity, expression of one of its subunits (gp91(phox)), and ROS production. The inhibitory effect of the D5 receptor activation on NADPH oxidase activity was independent of cAMP/PKA but was partially dependent on phospholipase D2. The ability of D-5 receptor stimulation to decrease ROS production may explain, in part, the antihypertensive action of D-5 receptor activation. C1 Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. CAMS, Inst Lab Anim Sci, Beijing, Peoples R China. PUMC, Beijing, Peoples R China. Montana State Univ, Dept Vet Mol Biol, Bozeman, MT 59717 USA. NINDS, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Pharmacol, Pittsburgh, PA USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA USA. RP Jose, PA (reprint author), Georgetown Univ, Med Ctr, Dept Pediat, 3800 Reservoir Rd,NW, Washington, DC 20007 USA. EM pjose01@georgetown.edu FU NHLBI NIH HHS [HL-074940, HL-23081, HL-68686]; NIAMS NIH HHS [AR-042426]; NIDDK NIH HHS [DK-39308, DK-52612] NR 61 TC 65 Z9 71 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD JAN PY 2006 VL 290 IS 1 BP R96 EP R104 DI 10.1152/ajpregu.00434.2005 PG 9 WC Physiology SC Physiology GA 993CS UT WOS:000233930900014 PM 16352863 ER PT J AU Fenton, RA Shodeinde, A Knepper, MA AF Fenton, RA Shodeinde, A Knepper, MA TI UT-A urea transporter promoter, UT-A alpha, targets principal cells of the renal inner medullary collecting duct SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE transgenic; kidney; beta-galactosidase ID NEPHROGENIC DIABETES-INSIPIDUS; TRANSGENIC MICE; GENE PROMOTER; CONCENTRATING DEFECT; CRE RECOMBINASE; WATER CHANNELS; KNOCKOUT MICE; MOUSE MODEL; EXPRESSION; KIDNEY AB The urea transporters, UT-A1 and UT-A3, two members of the UT-A gene family, are localized to the terminal portion of the inner medullary collecting duct (IMCD). In this manuscript, we demonstrate that 4.2 kb of the 5'-flanking region of the UT-A gene (UT-A alpha promoter) is sufficient to drive the IMCD-specific expression of a heterologous reporter gene, beta-galactosidase (beta-Gal), in transgenic mice. RT-PCR, immunoblotting, and immunohistochemistry demonstrate that within the kidney, transgene expression is confined to the terminal portion of the IMCD. Colocalization studies with aquaporin-2 show that expression is localized to the principal cells of the IMCD2 and IMCD3 regions. Utilizing beta-Gal activity assays, we further show that within the kidney, the beta-Gal transgene can be regulated by both water restriction and glucocorticoids, similar to the regulation of the endogenous UT-A gene. These results demonstrate that 4.2 kb of the UT-A alpha promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific and cell-specific fashion in transgenic mice. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Fenton, RA (reprint author), Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Bldg 233-234, DK-8000 Aarhus, Denmark. EM ROFE@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 40 TC 8 Z9 8 U1 0 U2 4 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 JAN PY 2006 VL 290 IS 1 BP F188 EP F195 DI 10.1152/ajprenal.00285.2005 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 991YJ UT WOS:000233850500021 PM 16091580 ER PT J AU Buller, DB Reynolds, KD Yaroch, A Cutter, GR Hines, JM Geno, CR Maloy, JA Brown, M Woodall, WG Grandpre, J AF Buller, DB Reynolds, KD Yaroch, A Cutter, GR Hines, JM Geno, CR Maloy, JA Brown, M Woodall, WG Grandpre, J TI Effects of the Sunny Days, Healthy Ways curriculum on students in grades 6 to 8 SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SKIN-CANCER PREVENTION; EXPOSURE; CHILDREN; SCHOOL; PROTECTION; ATTITUDES; ADULTS; AGE AB Background: There are few effective sun-safety education programs for use in secondary schools. Project aims were to create a sun-safety curriculum for grades 6 to 8, and to test whether exposure to the curriculum would increase children's sun-protection behavior. Design: A pair-matched, group-randomized, pre-post test, controlled trial was performed with middle schools as the unit of randomization. Teachers implemented the six-unit sun-safety curriculum in 2001-2003, and analyses were performed in 2003-2004. Setting/Participants: A total of 2038 children from 30 middle schools in Colorado, New Mexico, and Arizona. Main Outcome Measures: Self-reported sun-protection behavior using frequency ratings and diary. Results: Compared to control schools, children receiving the curriculum reported more frequent sun protection (p = 0.0035), and a greater proportion wore long-sleeved shirts during recess (p < 0.0001) and applied sunscreen (p < 0.0001). Exposure to the curriculum improved knowledge (p < 0.0001), decreased perceived barriers to using sunscreen (p = 0.0046), enhanced self-efficacy expectations (p = 0.0577) about sun safety, and reduced favorable attitudes toward sun tanning (p = 0.0026 to < 0.0001). In intent-to-treat analyses, the treatment effect was eliminated only under the most conservative assumptions about dropouts. Conclusions: Educational approaches to sun safety in middle school may be effective for improving children's sun safety. Potential trial limitations include measuring short-term outcomes, focusing on young adolescents, using active parental consent, and testing in the American Southwest. C1 Klein Buendel Inc, Golden, CO 80401 USA. Univ So Calif, Inst Prevent Res, Los Angeles, CA USA. NCI, Hlth Promot Res Branch, Bethesda, MD 20892 USA. Univ Alabama, Sch Publ Hlth, Birmingham, AL 35294 USA. Kaiser Permanente, Childrens Hosp, Sect Pediat Gastroenterol Hepatol Nutr, Denver, CO USA. Jefferson Cty Publ Sch, Golden, CO USA. Univ New Mexico, Ctr Alcoholism Subst Abuse & Addict, Albuquerque, NM 87131 USA. Wyoming Dept Hlth, Cheyenne, WY USA. RP Buller, DB (reprint author), Klein Buendel Inc, 1667 Cole Blvd,Suite 225, Golden, CO 80401 USA. EM dbuller@kleinbuendel.com FU NCI NIH HHS [R01 CA079701, CA81864, R01 CA081864] NR 27 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2006 VL 30 IS 1 BP 13 EP 22 DI 10.1016/j.amepre.2005.08.046 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 007TK UT WOS:000234992500003 PM 16414419 ER PT J AU Insel, TR AF Insel, TR TI Beyond efficacy: The STAR*D trial SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID PRACTICAL CLINICAL-TRIALS C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 6 TC 40 Z9 41 U1 1 U2 2 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 JAN PY 2006 VL 163 IS 1 BP 5 EP 7 DI 10.1176/appi.ajp.163.1.5 PG 3 WC Psychiatry SC Psychiatry GA 999CU UT WOS:000234367100003 PM 16390879 ER PT J AU Trivedi, MH Rush, AJ Wisniewski, SR Nierenberg, AA Warden, D Ritz, L Norquist, G Howland, RH Lebowitz, B McGrath, PJ Shores-Wilson, K Biggs, MM Balasubramani, GK Fava, M AF Trivedi, MH Rush, AJ Wisniewski, SR Nierenberg, AA Warden, D Ritz, L Norquist, G Howland, RH Lebowitz, B McGrath, PJ Shores-Wilson, K Biggs, MM Balasubramani, GK Fava, M CA STAR Study Team TI Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: Implications for clinical practice SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; ANTIDEPRESSANT EFFICACY TRIALS; DIAGNOSTIC SCREENING QUESTIONNAIRE; ILLNESS RATING-SCALE; REPORT QIDS-SR; MAJOR DEPRESSION; RELIEVE DEPRESSION; SOCIAL SUPPORT; DRUG RESPONSE; PSYCHOMETRIC EVALUATION AB Objective: Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, but the rates, timing, and baseline predictors of remission in "real world" patients are not established. The authors' primary objectives in this study were to evaluate the effectiveness of citalopram, an SSRI, using measurement-based care in actual practice, and to identify predictors of symptom remission in outpatients with major depressive disorder. Method: This clinical study included outpatients with major depressive disorder who were treated in 23 psychiatric and 18 primary care " real world" settings. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks. The clinicians were assisted by a clinical research coordinator in the application of measurement-based care, which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures. Remission was defined as an exit score of <= 7 on the 17-item Hamilton Depression Rating Scale (HAM-D) ( primary outcome) or a score of <= 5 on the 16-item Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) ( secondary outcome). Response was defined as a reduction of >= 50% in baseline QIDS-SR score. Results: Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders ( especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates. Conclusions: The response and remission rates in this highly generalizable sample with substantial axis I and axis III co-morbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results. C1 Univ Texas, SW Med Ctr, Mood Disorders Program & Clin, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, NIMH, Depress Clin & Res Program, Boston, MA 02114 USA. Univ Mississippi, Dept Psychiat, Jackson, MS 39216 USA. Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, Sch Med, San Diego, CA 92103 USA. Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. RP Trivedi, MH (reprint author), Univ Texas, SW Med Ctr, Mood Disorders Program & Clin, Dept Psychiat, Exchange Pk Express,Amer Gen Tower,6363 Forest Pk, Dallas, TX 75390 USA. RI Biggs, Dr. Melanie/C-1468-2010; McGrath, Patrick/I-6410-2013; Howland, Robert/K-6937-2015; OI McGrath, Patrick/0000-0001-7217-7321; Howland, Robert/0000-0002-6533-6010; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH-90003] NR 71 TC 1479 Z9 1517 U1 28 U2 168 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 JAN PY 2006 VL 163 IS 1 BP 28 EP 40 DI 10.1176/appi.ajp.163.1.28 PG 13 WC Psychiatry SC Psychiatry GA 999CU UT WOS:000234367100010 PM 16390886 ER PT J AU Parsey, RV Hastings, RS Oquendo, MA Hu, XZ Goldman, D Huang, YY Simpson, N Arcement, J Huang, YY Ogden, RT Van Heertum, RL Arango, V Mann, JJ AF Parsey, RV Hastings, RS Oquendo, MA Hu, XZ Goldman, D Huang, YY Simpson, N Arcement, J Huang, YY Ogden, RT Van Heertum, RL Arango, V Mann, JJ TI Effect of a triallelic functional polymorphism of the serotonin-transporter-linked promoter region on expression of serotonin transporter in the human brain SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SUICIDAL-BEHAVIOR; MAJOR DEPRESSION; ALLELIC VARIANTS; GENE; GENOTYPE; AVAILABILITY; 5-HTTLPR; BINDING; SYSTEM; SPECT AB Objective: The authors examined effects of a triallelic functional polymorphism of the human serotonin-transporter-linked promoter region (5-HTTLPR) on in vivo expression of serotonin transporter in the brain in healthy volunteers and subjects with major depressive disorder. Method: Twenty-five medication-free subjects with DSM-IV major depressive disorder during a major depressive episode and 42 healthy volunteers were clinically evaluated and genotyped. Serotonin transporter binding potential (f(1)Bmax/K-d) was determined by using positron emission tomography with the radiotracer [C-11] McN 5652 and metabolite-corrected arterial input functions. Results: There was no difference in serotonin transporter binding potential by genotype in healthy volunteers or in subjects with major depressive disorder. Allelic frequencies did not differ between subjects with major depressive disorder and healthy volunteers. Conclusions: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood. C1 New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, Dept Analyt Psychopharmacol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Radiol, New York, NY 10032 USA. Columbia Univ, Sch Publ Hlth, Dept Biostat, New York, NY USA. NIAAA, Neurogenet Lab, Washington, DC USA. RP Parsey, RV (reprint author), New York State Psychiat Inst & Hosp, Dept Neurosci, 1051 Riverside Dr,Box 42, New York, NY 10032 USA. EM rparsey@neuron.cpmc.columbia.edu RI Ogden, Todd/H-7946-2012; Arango, Victoria/K-9377-2015; Goldman, David/F-9772-2010; Parsey, Ramin/J-8254-2014 OI Arango, Victoria/0000-0001-8811-400X; Goldman, David/0000-0002-1724-5405; FU NIMH NIH HHS [MH-40210, MH-40695, MH-62185, P30 MH-46745] NR 17 TC 195 Z9 197 U1 0 U2 4 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 JAN PY 2006 VL 163 IS 1 BP 48 EP 51 DI 10.1176/appi.ajp.163.1.48 PG 4 WC Psychiatry SC Psychiatry GA 999CU UT WOS:000234367100012 PM 16390888 ER PT J AU Richards, M Rubinow, DR Daly, RC Schmidt, PJ AF Richards, M Rubinow, DR Daly, RC Schmidt, PJ TI Premenstrual symptoms and perimenopausal depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID DYSPHORIC DISORDER; MENOPAUSAL TRANSITION; PSYCHOLOGIC DISTRESS; REPRODUCTIVE LIFE; MENSTRUAL-CYCLE; MOOD DISORDERS; RISK-FACTORS; DOUBLE-BLIND; WOMEN; ESTRADIOL AB Objective: The role of ovarian steroids in both premenstrual dysphoria and perimenopausal depression has led to the suggestion that these conditions represent expressions of the same underlying disorder. Premenstrual mood symptoms were evaluated in women with perimenopause-related depression. Method: Self-reports and daily symptom ratings during one menstrual cycle were examined in 70 depressed perimenopausal women attending a menopause clinic and 35 nondepressed perimenopausal women. Results: Twenty-six percent of the depressed and 9% of the nondepressed women reported premenstrual symptoms. Thirty-one percent of the depressed and 20% of the nondepressed women met criteria for significant menses-related symptom cyclicity (at least a 30% increase in the average ratings of at least two of four measured negative mood symptoms in the premenstrual versus the postmenstrual week); 5 of these depressed women and none of the comparison subjects described premenstrual symptoms on self-reports. Finally, 21% of the depressed and 3% of the nondepressed women met criteria for premenstrual dysphoria ( symptom cyclicity and at least moderate severity, with symptoms exceeding a minimum luteal symptom severity threshold of 2.5). Conclusions: A higher-than-expected rate of menses-related symptom cyclicity and premenstrual dysphoria was observed in perimenopausal depressed women. However, neither menses-related symptom cyclicity nor premenstrual dysphoria was an invariant accompaniment of perimenopausal depression. Additionally, the rate of premenstrual dysphoria was not predicted by initial self-reports. C1 US Dept Hlth & Human Serv, Behav Endocrinol Branch, NIH, NIMH, Bethesda, MD USA. RP Schmidt, PJ (reprint author), Bldg 10-CRC,Rm 6-5340,10 Ctr Dr,MSC 1276, Bethesda, MD 20892 USA. EM schmidtp@intra.nimh.nih.gov NR 48 TC 30 Z9 33 U1 0 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 JAN PY 2006 VL 163 IS 1 BP 133 EP 137 DI 10.1176/appi.ajp.163.1.133 PG 5 WC Psychiatry SC Psychiatry GA 999CU UT WOS:000234367100024 PM 16390900 ER PT J AU Zarate, CA Singh, JB Quiroz, JA De Jesus, G Denicoff, KK Luckenbaugh, DA Manji, HK Charney, DS AF Zarate, CA Singh, JB Quiroz, JA De Jesus, G Denicoff, KK Luckenbaugh, DA Manji, HK Charney, DS TI A double-blind, placebo-controlled study of memantine in the treatment of major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID OPEN-LABEL TRIAL; RILUZOLE AB Objective: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate ( NMDA) receptor antagonist in humans. Method: In a double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned to receive memantine (5-20 mg/day) (N = 16) or placebo (N = 16) for 8 weeks. Primary efficacy was assessed by performance on the Montgomery-Asberg Depression Rating Scale (MADRS). Results: The linear mixed models for total MADRS scores showed no treatment effect. Conclusions: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder. C1 CRC, Bethesda, MD 20892 USA. NIMH, Dept Human Hlth Serv, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), CRC, 10 Ctr Dr,CRC,7 SE,Rm 7-3445, Bethesda, MD 20892 USA. EM zaratec@mail.nih.gov FU Intramural NIH HHS NR 6 TC 210 Z9 218 U1 0 U2 9 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 JAN PY 2006 VL 163 IS 1 BP 153 EP 155 DI 10.1176/appi.ajp.163.1.153 PG 3 WC Psychiatry SC Psychiatry GA 999CU UT WOS:000234367100029 PM 16390905 ER PT J AU Waring, B Fee, E AF Waring, B Fee, E TI The disasters of war SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Fee, E (reprint author), NIH, Hist Med Div, Natl Lib Med, Bldg 38,Room 1E-21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.gov NR 4 TC 1 Z9 1 U1 0 U2 0 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 JAN PY 2006 VL 96 IS 1 BP 51 EP 51 DI 10.2105/AJPH.2005.071506 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998JG UT WOS:000234314000012 PM 16322462 ER PT J AU Agostoni, C AF Agostoni, C TI Popular health education and propaganda in times of peace and war in Mexico City, 1890s-1920s SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID CHILDREN AB Health education and propaganda acquired importance during the late 19th and early 20th centuries in Mexico City, as physicians, hygienists, and schoolteachers attempted to teach the principles of public health to a culturally and socially heterogeneous urban population. I explore the organization of the Popular Hygiene Exhibition of 1910 and the importance of health education before and after the armed phase of the Mexican Revolution, and why children and the indigenous populations became the main recipients of health education programs. C1 Univ Nacl Autonoma Mexico, Inst Invest Hist, Mexico City 04510, DF, Mexico. NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20892 USA. RP Agostoni, C (reprint author), Univ Nacl Autonoma Mexico, Inst Invest Hist, Circuito Maestro Mario Cueva,Ciudad Univ, Mexico City 04510, DF, Mexico. EM agostoni@servidor.unam.mx RI Agostoni, Carlo/A-9303-2012; Agostoni, Carlo/B-3470-2015 OI Agostoni, Carlo/0000-0002-5006-0832 NR 62 TC 3 Z9 5 U1 0 U2 2 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 JAN PY 2006 VL 96 IS 1 BP 52 EP 61 DI 10.2105/AJPH.2004.044388 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998JG UT WOS:000234314000013 PM 16322465 ER PT J AU Brown, TM Cueto, M Fee, E AF Brown, TM Cueto, M Fee, E TI The World Health Organization and the transition from international to global public health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID ENVIRONMENTAL-CHANGE; GLOBALIZATION; POLICY; CARE; COMMISSION; DISEASES; LEADERS; CRISIS; BANK AB The term '' global health '' is rapidly replacing the older terminology of '' international health.'' We describe the role of the World Health Organization (WHO) in both international and global health and in the transition from one to the other. We suggest that the term '' global health '' emerged as part of larger political and historical processes, in which WHO found its dominant role challenged and began to reposition itself within a shifting set of power alliances. Between 1948 and 1998, WHO moved from being the unquestioned leader of international health to being an organization in crisis, facing budget shortfalls and diminished status, especially Oven the growing influence of new and powerful players. We argue that WHO began to refashion itself as the coordinator, strategic planner, and leader of global health initiatives as a strategy of survival in response to this transformed international political context. C1 Natl Inst Hlth, Hist Med Div, Natl Lib Med, Bethesda, MD 20974 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. Univ Peruana Cayetano Heredia, Fac Salud Publ, Lima, Peru. RP Fee, E (reprint author), Natl Inst Hlth, Hist Med Div, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20974 USA. EM elizabeth_fee@nlm.nih.gov NR 84 TC 170 Z9 181 U1 1 U2 31 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 JAN PY 2006 VL 96 IS 1 BP 62 EP 72 DI 10.2105/AJPH.2004.050831 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 998JG UT WOS:000234314000014 PM 16322464 ER PT J AU Hanna, N Bonifacio, L Weinberger, B Reddy, P Murphy, S Romero, R Sharma, S AF Hanna, N Bonifacio, L Weinberger, B Reddy, P Murphy, S Romero, R Sharma, S TI Evidence for interleukin-10-mediated inhibition of cyclo-oxygenase-2 expression and prostaglandin production in preterm human placenta SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE cyclo-oxygenase-2; inflammation; interleukin-10; placental explants; preterm labor ID LOW-BIRTH-WEIGHT; CYCLOOXYGENASE-2 EXPRESSION; INTRAAMNIOTIC INFECTION; INTRAUTERINE INFECTION; SPONTANEOUS RUPTURE; E-2 PRODUCTION; IFN-GAMMA; LABOR; TERM; PARTURITION AB Problem Interleukin-10 (IL-10) is thought to be a key cytokine for the maintenance of pregnancy. Here we examined the expression profiles of IL- 10 and cyclo-oxygenase-2 (COX-2), and the effect of IL-10 on COX-2 expression and prostaglandin release in the human placenta from pre-term labor deliveries associated with chorioamnionitis. Method of study. Placental tissues from preterm labor and term labor deliveries were processed for ex vivo placental explant culture system. IL-10 expression was assessed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analysis. COX-2 expression was evaluated by IHC, Western blotting and reverse transcriptase- polymerase chain reaction. Prostaglandin E-2 (PGE(2)) release was measured by ELISA. Results. IL-10 was significantly reduced in chorioamnionitis-associated preterm labor as well as in term labor placental tissues compared with second trimester normal pregnancy samples obtained from elective terminations. Similar results were obtained with freshly isolated cytotrophoblasts from these deliveries. As expected, COX-2 mRNA was detected at significant levels in tissues from term and preterm labor deliveries compared with no labor term deliveries. Importantly, IL-10 inhibited COX-2 expression in cultured placental explants from preterm labor deliveries, but not from term labor samples. Inhibition of COX-2 expression coincided with reduced PGE(2) release. Conclusion. These results demonstrate the importance of IL-10 in countering inflammation associated with preterm labor, and suggest that term and preterm parturition may, in part, represent different conditions. C1 Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02905 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat Neonatol, New Brunswick, NJ USA. Rutgers State Univ, Dept Pharmacol & Toxicol, Piscataway, NJ 08854 USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. RP Sharma, S (reprint author), Brown Univ, Women & Infants Hosp, Dept Pediat, 101 Dudley St, Providence, RI 02905 USA. EM ssharma@wihri.org FU Intramural NIH HHS; NICHD NIH HHS [HD41701] NR 44 TC 56 Z9 57 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JAN PY 2006 VL 55 IS 1 BP 19 EP 27 DI 10.1111/j.1600-0897.2005.00342x PG 9 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 996UF UT WOS:000234199800003 PM 16364008 ER PT J AU Ryu, JH Moss, J Beck, GJ Lee, JC Brown, KK Chapman, JT Finlay, GA Olson, EJ Ruoss, SJ Maurer, JR Raffin, TA Peavy, HH McCarthy, K Taveira-Da Silva, A McCormack, FX Avila, NA DeCastro, RM Jacobs, SS Stylianou, M Fanburg, BL AF Ryu, JH Moss, J Beck, GJ Lee, JC Brown, KK Chapman, JT Finlay, GA Olson, EJ Ruoss, SJ Maurer, JR Raffin, TA Peavy, HH McCarthy, K Taveira-Da Silva, A McCormack, FX Avila, NA DeCastro, RM Jacobs, SS Stylianou, M Fanburg, BL CA NHLBI LAM Registry Grp TI The NHLBI lymphangioleiomyomatosis registry - Characteristics of 230 patients at enrollment SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lymphangioleiomyomatosis; registry; tuberous sclerosis ID QUALITY-OF-LIFE; TUBEROUS SCLEROSIS COMPLEX; SMOOTH-MUSCLE-CELLS; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; DIFFUSING-CAPACITY; LUNG-FUNCTION; PROGESTERONE; DISEASE; WOMEN; COPD AB Rationale: Pulmonary lymphangioleiomyomatosis is a progressive cystic lung disease that is associated with infiltration of atypical smooth muscle-like cells. Previous descriptions of clinical characteristics of subjects with lymphangioleiomyomatosis have been based on a limited number of patients. Objectives: To describe the clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms. Methods: Over a 3-yr period, from 1998 to 2001, 243 subjects with pulmonary lymphangioleiomyomatosis were enrolled into a national registry; 13 subjects who had already undergone lung transplantation were excluded for the purposes of this report. Measurements and Main Results: All 230 subjects were women, aged 18 to 76 yr (mean +/- SE, 44.5 +/- 0.65 yr). The average age at onset of symptoms was 38.9 +/- 0.73 yr and at diagnosis was 41.0 +/- 0.65 yr. Tuberous sclerosis complex was present in 14.8% of subjects. Pulmonary manifestations, most commonly spontaneous pneumothorax, were the primary events leading to the diagnosis in 86.5% of cases. Nearly 55% of the subjects were being treated with a progesterone derivative. An obstructive pattern on pulmonary function testing was observed in 57.3% of the subjects, whereas 33.9% had normal spirometric results. Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form. Conclusions: The age range of women afflicted with pulmonary lymphangioleiomyomatosis is broader than previously appreciated and the degree of pulmonary function can be quite variable, with one-third of subjects having normal spirometry at enrollment into this registry. C1 Mayo Clin, Div Pulm & Crit Care Med, Rochester, MN 55905 USA. NHLBI, Pulm Crit Care Med Branch, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. NHLBI, Biostat Res Branch, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Div Lung Dis, Natl Heart Lung & Blood Inst Project Off, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Div Lung Dis, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci & Crit Care & Pulm Med, Cleveland, OH 44195 USA. Univ Cincinnati, Div Pulm & Crit Care Med, Cincinnati, OH USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Tufts Univ New England Med Ctr, Div Pulm & Crit Care, Boston, MA 02111 USA. Stanford Univ, Ctr Med, Div Pulm & Crit Care Med, Stanford, CA 94305 USA. CIGNA HealthCare, Bloomfield, NJ USA. RP Ryu, JH (reprint author), Mayo Clin, Div Pulm & Crit Care Med, Desk E 18,200 1st St SW, Rochester, MN 55905 USA. EM ryu.jay@mayo.edu OI McCormack, Francis/0000-0001-7168-9464 FU Intramural NIH HHS; NHLBI NIH HHS [U01 HL58440] NR 40 TC 180 Z9 192 U1 0 U2 5 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 JAN 1 PY 2006 VL 173 IS 1 BP 105 EP 111 DI 10.1164/rccm.200409-1298OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 001GA UT WOS:000234520400017 PM 16210669 ER PT J AU Johnson, KT Johnson, CD Fletcher, JG MacCarty, RL Summers, RL AF Johnson, KT Johnson, CD Fletcher, JG MacCarty, RL Summers, RL TI CT colonography using 360 circle virtual dissection: A feasibility study SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE colon polyps; CT colonography; virtual dissection ID COMPUTED TOMOGRAPHIC COLONOGRAPHY; COLORECTAL NEOPLASIA; POLYP DETECTION; COLONOSCOPY; SCREEN AB OBJECTIVE. Using a 3D rendering technique called "virtual dissection," we sought to evaluate polyp and fold distortion using a colon phantom, estimate the polyp detection performance in humans, and estimate the added benefit of double interpretation and computer-aided diagnosis. MATERIALS AND METHODS. A colon phantom containing 144 polyps of varying sizes (5-12 mm) and shapes (flat, sessile, pedunculated) was scanned. Polyp shape and distortion at virtual dissection were categorized as flame, club, pea, or bizarre. Haustral fold distortion was graded. The CT colonography examinations, in 20 consecutive patients (colonoscopically proven normal findings, n = 5; polyps >= 1 cm, n = 17 in 15 patients) were blindly reviewed by three radiologists using the virtual dissection technique, The added benefits of double interpretation and computer-aided diagnosis were tabulated. RESULTS. Sessile polyps appeared flame (35/48 [73%]) or pea (11/48 [23%]) in shape, Flat polyps appeared flame-shaped (31/47 [66%]) or pea-shaped (16/47 [34%]). Pedunculated polyps were flame (15/45 [33%]), club (20/45 [44%]), or pea (6/45 [13%]) in shape, Axial distortion occurred along the longitudinal axis. The sensitivities of the three observers for polyps, of 1 cm or more were 16/17 (94%), 14/17 (82%), and 15/17 (88%). The specificities were 5/5 (100%), 515 (100%), and 4/5 (80%). Sensitivities after double interpretation and computer-aided diagnosis improved but did not reach statistical significance. CONCLUSION. Although distortion of colonic structures exists at virtual dissection, it does so in recognizable patterns, so that sensitivity for polyp detection is not compromised. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. RP Johnson, CD (reprint author), Mayo Clin & Mayo Fdn, 200 1st St SW, Rochester, MN 55905 USA. NR 11 TC 24 Z9 25 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2006 VL 186 IS 1 BP 90 EP 95 DI 10.2214/AJR.04.1658 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 998NY UT WOS:000234327000018 PM 16357384 ER PT J AU Perry, CG Young, WF McWhinney, SR Bei, T Stergiopoulos, S Knudson, RA Ketterling, RP Eng, C Stratakis, CA Carney, JA AF Perry, CG Young, WF McWhinney, SR Bei, T Stergiopoulos, S Knudson, RA Ketterling, RP Eng, C Stratakis, CA Carney, JA TI Functioning paraganglioma and gastrointestinal stromal tumor of the jejunum in three women - Syndrome or coincidence SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE paraganglioma; GIST; jejunum; multiple neoplasia syndrome; Carney triad; genetics ID AUTONOMIC NERVE TUMORS; GERMLINE MUTATION; KIT GENE; HEREDITARY PARAGANGLIOMA; INTERSTITIAL-CELLS; CARNEY TRIAD; SDHD; SARCOMA; DISEASE; FUSION AB Functioning paraganglioma and gastrointestinal stromal tumor (GIST) are uncommon tumors that occur mostly in a sporadic and isolated form, occasionally as components of multiple neoplasia syndromes, either separately or together. Separately, they occur in several inherited syndromes including multiple endocrine neoplasia 2, and the GIST, lentigines, and mast cell tumor syndrome. Together, they are variably prominent components of three syndromes: the familial paraganglioma and gastric GIST syndrome, neurofibromatosis type 1, and the Carney triad. The two former conditions are inherited as autosomal dominant traits; the latter does not appear to be inherited and affects young women predominantly. This article reports the nonfamilial occurrence of functioning paraganglioma and GIST of the jejunum in 3 women, 1 young (22 years) at initial presentation. The occurrences were unexpected because of the infrequency of the tumors. The neoplasms, respectively, did not show germline SDHA, SDHB, SDHC, and SDHD, and KIT mutations associated with familial paraganglioma and familial GIST. The paraganglioma-jejunal GIST combination may be the harbinger of a rare genetic syndrome, a variant of the Carney triad or the paraganglioma-gastric stromal sarcoma syndrome, or be coincidental. C1 Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Mayo Clin, Dept Med Endocrinol, Rochester, MN USA. Ohio State Univ, Dept Med, Human Canc Genet Program, Columbus, OH 43210 USA. Natl Inst Child Hlth, Sect Endocrinol & Genet, Dev Endocrinol Branch, Bethesda, MD USA. RP Carney, JA (reprint author), Mayo Clin, Dept Lab Med & Pathol, 200 SW 1st St, Rochester, MN 55905 USA. EM carney.aidan@mayo.edu OI Eng, Charis/0000-0002-3693-5145 NR 30 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JAN PY 2006 VL 30 IS 1 BP 42 EP 49 DI 10.1097/01.pas.0000178087.69394.9f PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 998IV UT WOS:000234312900007 PM 16330941 ER PT J AU Copersino, ML Boyd, SJ Tashkin, DP Huestis, MA Heishman, SJ Dermand, JC Simmons, MS Gorelick, DA AF Copersino, ML Boyd, SJ Tashkin, DP Huestis, MA Heishman, SJ Dermand, JC Simmons, MS Gorelick, DA TI Cannabis withdrawal among non-treatment-seeking adult cannabis users SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT Annual Meeting of the International-Cannabinoid-Research-Society CY JUN 23-27, 2004 CL Paestum, ITALY SP Int Cannabinoid Res Soc ID SUBSTANCE USE DISORDERS; MARIJUANA WITHDRAWAL; ABSTINENCE SYMPTOMS; ORAL THC; DEPENDENCE; HUMANS; TOLERANCE; SMOKERS AB This study investigates the clinical significance of a cannabis withdrawal syndrome in 104 adult, nontreatment-seeking, primarily cannabis users who reported at least one serious attempt to stop using cannabis. Retrospective self-report data were obtained on eighteen potential cannabis withdrawal symptoms derived from the literature, including co-occurrence, time course, and any actions taken to relieve the symptom. Study findings provide evidence for the clinical significance of a cannabis withdrawal syndrome, based on the high prevalence and co-occurrence of multiple symptoms that follow a consistent time course and that prompt action by the subjects to obtain relief, including serving as negative reinforcement for cannabis use. C1 NIDA, IRP, Clin Pharmacol & Therapeut Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. RP Gorelick, DA (reprint author), NIDA, IRP, Clin Pharmacol & Therapeut Branch, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU NIDA NIH HHS [R0-1 DA03018] NR 26 TC 68 Z9 69 U1 3 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2006 VL 15 IS 1 BP 8 EP 14 DI 10.1080/10550490500418997 PG 7 WC Substance Abuse SC Substance Abuse GA 007TE UT WOS:000234991900003 PM 16449088 ER PT J AU Simon, SL Bouville, A Land, CE AF Simon, SL Bouville, A Land, CE TI Fallout from nuclear weapons tests and cancer risks - Exposures 50 years ago still have health implications today that will continue into the future SO AMERICAN SCIENTIST LA English DT Article ID NEVADA TEST-SITE; THYROID-CANCER; I-131 AB Exposure to nuclear fallout from nuclear weapons testing in the 1950's is still having implications today. The radiation dose and cancer risk to humans living in close proximity to test sites in the Nevada desert, Kazakhstan, The Marshall Islands is evaluated. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM ssimon@mail.nih.gov NR 19 TC 20 Z9 23 U1 1 U2 6 PU SIGMA XI-SCI RES SOC PI RES TRIANGLE PK PA PO BOX 13975, RES TRIANGLE PK, NC 27709 USA SN 0003-0996 J9 AM SCI JI Am. Scientist PD JAN-FEB PY 2006 VL 94 IS 1 BP 48 EP 57 DI 10.1511/2006.57.982 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 992LN UT WOS:000233885500018 ER PT S AU Silveira, JR Hughson, AG Caughey, B AF Silveira, Jay R. Hughson, Andrew G. Caughey, Byron BE Kheterpal, I Wetzel, R TI Fractionation of prion protein aggregates by asymmetrical flow field-flow fractionation SO AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID HUMAN PLASMA; SEPARATION; LIPOPROTEINS; INFECTIVITY; CHANNEL; ACIDS AB Achieving the successful separation and analysis of amyloid and other large protein aggregates can be a difficult proposition. Field-flow fractionation (FFF) is a flow-based separation method like chromatography; however, FFF is capable of high-resolution separations in the absence of a stationary matrix. Thus, FFF is a relatively gentle technique and is well suited to the task of separating large macromolecules and macromolecular complexes. Flow field-flow fractionation (FlFFF), one of the techniques in the FFF family, has been used to successfully fractionate a wide size range of prion protein aggregates, allowing their subsequent characterization by several biophysical and biochemical methods. The ability to easily adjust the strength of the field used during separation means that FlFFF could be applied to particles ranging from 1 nm to nearly 100 mu m in size. This flexibility, coupled with the ability to produce fast, high-resolution separations, makes FFF a potentially valuable tool in the field of amyloid research. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Silveira, JR (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. FU Intramural NIH HHS NR 31 TC 21 Z9 21 U1 0 U2 14 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182817-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 412 BP 21 EP 33 DI 10.1016/S0076-6879(06)12002-9 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFH12 UT WOS:000241828800002 PM 17046649 ER PT S AU Kocisko, DA Caughey, B AF Kocisko, David A. Caughey, Byron BE Kheterpal, I Wetzel, R TI Searching for anti-prion compounds: Cell-based high-throughput in vitro assays and animal testing strategies SO AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CULTURED-CELLS; INCUBATION PERIOD; PROTEIN-FORMATION; SHEEP SCRAPIE; RESISTANT; MICE; PRP; INHIBITION; INFECTION AB The transmissible spongiform encephalopathies (TSEs) or prion diseases are infectious neurodegenerative diseases of mammals. Protease-resistant prion protein (PrP-res) is only associated with TSEs and thus has been a target for therapeutic intervention. The most effective compounds known against scrapie in vivo are inhibitors of PrP-res in infected cells. Mouse neuroblastoma (N2a) cells have been chronically infected with several strains of mouse scrapie including RML and 22L. Also, rabbit epithelial cells that produce sheep prion protein in the presence of doxycycline (Rov9) have been infected with sheep scrapie. Here a high-throughput 96-well plate PrP-res inhibition assay is described for each of these scrapie-infected cell lines. With this dot-blot assay, thousands of compounds can easily be screened for inhibition of PrP-res formation. This assay is designed to find new PrP-res inhibitors, which may make good candidates for in vivo anti-scrapie testing. However, an in vitro assay can only suggest that a given compound might have in vivo anti-scrapie activity, which is typically measured as increased survival times. Methods for in vivo testing of compounds for anti-scrapie activity in transgenic mice, a much more lengthy and expensive process, are also discussed. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Kocisko, DA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NR 37 TC 18 Z9 20 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182817-4 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 412 BP 223 EP 234 DI 10.1016/S0076-6879(06)12014-5 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFH12 UT WOS:000241828800014 PM 17046661 ER PT S AU Tycko, R AF Tycko, Robert BE Kheterpal, I Wetzel, R TI Characterization of amyloid structures at the molecular level by solid state nuclear magnetic resonance spectroscopy SO AMYLOID, PRIONS, AND OTHER PROTEIN AGGREGATES, PT C SE Methods in Enzymology LA English DT Review; Book Chapter ID BETA-SHEET STRUCTURE; NMR-SPECTROSCOPY; DISTANCE MEASUREMENTS; SECONDARY-STRUCTURE; SUPRAMOLECULAR STRUCTURE; EXPERIMENTAL CONSTRAINTS; ALZHEIMERS-DISEASE; PROTEIN-STRUCTURE; FIBRIL FORMATION; ROTATIONAL-ECHO AB Solid state nuclear magnetic resonance (NMR) spectroscopy is particularly useful in structural studies of amyloid fibrils because solid state NMR techniques have unique capabilities as site-specific, molecular-level structural probes of noncrystalline materials. These techniques provide experimental data that strongly constrain the secondary, tertiary, and quaternary structures of amyloid fibrils, permitting the development of experimentally based structural models. Examples of techniques that are applicable to amyloid samples prepared with isotopic labeling of specific sites and to samples prepared with uniform isotopic labeling of selected residues are presented, illustrating the utility of the various techniques and labeling schemes. Information regarding the preparation of amyloid samples for solid state NMR measurements is also included. C1 NIDDK, Natl Inst Hlth, Phys Chem Lab, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDK, Natl Inst Hlth, Phys Chem Lab, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 64 TC 34 Z9 34 U1 1 U2 6 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182818-2 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 413 BP 103 EP 122 DI 10.1016/S0076-6879(06)13006-2 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFH13 UT WOS:000241828900006 PM 17046393 ER PT J AU Pan, J Davis, W Trushin, N Amin, S Nath, RG Salem, N Chung, FL AF Pan, J Davis, W Trushin, N Amin, S Nath, RG Salem, N Chung, FL TI A solid-phase extraction/high-performance liquid chromatography-based P-32-postlabeling method for detection of cyclic 1,N-2-propanodeoxyguanosine adducts derived from enals SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE 1,N-2-propanodG; enal-derived cyclic adducts; aldehyde-DNA adducts; acrolein; 4-hydroxy-2-nonenal; cyclic deoxyguanosine adducts; P-32-postlabeling; high-performance liquid chromatography; solid-phase extraction ID ENDOGENOUS DNA LESIONS; DEOXYGUANOSINE ADDUCTS; ALDEHYDES; RODENTS; HUMANS AB The cyclic 1,N-2-propanodeoxyguanosine (PdG) adducts are Michael addition products from reactions of deoxyguanosine (dG) with enals, including acrolein (Act), crotonaldehyde (Cro), pentenal (Pen), heptenal (Hep), and 4-hydroxy-2-nonenal (HNE). Although this is a general reaction, only the PdG adducts derived from Act, Cro, and FINE have been detected in vivo as endogenous DNA lesions. Our previous in vitro study demonstrated that PdG adducts of Acr, Cro, and Pen are predominantly derived from oxidation of omega-3 polyunsaturated fatty acids (PUFAs), whereas the long-chain Hep and HNE adducts are from omega-6 PUFAs. PdG adducts are important because they represent a new class of endogenous promutagenic DNA lesions with potential roles in carcinogenesis. Earlier, we developed a (32)p- postlabeling method for detecting PdG adducts from Acr and Cro and a modified method for the long-chain HNE adducts. Both methods require multiple high-performance liquid chromatography steps and, in some cases, time-consuming thin-layer chromatography for purification. There is a lack of a single, versatile, and efficient method for simultaneous detection of all five enal-derived PdG adducts. In this paper, we report an improved P-32-Post labeling method which permits detection of Acr, Cro, Pen, Hep, and HNE adducts in a single DNA sample. This method relies on solid-phase extraction for adduct enrichment before and after P-32-labeling; all five PdG adducts were converted to the ring-opened derivatives for confirmation of identities and quantification. The method was validated using the synthetic adducts and enal-modified DNA and was finally applied to rat liver DNA and rat liver DNA samples spiked with different amount of standards. The detection limit was determined to be as low as 0.5 fmol in 80 mu g DNA, corresponding to 9 adducts/10(9) dG. (c) 2005 Published by Elsevier Inc. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Penn State Univ Hosp, Coll Med, Hershey, PA 17033 USA. NIAAA, Rockville, MD 20852 USA. RP Chung, FL (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. EM flc6@georgetown.edu FU NCI NIH HHS [CA43159] NR 25 TC 20 Z9 21 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 2006 VL 348 IS 1 BP 15 EP 23 DI 10.1016/j.ab.2005.10.011 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 000GB UT WOS:000234447800002 PM 16289438 ER PT J AU McPhie, P AF McPhie, P TI Resonance light scattering profiles must be corrected for instrument performance SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID NANOGRAM LEVELS; PROTEINS; ENHANCEMENT; ACIDS C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP McPhie, P (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM pmcphie@helix.nih.gov FU Intramural NIH HHS NR 11 TC 17 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JAN 1 PY 2006 VL 348 IS 1 BP 157 EP 159 DI 10.1016/j.ab.2005.10.022 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 000GB UT WOS:000234447800021 PM 16298324 ER PT J AU Prasad, R Quezado, Z St Andre, A O'Grady, NP AF Prasad, R Quezado, Z St Andre, A O'Grady, NP TI Fires in the operating room and intensive care unit: Awareness is the key to prevention SO ANESTHESIA AND ANALGESIA LA English DT Article ID IGNITION; OXYGEN AB Recent recommendations from the Centers for Disease Control (CDC) to use alcohol-based substances for hand hygiene and skin antisepsis could introduce new fire hazards in the operating room (OR) (1). This potential for an increase in the number of fires in the hospital setting with wide spread use of alcohol-based agents warrants heightened awareness of the risks and implementation of safety measures when using these agents. Here, we report a patient who, during a tracheostomy, sustained severe bums resulting from a fire in the OR. In this case, the use of an alcohol-based antiseptic was the major contributing factor to the surgical fire. C1 NIH, Vasc Access Serv, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Conscious Sedat Serv, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Prasad, R (reprint author), NIH, Vasc Access Serv, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. EM nogrady@mail.cc.nih.gov RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 11 TC 19 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2006 VL 102 IS 1 BP 172 EP 174 DI 10.1213/01.ane.0000183641.09008.f2 PG 3 WC Anesthesiology SC Anesthesiology GA 997VA UT WOS:000234275700029 PM 16368825 ER PT J AU Manimala, JC Roach, TA Li, ZT Gildersleeve, JC AF Manimala, JC Roach, TA Li, ZT Gildersleeve, JC TI High-throughput carbohydrate microarray analysis of 24 lectins SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE carbohydrates; glycoconjugates; glycosides; lectins; microarrays ID GLYCAN MICROARRAYS; BINDING; ARRAYS; ANTIBODIES; REVEALS; SPECIFICITIES; RECOGNITION; PROTEINS; LIGANDS; CANCER C1 NCI, Ctr Canc Res, Med Chem Lab, Ft Detrick, MD 21702 USA. RP Gildersleeve, JC (reprint author), NCI, Ctr Canc Res, Med Chem Lab, 376 Boyles St,376-109, Ft Detrick, MD 21702 USA. EM gildersleevej@ncifcrf.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU Intramural NIH HHS NR 30 TC 106 Z9 107 U1 0 U2 8 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2006 VL 45 IS 22 BP 3607 EP 3610 DI 10.1002/anie.200600591 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 050DP UT WOS:000238068000006 PM 16639753 ER PT J AU Davidson, KW Kupfer, DJ Bigger, JT Califf, RM Carney, RM Coyne, JC Czajkowski, SM Frank, E Frasure-Smith, N Freedland, KE Froelicher, ES Glassman, AH Katon, WJ Kaufmann, PG Kessler, RC Kraemer, HC Krishnan, KRR Lesperance, F Rieckmann, N Sheps, DS Suls, JM AF Davidson, Karina. W. Kupfer, David J. Bigger, J. Thomas Califf, Robert M. Carney, Robert M. Coyne, James C. Czajkowski, Susan M. Frank, Ellen Frasure-Smith, Nancy Freedland, Kenneth E. Froelicher, Erika S. Glassman, Alexander H. Katon, Wayne J. Kaufmann, Peter G. Kessler, Ronald C. Kraemer, Helena C. Krishnan, K. Ranga R. Lesperance, Francois Rieckmann, Nina Sheps, David S. Suls, Jerry M. TI Assessment and treatment of depression in patients with cardiovascular disease: National Heart, Lung, and Blood Institute Working Group Report SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID MYOCARDIAL-INFARCTION; RANDOMIZED-TRIAL; PLATELET/ENDOTHELIAL BIOMARKERS; ENHANCING RECOVERY; COLLABORATIVE CARE; UNITED-STATES; SERTRALINE; EVENTS; COMORBIDITY; SENSITIVITY C1 Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Sch Med, Pittsburgh, PA 15213 USA. NHLBI, Behav Med & Prevent Res Grp, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. Washington Univ, Sch Med, Dept Psychiat, Behav Med Ctr, St Louis, MO 63110 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. McGill Univ, Dept Psychiat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Sch Nursing, Montreal, PQ H3A 2T5, Canada. Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada. Univ Montreal, Ctr Hosp, Res Ctr, Montreal, PQ H3C 3J7, Canada. Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Duke Univ, Sch Med, Dept Psychiat & Behav Sci, Durham, NC 27706 USA. Univ Florida, Div Cardiovasc Med, Gainesville, FL 32611 USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. RP Davidson, KW (reprint author), Columbia Univ Coll Phys & Surg, Dept Med, 622 W 168th St,PH9 Ctr,Room 941, New York, NY 10032 USA. EM kd2124@columbia.edu RI Lesperance, Francois/C-4716-2015 OI Lesperance, Francois/0000-0003-4604-2823 NR 24 TC 33 Z9 33 U1 3 U2 4 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2006 VL 32 IS 2 BP 121 EP 126 DI 10.1207/s15324796abm3202_9 PG 6 WC Psychology, Multidisciplinary SC Psychology GA 092DF UT WOS:000241076500009 PM 16972809 ER PT J AU Peters, E McCaul, KD Stefanek, M Nelson, W AF Peters, E McCaul, KD Stefanek, M Nelson, W TI A heuristics approach to understanding cancer risk perception: Contributions from judgment and decision-making research SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID BILATERAL PROPHYLACTIC MASTECTOMY; BREAST-CANCER; FAMILY-HISTORY; PSYCHOLOGICAL DISTRESS; RANDOMIZED TRIAL; SMOKING RISK; HEALTH; WOMEN; IMPACT; COMMUNICATION AB Background. The likelihood judgments that people make about their risks for cancer have important implications. At the individual level, risk estimates guide protective actions, such as cancer screening. However at the extremes, exaggerated risk judgments can also lead to anxiety that degrades quality of life or to aggressive self-protective actions that arc, unwarranted given the objective risks. At the policy level, risk judgments may serve as an indicator of societal perceptions of the "war" against cancer. Using risk judgments, the public expresses its belief about whether we are winning. Purpose: I've present theoretical perspectives from judgment and decision making, illustrate how they can explain some of the existing empirical findings in the cancer risk literature, and describe additional predictions that have not yet been tested. Conclusions: Overall, we suggest that theories from the judgment and decision-making perspective offer a potentially powerful view for understanding and improving risk judgments for cancer and other diseases. C1 Decis Res, Eugene, OR 97401 USA. Univ Oregon, Eugene, OR 97403 USA. N Dakota State Univ, Fargo, ND 58105 USA. NCI, Bethesda, MD 20892 USA. RP Peters, E (reprint author), Decis Res, 1201 Oak St,Suite 200, Eugene, OR 97401 USA. EM empeters@uoregon.edu FU NCI NIH HHS [K05 CA92633] NR 66 TC 49 Z9 49 U1 1 U2 12 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2006 VL 31 IS 1 BP 45 EP 52 DI 10.1207/s15324796abm3101_8 PG 8 WC Psychology, Multidisciplinary SC Psychology GA 014VB UT WOS:000235507300008 PM 16472038 ER PT J AU Koenig, KL Hatchett, RJ Mettler, FA Goans, RE Schumacher, TA Noji, EK Jarrett, DG AF Koenig, KL Hatchett, RJ Mettler, FA Goans, RE Schumacher, TA Noji, EK Jarrett, DG TI Use high awareness and judgment to screen emergency department patients for radiation exposure SO ANNALS OF EMERGENCY MEDICINE LA English DT Letter C1 Univ Calif Irvine, Dept Emergency Med, Sch Med, Orange, CA 92668 USA. NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. New Mexico Fed Reg Med Ctr, Dept Radiol, Albuquerque, NM USA. Tulane Univ, Sch Publ Hlth & Trop Med, MJW Corp, Clinton, TN USA. Richard L Roudebush VA Med Ctr, VA Med Emergency Radiol Response Team, Indianapolis, IN USA. Dept Homeland Secur, Washington, DC USA. Uniformed Serv Univ Hlth Sci, USA, Armed Forces Radiobiol Res Inst, Bethesda, MD 20814 USA. RP Koenig, KL (reprint author), Univ Calif Irvine, Dept Emergency Med, Sch Med, Orange, CA 92668 USA. NR 2 TC 1 Z9 1 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD JAN PY 2006 VL 47 IS 1 BP 120 EP 121 DI 10.1016/j.annemergmed.2005.08.032 PG 2 WC Emergency Medicine SC Emergency Medicine GA 001OO UT WOS:000234546400028 ER PT J AU Vaurs-Barriere, C Bonnet-Dupeyron, MN Combes, P Gauthier-Barichard, F Reveles, XT Schiffmann, R Bertini, E Rodriguez, D Vago, P Armour, JAL Saugier-Veber, P Frebourg, T Leach, RJ Boespflug-Tanguy, O AF Vaurs-Barriere, C Bonnet-Dupeyron, MN Combes, P Gauthier-Barichard, F Reveles, XT Schiffmann, R Bertini, E Rodriguez, D Vago, P Armour, JAL Saugier-Veber, P Frebourg, T Leach, RJ Boespflug-Tanguy, O TI Golli-MBP copy number analysis by FISH, QMPSF and MAPH in 195 patients with hypomyelinating leukodystrophies SO ANNALS OF HUMAN GENETICS LA English DT Article ID MYELIN BASIC-PROTEIN; SHIVERER MUTANT MICE; PELIZAEUS-MERZBACHER-DISEASE; CENTRAL-NERVOUS-SYSTEM; CONTROL INDIVIDUALS; KABUKI-SYNDROME; 8P22-8P23.1 DUPLICATION; ANXIETY DISORDERS; DEFICIENT-SHIMLD; PANIC DISORDER AB The inherited disorders of CNS myelin formation represent a heterogeneous group of leukodystrophies. The proteolipoprotein (PLP1) gene has been implicated in two X-linked forms, Pelizaeus-Merzbacher disease (PMD) and spastic paraplegia type 2, and the gap junction protein alpha 12 (GJA12) gene in a recessive form of PMD. The myelin basic protein (MBP) gene, which encodes the second most abundant CNS myelin protein after PLP1, presents rearrangements in hypomyelinating murine mutants and is always included in the minimal region deleted in 18q- patients with an abnormal hypomyelination pattern on cerebral MRI. In this study, we looked at the genomic copy number at the Golli-MBP locus in 195 patients with cerebral MRI suggesting a myelin defect, who do not have PLP1 mutation. Although preliminary results obtained by FISH suggested the duplication of Golli-MBP in 3 out of 10 patients, no abnormal gene quantification was found using Quantitative Multiplex PCR of Short Fluorescent fragments (QMPSF), Multiplex Amplifiable Probe Hybridization (MAPH), or another FISH protocol using directly-labelled probes. Pitfalls and interest in these different techniques to detect duplication events are emphasised. Finally, the study of this large cohort of patients suggests that Golli-MBP deletion or duplication is rarely involved in inherited defects of myelin formation. C1 Fac Med, INSERM, U384, F-63000 Clermont Ferrand, France. Fac Med CHU, F-63000 Clermont Ferrand, France. Univ Texas, Hlth Sci Ctr, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Osped Pediat Bambino Gesu, Inst Sci, IRCCS, Dept Mol Med, Rome, Italy. Fac Pitie Salpetriere, INSERM, U546, F-75013 Paris, France. Univ Nottingham, Inst Genet, Nottingham NG7 2UH, England. Fac Med & Pharm, INSERM, U614, F-76183 Rouen, France. RP Boespflug-Tanguy, O (reprint author), Fac Med, INSERM, U384, Pl Henri Dunant, F-63000 Clermont Ferrand, France. EM Odile.Boespflug@u-clermont1.fr NR 43 TC 10 Z9 11 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2006 VL 70 BP 66 EP 77 DI 10.1111/j.1529-8817.2005.00208.x PN 1 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 007MP UT WOS:000234974100006 PM 16441258 ER PT J AU Hageman, GS Hancox, LS Taiber, AJ Gehrs, KM Anderson, DH Johnson, LV Radeke, MJ Kavanagh, D Richards, A Atkinson, J Meri, S Bergeron, J Zernant, J Merriam, J Gold, B Allikmets, R Dean, M AF Hageman, Gregory S. Hancox, Lisa S. Taiber, Andrew J. Gehrs, Karen M. Anderson, Don H. Johnson, Lincoln V. Radeke, Monte J. Kavanagh, David Richards, Anna Atkinson, John Meri, Seppo Bergeron, Julie Zernant, Jana Merriam, Joanna Gold, Bert Allikmets, Rando Dean, Michael CA AMD Clinical Study Grp TI Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: Characterization, ethnic distribution and evolutionary implications SO ANNALS OF MEDICINE LA English DT Article DE age-related macular degeneration; alternative pathway; complement; deletion; evolution; factor H; factor H-related; haplotype; vision ID HEMOLYTIC-UREMIC SYNDROME; DENSE DEPOSIT DISEASE; HUMAN GENOME; STRONG ASSOCIATION; Y402H VARIANT; POLYMORPHISM; RISK; POPULATION; MUTATIONS; MACULOPATHY AB Background. Variants in the complement factor H gene (CFH) are associated with age-related macular degeneration (AMD). CFH and five CFH-related genes (CFHR1-5) lie within the regulators of complement activation (RCA) locus on chromosome 1q32. Aims and Methods. In this study, the structural and evolutionary relationships between these genes and AMD was refined using a combined genetic, molecular and immunohistochemical approach. Results. We identify and characterize a large, common deletion that encompasses both the CFHR1 and CFHR3 genes. CFHR1, an abundant serum protein, is absent in subjects homozygous for the deletion. Genotyping analyses of AMD cases and controls from two cohorts demonstrates that deletion homozygotes comprise 1.1% of cases and 5.7% of the controls (chi-square = 32.8; P = 1.6 E-09). CFHR1 and CFHR3 transcripts are abundant in liver, but undetectable in the ocular retinal pigmented epithelium/choroid complex. AMD-associated CFH/CFHR1/CFHR3 haplotypes are widespread in human populations. Conclusion. The absence of CFHR1 and/or CFHR3 may account for the protective effects conferred by some CFH haplotypes. Moreover, the high frequencies of the 402H allele and the delCFHR1/CFHR3 alleles in African populations suggest an ancient origin for these alleles. The considerable diversity accumulated at this locus may be due to selection, which is consistent with an important role for the CFHR genes in innate immunity. C1 Univ Iowa, Dept Ophthalmol & Visual Sci, Cell Biol & Funct Genom Lab, Iowa City, IA 52240 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Univ Calif Santa Barbara, Neurosci Res Inst, Santa Barbara, CA 93106 USA. Washington Univ, Sch Med, Dept Med, Div Rheumatol, St Louis, MO 63130 USA. Univ Helsinki, Haartman Inst, Dept Bacteriol & Immunol, FIN-00014 Helsinki, Finland. Columbia Univ, Dept Ophthalmol, New York, NY 10027 USA. Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10027 USA. RP Hageman, GS (reprint author), Univ Iowa, Dept Ophthalmol & Visual Sci, Cell Biol & Funct Genom Lab, 11190E PFP,200 Hawkins Dr, Iowa City, IA 52240 USA. EM dean@ncifcrf.gov RI Kavanagh, David/E-8498-2011; Dean, Michael/G-8172-2012; Richards, Anna/E-8337-2013 OI Kavanagh, David/0000-0003-4718-0072; Dean, Michael/0000-0003-2234-0631; FU Intramural NIH HHS [Z01 BC005652-15]; NCI NIH HHS [N01-CO-12400, N01CO12400]; NEI NIH HHS [R01 EY013435, R01 EY011515, R01 EY011515-07S2, R01 EY011521, R01 EY011527, R01 EY011527-07, R01 EY013435-05, R01 EY11515, R01 EY11521, R24 EY017404] NR 60 TC 146 Z9 147 U1 1 U2 14 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0785-3890 J9 ANN MED JI Ann. Med. PY 2006 VL 38 IS 8 BP 592 EP 604 DI 10.1080/07853890601097030 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 125GY UT WOS:000243431600006 PM 17438673 ER PT J AU Smemo, S Nowotny, P Hinrichs, AL Kauwe, JSK Cherny, S Erickson, K Myers, AJ Kaleem, M Marlowe, L Gibson, AM Hollingworth, P O'Donovan, MC Morris, CM Holmans, P Lovestone, S Morris, JC Thal, L Li, YH Grupe, A Hardy, J Owen, MJ Williams, J Goate, A AF Smemo, S Nowotny, P Hinrichs, AL Kauwe, JSK Cherny, S Erickson, K Myers, AJ Kaleem, M Marlowe, L Gibson, AM Hollingworth, P O'Donovan, MC Morris, CM Holmans, P Lovestone, S Morris, JC Thal, L Li, YH Grupe, A Hardy, J Owen, MJ Williams, J Goate, A TI Ubiquilin 1 polymorphisms are not associated with late-onset Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID CANDIDATE-GENE; GENOME SCREEN; FREQUENCY; DISEQUILIBRIUM; VARIANTS; LINKAGE; FAMILY; ALLELE AB Several studies have reported evidence for linkage of late-onset Alzheimer's disease (LOAD) to chromosome 9. Recently, an intronic polymorphism affecting alternative splicing of exon 8 of ubiquilin 1 (UBQLN1) was reported to be associated with LOAD. We attempted to replicate this observation by genotyping this polymorphism, rs12344615 (also known as UBQ-8i), in a large sample of 1,544 LOAD cases and 1,642 nondemented controls. We did not find any evidence that this single nucleotide polymorphism, or any of six others tested in UBQLN1, increases risk for LOAD. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. NIA, Bethesda, MD 20892 USA. Univ Newcastle Upon Tyne, Newcastle Gen Hosp, Inst Hlth & Aging, Newcastle Upon Tyne, Tyne & Wear, England. Cardiff Univ, Sch Med, Dept Med Psychol, Cardiff, Wales. Cardiff Univ, Biostat & Bioinformat Unit, Cardiff, Wales. Univ London Kings Coll, Inst Psychiat, London, England. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Celera Diagnost, Alameda, CA USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. RP Goate, A (reprint author), Washington Univ, Sch Med, Dept Psychiat, Campus Box 8134,660 S Euclid St, St Louis, MO 63110 USA. EM goate@icarus.wustl.edu RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Kauwe, John/B-2034-2009; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; OI Myers, Amanda/0000-0002-3100-9396; Kauwe, John/0000-0001-8641-2468; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379 FU Medical Research Council [G0300429, G0701075, G9810900]; NIA NIH HHS [P50 AG 05131, AG 16208, P01 AG 03991, P50 AG 05681] NR 22 TC 32 Z9 32 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2006 VL 59 IS 1 BP 21 EP 26 DI 10.1002/ana.20673 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 000FU UT WOS:000234447100003 PM 16278862 ER PT J AU Ristori, G Cannoni, S Stazi, MA Vanacore, N Cotichini, R Alfo, M Pugliatti, M Sotgiu, S Solaro, C Bomprezzi, R Di Giovanni, S Talamanca, LF Nistico, L Fagnani, C Neale, MC Cascino, I Giorgi, G Battaglia, MA Buttinelli, C Tosi, R Salvetti, M AF Ristori, G Cannoni, S Stazi, MA Vanacore, N Cotichini, R Alfo, M Pugliatti, M Sotgiu, S Solaro, C Bomprezzi, R Di Giovanni, S Talamanca, LF Nistico, L Fagnani, C Neale, MC Cascino, I Giorgi, G Battaglia, MA Buttinelli, C Tosi, R Salvetti, M CA Italian Study Grp on Multiple Scle TI Multiple sclerosis in twins from continental Italy and Sardinia: A nationwide study SO ANNALS OF NEUROLOGY LA English DT Article ID BRITISH-ISLES SURVEY; PREVALENCE; RISK; CONCORDANCE; CITY; ZYGOSITY; RATES; MS AB Knowledge about the balance between heritable and nonheritable risk in multiple sclerosis (MS) is based on twin studies in high-prevalence areas. In a study that avoided ascertainment limitations and directly compared continental Italy (medium-prevalence) and Sardinia (high-prevalence), we ascertained 216 pairs from 34,549 patients. This gives a twinning rate of 0.62% among MS patients, significantly less than that of the general population. In continental Italy, probandwise concordance was 14.5% (95% confidence interval, 5.1-23.8) for monozygotic and 4.0% (95% confidence interval, 0.8-7.1) for dizygotic twins. Results in Sardinia resemble those in northern populations but in limited numbers. Monozygotic concordance was 22.2% (95% confidence interval, 0-49.3) probandwise, but no concordant dizygotic pairs were identified. A questionnaire on 80 items possibly related to disease cause was administered to 70 twin pairs, 135 sporadic patients, and 135 healthy volunteers. Variables positively (7) or negatively (2) associated with predisposition and concordance in twins largely overlapped and were mainly linked to infection. If compared with previous studies, our data demonstrate that penetrance in twins appears to correlate with MS prevalence. They highlight the relevance of nonheritable variables in Mediterranean areas. The apparent underrepresentation of MS among Italian twins draws attention to protective factors, shared by twins, that may influence susceptibility. C1 Univ Roma La Sapienza, St Andreas Hosp, Ctr Expt Neurol Therapy, I-00189 Rome, Italy. Univ Roma La Sapienza, Ist Super Sanita, Rome, Italy. Univ Sassari, Inst Clin Neurol, Sassari, Italy. PA Micone Hosp, Dept Neurol, Genoa, Italy. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA USA. Consiglio Nazl Delle Ric, Inst Cell Biol, Rome, Italy. Italian Muliple Schlerosis Soc, Genoa, Italy. RP Salvetti, M (reprint author), Univ Roma La Sapienza, St Andreas Hosp, Ctr Expt Neurol Therapy, Via Grottarossa 1035-1039, I-00189 Rome, Italy. EM marco.salvetti@uniroma1.it RI Neale, Michael/B-1418-2008; Fagnani, Corrado/J-9069-2016; stazi, maria /K-4597-2016; OI Fagnani, Corrado/0000-0001-5771-7772; Alfo', Marco/0000-0001-7651-6052 NR 48 TC 36 Z9 37 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2006 VL 59 IS 1 BP 27 EP 34 DI 10.1002/ana.20683 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 000FU UT WOS:000234447100004 PM 16240370 ER PT J AU Parent, JM Elliott, RC Pleasure, SJ Barbaro, NM Lowenstein, DH AF Parent, JM Elliott, RC Pleasure, SJ Barbaro, NM Lowenstein, DH TI Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy SO ANNALS OF NEUROLOGY LA English DT Article ID ECTOPIC GRANULE CELLS; ADULT MAMMALIAN BRAIN; RAT DENTATE GYRUS; STATUS EPILEPTICUS; POSTNATAL NEUROGENESIS; SUBVENTRICULAR ZONE; NEURONAL MIGRATION; LIMBIC SEIZURES; OLFACTORY BULB; MESSENGER-RNAS AB Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures. C1 Univ Michigan, Med Ctr, Dept Neurol, Ann Arbor, MI 48109 USA. NINDS, NIH, Bethesda, MD USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. RP Parent, JM (reprint author), Univ Michigan, Med Ctr, Dept Neurol, 4412 Kresge 3,200 Zina Pitcher Pl, Ann Arbor, MI 48109 USA. EM parent@umich.edu FU NINDS NIH HHS [NS 02006, NS 32062] NR 50 TC 187 Z9 200 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2006 VL 59 IS 1 BP 81 EP 91 DI 10.1002/ana.20699 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 000FU UT WOS:000234447100010 PM 16261566 ER PT J AU Glasker, S Sohn, TS Okamoto, H Li, J Lonser, RR Oldfield, EH Vortmeyer, AO Zhuang, ZP AF Glasker, S Sohn, TS Okamoto, H Li, J Lonser, RR Oldfield, EH Vortmeyer, AO Zhuang, ZP TI Second hit deletion size in von Hippel-Lindau disease SO ANNALS OF NEUROLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; RENAL-CELL CARCINOMA; CLEAR-CELL; GERMLINE DELETION; INACTIVATION; MUTATION; HEMANGIOBLASTOMAS; PHENOTYPE; LOSSES AB von Hippel-Lindau (VHL) disease is caused by germline mutations of the VHL tumor suppressor gene. Affected individuals are predisposed to development of multiple neoplastic and preneoplastic lesions of different organs. A "second hit," which is usually represented by deletion in the wild-type VHL allele at 3p25, is necessary for initiation of tumor formation. The impact of the size of this deletion is thought to be critical, because other tumor suppressor genes are located nearby, but this has not yet been studied in detail. We mapped the deletion size of the "second hit" in micro-dissected tissue from 16 different VHL-associated lesions from the same patient using 10 polymorphic chromosome 3 markers. We found that the deletion size is highly variable, ranging from short deletions around the VHL gene to complete loss of the chromosome 3. The deletion sizes are not correlated with the site of the germline mutation, the affected organ, or the type or biological behavior of the tumor. Even preneoplastic cystic structures may harbor entire loss of the chromosome 3, suggesting that loss of VHL gene function alone is not immediately causative for neoplastic growth, but further events, either mutations and deletions in other chromosomes or epigenetic or other than genetic phenomena, are required for tumor formation. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Freiburg, Neurochirurg Univ Klin, Freiburg, Germany. Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Surg, Seoul, South Korea. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM zhuangp@mail.nih.gov FU Intramural NIH HHS NR 20 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2006 VL 59 IS 1 BP 105 EP 110 DI 10.1002/ana.20704 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 000FU UT WOS:000234447100012 PM 16261628 ER PT J AU Fujita, M Ichise, M Zoghbi, SS Liow, JS Ghose, S Vines, DC Sangare, J Lu, JQ Cropley, VL Iida, H Kim, KM Cohen, RM Bara-Jimenez, W Ravina, B Innis, RB AF Fujita, M Ichise, M Zoghbi, SS Liow, JS Ghose, S Vines, DC Sangare, J Lu, JQ Cropley, VL Iida, H Kim, KM Cohen, RM Bara-Jimenez, W Ravina, B Innis, RB TI Widespread decrease of nicotinic acetylcholine receptors in Parkinson's disease SO ANNALS OF NEUROLOGY LA English DT Article ID LINEAR-REGRESSION ANALYSIS; ALZHEIMERS-DISEASE; BRAIN; 5-IODO-A-85380; STRIATUM; DEMENTIA; SPECT AB Objective: Nicotinic acetylcholine receptors have close interactions with the dopaminergic system and play critical roles in cognitive function. The purpose of this study was to compare these receptors between living PD patients and healthy subjects. Methods: Nicotinic acetylcholine receptors were imaged in 10 nondemented Parkinson's disease patients and 15 age-matched healthy subjects using a single-photon emission computed tomography ligand [I-123]5-iodo-3-[2(S)-2-azetidinylmethoxy]pyridine. Using an arterial input function, we measured the total distribution volume (V; specific plus nondisplaceable), as well as the delivery (K,). Results. Parkinson's disease showed a widespread significant decrease (approximately 10%) of V in both cortical and subcortical regions without a significant change in K-1. Interpretation: These results indicate the importance of extending the study to demented patients. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 565, Japan. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, Bethesda, MD USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 1,Room B3-10,1 Ctr Dr,MSC-0135, Bethesda, MD 20892 USA. EM fujitam@intra.nimh.nih.gov RI Iida, Hidehiro/D-4582-2011; Ghose, Subroto/J-6732-2016 FU NIMH NIH HHS [2D1 MH 002796-04, Z01 MH002796-04] NR 20 TC 47 Z9 53 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2006 VL 59 IS 1 BP 174 EP 177 DI 10.1002/ana.20688 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 000FU UT WOS:000234447100020 PM 16374823 ER PT J AU Dennis, PA AF Dennis, PA TI The development of inhibitors of PI3K and Akt SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th International Symposium on Targeted Anticancer Therapies CY MAR 16-18, 2006 CL Amsterdam, NETHERLANDS SP Novartis, AstraZeneca, Bayer HealthCare, Centocor, Johnson & Johnson, Lilly, Merck, MSD, OSI, Schering C1 NCI, 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. PY 2006 VL 17 SU 3 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 046GZ UT WOS:000237800900019 ER PT J AU Wright, JJ AF Wright, JJ TI Dual kinase Src-Abl inhibitors: An emerging class of targeted agents with activity in hematologic malignancy and solid tumors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 4th International Symposium on Targeted Anticancer Therapies CY MAR 16-18, 2006 CL Amsterdam, NETHERLANDS SP Novartis, AstraZeneca, Bayer HealthCare, Centocor, Johnson & Johnson, Lilly, Merck, MSD, OSI, Schering C1 NCI, Canc Therapy Evaluat Program, 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. PY 2006 VL 17 SU 3 BP 24 EP 24 PG 1 WC Oncology SC Oncology GA 046GZ UT WOS:000237800900020 ER PT J AU Jacoby, R Cole, C Lubet, R AF Jacoby, R. Cole, C. Lubet, R. TI Drugs effective for prevention of colon adenomas SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT Satellite Symposium on New Horizons for Gastric Cancer held in conjunction with the 8th World Congress on Gastrointestinal Cancer CY JUN 29, 2006 CL Barcelona, SPAIN C1 Univ Wisconsin, Madison, WI USA. NCI, Chemoprevent 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. PY 2006 VL 17 SU 6 BP 36 EP 36 PG 1 WC Oncology SC Oncology GA 073ZS UT WOS:000239782000063 ER PT J AU Gulley, JL Arlen, PM Schlom, J AF Gulley, James L. Arlen, Philip M. Schlom, Jeffrey TI Recent clinical advances in cancer vaccines SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 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. PY 2006 VL 17 SU 9 BP 41 EP 41 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900056 ER PT J AU Agulnik, M Cohen, EE Cohen, RB Chen, EX Hotte, SJ Winquist, E Laurie, S Hayes, DN Dancey, JE Siu, LL AF Agulnik, Mark Cohen, Ezra E. Cohen, Roger B. Chen, Eric X. Hotte, Sebastien J. Winquist, Eric Laurie, Scott Hayes, D. N. Dancey, Janet E. Siu, Lillian L. TI A multicenter phase II study of lapatinib in recurrent or metastatic adenoid cystic (ACC) and non-ACC malignant tumors of the salivary glands (MSGT) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Princess Margaret Hosp, Phase Consortium 2, Toronto, ON M4X 1K9, Canada. Univ Chicago, Phase Consortium 2, Chicago, IL 60637 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 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. PY 2006 VL 17 SU 9 BP 179 EP 179 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900584 ER PT J AU Tang, P Siu, LL Chen, EX Hotte, SJ Chia, S Schwarz, JK Colevas, AD Johnson, C Pond, GR Winquist, E AF Tang, Patricia Siu, Lillian L. Chen, Eric X. Hotte, Sebastien J. Chia, Stephen Schwarz, James K. Colevas, A. Dimitrios Johnson, Caitlin Pond, Greg R. Winquist, Eric TI A phase II study of ispinesib in patients (PTS) with recurrent and/or metastatic head and neck squamous cell carcinoma (RMHNSC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Princess Margaret Hosp, Consortium Phase 2, Toronto, ON M4X 1K9, Canada. NCI, Canc Therapy Evaluat Program, Invest Drug Branch, Rockville, MD 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. PY 2006 VL 17 SU 9 BP 186 EP 186 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900612 ER PT J AU Yang, SH Meerzaman, D Mechanic, LE Gill, R Dracheva, T Han, SB Kim, SY Bowman, ED Harris, CC Jen, J AF Yang, Sei-Hoon Meerzaman, Daoud Mechanic, Leah E. Gill, Rajbir Dracheva, Tatiana Han, Seung-Bum Kim, Sam-Yong Bowman, Elise D. Harris, Curtis C. Jen, Jin TI Mutations of the LKB1/STK11 gene in non-small cell lung cancer with loss of heterozygosity SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 30th Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol C1 Wonkwang Univ Hosp, Iksan, South Korea. NIH, Lab Populat Genet, CCR, Bethesda, MD 20892 USA. NIH, Lab Human carcinogenesis, CCR, Bethesda, MD 20892 USA. Keimyung Univ Dongsan Med, Taegu, South Korea. Chungnam Natl Univ, Taejon, South Korea. 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. PY 2006 VL 17 SU 9 BP 246 EP 246 PG 1 WC Oncology SC Oncology GA 190SH UT WOS:000248078900850 ER PT J AU Sullivan, DC AF Sullivan, D. C. TI Molecular imaging in oncology SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 31st ESMO Congress CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP ESMO ID MAGNETIC-RESONANCE; DRUG DEVELOPMENT; GENE-EXPRESSION; CANCER; RECOMMENDATIONS; PROGRESS; THERAPY; TRIALS; PET C1 NCI, NIH, Bethesda, MD 20892 USA. RP Sullivan, DC (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 16 TC 3 Z9 3 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. PY 2006 VL 17 SU 10 BP X287 EP X292 DI 10.1093/annonc/mdl275 PG 6 WC Oncology SC Oncology GA 107OQ UT WOS:000242181300047 PM 17018740 ER PT J AU Feldman, ED Weinreich, DM Carroll, NM Burness, ML Feldman, AL Turner, E Xu, H Alexander, HR AF Feldman, ED Weinreich, DM Carroll, NM Burness, ML Feldman, AL Turner, E Xu, H Alexander, HR TI Interferon gamma-inducible protein 10 selectively inhibits proliferation and induces apoptosis in endothelial cells SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE angiogenesis; interferon gamma-inducible protein 10; CXCR3; A375 melanoma; endothelium ID X-C-CHEMOKINE; IP-10 CHEMOKINE; GROWTH-FACTOR; TUMOR-GROWTH; IN-VIVO; ANGIOGENESIS; PLATELET-FACTOR-4; CHEMOATTRACTANT; ANTIBODIES; BINDING AB Background: Interferon gamma-oinducible protein 10 (IP-10) has antitumor effects in various murine models. The IP-10 receptor has two distinct splice variants, CXCR3A and CXCR3B, that have paradoxical effects after ligand-receptor interaction. Methods: To characterize the putative antiangiogenic effects of IP-10, we measured proliferation rates and apoptosis in human umbilical vein endothelial cells (HUVECs), fibroblasts, and A375 melanoma or WIDR adenocarcinoma cell lines after exposure to the recombinant protein. CXCR3A (activating) and CXCR3B (inhibitory/proapoptotic) messenger RNA (mRNA) expression levels in fibroblasts, 2 human tumor cell lines, T lymphocytes, and HUVECs of varying cell densities were characterized. Results: IP-10 resulted in dose-dependent and selective inhibition of proliferation and countered the proliferative effects of vascular endothelial growth factor in HUVECs but did not affect fibroblasts or 2 human tumor cell lines. In addition, IP-10 resulted in potent and selective induction of apoptosis in HUVECS but had no effect on fibroblasts or A375 melanoma. Confluent HUVECs had a predominance of mRNA for the CXCR3B splice variant by reverse transcriptase-polymerase chain reaction, and the ratio of CXCR3B to CXCR3A mRNA was > 40 in HUVECs, compared with <= 10 in the other cell types. Moreover, CXCR3B mRNA levels were significantly higher in proliferating compared with confluent HUVECs. In vivo, systemic IP-10 administration resulted in slower A375 xenograft growth rates compared with control-treated animals, and immunohistochemical staining showed decreased microvessel density in xenografts of IP-10-treated mice. Conclusions: IP-10 has antiangiogenic properties and selective effects on endothelial tissue that may be secondary to higher levels of the CXCR3B inhibitory/proapoptotic receptor in that cell type, particularly in its actively proliferating state. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. EM richard_alexander@nih.gov RI Feldman, Andrew/D-5028-2012 NR 17 TC 36 Z9 40 U1 1 U2 1 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 JAN PY 2006 VL 13 IS 1 BP 125 EP 133 DI 10.1245/ASO.2006.03.038 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 004KP UT WOS:000234752000019 PM 16378159 ER PT J AU Moutsopoulos, NM Angelov, N Sankar, V Leakan, RA Pillemer, S Wahl, SM AF Moutsopoulos, NM Angelov, N Sankar, V Leakan, RA Pillemer, S Wahl, SM TI Immunological consequences of thalidomide treatment in Sjogren's syndrome SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CLASSIFICATION; CYTOKINES; CRITERIA AB Objective: To study the immunological consequences of systemic thalidomide treatment in patients with Sjogren's syndrome. Methods: Cytokine (tumour necrosis factor alpha (TNF alpha), interleukin (IL) 6) and soluble receptor (sIL2R) levels were measured in patient and control plasma (n = 7), before and after thalidomide treatment. Peripheral blood mononuclear cells were examined by FACS analysis for potential changes in specific cell populations (T cells, B cells, monocytes), and for the expression of activation markers (CD25, HLA-DR), costimulatory molecules (CD40, CD40L), TNF receptors, chemokine receptors, and adhesion molecules ((L)-selectin ((L)-sel)). Results: Owing to adverse effects of thalidomide, the treatment interval was limited. None the less, statistically significant changes in markers of cell activation were recorded in the four treated patients. Before treatment, HLA-DR, TNFRI, CXCRI, and CXCRII were raised in the patients compared with healthy controls (p < 0.05) and their expression was down regulated after treatment. B cell numbers and expression of the adhesion molecule (L)-sel also declined with thalidomide. Conclusion: Significant changes in measures of cell activation were detected during thalidomide treatment within this limited study, which upon further investigation may offer insight into the underlying immunoregulatory pathways of thalidomide. C1 Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branchg, NIH, Bethesda, MD 20892 USA. RP Wahl, SM (reprint author), Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branchg, NIH, Bldg 30,Room 323,30 Convent Dr,MSC4352, Bethesda, MD 20892 USA. EM smwahl@mail.nih.gov NR 9 TC 12 Z9 16 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JAN PY 2006 VL 65 IS 1 BP 112 EP 114 DI 10.1136/ard.2005.038406 PG 3 WC Rheumatology SC Rheumatology GA 992NW UT WOS:000233891800023 PM 16344495 ER PT S AU Hurley, JH Emr, SD AF Hurley, James H. Emr, Scott D. TI The ESCRT complexes: Structure and mechanism of a membrane-trafficking network SO ANNUAL REVIEW OF BIOPHYSICS AND BIOMOLECULAR STRUCTURE SE Annual Review of Biophysics LA English DT Review; Book Chapter DE ubiquitin; sorting; endocytosis; lysosomes ID EPIDERMAL-GROWTH-FACTOR; UBIQUITIN-INTERACTING MOTIF; YEAST SACCHAROMYCES-CEREVISIAE; MULTIVESICULAR BODY PATHWAY; ENDOSOME-ASSOCIATED COMPLEX; RECEPTOR DOWN-REGULATION; SRC HOMOLOGY-3 DOMAIN; CRYSTAL-STRUCTURE; FYVE DOMAIN; PHOSPHATIDYLINOSITOL 3-PHOSPHATE AB The ESCRT complexes and associated proteins comprise a major pathway for the lysosomal degradation of transmembrane proteins and are critical for receptor downregulation, budding of the HIV virus, and other normal and pathological cell processes. The ESCRT system is conserved from yeast to humans. The ESCRT complexes form a network that recruits monoubiquitinated proteins and drives their internalization into lumenal vesicles within a type of endosome known as a multivesicular body. The structures and interactions of many of the components have been determined over the past three years, revealing mechanisms for membrane and cargo recruitment and for complex assembly. C1 US Dept HHS, NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Hurley, JH (reprint author), US Dept HHS, NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov; semr@ucsd.edu FU Intramural NIH HHS NR 117 TC 359 Z9 368 U1 4 U2 23 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1056-8700 BN 978-0-8243-1835-2 J9 ANNU REV BIOPH BIOM JI Annu. Rev. Biophys. Biomolec. Struct. PY 2006 VL 35 BP 277 EP 298 DI 10.1146/annurev.biophys.35.040405.102126 PG 22 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 053SW UT WOS:000238326400012 PM 16689637 ER PT S AU Blehar, MC AF Blehar, Mary C. TI Women's mental health research: The emergence of a biomedical field SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY SE Annual Review of Clinical Psychology LA English DT Review; Book Chapter DE hormones; stress; diagnosis ID RANDOMIZED CONTROLLED-TRIAL; NATIONAL-COMORBIDITY-SURVEY; POSTTRAUMATIC-STRESS-DISORDER; ESTROGEN PLUS PROGESTIN; DSM-IV DISORDERS; GENDER-DIFFERENCES; DEPRESSIVE-DISORDERS; MAJOR DEPRESSION; SEX-DIFFERENCES; POSTMENOPAUSAL WOMEN AB This review surveys the field of women's mental health, with particular emphasis on its evolution into a distinct area of biomedical research. The field employs a biomedical disease model but it also emphasizes social and cultural influences on health outcomes. In recent years, its scope has expanded beyond studies of disorders occurring in women at times of reproductive transitions and it now encompasses a broader study of sex and gender differences. Historical and conceptual influences on the field are discussed. The review also surveys gender differences in the prevalence and clinical manifestations of mental disorders. Epidemiological findings have provided a rich resource for theory development, but without research tools to test theories adequately, findings of gender differences have begged the question of their biological, social, and cultural origins. Clinical depression is used to exemplify the usefulness of a sex/gender perspective in understanding mental illness; and major theories proposed to account for gender differences are critically evaluated. The National Institutes of Health (NIH) is the primary federal funding source for biomedical women's mental health research. The review surveys areas of emphasis in women's mental health research at the NIH as well as some collaborative activities that represent efforts to translate research findings into the public health and services arenas. As new analytic methods become available, it is anticipated that a more fundamental understanding of the biological and behavioral mechanisms underlying sex and gender differences in mental illness will emerge. Nonetheless, it is also likely that integration of findings predicated on different conceptual models of the nature and causes of mental illness will remain a challenge. These issues are discussed with reference to their impact on the field of women's mental health research. C1 NIH, Natl Canc Inst, Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Blehar, MC (reprint author), NIH, Natl Canc Inst, Dept Hlth & Human Serv, Rockville, MD 20852 USA. EM mblehar@mail.nih.gov NR 106 TC 19 Z9 19 U1 0 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1548-5943 BN 978-0-8243-3902-9 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2006 VL 2 BP 135 EP 160 DI 10.1146/annurev.clinpsy.2.022305.095344 PG 26 WC Psychology, Clinical; Psychology SC Psychology GA 295QD UT WOS:000255488100006 PM 17716067 ER PT S AU Valenzuela, L Kamakaka, RT AF Valenzuela, Lourdes Kamakaka, Rohinton T. TI Chromatin insulators SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE enhancers; silencers; chromatin domains; insulators; enhancer-blocking; barriers ID BETA-GLOBIN LOCUS; ENHANCER-PROMOTER COMMUNICATION; DROSOPHILA-BITHORAX COMPLEX; POLYCOMB-RESPONSE ELEMENT; IMPRINTING CONTROL REGION; TRITHORAX GROUP PROTEINS; CIS-REGULATORY DOMAINS; HISTONE VARIANT H2A.Z; RANGE GENE ACTIVATION; DNASE-I SENSITIVITY AB Active and silenced chromatin domains are often in close juxtaposition to one another, and enhancer and silencer elements operate over large distances to regulate the genes in these domains. The lack of promiscuity in the function of these elements suggests that active mechanisms exist to restrict their activity. Insulators are DNA elements that restrict the effects of long-range regulatory elements. Studies on different insulators from different organisms have identified common themes in their mode of action. Numerous insulators map to promoters of genes or have binding sites for transcription factors and like active chromatin hubs and silenced loci, insulators also cluster in the nucleus. These results bring into focus potential conserved mechanisms by which these elements might function in the nucleus. C1 NICHD, Unit Chromatin & Transcript, NIH, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Sinsheimer Labs, Dept MCD Biol, Santa Cruz, CA 95064 USA. RP Valenzuela, L (reprint author), NICHD, Unit Chromatin & Transcript, NIH, Bethesda, MD 20892 USA. EM rohinton@biology.ucsc.edu NR 180 TC 127 Z9 130 U1 4 U2 20 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1240-4 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2006 VL 40 BP 107 EP 138 DI 10.1146/annurev.genet.39.073003.113546 PG 32 WC Genetics & Heredity SC Genetics & Heredity GA 119UB UT WOS:000243038200005 PM 16953792 ER PT S AU Bashirova, AA Martin, MP McVicar, DW Carrington, M AF Bashirova, Arman A. Martin, Maureen P. McVicar, Daniel W. Carrington, Mary TI The killer immunoglobulin-like receptor gene cluster: Tuning the genome for defense SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE NK cell; innate immunity; immune genes; immune receptors ID IG-LIKE RECEPTOR; MHC CLASS-I; MAJOR HISTOCOMPATIBILITY COMPLEX; CELL INHIBITORY RECEPTORS; IFN-GAMMA PRODUCTION; C-VIRUS-INFECTION; ANTIGEN CLASS-I; HUMAN NK CELLS; HLA-C; CUTTING EDGE AB Killer immunoglobulin-like receptors (KIRs) are molecules expressed on the surface of natural killer (NK) cells, which play an important role in innate immunity. KIR recognition of major histocompatability complex (MITC) class I allotypes represents one component of the complex interactions between NK cells and their targets in determining NK cell reactivity. KIRs are encoded by a gene cluster at human chromosome 19q13.4. Despite their high degree of sequence identity, KIR genes encode proteins that have diverse recognition patterns (specific HLA class I allotypes) and confer opposing signals (activating or inhibitory) to the NK cell The KIR. gene cluster is highly polymorphic, with individual genes exhibiting allelic variability, and individual haplotypes differing in gene content The. polymorphism of the KIR locus parallels that of the MHC facilitating the adaptation of the immune system to a dynamic challenging environment. This variation is associated with a growing number of human diseases, which is likely to extend to levels observed for the HLA loci. Here we review current progress in understanding KIR biology and genetics. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. RP Bashirova, AA (reprint author), Johns Hopkins Univ, Sch Med, Baltimore, MD 21231 USA. EM carringt@ncifcrf.gov RI McVicar, Daniel/G-1970-2015 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [DA 13324] NR 155 TC 144 Z9 149 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3707-0 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2006 VL 7 BP 277 EP 300 DI 10.1146/annurev.genom.7.080505.11526 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA 105LT UT WOS:000242032200012 PM 16824023 ER PT S AU Schueler, MG Sullivan, BA AF Schueler, Mary G. Sullivan, Beth A. TI Structural and functional dynamics of human centromeric chromatin SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE centromere; kinetochore; alpha-satellite; histone; heterochromatin; methylation; cohesion; epigenctic ID ALPHA-SATELLITE DNA; HUMAN X-CHROMOSOME; CENP-C; TOPOISOMERASE-II; HUMAN GENOME; CELL-CYCLE; CONCERTED EVOLUTION; SEQUENCE VARIATION; GREAT APES; IN-VIVO AB Centromeres are the elements of chromosomes that assemble the proteinaceous kinetochore, maintain sister chromatid cohesion, regulate chromosome attachment to the spindle, and direct chromosome movement during cell division. Although the functions of centromeres and the proteins that contribute to their complex structure and function are conserved in eukaryotes, centromeric DNA diverges rapidly. Human centromeres are particularly complicated. Here, we review studies on the organization of homogeneous arrays of chromosoine-specific alpha-satellite repeats and evolutionary links among eukaryotic centromeric sequences. We also discuss epigenetic mechanisms of centromere identity that confer structural and functional features of the centromere through DNA-protein interactions and post-translational modifications, producing centromere-specific chromatin signatures. The assembly and organization of human centromeres, the contributions of satellite DNA to centromere identity and diversity, and the mechanism whereby centromeres are distinguished from the rest of the genome reflect ongoing puzzles in chromosome biology. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. RP Schueler, MG (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM beth.sullivan@duke.edu OI Sullivan, Beth/0000-0001-5216-4603 FU NIGMS NIH HHS [R01 GM069514] NR 80 TC 95 Z9 97 U1 2 U2 16 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3707-0 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2006 VL 7 BP 301 EP 313 DI 10.1146/annurev.genom.7.080505.115613 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 105LT UT WOS:000242032200013 PM 16756479 ER PT S AU Burke, B Stewart, CL AF Burke, Brian Stewart, Colin L. TI The laminopathies: The functional architecture of the nucleus and its contribution to disease SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE nuclear envelope; Lamins; cytoskeleton; progeria ID HUTCHINSON-GILFORD-PROGERIA; LAMIN A/C GENE; DREIFUSS MUSCULAR-DYSTROPHY; A-TYPE LAMINS; GERM CELL-LESS; FAMILIAL PARTIAL LIPODYSTROPHY; B RECEPTOR GENE; MEMBRANE-PROTEIN; PRELAMIN-A; DILATED CARDIOMYOPATHY AB Most inherited diseases are associated with mutations in a specific gene. Often, mutations in two or more different genes result in diseases with a similar phenotype. Rarely do different mutations in the same gene result in a multitude of seemingly different and unrelated diseases. Mutations in the Lamin A gene (LMNA), which encodes largely ubiquitously expressed nuclear proteins (A-type lamins), are associated with at least eight different diseases, collectively called the laminopathies. Studies examining how different tissue-specific diseases arise from unique LMNA mutations are providing unanticipated insights into the structural organization of the nucleus, and how disruption of this organization relates to novel mechanisms of disease. C1 Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. RP Burke, B (reprint author), Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. EM Stewartc@ncifcrf.gov NR 220 TC 86 Z9 90 U1 1 U2 7 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3707-0 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2006 VL 7 BP 369 EP 405 DI 10.1146/annurev.genom.7.080505.115732 PG 37 WC Genetics & Heredity SC Genetics & Heredity GA 105LT UT WOS:000242032200016 PM 16824021 ER PT S AU Bidere, N Su, HC Lenardo, MJ AF Bidere, Nicolas Su, Helen C. Lenardo, Michael J. TI Genetic disorders of programmed cell death in the immune system SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE cytokine; Fas/APO-1/CD95; caspase; tumor necrosis factor receptor; autoimmune lymphoproliferative syndrome (ALPS); caspase-eight deficiency state (CEDS) ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; NF-KAPPA-B; FAS-MEDIATED APOPTOSIS; TUMOR-NECROSIS-FACTOR; RECEPTOR-GAMMA-CHAIN; ACTIVATION-INDUCED APOPTOSIS; REGULATORY T-CELLS; FAMILY-MEMBER BIM; PROTEIN-KINASE-B; DEFICIENT MICE AB Human genetics offers new possibilities for understanding physiological regulatory mechanisms and disorders of the immune system. Genetic abnormalities of lymphocyte cell death programs have provided insights into mechanisms of receptor biology and principles of immune homeostasis and tolerance. Thus far, there are two major diseases of programmed cell death associated with inherited human mutations: the autoimmune lymphoproliferative syndrome and the caspase-eight deficiency state. We describe the details of their molecular pathogenesis and discuss how these diseases illustrate important concepts in immune regulation and genetics. C1 Natl Inst Allergy & Infect Dis, Lab Immunol, NIH, Bethesda, MD 20892 USA. RP Bidere, N (reprint author), Natl Inst Allergy & Infect Dis, Lab Immunol, NIH, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI Su, Helen/H-9541-2015; bidere, nicolas/K-8887-2015 OI Su, Helen/0000-0002-5582-9110; bidere, nicolas/0000-0001-9177-0008 FU Intramural NIH HHS NR 160 TC 120 Z9 122 U1 0 U2 8 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3024-8 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2006 VL 24 BP 321 EP 352 DI 10.1146/annurev.immunol.24.021605.090513 PG 32 WC Immunology SC Immunology GA 043ES UT WOS:000237583300011 PM 16551252 ER PT J AU Castellino, F Germain, RN AF Castellino, Flora Germain, Ronald N. TI Cooperation between CD4(+) and CD8(+) T cells: When, where, and how SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE dendritic cells; T cell help; cell-mediated immunity; chemokines ID CHEMOKINE RECEPTOR EXPRESSION; SECONDARY LYMPHOID ORGANS; COMPLEX CLASS-II; C-TYPE LECTINS; DENDRITIC CELL; IN-VIVO; ANTIGEN PRESENTATION; IL-2 PRODUCTION; CUTTING EDGE; SELECTIVE EXPRESSION AB Concepts of cell-cell interactions in adaptive immunity have alternated between the simple and the complex. The notion that one population of small, circulating lymphocytes is responsible for adaptive immunity was sequentially supplanted by the concept of separate T and B lymphocyte populations that cooperate to produce IgG antibody responses, by a three-cell model in which a myeloid APC initiates these cooperative lymphoid responses, by the recognition of T cell subsets, and by the idea that CD8(+) T cell subset responses to graft antigens depend on CD4(+) T cell subset activity. Simplicity was reintroduced with the revelation that CD8(+) T cells can act independently of CD4(+) T cells against acute viral infections. The pendulum has swung again toward complexity with recognition of the distinct and conjoint contributions of innate stimuli, APCs, NK and NKT cells, Tregs, and CD4(+) helper T cells to CD8(+) T cell behavior during acute and chronic infections or as memory cells. The renewed appreciation that multiple, sometimes rare cell types must communicate during cell-mediated immune responses has led to questions about how such interactions are orchestrated within organized lymphoid tissues. We review recent advances in deciphering the specific contribution of CD4(+) T cells to physiologically useful CD8(+) T cell responses, the signals involved in producing acute effectors versus long-lived memory cells, and the mechanisms underlying the cell-cell associations involved in delivery of such signals. We propose a model based on these new findings that may serve as a general paradigm for cellular interactions that occur in an inflamed lymph node during the initiation of immune responses. C1 Natl Inst Allergy & Infect Dis, Lab Immunol, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Castellino, F (reprint author), Natl Inst Allergy & Infect Dis, Lab Immunol, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. EM rgermain@nih.gov NR 152 TC 190 Z9 205 U1 4 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 EI 1545-3278 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2006 VL 24 BP 519 EP 540 DI 10.1146/annurev.immunol.23.021704.115825 PG 22 WC Immunology SC Immunology GA 043ES UT WOS:000237583300017 PM 16551258 ER PT S AU Waldmann, TA AF Waldmann, TA TI Effective cancertherapy through immunomodulation SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE monoclonal antibodies; cancer vaccines; immunological checkpoints; CTLA-4; Tregs; IL-15 ID REGULATORY T-CELLS; GROWTH-FACTOR-BETA; CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; MONOCLONAL-ANTIBODY; CTLA-4 BLOCKADE; ANTIGEN-4 BLOCKADE; PROSTATE-CANCER; FC-RECEPTORS; MURINE MODEL AB MAbs directed toward tumor cells, tumor neovasculature, and host negative immunoregulatory elements (checkpoints) have emerged as useful immunotherapeutic agents against cancer. However, effective active modulation of the immune response with anticancer vaccines will require identifying appropriate tumor-rejection antigens; optimizing the interactions of peptides, antigen-presenting cells, and T cells; and blockading negative immunological checkpoints that impede an effective immune response. Checkpoints being targeted include CTLA-4 and PD1 that are negative signaling receptors expressed on activated T cells, CD4(+)CD25(+) Foxp3-expressing Tregs (suppressor T cells), IL-2-mediated activation-induced cell death (AICD), and the cytokine TGF beta. C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. RP Waldmann, TA (reprint author), NIH, Natl Canc Inst, Bethesda, MD 20892 USA. EM tawald@helix.nih.gov FU Intramural NIH HHS NR 69 TC 58 Z9 59 U1 1 U2 9 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0557-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2006 VL 57 BP 65 EP 81 DI 10.1146/annurev.med.56.082103.104549 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 021KK UT WOS:000235981900005 PM 16409137 ER PT S AU Khanna, C Helman, LJ AF Khanna, C Helman, LJ TI Molecular approaches in pediatric oncology SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE cancer; biology; therapy; diagnosis; metastasis ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; GROWTH-FACTOR-II; REAL-TIME PCR; GENE-EXPRESSION; ALVEOLAR RHABDOMYOSARCOMA; MAMMALIAN TARGET; DNA MICROARRAYS; CANCER-THERAPY; EWING SARCOMA AB The use of molecular approaches has become part of the standard of care in the management of pediatric cancer patients. Molecular approaches are now included in the initial diagnosis, definition of prognostically distinct patient subgroups, selection of patients for specific therapies, prediction of risk for toxicities to therapy, and monitoring of patients receiving both conventional and novel targeted therapies. This clinical application of molecular medicine has been based on a growing molecular understanding of cancer biology. Studies of pediatric cancers have contributed to this understanding in many ways. We present a model for understanding cancer biology, using specific examples taken from pediatric oncology, and then discuss the application of molecular techniques to the clinical management of pediatric cancer patients. C1 NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Rockville, MD USA. NCI, Mol Oncol Sect, Pediat Oncol Branch, Rockville, MD USA. NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Bethesda, MD USA. NCI, Ctr Canc Res, Mol Oncol Sect, Pediat Oncol Branch, Bethesda, MD USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, Tumor & Metastasis Biol Sect, Rockville, MD USA. EM khannac@mail.nih.gov; helmanl@nih.gov NR 73 TC 9 Z9 10 U1 0 U2 0 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0557-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2006 VL 57 BP 83 EP 97 DI 10.1146/annurev.med.57.121304.131247 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 021KK UT WOS:000235981900006 PM 16409138 ER PT S AU Brady, RO AF Brady, RO TI Enzyme replacement for lysosomal diseases SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE sphingolipid storage disorders; mucopolysaccharidoses; glycogenoses ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; MANNOSE-TERMINAL GLUCOCEREBROSIDASE; NEURONOPATHIC GAUCHERS-DISEASE; FABRY-DISEASE; ALPHA-GLUCOSIDASE; GLOBOTRIAOSYLCERAMIDE STORAGE; PURIFIED GLUCOCEREBROSIDASE; MUCOPOLYSACCHARIDOSIS-I; INTRAVENOUS INFUSIONS; ANTIBODY-RESPONSE AB Following the demonstration of the nature of the enzymatic defects in the sphingolipid storage disorders in the mid-1960s, consideration was directed to the development of therapy for patients with these conditions. High on the list of possibilities was enzyme supplementation or replacement. Many years of arduous investigation and the development of novel protein targeting strategies were required to bring this concept to fruition. Enzyme replacement therapy (ERT) was eventually shown to be extraordinarily effective for patients with Gaucher disease, the most prevalent metabolic storage disorder of humans. Demonstration of the benefit of ERT in this disorder led to the extension of this approach to the treatment of other lysosomal storage disorders. This review presents the current status and anticipated developments in this field. C1 Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branc, NIH, Bethesda, MD 20892 USA. RP Brady, RO (reprint author), Natl Inst Neurol Disorders & Stroke, Dev & Metab Neurol Branc, NIH, Bethesda, MD 20892 USA. EM bradyr@ninds.nih.gov NR 55 TC 151 Z9 153 U1 4 U2 17 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0557-4 J9 ANNU REV MED JI Annu. Rev. Med. PY 2006 VL 57 BP 283 EP 296 DI 10.1146/annurev.med.57.110104.115650 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 021KK UT WOS:000235981900018 PM 16409150 ER PT S AU Montcouquiol, M Crenshaw, EB Kelley, MW AF Montcouquiol, Mireille Crenshaw, E. Bryan, III Kelley, Matthew W. TI Noncanonical Wnt signaling and neural polarity SO ANNUAL REVIEW OF NEUROSCIENCE SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE convergent extension; neurulation; gastrulation; planar cell polarity; inner car; migration; mechanosensory hair cell ID PLANAR CELL-POLARITY; CONVERGENT EXTENSION MOVEMENTS; BETA-CATENIN; TUBE DEFECTS; INNER-EAR; XENOPUS EMBRYOS; VERTEBRATE GASTRULATION; AXIS FORMATION; DISHEVELLED PROTEIN; MULTIPLE FUNCTIONS AB The Wnt signaling pathway regulates multiple events in development and disease in both vertebrates and invertebrates. Recently, the noncanonical Wnt signaling cascades, those that do not signal through beta-catenin, have gained prominence for their role in the regulation of cellular polarity It is not surprising that cellular polarization influences a number of different developmental events within the nervous system, including neurulation and neural tube closure, cellular migration, and uniform orientation of cells within an epithelial plane (planar cell polarity). In this review, we describe the differences between the canonical and noncanonical pathways, summarize recent data illustrating the roles of the noncanonical Wnt pathway in different polarizing events during neural development, and discuss the potential molecular mechanisms that underlie the generation of cellular asymmetry and polarity. C1 Childrens Hosp Philadelphia, Mammalian Neurogenet Grp, Ctr Childhood Commun, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Philadelphia, PA 19104 USA. NIDCD, Sect Dev Neurosci, NIH, Bethesda, MD 20982 USA. RP Montcouquiol, M (reprint author), Univ Bordeaux 2, Inst Francois Magendie, INSERM, F-33076 Bordeaux, France. EM kelleymt@nidcd.nih.gov OI montcouquiol, mireille/0000-0001-8739-6519 NR 104 TC 109 Z9 113 U1 3 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X BN 978-0-8243-2429-2 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2006 VL 29 BP 363 EP 386 DI 10.1146/annurev.neuro.29.051605.112933 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 074JF UT WOS:000239807800013 PM 16776590 ER PT S AU Gonzalez, FJ Yu, AM AF Gonzalez, FJ Yu, AM TI Cytochrome P450 and xenobiotic receptor humanized mice SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE CYP; nuclear receptor; transgenic mouse model; drug metabolism; pharmacokinetics; pharmacogenetics; cancer; toxicity; ligands; gene activation ID PROLIFERATOR-ACTIVATED-RECEPTOR; PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; HUMAN CYP3A4 GENE; ALPHA PPAR-ALPHA; ARYL-HYDROCARBON RECEPTOR; TRANSGENIC MOUSE MODEL; NUCLEAR RECEPTOR; DRUG-METABOLISM; PEROXISOME PROLIFERATION AB Most xenobiotics that enter the body are subjected to metabolism that functions primarily to facilitate their elimination. Metabolism of certain xenobiotics can also result in the production of electrophilic derivatives that can cause cell toxicity and transformation. Many xenobiotics can also activate receptors that in turn induce the expression of genes encoding xenobiotic-metabolizing enzymes and xenobiotic transporters. However, there are marked species differences in the way mammals respond to xenobiotics, which are due in large part to molecular differences in receptors and xenobiotic-metabolizing enzymes. This presents a problem in extrapolating data obtained with rodent model systems to humans. There are also polymorphisms in xenobiotic-metabolizing enzymes that can impact drug therapy and cancer susceptibility. In an effort to generate more reliable in vivo systems to study and predict human response to xenobiotics, humanized mice are under development. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU NCI NIH HHS [Z01 BC005562-18] NR 142 TC 94 Z9 98 U1 0 U2 4 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0445-4 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2006 VL 46 BP 41 EP 64 DI 10.1146/annurev.pharmtox.45.120403.100007 PG 30 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 021KE UT WOS:000235981300002 PM 16402898 ER PT J AU Dharmawardana, PG Peruzzi, B Giubellino, A Burke, TR Bottaro, DP AF Dharmawardana, PG Peruzzi, B Giubellino, A Burke, TR Bottaro, DP TI Molecular targeting of growth factor receptor-bound 2 (Grb2) as an anti-cancer strategy SO ANTI-CANCER DRUGS LA English DT Review DE angiogenesis; cancer; cell motility; Grb2; growth factor receptor-bound 2; metastasis ID SH2 DOMAIN-BINDING; RECEPTOR TYROSINE KINASE; PHOSPHATE-CONTAINING LIGANDS; HEPATOCYTE GROWTH-FACTOR; STRUCTURE-BASED DESIGN; SIGNALING GENE SEM-5; ACTIN-BASED MOTILITY; BREAST-CANCER CELLS; HOMOLOGY 2 DOMAIN; PHOSPHOTYROSYL MIMETICS AB Growth factor receptor-bound 2 (Grb2) is a ubiquitously expressed adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. As such, it has been implicated in the oncogenesis of several important human malignancies. In addition to this function, research over the last decade has revealed other fundamental roles for Grb2 in cell motility and angiogenesis-processes that also contribute to tumor growth, invasiveness and metastasis. This functional profile makes Grb2 a high priority target for anti-cancer drug development. Knowledge of Grb2 protein structure, its component Src homology domains and their respective structure-function relationships has facilitated the rapid development of sophisticated drug candidates that can penetrate cells, bind Grb2 with high affinity and potently antagonize Grb2 signaling. These novel compounds offer considerable promise in our growing arsenal of rationally designed anti-cancer therapeutics. C1 NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Med Chem Lab, CCR, NIH, Bethesda, MD 20892 USA. RP Bottaro, DP (reprint author), NCI, Urol Oncol Branch, CCR, NIH, Bldg 10,CRC 1,W Rm 3961,10 Ctr Dr,MSC 1107, Bethesda, MD 20892 USA. EM dbottaro@helix.nih.gov RI Bottaro, Donald/F-8550-2010; Burke, Terrence/N-2601-2014; OI Bottaro, Donald/0000-0002-5057-5334; Giubellino, Alessio/0000-0002-5352-0662 FU Intramural NIH HHS NR 73 TC 39 Z9 46 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0959-4973 J9 ANTI-CANCER DRUG JI Anti-Cancer Drugs PD JAN PY 2006 VL 17 IS 1 BP 13 EP 20 DI 10.1097/01.cad.0000185180.72604.ac PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 995QV UT WOS:000234119800002 PM 16317285 ER PT J AU Otto, M AF Otto, M. TI Bacterial evasion of antimicrobial pepticles by biofilm formation SO ANTIMICROBIAL PEPTIDES AND HUMAN DISEASE SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID PSEUDOMONAS-AERUGINOSA BIOFILMS; STAPHYLOCOCCUS-EPIDERMIDIS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; IMMUNE EVASION; POLYSACCHARIDE; ALGINATE; INNATE; VIRULENCE; PEPTIDES; MATRIX AB Biofilm formation is a main virulence determinant in many bacterial infections. It significantly increases bacterial resistance to antibiotics and innate host defense. in general, the specific physiology of biofilms and the barrier function of the extracellular biofilm matrix determine resistance to antibacterials. However, resistance to antimicrobial peptides appears to be mainly based on the interaction with biofilm and capsule exopolymers. These polymers may work by electrostatic repulsion and/or sequestration of antibacterial substances. As biofilm polymers play an eminent role in biofilm structuring and resistance, their destruction by dedicated enzymes is a promising attempt to prevent colonization and develop treatment for biofilm-associated infections. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 NR 30 TC 71 Z9 78 U1 2 U2 11 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 306 BP 251 EP 258 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA BEW29 UT WOS:000239845700010 PM 16909925 ER PT J AU Papaiahgari, S Zhang, Q Yleeberger, SR Cho, HY Reddy, SP AF Papaiahgari, S Zhang, Q Yleeberger, SR Cho, HY Reddy, SP TI Hyperoxia stimulates an Nrf2-ARE transcriptional response via ROS-EGFR-PI3K-Akt/ERK MAP kinase signaling in pulmonary epithelial cells SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID HUMAN NEUROBLASTOMA-CELLS; CUL3-BASED E3 LIGASE; OXIDATIVE STRESS; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEASOMAL DEGRADATION; REGULATED KINASE; AKT; ACTIVATION; PATHWAY; PROTEIN AB Nuclear factor erythroid 2-related factor (Nrf2) confers protection against cell death induced by hyperoxia and other proapoptotic stimuli. Because phosphoinositide-3-kinase (PI3K)/Akt signaling promotes cell survival, the significance of this pathway in mediating reactive oxygen species (ROS)-dependent hyperoxia-induced Nrf2 activation was investigated in the murine pulmonary epithelial cell line, C10. Inhibition of the PI3K pathway markedly attenuated hyperoxia-induced Nrf2 translocation and ARE (antioxidant response element)-mediated transcription. Consistent with this, hyperoxia markedly stimulated the activation of PI3K pathway, while an NADPH oxidase inhibitor and an antioxidant prevented such activation. The inhibition of Akt activity using a pharmacological inhibitor markedly attenuated Nrf2 translocation and ARE-driven expression. Moreover, overexpression of a dominant-negative Akt mutant attenuated the transcription, whereas a constitutively active mutant stimulated it. These results suggest that PI3K/Akt signaling regulates Nrf2 activation by hyperoxia. Inhibition of the PI3K pathway prevented hyperoxia-stimulated Akt and ERK1/2 kinase activation, which is critical for Nrf2-mediated transcription. Likewise, the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, AG1478, blocked hyperoxia-stimulated Akt and ERK1/2 phosphorylation, Nrf2 nuclear accumulation, and ARE-driven transcription. Consistent with this result, an NADPH oxidase inhibitor blocked byperoxia-stimulated EGFR phosphorylation, which was correlated with the attenuation of Akt and ERK activation. Collectively, our data suggest that EGFR-PI3K signaling through Akt and ERK kinases regulates ROS-dependent, hyperoxia-induced Nrf2 activation in pulmonary epithelial cells. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Div Physiol, Baltimore, MD 21205 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Div Physiol, Rm e7547,615 N Wolfe St, Baltimore, MD 21205 USA. EM sreddy@jhsph.edu FU NHLBI NIH HHS [1P50HL073994, HL66109]; NIEHS NIH HHS [ES11863] NR 42 TC 103 Z9 109 U1 0 U2 4 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN-FEB PY 2006 VL 8 IS 1-2 BP 43 EP 52 DI 10.1089/ars.2006.8.43 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 034XK UT WOS:000236964000003 PM 16487036 ER PT J AU Cho, HY Reddy, SP Kleeberger, SR AF Cho, HY Reddy, SP Kleeberger, SR TI Nrf2 defends the lung from oxidative stress SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID ANTIOXIDANT-RESPONSE ELEMENT; TRANSCRIPTION FACTOR NRF2; GLUTATHIONE-S-TRANSFERASE; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; ALVEOLAR EPITHELIAL-CELLS; EXTRACELLULAR-SUPEROXIDE DISMUTASE; IDIOPATHIC PULMONARY FIBROSIS; RESPIRATORY-DISTRESS-SYNDROME; ADENOVIRUS-MEDIATED TRANSFER; DRUG-METABOLIZING-ENZYMES AB Nuclear factor, erythroid 2 related factor 2 (Nrf2) belongs to the Cap'n'collar/basic region leucine zipper (CNC-bZIP) transcription factor family, and is activated by diverse oxidants, pro-oxidants, antioxidants, and chemopreventive agents. After phosphorylation and dissociation from the cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), Nrf2 translocates to the nucleus and binds to an antioxidant response element (ARE). Through transcriptional induction of ARE-bearing genes that encode antioxidant-detoxifying proteins, Nrf2 activates cellular rescue pathways against oxidative injury, inflammation/immunity, apoptosis, and carcinogenesis. ARE-driven genes include direct antioxidants (e.g., GPx), thiol metabolism-associated detoxifying enzymes (e.g., GSTs), stress-response genes (e.g., HO-1), and others (e.g., PSMB5). Application of nrJ2 germ-line mutant mice elucidated protective roles for Nrf2 in various models of human disorders in the liver, lung, kidney, brain, and circulation. In the lung, deficiency of nrJ2 augmented injury caused by bleomycin and environmental oxidants including hyperoxia, diesel exhaust particles, and cigarette smoke. Microarray analyses of lungs from nrJ2-deficient and -sufficient mice identified Nrf2-dependent genes that might be critical in pulmonary protection. Observations from these studies highlight the importance of the Nrf2-antioxidant pathway and may provide new therapeutic strategies for acute respiratory distress syndrome, idiopathic pulmonary fibrosis, cancer, and emphysema in which oxidative stress is implicated. 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. RP NIEHS, Lab Resp Biol, NIH, Bldg 101,MD D-201 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cho2@niehs.nih.gov NR 120 TC 226 Z9 239 U1 7 U2 30 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JAN-FEB PY 2006 VL 8 IS 1-2 BP 76 EP 87 DI 10.1089/ars.2006.8.76 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 034XK UT WOS:000236964000007 PM 16487040 ER PT J AU Dorjsuren, D Burnette, A Gray, GN Chen, XL Zhu, WM Roberts, PE Currens, MJ Shoemaker, RH Ricciardi, RP Sei, S AF Dorjsuren, D Burnette, A Gray, GN Chen, XL Zhu, WM Roberts, PE Currens, MJ Shoemaker, RH Ricciardi, RP Sei, S TI Chemical library screen for novel inhibitors of Kaposi's sarcoma-associated herpesvirus processive DNA synthesis SO ANTIVIRAL RESEARCH LA English DT Article DE Kaposi's sarcoma-associated herpesvirus; DNA polymerase; processivity factor; small molecule inhibitor screen ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 REVERSE-TRANSCRIPTASE; HUMAN-HERPESVIRUS-8 VIRAL LOAD; MULTICENTRIC CASTLEMAN-DISEASE; TOPOISOMERASE-II; ANTIVIRAL ACTIVITY; SELECTIVE-INHIBITION; PERIPHERAL-BLOOD; NATURAL-PRODUCTS; SMALL-MOLECULE AB Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi's sarcoma and certain lymphoproliferative disorders. The role of KSHV lytic replication has been implicated in the tumor pathogenesis. A highly specific molecular complex formed by the KSHV DNA polymerase (POL8) and processivity factor (PF8) is indispensable for lytic viral DNA synthesis and may serve as an excellent molecular anti-KSHV target. The majority of conventional nucleoside-based anti-herpetic DNA synthesis inhibitors require intracellular phosphorylation/activation before they can exert inhibitory activity as competitive substrates for viral DNA polymerases. Novel and more potent inhibitors of KSHV DNA synthesis may be discovered through POL8/PF8-targeted high throughput screening (HTS) of small molecule chemical libraries. We developed a microplate-based KSHV POL8/PF8-mediated DNA synthesis inhibition assay suitable for HTS and screened the NCI Diversity Set that comprised 1992 synthetic compounds. Twenty-eight compounds exhibited greater than 50% inhibition. The inhibitory activity was confirmed for 25 of the 26 hit compounds available for further testing, with the 50% inhibitory concentrations ranging from 0.12 +/- 0.07 mu M (mean +/- S.D.) to 10.83 +/- 4.19 mu M. Eighteen of the confirmed active compounds efficiently blocked KSHV processive DNA synthesis in vitro. One of the hit compounds, NSC 373989, a pyrimidoquinoline analog, was shown to dose-dependently reduce the levels of KSHV virion production and KSHV DNA in lytically induced KSHV-infected BCBL-1 cells, suggesting that the compound blocked lytic KSHV DNA synthesis. HTS for KSHV POL8/PF8 inhibitors is feasible and may lead to discovery of novel non-nucleoside KSHV DNA synthesis inhibitors. Published by Elsevier B.V. C1 NCI, SAIC, Lab Antiviral Drug Mechanisms, Frederick, MD 21702 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Frederick, MD 21702 USA. Univ Penn, Sch Med, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA. RP Sei, S (reprint author), NCI, SAIC, Lab Human Toxicol & Pharmacol, Dev Therapeut Program,, Bldg 439,POB B, Frederick, MD 21702 USA. EM sei@ncifcrf.gov FU NCI NIH HHS [CA80602, N01-CO-12400]; NIDCR NIH HHS [DE16665] NR 86 TC 20 Z9 20 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JAN PY 2006 VL 69 IS 1 BP 9 EP 23 DI 10.1016/j.antiviral.2005.09.005 PG 15 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 001ID UT WOS:000234525900002 PM 16337284 ER PT J AU Loomba, R Liang, TJ AF Loomba, R Liang, TJ TI Novel approaches to new therapies for hepatitis B virus infection SO ANTIVIRAL THERAPY LA English DT Review ID POSITIVE CHRONIC HEPATITIS; CONTROLLED PILOT TRIAL; T-CELL RESPONSES; TRANSGENIC MICE; DENDRITIC CELL; IN-VIVO; ADEFOVIR DIPIVOXIL; ALPHA-INTERFERON; VIRAL-HEPATITIS; HBV INFECTION AB Hepatitis B is one of the most prevalent viral diseases in the world. It leads to chronic liver disease in 10% of infected individuals, putting them at an increased risk for liver-related morbidity and mortality from complications of cirrhosis and hepatocellular carcinoma. Despite the success of universal hepatitis B vaccination in many countries, this disease remains a major public health problem, resulting in more than 500,000 deaths per year. Although the current therapy for chronic hepatitis B (CHB) is effective, it is not optimal; novel approaches to the management of CHB are needed. An improved understanding of virus-host interactions, advances in gene therapy, the development of molecular therapies targeted at different stages of the hepatitis B virus life cycle, and new insights into various approaches of immune modulation will lead to the development of better therapeutic agents for the management of CHB. These advances herald a new era of combination therapy. In this review, we will discuss emerging therapies and potential mechanisms, and highlight the promises and pitfalls of these new treatment strategies. C1 NIDDK, Liver Dis Branch, NIDDKD, Bethesda, MD 20892 USA. RP Liang, TJ (reprint author), NIDDK, Liver Dis Branch, NIDDKD, Bethesda, MD 20892 USA. EM JakeL@intra.niddk.nih.gov NR 121 TC 23 Z9 26 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 1 BP 1 EP 15 PG 15 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 026AL UT WOS:000236309000001 PM 16518955 ER PT J AU Dube, MP Wu, JW Aberg, JA Deeg, MA Alston-Smith, BL McGovern, ME Lee, D Shriver, SL Martinez, AI Greenwald, M Stein, JH AF Dube, Michael P. Wu, Julia W. Aberg, Judith A. Deeg, Mark A. Alston-Smith, Beverly L. McGovern, Mark E. Lee, Daniel Shriver, Sharon L. Martinez, Ana I. Greenwald, Martha Stein, James H. CA AIDS Clin Trials Grp A5248 TI Safety and efficacy of extended-release niacin for the treatment of dyslipidaemia in patients with HIV infection: AIDS Clinical Trials Group Study A5148 SO ANTIVIRAL THERAPY LA English DT Article ID ORAL GLUCOSE-TOLERANCE; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ANTIRETROVIRAL THERAPY; INSULIN-RESISTANCE; PROTEASE INHIBITORS; DIABETES-MELLITUS; NICOTINIC-ACID; SUSTAINED-RELEASE; RANDOMIZED-TRIAL; VIRUS INFECTION AB Background: Dyslipidaemia is very common in patients with HIV infection, but current therapies are often suboptimal. Since niacin may cause insulin resistance and hepatotoxicity it has generally been avoided in this setting. Methods: Non-diabetic male subjects (n=33) who had well-controlled HIV infection on antiretroviral therapy, fasting triglycerides >= 2.26 mmol/l and non-high density lipoprotein cholesterol (non-HDL-C) >= 4.66 mmol/l received escalating doses of extended-release niacin (ERN) up to 2,000 mg nightly for up to 44 weeks. Results: Fourteen subjects (42%) had pre-diabetes at entry. Twenty-three subjects (70%) received the maximum dose, eight (24%) received 1,500 mg. Niacin was well-tolerated. Only four subjects (12%) discontinued study treatment. There were small increases in fasting glycaemia and insulin resistance estimated by the homeostasis model assessment, but insulin resistance measures from the 2-h oral glucose tolerance test only transiently worsened. No subject developed persistent fasting hyperglycaemia; one had persistently elevated 2-h glucose >11.1 mmol/l. There were no significant changes in serum transaminases or uric acid. At week 48, the median change in fasting lipid levels in mmol/l (interquartile range) were: total cholesterol -0.21 (-1.35, -0.05), HDL-C +0.013 (-0.03,+0.28), non-HDL-C -0.49 (-1.37, +0.08) and triglycerides -1.73 (-3.68, -0.72). Favourable changes in large HDL and large very low density lipoprotein particle concentration were observed by nuclear magnetic resonance spectroscopy. Conclusions: ERN in doses up to 2,000 mg daily was safe, well-tolerated and efficacious in HIV-infected subjects with atherogenic dyslipidaemia. Increases in glycaemia and insulin resistance tended to be transient. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Div Infect Dis, Indianapolis, IN USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NYU, Dept Med, New York, NY 10016 USA. NYU, Div Infect Dis, New York, NY USA. Indiana Univ, Sch Med, Div Endocrinol, Indianapolis, IN USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. Kos Pharmaceut, Weston, FL USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Univ Wisconsin, Sch Med, Dept Med, Madison, WI USA. Univ Wisconsin, Sch Med, Div Cardiol, Madison, WI USA. RP Dube, MP (reprint author), Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. EM mpdube@iupui.edu RI Dube, Marie-Pierre/B-9364-2008 OI Dube, Marie-Pierre/0000-0001-8442-4393 FU NCRR NIH HHS [RR-00070, RR-00750]; NIAID NIH HHS [AI-27663, AI-25859, AI-38855, AI-38858, AI25859, AI27661, AI27670, AI27675, U01 AI025859, U01 AI027663, U01 AI027665, U01 AI027665-18, U01 AI027665-18S1, U01 AI027665-18S2, U01 AI038855, U01 AI038858] NR 42 TC 32 Z9 33 U1 1 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 8 BP 1081 EP 1089 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 121US UT WOS:000243183100014 PM 17302378 ER PT J AU Livingston, EG Cohn, SE Yang, Y Andersen, JW Watts, DH Bardeguez, AD Jones, TB Stevens, LM McComsey, GA AF Livingston, E. G. Cohn, S. E. Yang, Y. Andersen, J. W. Watts, D. H. Bardeguez, A. D. Jones, T. B. Stevens, L. M. McComsey, G. A. CA ACTG A5084 Team TI Effect of protease inhibitor-based antiretroviral therapy on lipid metabolism and lactate levels in pregnancy (ACTG A5084) SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 8th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY SEP 24-26, 2006 CL San Francisco, CA C1 Duke Univ, Durham, NC USA. Univ Rochester, Rochester, NY USA. Harvard Sch Publ Hlth, Boston, MA USA. NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Wayne State Univ, Detroit, MI USA. Frontier Sci Technol & Res Fdn, Amherst, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 7 BP L40 EP L41 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 104RG UT WOS:000241975800086 ER PT J AU Barnas, D Kearney, M Boltz, V Patel, S Maldarelli, F Hare, CB Havlir, D Su, Z Krambrink, A Margolis, D Palmer, S Coffin, J Mellors, J AF Barnas, D. Kearney, M. Boltz, V. Patel, S. Maldarelli, F. Hare, C. B. Havlir, D. Su, Z. Krambrink, A. Margolis, D. Palmer, S. Coffin, J. Mellors, J. TI Multi-genome sequencing (MGS): a new, sensitive method of detecting low frequency drug-resistant mutants SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Univ Pittsburgh, Pittsburgh, PA USA. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, SDAC, Boston, MA 02115 USA. Univ N Carolina, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S189 EP S189 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700189 ER PT J AU Brehm, J Koontz, D Pathak, V Sluis-Cremer, N Mellors, J AF Brehm, J. Koontz, D. Pathak, V. Sluis-Cremer, N. Mellors, J. TI AZT selects mutations in the connection (A371V) and RNase H (Q509L) domains of RT that increase AZT resistance in combination with TAMS and reduce susceptibility to other NRTIs SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Univ Pittsburgh, Pittsburgh, PA USA. NCI, Frederick, MD 21701 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S141 EP S141 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700145 ER PT J AU Castillo, A Adamson, C Doto, J Martin, D Wild, C Allaway, G Freed, E Salzwedel, K AF Castillo, A. Adamson, C. Doto, J. Martin, D. Wild, C. Allaway, G. Freed, E. Salzwedel, K. TI Genotypic analysis of the Gag CA/SP1 cleavage site in patients receiving the maturation inhibitor PA-457 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Panacos Pharmaceut, Gaithersburg, MD USA. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S37 EP S37 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700052 ER PT J AU Eshleman, SH Husnik, M Hudelson, S Donnell, D Huang, Y Hart, S Jackson, JB Coates, T Chesney, M Koblin, B AF Eshleman, S. H. Husnik, M. Hudelson, S. Donnell, D. Huang, Y. Hart, S. Jackson, J. B. Coates, T. Chesney, M. Koblin, B. TI Analysis of antiretroviral drug resistance and HIV-1 subtype among men who have sex with men recently infected with HIV-1 in the United States: the EXPLORE study SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Johns Hopkins Univ, Baltimore, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Emory Univ, Atlanta, GA 30322 USA. Frontier Sci & Technol Res Fdn Inc, Seattle, WA USA. Univ Calif Los Angeles, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. New York Blood Ctr, New York, NY 10021 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S122 EP S122 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700129 ER PT J AU Grossman, Z Hunt, P Deeks, SG AF Grossman, Z. Hunt, P. Deeks, S. G. TI Role of host factors in defining R5 versus X4 dominance during partially suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S56 EP S56 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700068 ER PT J AU Hare, CB Mellors, J Krambrink, A Su, Z Skiest, D Margolis, D Patel, S Barnas, D Frenkel, L Coombs, R Aweeka, F Morse, G Haas, DW Kim, R Boltz, V Palmer, S Coffin, J Havlir, DV AF Hare, C. B. Mellors, J. Krambrink, A. Su, Z. Skiest, D. Margolis, D. Patel, S. Barnas, D. Frenkel, L. Coombs, R. Aweeka, F. Morse, G. Haas, D. W. Kim, R. Boltz, V. Palmer, S. Coffin, J. Havlir, D. V. TI Selection of non-nucleoside reverse transcriptase inhibitor (NNRTI) resistant HIV-1 after discontinuation of a virologically suppressive regimen SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Harvard Univ, Sch Publ Hlth, SDAC, Boston, MA 02115 USA. Baystate Med Ctr, Springfield, MA USA. Univ N Carolina, Chapel Hill, NC USA. Univ Washington, Seattle, WA 98195 USA. SUNY Buffalo, Buffalo, NY 14260 USA. Vanderbilt Univ, Nashville, TN USA. NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S42 EP S42 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700054 ER PT J AU Johnson, VA Hazelwood, JD Andersen, J Miller, AB Liu, T Alston-Smith, B Brosgart, CL Rooney, JF Polsky, B Peters, MG AF Johnson, V. A. Hazelwood, J. D. Andersen, J. Miller, A. B. Liu, T. Alston-Smith, B. Brosgart, C. L. Rooney, J. F. Polsky, B. Peters, M. G. TI Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are effective in chronic hepatitis B virus (HBV) infection in subjects who are co-infected with HIV: HBV and HIV drug resistance results of ACTG Protocol A5127 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 Univ Alabama, Sch Med, Birmingham, AL 02115 USA. Birmingham VA Med Ctr, Birmingham, AL 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 94404 USA. NIAID, NIH, Bethesda, MD USA. Gilead Sci Inc, Foster City, CA USA. St Lukes Roosevelt Hosp, Div Infect Dis, New York, NY 94143 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Univ Calif San Francisco, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S11 EP S11 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700029 ER PT J AU Larder, BA Wang, D De Wolf, F Lange, J Revell, A Wegner, S Montaner, J Harrigan, R Metcalf, JA Lane, HC AF Larder, B. A. Wang, D. De Wolf, F. Lange, J. Revell, A. Wegner, S. Montaner, J. Harrigan, R. Metcalf, J. A. Lane, H. C. TI Accurate prediction of virological response to HAART using three computational modelling techniques SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 HIV Resistance Response Database Initiat, London, England. Netherlands HIV Monitoring Fdn, Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. US Mil HIV Res Program, Rockville, MD USA. BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. NIAID, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S177 EP S177 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700177 ER PT J AU Maldarelli, F Kearney, M Palmer, S Thawani, S Mican, J Rock-Kress, D Rehm, C Mellors, J Coffin, J AF Maldarelli, F. Kearney, M. Palmer, S. Thawani, S. Mican, J. Rock-Kress, D. Rehm, C. Mellors, J. Coffin, J. TI Independent patterns of sequence variation in HIV-1 pro and RT are facilitated by frequent recombination SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. NIAID, Lab LIR, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S168 EP S168 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700172 ER PT J AU Nikolenko, GN Frankenberry, KA Palmer, S Maldarelli, F Mellors, JW Coffin, JM Pathak, VK AF Nikolenko, G. N. Frankenberry, K. A. Palmer, S. Maldarelli, F. Mellors, J. W. Coffin, J. M. Pathak, V. K. TI The HIV-1 reverse transcriptase connection domain from treatment-experienced patients contributes to AZT resistance SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. Univ Pittsburgh, Pittsburgh, PA USA. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 5 Z9 5 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S142 EP S142 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700146 ER PT J AU Nissley, DV Church, JD Guay, LA Jackson, JB Strathern, JN Eshleman, SH AF Nissley, D. V. Church, J. D. Guay, L. A. Jackson, J. B. Strathern, J. N. Eshleman, S. H. TI Phenotypic NNRTI resistance and genetic diversity in drug-naive individuals SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 SAIC Frederick, BRP, Frederick, MD USA. NCI, GRCBL, Frederick, MD 21701 USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S154 EP S154 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700158 ER PT J AU Palmer, S King, M Wiegand, A Maldarelli, F Bernstein, B Hanna, G Brun, S Kempf, D Mellors, J Coffin, J AF Palmer, S. King, M. Wiegand, A. Maldarelli, F. Bernstein, B. Hanna, G. Brun, S. Kempf, D. Mellors, J. Coffin, J. TI Low-level viraemia persists for at least 7 years in patients on suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 15th International HIV Drug Resistance Workshop CY JUN 13-17, 2006 CL Sitges, SPAIN C1 NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21701 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2006 VL 11 IS 5 BP S63 EP S63 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 076UY UT WOS:000239984700075 ER PT J AU Llorente, A Brouwers, P Thompson, B Cheng, I Macmillan, C LaRussa, P Mofenson, L Blasini, I Chase, C AF Llorente, Antolin Brouwers, Pim Thompson, Bruce Cheng, Irene Macmillan, Carol LaRussa, Phillip Mofenson, Lynne Blasini, Ileana Chase, Cynthia TI Effects of polymorphisms of chemokine receptors on neurodevelopment and the onset of encephalopathy in children with perinatal HIV-1 infection SO APPLIED NEUROPSYCHOLOGY LA English DT Article DE chemokine receptors; children; HIV-1; neurodevelopment; polymorphisms ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE-DEFICIENCY SYNDROME; INFANTS TRANSMISSION; DISEASE PROGRESSION; TYPE-1 INFECTION; CCR5; ALLELES; WOMEN; AIDS; INDIVIDUALS AB This study examined the effects of chemokine receptor polymorphisms on neurodevelopment and the onset of encephalopathy in children with perinatal HIV-1 infection. Infected children (N = 121) between the ages of I and 72 months were categorized into dichotomous groups (heterozygous or homozygous mutant vs. homozygous wild type)for each chemokine receptor 2 (CCR2) and chemokine receptor 5 (CCR5) allele. Neurodevelopmental measures included the Bayley Scales of Infant Development (BSID)for children age:! 30 months and the McCarthy Scales of Children's Abilities (MSCA)for children aged > 30 months. A basic linear spline was used to model the mean value at each visit for the relevant test index, with determination of the slope between 4-12 months, 12-30 months, and 31-72 months of age. A mixed model analysis of variance was used to compare differences between slopes (Delta alpha) and intercepts (Delta alpha) according to the presence or absence of the specified CCR2 or CCR5 polymorphism. Survival analyses were used to compare the onset of encephalopathy by chemokine receptor allelic grouping. After adjusting for potential confounds, statistically significant differences emerged in CCR5-39353, 39356, and 39402. Although the protective effects appeared to be discrete and transient, children with mutant CCR5 genotypes exhibited better neurodevelopmental outcomes than children with the wild type alleles. Chemokine polymorphisms did not appear to impact the onset of encephalopathy. Although possibly a temporary effect, HIV-1 infected children with selected mutant chemokine receptor polymorphims CCR5-39353, 39356, and 39402 may exhibit better neurodevelopmental outcome than children with the wild type allele. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baylor Coll Med, Houston, TX 77030 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Univ Illinois, Chicago, IL USA. Columbia Univ Coll Phys & Surg, New York, NY USA. NICHHD, Rockville, MD USA. Univ Puerto Rico, San Juan, PR 00936 USA. Boston Med Ctr, Boston, MA USA. RP Llorente, A (reprint author), Univ Maryland, Sch Med, Mt Washington Pediat Hosp, 1708 W Rogers Ave,Suite 1141, Baltimore, MD 21209 USA. EM allorente@mwph.org OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [RR00188, RR00645]; NIAID NIH HHS [1 U0 AI 050274-01, 1 U01 AI 50274-01, N01 AI 85339, U01 AI 34841, U01 AI 34858]; NICHD NIH HHS [U01 HD 41983]; NIDA NIH HHS [9U01 DA 15054, U01 DA 15053] NR 36 TC 4 Z9 5 U1 2 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0908-4282 J9 APPL NEUROPSYCHOL JI Appl. Neuropsychol. PY 2006 VL 13 IS 3 BP 180 EP 189 DI 10.1207/s15324826an1303_6 PG 10 WC Clinical Neurology; Psychology SC Neurosciences & Neurology; Psychology GA 112KG UT WOS:000242524000006 PM 17361671 ER PT J AU Vidal, CN Rapoport, JL Hayashi, KM Geaga, JA Sui, YH McLemore, LE Alaghband, Y Giedd, JN Gochman, P Blumenthal, J Gogtay, N Nicolson, R Toga, AW Thompson, PM AF Vidal, CN Rapoport, JL Hayashi, KM Geaga, JA Sui, YH McLemore, LE Alaghband, Y Giedd, JN Gochman, P Blumenthal, J Gogtay, N Nicolson, R Toga, AW Thompson, PM TI Dynamically spreading frontal and cingulate deficits mapped in adolescents with schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CHILDHOOD-ONSET SCHIZOPHRENIA; GRAY-MATTER LOSS; MEDIAL PREFRONTAL CORTEX; VOXEL-BASED MORPHOMETRY; WHITE-MATTER; CEREBRAL-CORTEX; ALZHEIMERS-DISEASE; BRAIN; MRI; ABNORMALITIES AB Context: We previously detected a dynamic wave of gray matter loss in childhood-onset schizophrenia that started in parietal association cortices and proceeded frontally to envelop dorsolateral prefrontal and temporal cortices, including superior temporal gyri. Objective: To map gray matter loss rates across the me dial hemispheric surface, including the cingulate and me dial frontal cortex, in the same cohort studied previously Design: Five-year longitudinal study. Setting: National Institute of Mental Health, Bethesda, Md Subjects: Twelve subjects with childhood-onset schizophrenia, 12 healthy controls, and 9 medication- and IQ-matched subjects with psychosis not otherwise specified. Interventions: Three-dimensional magnetic resonance imaging at baseline and follow-up. Main Outcome Measures: Gyral pattern and shape variations encoded by means of high-dimensional etastic deformation mappings driving each subject's cortical anatomy onto a group average; changes in cortical gray matter mapped by computing warping fields that matched sulcal patterns across hemispheres, subjects, and time. Results: Selective, severe frontal gray matter loss occurred bilaterally in a dorsal-to-ventral pattern across the medial hemispheric surfaces in the schizophrenic subjects. A sharp boundary in the pattern of gray matter loss separated frontal regions and cingulate-limbic areas. Conclusion: Frontal and limbic regions may not be equally vulnerable to gray matter attrition, which is consistent with the cognitive, metabolic, and functional vulnerability of the frontal cortices in schizophrenia. C1 Univ Calif Los Angeles, David Geffen Sch Med, Reed Neurol Res Ctr, Dept Neurol,Brain Mapping Div,Lab Neuro Imaging, Los Angeles, CA 90095 USA. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Thompson, PM (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Reed Neurol Res Ctr, Dept Neurol,Brain Mapping Div,Lab Neuro Imaging, Room 4238,710 Westwood Plaza, Los Angeles, CA 90095 USA. EM thompson@loni.ucla.edu RI Gogtay, Nitin/A-3035-2008; Giedd, Jay/A-3080-2008; Nicolson, Robert/E-4797-2011; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 FU Intramural NIH HHS; NCRR NIH HHS [P41 RR13642, R21 RR019771]; NIBIB NIH HHS [R21 EB01561]; NIMH NIH HHS [P20 MH/DA52176]; NINDS NIH HHS [NS38753]; NLM NIH HHS [LM/MH05639] NR 75 TC 106 Z9 109 U1 4 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2006 VL 63 IS 1 BP 25 EP 34 DI 10.1001/archpsyc.63.1.25 PG 10 WC Psychiatry SC Psychiatry GA 000DK UT WOS:000234440900003 PM 16389194 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, H Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, H Roth, EJ Tate, DG TI Rehabilitation Medicine Summit: Building Research Capacity. Executive summary SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE physical medicine; rehabilitation; research priorities AB The general objective of the "Rehabilitation Medicine Summit: Building Research Capacity" was to advance and promote research in medical rehabilitation by making recommendations to expand research capacity. The 5 elements of research capacity that guided the discussions were researchers; research culture, environment, and infrastructure; funding; partnerships; and metrics. Participants included representatives of professional organizations, consumer groups, academic departments, researchers, governmental funding agencies, and the private sector. Small group discussions and plenary sessions generated an array of problems, possible solutions, and recommended actions. A post-Summit, multiorganizational initiative is called for to pursue the agendas outlined in this report. C1 Spaulding Rehabil Hosp, Harvard Med Sch, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Florida, Gainesville, FL USA. Powers Pyles Sutter & Verville PC, Washington, DC USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Spaulding Rehabil Hosp, Harvard Med Sch, 125 Nashua St, Boston, MA 02114 USA. EM wfrontera@partners.org OI Jette, Alan/0000-0002-2117-9973 NR 3 TC 15 Z9 15 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD JAN PY 2006 VL 87 IS 1 BP 148 EP 152 DI 10.1016/j.apmr.2005.10.021 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 003GT UT WOS:000234670500026 PM 16401455 ER PT J AU Hansen, A Reiter, K Pruss, A Loddenkemper, C Kaufmann, O Jacobi, AM Scholze, J Lipsky, PE Dorner, T AF Hansen, A Reiter, K Pruss, A Loddenkemper, C Kaufmann, O Jacobi, AM Scholze, J Lipsky, PE Dorner, T TI Dissemination of a Sjogren's syndrome-associated extranoda marginal-zone B cell lymphoma - Circulating lymphoma cells and invariant mutation pattern of nodal Ig heavy- and light-chain variable-region gene rearrangements SO ARTHRITIS AND RHEUMATISM LA English DT Article ID V-H GENES; MALT LYMPHOMA; SALIVARY-GLAND; MALIGNANT-LYMPHOMA; RHEUMATOID FACTORS; PERIPHERAL-BLOOD; TISSUE LYMPHOMA; GASTRIC-MUCOSA; P53 MUTATIONS; PATIENT AB Objective. Both the genesis and outgrowth of extranodal marginal-zone B cell lymphomas (MZLs) of the mucosa-associated lymphoid tissue (MALT) type are generally thought to represent antigen-driven processes. We undertook this study to analyze lymphoma progression and dissemination outside of the MALT-type lesions. Methods. Histopathologic and Ig heavy- and light-chain variable-region gene (V-H/L) analyses were performed in sequential tissue samples from a patient with primary Sjogren's syndrome (SS) with glandular (parotid) manifestations and subsequent nodal dissemination of a low-grade MZL. Results. This MZL expressed a CD20+,CD27+, sIgM/kappa+,IgD-,CD5-,CD10-,Bcl-6-,CD23-,p53-, p21-,MDM2- phenotype and mutated V(H)1-69/D2-21/J(H)4 alpha-V(kappa)A27/J(kappa)2 Ig rearrangements. Notably, circulating lymphoma cells from the parotid glands occurred transiently in the patient's blood, as detected by single-cell polymerase chain reaction. In addition, 2 minor B cell clones (clones 2 and 3, with V(H)3-O7/D3-22/J(H)3b-V(lambda)3L/J(lambda)2/3 and V(lambda)3-64/D3-03/J(H)2-V(kappa)A19/J(kappa)2 rearrangements, respectively) were also detected in the parotid glands and blood, and I of these (clone 2) was also detected in the lymph nodes. 19 VH/L analyses revealed ongoing (antigen-driven) mutations of the glandular lymphoma rearrangements, but an invariant mutation pattern of their nodal counterparts. Conclusion. These data indicate coexpansion and transient (re)circulation of the lymphoma clone and 2 additional glandular B cell clones in a primary SS-associated extranodal MZL. Combined histologic and molecular features of the nodal lymphoma subclone reflect a process of "follicular colonization" that eventually froze the mutation machinery after accumulation of additional (antigen-driven) 19 V-H/L mutations. C1 Charite Univ Med Berlin, Dept Med, Outpatient Dept, D-10098 Berlin, Germany. Carl Thiem Klinikum, Cottbus, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hansen, A (reprint author), Charite Univ Med Berlin, Dept Med, Outpatient Dept, Schumannstr 20-21, D-10098 Berlin, Germany. EM ahansen@charite.de NR 48 TC 16 Z9 19 U1 0 U2 2 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 JAN PY 2006 VL 54 IS 1 BP 127 EP 137 DI 10.1002/art.21558 PG 11 WC Rheumatology SC Rheumatology GA 002IO UT WOS:000234605200017 PM 16385504 ER PT J AU Aletaha, D AF Aletaha, D TI Pooled indices to measure rheumatoid arthritis activity: a good reflection of the physician's mind? SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID DISEASE-ACTIVITY; REMISSION AB Several pooled indices for the assessment of rheumatoid arthritis disease activity are available to rheumatologists. Face and criterion validity of these instruments can be assessed by determining the association of their measurements with opinions of physicians. Several confounding aspects must be considered in such analyses, especially blinding of the person( s) making the decisions to the instruments being studied and to the objective of the study in general. From several studies in the literature, there is currently no evidence that any one of the available composite indices is better or worse than any other. The choice of index in clinical practice should ideally be based on practical considerations related to the needs of the rheumatologist in the respective health care setting. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Aletaha, D (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM aletahad@mail.nih.gov NR 9 TC 6 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2006 VL 8 IS 1 AR 102 DI 10.1186/ar1870 PG 3 WC Rheumatology SC Rheumatology GA 018ZI UT WOS:000235803900002 PM 16542465 ER PT J AU Kapral, T Stamm, T Machold, KP Montag, K Smolen, JS Aletaha, D AF Kapral, Theresa Stamm, Tanja Machold, Klaus P. Montag, Karin Smolen, Josef S. Aletaha, Daniel TI Methotrexate in rheumatoid arthritis is frequently effective, even if re-employed after a previous failure SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID MODIFYING ANTIRHEUMATIC DRUGS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ERYTHROCYTE SEDIMENTATION-RATE; LOW-DOSE METHOTREXATE; C-REACTIVE PROTEIN; PRIVATE PRACTICES; CONTROLLED-TRIAL; THERAPY; EFFICACY; PROFILES AB Effectiveness of therapy with individual disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis ( RA) is limited, and the number of available DMARDs is finite. Therefore, at some stage during the lengthy course of RA, institution of traditional DMARDs that have previously been applied may have to be reconsidered. In the present study we investigated the effectiveness of re-employed methotrexate in patients with a history of previous methotrexate failure ( original course). A total of 1,490 RA patients (80% female, 59% rheumatoid factor positive) were followed from their first presentation, yielding a total of 6,470 patient-years of observation. We identified patients in whom methotrexate was re-employed after at least one intermittent course of a different DMARD. We compared reasons for discontinuation, improvement in acute phase reactants, and cumulative retention rates of methotrexate therapy between the original course of methotrexate and its reemployment. Similar analyses were peformed for other DMARDs. Methotrexate was re-employed in 86 patients. Compared with the original courses, re-employment was associated with a reduced risk for treatment termination because of ineffectiveness ( P = 0.02, by McNemar test), especially if the maximum methotrexate dose of the original course had been low (< 12.5 mg/week; P = 0.02, by logistic regression). In a Cox regression model, re-employed MTX was associated with a significantly reduced hazard of treatment termination compared with the original course of methotrexate, adjusting for dose and year of employment ( hazard ratio 0.64, 95% confidence interval 0.42 - 0.97; P = 0.04). These findings were not recapitulated in analyses of re- employment of other DMARDs. Re-employment of MTX despite prior inefficacy, but not re- employment of other DMARDs, is an effective therapeutic option, especially in those patients in whom the methotrexate dose of the original course was low. C1 Med Univ Vienna, Dept Rheumatol, Vienna, Austria. Lainz Hosp, Dept Med 2, Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Aletaha, D (reprint author), Med Univ Vienna, Dept Rheumatol, Vienna, Austria. EM aletahad@mail.nih.gov NR 38 TC 17 Z9 18 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2006 VL 8 IS 2 AR R46 DI 10.1186/ar1902 PG 9 WC Rheumatology SC Rheumatology GA 044CA UT WOS:000237648600018 PM 16507172 ER PT J AU Mattyasovszky, S Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Mattyasovszky, Stefan Skapenko, Alla Kalden, Joachim R. Lipsky, Peter E. Schulze-Koops, Hendrik TI IFNGR1 single nucleotide polymorphisms in rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; NATIONWIDE AB On the basis of their biological function, potential genetic candidates for susceptibility to rheumatoid arthritis can be postulated. IFNGR1, encoding the ligand-binding chain of the receptor for interferon gamma, IFN gamma R1, is one such gene because interferon gamma is involved in the pathogenesis of the disease. In the coding sequence of IFNGR1, two nucleotide positions have been described to be polymorphic in the Japanese population. We therefore investigated the association of those two IFNGR1 single nucleotide polymorphisms with rheumatoid arthritis in a case-control study in a central European population. Surprisingly, however, neither position was polymorphic in the 364 individuals examined, indicating that IFNGR1 does not contribute to susceptibility to rheumatoid arthritis, at least in Caucasians. C1 Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, D-8520 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Internal Med 3, D-8520 Erlangen, Germany. NIAMSD, Bethesda, MD 20892 USA. Univ Mainz, Dept Trauma Surg, D-6500 Mainz, Germany. RP Schulze-Koops, H (reprint author), Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, D-8520 Erlangen, Germany. EM schulze-koops@med3.imed.uni-erlangen.de NR 10 TC 1 Z9 1 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2006 VL 8 IS 3 AR R63 DI 10.1186/ar1927 PG 3 WC Rheumatology SC Rheumatology GA 044CE UT WOS:000237649000015 PM 16563189 ER PT J AU Romisch, K Miller, FW Dobberstein, B High, S AF Romisch, Karin Miller, Frederick W. Dobberstein, Bernhard High, Stephen TI Human autoantibodies against the 54 kDa protein of the signal recognition particle block function at multiple stages SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHY; TRANSFER RNA-SYNTHETASE; METHIONINE-RICH DOMAIN; ENDOPLASMIC-RETICULUM; SEQUENCE RECOGNITION; MEMBRANE INSERTION; CRYSTAL-STRUCTURE; 54-KD PROTEIN; SRP; RIBOSOME AB The 54 kDa subunit of the signal recognition particle (SRP54) binds to the signal sequences of nascent secretory and membrane proteins and it contributes to the targeting of these precursors to the membrane of the endoplasmic reticulum ( ER). At the ER membrane, the binding of the signal recognition particle (SRP) to its receptor triggers the release of SRP54 from its bound signal sequence and the nascent polypeptide is transferred to the Sec61 translocon for insertion into, or translocation across, the ER membrane. In the current article, we have characterized the specificity of anti-SRP54 autoantibodies, which are highly characteristic of polymyositis patients, and investigated the effect of these autoantibodies on the SRP function in vitro. We found that the anti-SRP54 autoantibodies had a pronounced and specific inhibitory effect upon the translocation of the secretory protein preprolactin when analysed using a cell-free system. Our mapping studies showed that the anti-SRP54 autoantibodies bind to the amino-terminal SRP54 N-domain and to the central SRP54 G-domain, but do not bind to the carboxy-terminal M-domain that is known to bind ER signal sequences. Nevertheless, anti-SRP54 autoantibodies interfere with signal-sequence binding to SRP54, most probably by steric hindrance. When the effect of anti-SRP autoantibodies on protein targeting the ER membrane was further investigated, we found that the autoantibodies prevent the SRP receptor-mediated release of ER signal sequences from the SRP54 subunit. This observation supports a model where the binding of the homologous GTPase domains of SRP54 and the alpha-subunit of the SRP receptor to each other regulates the release of ER signal sequences from the SRP54 M-domain. C1 Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. Univ Cambridge, Cambridge Inst Med Res, Cambridge, England. Univ Cambridge, Dept Clin Biochem, Cambridge, England. NIEHS, Environm Autoimmun Grp, NIH, HHS, Bethesda, MD USA. Univ Heidelberg ZMBH, Zentrum Mol Biol, Heidelberg, Germany. RP High, S (reprint author), Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. EM stephen.high@manchester.ac.uk OI Miller, Frederick/0000-0003-2831-9593; High, Stephen/0000-0002-4532-8152 FU Biotechnology and Biological Sciences Research Council [SF16973]; Wellcome Trust [042216] NR 44 TC 18 Z9 19 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2006 VL 8 IS 2 AR R39 DI 10.1186/ar1895 PG 13 WC Rheumatology SC Rheumatology GA 044CA UT WOS:000237648600011 PM 16469117 ER PT J AU Tao, XL Fan, F Hoffmann, V Longo, NS Lipsky, PE AF Tao, XL Fan, F Hoffmann, V Longo, NS Lipsky, PE TI Therapeutic impact of the ethyl acetate extract of Tripterygium wilfordii Hook F on nephritis in NZB/W F1 mice SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID CHINESE HERBAL REMEDY; FACTOR-KAPPA-B; MURINE LUPUS; AUTOANTIBODY PRODUCTION; RHEUMATOID-ARTHRITIS; GENE-TRANSCRIPTION; NITRIC-OXIDE; MICE; CELLS; TRIPTOLIDE AB This study was designed to examine the potential use of the ethyl acetate (EA) extract of Tripterygium wilfordii Hook F (TwHF), a Chinese herbal medicine, in the treatment of systemic lupus erythematosus. A total of 48 28-week-old female NZB/W F1 mice were randomly divided into three groups and orally administered vehicle or the EA extract of TwHF at 18.25 mg/kg (EA(low)) or 36.5 mg/kg (EA(high)) for 14 weeks. Proteinuria and serum anti-double-stranded (ds) DNA antibody titers were assayed before and after treatment. At the end of treatment, all animals were sacrificed and pathological changes in the kidneys were examined by observers blinded to the treatment regimens. Immunohistological studies were carried out on kidneys and spleens. At 28 weeks of age, proteinuria (> 30 mg/dl) and anti-dsDNA antibodies were found in all mice in the three groups. Fourteen, sixteen and fifteen mice in the vehicle, EA(low) and EA(high) groups, respectively, completed at least four weeks of treatment. At the end of treatment, the mean proteinuria of the EAlow and EAhigh groups was significantly less than that of the vehicle group and no different from proteinuria at the onset of treatment. Histological evidence of glomerulonephritis, glomerular deposition of IgG and complement 3 and cellular infiltration in the interstitium and perivascular regions were significantly less severe in the EA extract treated mice than in vehicle treated mice. Treatment with the EA extract significantly inhibited the progression of kidney disease in NZB/W F1 mice, though had no significant effect on the levels of anti-dsDNA antibody. C1 NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Off Res Serv, Div Vet Resources, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov NR 42 TC 9 Z9 10 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2006 VL 8 IS 1 AR R24 DI 10.1186/ar1879 PG 11 WC Rheumatology SC Rheumatology GA 018ZI UT WOS:000235803900033 PM 16507125 ER PT J AU Stewart, DJ Fahmy, H Roth, BL Yan, F Zjawiony, JK AF Stewart, DJ Fahmy, H Roth, BL Yan, F Zjawiony, JK TI Bioisosteric modification of salvinorin A, a potent and selective kappa-opioid receptor agonist SO ARZNEIMITTEL-FORSCHUNG-DRUG RESEARCH LA English DT Article DE CAS 83729-01-5; kappa-opioid receptor agonist; Salvia divinorum; salvinorin A ID PLANT-DERIVED HALLUCINOGEN; SALVIA-DIVINORUM; RATS; DYNORPHIN; SPIRADOLINE AB Salvinorin A ((2S,4aR,6aR,7R,9S,10aS, 10bR)-2H-naphtho[2,1-c]pyran-7carboxylic acid, 9-(acetyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10- dioxo methyl ester, 1, CAS 83729-01-5) has been shown to bind with high affinity and selectivity to the kappa-opioid receptor (KOR) as an agonist. Bioisosteres of I were developed and biologically evaluated in binding and functional assays. The C-2 thioacetate isoster produced comparable activity to 1, but nitrogen substitution had a diminishing effect. Intermediates, which lack a P-carbonyl at C-2, displayed moderate affinity. The derivatives were tested against all opioid subtypes and were selective towards KOR. C1 Univ Mississippi, Dept Pharmacognosy, Sch Pharm, University, MS 38677 USA. Univ Mississippi, Natl Ctr Nat Prod Res, Sch Pharm, Res Inst Pharmaceut Sci, University, MS 38677 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Zjawiony, JK (reprint author), Univ Mississippi, Dept Pharmacognosy, Sch Pharm, University, MS 38677 USA. EM jordan@olemiss.edu RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01DA017204] NR 24 TC 13 Z9 13 U1 0 U2 2 PU ECV-EDITIO CANTOR VERLAG MEDIZIN NATURWISSENSCHAFTEN PI AULENDORF PA BANDELSTOCKWEG 20, POSTFACH 1255, D-88322 AULENDORF, GERMANY SN 0004-4172 J9 ARZNEIMITTEL-FORSCH JI Arzneimittelforschung PY 2006 VL 56 IS 4 BP 269 EP 275 PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 046BZ UT WOS:000237787700001 PM 16724512 ER PT B AU Iwasa, KH AF Iwasa, K. H. BE Nuttal, AL TI "Area change paradox" in outer hair cells' membrane motor SO Auditory Mechanisms: Processes and Models LA English DT Proceedings Paper CT 9th International Symposium on Auditory Mechanisms CY JUL 23-28, 2005 CL Portland, OR ID COCHLEAR AMPLIFIER; SOMATIC STIFFNESS; MOTILITY; MODEL; CAPACITANCE; PRESTIN AB Outer hair cells in the cochlea have motility which directly uses electrical energy available at their plasma membrane. It has been shown that this motility can be reasonably explained by a simple two state model in which two states differ in charge and membrane area but not in the mechanical compliance. The model leads to a biphasic dependence of the axial stiffness analogous of gating compliance. However, the experimentally observed axial compliance monotonically increases with depolarization. Such observation appears to be explained by assuming that a large compliance of the state with smaller membrane area. However, such an assumption leads to incorrect tension dependence of the motor. It is found that this inconsistency is associated with the condition that increased membrane tension reverses the size of membrane areas of the two states. To avoid this paradox, the compliance of the state with smaller membrane area must decrease as membrane tension increases. That means that the axial compliance that is monotonic with respect to voltage can be predicted only if turgor pressure is less than 0.1 kPa, somewhat less than reported estimates. C1 NIDCD, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Iwasa, KH (reprint author), NIDCD, Biophys Sect, NIH, 50 South Dr, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-824-7 PY 2006 BP 155 EP 161 DI 10.1142/9789812773456_0027 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA BFD85 UT WOS:000241277000027 ER PT B AU Chadwick, RS Manoussaki, D Dimitriadis, EK Shoelson, B Ketten, DR Arruda, J O'Malley, JT AF Chadwick, R. S. Manoussaki, D. Dimitriadis, E. K. Shoelson, B. Ketten, D. R. Arruda, J. O'Malley, J. T. BE Nuttal, AL TI Cochlear coiling and low-frequency hearing SO Auditory Mechanisms: Processes and Models LA English DT Proceedings Paper CT 9th International Symposium on Auditory Mechanisms CY JUL 23-28, 2005 CL Portland, OR AB Surface gravity waves in a spiral channel can be used as an analogue for cochlear macromechanics (Manoussaki et a]. [1]). We found that in a vertical-walled channel with uniform cross section, as a low-frequency wave propagates inward from larger to smaller spiral radii, the wave amplitude near the outside wall grows while the amplitude near the inside wall decreases. This relative amplitude change induces a radial tilt of the free surface, the magnitude of which increases in inverse proportion to the spiral radius. The tilt, which can be interpreted in terms of energy redistribution, can be explained by a "whispering gallery effect," can develop dynamically on the cochlear partition and, by contributing to the bending of apical stereocilia (Cai et al. [2]), can augment low-frequency hearing by as much as 20 dB. We therefore hypothesized that cochlear spiral radii ratios (largest/smallest) could account for interspecies differences in low-frequency hearing. Preliminary analyses of spiral parameters obtained from published data on mammalian species, as well as from histological sections and 3D CT scans of the cochleae of low-frequency baleen whales and high-frequency dolphins and porpoises, tend to support our hypothesis: species with good low-frequency hearing have larger spiral ratios than do those with poor low-frequency hearing. C1 NIDCD, Sect Auditory Mech, Bethesda, MD 20892 USA. RP Chadwick, RS (reprint author), NIDCD, Sect Auditory Mech, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 2 U2 2 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-824-7 PY 2006 BP 417 EP 424 DI 10.1142/9789812773456_0067 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA BFD85 UT WOS:000241277000067 ER PT B AU Cai, H Chadwick, RS Manoussaki, D AF Cai, H. Chadwick, R. S. Manoussaki, D. BE Nuttal, AL TI Wave propagation in a complex cochlear micromechanics model with curvature SO Auditory Mechanisms: Processes and Models LA English DT Proceedings Paper CT 9th International Symposium on Auditory Mechanisms CY JUL 23-28, 2005 CL Portland, OR AB We use our recently developed hybrid analytical/finite-element approach to investigate the significance of curvature in cochlear micromechanics. The new computational model includes the detailed cellular structures within the organ of Corti, the interactions between the cochlear partition and fluid, as well as the coiling effects of the cochlear geometry. Gorverning equations are formulated in a curvilinear coordinate system. We develop an iterative algorithm to solve a fluid-solid interaction eigenvalue problem. We find that the cochlear curvature greatly increases the apical shear gain of the cochlear partition, which is a measure of the bending efficiency of the outer hair cell stereocilia. C1 NIDCD, NIH, Sect Auditory Mech, Bethesda, MD 20892 USA. RP Cai, H (reprint author), NIDCD, NIH, Sect Auditory Mech, Bldg 10,Rm 5D49, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 981-256-824-7 PY 2006 BP 498 EP 499 DI 10.1142/9789812773456_0078 PG 2 WC Otorhinolaryngology SC Otorhinolaryngology GA BFD85 UT WOS:000241277000078 ER PT J AU Rosser, BWC Viswanathan, M AF Rosser, BWC Viswanathan, M TI In memoriam: John Caleekal George, 1921-2005 SO AUK LA English DT Biographical-Item C1 Univ Saskatchewan, Dept Anat & Cell Biol, Saskatoon, SK S7N 5E5, Canada. NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Rosser, BWC (reprint author), Univ Saskatchewan, Dept Anat & Cell Biol, Saskatoon, SK S7N 5E5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ORNITHOLOGISTS UNION PI LAWRENCE PA ORNITHOLOGICAL SOC NORTH AMER PO BOX 1897, LAWRENCE, KS 66044-8897 USA SN 0004-8038 J9 AUK JI AUK PD JAN PY 2006 VL 123 IS 1 BP 279 EP 280 DI 10.1642/0004-8038(2006)123[0279:IMJCG]2.0.CO;2 PG 2 WC Ornithology SC Zoology GA 011UG UT WOS:000235293300027 ER PT J AU Miller, FW AF Miller, Frederick W. BE Rose, NR Mackay, IR TI Noninfectious Environmental Agents and Autoimmunity SO AUTOIMMUNE DISEASES, 4TH EDITION LA English DT Article; Book Chapter ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; TYPE-1 DIABETES-MELLITUS; IDIOPATHIC INFLAMMATORY MYOPATHIES; SILICONE BREAST IMPLANTS; ULTRAVIOLET-RADIATION; RHEUMATOID-ARTHRITIS; DISEASE; ONSET; AUTOANTIBODIES; EPIDEMIOLOGY C1 NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), NIEHS, Environm Autoimmun Grp, Off Clin Res, NIH, Bethesda, MD 20892 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 62 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045474-0 PY 2006 BP 297 EP 307 DI 10.1016/B978-012595961-2/50026-3 PG 11 WC Immunology SC Immunology GA BCW76 UT WOS:000311707200024 ER PT J AU Levy-Clarke, GA Li, ZQ Kump, LI Nussenblatt, RB AF Levy-Clarke, Grace A. Li, Zhuqing Kump, Leila I. Nussenblatt, Robert B. BE Rose, NR Mackay, IR TI Ocular Disease SO AUTOIMMUNE DISEASES, 4TH EDITION LA English DT Article; Book Chapter ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; TUMOR-NECROSIS-FACTOR; FAMILIAL PARS PLANITIS; JUVENILE RHEUMATOID-ARTHRITIS; EXPERIMENTAL ALLERGIC UVEITIS; PROTEIN-INDUCED UVEITIS; IFN-GAMMA PRODUCTION; HEPATITIS-B VACCINE; RETINAL-S-ANTIGEN; LEWIS RATS C1 [Levy-Clarke, Grace A.; Li, Zhuqing; Kump, Leila I.; Nussenblatt, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Levy-Clarke, GA (reprint author), NEI, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 108 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045474-0 PY 2006 BP 669 EP 679 DI 10.1016/B978-012595961-2/50052-4 PG 11 WC Immunology SC Immunology GA BCW76 UT WOS:000311707200050 ER PT S AU Lewis-Tuffin, LJ Cidlowski, JA AF Lewis-Tuffin, Laura J. Cidlowski, John A. BE Cutolo, M TI The physiology of human glucocorticoid receptor beta (hGR beta) and glucocorticoid resistance SO BASIC AND CLINICAL ASPECTS OF NEUROENDOCRINE IMMUNOLOGY IN RHEUMATIC DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 10-12, 2005 CL Genova, ITALY SP Abbott Spa, Schering-Plough Spa, Wyeth Lederle Spa DE glucocorticoid receptor beta (GR beta); glucocorticoid resistance; insensitivity; asthma; ulcerative colitis; leukemia; nasal polyps ID ACUTE LYMPHOBLASTIC-LEUKEMIA; MOLECULAR-MECHANISMS; MESSENGER-RNA; EXPRESSION; ISOFORM; CELLS; ACTIVATION; HORMONES; DOMAINS; BINDING AB The development of glucocorticoid (GC) resistance is a serious problem that complicates the treatment of immune-related diseases, such as asthma, ulcerative colitis, and hematologic cancers. hGR alpha and hGR beta are two isoforms of the human glucocorticoid receptor, which differ in the structural composition of the carboxy-terminal end of the ligand-binding domain and therefore in their ability to bind glucocorticoid ligand and in their physiological function. hGR alpha is the classically functional GR, while hGR beta seems to act mainly as a dominant negative to the function of hGR alpha. Because of the ability of hGR beta to antagonize the action of hGR alpha, it has been hypothesized that changes in the expression of hGR beta may underlie the development of glucocorticoid resistance. In this article we review what is known about the expression and physiological action of hGR beta in normal cells and tissue as well as in several disease states. Taken together, the evidence suggests that the ratio of hGR alpha:hGR beta expression is indeed critical to the glucocorticoid responsiveness of various cells. This ratio can be altered by changing the expression level of hGR alpha, hGR beta, or both receptors simultaneously. High er ratios correlate with glucocorticoid sensitivity, while lower ratios correlate with glucocorticoid resistance. Thus hGR beta can be an important modulator of glucocorticoid responsiveness. C1 NIEHS, Lab Signal Transductr, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Mayo Clin, Dept Canc Cell Biol, Jacksonville, FL 32224 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transductr, NIH, Dept Hlth & Human Serv, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlowski@niehs.nih.gov NR 57 TC 109 Z9 123 U1 2 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-593-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1069 BP 1 EP 9 DI 10.1196/annals.1351.001 PG 9 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Clinical Neurology; Rheumatology SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology; Rheumatology GA BEX21 UT WOS:000239951000001 PM 16855130 ER PT S AU Levine, JD Khasar, SG Green, PG AF Levine, Jon D. Khasar, Sachia G. Green, Paul G. BE Cutolo, M TI Neurogenic inflammation and arthritis SO BASIC AND CLINICAL ASPECTS OF NEUROENDOCRINE IMMUNOLOGY IN RHEUMATIC DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd International Conference on Neuroendocrine Immune Basis of the Rheumatic Diseases CY SEP 10-12, 2005 CL Genova, ITALY SP Abbott Spa, Schering-Plough Spa, Wyeth Lederle Spa DE nociception; pain; hyperalgesia; inflammation; inflammatory diseases; sympathoadrenal axis; adrenal medulla; hypothalamic-pituitary-adrenal axis; plasma extravasation; sex differences; 17 beta-estradiol; testosterone; chemotaxis; beta-adrenergic receptor; polymorphonuclear leukocytes ID INDUCED PLASMA EXTRAVASATION; PROTEIN-KINASE-C; INDUCED MECHANICAL HYPERALGESIA; CONNECTIVE-TISSUE DISEASES; WALL INDUCED POLYARTHRITIS; NECROSIS-FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; VAGAL MODULATION; SEXUAL-DIMORPHISM; PAIN THRESHOLD AB Inflammation and inflammatory diseases are sexually dimorphic, but the underlying causes for this observed sexual dimorphism are poorly understood. We discuss neural-immune mechanisms that underlie sexual dimorphism in three critical aspects of the inflammatory process-plasma extravasation, neutrophil function, and inflammatory hyperalgesia. Plasma extravasation and accumulation/activation of leukocytes into tissues are critical components in inflammation and are required for several other aspects of the inflammatory response. Pain (hyperalgesia) also markedly influences the magnitude of other components of the inflammatory response and induces a feedback control of plasma extravasation and neutrophil function. More important, this feedback control itself is powerfully modulated by vagal afferent activity and both the function of the primary afferent nociceptor and the modulation of inflammatory hyperalgesia by vagal afferent activity are highly sexually dimorphic. C1 Univ Calif San Francisco, NIH Pain Ctr, Dept Med, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH Pain Ctr, Dept Med, C522 Box 0440,521 Parnassus Ave, San Francisco, CA 94143 USA. EM Jon.Levine@ucsf.edu NR 91 TC 20 Z9 21 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-593-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1069 BP 155 EP 167 DI 10.1196/annals.1351.014 PG 13 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Clinical Neurology; Rheumatology SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology; Rheumatology GA BEX21 UT WOS:000239951000014 PM 16855143 ER PT J AU Jensen, RT AF Jensen, RT TI Consequences of long-term proton pump blockade: Insights from studies of patients with gastrinomas SO BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY LA English DT Review ID ZOLLINGER-ELLISON-SYNDROME; HELICOBACTER-PYLORI INFECTION; ENTEROCHROMAFFIN-LIKE-CELL; GASTROESOPHAGEAL-REFLUX DISEASE; MULTIPLE ENDOCRINE NEOPLASIA; REBOUND ACID HYPERSECRETION; RANDOMIZED CONTROLLED-TRIAL; SERUM VITAMIN-B-12 LEVELS; HISTAMINE H-2 BLOCKADE; PERNICIOUS-ANEMIA AB Proton pump inhibitors are being increasingly used and for longer periods of time, especially in patients with gastroesophageal reflux disease. Each of these trends has led to numerous studies and reviews of the potential risk-benefit ratio of the long-term use of proton pump inhibitors. Both long-term effects of hypergastrinaemia due to the profound acid suppression caused by proton pump inhibitors as well as the effects of hypo-/achlorhydria per se have been raised and studied. Potential areas of concern that have been raised in the long-term use of proton pump inhibitors, which could alter this risk-benefit ratio include: gastric carcinoid formation; the development of rebound acid hypersecretion when proton pump inhibitor treatment is stopped; the development of tolerance; increased oxyntic gastritis in H. pylori patients and the possibility of increasing the risk of gastric cancer; the possible stimulation of growth of non-gastric tumours due to hypergastrinaemia; and the possible effect of the hypo/achlorhydria on nutrient absorption, particularly iron and vitamin B12. Because few patients with idiopathic gastro-oesophageal reflux disease/peptic ulcer disease have been treated long-term (i.e., > 10 years), there is little known to address the above areas of potential concern. Most patients with gastrinomas with Zollinger-Ellison syndrome have life-long hypergastrinaemia, require continuous proton pump inhibitors treatment and a number of studies report results of > 5-10 years of tratment and follow-up. Therefore, an analysis of Zollinger-Ellison syndrome patients can provide important insights into some of the safety concerns raised above. In this paper, results from studies of Zollinger-Ellison syndrome patients and other recent studies dealing with the safety concerns above, are briefly reviewed. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 221 TC 63 Z9 70 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-7835 J9 BASIC CLIN PHARMACOL JI Basic Clin. Pharmacol. Toxicol. PD JAN PY 2006 VL 98 IS 1 BP 4 EP 19 DI 10.1111/j.1742-7843.2006.pto_378.x PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 006ED UT WOS:000234877400002 PM 16433886 ER PT J AU Kwon, D Kim, S Dahl, DB Swartz, M Tadesse, MG Vannucci, M AF Kwon, Deukwoo Kim, Sinae Dahl, David B. Swartz, Michael Tadesse, Mahlet G. Vannucci, Marina BE Do, KA Muller, P Vannucci, M TI Identification of DNA Regulatory Motifs and Regulators by Integrating Gene Expression and Sequence Data SO BAYESIAN INFERENCE FOR GENE EXPRESSION AND PROTEOMICS LA English DT Article; Book Chapter ID BAYESIAN VARIABLE SELECTION; DISCOVERY; SITES; YEAST; DICTIONARY; ALIGNMENT; MODULES; PROTEIN; GENOMES; MODEL AB We discuss methods to identify DNA regulatory elements by exploiting the correlation between sequence data and gene expression. We start by reviewing the contribution of M. G. Tadesse et al. (Identification of DNA regulatory motifs using Bayesian variable selection. Bioinformatics, 20 (2005), 2553-2561) in the use of Bayesian methods for variable selection for the identification of binding sites for regulatory factors. We then propose an extension of their model to include gene regulators. Although the modeling frameworks for variable selection has been extensively studied in the literature, their application in genomic studies for the identification of regulatory elements represents a novel contribution. We report performances of the methodologies on the well-studied regulatory systems of Saccharomyces cerevisiae under heat shock. C1 [Kwon, Deukwoo] NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. [Kim, Sinae] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Dahl, David B.; Swartz, Michael; Vannucci, Marina] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. [Swartz, Michael] Univ Texas MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. [Tadesse, Mahlet G.] Univ Penn, Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Kwon, D (reprint author), NCI, Radiat Epidemiol Branch, 6120 Execut Blvd,MSC 7238,Execut Plaza S,Room 704, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52186-092-5 PY 2006 BP 333 EP 346 D2 10.2277/ 052186092X PG 14 WC Biochemistry & Molecular Biology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA BXO55 UT WOS:000296575700018 ER PT J AU Shore, D Hayes-Shell, P Moretto-Wishnoff, C AF Shore, David Hayes-Shell, Pamela Moretto-Wishnoff, Christine TI Commentary on Eyler and Jeste: Practical issues in consent capacity and mental disorders SO BEHAVIORAL SCIENCES & THE LAW LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. RP Shore, D (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM dshore@mail.nih.gov NR 5 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PY 2006 VL 24 IS 4 BP 569 EP 572 DI 10.1002/bsl.690 PG 4 WC Psychology, Applied; Law SC Psychology; Government & Law GA 079FP UT WOS:000240161200015 PM 16705662 ER PT J AU Kreitman, RJ Pastan, I AF Kreitman, Robert J. Pastan, Ira TI BL22 and lymphoid malignancies SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE toxin; leukemia; lymphoma; Fv; Pseudomonas exotoxin; CD22; CD25; monoclonal antibody; leukemia; hairy cell; purine analog ID HAIRY-CELL LEUKEMIA; PSEUDOMONAS EXOTOXIN-A; CHRONIC LYMPHOCYTIC-LEUKEMIA; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; ANTI-CD20 MONOCLONAL-ANTIBODY; MINIMAL RESIDUAL DISEASE; TERM-FOLLOW-UP; RECOMBINANT IMMUNOTOXIN; PHASE-I; CYTOTOXIC ACTIVITY AB BL22 is a recombinant immunotoxin containing a truncated form of the bacterial toxin Pseudomonas exotoxin A attached to an Fv fragment of an anti-CD22 monoclonal antibody. Its mechanism of action involves binding to CD22, being internalized into the target cell by endocytosis, being processed to generate a free toxin fragment which is translocated into the cytoplasm, and finally induction of cell death by catalytic inactivation of elongation factor 2. In phase-I testing BL22 was very active in chemoresistant hairy-cell leukemia (HCL), with 19 (61%) of 31 patients achieving complete remission (CR). The low blood counts (cytopenias) which are characteristic of HCL improved in all complete and partial responders. Dose-limiting toxicity in HCL was due to a reversible hemolytic uremic syndrome (HUS), observed only during cycles 2 or 3. Already under way are a phase-II trial in HCL and phase-I trials in chronic lymphocytic leukemia (CLL) and acute lymphocytic leukemia (ALL) administering BL22 in a modified protocol in an effort to prevent HUS. C1 NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Kreitman, RJ (reprint author), NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, 9000 Rockville Pike,Bldg 37,Room 5124b, Bethesda, MD 20892 USA. EM kreitmar@mail.nih.gov FU Intramural NIH HHS NR 82 TC 13 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PY 2006 VL 19 IS 4 BP 685 EP 699 DI 10.1016/j.beha.2006.06.009 PG 15 WC Hematology SC Hematology GA 096UZ UT WOS:000241403600005 PM 16997177 ER PT B AU Yang, MQ Yang, JY AF Yang, Mary Qu Yang, Jack Y. GP IEEE COMPUTER SOC TI IUP: Intrinsically unstructured protein predictor - A software tool for analyzing polypeptide sequences SO BIBE 2006: SIXTH IEEE SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, PROCEEDINGS LA English DT Proceedings Paper CT 6th IEEE Syposium on BioInformatics and BioEngineering (BIBE 2006) CY OCT 16-18, 2006 CL Arlington, VA SP IEEE Comp Soc, Biol & Artificial Intelligence Soc, ITRI DE intrinsically unstructured proteins (IUP); feature selection; classification; ensemble methods ID DISORDER AB Many protein regions and some entire proteins have no definite tertiary structure, presenting instead as dynamic, disorder ensembles under different physiochemical circumstances. These proteins and regions are known as Intrinsically Unstructured Proteins (IUP). IUP have been associated with a wide range of protein functions and play essential roles in diseases characterized by protein misfolding and aggregation. Identifying IUP is an important but difficult task in today's structural and functional genomics. We exact useful features from polypeptide sequences and develop machine learning algorithms for the above task. We compare our IUP predictor with PONDR (R) (mainly neural-network-based predictors), disEMBL (also based on neural networks) and Globplot (based on IUP propensity). We find that augmenting features derived from physiochemical properties of amino acids (such as 9-gram encoding scheme and hydrophobicity) and using ensemble methods proved beneficial. The IUP predictor is a viable alternative software tool for identifying IUP regions and proteins. C1 [Yang, Mary Qu] US Dept HHS, NHGRI, Natl Inst Hlth, Bethesda, MD 20852 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Radiat Oncol, Boston, MA 02114 USA. RP Yang, MQ (reprint author), US Dept HHS, NHGRI, Natl Inst Hlth, Bethesda, MD 20852 USA. EM yangma@mail.NIH.gov; jyang@hadron.mgh.Harvard.edu NR 16 TC 2 Z9 2 U1 0 U2 3 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2727-2 PY 2006 BP 3 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BFK64 UT WOS:000242503800001 ER PT B AU Yang, JY Yang, MQ AF Yang, Jack Y. Yang, Mary Qu GP IEEE COMPUTER SOC TI Assessing protein function using a combination of supervised and unsupervised learning SO BIBE 2006: SIXTH IEEE SYMPOSIUM ON BIOINFORMATICS AND BIOENGINEERING, PROCEEDINGS LA English DT Proceedings Paper CT 6th IEEE Syposium on BioInformatics and BioEngineering (BIBE 2006) CY OCT 16-18, 2006 CL Arlington, VA SP IEEE Comp Soc, Biol & Artificial Intelligence Soc, ITRI AB The determination of protein function using experimental techniques is time-consuming and expensive; the use of machine learning techniques to rapidly assess protein function may be useful in streamlining this process. The problem of assigning functional classes to proteins is complicated by the fact that a single protein can participate in several different pathways and thus can have multiple functions. It follows that the instances in the resulting classification problem can carry multiple class labels. We have developed a tree-based classifier that capable of handling multiply-labeled data: we call the resulting tree a Recursive Maximum-Contrast Tree (RMCT). The name derives from the way in which nodes in the tree are split; this is done by selecting the two training instances with maximum contrast (that is, the two training instances with maximum separation according to some distance measure) and using them as seeds in a clustering algorithm to form a partition of the training instances and hence of the feature space. We test our algorithm on protein phylogenetic profiles generated from 60 completely sequenced genomes, and we compare our results to those achieved using existing algorithms such as support vector machines and decision trees. C1 [Yang, Jack Y.] Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Jack Y.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Yang, Mary Qu] Natl Human Genome Res Inst, Natl Inst Hlth, US Dept Hlth & Human Serv, Rockville, MD 20852 USA. RP Yang, JY (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. EM jyang@hadron.mgh.harvard.edu; yangma@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2727-2 PY 2006 BP 35 EP + PG 3 WC Biochemical Research Methods; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BFK64 UT WOS:000242503800005 ER PT J AU Zorov, DB Juhaszova, M Sollott, SJ AF Zorov, D. B. Juhaszova, M. Sollott, S. J. TI Mitochondrial ROS-induced ROS-release: An update and review SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 14th European Bioenergetic Conference CY JUL 22-27, 2006 CL Moscow, RUSSIA ID PERMEABILITY TRANSITION C1 Moscow MV Lomonosov State Univ, Dept Bioenerget, AN Belozersky Inst, Moscow, Russia. NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 6 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2006 SU S BP 52 EP 53 PG 2 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 068UR UT WOS:000239400500018 ER PT J AU Karbowski, M Norris, K Youle, R AF Karbowski, M. Norris, K. Youle, R. TI Dynamins, endophilins and Bcl-2 family members: Involvement in mitochondrial outer membrane dynamics SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 14th European Bioenergetic Conference CY JUL 22-27, 2006 CL Moscow, RUSSIA C1 NINDS, Biochem Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2006 SU S BP 66 EP 66 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 068UR UT WOS:000239400500028 ER PT J AU Zorov, DB Juhaszova, M Sollott, SJ AF Zorov, D. B. Juhaszova, M. Sollott, S. J. TI Targets for cardioprotection and neuroprotection SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 14th European Bioenergetic Conference CY JUL 22-27, 2006 CL Moscow, RUSSIA C1 NIA, Cardioprotect Unit, Cardiovasc Sci Lab, Gerontol Res Ctr,Intramural Res Program,NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2006 SU S BP 117 EP 117 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 068UR UT WOS:000239400500074 ER PT J AU Juhaszova, M Wang, S Zorov, DB Sollott, SJ AF Juhaszova, M. Wang, S. Zorov, D. B. Sollott, S. J. TI Effect of intracellular Ca2+ on MPT induction in excitable cells SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS LA English DT Meeting Abstract CT 14th European Bioenergetic Conference CY JUL 22-27, 2006 CL Moscow, RUSSIA C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Moscow MV Lomonosov State Univ, AN Belozersky Inst, Dept Bioenerget, Moscow, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2728 J9 BBA-BIOENERGETICS JI Biochim. Biophys. Acta-Bioenerg. PY 2006 SU S BP 182 EP 182 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 068UR UT WOS:000239400500119 ER PT J AU Vinson, C Acharya, A Taparowsky, EJ AF Vinson, C Acharya, A Taparowsky, EJ TI Deciphering B-ZIP transcription factor interactions in vitro and in vivo SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE B-ZIP; dimerization specificity; repeat protein; leucine zipper; coiled coil; double mutant thermodynamic cycle ID HELICAL COILED COILS; DNA-BINDING SPECIFICITY; LEUCINE-ZIPPER; FLUORESCENCE COMPLEMENTATION; PROTEIN INTERACTIONS; CRYSTAL-STRUCTURE; LIVING CELLS; AMINO-ACID; DIMERIZATION SPECIFICITY; BASIC REGION AB Over the last 15 years, numerous studies have addressed the structural rules that regulate dimerization stability and dimerization specificity of the leucine zipper, a dimeric parallel coiled-coil domain that can either homodimerize or heterodimerize. Initially, these studies were performed with a limited set of B-ZIP proteins, sequence-specific DNA binding proteins that dimerize using the leucine zipper domain to bind DNA. A global analysis of B-ZIP leucine zipper dimerization properties can be rationalized using a limited number of structural rules [J.R. Newman, A.E. Keating, Comprehensive identification of human bZIP interactions with coiled-coil arrays, Science 300 (2003) 2097-2101]. Today, however, access to the genomic sequences of many different organisms has made possible the annotation of all B-ZIP proteins from several species and has generated a bank of data that can be used to refine, and potentially expand, these rules. Already, a comparative analysis of the B-ZIP proteins from Arabidopsis thaliana and Homo sapiens has revealed that the same amino acids are used in different patterns to generate diverse B-ZIP dimerization patterns [C.D. Deppmann, A. Acharya, V. Rishi, B. Wobbes, S. Smeekens, E.J. Taparowsky, C. Vinson, Dimerization specificity of all 67 B-ZIP motifs in Arabidopsis thaliana: a comparison to Homo sapiens B-ZIP motifs, Nucleic Acids Res. 32 (2004) 3435-3445]. The challenge ahead is to investigate the biological significance of different B-ZIP protein-protein interactions. Gaining insight at this level will rely on ongoing investigations to (a) define the role of target DNA on modulating B-ZIP dimerization partners, (b) characterize the B-ZIP transcriptome in various cells and tissues through mRNA microarray analysis, (c) identify the genomic localization of B-ZIP binding at a genomic level using the chromatin immunoprecipitation assay, and (d) develop more sophisticated imaging technologies to visualize dimer dynamics in single cells and whole organisms. Studies of B-ZIP family leucine zipper dimerization and the regulatory mechanisms that control their biological activities could serve as a paradigm for deciphering the biophysical and biological parameters governing other well-characterized protein-protein interaction motifs. This review will focus on the dimerization specificity of coiled-coil proteins, particularly the human B-ZIP transcription family that consists of 53 proteins that use the leucine zipper coiled-coil as a dimerization motif. (c) 2006 Elsevier B.V. All rights reserved. C1 NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. RP Vinson, C (reprint author), NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. EM vinsonc@dc37a.nci.nih.gov FU NCI NIH HHS [CA-78264] NR 60 TC 102 Z9 107 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD JAN-FEB PY 2006 VL 1759 IS 1-2 BP 4 EP 12 DI 10.1016/j.bbaexp.2005.12.005 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 046FY UT WOS:000237798000001 PM 16580748 ER PT J AU Xu, GH Sztalryd, C Londos, C AF Xu, GH Sztalryd, C Londos, C TI Degradation of perilipin is mediated through ubiquitination-proteasome pathway SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE perilipin; ubiquitination; proteasome; degradation; lipid droplet; fatty acid; triacylglycerol; adipose differentiation-related protein ID HORMONE-SENSITIVE LIPASE; LIPID STORAGE DROPLET; DIFFERENTIATION-RELATED PROTEIN; ACTIVATED RECEPTOR-GAMMA; POSTTRANSLATIONAL REGULATION; STIMULATED LIPOLYSIS; ADIPOCYTE LIPOLYSIS; TRANSLOCATION; EXPRESSION; APOLIPOPROTEIN AB Perilipin protein coats the surface of intracellular lipid droplets and plays fundamental roles in lipid droplet formation and triacylglycerol hydrolysis. Perilipin is transcriptionally regulated through peroxisome proliferator-activated receptor and post-translationally stabilized by stored intracellular neutral lipids. In this study, we show that perilipin protein accumulates in transfected Chinese hamster ovary cells cultured in the presence of fatty acids but in turn is destabilized when lipid precursors for triacylglycerol synthesis are removed from culture serum. Adding fatty acids in the culture medium prevents the degradation of perilipin. Moreover, specific proteasome inhibitors, MG132, lactacystin, and ALLN, block the degradation, whereas inhibitors of other proteases are ineffective. Pulse-chase experiments confirm that perilipin is degraded through proteasome, a process that is inhibited by MG132 or ALLN and blunted by the addition of oleic acid. We have detected the coimmunoprecipitation of perilipin and ubiquitin, thus confirming that perilipin is conjugated to poly-ubiquitin and targeted for proteasomal degradation. Treatment with MG132 increases the expression of perilipin associated with lipid droplets as well as modestly throughout the cytosol. We conclude that the degradation of perilipin is mediated through all ubiquitination-proteasome pathway, which suggests another mode for the post-translational regulation of perilipin. Published by Elsevier B.V. C1 Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Beijing 100083, Peoples R China. Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100083, Peoples R China. NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA. RP Xu, GH (reprint author), Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, 38 Xueyuan Rd, Beijing 100083, Peoples R China. EM xug@bjmu.edu.cn NR 42 TC 53 Z9 56 U1 0 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD JAN PY 2006 VL 1761 IS 1 BP 83 EP 90 DI 10.1016/j.bbalip.2005.12.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 027SI UT WOS:000236435300010 PM 16448845 ER PT J AU Tapia, JA Jensen, RT Garcia-Marin, LJ AF Tapia, JA Jensen, RT Garcia-Marin, LJ TI Rottlerin inhibits stimulated enzymatic secretion and several intracellular signaling transduction pathways in pancreatic acinar cells by a non-PKC-delta-dependent mechanism SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE cholecystokinin; protein kinase C; pancreatic acini; exocrine secretion; PKC inhibitors; rottlerin ID PROTEIN-KINASE-C; TYROSINE PHOSPHORYLATION; INDUCED APOPTOSIS; AMYLASE SECRETION; PHORBOL ESTER; CHOLECYSTOKININ; ACTIVATION; RECEPTORS; GROWTH; CCK AB Protein kinase C-delta (PKC-delta) becomes activated in pancreatic acini in response to cholecystokinin (CCK) and plays a pivotal role in the exocrine pancreatic secretion. Rottlerin, a polyphenolic compound, has been widely used as a potent and specific PKC-delta inhibitor. However, some recent studies showed that rottlerin was not effective in inhibiting PKC delta activity in vitro and that may display unspecific effects. The aims of this work were to investigate the specificity of rottlerin as an inhibitor of PKC-delta activity in intact cells and to elucidate the biochemical causes of its unspecificity. Preincubation of pancreatic acini with rottlerin (6 mu M) inhibited CCK-stimulated translocation, tyrosine phosphorylation (TyrP) and activation of PKC-delta in pancreatic acini in a time-dependent manner. Rottlerin inhibited amylase secretion stimulated by both PKC-dependent pathways (CCK, bombesin, carbachol, TPA) and also by PKC-independent pathways (secretin, VIP, cAMP analogue). CCK-stimulation of MAPK activation and p125(FAK) TyrP which are mediated by PKC-dependent and -independent pathways were also inhibited by rottlerin. Moreover, rottlerin rapidly depleted ATP content in pancreatic acini in a similar way as the mitochondrial uncouplers CCCP and FCCP. All studied inhibitory effects of rottlerin in pancreatic acini were mimicked by FCCP (agonists-stimulated amylase secretion, p125(FAK) TyrP, MAPK activation and PKC-delta TyrP and translocation). Finally, rottlerin as well as FCCP display a potent inhibitory effect on the activation of other PKC isoforms present in pancreatic acini. Our results suggest that rottlerin effects in pancreatic acini are not due to a specific PKC-delta blockade, but likely due to its negative effect on acini energy resulting in ATP depletion. Therefore, to study the role of PKC-delta in cellular processes using rottlerin it is essential to keep in mind that may deplete ATP levels and inhibit different PKC isoforms. Our results give reasons for a more careful choice of rottlerin for PKC-delta investigation. (c) 2005 Elsevier B.V All rights reserved. C1 Univ Extremadura, Dept Fisiol, Caceres 10071, Spain. NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Garcia-Marin, LJ (reprint author), Univ Extremadura, Dept Fisiol, Ave Univ S-N, Caceres 10071, Spain. EM ljgarcia@unex.es RI Garcia-Marin, Luis /L-4680-2014; Tapia, Jose/C-5181-2008 OI Garcia-Marin, Luis /0000-0002-1795-7381; Tapia, Jose/0000-0002-3614-6867 NR 85 TC 40 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JAN PY 2006 VL 1763 IS 1 BP 25 EP 38 DI 10.1016/j.bbamcr.2005.10.007 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 019QB UT WOS:000235850700004 PM 16364465 ER PT J AU Nakamura, Y Miyoshi, N AF Nakamura, Yoshimasa Miyoshi, Noriyuki TI Cell death induction by isothiocyanates and their underlying molecular mechanisms SO BIOFACTORS LA English DT Article DE benzyl isothiocyanate; apoptosis; cell cycle arrest; necrosis; MAP kinase ID CANCER-PREVENTIVE ISOTHIOCYANATES; URINARY-BLADDER CARCINOGENESIS; HUMAN GLUTATHIONE TRANSFERASES; N-TERMINAL KINASE; BENZYL ISOTHIOCYANATE; OXIDATIVE STRESS; PHENETHYL ISOTHIOCYANATE; INDUCED APOPTOSIS; CYCLE ARREST; ANTICARCINOGENIC ISOTHIOCYANATES AB An important and promising group of compounds that have a chemopreventive property are organosulfur compounds, such as isothiocyanates (ITCs). In recent years, it has been shown that ITCs induce apoptosis in various cancer cell lines and experimental rodents. During the course of apoptosis induction by ITC, multiple signal-transduction pathways and apoptosis intermediates are modulated. We have also clarified the molecular mechanism underlying the relationship between cell cycle arrest and apoptosis induced by benzyl isothiocyanate ( BITC), a major ITC compound isolated from papaya. The exposure of cells to BITC resulted in the inhibition of the G(2)/M progression that coincided with not only the up-regulated expression of the G(2)/M cell cycle arrest-regulating genes but also the apoptosis induction. The experiment using the phase-specific synchronized cells demonstrated that the G(2)/M phase-arrested cells are more sensitive to undergoing apoptotic stimulation by BITC than the cells in other phases. We identified the phosphorylated Bcl-2 as a key molecule linking the p38 MAPK-dependent cell cycle arrest with the JNK activation by BITC. We also found that BITC induced the cytotoxic effect more preferentially in the proliferating normal human colon epithelial cells than in the quiescent cells. Conversely, treatment with an excessive concentration of BITC resulted in necrotic cell death without DNA ladder formation. This review addresses the biological impact of cell death induction by BITC as well as other ITCs and the involved signal transduction pathways. C1 Okayama Univ, Fac Agr, Grad Sch Nat Sci & Technol, Div Biosci,Dept Biofunct Chem, Okayama 7008530, Japan. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Nakamura, Y (reprint author), Okayama Univ, Fac Agr, Grad Sch Nat Sci & Technol, Div Biosci,Dept Biofunct Chem, Okayama 7008530, Japan. EM yossan@cc.okayama-u.ac.jp RI Miyoshi, Noriyuki/F-4554-2010 NR 56 TC 25 Z9 26 U1 1 U2 4 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 2006 VL 26 IS 2 BP 123 EP 134 PG 12 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 057FA UT WOS:000238580500003 PM 16823098 ER PT J AU Amikam, D Galperin, MY AF Amikam, D Galperin, MY TI PilZ domain is part of the bacterial c-di-GMP binding protein SO BIOINFORMATICS LA English DT Article ID CELLULOSE SYNTHASE GENE; CYCLIC DIGUANYLIC ACID; BIOFILM FORMATION; PSEUDOMONAS-AERUGINOSA; ACETOBACTER-XYLINUM; TWITCHING MOTILITY; YERSINIA-PESTIS; EAL DOMAINS; ALG44 GENES; PHOSPHODIESTERASE AB Recent studies identified c-di-GMP as a universal bacterial secondary messenger regulating biofilm formation, motility, production of extracellular polysaccharide and multicellular behavior in diverse bacteria. However, except for cellulose synthase, no protein has been shown to bind c-di-GMP and the targets for c-di-GMP action remain unknown. Here we report identification of the PilZ ('pills') domain (Pfam domain PF07238) in the sequences of bacterial cellulose synthases, alginate biosynthesis protein Alg44, proteins of enterobacterial YcgR and firmicute YpfA families, and other proteins encoded in bacterial genomes and present evidence indicating that this domain is ( part of) the long-sought c-di-GMP-binding protein. Association of the PilZ domain with a variety of other domains, including likely components of bacterial multidrug secretion system, could provide clues to multiple functions of the c-di-GMP in bacterial pathogenesis and cell development. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Tel Hai Acad Coll, Dept Biotechnol & Environm Sci, Tal Hai, Israel. Hadassah Univ, Ctr Med, Sharett Inst Oncol, Jerusalem, Israel. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 37 TC 245 Z9 261 U1 2 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2006 VL 22 IS 1 BP 3 EP 6 DI 10.1093/bioinformatics/bti739 PG 4 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 000AO UT WOS:000234433500004 PM 16249258 ER PT J AU Huang, WC Umbach, DM Li, LP AF Huang, WC Umbach, DM Li, LP TI Accurate anchoring alignment of divergent sequences SO BIOINFORMATICS LA English DT Article ID MULTIPLE ALIGNMENT; GENOMIC DNA; DATABASE; SEARCH; ALGORITHM; PROGRAMS; PROTEIN; BLAST; TOOL; IDENTIFICATION AB Motivation: Obtaining high quality alignments of divergent homologous sequences for cross-species sequence comparison remains a challenge. Results: We propose a novel pairwise sequence alignment algorithm, ACANA (ACcurate ANchoring Alignment), for aligning biological sequences at both local and global levels. Like many fast heuristic methods, ACANA uses an anchoring strategy. However, unlike others, ACANA uses a Smith-Waterman-like dynamic programming algorithm to recursively identify near-optimal regions as anchors for a global alignment. Performance evaluations using a simulated benchmark dataset and real promoter sequences suggest that ACANA is accurate and consistent, especially for divergent sequences. Specifically, we use a simulated benchmark dataset to show that ACANA has the highest sensitivity to align constrained functional sites compared to BLASTZ, CHAOS and DIALIGN for local alignment and compared to AVID, ClustalW, DIALIGN and LAGAN for global alignment. Applied to 6007 pairs of human-mouse orthologous promoter sequences, ACANA identified the largest number of conserved regions (defined as over 70% identity over 100 bp) compared to AVID, ClustalW, DIALIGN and LAGAN. In addition, the average length of conserved region identified by ACANA was the longest. Thus, we suggest that ACANA is a useful tool for identifying functional elements in cross-species sequence analysis, such as predicting transcription factor binding sites in non-coding DNA. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27606 USA. Duke Univ, Ctr Med, Inst Genome Sci & Policy, Durham, NC 27708 USA. RP Li, LP (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM li3@niehs.nih.gov FU Intramural NIH HHS NR 36 TC 20 Z9 22 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD JAN 1 PY 2006 VL 22 IS 1 BP 29 EP 34 DI 10.1093/bioinformatics/bti772 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 000AO UT WOS:000234433500008 PM 16301203 ER PT J AU Li, H Zhan, M AF Li, H Zhan, M TI Systematic intervention of transcription for identifying network response to disease and cellular phenotypes SO BIOINFORMATICS LA English DT Article ID PROBABILISTIC BOOLEAN NETWORKS; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; CAENORHABDITIS-ELEGANS; REGULATORY NETWORKS; EXPRESSION DATA; GENE NETWORKS; DAF-16; DIFFERENTIATION; PATHWAYS AB Motivation: A major challenge in post-genomic research has been to understand how physiological and pathological phenotypes arise from the networks of expressed genes. Here, we addressed this issue by developing an algorithm to mimic the behavior of regulatory networks in silico and to identify the dynamic response to disease and changing cellular conditions. Results: With regulatory pathway and gene expression data as input, the algorithm provides quantitative assessments of a wide range of responses, including susceptibility to disease, potential usefulness of a given drug, or consequences to such external stimuli as pharmacological interventions or caloric restriction. The algorithm is particularly amenable to the analysis of systems that are difficult to recapitulate in vitro, yet they may have important clinical value. The hypotheses derived from the algorithm were biologically relevant and were successfully validated via independent experiments, as illustrated here in the analysis of the leukemia-associated BCR-ABL pathway and the insulin/IGF pathway related to longevity. The algorithm correctly identified the leukemia drug target and genes important for longevity, and also provided new insights into our understanding of these two processes. C1 NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. RP Zhan, M (reprint author), NIA, Bioinformat Unit, Branch Res Resources, NIH, Baltimore, MD 21224 USA. EM zhanmi@mail.nih.gov NR 35 TC 20 Z9 22 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 JAN 1 PY 2006 VL 22 IS 1 BP 96 EP 102 DI 10.1093/bioinformatics/bti752 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 000AO UT WOS:000234433500016 PM 16278241 ER PT B AU Bazykin, G Ogurtsov, A Kondrashov, A AF Bazykin, G Ogurtsov, A Kondrashov, A BE Kolchanov, N Hoffestaedt, R Milanesi, L TI Change in CpG context is a leading cause of correlation between the rates of non-synonymous and synonymous substitutions in rodents SO BIOINFORMATICS OF GENOME REGULATION AND STRUCTURE II LA English DT Proceedings Paper CT 4th International Conference on Bioinformatics of Genome Regulation and Structure (BGRS 2004) CY JUL 25-30, 2004 CL Novosibirsk, RUSSIA SP Russian Acad Sci, Siberian Branch, Inst Cytol & Genet, Lab Theoret Genet DE evolution; point substitution rate; mutation bias; CpG deamination; dinucleotides AB Correlation between the rates of synonymous (silent) and non-synonymous (amino acid-changing) nucleotide substitutions in genes is a widespread and yet unexplained genome-level phenomenon, which is in disagreement with the neutral theory of molecular evolution (Kimura, 1983). Comparison of 7732 orthologous genes of mouse and rat confirms the previously observed correlation between the rates of substitutions in non-synonymous and synonymous nucleotide sites. In rodents, this correlation is primarily caused by tandem substitutions and, in particular, by CpG mutation bias leading to doublet nucleotide substitutions. The nature of correlation between the rates of synonymous and non-synonymous substitutions in seven pairs of prokaryotic genomes is unclear. C1 Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08540 USA. EM gbazykin@princeton.edu RI Bazykin, Georgii/E-4601-2012 OI Bazykin, Georgii/0000-0003-2334-2751 FU Burroughs Wellcome Fund Training Program in Biological Dynamics [1001781]; Pew Charitable Trusts Program in Biocomplexity [2000-002558] FX G,B. gratefully acknowledges support from the Burroughs Wellcome Fund Training Program in Biological Dynamics (award No. 1001781) and the Pew Charitable Trusts Program in Biocomplexity (award No. 2000-002558). NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 0-387-29450-3 PY 2006 BP 147 EP 151 DI 10.1007/0-387-29455-4_16 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Genetics & Heredity; Mathematics, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Genetics & Heredity; Mathematics GA BDN75 UT WOS:000234508700017 ER PT S AU Keselman, A Massengale, L Ngo, L Browne, A Zeng, Q AF Keselman, Alla Massengale, Lisa Ngo, Long Browne, Allen Zeng, Qing BE Maglaveras, N Chouvarda, I Koutkias, V Brause, R TI The effect of user factors on consumer familiarity with health terms: Using gender as a proxy for background knowledge about gender-specific illnesses SO BIOLOGICAL AND MEDICAL DATA ANALYSIS, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 7th International Symposium on Biological and Medical Data Analysis CY DEC 07-08, 2006 CL Thessaloniki, GREECE DE consumer health informatics; readability formulas; consumer health vocabularies ID INFORMATION; LITERACY; QUALITY; SPANISH AB An algorithm estimating vocabulary complexity of a consumer health text can help improve readability of consumer health materials. We had previously developed and validated an algorithm predicting lay familiarity with health terms on the basis of the terms' frequency in consumer health texts and experimental data. Present study is part of the program studying the influence of reader factors on familiarity with health terms and concepts. Using gender as a proxy for background knowledge, the study evaluates male and female participants' familiarity with terms and concepts pertaining to three types of health topics: male-specific, female-specific and gender-neutral. Of the terms / concepts of equal predicted difficulty, males were more familiar with those pertaining to neutral and male-specific topics (the effect was especially pronounced for "difficult" terms); no topic effect was observed for females. The implications for tailoring health readability formulas to various target populations are discussed. C1 [Keselman, Alla; Massengale, Lisa; Browne, Allen] NIH, Natl Lib Med, LHNCBC, DHHS, Bldg 10, Bethesda, MD 20892 USA. [Keselman, Alla] Aquilent Inc, Laurel, MD USA. [Ngo, Long] Harvard Med Sch, Brigham & Womens Hosp, DSG, Boston, MA USA. [Zeng, Qing] Harvard Med Sch, Beth Israel Deaconess Med Ctr, DSG, Boston, MA USA. RP Keselman, A (reprint author), NIH, Natl Lib Med, LHNCBC, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM keselmana@mail.nih.gov FU Intramural Research Program; Association Fellowship of the US National Library of Medicine; US National Institutes of Health; NIH [R01 LM007222-05] FX This research was supported by the Intramural Research Program and the Association Fellowship of the US National Library of Medicine, US National Institutes of Health (AK, LM, AB) and NIH grant R01 LM007222-05 (LN, QZ). The authors thank Tony Tse and Guy Divita for their comments on the earlier versions of this manuscript. NR 14 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-68063-5 J9 LECT NOTES COMPUT SC PY 2006 VL 4345 BP 472 EP + PG 3 WC Biology; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Computer Science; Research & Experimental Medicine GA BFT86 UT WOS:000244560100043 ER PT J AU Stojilkovic, SS AF Stojilkovic, Stanko S. TI Pituitary cell type-specific electrical activity, calcium signaling and secretion SO BIOLOGICAL RESEARCH LA English DT Review DE somatotrophs; lactotrophs; gonadotrophs; GH(3) cells; SK channels; BK channels; action potentials; exocytosis ID RAT ANTERIOR-PITUITARY; GONADOTROPIN-RELEASING-HORMONE; PROTEIN-KINASE-C; ACTIVATED POTASSIUM CHANNELS; P2X(2) RECEPTOR-CHANNEL; MOTOR-NERVE ENDINGS; GATED CA2+ INFLUX; ENDOPLASMIC-RETICULUM; ACTION-POTENTIALS; (I) OSCILLATIONS AB All secretory anterior pituitary cells exhibit spontaneous and extracellular calcium-dependent electrical activity, but differ with respect to the patterns of firing and associated calcium signaling and hormone secretion. Thus, somatotrophs and lactotrophs fire plateau-bursting action potentials spontaneously and without coupling to calcium release from intracellular stores, which generate calcium signals of sufficient amplitude to keep steady hormone release. In these cells, both spontaneous electrical activity and basal hormone secretion can be further amplified by activation of G(q/11) and G(s)-coupled receptors and inhibited by G(i/o/z)-coupled receptors. In contrast, gonadotrophs fire single, higb-amplitude spikes with limited ability to promote calcium influx and exocytosis, whereas activated G(q/11)-coupled receptors in these cells transform single-action potential spiking into the plateau-bursting type of electrical activity and trigger periodic high-amplitude calcium signals and exocytosis of prestored secretory vesicles. Here, we review biochemical and biophysical aspects of spontaneous and receptor-controlled electrical activity, calcium signaling, and hormone secretion in pituitary cells. C1 NICHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov FU Intramural NIH HHS NR 107 TC 28 Z9 28 U1 0 U2 1 PU SOCIEDAD BIOLGIA CHILE PI SANTIAGO PA CASILLA 16164, SANTIAGO 9, CHILE SN 0716-9760 J9 BIOL RES JI Biol. Res. PY 2006 VL 39 IS 3 BP 403 EP 423 PG 21 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 094FV UT WOS:000241226100004 PM 17106574 ER PT J AU Caviedes, P Caviedes, R Rapoport, SI AF Caviedes, Pablo Caviedes, Raul Rapoport, Stanley I. TI Altered calcium currents in cultured sensory neurons of normal and trisomy 16 mouse fetuses, an animal model for human trisomy 21 (Down Syndrome) SO BIOLOGICAL RESEARCH LA English DT Article DE trisomy 16; dorsal root ganglion; calcium current; tissue culture; patch clamp; Down syndrome ID DORSAL-ROOT GANGLION; ELECTRICAL MEMBRANE-PROPERTIES; NERVE GROWTH-FACTOR; 16 FETAL MICE; CHOLINERGIC FUNCTION; ELECTROPHYSIOLOGICAL PROPERTIES; NEUROBIOLOGICAL CONSEQUENCES; HIPPOCAMPAL-NEURONS; SODIUM CURRENTS; PATCH-CLAMP AB Down syndrome is determined by the presence of an extra copy of autosome 21 and is expressed by multiple abnormalities, with mental retardation being the most striking feature. The condition results in altered electrical membrane properties of fetal dorsal root ganglia (DRG) neurons, as in the trisomy 16 fetal mouse, an animal model of the human condition. Cultured trisomic DRG neurons from human and mouse fetuses present faster rates of depolarization and repolarization in the action potential compared to normal controls and a shorter spike duration. Also, trisomy 16 brain and spinal cord tissue exhibit reduced acetylcholine secretion. Therefore, we decided to study Ca2+ currents in cultured DRG neurons from trisomy 16 and age-matched control mice, using the whole-cell patch-clamp technique. Trisomic neurons exhibited a 62% reduction in Ca2+ current amplitude and reduced voltage dependence of current activation at -30 and -20 mV levels. Also, trisomic neurons showed slower activation kinetics for Ca2+ currents, with up to 80% increase in time constant values. Kinetics of the inactivation phase were similar in both conditions. The results indicate that murine trisomy 16 alter Ca2+ currents, which may contribute to impaired cell function, including neurotransmitter release. These abnormalities also may alter neural development. C1 Univ Chile, Fac Med, Programa Farmacol Mol & Clin, ICBM, Santiago 7, Chile. NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. RP Caviedes, P (reprint author), Univ Chile, Fac Med, Programa Farmacol Mol & Clin, ICBM, Independencia 1027, Santiago 7, Chile. EM pcaviede@med.uchile.cl NR 37 TC 8 Z9 8 U1 0 U2 1 PU SOCIEDAD BIOLGIA CHILE PI SANTIAGO PA CASILLA 16164, SANTIAGO 9, CHILE SN 0716-9760 J9 BIOL RES JI Biol. Res. PY 2006 VL 39 IS 3 BP 471 EP 481 PG 11 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 094FV UT WOS:000241226100009 PM 17106579 ER PT J AU Wilson, DE Schmitt, JM AF Wilson, Deborah E. Schmitt, James M. BE Fleming, DO Hunt, DL TI Occupational Medicine in a Biomedical Research Setting SO BIOLOGICAL SAFETY: PRINCIPLES AND PRACTICES, 4TH EDITION LA English DT Article; Book Chapter ID LABORATORY EXPOSURES; BIOTERRORISM; MANAGEMENT; AGENTS C1 [Wilson, Deborah E.; Schmitt, James M.] NIH, Div Occupat Hlth & Safety, Bethesda, MD 20892 USA. RP Wilson, DE (reprint author), NIH, Div Occupat Hlth & Safety, Bldg 13,Rm 3K04,13 South Dr, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-339-0 PY 2006 BP 437 EP 444 PG 8 WC Medical Laboratory Technology; Microbiology SC Medical Laboratory Technology; Microbiology GA BOY56 UT WOS:000278066800025 ER PT J AU Hawley, RJ Duley, TD AF Hawley, Robert J. Duley, Theresa D. BE Fleming, DO Hunt, DL TI Biosafety and Biosecurity: Regulatory Impact SO BIOLOGICAL SAFETY: PRINCIPLES AND PRACTICES, 4TH EDITION LA English DT Article; Book Chapter ID INHALATIONAL ANTHRAX; BIOLOGICAL WARFARE; BIOTERRORISM C1 [Hawley, Robert J.] Midwest Res Inst, Frederick, MD 21701 USA. [Duley, Theresa D.] NCI, SAIC Frederick, Ft Detrick, MD 21702 USA. RP Hawley, RJ (reprint author), Midwest Res Inst, 365 W Patrick St,Suite 223, Frederick, MD 21701 USA. NR 40 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-339-0 PY 2006 BP 587 EP 596 PG 10 WC Medical Laboratory Technology; Microbiology SC Medical Laboratory Technology; Microbiology GA BOY56 UT WOS:000278066800034 ER PT J AU Yamashita, K Horwitz, ME Kwatemaa, A Nomicos, E Castro, K Sokolic, R Foster, SF Garofalo, M Choi, U Ryherd, M Brown, MR Leitman, SF Wayne, AS Fowler, DH Bishop, MR Childs, RW Barrett, AJ Pavletic, SZ Malech, HL AF Yamashita, K Horwitz, ME Kwatemaa, A Nomicos, E Castro, K Sokolic, R Foster, SF Garofalo, M Choi, U Ryherd, M Brown, MR Leitman, SF Wayne, AS Fowler, DH Bishop, MR Childs, RW Barrett, AJ Pavletic, SZ Malech, HL TI Unique abnormalities of CD4(+) and CD8(+) central memory cells associated with chronic graft-versus-host disease improve after extracorporeal photopheresis SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE chronic GVHD; central memory T cell; extracorporeal photopheresis; bone marrow transplantation; alloimmune ID PERIPHERAL-BLOOD; T-CELLS; TRANSPLANTATION; EFFECTOR; PHOTOCHEMOTHERAPY; SUBSETS; LYMPHOCYTE; DISTINCT; THERAPY AB Chronic graft-versus-host disease (cGVHD) remains a problematic complication of allogeneic hematopoietic stem cell transplantation. Laboratory parameters correlated with cGVHD have not been fully defined, although changes in CD4/CD8 ratios occur and a decrease in CD4(+) central memory T cells has been noted. Extracorporeal photopheresis (ECP) is an effective therapy for steroid-refractory cGVHD. We have noted changes in lymphocyte subsets after ECP. CD4(+) and CD8(+) T-cell central and effector memory populations were enumerated by flow cytometry in a cohort of 37 patients postallogeneic transplantation with symptomatic cGVHD. Of the patients with symptomatic cGVHD, 7 were treated with ECP over 6 months and prospectively assessed for changes in lymphocyte subsets. There was a highly significant correlation of an increase in CD8(+) central memory cells and a concomitant decrease in CD4(+) central memory cells in patients with symptomatic cGVHD. These changes were not detected in patients without cGVHD posttransplantation. In all, 7 patients with cGVHD followed up prospectively during ECP treatment showed a statistically significant normalization of the pattern of CD4(+) and a trend toward normalization of CD8(+) central memory T cells coincident with improvement of cGVHD. These data indicate a high correlation between disturbances in the balance of central and effector memory populations and cGVHD suggesting use in following up responses to therapy. The normalization of central and effector memory populations in response to ECP coincident with clinical improvement of cGVHD support a correlation between these laboratory parameters and cGVHD. Further studies are needed to demonstrate whether laboratory measurements of the magnitude of changes in central and effector memory populations are useful prognostically or can be used to guide response to therapy. The contrasting change in central memory cells (CD8(+) increased versus CD4(+) decreased) in cGVHD provide support for recent reports suggesting unique differences in the differentiation pathways for CD8(+) versus CD4(+) T cells. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Bone Marrow Transplant Program, Durham, NC USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,MSC 1456,Bldg 10,Room 5-3750, Bethesda, MD 20892 USA. EM hmalech@nih.gov RI Sokolic, Robert/I-6072-2012; OI Malech, Harry/0000-0001-5874-5775 NR 23 TC 15 Z9 15 U1 0 U2 0 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 JAN PY 2006 VL 12 IS 1 SU 2 BP 22 EP 30 DI 10.1016/j.bbmt.2005.11.004 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 010FD UT WOS:000235171400004 PM 16399598 ER PT J AU Shulman, HM Kleiner, D Lee, SJ Morton, T Pavletic, SZ Farmer, E Moresi, JM Greenson, J Janin, A Martin, PJ McDonald, G Flowers, MED Turner, M Atkinson, J Lefkowitch, J Washington, MK Prieto, VG Kim, SK Argenyi, Z Diwan, AH Rashid, A Hiatt, K Couriel, D Schultz, K Hymes, S Vogelsang, GB AF Shulman, HM Kleiner, D Lee, SJ Morton, T Pavletic, SZ Farmer, E Moresi, JM Greenson, J Janin, A Martin, PJ McDonald, G Flowers, MED Turner, M Atkinson, J Lefkowitch, J Washington, MK Prieto, VG Kim, SK Argenyi, Z Diwan, AH Rashid, A Hiatt, K Couriel, D Schultz, K Hymes, S Vogelsang, GB TI Histopathologic diagnosis of chronic graft-versus-host disease: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-Versus-Host Disease: II. Pathology Working Group report SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE chronic graft-versus-host disease; allogeneic hematopoietic cell transplantation; consensus diagnosis; pathology ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; HEPATITIS-C; ALLOGRAFT-REJECTION; LIVER; EYE; RECIPIENTS; INFECTION; CIRRHOSIS; MUCOSAL AB This consensus document provides an update for pathologists and clinicians about the interpretation of biopsy results and use of this information in the management of hematopoietic cell transplantation patients. Optimal sampling and tissue preparation are discussed. Minimal criteria for the diagnosis of graft-versus-host disease (GVHD) are proposed, together with specific requirements for the diagnosis of chronic GVHD. Four final diagnostic categories (no GVHD, possible GVHD, consistent with GVHD, and definite GVHD) reflect the integration of histopathology with clinical, laboratory, and radiographic information. Finally, the Working Group developed a set of worksheets to facilitate communication of clinical information to the interpreting pathologist and to aid in clinicopathologic correlation studies. Forms are available at http://www.asbmt.org/cGvHD_Guidelines. The recommendations of the Working Group represent a consensus opinion supplemented by evaluation of available peer-reviewed literature. Consensus recommendations and suggusted data-capture forms should be validated in prospective clinicopathologic studies. (c) 2006 American Society for Blood and Marrow Transplantation. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, Seattle, WA 98109 USA. Univ Washington, Seattle Canc Care Alliance, Dept Pathol, Seattle, WA 98109 USA. NCI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Washington, Sch Dent, Seattle, WA 98195 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Michigan Hosp, Ann Arbor, MI 48109 USA. Hosp St Louis, Paris, France. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Columbia Univ, New York, NY USA. Vanderbilt Univ, Nashville, TN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Washington, Med Ctr, Seattle, WA 98195 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ British Columbia, British Columbia Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. RP Shulman, HM (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Sch Med, 825 Eastlake Ave E, Seattle, WA 98109 USA. EM hshulman@seattlecca.org OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 49 TC 199 Z9 214 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 JAN PY 2006 VL 12 IS 1 BP 31 EP 47 DI 10.1016/j.bbmt.2005.10.023 PG 17 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 009DW UT WOS:000235092500002 PM 16399567 ER PT J AU Crooks, GM Weinberg, K Mackall, C AF Crooks, GM Weinberg, K Mackall, C TI Immune reconstitution: From stem cells to lymphocytes SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID BONE-MARROW-TRANSPLANTATION; COMMON LYMPHOID PROGENITORS; THYMIC FUNCTION; IDENTIFICATION; EXPANSION; AGE C1 Childrens Hosp Los Angeles, Div Immunol Res, Los Angeles, CA 90027 USA. Childrens Hosp Los Angeles, Div Bone Marrow Transplant, Los Angeles, CA 90027 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Weinberg, K (reprint author), Lucile Packard Childrens Hosp, Div Pediat Stem Cell Transplantat, 1000 Welch Rd, Stanford, CA 94305 USA. EM kweinberg@chla.usc.edu FU NHLBI NIH HHS [HL54729, HL77912, HL70005, HL73104]; NIAID NIH HHS [AI50765] NR 13 TC 25 Z9 25 U1 0 U2 0 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 JAN PY 2006 VL 12 IS 1 SU 1 BP 42 EP 46 DI 10.1016/j.bbmt.2005.10.015 PG 5 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 010FB UT WOS:000235171200008 PM 16399583 ER PT J AU Dave, S AF Dave, S TI Gene expression profiling and outcome prediction in non-Hodgkin lymphoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID B-CELL LYMPHOMA; FOLLICULAR LYMPHOMA; SURVIVAL AB Gene expression profiling with microarrays; has provided new insights into the molecular biology of tumors can that underlie differences in responses to therapy and patient outcomes. In diffuse large B-cell lymphoma, gene expression profiling has revealed at least 2 diseases that are strikingly different in their response to chemotherapy and the inhibition of critical oncogenic pathways. In follicular lymphoma, gene expression profiling showed that the host immune response to tumors is an important determinant of outcome and can strongly predict survival at the time of diagnosis. The application of immunologic therapies that modify the host immune response could have a major effect on survival in patients with follicular lymphoma. Thus, the application of gene expression profiling in non-Hodgkin lymphoma provides important prognostic information at the time of diagnosis and can be translated into therapeutic options that improve patient outcomes. (C) 2006 American Society for Blood and Marrow Transplantation. C1 NCI, Bethesda, MD 20892 USA. RP Dave, S (reprint author), NCI, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM daves@mail.nih.gov NR 6 TC 3 Z9 3 U1 0 U2 0 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 JAN PY 2006 VL 12 IS 1 SU 1 BP 50 EP 52 DI 10.1016/j.bbmt.2005.10.017 PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 010FB UT WOS:000235171200010 PM 16399585 ER PT J AU Ershler, WB Artz, AS Keller, ET AF Ershler, WB Artz, AS Keller, ET TI Issues of aging and geriatric medicine: Relevance to cancer treatment and hematopoietic reconstitution SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE aging; hematopoietic cell transplantation; cancer treatment; hematopoietic reconstitution ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOID-LEUKEMIA; MYELODYSPLASTIC SYNDROME; PROGNOSTIC-FACTORS; COMORBIDITY INDEX; MAILLARD REACTION; OXIDATIVE DAMAGE; ELDERLY-PATIENTS; OLDER PATIENTS AB Aging is not a disease. Nevertheless, diseases, including most malignancies, increase in frequency with advancing age. Although there are many reasons why this might be the case, perhaps most important is that it takes time to progress through the many steps of carcinogenesis and growth to reach a threshold for diagnosis. Other factors, including accumulated nonlethal damage to DNA (eg, by free radicals), increased proinflammatory factors, and age-associated declines in DNA repair and immune competence, are to some degree important. The median age for all cancer is approximately 70 years and will become even older over the next several decades. Myelodysplasia and hematologic malignancies, including lymphoma, myeloma, and leukemia, can be effectively treated in older age groups, but advanced age presents a number of additional challenges. With appropriate pretreatment assessment of organ reserve, physical performance, and cognitive function, individualized (tailored) therapy may ultimately prove to offer the greatest chance for successful outcomes. Such assessment would also identify those who are likely to benefit from more aggressive treatments, including bone marrow or stem cell transplantation. (C) 2006 American Society for Blood and Marrow Transplantation. C1 Inst Adv Studies Aging, Washington, DC 20007 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Chicago, Dept Med, Div Hematol Oncol, Chicago, IL 60637 USA. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. RP Ershler, WB (reprint author), Inst Adv Studies Aging, 1700 Wisconsin Ave NW, Washington, DC 20007 USA. EM wershler@iasia.org RI Keller, Evan/M-1446-2016 OI Keller, Evan/0000-0002-7592-7535 NR 62 TC 4 Z9 4 U1 1 U2 4 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 JAN PY 2006 VL 12 IS 1 SU 1 BP 100 EP 106 DI 10.1016/j.bbmt.2005.10.007 PG 7 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 010FB UT WOS:000235171200018 PM 16399593 ER PT J AU Jefferson, W Newbold, R Padilla-Banks, E Pepling, M AF Jefferson, W Newbold, R Padilla-Banks, E Pepling, M TI Neonatal genistein treatment alters ovarian differentiation in the mouse: Inhibition of oocyte nest breakdown and increased oocyte survival SO BIOLOGY OF REPRODUCTION LA English DT Article DE developmental biology; environment; mechanisms of hormone action; ovary ID ESTROGEN-RECEPTOR-BETA; POLYOVULAR FOLLICLES; BREAST-CANCER; PHYTOESTROGEN GENISTEIN; CELL-DEATH; MAMMARY TUMORIGENESIS; PRIMORDIAL FOLLICLES; FREQUENT OCCURRENCE; FEMALE MICE; GERM-CELLS AB Early in ovarian differentiation, female mouse germ cells develop in clusters called oocyte nests or germline cysts. After birth, mouse germ cell nests break down into individual oocytes that are surrounded by somatic pregranulosa cells to form primordial follicles. Previously, we have shown that mice treated neonatally with genistein, the primary soy phytoestrogen, have multi-oocyte follicles (MOFs), an effect apparently mediated by estrogen receptor 2 (ESR2, more commonly known as ERbeta). To determine if genistein treatment leads to MOFs by inhibiting breakdown of oocyte nests, mice were treated neonatally with genistein (50 mg/kg per day) on Days 1-5, and the differentiation of the ovary was compared with untreated controls. Mice treated with genistein had fewer single oocytes and a higher percentage of oocytes not enclosed in follicles. Oocytes from genistein-treated mice exhibited intercellular bridges at 4 days of age, long after disappearing in controls by 2 days of age. There was also an increase in the number of oocytes that survived during the nest breakdown period and fewer oocytes undergoing apoptosis on Neonatal Day 3 in genistein-treated mice as determined by poly (ADP-ribose) polymerase (PARP1) and deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end-labeling (TUNEL). These data taken together suggest that genistein exposure during development alters ovarian differentiation by inhibiting oocyte nest breakdown and attenuating oocyte cell death. C1 NIEHS, Dev Endocrinol & Endocrine Disruptor Sect, Mol Toxicol Lab, NIH,DHHS, Res Triangle Pk, NC 27709 USA. Syracuse Univ, Dept Biol, Syracuse, NY 13210 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27605 USA. RP Jefferson, W (reprint author), NIEHS, Dev Endocrinol & Endocrine Disruptor Sect, Mol Toxicol Lab, NIH,DHHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM jeffers1@niehs.nih.gov NR 62 TC 108 Z9 115 U1 1 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JAN PY 2006 VL 74 IS 1 BP 161 EP 168 DI 10.1095/biolreprod.105.045724 PG 8 WC Reproductive Biology SC Reproductive Biology GA 996TG UT WOS:000234197100021 PM 16192398 ER PT J AU Zelinski, MB Wu, JM Takahashi, D Lawson, M Lawson, M Tilmont, E Hobbs, A Mattison, JA Ottinger, MA Lane, MA Roth, GS Ingram, DK AF Zelinski, Mary B. Wu, Julie M. Takahashi, Diana Lawson, Maralee Lawson, Maralee Tilmont, Ed Hobbs, April Mattison, Julie A. Ottinger, Mary Ann Lane, Mark A. Roth, George S. Ingram, Donald K. TI Is caloric restriction an ovarian fountain of youth in primates?. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Oregon Natl Primate Res Ctr, Beaverton, OR USA. Univ Maryland, College Pk, MD 20742 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 64 EP 64 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500026 ER PT J AU Jayes, FL Couse, JF Korach, KS AF Jayes, Friederike L. Couse, John F. Korach, Kenneth S. TI Subfertility in female estrogen receptor-b null mice is partially due to a submaximal luteinizing hormone (LH) surge. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 76 EP 76 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500078 ER PT J AU Schedl, T Arur, S Ohmachi, M Nayak, S Golden, A AF Schedl, Tim Arur, Swathi Ohmachi, Mitsue Nayak, Sudhir Golden, Andy TI Functional genomics approach to identify targets of MPK-1 ERK signaling in germline development. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Washington Univ, Sch Med, St Louis, MO USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 95 EP 95 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500159 ER PT J AU Catherino, W Malik, M Segars, J AF Catherino, William Malik, Minnie Segars, James TI Microarray analysis demonstrates accelerated retinoic acid metabolism and decreased formation in human uterine leiomyomata that is confirmed in primary culture. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 106 EP 106 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500206 ER PT J AU Castrillon, DH Gallardo, TD John, GB Bradshaw, K Welt, C Reijo-Pera, R Vogt, PH Touraine, P Bione, S Toniolo, D Nelson, L Zinn, AR AF Castrillon, Diego H. Gallardo, Teresa D. John, George B. Bradshaw, Karen Welt, Corrine Reijo-Pera, Renee Vogt, Peter H. Touraine, Philippe Bione, Silvia Toniolo, Daniela Nelson, Larry Zinn, Andrew R. TI Sequence variation at the human FOXO3 locus: A study of premature ovarian failure and primary amenorrhea. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 94143 USA. Univ Texas, SW Med Ctr, Simmond Comprehens Canc Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Reprod Endocrinol, Boston, MA USA. Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, I-20132 San Francisco, CA USA. Heidelberg Univ, Dept Gynecol Endocrinol & Reprod Med, Heidelberg, Germany. Univ Paris 05, Necker Hosp, Dept Endocrinol & Reprod Med, Paris, France. Inst Mol Genet, Dept Human Genet & Genom, Pavia, Italy. Ist Sci San Raffaele, Dept Mol Biol & Genom, Milan, Italy. NICHHD, NIH, Rockville, MD USA. Univ Texas, SW Med Ctr, McDermott Ctr Human Growth & Dev, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 121 EP 121 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500274 ER PT J AU Falco, G Stanghellini, I Ko, MSH AF Falco, Geppino Stanghellini, Ilaria Ko, Minoru S. H. TI Use of Chuk to normalize gene expression levels in preimplantation mouse embryos. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 NIA, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 127 EP 128 PG 2 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500303 ER PT J AU Rodriguez, KF Taniguchi, F Couse, JF Korach, KS AF Rodriguez, Karina F. Taniguchi, Fuminori Couse, John F. Korach, Kenneth S. TI Estrogen receptor-B facilitates gonadotropin-induced cyclic-AMP synthesis and action in granulosa cells during follicle growth and ovulation. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 39th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 29-AUG 01, 2006 CL Univ Nebraska Med Ctr, Omaha, NE SP Soc Study Reprod HO Univ Nebraska Med Ctr C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2006 SI SI BP 175 EP 175 PG 1 WC Reproductive Biology SC Reproductive Biology GA 063ZW UT WOS:000239059500517 ER PT J AU Saugstad, OD Hansen, TWR Nakstad, B Tollofsrud, PA Reinholt, F Hamvas, A Cole, FS Sulenin, S Dean, M Wert, S Whitsett, JA Nogee, LM AF Saugstad, OD Hansen, TWR Nakstad, B Tollofsrud, PA Reinholt, F Hamvas, A Cole, FS Sulenin, S Dean, M Wert, S Whitsett, JA Nogee, LM TI Novel mutations in the gene encoding ABCA3 resulting in fatal neonatal lung disease SO BIOLOGY OF THE NEONATE LA English DT Meeting Abstract C1 Univ Hosp Oslo, Dept Pediat, Oslo, Norway. Radiumhosp HF, Rikshosp, Dept Pediat Res, Oslo, Norway. Radiumhosp HF, Rikshosp, Dept Pediat, Oslo, Norway. Radiumhosp HF, Rikshosp, Dept Pathol, Oslo, Norway. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. St Louis Childrens Hosp, St Louis, MO 63178 USA. NCI, Human Genet Sector, Frederick, MD 21701 USA. Childrens Hosp, Coll Med, Cincinnati, OH 45229 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0006-3126 J9 BIOL NEONATE JI Biol. Neonate PY 2006 VL 89 IS 4 BP 349 EP 349 PG 1 WC Pediatrics SC Pediatrics GA 054DR UT WOS:000238357500037 ER PT S AU Sollers, JJ Merritt, MM Silver, RA Sadle, TN Ferrucci, L Thayer, JF AF Sollers, John J., III Merritt, Marcellus M. Silver, Rebecca A. Sadle, Tammy N. Ferrucci, Luigi Thayer, Julian F. BE Waite, L TI Comparison of arterial compliance indices derived via Beat-toBeat blood pressure waveforms: Aging and ethnicity SO Biomedical Sciences Instrumentation, Vol 42 SE BIOMEDICAL SCIENCES INSTRUMENTATION LA English DT Proceedings Paper CT 43rd Annual Rocky Mountain Bioengineering Symposium/43rd International ISA Biomedical Sciences Instrumentation Symposium CY APR 07-09, 2006 CL Rose Hulman Inst Technol, Terre Haute, IN SP ISA HO Rose Hulman Inst Technol DE arterial compliance; BLSA; aging; ethnicity ID RATIO AB Reduced arterial compliance has been implicated as a risk factor for future cardiovascular events in hypertensive patients. Recently, several non-invasive techniques have been used to access arterial compliance. However, comparisons of these techniques with older individuals and African-Americans have not been done. In the present study, beat-to-beat blood pressure was examined in 75 males and females (n=24 old Caucasian; n =24 young Caucasian; n=27 AfricanAmericans) who were part of the Baltimore Longitudinal Study of Aging (BLSA). Resting beatto-beat blood pressure (5 minutes) was assessed using the PORTAPRES Ambulatory Blood Pressure Device. Results indicated that the three-element windkessel and the stroke volumepulse pressure ratio measures of arterial compliance provide comparable estimates. Specifically, arterial compliance is reduced in the oldest individuals in our sample with young and AfricanAmericans showing higher compliance. These results indicate that the simpler stroke volumepulse pressure ratio provides reliable estimates of arterial compliance in both older adults and African-Americans. This technique is an excellent means to assess arterial compliance and is a useful measure to determine risk for adverse cardiovascular events. C1 NIA, Baltimore, MD 21224 USA. RP Sollers, JJ (reprint author), NIA, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. FU Intramural NIH HHS NR 4 TC 5 Z9 5 U1 0 U2 1 PU INSTRUMENT SOC AMER PI RESEARCH TRIANGLE PARK PA 67 ALEXANDER DR, PO BOX 12277, RESEARCH TRIANGLE PARK, NC 27709 USA SN 0067-8856 J9 BIOMED SCI INSTRUM PY 2006 VL 42 BP 518 EP 523 PG 6 WC Engineering, Biomedical; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA BES79 UT WOS:000239353700086 PM 16817661 ER PT J AU Klecker, RW Cysyk, RL Collins, JM AF Klecker, RW Cysyk, RL Collins, JM TI Zebularine metabolism by aldehyde oxidase in hepatic cytosol from humans, monkeys, dogs, rats, and mice: Influence of sex and inhibitors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE aldehyde oxidase; zebularine; raloxifene; 5-benzylacyclouridine; hepatic metabolism inhibition ID URIDINE PHOSPHORYLASE INHIBITOR; LIVER; 5-BENZYLACYCLOURIDINE; BENZYLACYCLOURIDINE; PHARMACOKINETICS; RALOXIFENE; 5-FLUOROURACIL; PURIFICATION AB To aid in the clinical evaluation of zebillarine, a potential oral antitumor agent, we initiated Studies on the metabolism of zebularine in liver cytosol from humans and other mammals. Metabolism by aldehyde oxidase (AO, EC 1.2.3.1) was the major catabolic route, Yielding Uridine as the primary metabolite, which was metabolized further to Uracil by Uridine phosphorylase. The inhibition of zebularine metabolism was Studied using raloxifene, a known potent inhibitor of AO, and 5-benzylacyclouridine (BAU), a previously undescribed inhibitor of AO. The Michaelis-Menten kinetics of aldehyde oxidase and its inhibition by raloxifene and BAU were highly variable between species. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NCI, Mol Therapeut Program, Ctr Canc Res, Bethesda, MD 20892 USA. RP Klecker, RW (reprint author), US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM klecker@cder.fda.gov NR 23 TC 38 Z9 41 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2006 VL 14 IS 1 BP 62 EP 66 DI 10.1016/j.bmc.2005.07.053 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 989YB UT WOS:000233708900006 PM 16143537 ER PT J AU Mihailescu, M Gawrisch, K AF Mihailescu, M Gawrisch, K TI The structure of polyunsaturated lipid bilayers important for rhodopsin function: A neutron diffraction study SO BIOPHYSICAL JOURNAL LA English DT Letter ID JOINT REFINEMENT; X-RAY; ACID AB The structure of oriented 1-stearoyl-2-docosahexaenoyl-sn-glycero-3- phosphocholine bilayers with perdeuterated stearoyl-or docosahexaenoyl hydrocarbon chains was investigated by neutron diffraction. Experiments were conducted at two different relative humidities, 66 and 86%. At both humidities we observed that the polyunsaturated docosahexaenoyl chain has a preference to reside near the lipid water interface. That leaves voids in the bilayer center that are occupied by saturated stearoyl chain segments. This uneven distribution of saturated-and polyunsaturated chain densities is likely to result in membrane elastic stress that modulates function of integral receptor proteins like rhodopsin. C1 Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Gawrisch, K (reprint author), Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA. EM gawrisch@helix.nih.gov FU Intramural NIH HHS NR 10 TC 17 Z9 18 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2006 VL 90 IS 1 BP L4 EP L6 DI 10.1529/biophysj.105.071712 PG 3 WC Biophysics SC Biophysics GA 992LJ UT WOS:000233885100002 PM 16258049 ER PT J AU Baker, SG Fitzmaurice, GM Freedman, LS Kramer, BS AF Baker, SG Fitzmaurice, GM Freedman, LS Kramer, BS TI Simple adjustments for randomized trials with nonrandomly missing or censored outcomes arising from informative covariates SO BIOSTATISTICS LA English DT Article DE binary; longitudinal; maximum likelihood; propensity score; survival ID GROUPED SURVIVAL-DATA; REGRESSION-ANALYSIS; CATEGORICAL-DATA; PROPENSITY SCORE; NONRESPONSE; INFERENCE; SUBJECT; MODELS AB In randomized trials with missing or censored outcomes, standard maximum likelihood estimates of the effect of intervention on outcome are based on the assumption that the missing-data mechanism is ignorable. This assumption is violated if there is an unobserved baseline covariate that is informative, namely a baseline covariate associated with both outcome and the probability that the outcome is missing or censored. Incorporating informative covariates in the analysis has the desirable result of ameliorating the violation of this assumption. Although this idea of including informative covariates is recognized in the statistics literature, it is not appreciated in the literature on randomized trials. Moreover, to our knowledge, there has been no discussion on how to incorporate informative covariates into a general likelihood-based analysis with partially missing outcomes to estimate the quantities of interest. Our contribution is a simple likelihood-based approach for using informative covariates to estimate the effect of intervention on a partially missing outcome in a randomized trial. The first step is to create a propensity-to-be-missing score for each randomization group and divide the scores into a small number of strata based on quantiles. The second step is to compute stratum-specific estimates of outcome derived from a likelihood-analysis conditional on the informative covariates, so that the missing-data mechanism is ignorable. The third step is to average the stratum-specific estimates and compute the estimated effect of interventionon outcome. We discuss the computations for univariate, survival, and longitudinal outcomes, and present an application involving a randomized study of dual versus triple combinations of HIV-1 reverse transcriptase inhibitors. C1 NCI, Biometry Res Grp, Div Canc Inst, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Bar Ilan Univ, Dept Math Stat & Comp Sci, IL-52900 Ramat Gan, Israel. NIH, Off Dis Prevent, Bethesda, MD USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Div Canc Inst, Bethesda, MD 20892 USA. EM sb16i@nih.gov FU NIGMS NIH HHS [GM29745] NR 27 TC 13 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2006 VL 7 IS 1 BP 29 EP 40 DI 10.1093/biostatistics/kxi038 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 997BV UT WOS:000234220900003 PM 15923407 ER PT J AU Baker, SG AF Baker, SG TI A simple meta-analytic approach for using a binary surrogate endpoint to predict the effect of intervention on true endpoint SO BIOSTATISTICS LA English DT Article DE colorectal cancer random effects; randomized trials ID RANDOMIZED CLINICAL-TRIALS; ADVANCED COLORECTAL-CANCER; MIXED MODELS; VALIDATION; CRITERIA AB A surrogate endpoint is an endpoint that is obtained sooner, at lower cost, or less invasively than the true endpoint for a health outcome and is used to make conclusions about the effect of intervention on the true endpoint. In this approach, each previous trial with surrogate and true endpoints contributes an estimated predicted effect of intervention on true endpoint in the trial of interest based on the surrogate endpoint in the trial of interest. These predicted quantities are combined in a simple random-effects meta-analysis to estimate the predicted effect of intervention on true endpoint in the trial of interest. Validation involves comparing the average prediction error of the aforementioned approach with (i) the average prediction error of a standard meta-analysis using only true endpoints in the other trials and (ii) the average clinically meaningful difference in true endpoints implicit in the trials. Validation is illustrated using data from multiple randomized trials of patients with advanced colorectal cancer in which the surrogate endpoint was tumor response and the true endpoint was median survival time. C1 NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Baker, SG (reprint author), NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 23 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2006 VL 7 IS 1 BP 58 EP 70 DI 10.1093/biostatistics/kxi040 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 997BV UT WOS:000234220900005 PM 15972889 ER PT J AU Salicrup, LA Fedorkova, L AF Salicrup, LA Fedorkova, L TI Challenges and opportunities for enhancing biotechnology and technology transfer in developing countries SO BIOTECHNOLOGY ADVANCES LA English DT Review DE technology transfer; biomedical innovation; license strategies; developing countries; neglected diseases; capacity building; international partnerships ID BIOMEDICAL-RESEARCH; GLOBAL HEALTH; INDUSTRY AB Biotechnological innovation is gaining increased recognition as an important tool for improving global health. The challenge, however, lies in defining the role of technology transfer to develop therapies for diseases prevalent in developing countries. During the past decade, a large disparity emerged between the developed and developing world in accessing affordable medicines because of the pharmaceutical industry's focus on health areas bearing greatest profits. Discussed herein are several mechanisms that provide partial solutions to this challenge. The Office of Technology Transfer of the US National Institutes of Health has increased its technology licensing pertaining to neglected diseases to partners in developing regions. Establishing partnerships through the transfer of technologies and assisting indigenous institutions build R and D capacity may positively impact policies on protection of intellectual property rights and increase multinational company investments in lesser-developed countries. This will most probably result in the development of more accessible therapies for those in need. Published by Elsevier Inc. C1 US Dept HHS, Off Director, Off Technol Transfer, NIH, Rockville, MD 20852 USA. RP Salicrup, LA (reprint author), US Dept HHS, Off Director, Off Technol Transfer, NIH, 6011 Execut Blvd,Suite 325, Rockville, MD 20852 USA. EM salicrul@mail.nih.gov NR 52 TC 18 Z9 18 U1 1 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD JAN-FEB PY 2006 VL 24 IS 1 BP 69 EP 79 DI 10.1016/j.biotechadv.2005.06.004 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 005TX UT WOS:000234847800006 PM 16098701 ER PT J AU Post, RM Speer, AM Leverich, GS AF Post, Robert M. Speer, Andrew M. Leverich, Gabriele S. BE Akiskal, HS Tohen, M TI Complex Combination Therapy: The Evolution Toward Rational Polypharmacy in Lithium-Resistant Bipolar Illness SO BIPOLAR PSYCHOPHARMACOTHERAPY: CARING FOR THE PATIENT LA English DT Article; Book Chapter ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; REFRACTORY MOOD DISORDERS; LONG-TERM TREATMENT; HIGH-DOSE THYROXINE; OPEN CLINICAL-TRIAL; DOUBLE-BLIND; MAINTENANCE TREATMENT; I DISORDER; ATYPICAL ANTIPSYCHOTICS C1 [Post, Robert M.; Speer, Andrew M.; Leverich, Gabriele S.] NIMH, Biol Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, DHHS, Bldg 10,Rm 3S239,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 129 TC 5 Z9 5 U1 1 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47001-795-1 PY 2006 BP 135 EP 167 DI 10.1002/0470017953.ch9 PG 33 WC Psychiatry SC Psychiatry GA BXY93 UT WOS:000297645900010 ER PT J AU Krause, RM AF Krause, Richard M. BA Leung, PC Tambyah, P BF Leung, PC Tambyah, P TI Influenza, the Rockefeller Institute and, "The Swine Flu Episode(a), 1976" SO BIRD FLU: A RISING PANDEMIC IN ASIA AND BEYOND LA English DT Article; Book Chapter ID STREPTOCOCCUS HAEMOLYTICUS; IMMUNOLOGICAL-PROPERTIES; ANTIGENIC COMPLEX; VIRUS C1 [Krause, Richard M.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 19 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-270-733-8 PY 2006 BP 221 EP 241 DI 10.1142/9789812707338_0016 PG 21 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA BZD18 UT WOS:000301142700018 ER PT J AU Zhang, J Randall, MS Loyd, MR Li, WM Schweers, RL Persons, DA Rehg, JE Noguchi, CT Ihle, JN Ney, PA AF Zhang, J Randall, MS Loyd, MR Li, WM Schweers, RL Persons, DA Rehg, JE Noguchi, CT Ihle, JN Ney, PA TI Role of erythropoietin receptor signaling in Friend virus-induced erythroblastosis and polycythemia SO BLOOD LA English DT Article ID FOCUS-FORMING VIRUS; ERYTHROID COLONY FORMATION; CELL-FACTOR RECEPTORS; TYROSINE KINASE; TRANSMEMBRANE DOMAIN; INDEPENDENT GROWTH; GP55 GLYCOPROTEIN; TRUNCATED FORM; GENE; ERYTHROLEUKEMIA AB Friend virus is an acutely oncogenic retrovirus that causes erythroblastosis and polycythemia in mice. Previous studies suggested that the Friend virus oncoprotein, gp55, constitutively activates the erythropoietin receptor (EPOR), causing uncontrolled erythroid proliferation. Those studies showed that gp55 confers growth factor independence on an interleukin-3 (IL-3)-dependent cell line (Ba/F3) when the EPOR is coexpressed. Subsequently, we showed that a truncated form of the stem-cell kinase receptor (sf-STK) is required for susceptibility to Friend disease. Given the requirement for sf-STK, we sought to establish the in vivo significance of gp55-mediated activation of the EPOR. We found that the cytoplasmic tyrosine residues of the EPOR, and signal transducer and activator of transcription-5 (STAT5), which acts through these sites, are not required for Friend virusinduced erythroblastosis. The EPOR itself was required for the development of erythroblastosis but not for gp55-mediated erythrold proliferation. Interestingly, the murine EPOR, which Is required for gp55-mediated Ba/F3-cell proliferation, was dispensable for erythroblastosis in vivo. Finally, gp55-mediated activation of the EPOR and STAT5 are required for Friend virus-induced polycythemia. These results suggest that Friend virus activates both sf-STK and the EPOR to cause deregulated erythroid proliferation and differentiation. C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Expt Hematol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. Univ Tennessee, Hlth Sci Ctr, Integrated Program Biomed Sci, Memphis, TN 37996 USA. Natl Inst Diabet & Digest & Kidney Dis, NIH, Bethesda, MD USA. RP Ney, PA (reprint author), St Jude Childrens Res Hosp, Dept Biochem, 332 N Lauderdale St, Memphis, TN 38105 USA. EM paul.ney@stjude.org FU NCI NIH HHS [R01 CA084214-08, R01 CA084214, P30 CA21765, R01 CA084214-07, R01 CA084214-10, R01 CA084214-09] NR 39 TC 16 Z9 16 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 JAN 1 PY 2006 VL 107 IS 1 BP 73 EP 78 DI 10.1182/blood-2005-05-1784 PG 6 WC Hematology SC Hematology GA 997HD UT WOS:000234235200020 PM 16174761 ER PT J AU Bryceson, YT March, ME Ljunggren, HG Long, EO AF Bryceson, YT March, ME Ljunggren, HG Long, EO TI Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion SO BLOOD LA English DT Article ID VIRUS-INFECTED CELLS; PROTEIN-KINASE-C; KILLER-CELLS; IMMUNOGLOBULIN SUPERFAMILY; SIGNAL-TRANSDUCTION; FC-RECEPTOR; IMMUNOLOGICAL SYNAPSE; LIGAND INTERACTIONS; ADHESION MOLECULE; GLYCOPROTEIN UL16 AB Freshly isolated, resting natural killer (NK) cells are generally less lytic against target cells than in vitro interleukin 2 (IL-2)activated INK cells. To investigate the basis for this difference, the contribution of several receptors to activation of human NK cells was examined. Target-cell lysis by IL-2-activated NK cells in a redirected, anti body-dependent cytotoxicity assay was triggered by a number of receptors. In contrast, cytotoxicity by resting NK cells was induced only by CD16, and not by NKp46, NKG2D, 2134 (CD244), DNAM-1 (CD226), or CD2. Calcium flux in resting NK cells was induced with antibodies to CD16 and, to a weaker extent, antibodies to NKp46 and 2B4. Although NKp46 did not enhance CD16-mediated calcium flux, it synergized with all other receptors. 2B4 synergized with 3 other receptors, NKG2D and DNAM-1 each synergized with 2 other receptors, and CD2 synergized with NKp46 only. Resting NK cells were induced to secrete tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma), and to kill target cells by engagement of specific, pair-wise combinations of receptors. Therefore, natural cytotoxicity by resting NK cells is induced only by mutual costimulation of nonactivating receptors. These results reveal distinct and specific patterns of synergy among receptors on resting NK cells. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Karolinska Univ, Hosp Huddinge, Karolinska Inst, Ctr Infect Med,Dept Med, Stockholm, Sweden. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM elong@nih.gov RI Long, Eric/G-5475-2011; OI Long, Eric/0000-0002-7793-3728; Bryceson, Yenan/0000-0002-7783-9934 FU Intramural NIH HHS NR 63 TC 331 Z9 339 U1 0 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2006 VL 107 IS 1 BP 159 EP 166 DI 10.1182/blood-2005-04-1351 PG 8 WC Hematology SC Hematology GA 997HD UT WOS:000234235200032 PM 16150947 ER PT J AU Zeng, WH Miyazato, A Chen, GB Kajigaya, S Young, NS Maciejewski, JP AF Zeng, WH Miyazato, A Chen, GB Kajigaya, S Young, NS Maciejewski, JP TI Interferon-gamma-induced gene expression in CD34 cells: identification of pathologic cytokine-specific signature profiles SO BLOOD LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; HEMATOPOIETIC PROGENITOR CELLS; APLASTIC-ANEMIA PATIENTS; ACUTE MYELOID-LEUKEMIA; BONE-MARROW FAILURE; CD8(+) T-CELLS; IMMUNOSUPPRESSIVE THERAPY; CYTOGENETIC ABNORMALITIES; MOLECULAR-CLONING; STRANDED-RNA AB Hematopoietic effects of interferon-gamma (IFN-y) may be responsible for certain aspects of the pathology seen in bone marrow failure syndromes, including aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH), and some forms of myelodysplasia (MDS). Overexpression of and hematopoietic inhibition by IFN-gamma has been observed in all of these conditions. In vitro, IFN-gamma exhibits strong inhibitory effects on hematopoietic progenitor and stem cells. Previously, we have studied the transcriptome of CD34 cells derived from patients with bone marrow failure syndromes and identified characteristic molecular signatures common to some of these conditions. In this report, we have investigated genome-wide expression patterns after exposure of CD34 and bone marrow stroma cells derived from normal bone marrow to IFN-gamma in vitro and have detected profound changes in the transcription profile. Some of these changes were concordant in both stroma and CD34 cells, whereas others were specific to CD34 cells. In general, our results were in agreement with the previously described function of IFN-gamma in CD34 cells involving activation of apoptotic pathways and immune response genes. Comparison between the IFN-gamma transcriptome in normal CD34 cells and changes previously detected in CD34 cells from AA and PNH patients reveals the presence of many similarities that may reflect molecular signature of in vivo IFN-gamma exposure. C1 Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Taussig Canc Ctr, Cleveland, OH 44195 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Taussig Canc Ctr, R40,9500 Euclid Ave, Cleveland, OH 44195 USA. EM maciejj@cc.ccf.org NR 52 TC 61 Z9 70 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 JAN 1 PY 2006 VL 107 IS 1 BP 167 EP 175 DI 10.1182/blood-2005-05-1884 PG 9 WC Hematology SC Hematology GA 997HD UT WOS:000234235200033 PM 16131564 ER PT J AU Takeuchi, S Katz, SI AF Takeuchi, S Katz, SI TI Use of interleukin 7 receptor-alpha knockout donor cells demonstrates the lymphoid independence of dendritic cells5 SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; THYMIC PRECURSOR CELLS; LANGERHANS CELLS; BONE-MARROW; T-CELL; EPIDERMAL-CELLS; DIFFERENTIATION; MICE; PROGENITORS; POPULATION AB The precise lineage of dendritic cells (DCs), including skin Langerhans cells (LCs), is unclear. Interleukin 7 (IL-7) and its receptor (IL-7R alpha) are known to mediate lymphopoiesis, and IL-7 is also known to be essential for the generation of DCs from lymphoid-committed precursors in vitro. Thus, to determine the developmental lymphoid (or IL-7Ra) dependency of various DCs and to examine the importance of IL-7/IL-7R alpha for DC development in vivo, we used IL-7R alpha knockout (KO) donor cells to reconstitute DCs/LCs in sublethally irradiated recipients and compared the results to those obtained using wild-type (WT) donor cells. We found that lymphoid lineage cells (except natural killer [NK] cells), including thymocytes, were less efficiently reconstituted by IL-7R alpha KO donor cells, whereas myeloid lineage cells and DCs/LCs were equally well reconstituted by both the IL-7R alpha KO and WT donor cells. Overall, we conclude that IL-7R alpha is not required for the development of DCs/LC in vivo. C1 NCI, Dermatol Branch, NIH, Bethesda, MD USA. RP Katz, SI (reprint author), Natl Inst Arthritis & Metab Dis, NIH, Bldg 31-4C32, Bethesda, MD 20892 USA. EM katzs@od.niams.nih.gov FU NCI NIH HHS [Z01 SC003657-31] NR 24 TC 7 Z9 7 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 JAN 1 PY 2006 VL 107 IS 1 BP 184 EP 186 DI 10.1182/blood-2005-02-0647 PG 3 WC Hematology SC Hematology GA 997HD UT WOS:000234235200035 PM 16166595 ER PT J AU Morton, LM Wang, SS Devesa, SS Hartge, P Weisenburger, DD Linet, MS AF Morton, LM Wang, SS Devesa, SS Hartge, P Weisenburger, DD Linet, MS TI Lymphorna incidence patterns by WHO subtype in the United States, 1992-2001 SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC LYMPHOCYTIC-LEUKEMIA; CANCER SURVEILLANCE SERIES; TIME TRENDS; INCREASING INCIDENCE; DISEASE INCIDENCE; CHILDHOOD-CANCER; KAPOSIS-SARCOMA AB Because the causes of most lymphoid neoplasms remain unknown, comparison of incidence patterns by disease subtype may provide critical clues for future etiologic investigations. We therefore conducted a comprehensive assessment of 114548 lymphold neoplasms diagnosed during 1992-2001 in 12 Surveillance, Epidemiology, and End Results (SEER) registries according to the internationally recognized World Health Organization (WHO) lymphoma classification introduced in 2001. Cases coded in International Classification of Diseases for Oncology, Second Edition (ICD-O-2), were converted to ICD-O-3 for WHO subtype assignment. Age-specific and age-adjusted rates were compared by sex and race (white, black, Asian). Age-adjusted trends in incidence were estimated by sex and race using weighted least squares log-linear regression. Diverse incidence patterns and trends were observed by lymphoid neoplasm subtype and population. In the elderly (75 years or older), rates of diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma increased 1.4% and 1.8% per year, respectively, whereas rates of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLUSLL) declined 2.1% per year. Although whites bear the highest incidence burden for most lymphold neoplasm subtypes, most notably for hairy cell leukemia and follicular lymphoma, black predominance was observed for plasma cell and T-cell neoplasms. Asians have considerably lower rates than whites and blacks for CLL/SLL and Hodgkin lymphoma. We conclude that the striking differences in incidence patterns by histologic subtype strongly suggest that there is etiologic heterogeneity among lymphoid neoplasms and support the pursuit of epidemiologic analysis by subtype. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Lincoln, NE 68583 USA. RP Morton, LM (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS-7055, Rockville, MD 20852 USA. EM mortonli@mail.nih.gov RI Morton, Lindsay/B-5234-2015 OI Morton, Lindsay/0000-0001-9767-2310 FU Intramural NIH HHS NR 91 TC 635 Z9 663 U1 6 U2 16 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 JAN 1 PY 2006 VL 107 IS 1 BP 265 EP 276 DI 10.1182/blood-2005-06-2508 PG 12 WC Hematology SC Hematology GA 997HD UT WOS:000234235200046 PM 16150940 ER PT J AU Welniak, LA Kuprash, DV Tumanov, AV Panoskaltsis-Mortari, A Blazar, BR Sun, K Nedospasov, SA Murphy, WJ AF Welniak, LA Kuprash, DV Tumanov, AV Panoskaltsis-Mortari, A Blazar, BR Sun, K Nedospasov, SA Murphy, WJ TI Peyer patches are not required for acute graft-versus-host disease after myeloablative conditioning and murine allogeneic bone marrow transplantation SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; PERIPHERAL LYMPHOID ORGANS; T-CELLS; FACTOR-DEFICIENT; MICE DEFICIENT; ORGANOGENESIS; LYMPHOTOXIN; TNF; MATURATION; FOLLICLES AB Graft-versus-host disease (GVHD) is a multistep disease process following allogeneic bone marrow transplantation (BMT). It has been postulated that the induction of acute GVHD requires the presence of Peyer patches (PPs). A new tumor necrosis factor (TNF)-deficient strain has been developed that totally lacks PPs and displays the defects characteristic of TNF ablation but not lymphotoxin-associated defects characterized by lack of both PPs and lymph nodes. To determine the necessity of PPs in acute lethal GVHD induction, we transplanted full major histocompatibility complex (MHC)-mismatched grafts into myeloablated TNF knockout recipients. No differences in the survival or GVHD-associated histopathologic lesions were observed between the recipients. We conclude that neither PPs nor host TNIF-alpha is required for the development of acute lethal GVHD in mice that undergo myeloablative conditioning and allogeneic BMT. C1 Univ Nevada, Sch Med, Dept Immunol & Microbiol, Reno, NV 89557 USA. Russian Acad Sci, Inst Mol Biol, Lab Mol Immunol, Moscow, Russia. Univ Minnesota, Ctr Canc, Div BMT, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pediat, Div BMT, Minneapolis, MN 55455 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. Natl Canc Inst, Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD USA. RP Welniak, LA (reprint author), Univ Nevada, Sch Med, Dept Immunol & Microbiol, Mail Stop 199, Reno, NV 89557 USA. EM lwelniak@unr.edu RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-12400, R01 CA102282]; NCRR NIH HHS [P20 RR016464]; NHLBI NIH HHS [R01 HL63452, 2R37 HL56067]; NIAID NIH HHS [R01 AI 34495] NR 20 TC 26 Z9 27 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 JAN 1 PY 2006 VL 107 IS 1 BP 410 EP 412 DI 10.1182/blood-2004-11-4565 PG 3 WC Hematology SC Hematology GA 997HD UT WOS:000234235200066 PM 16160014 ER PT J AU Mougin, F Burgun, A Bodenreider, O AF Mougin, Fleur Burgun, Anita Bodenreider, Olivier TI Mapping data elements to terminological resources for integrating biomedical data sources SO BMC BIOINFORMATICS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Semantic Mining in Biomedicine CY APR 09-12, 2006 CL Jena, GERMANY AB Background: Data integration is a crucial task in the biomedical domain and integrating data sources is one approach to integrating data. Data elements (DEs) in particular play an important role in data integration. We combine schema-and instance-based approaches to mapping DEs to terminological resources in order to facilitate data sources integration. Methods: We extracted DEs from eleven disparate biomedical sources. We compared these DEs to concepts and/or terms in biomedical controlled vocabularies and to reference DEs. We also exploited DE values to disambiguate underspecified DEs and to identify additional mappings. Results: 82.5% of the 474 DEs studied are mapped to entries of a terminological resource and 74.7% of the whole set can be associated with reference DEs. Only 6.6% of the DEs had values that could be semantically typed. Conclusion: Our study suggests that the integration of biomedical sources can be achieved automatically with limited precision and largely facilitated by mapping DEs to terminological resources. C1 Univ Rennes 1, Fac Med, IFR 140, EA 3888, F-35014 Rennes, France. Natl Lib Med, Bethesda, MD USA. RP Mougin, F (reprint author), Univ Rennes 1, Fac Med, IFR 140, EA 3888, F-35014 Rennes, France. EM fleur.mougin@univ-rennes1.fr; anita.burgun@univ-rennes1.fr; olivier@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 14 TC 6 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2006 VL 7 SU 3 AR S6 DI 10.1186/1471-2105-7-S3-S6 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 144IK UT WOS:000244789500006 PM 17134479 ER PT J AU Russo, CR Lauretani, F Seeman, E Bartali, B Bandinelli, S Di Iorio, A Guralnik, J Ferrucci, L AF Russo, CR Lauretani, F Seeman, E Bartali, B Bandinelli, S Di Iorio, A Guralnik, J Ferrucci, L TI Structural adaptations to bone loss in aging men and women SO BONE LA English DT Article DE aging; computed tomography; bone biomechanics; cross-sectional area ID CORTICAL BONE; COMPUTED-TOMOGRAPHY; GENDER-DIFFERENCES; MINERAL DENSITY; AGE; FRAGILITY; HEALTH; FEMUR; METACARPAL; POROSITY AB Introduction: Bone apposition on the subperiosteal surface and bone loss from the endocortical surface during aging establish the external diameter, total cross-sectional area (tCSA), cortical thickness (Ct.Th) and the distance the cortex is placed from the neutral axis of a long bone, all determinants of bone strength. We tested the hypothesis that sex-related differences in these processes produces a sexual dimorphism in tibial fragility. Methods: The above traits were assessed in 688 women and 561 men (20-102 years old) using peripheral QCT. Results: Total and medullary areas were greater in young adult men than young adult women. As age advanced, in men, tCSA area increased by 0.79 SD, and medullary area increased by 0.54 SD so that cortical area, cortical thickness and minimum and maximum moments of inertia (I-min and I-max were similar at all ages. In women, tCSA increased by 0.2 SD, while medullary area increased by 2.6 SD so that cortical area and thickness and the moments of inertia diminished. Cortical apparent volumetric bone mineral density (vBMD) declined more in women (by 3.1 SD) than men (by 0.5 SD). In both sexes, the lower the cortical apparent vBMD, the higher the tCSA (women R-2 = 0. 13, men R-2 = 0.16, both P < 0.0001), whereas the lower the Ct.Th, the lower the tCSA (women R-2 = 0.30, men R-2 = 0.32, both P < 0.0001). Conclusions: Bone loss reduces cortical thickness and increases intracortical porosity. These changes tend to be compensated for by periosteal apposition in both sexes but more greatly in men than in women, perhaps because this mechanism may be ineffective when cortical thinning is severe. (c) 2005 Elsevier Inc. All rights reserved. C1 NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21225 USA. INRCA Geriatr Dept, Lab Clin Epidemiol, Florence, Italy. Univ Melbourne, Austin Hosp, Dept Endocrinol, Melbourne, Vic, Australia. Cornell Univ, Div Nutr sci, Ithaca, NY 14853 USA. Univ Chieti, Dept Med & Aging, Chieti, Italy. RP Ferrucci, L (reprint author), NIA, Clin Res Branch, Longitudinal Studies Sect, 3001 S Hanover St Rm NH534, Baltimore, MD 21225 USA. EM russo7@tiscalinet.it; FerrucciLu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Seeman, Ego/0000-0002-9692-048X; Lauretani, Fulvio/0000-0002-5287-9972 FU PHS HHS [821336, 916413] NR 22 TC 85 Z9 85 U1 1 U2 4 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 JAN PY 2006 VL 38 IS 1 BP 112 EP 118 DI 10.1016/j.bone.2005.07.025 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 003QI UT WOS:000234696300013 PM 16242391 ER PT J AU Booth, BW Smith, GH AF Booth, Brian W. Smith, Gilbert H. TI Estrogen receptor-alpha and progesterone receptor are expressed in label-retaining mammary epithelial cells that divide asymmetrically and retain their template DNA strands SO BREAST CANCER RESEARCH LA English DT Article ID STEROID-RECEPTORS; BREAST-CANCER; STEM-CELLS; GLAND; PROLIFERATION; SEGREGATION AB Introduction Stem cells of somatic tissues are hypothesized to protect themselves from mutation and cancer risk through a process of selective segregation of their template DNA strands during asymmetric division. Mouse mammary epithelium contains label-retaining epithelial cells that divide asymmetrically and retain their template DNA. Method Immunohistochemistry was used in murine mammary glands that had been labeled with [H-3] thymidine during allometric growth to investigate the co-expression of DNA label retention and estrogen receptor (ER)-alpha or progesterone receptor ( PR). Using the same methods, we investigated the colocalization of [H-3] thymidine and ER-alpha or PR in mammary tissue from mice that had received treatment with estrogen, progesterone, and prolactin subsequent to a long chase period to identify label-retaining cells. Results Label-retaining epithelial cells (LRECs) comprised approximately 2.0% of the entire mammary epithelium. ER-alpha-positive and PR-positive cells represented about 30 - 40% of the LREC subpopulation. Administration of estrogen, progesterone, and prolactin altered the percentage of LRECs expressing ER alpha. Conclusion The results presented here support the premise that there is a subpopulation of LRECs in the murine mammary gland that is positive for ER-alpha and/or PR. This suggests that certain mammary LRECs ( potentially stem cells) remain stably positive for these receptors, raising the possibility that LRECs comprise a hierarchy of asymmetrically cycling mammary stem/ progenitor cells that are distinguished by the presence or absence of nuclear steroid receptor expression. C1 NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. EM gs4d@nih.gov FU Intramural NIH HHS NR 14 TC 79 Z9 84 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 4 AR R49 DI 10.1186/bcr1538 PG 8 WC Oncology SC Oncology GA 087UI UT WOS:000240767500023 PM 16882347 ER PT J AU Cox, DG Blanche, H Pearce, CL Calle, EE Colditz, GA Pike, MC Albanes, D Allen, NE Amiano, P Berglund, G Boeing, H Buring, J Burtt, N Canzian, F Chanock, S Clavel-Chapelon, F Feigelson, HS Freedman, M Haiman, CA Hankinson, SE Henderson, BE Hoover, R Hunter, DJ Kaaks, R Kolonel, L Kraft, P LeMarchand, L Lund, E Palli, D Peeters, PHM Riboli, E Stram, DO Thun, M Tjonneland, A Trichopoulos, D Yeager, M AF Cox, David G. Blanche, Helene Pearce, Celeste L. Calle, Eugenia E. Colditz, Graham A. Pike, Malcolm C. Albanes, Demetrius Allen, Naomi E. Amiano, Pilar Berglund, Goran Boeing, Heiner Buring, Julie Burtt, Noel Canzian, Federico Chanock, Stephen Clavel-Chapelon, Francoise Feigelson, Heather Spencer Freedman, Matthew Haiman, Christopher A. Hankinson, Susan E. Henderson, Brian E. Hoover, Robert Hunter, David J. Kaaks, Rudolf Kolonel, Laurence Kraft, Peter LeMarchand, Loic Lund, Eiliv Palli, Domenico Peeters, Petra H. M. Riboli, Elio Stram, Daniel O. Thun, Michael Tjonneland, Anne Trichopoulos, Dimitrios Yeager, Meredith CA Breast Prostate Canc TI A comprehensive analysis of the androgen receptor gene and risk of breast cancer: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) SO BREAST CANCER RESEARCH LA English DT Article ID BASE-LINE CHARACTERISTICS; CAG REPEAT POLYMORPHISM; SEX-HORMONE LEVELS; VITAMIN-D-RECEPTOR; POSTMENOPAUSAL WOMEN; DEHYDROEPIANDROSTERONE-SULFATE; POLYGLUTAMINE TRACTS; MULTIETHNIC COHORT; NURSES HEALTH; CELL-LINES AB Introduction Androgens have been hypothesised to influence risk of breast cancer through several possible mechanisms, including their conversion to estradiol or their binding to the oestrogen receptor and/ or androgen receptor ( AR) in the breast. Here, we report on the results of a large and comprehensive study of the association between genetic variation in the AR gene and risk of breast cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium ( BPC3). Methods The underlying genetic variation was determined by first sequencing the coding regions of the AR gene in a panel of 95 advanced breast cancer cases. Second, a dense set of markers from the public database was genotyped in a panel of 349 healthy women. The linkage disequilibrium relationships ( blocks) across the gene were then identified, and haplotypetagging single nucleotide polymorphisms ( htSNPs) were selected to capture the common genetic variation across the locus. The htSNPs were then genotyped in the nested breast cancer cases and controls from the Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study, and Women's Health Study cohorts ( 5,603 breast cancer cases and 7,480 controls). Results We found no association between any genetic variation ( SNP, haplotype, or the exon 1 CAG repeat) in the AR gene and risk of breast cancer, nor were any statistical interactions with known breast cancer risk factors observed. Conclusion Among postmenopausal Caucasian women, common variants of the AR gene are not associated with risk of breast cancer. C1 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Channing Lab, Boston, MA 02115 USA. Ctr Etud Polymorphisme Humain, Fdn Jean Dausset, F-75010 Paris, France. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. Epidemiol & Surveillance Res Amer Canc Soc, Atlanta, GA 30329 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Oxford, Canc Res UK Epidemiol Unit, Oxford OX3 7LF, England. Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, I-50131 Florence, Italy. Lund Univ, Dept Med, S-22100 Lund, Sweden. German Inst Human Nutr, Dept Epidemiol, D-14558 Nuthetal, Germany. Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA. MIT, Cambridge Ctr 7, Cambridge, MA 02142 USA. Harvard Univ, Broad Inst, Cambridge, MA 02142 USA. German Canc Res Ctr, Genom Epidemiol Grp, Div Mol Genet Epidemiol, D-69121 Heidelberg, Germany. NCI, Core Genotyping Facil, Gaithersburg, MD 20892 USA. Inst Gustave Roussy, INSERM, F-94805 Villejuif, France. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Int Agcy Res Canc, Nutr & Hormones Grp, F-69008 Lyon, France. Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96813 USA. Univ Tromso, Inst Community Med, N-9037 Tromso, Norway. Univ Utrecht, Med Ctr, Julius Ctr Hlth Sci & Primary Care, NL-3508 Utrecht, Netherlands. Univ London Imperial Coll Sci & Technol, Fac Med, Div Epidemiol Publ Hlth & Primary Care, London W2 1PG, England. Danish Canc Soc, Inst Canc Epidemiol, DK-2100 Copenhagen, Denmark. Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. RP Cox, DG (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Program Mol & Genet Epidemiol, 677 Huntington Ave, Boston, MA 02115 USA. EM dcox@hsph.harvard.edu RI Cox, David/A-2023-2009; Clavel-Chapelon, Francoise/G-6733-2014; Albanes, Demetrius/B-9749-2015; Colditz, Graham/A-3963-2009; OI Cox, David/0000-0002-2152-9259; Colditz, Graham/0000-0002-7307-0291; PALLI, Domenico/0000-0002-5558-2437 NR 49 TC 31 Z9 31 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 5 AR R54 DI 10.1186/bcr1602 PG 9 WC Oncology SC Oncology GA 121PI UT WOS:000243169100007 PM 16987421 ER PT J AU Crawford, NPS Ziogas, A Peel, DJ Hess, J Anton-Culver, H Hunter, KW AF Crawford, NPS Ziogas, A Peel, DJ Hess, J Anton-Culver, H Hunter, KW TI Germline polymorphisms in SIPA1 are associated with metastasis and other indicators of poor prognosis in breast cancer SO BREAST CANCER RESEARCH LA English DT Article ID GTPASE-ACTIVATING PROTEIN; RAP1 ACTIVATION; CELL-ADHESION; PROGRESSION; CANDIDATE; MOUSE; SPA-1; GENE; IDENTIFICATION; EXPRESSION AB Introduction There is growing evidence that heritable genetic variation modulates metastatic efficiency. Our previous work using a mouse mammary tumor model has shown that metastatic efficiency is modulated by the GTPase-activating protein encoded by Sipa1 ('signal-induced proliferation-associated gene 1'). The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) within the human SIPA1 gene are associated with metastasis and other disease characteristics in breast cancer. Method The study population (n=300) consisted of randomly selected non-Hispanic Caucasian breast cancer patients identified from a larger population-based series. Genomic DNA was extracted from peripheral leukocytes. Three previously described SNPs within SIPA1 (one within the promoter [-313G>A] and two exonic [545C>T and 2760G>A]) were characterized using SNP-specific PCR. Results The variant 2760G>A and the -313G>A allele were associated with lymph node involvement (P=0.0062 and P=0.0083, respectively), and the variant 545C>T was associated with estrogen receptor negative tumors (P=0.0012) and with progesterone negative tumors (P=0.0339). Associations were identified between haplotypes defined by the three SNPs and disease progression. Haplotype 3 defined by variants -313G>A and 2760G>A was associated with positive lymph node involvement (P=0.0051), and haplotype 4 defined by variant 545C>T was associated with estrogen receptor and progesterone receptor negative status (P=0.0053 and P=0.0199, respectively). Conclusion Our findings imply that SIPA1 germline polymorphisms are associated with aggressive disease behavior in the cohort examined. If these results hold true in other populations, then knowledge of SIPA1 SNP genotypes could potentially enhance current staging protocols. C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92717 USA. RP Hunter, KW (reprint author), NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [CA 58860-09, CA58860, R01 CA058860, U01 CA058860, Z01 CP010146-06] NR 31 TC 71 Z9 73 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 2 AR R16 DI 10.1186/bcr1389 PG 9 WC Oncology SC Oncology GA 039HX UT WOS:000237297700011 PM 16563182 ER PT J AU Dimitrakakis, C Zhou, J Wang, J Matyakhina, L Mezey, E Wood, JXY Wang, D Bondy, C AF Dimitrakakis, C Zhou, J Wang, J Matyakhina, L Mezey, E Wood, JXY Wang, D Bondy, C TI Co-expression of estrogen receptor-alpha and targets of estrogen receptor action in proliferating monkey mammary epithelial cells SO BREAST CANCER RESEARCH LA English DT Article ID EXPRESSION; BREAST; TESTOSTERONE; ESTRADIOL; MYC AB Introduction Failure to detect co-expression of estrogen receptor-alpha (ER alpha) and proliferation 'markers' such as Ki67 in human mammary epithelium led to the view that estrogen acts indirectly to stimulate mammary epithelial proliferation. The mitotic index was so low in prior studies, however, that transient co-expression of ER alpha and Ki67 during the cell cycle could have been below detection limits. Methods Immunohistochemistry was used on mammary tissue sections from estrogen treated rhesus monkeys to investigate co-expression of ER alpha and the proliferation antigen Ki67. Using the same methods, we investigated the cell localization of proteins involved in estrogen-induced proliferation, including cyclin D1, stromal cell-derived factor (SDF)-1, and MYC. Results ER alpha was co-expressed with the proliferation marker Ki67 as well as with SDF-1, MYC and cyclin D1 in mammary epithelial cells from estrogen-treated monkeys. Conclusion ER alpha is expressed in proliferating mammary epithelial cells together with the estrogen-induced proteins MYC, cyclin D1 and SDF-1, consistent with a direct mitogenic action by estrogen in primate mammary epithelium. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD 20892 USA. RP Bondy, C (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM bondyc@mail.nih.gov NR 10 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 1 AR R10 DI 10.1186/bcr1374 PG 4 WC Oncology SC Oncology GA 039HV UT WOS:000237297500019 PM 16417658 ER PT J AU Martin, RCG Ahn, J Nowell, SA Hein, DW Doll, MA Martini, BD Ambrosone, CB AF Martin, Robert C. G. Ahn, Jiyoung Nowell, Susan A. Hein, David W. Doll, Mark A. Martini, Benjamin D. Ambrosone, Christine B. TI Association between manganese superoxide dismutase promoter gene polymorphism and breast cancer survival SO BREAST CANCER RESEARCH LA English DT Article ID GASTRIC-CANCER; TRANSGENIC MICE; EXPRESSION; MNSOD; RISK; ESOPHAGEAL; CHEMOSENSITIVITY; CARDIOMYOPATHY; MITOCHONDRIA; ANTIOXIDANTS AB Background Manganese superoxide dismutase (MnSOD) plays a critical role in the detoxification of mitochondrial reactive oxygen species, constituting a major cellular defense mechanism against agents that induce oxidative stress. A genetic polymorphism in the mitochondrial targeting sequence of this gene has been associated with increased cancer risk and survival in breast cancer. This base pair transition (- 9 T > C) leads to a valine to alanine amino acid change in the mitochondrial targeting sequence. A polymorphism has also been identified in the proximal region of the promoter (- 102 C> T) that alters the recognition sequence of the AP-2 transcription factor, leading to a reduction in transcriptional activity. The aim of our study was to investigate possible associations of the - 102 C> T polymorphism with overall and relapse-free breast cancer survival in a hospital-based case-only study. Materials and methods The relationship between the MnSOD - 102 C> T polymorphism and survival was examined in a cohort of 291 women who received chemotherapy and/or radiotherapy for incident breast cancer. The MnSOD - 102 C> T genotype was determined using a TaqMan allele discrimination assay. Patient survival was evaluated according to the MnSOD genotype using Kaplan-Meier survival functions. Hazard ratios were calculated from adjusted Cox proportional hazards modeling. All statistical tests were two-sided. Results In an evaluation of all women, there was a borderline significant reduction in recurrence-free survival with either one or both variant alleles (CT + TT) when compared with patients with wild-type alleles ( CC) ( odds ratio, 0.65; 95% confidence interval, 0.42 - 1.01). When the analysis was restricted to patients receiving radiation therapy, there was a significant reduction in relapse-free survival in women who were heterozygous for the MnSOD - 102 genotype ( relative risk, 0.40; 95% confidence interval, 0.18 - 0.86). Similarly, when the homozygous and heterozygous variant genotypes were combined, there remained a significant reduction in relapse-free survival in this group ( hazard ratio, 0.42; 95% confidence interval, 0.20 - 0.87). Conclusion The MnSOD - 102 variant allele appears to be associated with an improved recurrence-free survival in all patients, and more dramatically in subjects who received adjuvant radiation therapy. C1 Univ Louisville, Sch Med, Dept Surg, Div Surg Oncol, Louisville, KY 40292 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Louisville, Sch Med, James Graham Brown Canc Ctr, Louisville, KY 40292 USA. RP Martin, RCG (reprint author), Univ Louisville, Sch Med, Dept Surg, Div Surg Oncol, Louisville, KY 40292 USA. EM Robert.martin@louisville.edu RI Hein, David/A-9707-2008 FU NCI NIH HHS [CA34627, R01 CA034627, R01 CA034627-21] NR 34 TC 14 Z9 15 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2006 VL 8 IS 4 AR R45 DI 10.1186/bcr1532 PG 9 WC Oncology SC Oncology GA 087UI UT WOS:000240767500019 PM 16859522 ER PT J AU Anderson, WF Matsuno, RK Yang, X Sherman, ME Garcia-Closas, M AF Anderson, W. F. Matsuno, R. K. Yang, X. Sherman, M. E. Garcia-Closas, M. TI Risk factor- and age-specific interactions suggest different etiologies for early-onset and late-onset types of breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S228 EP S228 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101232 ER PT J AU Arun, B Valero, V Logan, C Rivera, E Brewster, A Green, M Buzdar, A Browne, D Hortobagyi, GN Sneige, N AF Arun, B. Valero, V. Logan, C. Rivera, E. Brewster, A. Green, M. Buzdar, A. Browne, D. Hortobagyi, G. N. Sneige, N. TI Random periareolar fine needle aspiration compared to ductal lavage for tissue acquisition in short-term breast cancer chemoprevention studies. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 MD Anderson Canc Ctr, Houston, TX USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S54 EP S54 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100155 ER PT J AU Baehner, FL Habel, LA Quesenberry, CP Capra, A Tang, G Paik, S Wolmark, N Watson, D Shak, S AF Baehner, F. L. Habel, L. A. Quesenberry, C. P. Capra, A. Tang, G. Paik, S. Wolmark, N. Watson, D. Shak, S. TI Quantitative RT-PCR analysis of ER and PR by oncotype DX indicates distinct and different associations with prognosis and prediction of tamoxifen benefit. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Kaiser Permanente, Oakland, CA USA. NSABP, Pittsburgh, PA USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S20 EP S20 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100059 ER PT J AU Chamberlain, CS Schmelze, KH Anderson, JR Khan, SA Dooley, WC Krontiras, H Browne, D Kimler, BF Fabian, CJ AF Chamberlain, C. S. Schmelze, K. H. Anderson, J. R. Khan, S. A. Dooley, W. C. Krontiras, H. Browne, D. Kimler, B. F. Fabian, C. J. TI High risk women report minimal pain rating score with random periareolar fine needle aspirations compared to ductal lavage. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. No Univ Chicago, Chicago, IL USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Alabama, Birmingham, AL USA. Natl Canc Inst, Bethesda, MD USA. RI Dooley, William/E-7660-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S54 EP S55 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100156 ER PT J AU Christov, K Grubbs, C Lubet, R AF Christov, K. Grubbs, C. Lubet, R. TI Altered cell proliferation and apoptosis as biomarkers for identifying preventive/therapeutic agents against chemically induced mammary cancers. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Illinois, Chicago, IL USA. Univ Alabama, Birmingham, AL USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S58 EP S58 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100166 ER PT J AU Cohen, EJ Schreiner, J Tyler, J Deering, MJ Grama, LM Duggan, B Laird, JI Bhatia, V Hogarth, M Lieberman, M Esserman, LJ Park, JW AF Cohen, E. J. Schreiner, J. Tyler, J. Deering, M. J. Grama, L. M. Duggan, B. Laird, J., I Bhatia, V Hogarth, M. Lieberman, M. Esserman, L. J. Park, J. W. TI BreastCancerTrials.org: feasibility of an online, patient-centered, clinical trial matching service. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Davis, Davis, CA 95616 USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S96 EP S97 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100279 ER PT J AU Dookeran, KA Gao, X Wang, Y Lukaszczyk, B DeLaTorre, R Roman, G Ferrer, K Sekosan, M McCaskill-Stevens, W Zaren, HA AF Dookeran, K. A. Gao, X. Wang, Y. Lukaszczyk, B. DeLaTorre, R. Roman, G. Ferrer, K. Sekosan, M. McCaskill-Stevens, W. Zaren, H. A. TI p53 gene mutations in African-American women with breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Illinois, Chicago, IL USA. Stroger Hosp Cook Cty, Chicago, IL USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S145 EP S145 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100420 ER PT J AU Ford, LG AF Ford, L. G. TI Can we prevent breast cancer? Results of phase III clinical trials and beyond. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S4 EP S4 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100013 ER PT J AU Hwang, ESS Miglioretti, DL Lahiff, M Barbash-Ballard, R Kerlikowske, K AF Hwang, E-S S. Miglioretti, D. L. Lahiff, M. Barbash-Ballard, R. Kerlikowske, K. TI Breast density as a predictor of invasive events after treatment for ductal carcinoma in situ. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Grp Hlth Ctr Hlth Sci, Seattle, WA USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S15 EP S15 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100044 ER PT J AU Julian, B Fourchotte, V Anderson, S Mamounas, T Costantino, JP Boudros, E Wolmark, N AF Julian, B. Fourchotte, V Anderson, S. Mamounas, T. Costantino, J. P. Boudros, E. Wolmark, N. TI Predictive factors that identify patients not requiring a sentinel node biopsy: Continued analysis of the NSABP B-32 sentinel node trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 NSABP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S80 EP S81 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100233 ER PT J AU Julian, T Anderson, S Fourchotte, V Zieger, S Mamounas, E Bear, H Costantino, J Wolmark, N AF Julian, T. Anderson, S. Fourchotte, V Zieger, S. Mamounas, E. Bear, H. Costantino, J. Wolmark, N. TI Is invasive lobular breast cancer a prognostic factor for neoadjuvant chemotherapy response and long term outcomes? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 NSABP, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S146 EP S146 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100423 ER PT J AU Kaufman, PA Mayer, M Paik, S Ulcickas, YM Yardley, D Tan-Chiu, E Brufsky, A Rugo, H Tripathy, D Thomas, E Dolezal, M AF Kaufman, P. A. Mayer, M. Paik, S. Ulcickas, Yood M. Yardley, D. Tan-Chiu, E. Brufsky, A. Rugo, H. Tripathy, D. Thomas, E. Dolezal, M. TI RegistHER: trastuzumab-based taxane or vinorelbine treatment selection in patients with HER2/neu-positive metastatic breast cancer: patient characteristics and preliminary outcomes. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Patient Advocate, New York, NY USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Yale Univ, Sch Med, New Haven, CT USA. EpiSource LLC, New Haven, CT USA. Sarah Cannon Canc Ctr, Nashville, TN USA. Florida Canc Ctr, Tamarac, FL USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Genentech Inc, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S102 EP S103 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100296 ER PT J AU Kim, C Tang, G Baehner, FL Watson, D Costantino, JP Paik, S Shak, S Wolmark, N AF Kim, C. Tang, G. Baehner, F. L. Watson, D. Costantino, J. P. Paik, S. Shak, S. Wolmark, N. TI A comparison of estrogen receptor (ER) measurement by three methods in node negative, estrogen receptor (ER) positive breast cancer: ligand binding (LB), immunohistochemistry (IHC), and quantitative RT-PC. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 NSABP, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S162 EP S163 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101037 ER PT J AU Korde, L Zujewski, J McShane, L Lukes, L Lebowitz, P Finney, R Hunter, K AF Korde, L. Zujewski, J. McShane, L. Lukes, L. Lebowitz, P. Finney, R. Hunter, K. TI Gene expression profiling to predict response to neoadjuvant docetaxel and capecitabine for breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S137 EP S138 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100398 ER PT J AU Levine, PH Young, HA Hafi, M Tao, G Devesas, SS Davies-Cole, J Adade, A Kidane, G AF Levine, P. H. Young, H. A. Hafi, M. Tao, G. Devesas, S. S. Davies-Cole, J. Adade, A. Kidane, G. TI The role of race and poverty in determining breast cancer patterns in the District of Columbia. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 George Washington Univ, Washington, DC USA. Natl Canc Inst, Bethesda, MD USA. Dept Hlth, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S145 EP S146 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100421 ER PT J AU Lubet, RA Ruppert, MJ Juliana, MM Lobo-Ruppert, SM Grubbs, CJ AF Lubet, R. A. Ruppert, M. J. Juliana, M. M. Lobo-Ruppert, S. M. Grubbs, C. J. TI Use of dimethylbenzanthracene (DMBA) to facilitate carcinogenesis in virgin female FVB mice expressing MMTV-Neu or MMTV-Neu/p53 knock-out. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Natl Canc Inst, Bethesda, MD USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S58 EP S59 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100168 ER PT J AU Portera, CC Yang, SX Wedam, SB Nguyen, D Vatas, U Takikita, M Hewitt, SM Liewehr, DJ Steinberg, SM Sherman, M Levine, PH Swain, SM AF Portera, C. C. Yang, S. X. Wedam, S. B. Nguyen, D. Vatas, U. Takikita, M. Hewitt, S. M. Liewehr, D. J. Steinberg, S. M. Sherman, M. Levine, P. H. Swain, S. M. TI Evaluation of E-cadherin expression and lymphatic involvement in inflammatory breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Natl Canc Inst, NCTVL, DCTD, BSMS CCR, Bethesda, MD USA. George Washington Univ, Washington, DC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S177 EP S177 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101079 ER PT J AU Ravdin, PM Cronin, KA Howlander, N Chlebowski, RT Berry, DA AF Ravdin, P. M. Cronin, K. A. Howlander, N. Chlebowski, R. T. Berry, D. A. TI A sharp decrease in breast cancer incidence in the United States in 2003. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 NCI, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S6 EP S6 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100019 ER PT J AU Silverman, P Lyons, J Fu, P Remick, S Chen, H Ziats, N Wasman, J Hartman, P Jesberger, J Leeming, R Shenk, R Dumadag, L Overmoyer, B AF Silverman, P. Lyons, J. Fu, P. Remick, S. Chen, H. Ziats, N. Wasman, J. Hartman, P. Jesberger, J. Leeming, R. Shenk, R. Dumadag, L. Overmoyer, B. TI Randomized phase II study of docetaxel +/- bevacizumab for locally advanced unresectable breast cancer: Impact on biomarkers of angiogenesis. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Case Comprehens Canc Ctr, Cleveland, OH USA. Natl Canc Inst, Bethesda, MD USA. US Oncol, Torrington, CT USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S242 EP S242 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101271 ER PT J AU Steeg, PS Palmieri, D Bronder, JL Halverson, D Yoneda, T Weil, RJ Stark, AM Vortmeyer, AO Kurek, R Davis, S Meltzer, PS AF Steeg, P. S. Palmieri, D. Bronder, J. L. Halverson, D. Yoneda, T. Weil, R. J. Stark, A. M. Vortmeyer, A. O. Kurek, R. Davis, S. Meltzer, P. S. TI Microarray analysis of resected brain metastases of breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 NCI, Bethesda, MD 20892 USA. UT San Antonio, San Antonio, TX USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Schleswig Holstein, Ctr Med, Kiel, Germany. NINDS, Bethesda, MD 20892 USA. Univ Tubingen, Tubingen, Germany. NHGRI, Bethesda, MD 20892 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S207 EP S207 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101167 ER PT J AU Steeg, PS Palmieri, D Bronder, JL Herring, JL Halverson, D Vega-Valle, E Feigenbaum, L Yoneda, T Weil, RJ Stark, AM Vortmeyer, AO Kurek, R Aldape, K AF Steeg, P. S. Palmieri, D. Bronder, J. L. Herring, J. L. Halverson, D. Vega-Valle, E. Feigenbaum, L. Yoneda, T. Weil, R. J. Stark, A. M. Vortmeyer, A. O. Kurek, R. Aldape, K. TI Her-2 overexpression promotes the brain metastasis of breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Natl Canc Inst, Bethesda, MD USA. UT San Antonio, San Antonio, TX USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Schleswig Holstein, Ctr Med, Kiel, Germany. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. Univ Tubingen, Tubingen, Germany. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S206 EP S207 PG 2 WC Oncology SC Oncology GA 105QJ UT WOS:000242047101166 ER PT J AU Vogel, VG Costantino, JP Wickerham, DL Wolmark, N AF Vogel, V. G. Costantino, J. P. Wickerham, D. L. Wolmark, N. TI The effects of tamoxifen versus raloxifene on the risk of developing noninvasive breast cancer in the NSABP study of tamoxifen and raloxifene (STAR) P-2 trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 29th Annual San Antonio Breast Cancer Symposium CY DEC 14-17, 2006 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, Canc Therapy Res Ctr, Univ Texas, Hlth Sci Ctr C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. NSABP, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2006 VL 100 SU 1 BP S16 EP S16 PG 1 WC Oncology SC Oncology GA 105QJ UT WOS:000242047100047 ER PT J AU Koduri, S Goldhar, AS Vonderhaar, BK AF Koduri, S Goldhar, AS Vonderhaar, BK TI Activation of vascular endothelial growth factor (VEGF) by the ER-alpha variant, ER Delta 3 SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE estrogen; estrogen receptor alpha variant; transcription factor; vascular endothelial growth factor ID ESTROGEN-RECEPTOR-ALPHA; BREAST-CANCER CELLS; MESSENGER-RNAS; GENE-TRANSCRIPTION; TUMOR ANGIOGENESIS; FACTOR EXPRESSION; IDENTIFICATION; TISSUES; ESTRADIOL; CARCINOMA AB Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis in estrogen responsive tissues. Estrogen receptors alpha and beta regulate production of VEGF in both breast and endometrial cancer cells. Alternative splicing of ER-alpha mRNA generates a mixture of transcripts with various exon deletions in normal breast and breast cancer cells and some of these variants are overexpressed in breast cancer. We analyzed the role of exon-deleted variants of ER-alpha in regulation of VEGF production by simultaneous transient transfection of CHO and MDA-MB-231 cells with a VEGF promoter luciferase construct. Estrogen (10 nM) treatment resulted in a 6-fold increase in luciferase activity in cells transfected with the exon 3 deleted variant (ER Delta 3) compared to a 2-fold activity induction in cells transfected with wild type ER-alpha. Exon 5 and exon 7 deleted variants were unable to induce activation of the VEGF promoter. Using specific deletion constructs of the VEGF promoter linked to luciferase, we showed that the majority of activation by ER Delta 3 was restricted to the -70 to -88 bp fragment that contains two Sp1 sites. Site-directed mutagenesis of both Sp1 sites indicated that ER Delta 3 activates the VEGF promoter through interaction with Sp1 proteins. ER Delta 3, a variant frequently overexpressed in breast cancer, may significantly contribute to the production of VEGF thus resulting in enhanced tumor growth in vivo. C1 Georgetown Univ, Dept Oncol, Washington, DC USA. NCI, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, NIH, Bethesda, MD USA. RP Koduri, S (reprint author), Bioqual Inc, 9600 Med Ctr Dr, Rockville, MD 20850 USA. EM skoduri@bioqual.com NR 39 TC 11 Z9 15 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2006 VL 95 IS 1 BP 37 EP 43 DI 10.1007/s10549-005-9028-4 PG 7 WC Oncology SC Oncology GA 011ZC UT WOS:000235307000006 PM 16267616 ER PT J AU Brewster, AM Jorgensen, TJ Ruczinski, I Huang, HY Hoffman, S Thuita, L Newschaffer, C Lunn, RM Bell, D Helzlsouer, KJ AF Brewster, AM Jorgensen, TJ Ruczinski, I Huang, HY Hoffman, S Thuita, L Newschaffer, C Lunn, RM Bell, D Helzlsouer, KJ TI Polymorphisms of the DNA repair genes XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp): relationship to breast cancer risk and familial predisposition to breast cancer SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer risk; DNA repair genes; family history of breast cancer; imputation methods; nested case-control; XPD polymorphisms; XRCC1 polymorphisms ID IONIZING-RADIATION; SUSCEPTIBILITY; ADDUCTS; BLOOD; POPULATION; MODULATION; GENOTYPES; VARIANTS; DAMAGE; CELLS AB Family history is a risk factor for breast cancer and could be due to shared environmental factors or polymorphisms of cancer susceptibility genes. Deficient function of DNA repair enzymes may partially explain familial risk as polymorphisms of DNA repair genes have been associated, although inconsistently, with breast cancer. This population based case-control study examined the association between polymorphisms in XPD (Lys751Gln) and XRCC1 (Arg399Gln and Arg194Trp) genes, and breast cancer. Breast cancer cases (n=321) and controls (n=321) were matched on age and menopausal status. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). The analysis was conducted omitting observations with missing data, and by using imputation methods to handle missing data. No significant association was observed between the XPD 751Gln/Lys (OR 1.37, 95% CI 0.96-1.96) and Gln/Gln genotypes (OR 1.08, 95% CI 0.62-1.86) (referent Lys/Lys), XRCC1 399Arg/Gln (OR 1.48, 95% CI 0.92-2.38) and Gln/Gln genotypes (1.11, 95% CI 0.67-1.83) (referent Arg/Arg) or the XRCC1 Arg/Trp and Trp/Trp genotypes (OR 1.12, 95% CI 0.69-1.83) (referent Arg/Arg) and breast cancer. In multivariate analysis, the adjusted odds ratios for the XPD and XRCC1 399 polymorphisms increased and became statistically significant, however, were attenuated when imputation methods were used to handle missing data. There was no interaction with family history. These results indicate that these polymorphisms in XPD and XRCC1 genes are only weakly associated with breast cancer. Without imputation methods for handling missing data, a statistically significant association was observed between the genotypes and breast cancer, illustrating the potential for bias in studies that inadequately handle missing data. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Unit 1360, Houston, TX 77230 USA. Georgetown Univ, Med Ctr, Dept Radiat Med, Washington, DC 20007 USA. Johns Hopkins Univ, Sch Med, Dept Biostat, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Dept Epidemiol, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NIEHS, Toxicol Operat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Genom Sect, Res Triangle Pk, NC 27709 USA. St Johns Mercy Med Ctr, Prevent Res Ctr, Baltimore, MD USA. RP Brewster, AM (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Unit 1360, POB 301439, Houston, TX 77230 USA. EM abrewster@mdanderson.org FU NCI NIH HHS [CA074841, F33 CA09817-01, K12-CA01709, P50CA88843]; NIA NIH HHS [5U01AG018033] NR 26 TC 35 Z9 36 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2006 VL 95 IS 1 BP 73 EP 80 DI 10.1007/s10549-005-9045-3 PG 8 WC Oncology SC Oncology GA 011ZC UT WOS:000235307000010 PM 16319991 ER PT J AU Irwin, ML Aiello, EJ McTiernan, A Baumgartner, RN Baumgartner, KB Bernstein, L Gilliland, FD Ballard-Barbash, R AF Irwin, ML Aiello, EJ McTiernan, A Baumgartner, RN Baumgartner, KB Bernstein, L Gilliland, FD Ballard-Barbash, R TI Pre-diagnosis physical activity and mammographic density in breast cancer survivors SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE body fat; breast cancer; exercise; obesity; weight ID POSTMENOPAUSAL WOMEN; BODY-MASS; RISK; TRIAL; ASSOCIATION; EXERCISE; PATTERNS; ESTROGEN; HEALTH AB Purpose. To investigate the association between physical activity (PA) and mammographic density in the year before diagnosis in a population-based sample of 474 women diagnosed with stage 0-IIIA breast cancer and enrolled in the Health, Eating, Activity, and Lifestyle Study. Methods. We collected information on PA during an interview administered at a baseline visit scheduled within the first year after diagnosis. Participants recalled the type, duration, and frequency of different PAs for the year prior to their diagnosis. Dense area and percent density were estimated, from mammograms imaged approximately I year before diagnosis, as a continuous measure using a computer-assisted software program. Analysis of covariance methods were used to obtain mean density across PA tertiles adjusted for confounders. We stratified analyses by menopausal status and body mass index (BMI) because these factors strongly influence density. Results. We observed a statistically significant decline in mammographic dense area (p for trend = 0.046) and percent density (p for trend = 0.026) with increasing level of sports/recreational PA in postmenopausal women with a BMI >= 30 kg/m(2). Conversely, in premenopausal women with a BMI < 30 kg/m(2), we observed a statistically significant increase in percent density with increasing level of sports/recreational PA (p for trend = 0.037). Conclusions. Both mammographic dense area and percent density are inversely related to level of sports/recreational PA in obese postmenopausal women. Increasing PA among obese postmenopausal women may be a reasonable intervention approach to reduce mammographic density. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ New Mexico, Canc Res & Treatment Ctr, Dept Internal Med, Albuquerque, NM 87131 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA USA. Natl Canc Inst, Div Canc Control & Populat Sci, Appl Res Program, Bethesda, MD USA. RP Irwin, ML (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, POB 208034, New Haven, CT 06520 USA. EM melinda.irwin@yale.edu FU NCI NIH HHS [N01 PC067010, N01 CN005228, N01-CN-05228, N01-CN-75036-20, T32 CA09661, N01 PC035138-22, T32 CA009661]; NCRR NIH HHS [M01-RR-0997, M01-RR-00037, M01 RR000997, M01 RR000037] NR 25 TC 24 Z9 24 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD JAN PY 2006 VL 95 IS 2 BP 171 EP 178 DI 10.1007/s10549-005-9063-1 PG 8 WC Oncology SC Oncology GA 034XV UT WOS:000236965100011 PM 16319988 ER PT J AU Owens, BM Hawley, TS Spain, LM Kerkel, KA Hawley, RG AF Owens, BM Hawley, TS Spain, LM Kerkel, KA Hawley, RG TI TLX1/HOX11-mediated disruption of primary thymocyte differentiation prior to the CD4(+)CD8(+) double-positive stage SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE TLX1/HOX11 oncogene; T-cell acute lymphoblastic leukaemia; differentiation arrest; double-negative thymocytes; fetal thymic organ culture ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; HEMATOPOIETIC STEM-CELLS; RECEPTOR-DEFICIENT MICE; IMMATURE THYMOCYTES; HOMEOBOX GENE; ALLELIC EXCLUSION; PROGENITOR CELLS; GAMMA-CHAIN; INK4A LOCUS AB The TLX1/HOX11 homeobox gene is frequently activated in T-cell acute lymphoblastic leukaemia (T-ALL) by the t(10; 14)(q24; q11) and t(7; 10)(q35; q24) chromosomal translocations or by as yet unknown transcriptional mechanisms in the absence of 10q24 cytogenetic abnormalities. Almost all TLX1(+) T-ALLs exhibit a CD4(+) CD8(+) doublepositive (DP) phenotype. To investigate the role of TLX1 as an initiating oncogene in T- ALL pathogenesis, we assessed the consequences of retroviral vector-directed TLX1 expression during the differentiation of murine and human thymocytes in fetal thymic organ cultures. Interestingly, enforced expression of TLX1 disrupted the differentiation of murine fetal liver precursors and human cord blood CD34(+) stem/progenitor cells prior to the DP thymocyte stage. Although differentiation arrest was associated with an increased percentage of apoptotic thymocytes, it could only be partially bypassed by coexpression of transgenic BCL2. Mutation of the invariant asparagine residue at position 51 of the homeodomain - which is required for efficient DNA binding - released the block, consistent with the notion that TLX1 inhibits thymocyte differentiation and promotes T- cell oncogenesis by functioning as a transcription factor. The relevance of these findings is discussed in the context of activating NOTCH1 mutations and the other genetic lesions implicated in the multistep transformation process of TLX1+ T- ALL. C1 George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Grad Program Mol & Cellular Oncol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Flow Cytometry Core Facil, Washington, DC 20037 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Hawley, RG (reprint author), George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Grad Program Mol & Cellular Oncol, 2300 I St NW, Washington, DC 20037 USA. EM rghawley@gwu.edu FU NCRR NIH HHS [R24 RR016209, R24RR16209]; NHLBI NIH HHS [R01HL65519, R01 HL065519, R01 HL066305, R01 HL066305-05, R01HL66305] NR 73 TC 16 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2006 VL 132 IS 2 BP 216 EP 229 DI 10.1111/j.1365-2141.2005.05850.x PG 14 WC Hematology SC Hematology GA 991SW UT WOS:000233835000010 PM 16398656 ER PT B AU Gong, JD Jensen, G Bhirde, A Yu, X Munge, B Patel, V Kim, S Gutkind, JS Papadimitrakopoulos, F Rusling, JF AF Gong, Joseph D. Jensen, Gary Bhirde, Ashwin Yu, Xin Munge, Bernard Patel, Voymesh Kim, SangNyon Gutkind, J. Silvio Papadimitrakopoulos, Fotios Rusling, James F. GP IEEE COMPUTER SOC TI Single-walled carbon-nanotube forest immunosensor for amplified detection of cancer biomarkers SO BSN 2006: International Workshop on Wearable and Implantable Body Sensor Networks, Proceedings LA English DT Proceedings Paper CT International Workshop on Wearable and Implantable Body Sensor Networks CY APR 03-05, 2006 CL MIT, Cambridge, MA SP EMB, IEEE CAS Soc HO MIT ID SYSTEMS BIOLOGY; PROTEOMICS AB Prostate Specific Antigen (PSA) is a major biomarker used clinically in the detection of prostate cancer. Current commercial immunoassays for detection of this biomarker rely on spectroscopic absorbance and electrochemiluminescence which are able to detect as low as 0.03 ng/mL of PSA within 100 mu L of serum. In this paper a novel amplified electrochemical technique for detection of Prostate specific antigen will be described. This electrochemical approach is a highly sensitive method that can have detection limit of 0.004 ng/mL in only 10 mu L of serum, a mass detection limit 75 times lower than current commercial techniques. This highly sensitive, low cost and fast detection method not only allows for detection of cancer biomarkers in serum, but also in tissue and cells. Moreover, immunoassay arrays based on this methodology will be highly promising for application in large-scale clinical screening and point-of-care diagnostics. Characterization of the anti-PSA amplification tag in this amplification system using TEM, AFM, SEM, and CE will also be described. C1 Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06032 USA. Salve Regina Univ, Dept Chem, Newport, RI 02840 USA. NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. Univ Connecticut, Inst Sci Mat, Storrs, CT 06269 USA. RP Gong, JD (reprint author), Univ Connecticut, Dept Chem, 55 N Eagleville Rd, Storrs, CT 06269 USA. NR 12 TC 1 Z9 1 U1 0 U2 2 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-2547-4 PY 2006 BP 203 EP 207 PG 5 WC Computer Science, Cybernetics; Engineering, Biomedical; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BEE18 UT WOS:000236909800050 ER PT J AU Karasik, D Kiel, DP Kiely, DK Cupples, LA Wilson, PWF O'Donnell, CJ Felson, DT AF Karasik, D Kiel, DP Kiely, DK Cupples, LA Wilson, PWF O'Donnell, CJ Felson, DT TI Abdominal aortic calcification and exostoses at the hand and lumbar spine: The Framingham Study SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE vascular calcification; exostosis; osteophyte ID BONE MORPHOGENETIC PROTEIN; CORONARY-HEART-DISEASE; DISC DEGENERATION; BACK-PAIN; RADIOGRAPHIC FEATURES; PHYSICAL-ACTIVITY; OSTEOARTHRITIS; PROGRESSION; RISK; ATHEROSCLEROSIS AB Bony proliferation (exostoses) and vascular calcification are common in elderly men and women, but it is unclear whether they have a common etiology. Lateral lumbar and hand radiographs were obtained (1967-1970) in 777 men and 1,241 women (mean age 59, range 47-80 years) from the Framingham Heart Study. Each group of hand exostoses, specifically apiostoses (tufting), enthesophytes, and osteophytes, was graded on a scale of 0-3 (absent to severe) and summed across phalanges of digits 2-5. Anterior lumbar osteophytes were assessed in intervertebral spaces T12-L5 and abdominal aortic calcification (AAC) at lumbar segments L1-L4. Information on age, sex, body mass index, smoking, alcohol consumption, physical activity, systolic blood pressure, total cholesterol level, diabetes, and estrogen replacement therapy in women was obtained at the time of radiography and adjusted for in multivariate analyses. We used multivariable logistic regression models to assess the relationship between AAC (dependent variable) and exostoses for each sex. Multivariable adjusted logistic regression revealed a significant association between increased anterior lumbar osteophytes and prevalent AAC in men [odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.1-1.3 per unit increase in osteophytes] and in women (OR = 1.25, 95% CI 1.1-1.4). There also was an inverse association between enthesophytes and AAC in women only (OR = 0.82, 95% CI 0.73-0.92). Apiostoses were weakly associated with AAC in men only. Hand osteophytes were not associated with AAC. In conclusion, in this cross-sectional study, anterior lumbar osteophytes and AAC occurred in the same individuals after adjustment for age and other covariates. In general, hand exostoses were not associated with aortic calcification. C1 Hebrew SeniorLife, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Med Univ S Carolina, Dept Endocrinol Diabet & Med Genet, Charleston, SC 29425 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Clin Epidemiol, Boston, MA 02118 USA. RP Karasik, D (reprint author), Hebrew SeniorLife, Boston, MA USA. EM karasik@mail.hrca.harvard.edu OI Felson, David/0000-0002-2668-2447; Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530 FU NHLBI NIH HHS [N01-HC-25195]; NIAMS NIH HHS [AR47785, R01 AR41398] NR 49 TC 14 Z9 14 U1 6 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD JAN PY 2006 VL 78 IS 1 BP 1 EP 8 DI 10.1007/s00223-005-0054-3 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 003NV UT WOS:000234689800001 PM 16397734 ER PT J AU Rozhansky, F Chen, MH Cox, MC Dahut, W Figg, WD D'Amico, AV AF Rozhansky, F Chen, MH Cox, MC Dahut, W Figg, WD D'Amico, AV TI Prostate-specific antigen velocity and survival for patients with hormone-refractory metastatic prostate carcinoma SO CANCER LA English DT Article DE cytostatic therapy; prostate carcinoma; survival; prostate-specific antigen ID PHASE-II TRIAL; RADICAL RETROPUBIC PROSTATECTOMY; LEUKEMIA GROUP-B; PROGNOSTIC FACTORS; CLINICAL-TRIALS; CANCER; THERAPY; ESTRAMUSTINE; DOCETAXEL; BONE AB BACKGROUND. The authors investigated whether prostate-specific antigen (PSA) velocity was associated significantly with the time to death after randomization among patients with hormone-refractory metastatic prostate carcinoma (HRMPC) who were treated with cytotoxic, cytotatic, or combination therapy. METHODS. The study cohort included 213 men with HRMPC who were treated on 3 prospective, randomized Phase II studies between February 1996 and October 2001. Cox regression analysis was used to evaluate whether there was a significant association between PSA velocity and the time to death after randomization, controlling for treatment and known prognostic factors. RESULTS. increasing PSA velocity was associated significantly with shorter survival after randomization (P = 0.005) controlling for treatment and known prognostic factors. The adjusted hazard ratic, for death was 1.8 (95% confidence interval [95% CI], 1.3-2.5; P = 0.0004) for men who had a PSA velocity > 0.0 ng/mL per month compared with men who had a PSA velocity : 0.0 ng/mL per month. Estimates of Survival 2 years after randomization for these men were 16% (95% CI, 7-25%) and 44% (95% CI, 35-53%), respectively. CONCLUSIONS. PSA velocity was associated significantly with the length of survival among men with HRMPC who received cytotoxic, cytostatic, or combination therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02215 USA. EM adamico@lroc.harvard.edu RI Figg Sr, William/M-2411-2016 NR 34 TC 20 Z9 21 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 JAN 1 PY 2006 VL 106 IS 1 BP 63 EP 67 DI 10.1002/cncr.21576 PG 5 WC Oncology SC Oncology GA 998ZK UT WOS:000234358200009 PM 16333854 ER PT J AU Dahut, WL Lakhani, NJ Gulley, JL Arlen, PM Kohn, EC Kotz, H McNally, D Parr, A Nguyen, D Yang, SX Steinberg, SM Venitz, J Sparreboom, A Figg, WD AF Dahut, WL Lakhani, NJ Gulley, JL Arlen, PM Kohn, EC Kotz, H McNally, D Parr, A Nguyen, D Yang, SX Steinberg, SM Venitz, J Sparreboom, A Figg, WD TI Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors SO CANCER BIOLOGY & THERAPY LA English DT Article DE 2-methoxyestradiol (2ME2); phase I; clinical trial; angiogenesis; solid tumor; apoptosis ID CANCER RESISTANCE PROTEIN; CLEAR-CELL CARCINOMA; BREAST-CANCER; MAMMALIAN METABOLITE; P-GLYCOPROTEIN; GROWTH; ANGIOGENESIS; OVARY; BIOAVAILABILITY; CHEMOTHERAPY AB Purpose: To determine the maximum-tolerated dose (MTD) and toxicity profile of the novel anticancer agent, 2-methoxyestradiol (2ME2) administered orally, in patients with solid tumors. Materials and methods: Twenty patients with refractory solid tumors were enrolled. 2ME2 was given orally starting at 400 mg bid with dose escalation until 3000 mg bid. Tumor biopsies were taken before and after starting the drug to assess for microvessel density by CD 31 and cell proliferation by Ki67 immunohistochemistry. Serial plasma samples collected up to 50 hours after first single oral dose for characterization of pharmacokinetics, were analyzed using liquid chromatography tandem mass-spectrometry. Results: Eleven men and nine women received 2ME2 at dose levels of 400 mg bid (n=3), 800 mg bid (n=3), 1600 mg bid (n=6), 2200 mg bid (n=5) and 3000 mg bid (n=3). There were no dose limiting toxicities, therefore the MTD was not defined. There was one episode of grade 4 angioedema in the 1600 mg bid dose level 38 days into 2ME2 treatment. Other toxicities were mild to moderate. A patient with clear cell carcinoma of the ovary had a partial response at 1600 mg bid dose level lasting over three years. Conclusion: MTD for 2ME2 was not reached at dose of 3000 mg bid. The trial was closed due to extremely low plasma concentrations of 2ME2 relative to the doses administered. 2ME2 treatment had no effect on microvessel density (CD31 immunostaining) and cell proliferation (Ki-67 immunostaining). A new formulation of 2ME2 with improved bioavailability is currently being developed. C1 NCI, Med Oncol Clin Res Unit, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Dept Pharmaceut, Richmond, VA USA. RP Figg, WD (reprint author), 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 32 TC 102 Z9 106 U1 1 U2 9 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JAN PY 2006 VL 5 IS 1 BP 22 EP 27 PG 6 WC Oncology SC Oncology GA 022GW UT WOS:000236044500012 PM 16357512 ER PT J AU Kuo, YH Landrette, SF Heilman, SA Perrat, PN Garrett, L Liu, PP Le Beau, MM Kogan, SC Castilla, LH AF Kuo, YH Landrette, SF Heilman, SA Perrat, PN Garrett, L Liu, PP Le Beau, MM Kogan, SC Castilla, LH TI Cbf beta-SMMHC induces distinct abnormal myeloid progenitors able to develop acute myeloid leukemia SO CANCER CELL LA English DT Article ID HEMATOPOIETIC STEM-CELLS; FETAL LIVER HEMATOPOIESIS; AML1-ETO FUSION GENE; CORE-BINDING-FACTOR; TRANSCRIPTION-FACTOR; ADULT HEMATOPOIESIS; EMBRYONIC LETHALITY; MURINE MODEL; IN-VIVO; CBFB-MYH11 AB The acute myeloid leukemia (AML)-associated CBF beta-SMMHC fusion protein impairs hematopoietic differentiation and predisposes to leukemic transformation. The mechanism of leukemia progression, however, is poorly understood. In this study, we report a conditional Cbfb-MYH11 knockin mouse model that develops AML with a median latency of 5 months. Cbf beta-SMMHC expression reduced the multilineage repopulation capacity of hematopoietic stem cells (HSCs) while maintaining their numbers under competitive conditions. The fusion protein induced abnormal myeloid progenitors (AMPs) with limited proliferative potential but leukemic predisposition similar to that of HSCs in transplanted mice. In addition, Cbf beta-SMMHC blocked megakaryocytic maturation at the CFU-Meg to megakaryocyte transition. These data show that a leukemia oncoprotein can inhibit differentiation and proliferation while not affecting the maintenance of long-term HSCs. C1 Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Castilla, LH (reprint author), Univ Massachusetts, Sch Med, Program Gene Funct & Express, Worcester, MA 01605 USA. EM lucio.costilla@umassmed.edu RI Kuo, Ya-Huei/A-4475-2012; Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [CA84221, F32CA101571, R01-CA096983] NR 47 TC 62 Z9 65 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2006 VL 9 IS 1 BP 57 EP 68 DI 10.1016/j.ccr.2005.12.014 PG 12 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 004ZA UT WOS:000234790100010 PM 16413472 ER PT J AU Rao, K Alper, O Opheim, KE Bonnet, G Wolfe, K Bryant, E Larivee, SO Porter, P McDougall, JK AF Rao, Krishna Alper, Oezge Opheim, Kent E. Bonnet, George Wolfe, Kristine Bryant, Eileen Larivee, Siobhan O'Hara Porter, Peggy McDougall, James K. TI Cytogenetic characterization and H-ras associated transformation of immortalized human mammary epithelial cells SO CANCER CELL INTERNATIONAL LA English DT Article AB Introduction: Immortalization is a key step in malignant transformation, but immortalization alone is insufficient for transformation. Human mammary epithelial cell (HMEC) transformation is a complex process that requires additional genetic changes beyond immortalization and can be accomplished in vitro by accumulation of genetic changes and expression of H-ras. Methods: HMEC were immortalized by serial passaging and transduction with the catalytic subunit of the human telomerase gene (hTERT). The immortalized cells were passaged in vitro and studied by a combination of G-banding and Spectral Karyotyping (SKY). H-ras transduced, hTERT immortalized cells were cloned in soft agar and injected into nude mice. Extensive analysis was performed on the tumors that developed in nude mice, including immunohistochemistry and western blotting. Results: Immortal HMEC alone were not tumorigenic in gamma-irradiated nude mice and could not grow in soft agar. Late passage hTERT immortalized HMEC from a donor transduced with a retroviral vector containing the mutant, autoactive, human H-ras61L gene acquired anchorage independent growth properties and the capacity for tumorigenic growth in vivo. The tumors that developed in the nude mice were poorly differentiated epithelial carcinomas that continued to overexpress ras. These cells were resistant to doxorubicin mediated G1/S phase arrest but were sensitive to treatment with a farnesyltransferase inhibitor. Conclusion: Some of the cytogenetic changes are similar to what is observed in premalignant and malignant breast lesions. Despite these changes, late passage immortal HMEC are not tumorigenic and could only be transformed with overexpression of a mutant H-ras oncogene. C1 [Rao, Krishna] So Illinois Univ, Sch Med, Inst Canc, Springfield, IL 62794 USA. [Alper, Oezge] Natl Inst Neurol Disorders, NIH, Bethesda, MD 20892 USA. [Opheim, Kent E.] Childrens Hosp & Reg Med Ctr, Dept Labs, Seattle, WA 98105 USA. [Bonnet, George] Cytogenet Studio Inc, Cambridge, MA 02138 USA. [Bryant, Eileen] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Bryant, Eileen; Larivee, Siobhan O'Hara] Seattle Canc Care Alliance, Seattle, WA 98109 USA. [Porter, Peggy; McDougall, James K.] Fred Hutchinson Canc Res Ctr, Canc Biol Program, Seattle, WA 98109 USA. [Porter, Peggy; McDougall, James K.] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. RP Rao, K (reprint author), So Illinois Univ, Sch Med, Inst Canc, POB 19678, Springfield, IL 62794 USA. EM krao@siumed.edu; alpero@ninds.nih.gov; opheim@u.washington.edu; gbonnet@cytostudio.com; opheim@u.washington.edu; ebryant@fhcrc.org; sohara@seattlecca.org; pporter@fhcrc.org; mcdouga@fhcrc.org NR 38 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2867 J9 CANCER CELL INT JI Cancer Cell Int. PY 2006 VL 6 AR 15 DI 10.1186/1475-2867-6-15 PG 11 WC Oncology SC Oncology GA V24IV UT WOS:000208405000015 PM 16729884 ER PT J AU Verschoyle, RE Greaves, P Cai, H Arndt, B Broggini, M D'Incalci, M Riccio, E Doppalapudi, R Kapetanovic, IM Steward, WP Gescher, AJ AF Verschoyle, RE Greaves, P Cai, H Arndt, B Broggini, M D'Incalci, M Riccio, E Doppalapudi, R Kapetanovic, IM Steward, WP Gescher, AJ TI Preliminary safety evaluation of the putative cancer chemopreventive agent tricin, a naturally occurring flavone SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE flavonoids; chemoprevention; genotoxicity; toxicity ID SUPPRESSES MAMMARY-CANCER; COLON-CANCER; QUERCETIN; GENISTEIN; INHIBITION; NEOPLASIA; CELLS; RATS AB Purpose: Naturally occurring flavonoids such as quercetin and genistein possess cancer chemopreventive properties in experimental models. However, adverse effects such as their mutagenicity confound their potential clinical usefulness. Furthermore in leukaemia cells some flavonoids cleave the breakpoint cluster region of the mixed lineage leukaemia (MLL) gene as a consequence of inhibition of topoisomerase II. The choice of flavonoids to be developed as cancer chemopreventive agents depends crucially on their safety. Here, we explored safety aspects of the novel flavone tricin, a constituent of rice bran and other grass species, which has, recently been found to interfere with murine gastrointestinal carcinogenesis. Methods: Evidence of pathological or morphological changes in liver, lung, heart, spleen, kidney, adrenal gland, pancreas or thymus tissues was studied in mice which received tricin, genistein or quercetin 1,000 mg/kg daily by the oral route on five consecutive days. The ability of tricin (50 mu M) to cleave the MLL gene was studied in human leukaemia cells by Southern blotting, and its effect on human topoisomerase 11 activity was investigated in incubations with supercoiled DNA. The mutagenicity of tricin was assessed in the Salmonella/Escherichia coli assay, and its clastogenicity was adjudged by chromosomal aberrations in Chinese hamster ovary cells and occurrence of micronuclei in bone marrow erythrocytes in Swiss-Webster mice. Results: Neither tricin, quercetin, or genistein caused pathological or morphological changes in any of the murine tissues studied. Tricin (50 mu M) failed to cause MLL gene breakage, and it inhibited topoisomerase II only at 500 mu M, but not at 10, 50 or 100 mu M. Tricin lacked genotoxic properties in the systems studied here. Conclusion: The results tentatively suggest that tricin may be considered safe enough for clinical development as a cancer chemopreventive agent. C1 Univ Leicester, Dept Canc Studies, RKCSB, LRI, Leicester LE2 7LX, Leics, England. Univ Leicester, MRC, Toxicol Unit, Leicester LE1 9HN, Leics, England. Univ Munich, Dr Von Haunerschen Kinderspital, D-80337 Munich, Germany. Mario Negri Inst Pharmacol Res, Dept Oncol, I-20157 Milan, Italy. SRI Int, Biosci Div, Toxicol & Pharmacol Lab, Menlo Pk, CA 94025 USA. NCI, NIH, Div Canc Prevent, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP Gescher, AJ (reprint author), Univ Leicester, Dept Canc Studies, RKCSB, LRI, Leicester LE2 7LX, Leics, England. EM agl5@le.ac.uk OI BROGGINI, MASSIMO/0000-0002-8138-9358; D'Incalci, Maurizio/0000-0001-8784-1360 NR 17 TC 32 Z9 35 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2006 VL 57 IS 1 BP 1 EP 6 DI 10.1007/s00280-005-0039-y PG 6 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 990XG UT WOS:000233776100001 PM 16001171 ER PT J AU Berman, JJ Albores-Saavedra, J Bostwick, D DeLellis, R Eble, J Hamilton, SR Hruban, RH Mutter, GL Page, D Rohan, T Travis, W Henson, DE AF Berman, Jules J. Albores-Saavedra, Jorge Bostwick, David DeLellis, Ronald Eble, John Hamilton, Stanley R. Hruban, Ralph H. Mutter, George L. Page, David Rohan, Thomas Travis, William Henson, Donald E. TI Precancer: A conceptual working definition results of a consensus conference SO CANCER DETECTION AND PREVENTION LA English DT Review DE precancer; premalignant; in situ carcinoma; severe dysplasia; atypical hyperplasia; intraepithelial neoplasia; incipient neoplasia; preinvasive; classification; definition; cytologic atypia; immunosuppression; regression; chronologic precedence; taxonomy; criteria ID INTRAEPITHELIAL NEOPLASIA; CHEMOPREVENTIVE AGENTS; PRENEOPLASTIC LESIONS; CANCER; CLASSIFICATION; PREVENTION; HYPERPLASIA; PROGRESSION; DYSPLASIA; PANCREAS AB Background: Precancers are lesions that precede the appearance of invasive cancers. The successful prevention or treatment of precancers has the potential to eliminate deaths due to cancer. Methods: A National Cancer Institute-sponsored Conference on Precancer was convened on November 8-9, 2004, at The George Washington University Medical Center, Washington, DC. A definition of precancers was developed over 2 days of Conference discussions. Results: The following five criteria define a precancer: (1) evidence must exist that the precancer is associated with an increased risk of cancer; (2) when a precancer progresses to cancer, the resulting cancer arises from cells within the-precancer; (3) a precancer differs from the normal tissue from which it arises; (4) a precancer differs from the cancer into which it develops, although it has some, but not all, of the molecular and phenotypic properties that characterize the cancer; (5) there is a method by which the precancer can be diagnosed. Conclusions: The Conference participants developed a general definition for precancers that would provide a consistent and clinically useful way of distinguishing precancers from all other types of lesions. It was recognized that many precancerous lesions may not meet this strict definition, but the group felt it was necessary to define criteria that will help standardize clinical and biological studies. Furthermore, a set of defining criteria for putative precancer lesions will permit pathologists to build a diagnostically useful taxonomy of precancers based on specified clinical and biological properties. Precancers thus characterized - can be classified into clinically relevant sub-groups based on shared properties (i.e. biomarkers, oncogenes, common metabolic pathways, responses to therapy, etc.). Publications that introduce newly described precancer entities should describe how each of the five defining criteria apply. This manuscript reviews the proposed definition of precancers and suggests how pathologists, oncologists and cancer researchers may determine when these criteria are satisfied. (c) 2006 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 Louisiana State Univ, Dept Pathol, Hlth Sci Ctr, Shreveport, LA 71130 USA. NCI, Canc Diag Program, NIH, Bethesda, MD 20892 USA. Bostwick Labs, Richmond, VA USA. Brown Univ, Dept Pathol, Providence, RI 02912 USA. Indiana Sch Med, Dept Pathol, Indianapolis, IN USA. Univ Texas, MD Anderson Canc Ctr, Div Pathol & Lab Med, Houston, TX 77030 USA. Johns Hopkins Univ Hosp, Dept Pathol, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD 21287 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Vanderbilt Univ, Ctr Med, Dept Pathol, Nashville, TN 37232 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. George Washington Univ, Inst Canc, Washington, DC USA. RP Albores-Saavedra, J (reprint author), Louisiana State Univ, Dept Pathol, Hlth Sci Ctr, 1501 Kings Highway, Shreveport, LA 71130 USA. EM jalbor@lsuhsc.edu RI Mutter, George/C-5819-2009 NR 37 TC 28 Z9 34 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2006 VL 30 IS 5 BP 387 EP 394 DI 10.1016/j.cdp.2006.09.002 PG 8 WC Oncology SC Oncology GA 115VR UT WOS:000242762400001 PM 17079091 ER PT J AU Lim, MJ Wang, XW AF Lim, Mi Jung Wang, Xin Wei TI Nucleophosmin and human cancer SO CANCER DETECTION AND PREVENTION LA English DT Review DE nucleophosmin; phosphorylation; centrosome duplication; Ran/CRM1; nucleophosmin structure; CDK1/cyclin E; DNA replication; acute myeloid leukernia; myelodysplastic syndromes; cell proliferation ID NUCLEOLAR PROTEIN B23; NUCLEAR-MATRIX PROTEIN; ACUTE MYELOGENOUS LEUKEMIA; TUMOR-SUPPRESSOR PROTEIN; CELL-CYCLE; PHOSPHORYLATION SITE; CENTROSOME DUPLICATION; LOCALIZATION SIGNALS; RIBOSOME BIOGENESIS; PHOSPHOPROTEIN B23 AB Nucleophosmin (NPM) is a nucleolar phosphoprotein that shuttles between the nucleus and cytoplasm during the cell cycle. NPM has several interacting partners and diverse cellular functions, including the processing of ribosomal RNA, centrosome duplication and the control of cellular processes to ensure genomic stability. Subcellular localization of NPM appears to be strongly correlated with NPM functions and cell proliferation. NPM is phosphorylated mainly at its central acidic domain by several upstream kinases, and its phosphorylation appears to be involved in regulating its functions in ribosome biogenesis and centrosome duplication. Recent studies suggest that NPM may act as a licensing factor to maintain proper centrosome duplication and that the Ran/CRM1 nucleocytoplasmic complex regulates local trafficking of NPM to centrosomes by interacting through its nuclear export sequence motif. Here, we provide a brief overview of NPM functions and its roles in human carcinogenesis, and discuss our recent findings related to the potential mechanisms underlying its regulation of centrosome duplication. (c) 2006 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 NCI, Lab Human Carcinogenesis, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Lab Human Carcinogenesis, Canc Res Ctr, NIH, 37 Convent Dr,MSC 4258,Bldg 37,Room 3044A, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005793-11] NR 66 TC 72 Z9 86 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2006 VL 30 IS 6 BP 481 EP 490 DI 10.1016/j.cdp.2006.10.008 PG 10 WC Oncology SC Oncology GA 122AI UT WOS:000243197700001 PM 17113241 ER PT J AU Spurdle, AB Antoniou, AC Kelemen, L Holland, H Peock, S Cook, MR Smith, PL Greene, MH Simard, J Plourde, M Southey, MC Godwin, AK Beck, J Miron, A Daly, MB Santella, RM Hopper, JL John, EM Andrulis, IL Durocher, F Struewing, JP Easton, DF Chenevix-Trench, G AF Spurdle, AB Antoniou, AC Kelemen, L Holland, H Peock, S Cook, MR Smith, PL Greene, MH Simard, J Plourde, M Southey, MC Godwin, AK Beck, J Miron, A Daly, MB Santella, RM Hopper, JL John, EM Andrulis, IL Durocher, F Struewing, JP Easton, DF Chenevix-Trench, G TI The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID RECEPTOR COACTIVATOR AIB1; OVARIAN-CANCER; GENE; POLYMORPHISM; ESTROGEN; FAMILY; SUSCEPTIBILITY; AMPLIFICATION; EXPRESSION; POSITIVITY AB This is by far the largest study of its kind to date, and further suggests that AIB1 does not play a substantial role in modifying the phenotype of BRCA1 and BRCA2 carriers. The AIB1 gene encodes the AIB1/SRC-3 steroid hormone receptor coactivator, and amplification of the gene and/or protein occurs in breast and ovarian tumors. A CAG/CAA repeat length polymorphism encodes a stretch of 17 to 29 glutamines in the HR-interacting carboxyl-terminal region of the protein which is somatically unstable in tumor tissues and cell lines. There is conflicting evidence regarding the role of this polymorphism as a modifier of breast cancer risk in BRCA1 and BRCA2 carriers. To further evaluate the evidence for an association between AM glutamine repeat length and breast cancer risk in BRCA1 and BRCA2 mutation carriers, we have genotyped this polymorphism in 1,090 BRCA1 and 661 BRCA2 mutation carriers from Australia, Europe, and North America. There was no evidence for an increased risk associated with AIB1 glutamine repeat length. Given the large sample size, with more than adequate power to detect previously reported effects, we conclude that the AM glutamine repeat does not substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers. C1 Queensland Inst Med Res, Canc & Cell Biol Div, Brisbane, Qld 4029, Australia. Univ Cambridge, Canc Res UK Genet Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England. NCI, Clin Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. Univ Quebec, Canc Genom Lab, Oncol & Mol Endocrinol Res Ctr, Ctr Hosp, Quebec City, PQ, Canada. Univ Laval, Quebec City, PQ, Canada. Univ Melbourne, Ctr Genet Epidemiol, Parkville, Vic 3052, Australia. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Coriell Inst Med Res, Camden, NJ USA. Dana Farber Canc Inst, Boston, MA 02115 USA. No Calif Canc Ctr, Union City, CA USA. Univ Toronto, Dept Mol & Med Genet, Toronto, ON, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada. RP Spurdle, AB (reprint author), Queensland Inst Med Res, Canc & Cell Biol Div, PO Royal Brisbane Hosp, Brisbane, Qld 4029, Australia. EM Amanda.Spurdle@qimr.edu.au RI Struewing, Jeffery/C-3221-2008; Spurdle, Amanda/A-4978-2011; Andrulis, Irene/E-7267-2013; Struewing, Jeffery/I-7502-2013 OI Spurdle, Amanda/0000-0003-1337-7897; Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [CA 69638, CA-95-003, U01 CA069417, U01 CA069417-10]; NIEHS NIH HHS [P30 ES009089] NR 19 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2006 VL 15 IS 1 BP 76 EP 79 DI 10.1158/1055-9965.EPI-05-0709 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200015 PM 16434590 ER PT J AU Kirsh, VA Mayne, ST Peters, U Chatterjee, N Leitzmann, MF Dixon, LB Urban, DA Crawford, ED Hayes, RB AF Kirsh, VA Mayne, ST Peters, U Chatterjee, N Leitzmann, MF Dixon, LB Urban, DA Crawford, ED Hayes, RB TI A prospective study of lycopene and tomato product intake and risk of prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DIETARY CAROTENOIDS; FRUIT CONSUMPTION; PLASMA LYCOPENE; BETA-CAROTENE; RETINOL; FOODS; QUESTIONNAIRES; MECHANISMS; VEGETABLES; DATABASE AB Background: Dietary lycopene and tomato products may reduce risk of prostate cancer; however, uncertainty remains about this possible association. Methods: We evaluated the association between intake of lycopene and specific tomato products and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to investigate cancer early detection methods and etiologic determinants. Participants completed both a general risk factor and a 137-item food frequency questionnaire at baseline. A total of 1,338 cases of prostate cancer were identified among 29,361 men during an average of 4.2 years of follow-up. Results: Lycopene intake was not associated with prostate cancer risk. Reduced risks were also not found for total tomato servings or for most tomato-based foods. Statistically nonsignificant inverse associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.67-1.03 for >= 1 serving/wk versus < 0.5 serving/mo; P-trend = 0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P-trend = 0.12] and spaghetti/tomato sauce consumption (advanced prostate cancer: RR = 0.81, 95% Cl, 0.57-1.16 for >= 2 servings/wk versus < 1 serving/mo; P-trend = 0.31). Among men with a family history of prostate cancer, risks were decreased in relation to increased consumption of lycopene (P-trend = 0.04) and specific tomato-based foods commonly eaten with fat (spaghetti, P-trend = 0.12; pizza, P-trend = 0.15; lasagna, P-trend = 0.02). Conclusions: This large study does not support the hypothesis that greater lycopene/tomato product consumption protects from prostate cancer. Evidence for protective associations in subjects with a family history of prostate cancer requires further corroboration. C1 NCI, Div Canc Epidemiol & Genet, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NYU, Dept Nutr Food Studies & Publ Hlth, New York, NY USA. Univ Alabama, Dept Surg, Div Urol, Birmingham, AL 35294 USA. Univ Colorado, Div Urol Oncol, Aurora, CO USA. RP Hayes, RB (reprint author), NCI, Div Canc Epidemiol & Genet, Intramural Res Program, NIH,Dept Hlth & Human Serv, EPN 8114, Bethesda, MD 20892 USA. EM hayesr@mail.nih.gov OI Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS NR 55 TC 83 Z9 87 U1 0 U2 4 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 JAN PY 2006 VL 15 IS 1 BP 92 EP 98 DI 10.1158/1055-9965.EPI-05-0563 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200018 PM 16434593 ER PT J AU Taylor, JA Xu, ZL Kaplan, NL Morris, RW AF Taylor, JA Xu, ZL Kaplan, NL Morris, RW TI How well do HapMap haplotypes identify common haplotypes of genes? A comparison with haplotypes of 334 genes resequenced in the environmental genome project SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article AB One of the goals of the International HapMap Project is the identification of common haplotypes in genes. However, HapMap uses an incomplete catalogue of single nucleotide polymorphisms (SNPs) and might miss some common haplotypes. We examined this issue using data from the Environmental Genome Project (EGP) which resequenced 335 genes in 90 people, and thus, has a nearly complete catalogue of gene SNPs. The EGP identified a total of 45,243 SNPs, of which 10,780 were common SNPs (minor allele frequency >= 0.1). Using EGP common SNP genotype data, we identified 1,459 haplotypes with frequency >= 0.05 and we use these as "benchmark" haplotypes. HapMap release 16 had genotype information for 1,573 of 10,780 (15%) EGP common SNPs. Using these SNPs, we identified common HapMap haplotypes (frequency >= 0.05) in each of the four HapMap ethnic groups. To compare common HapMap haplotypes to EGP benchmark haplotypes, we collapsed benchmark haplotypes to the set of 1,573 SNPs. Ninety-eight percent of the collapsed benchmark haplotypes could be found as common HapMap haplotypes in one or more of the four HapMap ethnic groups. However, collapsing benchmark haplotypes to the set of SNPs available in HapMap resulted in a loss of haplotype information: 545 of 1,459 (37%) benchmark haplotypes were uniquely identified, and only 25% of genes had all their benchmark haplotypes uniquely identified. We resampled the EGP data to examine the effect of increasing the number of HapMap SNPs to 5 million, and estimate that similar to 40% of common SNPs in genes will be sampled and that half of the genes will have sufficient SNPs to identify all common haplotypes. This inability to distinguish common haplotypes of genes may result in loss of power when examining haplotype-disease association. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. RP Taylor, JA (reprint author), NIEHS, Mol Carcinogenesis Lab, MD A3-05,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI xu, zongli/0000-0002-9034-8902; taylor, jack/0000-0001-5303-6398 FU Intramural NIH HHS NR 10 TC 11 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 JAN PY 2006 VL 15 IS 1 BP 133 EP 137 DI 10.1158/1055-9965.EPI-05-0641 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200023 PM 16434598 ER PT J AU Franken, FH Pickworth, WB Epstein, DH Moolchan, ET AF Franken, FH Pickworth, WB Epstein, DH Moolchan, ET TI Smoking rates and topography predict adolescent smoking cessation following treatment with nicotine replacement therapy SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FAGERSTROM TOLERANCE QUESTIONNAIRE; TOBACCO SMOKING; DEPENDENCE; SMOKERS; ABSTINENCE; SYMPTOMS; YOUTH AB Establishing measurement invariance of tobacco addiction among adolescents remains challenging. In adult smoking cessation trials, poor outcome is predicted by high cigarette consumption and large puff volume at baseline. We examined the predictive value of pretreatment smoking rates and topography variables for abstinence outcomes among 66 adolescents enrolled in a 3-month smoking cessation trial using nicotine replacement and cognitive behavioral therapy. Pretreatment variables included cigarettes per day (CPD), puff volume, puff duration, and several youth-adapted Fagerstrom-derived questionnaire scores. Outcome measures included prolonged abstinence at end of treatment and point-prevalent abstinence 3 months after the end of the trial. Logistic regression controlling for treatment group showed that increases in baseline CPD (odds ratio, 1.438; 95% confidence interval, 1.051-1.967) and average puff volume (odds ratio, 1.168; 95% confidence interval, 1.030-1.326) predicted continued smoking at the end of treatment. Puff volume (P = 0.013), but not CPD, predicted abstinence at the 3-month follow-up. None of the youth-adapted Fagerstrom questionnaires predicted outcome on either abstinence measure. If confirmed in a larger sample, our findings suggest that puff topography, and possibly CPD, might predict cessation outcome better than Fagerstrom scores in adolescent smokers. C1 NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. Battelle Mem Inst, Ctr Publ Hlth Res, Baltimore, MD USA. Battelle Mem Inst, Ctr Evaluat, Baltimore, MD USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, Dept Hlth & Human Serv,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 24 TC 24 Z9 24 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2006 VL 15 IS 1 BP 154 EP 157 DI 10.1158/1055-9965.EPI-05-0167 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 005ZZ UT WOS:000234866200028 PM 16434603 ER PT J AU Sayers, TJ Murphy, WJ AF Sayers, TJ Murphy, WJ TI Combining proteasome inhibition with TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) for cancer therapy SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article; Proceedings Paper CT Conference on Progress in Vaccination Against Cancer CY SEP 22-25, 2004 CL Frendenstadt Lauterbad, GERMANY ID NF-KAPPA-B; TRAIL-MEDIATED APOPTOSIS; FADD-DEPENDENT APOPTOSIS; DEATH RECEPTOR 5; IN-VIVO; CELL-DEATH; TUMORICIDAL ACTIVITY; CHEMOTHERAPEUTIC-AGENTS; MONOCLONAL-ANTIBODIES; IONIZING-RADIATION AB Apoptosis has an essential role in embryogenesis, adult tissue homeostasis and cellular responses to stressful stimuli. Therefore, increased apoptosis is involved in the pathogenesis of various ischaemic, degenerative and immune disorders. Conversely, genetic aberration that results in a reduction or abolition of apoptosis can promote tumorigenesis and underlie the resistance of cancer cells to various genotoxic anticancer agents. Therefore, a detailed knowledge of the control of apoptotic pathways could aid in the rational design of effective therapeutics for a variety of human diseases including cancer. One major way to promote apoptosis involves signaling through members of the tumor necrosis factor (TNF) superfamily. On binding to their appropriate receptors, some TNF family members can promote caspase activation and apoptosis. Early studies on TNF indicated that a limited number of tumor cell lines could be induced to undergo apoptosis on exposure to TNF. Another member of the TNF family Fas ligand (FasL) is also known to induce apoptosis in a variety of tumor cells. Although TNF and FasL can efficiently induce apoptosis in a limited number of tumor cells, administration of either of these agents is associated with extreme toxicity. This toxicity has precluded further development of either TNF or FasL for cancer therapy. However, within the last 8 years another member of the TNF family, TNF-related apoptosis-inducing ligand (Apo2L/TRAIL) has been characterized, which induces apoptosis of a wider range of cancer cells than either TNF or FasL. Surprisingly, most normal non-transformed cells are quite resistant to the apoptotic effects of Apo2L/TRAIL. This selective toxicity for cancer cells is the basis for the current enthusiasm for Apo2L/TRAIL as a potential novel anticancer therapy. In this symposium report, we provide a brief overview of Apo2L/TRAIL, its receptors and their signaling pathways. We discuss findings on the antitumor effects of Apo2L/TRAIL alone or in combination with radiotherapy or chemotherapy. In addition, we present recent information from our groups concerning the possible therapeutic benefits of combining Apo2L/TRAIL with the proteasome inhibitor bortezomib. C1 NCI, Intramural Res Program, SAIC Frederick, Expt Immunol Lab,Ctr Canc Res, Frederick, MD 21702 USA. Nevada Canc Inst, Reno, NV USA. RP Sayers, TJ (reprint author), NCI, Intramural Res Program, SAIC Frederick, Expt Immunol Lab,Ctr Canc Res, Frederick, MD 21702 USA. EM sayers@mail.ncifcrf.gov RI Sayers, Thomas/G-4859-2015 FU NCI NIH HHS [CA102282]; PHS HHS [N01-C0-12400] NR 74 TC 67 Z9 73 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD JAN PY 2006 VL 55 IS 1 BP 76 EP 84 DI 10.1007/s00262-005-0676-3 PG 9 WC Oncology; Immunology SC Oncology; Immunology GA 993FJ UT WOS:000233939700010 PM 15864587 ER PT J AU Kolonin, MG Bover, L Sun, J Zurita, AJ Do, KA Lahdenranta, J Cardo-Vila, M Giordano, RJ Jaalouk, DE Ozawa, MG Moya, CA Souza, GR Staquicini, FI Kunyiasu, A Scudiero, DA Holbeck, SL Sausville, EA Arap, W Pasqualini, R AF Kolonin, MG Bover, L Sun, J Zurita, AJ Do, KA Lahdenranta, J Cardo-Vila, M Giordano, RJ Jaalouk, DE Ozawa, MG Moya, CA Souza, GR Staquicini, FI Kunyiasu, A Scudiero, DA Holbeck, SL Sausville, EA Arap, W Pasqualini, R TI Ligand-directed surface profiling of human cancer cells with combinatorial peptide libraries SO CANCER RESEARCH LA English DT Article ID MOLECULAR PHARMACOLOGY; EXPRESSION DATABASE; GROWTH-INHIBITION; PHAGE DISPLAY; SCREEN; TARGET; VASCULATURE; TRANSPORTER; RECEPTOR; GENES AB A collection of 60 cell lines derived from human tumors (NCI-60) has been widely explored as a tool for anticancer drug discovery. Here, we profiled the cell surface of the NCI-60 by high-throughput screening of a phage-displayed random peptide library and classified the cell lines according to the binding selectivity of 26,031 recovered tripeptide motifs. By analyzing selected cell-homing peptide motifs and their NCI-60 recognition patterns, we established that some of these motifs (a) are similar to domains of human proteins known as ligands for tumor cell receptors and (b) segregate among the NCI-60 in a pattern correlating with expression profiles of the corresponding receptors. We biochemically validated some of the motifs as mimic peptides of native ligands for the epidermal growth factor receptor. Our results indicate that ligand-directed profiling of tumor cell lines can select functional peptides from combinatorial libraries based on the expression of tumor cell surface molecules, which in turn could be exploited as "druggable" receptors in specific types of cancer. C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Natl Canc Inst, Dev Therapeut Program, Div Canc Treatment & Diag, NCI, Bethesda, MD USA. RP Pasqualini, R (reprint author), Univ Texas, MD Anderson Canc Ctr, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM warap@mdanderson.org; rpasqual@mdanderson.org RI Giordano, Ricardo/A-2074-2010; OI Giordano, Ricardo/0000-0001-8116-6771; Kolonin, Mikhail/0000-0002-3743-7869 FU NCI NIH HHS [P30 CA016672] NR 24 TC 55 Z9 57 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 34 EP 40 DI 10.1158/0008-5471CAN-05-2748 PG 7 WC Oncology SC Oncology GA 001JN UT WOS:000234529500006 PM 16397212 ER PT J AU Bera, TK Fleur, AS Lee, Y Kydd, A Hahn, K Popescu, NC Zimonjic, DB Lee, B Pastan, I AF Bera, TK Fleur, AS Lee, Y Kydd, A Hahn, K Popescu, NC Zimonjic, DB Lee, B Pastan, I TI POTE paralogs are induced and differentially expressed in many cancers SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER; GENE; TESTIS; CHROMOSOMES; IDENTIFICATION; CELLS AB To identify new antigens that are targets for the immunotherapy of prostate and breast cancer, we used expressed sequence tag and genomic databases and discovered POTE, a new primate-specific gene family. Each POTE gene encodes a protein that contains three domains, although the proteins vary greatly in size. The NH2-terminal domain is novel and has properties of an extracellular domain but does not contain a signal sequence. The second and third domains are rich in ankyrin repeats and spectrin-like helices, respectively. The protein encoded by POTE-21, the first family member discovered, is localized on the plasma membrane of the cell. In humans, 13 highly homologous paralogs are dispersed among eight chromosomes. The expression of POTE genes in normal tissues is restricted to prostate, ovary, testis, and placenta. A survey of several cancer samples showed that POTE was expressed in 6 of 6 prostate, 12 of 13 breast, 5 of 5 colon, 5 of 6 lung, and 4 of 5 ovarian cancers. To determine the relative expression of each POTE paralog in cancer and normal samples, we employed a PCR-based cloning and analysis method. We found that POTE-2 alpha, POTE-2 beta, POTE-2 gamma, and POTE-22 are predominantly expressed in cancers whereas POTE expression in normal tissues is somewhat more diverse. Because POTE is primate specific and is expressed in testis and many cancers but only in a few normal tissues, we conclude POTE is a new primate-specific member of the cancer-testis antigen family. It is likely that POTE has a unique role in primate biology. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, NIH, Room 5106,37 Convent Dr, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov FU Intramural NIH HHS NR 13 TC 29 Z9 32 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 52 EP 56 DI 10.1158/0008-5472.CAN-05-3014 PG 5 WC Oncology SC Oncology GA 001JN UT WOS:000234529500009 PM 16397215 ER PT J AU Reilly, KM Broman, KW Bronson, RT Tsang, S Loisel, DA Christy, ES Sun, ZH Diehl, J Munroe, DJ Tuskan, RG AF Reilly, KM Broman, KW Bronson, RT Tsang, S Loisel, DA Christy, ES Sun, ZH Diehl, J Munroe, DJ Tuskan, RG TI An imprinted locus epistatically influences Nstr1 and Nstr2 to control resistance to nerve sheath tumors in a neurofibromatosis type 1 mouse model SO CANCER RESEARCH LA English DT Article ID QUANTITATIVE TRAIT LOCI; HUMAN GRB10; GENOME; CANCER; GENES; NF1; SUSCEPTIBILITY; RHABDOMYOSARCOMA; RELAXATION; MUTATION AB Cancer is a complex disease in which cells acquire many genetic and epigenetic alterations. We have examined how three types of alterations, mutations in tumor suppressor genes, changes in an imprinted locus, and polymorphic loci, interact to affect tumor susceptibility in a mouse model of neurofibromatosis type 1 (NF1). Mutations in tumor suppressor genes such as TP53 and in oncogenes such as KRAS have major effects on tumorigenesis due to the central roles of these genes in cell proliferation and cell survival. Imprinted genes expressed from only one parental chromosome affect tumorigenesis if their monoallelic expression is lost or duplicated. Because imprinted loci are within regions deleted or amplified in cancer, the parental origin of genomic rearrangements could affect tumorigenesis. Gene polymorphisms can vary tumor incidence by affecting rate-limiting steps in tumorigenesis within tumor cells or surrounding stroma. In our mouse model of NF1, the incidence of tumors mutant for the tumor suppressor genes Nf1 and Trp53 is strongly modified by a linked imprinted locus acting epistatically on two unlinked polymorphic loci, Nstr1 and Nstr2. This interaction of an imprinted locus and polymorphic susceptibility loci has profound implications for human mapping studies where the parental contribution of alleles is often unknown. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. Sci Applicat Int Corp Frederick, Lab Mol Technol, Frederick, MD 21702 USA. Johns Hopkins Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Dana Farber Canc Ctr, Dept Pathol, Boston, MA USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. RP Reilly, KM (reprint author), NCI, Mouse Canc Genet Program, Room 32-31B,Bldg 560,W 7th St Ft Detrick,POB B, Frederick, MD 21702 USA. EM kreilly@ncifcrf.gov RI Loisel, Dagan/A-6671-2010 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400, Z01 BC010539-03] NR 44 TC 27 Z9 29 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 62 EP 68 DI 10.1158/0008-5472.CAN-05-1t8O PG 7 WC Oncology SC Oncology GA 001JN UT WOS:000234529500011 PM 16397217 ER PT J AU Zheng, SL Ju, JH Chang, BL Ortner, E Sun, JL Isaacs, SD Sun, JS Wiley, KE Liu, WN Zemedkun, M Walsh, PC Ferretti, J Gruschus, J Isaacs, WB Gelmann, EP Xu, JF AF Zheng, SL Ju, JH Chang, BL Ortner, E Sun, JL Isaacs, SD Sun, JS Wiley, KE Liu, WN Zemedkun, M Walsh, PC Ferretti, J Gruschus, J Isaacs, WB Gelmann, EP Xu, JF TI Germ-line mutation of NKX3.1 cosegregates with hereditary prostate cancer and alters the homeodomain structure and function SO CANCER RESEARCH LA English DT Article ID GENOMEWIDE LINKAGE ANALYSIS; DNA-BINDING; SUSCEPTIBILITY GENES; LUNG MORPHOGENESIS; SEQUENCE VARIANTS; PROTEIN FUNCTION; HOMEOBOX GENE; ASSOCIATION; EXPRESSION; FAMILIES AB NKX3.1, a gene mapped to 8p21, is a member of the NK class of homeodomain proteins and is expressed primarily in the prostate. NKX3.1 exerts a growth-suppressive and differentiating effect on prostate epithelial cells. Because of its known functions and its location within a chromosomal region where evidence for prostate cancer linkage and somatic loss of heterozygosity is found, we hypothesize that sequence variants in the NKX3.1 gene increase prostate cancer risk. To address this, we first resequenced the NKX3.1 gene in 159 probands of hereditary prostate cancer families recruited at Johns Hopkins Hospital; each family has at. least three first-degree relatives affected with prostate cancer. Twenty-one germ-line variants were identified in this analysis, including one previously L, described common nonsynonymous change (R52C), two novel rare nonsynonymous changes (A17T and T164A), and a novel common 18-bp deletion in the promoter. Overall, the germline variants were significantly linked to prostate cancer, with a peak heterogeneity logarithm of odds of 2.04 (P = 0.002) at the NKX3.1 gene. The rare nonsynonymous change, T164A, located in the homeobox domain of the gene, segregated with prostate cancer in a family with three affected brothers and one unaffected brother. Importantly, nuclear magnetic resonance solution structure analysis and circular dichroism studies showed this specific mutation to affect the stability of the homeodomain of the NKX3.1 protein and decreased binding to its cognate DNA recognition sequence. These results suggest that germ-line sequence variants in NKV3.1 may play a role in susceptibility to hereditary prostate cancer and underscore a role for NAX3.1 as a prostate cancer gatekeeper. C1 Wake Forest Univ, Ctr Human Genom, Winston Salem, NC 27109 USA. Georgetown Univ, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Georgetown Univ, Dept Med, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21205 USA. NHLBI, Biophys Chem Lab, Baltimore, MD 21205 USA. RP Isaacs, WB (reprint author), Johns Hopkins Univ, Sch Med, Dept Urol, 600 N Wolfe St,Marburg 115, Baltimore, MD 21287 USA. EM wisaacs@jhmi.edu FU NCI NIH HHS [CA89600, CA95052-01, CA58236, CA96854]; NIEHS NIH HHS [ES09888] NR 49 TC 31 Z9 32 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 69 EP 77 DI 10.1158/0008-5472.CAN-05-1550 PG 9 WC Oncology SC Oncology GA 001JN UT WOS:000234529500012 PM 16397218 ER PT J AU Lin, QC Clark, AB McCulloch, SD Yuan, T Bronson, RT Kunkel, TA Kucherlapati, R AF Lin, QC Clark, AB McCulloch, SD Yuan, T Bronson, RT Kunkel, TA Kucherlapati, R TI Increased susceptibility to UV-induced skin carcinogenesis in polymerase eta-deficient mice SO CANCER RESEARCH LA English DT Article ID PIGMENTOSUM VARIANT CELLS; THYMINE DIMER BYPASS; DNA-POLYMERASE; XERODERMA-PIGMENTOSUM; TRANSLESION SYNTHESIS; SOMATIC HYPERMUTATION; EXCISION-REPAIR; MUTATIONS; FIDELITY; REPLICATION AB Xeroderma pigmentosum variant (XPV) patients with mutations in the DNA polymerase eta (pol eta) gene are hypersensitive to sunlight and have greatly increased susceptibility to sunlight-induced skin cancer. Consistent with the ability of Pot eta to efficiently bypass UV light-induced cyclobutane pyrimidine dimers, XPV cells lacking Pot eta have diminished capacity to replicate UV-damaged DNA and are sensitive to UV light-induced killing and mutagenesis. To better understand these and other Pol eta functions, we generated Pot eta-deficient mice. Mice homozygous for a null mutation in pol eta are viable, fertile, and do not show any obvious spontaneous defects during the first year of life. However, fibroblasts derived from these mutant mice are sensitive to killing by exposure to UV light, and all Pot eta-deficient mice develop skin tumors after UV irradiation, in contrast to the wild-type littermate controls that did not develop such tumors. These results and biochemical studies of translesion synthesis by mouse Pol eta indicate that Pot eta-dependent bypass of cyclobutane pyrimidine dimers suppresses UV light-induced skin cancer in mice. Moreover, 37.5% of pol eta heterozygous mice also developed skin cancer during 5 months after a 5-month exposure to UV light, suggesting that humans who are heterozygous for mutations in pol eta may also have an increased risk of skin cancer. C1 Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, Boston, MA 02115 USA. Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. RP Kucherlapati, R (reprint author), Harvard Univ, Sch Med, Partners Healthcare Ctr Genet & Genom, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM rkucherlapati@partners.org NR 39 TC 56 Z9 58 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 87 EP 94 DI 10.1158/0008-5472.CAN-05-1862 PG 8 WC Oncology SC Oncology GA 001JN UT WOS:000234529500014 PM 16397220 ER PT J AU Muftuoglu, M Wong, HK Imam, SZ Wilson, DM Bohr, VA Opresko, PL AF Muftuoglu, M Wong, HK Imam, SZ Wilson, DM Bohr, VA Opresko, PL TI Telomere repeat binding factor 2 interacts with base excision repair proteins and stimulates DNA synthesis by DNA polymerase beta SO CANCER RESEARCH LA English DT Article ID HUMAN TELOMERES; OXIDATIVE STRESS; FLAP ENDONUCLEASE-1; MAMMALIAN TELOMERES; HELICASE ACTIVITY; BINDING-SITE; GGG SEQUENCE; MAJOR HUMAN; HUMAN POT1; TRF2 AB The ends of linear chromosomes are capped and protected by protein-DNA complexes termed telomeres. Consequences of telomere dysfunction include genomic instability that can contribute to neoplastic transformation and progression. Telomere binding proteins interact with numerous proteins involved in DNA repair, underscoring the importance of regulating DNA repair pathways at telomeres. Telomeric DNA is particularly susceptible to oxidative damage, and such damage is repaired primarily via the base excision repair (BER) pathway. Using a screen for potential interactions between telomere repeat binding factor 2 (TRF2) and proteins involved in BER of oxidized bases in vitro, we found that TRF2 physically bound DNA polymerase beta (Pol beta) and flap endonuclease 1 (FEN-1). The interactions with endogenous proteins in human cell extracts were confirmed by coimmunoprecipitation experiments. The primary binding sites for both Pol beta anti FEN-1 mapped to the TRF2 NH2-terminal and COOH-terminal domains. We further tested the ability of TRF2 to modulate BER protein partners individually on a variety of substrates in vitro. TRF2 stimulated Pol 0 primer extension DNA synthesis on telomeric and nontelomeric primer/template substrates, resulting in up to a 75% increase in the proportion of longer products. TRF2 also stimulated Pol beta strand displacement DNA synthesis in reconstituted BER reactions and increased the percent, of long-patch BER intermediates on both telomeric and nontelomeric substrates. Potential roles of TRF2 in cooperation with BER proteins for DNA repair pathways at telomeres, as well as other genomic regions, are discussed. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Opresko, PL (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Hlth, 100 Technol Dr,Cellom Bldg, Pittsburgh, PA 15260 USA. EM vbohr@nih.gov; popresko@eoh.pitt.edu OI Opresko, Patricia/0000-0002-6470-2189 NR 51 TC 40 Z9 42 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 113 EP 124 DI 10.1158/0008-5472.CAN-05-2742 PG 12 WC Oncology SC Oncology GA 001JN UT WOS:000234529500017 PM 16397223 ER PT J AU Montaner, S Sodhi, A Ramsdell, AK Martin, D Hu, JD Sawai, ET Gutkind, JS AF Montaner, S Sodhi, A Ramsdell, AK Martin, D Hu, JD Sawai, ET Gutkind, JS TI The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor as a therapeutic target for the treatment of Kaposi's sarcoma SO CANCER RESEARCH LA English DT Article ID PARACRINE NEOPLASIA; ENDOTHELIAL-CELLS; RECEPTOR; EXPRESSION; ACTIVATION; SECRETION; PATHWAYS; KINASE; VIRUS; ORF74 AB The Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a G protein-coupled receptor (vGPCR) that has been implicated in the initiation of Kaposi's sarcoma, identifying vGPCR as an attractive target for preventing Kaposi's sarcoma. However, as only a fraction of cells in advanced Kaposi's sarcoma lesions express vGPCR, it is unclear whether this unique viral oncogene contributes to Kaposi's sarcoma progression. We therefore set out to determine whether the few cells that express vGPCR in established tumors represent an appropriate therapeutic target for the treatment of patients with preexisting Kaposi's sarcoma. To this end, we generated endothelial cell lines stably expressing vGPCR or key KSHV latently expressed proteins (vCyclin, vFlip, and LANA1). The endothelial cell line expressing vGPCR was rendered sensitive to treatment with the nucleoside analogue ganciclovir by using a bicistronic construct coexpressing the herpes simplex virus 1 thymidine kinase. S.c. injection into nude mice with mixed-cell populations formed tumors that approximate the ratio of vGPCR-expressing and KSHV latent gene-expressing cells. These mice were then treated with ganciclovir to specifically target only the vGPCR-expressing cells. Surprisingly, despite the expression of KSHV latent genes in the vast majority of tumor cells, specifically targeting only the few vGPCR-expressing cells in established tumors resulted in tumor regression. Moreover, we observed an increase in apoptosis of latent gene-expressing cells after the pharmacologic deletion of the vGPCR-expressing cells. These findings indicate that vGPCR may play a key role in Kaposi's sarcoma progression and provide experimental justification for developing molecular-based therapies specifically targeting vGPCR and its effectors for the treatment of Kaposis sarcoma patients. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Diagnost Sci & Pathol, College Pk, MD 20742 USA. Univ Maryland, Greenebaum Canc Ctr, College Pk, MD 20742 USA. Univ Calif Davis, Dept Comparat Pathol, Davis, CA 95616 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 211, Bethesda, MD 20892 USA. EM SMontaner@umaryland.edu; sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 FU Intramural NIH HHS NR 20 TC 59 Z9 59 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 168 EP 174 DI 10.1158/0008-5472.CAN-05-1026 PG 7 WC Oncology SC Oncology GA 001JN UT WOS:000234529500023 PM 16397229 ER PT J AU Grade, M Ghadimi, BM Varma, S Simon, R Wangsa, D Barenboim-Stapleton, L Liersch, T Becker, H Ried, T Difilippantonio, MJ AF Grade, M Ghadimi, BM Varma, S Simon, R Wangsa, D Barenboim-Stapleton, L Liersch, T Becker, H Ried, T Difilippantonio, MJ TI Aneuploidy-dependent massive deregulation of the cellular transcriptome and apparent divergence of the Wnt/beta-catenin signaling pathway in human rectal carcinomas SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; COLORECTAL-CANCER; COPY NUMBER; BREAST-CANCER; TUMORIGENESIS; WNT; REVEALS; ADENOMA; TUMORS; MODEL AB To identify genetic alterations underlying rectal carcinogenesis, we used global gene expression profiling of a series of 17 locally advanced rectal adenocarcinomas and 20 normal rectal mucosa biopsies on oligonucleotide arrays. A total of 351 genes were differentially expressed (P < 1.0e-7) between normal rectal mucosa and rectal carcinomas, 77 genes had a > 5-fold difference, and 85 genes always had at least a 2-fold change in all of the matched samples. Twelve genes satisfied all three of these criteria. Altered expression of genes such as PTGS2 (COX-2), WNT1, TGFB1, VEGF, and MYC was confirmed, whereas our data for other genes, like PPARD and LEF1, were inconsistent with previous reports. In addition, we found deregulated expression of many genes whose involvement in rectal carcinogenesis has not been reported. By mapping the genomic imbalances in the tumors using comparative genomic hybridization, we could show that DNA copy number gains of recurrently aneuploid chromosome arms 7p, 8q, 13q, l8q, 20p, and 20q correlated significantly with their average chromosome arm expression profile. Taken together, our results show that both the high-level, significant transcriptional deregulation of specific genes and general modification of the average transcriptional activity of genes residing on aneuploid chromosomes coexist in rectal adenocarcinomas. C1 NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Univ Gottingen, Med Ctr, Dept Gen Surg, D-3400 Gottingen, Germany. RP Difilippantonio, MJ (reprint author), NCI, Genet Branch, Canc Res Ctr, NIH, Room 1408,Bldg 50,50 S Dr, Bethesda, MD 20892 USA. EM difilipm@mail.nih.gov RI Varma, Sudhir/N-8763-2014 OI Varma, Sudhir/0000-0002-4096-4782 FU Intramural NIH HHS [Z99 CA999999] NR 35 TC 33 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2006 VL 66 IS 1 BP 267 EP 282 DI 10.1158/0008-5472.CAN-05-2533 PG 16 WC Oncology SC Oncology GA 001JN UT WOS:000234529500034 PM 16397240 ER PT J AU Homma, N Tamura, G Honda, T Matsumoto, Y Nishizuka, S Kawata, S Motoyama, T AF Homma, N Tamura, G Honda, T Matsumoto, Y Nishizuka, S Kawata, S Motoyama, T TI Spreading of methylation within RUNX3 CpG island in gastric cancer SO CANCER SCIENCE LA English DT Article ID TUMOR-RELATED GENES; PROMOTER METHYLATION; DNA METHYLATION; DAP-KINASE; EXPRESSION; MUCOSA; AGE; HYPERMETHYLATION; SUPPRESSOR; EPITHELIA AB RUNX3 is a novel tumor suppressor gene that is frequently silenced by promoter hypermethylation in gastric cancer. The methylation status of multiple regions within the RUNX3 promoter CpG island (3478 bp) was examined in gastric cancer cell lines, primary gastric cancers and non-neoplastic gastric mucosa to clarify how methylation spreads within the CpG island. The critical regions for RUNX3 silencing were evaluated by analysis of cell lines. The most 5' region of the CpG island was methylated in 90% (9/10) of gastric cancer cell lines, 96% (43/45) of primary gastric cancers and in 96% (43/45) of non-neoplastic gastric mucosa. The frequencies of methylation were less near the transcription start site and were 40% (4/10) in cell lines, 53% (24/45) in primary gastric cancers and 11% (5/45) in non-neoplastic gastric mucosa, where methylation was proven to be critical for gene silencing. Thus, hypermethylation initially occurs at the most 5' region of the RUNX3 CpG island and spreads to the transcription start site before ultimately shutting down RUNX3 mRNA expression. The detection of hypermethylation at multiple regions within the RUNX3 CpG island may be useful in the diagnosis and risk assessment of gastric cancer. C1 Yamagata Univ, Sch Med, Dept Pathol, Yamagata 9909585, Japan. Yamagata Univ, Sch Med, Dept Gastroenterol, Yamagata 9909585, Japan. NCI, Mol Therapeut Program, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. RP Tamura, G (reprint author), Yamagata Univ, Sch Med, Dept Pathol, 2-2-2 Iidanishi, Yamagata 9909585, Japan. EM gtamura@med.id.yamagata-u.ac.jp NR 26 TC 45 Z9 53 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD JAN PY 2006 VL 97 IS 1 BP 51 EP 56 DI 10.1111/j.1349-7006.2006.00133.x PG 6 WC Oncology SC Oncology GA 998VR UT WOS:000234348500008 PM 16367921 ER PT J AU King, KE Ponnamperuma, RM Gerdes, MJ Tokino, T Yamashita, T Baker, CC Weinberg, WC AF King, KE Ponnamperuma, RM Gerdes, MJ Tokino, T Yamashita, T Baker, CC Weinberg, WC TI Unique domain functions of p63 isotypes that differentially regulate distinct aspects of epidermal homeostasis SO CARCINOGENESIS LA English DT Article ID SQUAMOUS-CELL CARCINOMAS; HAY-WELLS-SYNDROME; P53 TARGET GENES; COLLAGEN XVII; LUNG-CANCER; SKIN TUMORS; CRABP-II; EXPRESSION; KERATINOCYTES; PROTEIN AB p63 is critical for squamous development and exists as multiple isotypes of two subclasses, TA and Delta N. Delta Np63 isotypes can antagonize transcription by TAp63 and p53, and are highly expressed in squamous cell cancers. Using mouse keratinocytes as a biological model of squamous epithelium, we show that multiple p63 isotypes, Delta N- and TA-containing, are expressed and differentially modulated during in vitro murine keratinocyte differentiation. Delta Np63 alpha declines with Ca2+-induced differentiation, while a smaller Delta N-form, Delta Np63(s), persists, suggesting unique functions of the two Delta N-forms. To investigate the impact of dysregulated p63 expression that is observed in cancers and to define the biological contribution of the different domains of the p63 isotypes, Delta Np63 alpha, Delta Np63(p40), TAp63 alpha, TAp63 gamma or beta-galactosidase were overexpressed in primary murine keratinocytes. Microarray, RT-PCR and western blot analyses revealed that overexpression of Delta Np63(p40), which lacks the entire alpha-tail present in Delta Np63 alpha, permits expression of a full panel of differentiation markers. This is in contrast to overexpression of the full-length Delta Np63 alpha, which blocks induction of keratin 10, loricrin and filaggrin. These findings support a role for the alpha-tail of Delta Np63 alpha in blocking differentiation-specific gene expression. Overexpression of either TAp63 isotype permits keratin 10 and loricrin expression, thus the alpha-terminus requires the cooperation of the Delta N domain in blocking early differentiation. However, both TA isotypes block filaggrin induction. The Delta N-terminus is sufficient to maintain keratinocytes in a proliferative state, as both Delta N forms block Ca2+-mediated p21(WAF1) induction and S-phase arrest, while sustaining elevated PCNA levels. No alteration in cell cycle regulation was observed in keratinocytes overexpressing TAp63 alpha or TAp63 gamma. Clarifying the functional distinctions between p63 isotypes and domains will help to elucidate how their dysregulation impacts tumor biology and may suggest novel therapeutic strategies for modulating behavior of tumor cells with altered expression of p53 family members. C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod, Bethesda, MD 20892 USA. Sapporo Med Univ, Sch Med, Sapporo, Hokkaido 0608556, Japan. NCI, NIH, Bethesda, MD 20892 USA. RP Weinberg, WC (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Off Biotechnol Prod, 29B Lincoln Dr,HFD-123,Bldg 29B,Room 3NN04, Bethesda, MD 20892 USA. EM weinberg@cber.fda.gov RI Weinberg, Wendy/A-8920-2009 FU Intramural NIH HHS NR 55 TC 38 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2006 VL 27 IS 1 BP 53 EP 63 DI 10.1093/carcin/bgi200 PG 11 WC Oncology SC Oncology GA 997BF UT WOS:000234219300005 PM 16081516 ER PT J AU Khan, SG Oh, KS Shahlavi, T Ueda, T Busch, DB Inui, H Emmert, S Imoto, K Muniz-Medina, V Baker, CC DiGiovanna, JJ Schmidt, D Khadavi, A Metin, A Gozukara, E Slor, H Sarasin, A Kraemer, KH AF Khan, SG Oh, KS Shahlavi, T Ueda, T Busch, DB Inui, H Emmert, S Imoto, K Muniz-Medina, V Baker, CC DiGiovanna, JJ Schmidt, D Khadavi, A Metin, A Gozukara, E Slor, H Sarasin, A Kraemer, KH TI Reduced XPC DNA repair gene mRNA levels in clinically normal parents of xeroderma pigmentosum patients SO CARCINOGENESIS LA English DT Article ID GROUP-C PROTEIN; NUCLEOTIDE EXCISION-REPAIR; MUTANT MICE; COCKAYNE-SYNDROME; CANCER PREDISPOSITION; INFORMATION-CONTENT; MOLECULAR ANALYSIS; MAMMALIAN-CELLS; SKIN-CANCER; MUTATIONS AB Xeroderma pigmentosum group C (XP-C) is a rare autosomal recessive disorder. Patients with two mutant alleles of the XPC DNA repair gene have sun sensitivity and a 1000-fold increase in skin cancers. Clinically normal parents of XP-C patients have one mutant allele and one normal allele. As a step toward evaluating cancer risk in these XPC heterozygotes we characterized cells from 16 XP families. We identified 15 causative mutations (5 frameshift, 6 nonsense and 4 splicing) in the XPC gene in cells from 16 XP probands. All had premature termination codons (PTC) and absence of normal XPC protein on western blotting. The cell lines from 26 parents were heterozygous for the same mutations. We employed a real-time quantitative reverse transcriptase-PCR assay as a rapid and sensitive method to measure XPC mRNA levels. The mean XPC mRNA levels in the cell lines from the XP-C probands were 24% (P < 10(-7)) of that in 10 normal controls. This reduced XPC mRNA level in cells from XP-C patients was caused by the PTC that induces nonsense-mediated mRNA decay. The mean XPC mRNA levels in cell lines from the heterozygous XP-C carriers were intermediate (59%, P = 10(-4)) between the values for the XP patients and the normal controls. This study demonstrates reduced XPC mRNA levels in XP-C patients and heterozygotes. Thus, XPC mRNA levels may be evaluated as a marker of cancer susceptibility in carriers of mutations in the XPC gene. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, CCR, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Brown Med Sch, Dept Dermatol, Providence, RI USA. Yuzuncu Yil Univ, Sch Med, Dept Dermatol, Van, Turkey. Inonu Univ, Sch Med, Dept Biochem, Malatya, Turkey. Tel Aviv Univ, Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. Inst Gustave Roussy, CNRS, UPR 2169, Lab Genet Instabil & Canc, Villejuif, France. RP Kraemer, KH (reprint author), NCI, Basic Res Lab, Bethesda, MD 20892 USA. EM kraemerk@nih.gov FU Intramural NIH HHS [Z01 BC004517-31] NR 61 TC 54 Z9 55 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2006 VL 27 IS 1 BP 84 EP 94 DI 10.1093/carcin/bgi204 PG 11 WC Oncology SC Oncology GA 997BF UT WOS:000234219300008 PM 16081512 ER PT J AU Knight, ZA Gonzalez, B Feldman, ME Zunder, ER Goldenberg, DD Williams, O Loewith, R Stokoe, D Balla, A Toth, B Balla, T Weiss, WA Williams, RL Shokat, KM AF Knight, Zachary A. Gonzalez, Beatriz Feldman, Morri E. Zunder, Eli R. Goldenberg, David D. Williams, Olusegun Loewith, Robbie Stokoe, David Balla, Andras Toth, Balazs Balla, Tamas Weiss, William A. Williams, Roger L. Shokat, Kevan M. TI A pharmacological map of the PI3-K family defines a role for p110 alpha in insulin signaling SO CELL LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE INHIBITORS; DEPENDENT PROTEIN-KINASE; P85 REGULATORY SUBUNIT; CATALYTIC SUBUNIT; EMBRYONIC LETHALITY; TYROSINE KINASE; MICE; ACTIVATION; ATM; INSIGHTS AB Phosphoinositide 3-kinases (PI3-Ks) are an important emerging class of drug targets, but the unique roles of PI3-K isoforms remain poorly defined. We describe here an approach to pharmacologically interrogate the PI3-K family. A chemically diverse panel of PI3-K inhibitors was synthesized, and their target selectivity was biochemically enumerated, revealing cryptic homologies across targets and chemotypes. Crystal structures of three inhibitors bound to p110 gamma identify a conformationally mobile region that is uniquely exploited by selective compounds. This chemical array was then used to define the PI3-K isoforms required for insulin signaling. We find that p110 alpha is the primary insulin-responsive PI3-K in cultured cells, whereas p110 beta is dispensable but sets a phenotypic threshold for p110 alpha activity. Compounds targeting p110 alpha block the acute effects of insulin treatment in vivo, whereas a p110 beta inhibitor has no effect. These results illustrate systematic target validation using a matrix of inhibitors that span a protein family. C1 Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Brain Tumor Res Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Univ Geneva, Dept Mol Biol, CH-1211 Geneva 4, Switzerland. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM shokat@cmp.ucsf.edu NR 50 TC 5 Z9 5 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PY 2006 VL 127 IS 3 SU S BP 27 EP 41 DI 10.1016/j.cell.2006.03.035 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 105HV UT WOS:000242021900004 ER PT J AU Spivak, CE Oz, M Beglan, CL Shrager, RI AF Spivak, CE Oz, M Beglan, CL Shrager, RI TI Diffusion delays and unstirred layer effects at monolayer cultures of chinese hamster ovary cells - Radioligand binding, confocal microscopy, and mathematical simulations SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE mu-opioid receptor; confocal microscopy; binding kinetics; nonspecific binding; cerebroside sulfate; mathematical modeling; Crank-Nicolson method ID OPIATE RECEPTOR-BINDING; MU-OPIOID RECEPTORS; CEREBROSIDE SULFATE; EXTRACELLULAR-SPACE; LIGAND-BINDING; MODEL SYSTEM; AZURE-A; MEMBRANE; BRAIN; KINETICS AB Cells grown in monolayer culture offer a convenient system for binding and other experiments under conditions that preserve the complexity of the living state. Kinetics experiments, however, may be distorted by the time course of drug penetration into even so simple a "tissue" as the monolayer. The impediments include unstirred layers both above and between the cells, the congregation of receptors within the confined space between cells, and nonspecific binding to membrane components. The contributions of these factors were investigated in cultures of Chinese hamster ovary (CHO) cells either nontransfected or stably transfected with It opioid receptors. The dissociation of [H-3]naloxone was four times faster under displacement than under infinite dilution conditions, clearly demonstrating the "retention effect" of receptors confined in space. Even the penetration of this ligand between nontransfected cells showed salient delays with respect to diffusion into a slab, indicating that nonspecific, low-affinity binding to membrane components was arresting its progress. The optical sectioning capabilities of confocal microscopy demonstrated that the kinetics of two fluorescent antagonists depended on the vertical plane, providing direct evidence for slowed diffusion down a single cell depth. Modeling shows that kinetic errors increase with receptor density forward rate constant, and the thickness of the unstirred layer. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, US Dept HHS,NIH, Baltimore, MD 21224 USA. NIH, Ctr Informat Technol, Math & Stat Comp Lab, US Dept HHS, Bethesda, MD 20892 USA. RP Spivak, CE (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, US Dept HHS,NIH, Baltimore, MD 21224 USA. EM cspivak@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 44 TC 15 Z9 16 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2006 VL 45 IS 1 BP 43 EP 58 DI 10.1385/CBB:45:1:43 PG 16 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 040TT UT WOS:000237404000004 PM 16679563 ER PT J AU Hebert, TE Gales, C Rebois, RV AF Hebert, TE Gales, C Rebois, RV TI Detecting and imaging protein-protein interactions during g protein-mediated signal transduction in vivo and in situ by using fluorescence-based techniques SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Review DE signal transduction; heptahelical receptors; G proteins; protein-protein interaction; GFP; BRET; FRET; BiFC; imaging; fluorescence; bioluminescence ID RESONANCE ENERGY-TRANSFER; LUTEINIZING-HORMONE RECEPTORS; HUMAN OXYTOCIN RECEPTOR; LIGAND-INDEPENDENT DIMERIZATION; FUNCTIONAL GABA(B) RECEPTOR; HETEROTRIMERIC G-PROTEINS; LIVING CELLS; BIOLUMINESCENCE-RESONANCE; COUPLED RECEPTORS; BETA(2)-ADRENERGIC RECEPTOR AB An important goal in cell biology has been to observe dynamic interactions between protein molecules within a living cell as they execute the reactions of a particular biochemical pathway. An important step toward achieving this goal has been the development of noninvasive fluorescence-based detection and imaging techniques for determining whether and when specific biomolecules in a cell become associated with one another. Furthermore, these techniques, which take advantage of phenomena known as bioluminescence- and fluorescence resonance energy transfer (BRET and FRET, respectively) as well as bimolecular fluorescence complementation (BiFC), can provide information about where and when protein-protein interactions occur in the cell. Increasingly BRET, FRET, and BiFC are being used to probe interactions between components involved in G protein-mediated signal transduction. Heptahelical (7TM) receptors, heterotrimeric guanine nucleotide binding proteins (G proteins) and their proximal downstream effectors constitute the core components of these ubiquitous signaling pathways. Signal transduction is initiated by the binding of agonist to heptahelical (7TM) receptors that in turn activate their cognate G proteins. The activated G protein subsequently regulates the activity of specific effectors. 7TM receptors, G proteins, and effectors are all membrane-associated proteins, and for decades two opposing hypotheses have vied for acceptance. The predominant hypothesis has been that these proteins move about independently of one another in membranes and that signal transduction occurs when they encounter each other as the result of random collisions. The contending hypothesis is that signaling is propagated by organized complexes of these proteins. Until recently, the data supporting these hypotheses came from studying signaling proteins in solution, in isolated membranes, or in fixed cells. Although the former hypothesis has been favored, recent studies using BRET and FRET have generally supported the latter hypothesis as being the most likely scenario operating in living cells. In addition to the core components, there are many other proteins involved in G protein signaling, and BRET and FRET studies have been used to investigate their interactions as well. This review describes various BRET, FRET, and BiFC techniques, how they have been or can be applied to the study of G protein signaling, what caveats are involved in interpreting the results, and what has been learned about G protein signaling from the published studies. C1 Natl Inst Deafness & Commun Disorders, Lab Cellular Signaling, NIH, Rockville, MD USA. Univ Montreal, Inst Cardiol Montreal, Ctr Rech, Montreal, PQ, Canada. Univ Montreal, Dept Anesthesiol, Montreal, PQ, Canada. Univ Montreal, Dept Biochim, Montreal, PQ H3C 3J7, Canada. RP Rebois, RV (reprint author), Natl Inst Deafness & Commun Disorders, Lab Cellular Signaling, NIH, Rockville, MD USA. EM reboisv@nidcd.nih.gov NR 146 TC 47 Z9 48 U1 1 U2 11 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2006 VL 45 IS 1 BP 85 EP 109 DI 10.1385/CBB:45:1:85 PG 25 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 040TT UT WOS:000237404000007 PM 16679566 ER PT J AU Rodriguez, O Fricke, S Chien, C Dettin, L VanMeter, J Shapiro, E Dai, HN Casimiro, M Ileva, L Dagata, J Johnson, MD Lisanti, MP Koretsky, A Albanese, C AF Rodriguez, O Fricke, S Chien, C Dettin, L VanMeter, J Shapiro, E Dai, HN Casimiro, M Ileva, L Dagata, J Johnson, MD Lisanti, MP Koretsky, A Albanese, C TI Contrast-enhanced in vivo imaging of breast and prostate cancer cells by MRI SO CELL CYCLE LA English DT Article DE MRI; breast cancer; prostate cancer; superparamagnetic; nanoparticle; fluorescence; xenograft ID MAGNETIC-RESONANCE TRACKING; IRON-OXIDE NANOPARTICLES; EMBRYONIC STEM-CELLS; MAMMARY-TUMORS; SPINAL-CORD; CYCLIN D1; BRAIN; PARTICLES; DIFFERENTIATION; CHEMOTHERAPY AB The development of effective cancer therapies has been hampered, in part, by the inability to noninvasively follow tumor progression from the initial cancerous lesion through to metastasis. We have previously shown that superparamagnetic iron oxide particles can be used as magnetic resonance imaging contrast agents to label embryonic, mesenchymal and hematopoietic stem cells in vivo. Improving the capacity to non-invasively image cancer progression is an appealing method that could be useful for assessing the efficacy of anticancer therapies. We have established that human prostate (LNCaP, DU145, PC3), rodent prostate (TRAMPC1, YPEN-1), human breast (MDA-MB-231) and mouse mammary (Myc/VEGF) cancer cell lines were readily labeled by fluorescent superparamagnetic sub-micron particles of iron oxide (MPIOs). The MPIOs were essentially inert with respect to cell proliferation and tumor formation. Fluorescence stereomicroscopy and three dimensional magnetic resonance imaging (MRI) determined that subcutaneous, intramuscular or orthotopically implanted labeled cancer cells could be imaged, in vivo, despite in some cases being undetectable by manual palpation. The MPIO-labeled cancer cells could also be imaged, in vivo, at least 6 weeks after implantation. The fluorescent MPIOs further allowed for the ex vivo identification of tumors cells from histological sections. This study demonstrates the feasibility of using fluorescent MPIOs in prostate and breast cancer cell lines as both a negative contrast agent for in vivo MRI as well as a fluorescent tumor marker for optical imaging in vivo and ex vivo. C1 Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Neurosci, Washington, DC 20057 USA. Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20057 USA. NIH, Lab Funct Mol Imaging, Bethesda, MD 20892 USA. NIST, Gaithersburg, MD 20899 USA. Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. RP Albanese, C (reprint author), Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA. EM albanese@georgetown.edu RI Lisanti, Michael/C-6866-2013; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU Intramural NIH HHS [Z01 NS003047-01]; NCI NIH HHS [2P30-CA-51008, CA09686T32, R03CA20337, U54 CA100970-02]; NCRR NIH HHS [1S10 RR15768-01] NR 33 TC 39 Z9 39 U1 3 U2 13 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2006 VL 5 IS 1 BP 113 EP 119 DI 10.4161/cc.5.1.2295 PG 7 WC Cell Biology SC Cell Biology GA 016HG UT WOS:000235610700020 PM 16340310 ER PT J AU Kim, DJ Bility, MT Billin, AN Willson, TM Gonzalez, FJ Peters, JM AF Kim, DJ Bility, MT Billin, AN Willson, TM Gonzalez, FJ Peters, JM TI PPAR beta/delta selectively induces differentiation and inhibits cell proliferation SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE peroxisome proliferator-activated receptor; receptor-beta; differentiation; cell proliferation; anti-inflammatory; null mouse; ligand activation ID ACTIVATED RECEPTOR-BETA; KERATINOCYTE DIFFERENTIATION; EPIDERMAL-KERATINOCYTES; GENE-EXPRESSION; PHASE-II; MOUSE; DELTA; GAMMA; CARCINOGENESIS; TROGLITAZONE AB Peroxisome proliferator-activated receptor ( PPAR) beta-null mice exhibit exacerbated epithelial cell proliferation and enhanced sensitivity to skin carcinogenesis, suggesting that ligand activation of PPAR beta will inhibit keratinocyte proliferation. By using of a highly specific ligand ( GW0742) and the PPAR beta-null mouse model, activation of PPARb was found to selectively induce keratinocyte terminal differentiation and inhibit keratinocyte proliferation. Additionally, GW0742 was found to be anti-inflammatory due to inhibition of myeloperoxidase activity, independent of PPARb. These data suggest that ligand activation of PPARb could be a novel approach to selectively induce differentiation and inhibit cell proliferation, thus representing a new molecular target for the treatment of skin disorders resulting from altered cell proliferation such as psoriasis and cancer. C1 Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, Grad Program Mol Toxicol, University Pk, PA 16802 USA. GlaxoSmithKline Inc, Discovery Res, Bethesda, MD 20892 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Billin, Andrew/0000-0001-7752-0934 FU NCI NIH HHS [CA89607, CA97999] NR 31 TC 102 Z9 105 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2006 VL 13 IS 1 BP 53 EP 60 DI 10.1038/sj.cdd.4401713 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 991OD UT WOS:000233822400007 PM 16021179 ER PT J AU Le, SB Holmuhamedov, EL Narayanan, VL Sausville, EA Kaufmann, SH AF Le, SB Holmuhamedov, EL Narayanan, VL Sausville, EA Kaufmann, SH TI Adaphostin and other anticancer drugs quench the fluorescence of mitochondrial potential probes SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE mitochondrial membrane potential; fluorescence; chemotherapy; quenching; probe ID CELL-DEATH; BETA-CYCLODEXTRIN; ELECTRON-TRANSFER; AROMATIC-AMINES; LEUKEMIA-CELLS; CYTOCHROME-C; MEMBRANE; APOPTOSIS; PHOSPHORYLATION; QUANTITATION AB Fluorescent dyes are widely used to monitor changes in mitochondrial transmembrane potential (Delta psi m). When MitoTracker Red CMXRos, tetramethylrhodamine methyl ester (TMRM), and 3,3'dihexyloxacarbocyanine iodide (DiOC6(3)) were utilized to examine the effects of the experimental anticancer drug adaphostin on intact cells or isolated mitochondria, decreased fluorescence was observed. In contrast, measurement of tetraphenylphosphonium uptake by the mitochondria using an ion-selective microelectrode failed to show any effect of adaphostin on Delta psi m. Instead, further experiments demonstrated that adaphostin quenches the fluorescence of the mitochondrial dyes. Structure-activity analysis revealed that the adamantyl and p-aminobenzoic acid moieties of adaphostin are critical for this quenching. Anticancer drugs containing comparable structural motifs, including mitoxantrone, aminoflavone, and amsacrine, also quenched the mitochondrial probes. These results indicate the need for caution when mitochondrial dyes are utilized to examine the effects of xenobiotics on Delta psi m and suggest that some previously reported direct effects of anticancer drugs on mitochondria might need re-evaluation. C1 Mayo Clin, Div Oncol Res, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Oncol, Rochester, MN 55905 USA. Mayo Clin, Coll Med, Dept Mol Pharmacol, Rochester, MN 55905 USA. NCI, Div Canc Treatment & Diagnosis, Bethesda, MD 20892 USA. RP Kaufmann, SH (reprint author), Mayo Clin, Div Oncol Res, Guggenheim 1342 C,200 1st St,SW, Rochester, MN 55905 USA. EM Kaufmann.scott@mayo.edu OI Kaufmann, Scott/0000-0002-4900-7145 FU NCI NIH HHS [R01 CA69008, R01 CA85972] NR 47 TC 14 Z9 14 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2006 VL 13 IS 1 BP 151 EP 159 DI 10.1038/sj.cdd.4401732 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 991OD UT WOS:000233822400016 PM 16052237 ER PT J AU Thomas, LR Bender, LM Morgan, MJ Thorburn, A AF Thomas, LR Bender, LM Morgan, MJ Thorburn, A TI Extensive regions of the FADD death domain are required for binding to the TRAIL receptor DR5 SO CELL DEATH AND DIFFERENTIATION LA English DT Article ID EFFECTOR DOMAIN; SIGNAL-TRANSDUCTION; FAS; LIGAND; RECRUITMENT; CASPASE-8; SURFACE; MODEL C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Aurora, CO 80045 USA. Univ Colorado, Hlth Sci Ctr, Ctr Canc, Aurora, CO 80045 USA. Wake Forest Univ, Sch Med, Dept Canc Biol, Winston Salem, NC 27157 USA. NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. RP Thorburn, A (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, L18-6100,RC1 S Tower,POB 6511,Mail Stop 8303, Aurora, CO 80045 USA. EM Andrew.Thorburn@uchsc.edu NR 16 TC 8 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2006 VL 13 IS 1 BP 160 EP 162 DI 10.1038/sj.cdd.4401714 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 991OD UT WOS:000233822400017 PM 16003390 ER PT J AU Berthet, C Kaldis, P AF Berthet, Cyril Kaldis, Philipp TI Cdk2 and Cdk4 cooperatively control the expression of Cdc2 SO CELL DIVISION LA English DT Article AB Progression through the mammalian cell cycle is associated with the activity of four cyclin dependent kinases (Cdc2/Cdk1, Cdk2, Cdk4, and Cdk6). Knockout mouse models have provided insight into the interplay of these Cdks. Most of these models do not exhibit major cell cycle defects revealing redundancies, and suggesting that a single Cdk might be sufficient to drive the cell cycle, similar as in yeast. Recent work on Cdk2/Cdk4 double knockouts has indicated that these two Cdks are required to phosphorylate Rb during late embryogenesis. The lack of Rb phosphorylation is progressive and associated with reduced E2F-inducible gene expression. Cdk2 and Cdk4 share the essential function of coupling the G1/S transition with mitosis. However, proliferation in early embryogenesis appears to be independent of Cdk2 and Cdk4. We discuss these observations and propose molecular mechanisms that establish the requirement for Cdk2 and Cdk4 at the G1/S transition. We are considering that the balance between proliferation and differentiation is disturbed, which affects especially heart development and leads to embryonic lethality in Cdk2(-/-) Cdk4(-/-) mutants. We also discuss the specific functions of Cdk4 and Cdk6, which ironically do not compensate for each other. C1 [Berthet, Cyril; Kaldis, Philipp] NCI, Mouse Canc Genet Program, NCI Frederick, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), NCI, Mouse Canc Genet Program, NCI Frederick, Bldg 560-22-56,1050 Boyles St, Frederick, MD 21702 USA. EM cberthet@ncifcrf.gov; kaldis@ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU Kaldis laboratory; MCGP; NIH, National Cancer Institute, Center for Cancer Research FX We thank the Kaldis laboratory and MCGP for support, and Satya Ande, Shuhei Kotoshiba, Weimin Li, Kristy McDowell, and Padmakumar VC for comments on the manuscript. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 19 TC 22 Z9 22 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2006 VL 1 AR 10 DI 10.1186/1747-1028-1-10 PG 6 WC Cell Biology SC Cell Biology GA V14GT UT WOS:000207723600010 PM 16759374 ER PT J AU Dib, A Peterson, TR Raducha-Grace, L Zingone, A Zhan, FH Hanamura, I Barlogie, B Shaughnessy, J Kuehl, WM AF Dib, Amel Peterson, Timothy R. Raducha-Grace, Laura Zingone, Adriana Zhan, Fenghuang Hanamura, Ichiro Barlogie, Bart Shaughnessy, John, Jr. Kuehl, W. Michael TI Paradoxical expression of INK4c in proliferative multiple myeloma tumors: bi-allelic deletion vs increased expression SO CELL DIVISION LA English DT Article AB Background: A high proliferative capacity of tumor cells usually is associated with shortened patient survival. Disruption of the RB pathway, which is critically involved in regulating the G1 to S cell cycle transition, is a frequent target of oncogenic events that are thought to contribute to increased proliferation during tumor progression. Previously, we determined that p18INK4c, an essential gene for normal plasma cell differentiation, was bi-allelically deleted in five of sixteen multiple myeloma (MM) cell lines. The present study was undertaken to investigate a possible role of p18INK4c in increased proliferation of myeloma tumors as they progress. Results: Thirteen of 40 (33%) human myeloma cell lines do not express normal p18INK4c, with bi-allelic deletion of p18 in twelve, and expression of a mutated p18 fragment in one. Bi-allelic deletion of p18, which appears to be a late progression event, has a prevalence of about 2% in 261 multiple myeloma (MM) tumors, but the prevalence is 6 to 10% in the 50 tumors with a high expression-based proliferation index. Paradoxically, 24 of 40 (60%) MM cell lines, and 30 of 50 (60%) MM tumors with a high proliferation index express an increased level of p18 RNA compared to normal bone marrow plasma cells, whereas this occurs in only five of the 151 (3%) MM tumors with a low proliferation index. Tumor progression is often accompanied by increased p18 expression and an increased proliferation index. Retroviral-mediated expression of exogenous p18 results in marked growth inhibition in three MM cell lines that express little or no endogenous p18, but has no effect in another MM cell line that already expresses a high level of p18. Conclusion: Paradoxically, although loss of p18 appears to contribute to increased proliferation of nearly 10% of MM tumors, most MM cell lines and proliferative MM tumors have increased expression of p18. Apart from a small fraction of cell lines and tumors that have inactivated the RB1 protein, it is not yet clear how other MM cell lines and tumors have become insensitive to the anti-proliferative effects of increased p18 expression. C1 [Dib, Amel; Peterson, Timothy R.; Raducha-Grace, Laura; Zingone, Adriana; Kuehl, W. Michael] NCI, Genet Branch, Ctr Canc Res, Naval Hosp, Bethesda, MD 20889 USA. [Peterson, Timothy R.] MIT, Dept Biol, Whitehead Inst, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Raducha-Grace, Laura] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. [Zhan, Fenghuang; Hanamura, Ichiro; Barlogie, Bart; Shaughnessy, John, Jr.] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. [Hanamura, Ichiro] Aichi Med Univ, Div Hematol, Dept Internal Med, Nagakute, Aichi 4801195, Japan. RP Kuehl, WM (reprint author), NCI, Genet Branch, Ctr Canc Res, Naval Hosp, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM dibmalti@yahoo.com; petersti@MIT.edu; raduchagrace.laura@medstudent.pitt.edu; zingonad@mail.nih.gov; ZhanFenghuang@uams.edu; Hanamura@aichi-med-u.ac.ip; barlogiebart@uams.edu; ShaughnessyJohn@uams.edu; wmk@helix.nih.gov FU NIH, NCI [CA55819, CA97513]; Fund to Cure Myeloma FX The authors thank Leslie Brents for technical help, and also Leif Bergsagel and Conny Cultraro for helpful discussions. This research was supported in part by the Intramural Research Program of the NIH, NCI (AD, TRP, LRG, AZ, WMK), by The Fund to Cure Myeloma (JS and AD), and by NIH grants CA55819 (BB and JS) and CA97513 (JS) from the NCI. NR 45 TC 27 Z9 30 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2006 VL 1 AR 23 DI 10.1186/1747-1028-1-23 PG 10 WC Cell Biology SC Cell Biology GA V14GT UT WOS:000207723600023 PM 17049078 ER PT J AU Kaldis, P Pagano, M AF Kaldis, Philipp Pagano, Michele TI Cell Division, a new open access online forum for and from the cell cycle community SO CELL DIVISION LA English DT Editorial Material AB Cell Division is a new, open access, peer-reviewed online journal that publishes cutting-edge articles, commentaries and reviews on all exciting aspects of cell cycle control in eukaryotes. A major goal of this new journal is to publish timely and significant studies on the aberrations of the cell cycle network that occur in cancer and other diseases. C1 [Kaldis, Philipp] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. [Pagano, Michele] NYU, Sch Med, Dept Pathol, NYU Canc Inst, New York, NY 10016 USA. RP Kaldis, P (reprint author), NCI, Mouse Canc Genet Program, Bldg 560-22-56,1050 Boyles St, Frederick, MD 21702 USA. EM kaldis@ncifcrf.gov; michele.pagano@med.nyu.edu RI Kaldis, Philipp/G-2714-2010; OI Kaldis, Philipp/0000-0002-7247-7591; pagano, michele/0000-0003-3210-2442 NR 1 TC 0 Z9 0 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2006 VL 1 AR 1 DI 10.1186/1747-1028-1-1 PG 2 WC Cell Biology SC Cell Biology GA V14GT UT WOS:000207723600001 PM 16759411 ER PT J AU Zhu, JF Yamane, H Cote-Sierra, J Guo, LY Paul, WE AF Zhu, JF Yamane, H Cote-Sierra, J Guo, LY Paul, WE TI GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors SO CELL RESEARCH LA English DT Review DE GATA-3; Stat5; Gfi-1; Th2 cell differentiation; cell expansion; transcription factors ID TRANSCRIPTION FACTOR GATA-3; HEMATOPOIETIC STEM-CELLS; CD4(+) T-CELLS; GENE-EXPRESSION; IL-4 PRODUCTION; IN-VIVO; REPRESSOR GFI1; COORDINATE REGULATOR; LINEAGE COMMITMENT; INTERFERON-GAMMA AB Naive CD4 T cells can differentiate into at least two different types of T helpers, Th1 and Th2 cells. Th2 cells, capable of producing IL-4, IL-5 and IL-13, are involved in humoral immunity against extracellular pathogens and in the induction of asthma and other allergic diseases. In this review, we summarize recent reports regarding the transcription factors involved in Th2 differentiation and cell expansion, including Stat5, Gfi-1 and GATA-3. Stat5 activation is necessary and sufficient for IL-2-mediated function in Th2 differentiation. Enhanced Stat5 signaling induces Th2 differentiation independent of IL-4 signaling; although it does not up-regulate GATA-3 expression, it does require the presence of GATA-3 for its action. Gfi-1, induced by IL-4, promotes the expansion of GATA-3-expressing cells. Analysis of conditional Gata3 knockout mice confirmed the critical role of GATA-3 in Th2 cell differentiation (both IL-4 dependent and IL-4 independent) and in Th2 cell proliferation and also showed the importance of basal GATA-3 expression in inhibiting Th1 differentiation. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM jfzhu@niaid.nih.gov RI Zhu, Jinfang/B-7574-2012 NR 55 TC 170 Z9 186 U1 0 U2 14 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD JAN PY 2006 VL 16 IS 1 BP 3 EP 10 DI 10.1038/sj.cr.7310002 PG 8 WC Cell Biology SC Cell Biology GA 034WK UT WOS:000236961100002 PM 16467870 ER PT J AU Young, HA Ortaldo, J AF Young, HA Ortaldo, J TI Cytokines as critical co-stimulatory molecules in modulating the immune response of natural killer cells SO CELL RESEARCH LA English DT Review DE NK cells; cytokines; IL-12; IL-18; IFN gamma; innate immune response; synergy ID NK RECEPTORS; IFN-GAMMA; INNATE IMMUNITY; IL-12; ACTIVATION; EXPRESSION; LY-49D AB Cytokines are involved in directing the activation of natural killer (NK) cells. NK cells are involved in the recognition of cells that have been altered; thus they do not recognize specific insults to the host, but when activated, are capable of destroying infected cells directly, as well as promoting the recruitment and response of the other components of the immune system by the release of cytokines and chemokines. It is these properties that have made NK cells a critical part of innate immunity and adaptive immunity, and they play a principal role linking innate and adaptive immunity by the recruitment of an adaptive immune response to an innate immune reaction. C1 NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Young, HA (reprint author), NCI, Expt Immunol Lab, Canc Res Ctr, Frederick, MD 21702 USA. EM youngh@ncifcrf.gov FU Intramural NIH HHS NR 14 TC 29 Z9 35 U1 1 U2 1 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 EI 1748-7838 J9 CELL RES JI Cell Res. PD JAN PY 2006 VL 16 IS 1 BP 20 EP 24 DI 10.1038/sj.cr.7310004 PG 5 WC Cell Biology SC Cell Biology GA 034WK UT WOS:000236961100004 PM 16467872 ER PT J AU Chitnis, A AF Chitnis, Ajay BE Unsicker, K Krieglstein, K TI Generating Cell Diversity SO CELL SIGNALING AND GROWTH FACTORS IN DEVELOPMENT: FROM MOLECULES TO ORGANOGENESIS LA English DT Article; Book Chapter ID MIDBRAIN-HINDBRAIN BOUNDARY; FGF SIGNALING CONTROLS; MOTOR-NEURON POOLS; ETS GENE PEA3; SPINAL-CORD; ZEBRAFISH ORGANIZER; VERTEBRATE EMBRYO; PRECHORDAL PLATE; XENOPUS EMBRYOS; NERVOUS-SYSTEM C1 NICHHD, Univ Vertebrate Neural Dev, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Chitnis, A (reprint author), NICHHD, Univ Vertebrate Neural Dev, Mol Genet Lab, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. NR 92 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-52761-968-9 PY 2006 BP 287 EP 320 PG 34 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BYB14 UT WOS:000297805000009 ER PT J AU Mackem, S AF Mackem, Susan BE Unsicker, K Krieglstein, K TI Limb Development SO CELL SIGNALING AND GROWTH FACTORS IN DEVELOPMENT: FROM MOLECULES TO ORGANOGENESIS LA English DT Article; Book Chapter ID APICAL ECTODERMAL RIDGE; PROGRAMMED CELL-DEATH; RETINOIC ACID SYNTHESIS; HEDGEHOG SIGNAL-TRANSDUCTION; BONE MORPHOGENETIC PROTEINS; GROWTH-FACTOR RECEPTORS; NAIL-PATELLA SYNDROME; SKELETAL PATTERNING DEFECTS; EMBRYONAL CARCINOMA-CELLS; SYNOVIAL JOINT FORMATION C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Mackem, S (reprint author), NCI, Pathol Lab, Bldg 10,Room 2A33,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 553 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-3-52761-968-9 PY 2006 BP 523 EP 618 PG 96 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA BYB14 UT WOS:000297805000016 ER PT J AU Averina, IV Tapilskaya, NI Reznik, VA Frolova, EV Fedorova, OV Lakatta, EG Bagrov, AY AF Averina, I. V. Tapilskaya, N. I. Reznik, V. A. Frolova, E. V. Fedorova, O. V. Lakatta, E. G. Bagrov, A. Y. TI ENDOGENOUS Na/K-ATPase INHIBITORS IN PATIENTS WITH PREECLAMPSIA SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE Preeclampsia; Na/K-ATPase; vasoconstriction; marinobufagenin; DIGIBIND AB Although preeclampsia (PE) is a major cause of maternal and fetal mortality, its pathogenesis is not fully understood. Digitalis-like cardiotonic steroids (CTS) are believed to be involved in the pathophysiology of PE, as illustrated by clinical observations that DIGIBIND, a digoxin antibody which binds CTS, lowers blood pressure in PE. Recently we reported that plasma levels of marinobufagenin (MBG), a vasoconstrictor CTS, are increased fourfold in patients with severe PE. In the present study, we tested whether anti-MBG, or anti-ouabain antibodies, or DIGIBIND can reverse inhibition of erythrocyte Na/K-ATPase (NKA) from patients with mild PE (blood pressure, 149 +/- 3/93 +/- 3 mm Hg; age, 28 +/- 2 years; gestational age, 37 +/- 1 weeks). Development of PE was associated with twofold rise in plasma MBG levels (1.58 +/- 0.15 vs. 0.80 +/- 0.11 nmol/L; P<0.01). The activity of erythrocyte NKA in 12 patients with PE was lower than in 6 normotensive gestational age-matched subjects (1.56 +/- 0.18 vs. 3.11 +/- 0.16 mu mol P(i)/ml/hr; P<0.001). In vitro treatment of erythrocytes from PE patients with anti-MBG antibody fully restored the NKA activity (3.26 +/- 0.41 mu mol Pi/ml/hr; P<0.01). The effects of DIGIBIND was marginally significant (2.53 +/- 0.32 mu mol P(i)/ml/hr), while the anti-ouabain antibody was not effective (2.25 +/- 0.25 mu mol P(i)/ml/hr, P>0.5). The present observations provide evidence for a role for MBG in the pathogenesis of PE, and suggest that antibodies against MBG may be useful in the treatment of this syndrome. C1 [Fedorova, O. V.; Lakatta, E. G.; Bagrov, A. Y.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. [Averina, I. V.; Tapilskaya, N. I.; Reznik, V. A.] State Acad Pediat Med, Dept Obstet & Gynecol, St Petersburg, Russia. [Frolova, E. V.] IM Sechenov Evolutionary Physiol & Biochem Inst, Pharmacol Lab, St Petersburg 194223, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BagrovA@mail.nih.gov FU National Institute on Aging, NIH FX Supported by Intramural Research Program, National Institute on Aging, NIH. Authors gratefully acknowledge critical comments of Dr. David E. Anderson, National Institute on Aging, NIH, Baltimore, MD. NR 30 TC 30 Z9 30 U1 1 U2 2 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2006 VL 52 IS 8 BP 19 EP 23 DI 10.1170/T755 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V11DQ UT WOS:000207512700004 PM 17535731 ER PT J AU Rouzaud, F Hearing, VJ AF Rouzaud, F. Hearing, V. J. TI Analysis of the transcriptional regulation of melanocytic genes by alpha MSH using the CDNA microarray technique SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Review DE alpha MSH; melanocyte; microarray; mRNA expression ID TYROSINASE-RELATED PROTEIN-1; LOCALLY WEIGHTED REGRESSION; HUMAN-MELANOMA CELLS; YELLOW OBESE MOUSE; MELANOCORTIN-1 RECEPTOR; STIMULATING-HORMONE; MESSENGER-RNA; DOPACHROME-TAUTOMERASE; SMOOTHING SCATTERPLOTS; LEGIONELLA-PNEUMOPHILA AB Studies of mammalian pigmentation have identified many genes involved in the development, migration, and function of melanocytest Molecular and biochemical mechanisms that switch melanocytes between the production of eumelanin or pheomelanin involve the opposing action of two signaling molecules, alpha-Melanocyte Stimulating Hormone (alpha MSH) and Agouti Signal Protein affects various aspects of melanocyte behavior stimulating melanocyte dendricity, attachment to extracellular matrix proteins, but also up-regulating the expression of eumelanogenic genes In response to ASP melanocytes switch from producing eumelanin to pheomelanin concomitant with the down-regulation of melanogenic genes transcriptiont Since activation of signaling pathways leads to mRNA expression, microarray technology can provide a quantitative assessment of the consequences of this activation. Significant up/down regulation of all known melanogenic genes by alpha MSH/ASP in cultured melanocytes has been previously reported. We have now used the cDNA microarray technique to screen alpha MSH-treated melanocytes to identify genes that are transcriptionally enhanced by this factort We report the melanocytic expression and alpha MSH up-regulation of 11 genes spanning; functional categories such as apoptosis, body weight control intracellular transport, signal transduction, oncogenic transformation, transcription factors and genes coding for keratin associated proteins. C1 NCI, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Rouzaud, F (reprint author), NCI, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 120 TC 1 Z9 1 U1 0 U2 4 PU C M B ASSOCIATION PI SARREGUEMINES PA 2 RUE DE ROUHLING, 57200 SARREGUEMINES, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2006 VL 52 IS 2 BP 21 EP 31 DI 10.1170/T704 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 071IQ UT WOS:000239594500003 PM 16914083 ER PT J AU Zvartau, NE Conrady, AO Sviryaev, YV Rotari, OP Merkulova, NK Kalinkin, AL Shlyakhto, EV Bagrov, AY AF Zvartau, N. E. Conrady, A. O. Sviryaev, Y. V. Rotari, O. P. Merkulova, N. K. Kalinkin, A. L. Shlyakhto, E. V. Bagrov, A. Y. TI MARINOBUFAGENIN IN HYPERTENSIVE PATIENTS WITH OBSTRUCTIVE SLEEP APNEA SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE Obstructive sleep apnea; hypertension; Na/K-ATPase; marinobufagenin AB Although obstructive sleep apnea (OSA) is an independent risk factor for hypertension, the underlying mechanisms are not clearly understood. Apnea and hypopnea episodes during sleep lead to sympathoactivation, decrease plasma pH, and predispose to sodium and volume retention. We hypothesized that, the latter could stimulate digitalis-like natriuretic/vasopressor hormones, endogenous ouabain (EO) and marinobufagenin (MBG). Overnight polysomnography (Embletta) and 24hrs blood pressure monitoring (SpaceLab 90207) was conducted in 52 consecutive patients with OSA (51 +/- 8 years; 40 males, 12 females) and in 48 age-matched hypertensive subjects without OSA. According to the polysomnography data, 17 patients had a mild degree of OSA (apnea/hypopnea index (AHI) 5-15), 17 patients-moderate (AHI 15-30) and 18 - severe OSA (AHI > 30). Levels of MBG excretion co-varied with OSA severity (0.5 +/- 0.1, 0.9 +/- 0.04 and 1.2 +/- 0.06nmoles per 24hrs, respectively), while excretion of EO did not differ in patients with different degrees of OSA severity. Our observations suggest that MBG may be involved in the pathogenesis of hypertension in OSA, and may be a marker of OSA severity. C1 [Bagrov, A. Y.] IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. [Zvartau, N. E.; Conrady, A. O.; Sviryaev, Y. V.; Rotari, O. P.; Merkulova, N. K.; Shlyakhto, E. V.] Almazov Res Inst Cardiol, St Petersburg, Russia. [Kalinkin, A. L.] City Hosp 83, Ctr Sleep Disorders, Moscow, Russia. RP Bagrov, AY (reprint author), NIA, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD USA. EM BagrovA@mail.nih.gov OI Shlyakhto, Evgeny/0000-0003-2929-0980; Konradi, Alexandra/0000-0001-8169-7812 NR 28 TC 4 Z9 4 U1 0 U2 1 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2006 VL 52 IS 8 BP 24 EP 27 DI 10.1170/T756 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA V11DQ UT WOS:000207512700005 PM 17535732 ER PT S AU Cai, NS McCoy, MT Ladenheim, B Lyles, J Ali, SF Cadet, JL AF Cai, Ning Sheng McCoy, Michael T. Ladenheim, Bruce Lyles, Johnalyn Ali, Syed F. Cadet, Jean Lud BE Ali, SF Fornai, F TI Serial analysis of gene expression in the rat striatum following methamphetamine administration SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE METH; SAGE; neurotoxicity; CHOP; carbonic anhydrase ID INDUCED NEUROTOXICITY; NEURONAL APOPTOSIS; TYROSINE-HYDROXYLASE; MOUSE STRIATUM; CDNA ARRAY; ABUSE; MICE; PROTEIN; IDENTIFICATION; CONSEQUENCES AB Methamphetamine (METH), a highly addictive drug, can cause degeneration of monoaminergic terminals and neuronal apoptosis in the mammalian brain. In the present article, we have used serial analysis of gene expression (SAGE) to investigate patterns of gene expression in the striata of rats that were given a neurotoxic dose of the drug. SAGE libraries were generated from animals treated with either saline or METH (40 mg/kg) and sacrificed 2 h later. A total of 315 transcripts were differentially expressed between the two libraries (P < 0.05), with 179 (56%) being upregulated and 136 (44%) being downregulated by the METH injection. Of these, CAATT enhancer-binding protein homologous protein (CHOP)/GADD153 (growth arrest- and DNA damage-inducible gene 153) was found to be upregulated by about threefold. Analysis of the expression of genes downstream of CHOP (DOCs) revealed significant METH-induced increases in their expression. Because DOC1 is an analog of carbonic anhydrase (CA) which is involved in the interconversion between carbon dioxide and the bicarbonate ion, we also measured the effects of METH on the expression of several CAs. These were significantly upregulated by METH in a time-dependent fashion. These results indicate that METH toxicity is mediated, in part, by drug-induced perturbations of physiological processes that are dependent on normal pH and CO2 homeostasis. C1 Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Abuse Intramural Res Program, NIH, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Cadet, JL (reprint author), Natl Inst Drug Abuse, Mol Neuropsychiat Branch, Abuse Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov NR 43 TC 5 Z9 6 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 13 EP 30 DI 10.1196/annals.1369.002 PG 18 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100002 PM 17105900 ER PT S AU Rothman, RB Baumann, MH AF Rothman, Richard B. Baumann, Michael H. BE Ali, SF Fornai, F TI Balance between dopamine and serotonin release modulates behavioral effects of amphetamine-type drugs SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE agonist therapy; dopamine (DA); serotonin (5-HT); releasing agent; stimulant dependence ID COCAINE-DEPENDENCE; NUCLEUS-ACCUMBENS; INTRAVENOUS COCAINE; SQUIRREL-MONKEY; RHESUS-MONKEY; AGONIST-LIKE; FENFLURAMINE; RATS; PHENTERMINE; WITHDRAWAL AB The abuse of illicit stimulants is a worldwide crisis, yet few medicines are available for treating stimulant addiction. We have advocated the idea of "agonist therapy" for cocaine dependence. This strategy involves administration of stimulant-like medications (e.g., monoamine releasers) to alleviate cocaine withdrawal symptoms and prevent relapse. A chief limitation of this strategy is that many candidate medicines possess high abuse liability due to activation of mesolimbic dopamine (DA) neurons in reward pathways. Evidence suggests that serotonin (5-HT) neurons can provide an inhibitory influence over mesolimbic DA neurons. Thus, it might be predicted that the balance between DA and 5-HT transmission is a critical variable when developing medications with reduced stimulant side effects. In this article, we review recent studies from our laboratory that examined neurochemical and behavioral effects of a series of monoamine releasers which displayed different potencies at DA and 5-HT transporters. The data show that increasing 5-HT release can attenuate stimulant effects mediated by DA release, such as motor stimulation and drug self-administration. Our findings support the work of others and indicate that elevated synaptic 5-HT can dampen certain behavioral effects of DA-releasing agents. Moreover, the relationship between DA and 5-HT releasing potency is an important determinant in developing new agonist medications with reduced stimulant properties. C1 NIDA, CPS, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, CPS, IRP, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@mail.nih.gov FU Intramural NIH HHS NR 59 TC 63 Z9 63 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 245 EP 260 DI 10.1196/annals.1369.064 PG 16 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100023 PM 17105921 ER PT S AU Crespo, JA Panlilio, LV Schindler, CW Sturm, K Saria, A Zernig, G AF Crespo, Jose A. Panlilio, Leigh V. Schindler, Charles W. Sturm, Katja Saria, Alois Zernig, Gerald BE Ali, SF Fornai, F TI Peri-response pharmacokinetics of remifentanil during a self-administration session indicates that neither blood nor brain levels are titrated SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res HO Venice Int Univ DE remifentanil; pharmacokinetics; accumbens; core; dopamine; titration; threshold; satiation; reinforcement; self-administration; mu; opioid; brain; blood; plasma; contingent; noncontingent ID SUBSECOND DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; COCAINE-SEEKING; DRUG-ADDICTION; BEHAVIOR; RATS; REINFORCEMENT; VOLTAMMETRY; MECHANISMS; NEURONS AB An individual's drug abuse pattern is determined by a multitude of factors. Among these, simple pharmacological determinants of within-binge drug consumption are sorely underinvestigated. We therefore determined if within-session operant responsing to the ultra-short-acting mu opioid agonist remifentanil (RMF) was determined by blood or brain RMF levels or changes thereof. Our peri-response analysis did not detect any "threshold" RMF level, either in blood or in the nucleus accumbens (NAc) core as a deep brain region that might determine a rat's "decision" to re-emit a response during a multiple-injection drug self-administration session. The peri-response analysis also failed to find any peak RMF level, either in blood or in the NAc core, which could serve as a "ceiling" level. Thus, our findings strongly suggest that titration of blood or brain RMF levels does not determine a rat's intra-session operant response. C1 Univ Innsbruck, Dept Psychiat, Div Neurochem, A-6020 Innsbruck, Austria. NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA. RP Zernig, G (reprint author), Univ Innsbruck, Dept Psychiat, Div Neurochem, Anichstr 35, A-6020 Innsbruck, Austria. EM gerald.zernig@uibk.ac.at NR 27 TC 6 Z9 6 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN STREET, MALDEN 02148, MA USA SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 497 EP 504 DI 10.1196/annals.1369.050 PG 8 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100050 PM 17105948 ER PT S AU Onaivi, ES Ishiguro, H Gong, JP Patel, S Perchuk, A Meozzi, PA Myers, L Mora, Z Tagliaferro, P Gardner, E Brusco, A Akinshola, BE Liu, QR Hope, B Iwasaki, S Arinami, T Teasenfitz, L Uhl, GR AF Onaivi, Emmanuel S. Ishiguro, Hiroki Gong, Jian-Ping Patel, Sejal Perchuk, Alex Meozzi, Paul A. Myers, Lester Mora, Zoila Tagliaferro, Patricia Gardner, Eileen Brusco, Alicia Akinshola, Babatunde E. Liu, Qing-Rong Hope, Bruce Iwasaki, Shinya Arinami, Tadao Teasenfitz, Lindsey Uhl, George R. BE Ali, SF Fornai, F TI Discovery of the presence and functional expression of cannabinoid CB2 receptors in brain SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY: COCAINE, GHB, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Satellite Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse and Neurotoxicity - Cocaine, GHB and Substituted Amphetamines CY AUG 16-19, 2005 CL Venice Int Univ, Venice, ITALY SP Int Soc Neurochem, Neuromed Pozzilli, FDA, Natl Ctr Toxicol Res, Reg Veneto, Prov Venezia HO Venice Int Univ DE CB2 cannabinoid receptor; brain; immunohistochemistry; CB2 polyclonal antibody; CB2 blocking peptide; hippocampal cultures; RT PCR; in situ hybridization; mRNA; CB2 knockout mice; CB2 electron micrograph ID CENTRAL-NERVOUS-SYSTEM; IMMUNOHISTOCHEMICAL LOCALIZATION; MOLECULAR CHARACTERIZATION; DIFFERENTIAL EXPRESSION; ENDOCANNABINOID SYSTEM; ALZHEIMERS-DISEASE; IMMUNE MODULATION; MESSENGER-RNA; MAST-CELLS; RAT-BRAIN AB Two well-characterized cannabinoid receptors (CBrs), CB1 and CB2, mediate the effects of cannabinoids and marijuana use, with functional evidence for other CBrs. CB1 receptors are expressed primarily in brain and peripheral tissues. For over a decade several laboratories were unable to detect CB2 receptors in brain and were known to be intensely expressed in peripheral and immune tissues and have traditionally been referred to as peripheral CB2 CBrs. We have reported the discovery and functional presence of CB2 cannabinoid receptors in mammalian brain that may be involved in depression and drug abuse and this was supported by reports of identification of neuronal CB2 receptors that are involved in emesis. We used RT-PCR, immunoblotting, hippocampal cultures, immunohistochemistry, transmission electron microscopy, and stereotaxic techniques with behavioral assays to determine the functional expression of CB2 CBrs in rat brain and mice brain exposed to chronic mild stress (CMS) or those treated with abused drugs. RT PCR analyses supported the expression of brain CB2 receptor transcripts at levels much lower than those of CB1 receptors. In situ hybridization revealed CB2 mRNA in cerebellar neurons of wild-type but not of CB2 knockout mice. Abundant CB2 receptor immunoreactivity (iCB2) in neuronal and glial processes was detected in brain and CB2 expression was detected in neuron-specific enolase (NSE) positive hippocampal cell cultures. The effect of direct CB2 antisense oligonucleotide injection into the brain and treatment with JWH015 in motor function and plus-maze tests also demonstrated the functional presence of CB2 cannabinoid receptors in the central nervous system (CNS). Thus, contrary to the prevailing view that CB2 CBrs are restricted to peripheral tissues and predominantly in immune cells, we demonstrated that CB2 CBrs and their gene transcripts are widely distributed in the brain. This multifocal expression of CB2 immunoreactivity in brain suggests that CB2 receptors may play broader roles in the brain than previously anticipated and may be exploited as new targets in the treatment of depression and substance abuse. C1 William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. NIDA, MNB, Baltimore, MD 21224 USA. Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 305, Japan. Univ Buenos Aires, RA-1053 Buenos Aires, DF, Argentina. Howard Univ, Washington, DC 20059 USA. NIDA, Behav Neurosci Branch, Baltimore, MD 21224 USA. RP Onaivi, ES (reprint author), William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. EM Onaivie@wpunj.edu RI Hope, Bruce/A-9223-2010; Liu, Qing-Rong/A-3059-2012 OI Hope, Bruce/0000-0001-5804-7061; Liu, Qing-Rong/0000-0001-8477-6452 NR 53 TC 246 Z9 256 U1 0 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 1-57331-629-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1074 BP 514 EP 536 DI 10.1196/annals.1369.052 PG 23 WC Cell Biology; Substance Abuse; Multidisciplinary Sciences; Clinical Neurology; Pharmacology & Pharmacy SC Cell Biology; Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BFJ04 UT WOS:000242168100052 PM 17105950 ER PT J AU Weber, A Gutierrez, MI Levens, D AF Weber, A Gutierrez, MI Levens, D TI The CT-element of the c-myc gene does not predispose to chromosomal breakpoints in Burkitt's lymphoma SO CELLULAR ONCOLOGY LA English DT Article DE DNA-conformation; chromosomal breakpoints; c-myc; Burkitt's lymphoma; LM-PCR ID DNA-STRUCTURE; IN-VIVO; REGION AB Background: Chromosomal translocations are causally related to the development of many tumors. In Burkitt's lymphoma, abnormalities involving the c-myc gene are essential. The CT-element of the c-myc promoter adopts non-B-conformation in vivo and in vitro, and therefore provides a potential fragile site. Methods: We have developed a LM-PCR-based approach to test if chromosomal breakpoints indeed cluster in this region. Results: Amplifying both, wild-type as well as the translocated c-myc gene by LM-PCR, it was shown that chromosomal breakpoints did not cluster within the CT-element. Conclusions: Therefore, the CT-element is not especially susceptible to the formation of breakpoints leading to chromosomal translocations in Burkitt's lymphoma. C1 Univ Mainz, Inst Pathol, D-55101 Mainz, Germany. NCI, Pathol Lab, Gene Regulat Sect, NIH, Bethesda, MD 20892 USA. King Faisal Specialist Hosp & Res Ctr, Childrens Canc Ctr, Riyadh 11211, Saudi Arabia. RP Weber, A (reprint author), Univ Mainz, Inst Pathol, Langenbeckstr 1, D-55101 Mainz, Germany. EM weber@pathologie.klinik.uni-mainz.de RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 11 TC 1 Z9 1 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2006 VL 28 IS 1-2 BP 31 EP 35 PG 5 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 059WF UT WOS:000238762200003 PM 16675879 ER PT J AU Grade, M Becker, H Liersch, T Ried, T Ghadimi, BM AF Grade, Marian Becker, Heinz Liersch, Torsten Ried, Thomas Ghadimi, B. Michael TI Molecular cytogenetics: Genomic imbalances in colorectal cancer and their clinical impact SO CELLULAR ONCOLOGY LA English DT Review ID IN-SITU-HYBRIDIZATION; GROWTH-FACTOR-RECEPTOR; HUMAN COLON-CANCER; NUMERICAL CHROMOSOMAL-ABERRATIONS; SPECTRAL KARYOTYPE ANALYSIS; CHRONIC MYELOID-LEUKEMIA; HIGH-RESOLUTION ANALYSIS; ABL TYROSINE KINASE; COPY NUMBER CHANGES; HUMAN BREAST-CANCER AB Chromosomal aberrations play a dominant role in colorectal carcinogenesis. The application of fluorescence in situ hybridization (FISH) based techniques such as comparative genomic hybridization (CGH) and spectral karyotyping (SKY) revealed that colorectal carcinomas are characterized by a specific pattern of chromosomal imbalances which sequentially accumulate during cancer progression. This review aims to summarize molecular cytogenetic studies, provides a background on the functional relevance of chromosomal aberrations for colorectal cancer progression and discusses their potential clinical impact. C1 Univ Gottingen, Med Ctr, Dept Gen Surg, D-37075 Gottingen, Germany. Natl Canc Inst, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD USA. RP Ghadimi, BM (reprint author), Univ Gottingen, Med Ctr, Dept Gen Surg, Robert Koch Str 40, D-37075 Gottingen, Germany. EM mghadim@uni-goettingen.de NR 144 TC 32 Z9 32 U1 0 U2 3 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 1570-5870 J9 CELL ONCOL JI Cell. Oncol. PY 2006 VL 28 IS 3 BP 71 EP 84 PG 14 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 078YV UT WOS:000240143600002 PM 16823176 ER PT J AU Burdick, AD Kim, DJ Peraza, MA Gonzalez, FJ Peters, JM AF Burdick, AD Kim, DJ Peraza, MA Gonzalez, FJ Peters, JM TI The role of peroxisome proliferator-activated receptor-beta/delta in epithelial cell growth and differentiation SO CELLULAR SIGNALLING LA English DT Review DE peroxisome proliferator-activated receptor-beta/delta; PPAR beta/delta; epithelium; skin; differentiation; cell proliferation; apoptosis; cancer ID INTESTINAL POLYP FORMATION; ACID-BINDING PROTEIN; RETINOID-X RECEPTOR; COLON-CANCER CELLS; PPAR-GAMMA; GENE-EXPRESSION; COLORECTAL-CANCER; FATTY-ACIDS; TISSUE DISTRIBUTION; SIGNALING PATHWAY AB The physiological and pharmacological roles of peroxisome proliferator-activated receptor-beta (PPAR beta-also referred to as PPAR delta) are just beginning to emerge. It has recently become clear that PPAR beta has a function in epithelial tissues, but controversy exists due to inconsistencies in the literature. There is strong evidence that ligand activation of PPAR can induce terminal differentiation of keratinocytes, with a concomitant inhibition of cell proliferation. However, the role of PPAR beta in keratinocyte-specific apoptosis is less clear. Additionally, the role of PPAR beta in colonic epithelium remains unclear due to conflicting evidence suggesting that ligand activation of PPAR beta can potentiate, as well as attenuate, intestinal cancer. Recent studies revealed that ligand activation of PPAR beta can induce fatty acid catabolism in skeletal muscle and is associated with improved insulin sensitivity, attenuated weight gain and elevated HDL levels thus demonstrating promising potential for targeting PPAR beta for treating obesity, dyslipidemias and type 2 diabetes. Therefore, it becomes critical to determine the safety of PPAR beta ligands. This review focuses on recent literature describing the role of PPAR beta in epithelial tissues and highlights critical discrepancies that need to be resolved for a more comprehensive understanding of how this receptor modulates epithelial homeostasis. (c) 2005 Elsevier Inc. All rights reserved. C1 Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp2l@psu.edu RI Peters, Jeffrey/D-8847-2011; OI Burdick, Andrew/0000-0002-4584-1378 FU NCI NIH HHS [CA89607, CA97999] NR 100 TC 109 Z9 114 U1 0 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2006 VL 18 IS 1 BP 9 EP 20 DI 10.1016/j.cellsig.2005.07.009 PG 12 WC Cell Biology SC Cell Biology GA 978LG UT WOS:000232874200002 PM 16109478 ER PT J AU Steiner, D Saya, D Schallmach, E Simonds, WF Vogel, Z AF Steiner, D Saya, D Schallmach, E Simonds, WF Vogel, Z TI Adenylyl cyclase type-VIII activity is regulated by G(beta gamma) subunits SO CELLULAR SIGNALLING LA English DT Article DE adenylyl cyclase type VIII; G(beta gamma); G(alpha i); G(beta gamma) scavengers; G-protein coupled receptors; pertussis toxin; ionomycin ID BETA-GAMMA-SUBUNITS; G-PROTEIN; DIFFERENTIAL MODULATION; DEPENDENT ACTIVATION; CA2+ CHANNELS; RECEPTORS; ISOFORMS; DISSOCIATION; KINASE; SUPERACTIVATION AB The Ca2+-activated adenylyl cyclase type VIII (AC-VIII) has been implicated in several forms of neural plasticity, including drug addiction and teaming and memory. It has not been clear whether G(i/o) proteins and G-protein coupled receptors regulate the activity of AC-VIII. Here we show in intact mammalian cell system that AC-VIII is inhibited by mu-opioid receptor activation and that this inhibition is pertussis toxin sensitive. Moreover, we show that G,, subunits inhibit AC-VIII activity, while constitutively active alpha(i/v). subunits do not. Different G(beta) isoforms varied in their efficacies, with G(beta 1 gamma 2) or G(beta 2 gamma 2) being more efficient than G(beta 3 gamma 2) and G(beta 4 gamma 2), while G(beta 5) (transfected with gamma(2)) had no effect. As for the G(gamma) subunits, G(beta i) inhibited AC-VIII activity in the presence of all gamma subunits tested except for gamma(5) that had only a marginal activity. Moreover, cotransfection with proteins known to serve as scavengers of G(beta gamma) dimers, or to reduce G(beta gamma) plasma membrane anchorage, markedly attenuated the mu-opioid receptor-induced inhibition of AC-VIII. These results demonstrate that G(beta gamma) (originating from agonist activation of these receptors) and probably not G(alpha i)/o. subunits are involved in the agonist inhibition of AC-vIII. (0 2005 Elsevier Inc. All rights reserved. C1 Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Vogel, Z (reprint author), Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. EM zvi.vogel@weizmann.ac.il FU NIDA NIH HHS [DA-06265] NR 51 TC 20 Z9 22 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2006 VL 18 IS 1 BP 62 EP 68 DI 10.1016/j.cellsig.2005.03.014 PG 7 WC Cell Biology SC Cell Biology GA 978LG UT WOS:000232874200007 PM 15925485 ER PT J AU Warach, S Kaufman, D Chiu, D Devlin, T Luby, M Rashid, A Clayton, L Kaste, M Lees, KR Sacco, R Fisher, M AF Warach, S Kaufman, D Chiu, D Devlin, T Luby, M Rashid, A Clayton, L Kaste, M Lees, KR Sacco, R Fisher, M CA GAINS Americas GAIN International TI Effect of the glycine antagonist gavestinel on cerebral infarcts in acute stroke patients, a randomized placebo-controlled trial: The GAIN MRI substudy SO CEREBROVASCULAR DISEASES LA English DT Article DE placebo-controlled clinical trial; gavestinel; neuroprotection; diffusion MRI ID ACUTE ISCHEMIC-STROKE; PERFUSION-WEIGHTED MRI; CLINICAL-TRIALS; LESION VOLUMES; DIFFUSION; THROMBOLYSIS; NEUROPROTECTION; RECOMMENDATIONS; CITICOLINE AB Background and Purpose: Gavestinel, GV150526, is a selective antagonist at the glycine site of the N- methyl- D aspartate receptor. The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials]. A planned MRI substudy within these trials investigated the effect of gavestinel on infarct volume. Methods: Patients enrolled in the GAIN trials at designated MRI substudy sites were eligible if they had a pretreatment acute cortical lesion on diffusion- weighted MRI of at least 1.5 cm diameter or 5 cm(3). Final lesion assessment was performed on T-2-weighted MRI at month 3. Blinded image analysis was performed centrally. The primary hypothesis was that gavestinel would attenuate lesion growth from baseline relative to placebo. Results: A total of 106 patients were eligible, 75 (34 gavestinel, 41 placebo) of whom had month 3 scans (primary analysis population). No effects of gavestinel on infarct volume were observed in the primary or other analyses. However, significant associations of lesion volume to clinical severity and outcomes were observed. Ischemic lesion volume decrease was predictive of substantial clinical improvement. Conclusion: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed. Concordance of results of the clinical outcome trials with those of this infarct volume substudy as well the associations of infarct volume to clinical outcomes further support the potential role of infarct volume as a marker of outcome in dose finding and proof of principle acute stroke trials. Copyright (c) 2006 S. Karger AG, Basel. C1 NINDS, Bethesda, MD 20892 USA. Michigan State Univ, E Lansing, MI 48824 USA. Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Erlanger Med Ctr, Chattanooga, TN USA. Percept Informat, Waltham, MA USA. GlaxoSmithKline Inc, Greenford, Middx, England. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. Univ Helsinki, Helsinki, Finland. Univ Glasgow, Glasgow, Lanark, Scotland. Columbia Univ, New York, NY USA. Univ Massachusetts, Worcester, MA 01605 USA. RP Warach, S (reprint author), NINDS, 10 Ctr Dr,MSC 1063,Bldg 10,Room B1D733, Bethesda, MD 20892 USA. EM warachs@ninds.nih.gov OI Kaste, Markku/0000-0001-6557-6412 FU Intramural NIH HHS [Z99 NS999999] NR 25 TC 39 Z9 39 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-9770 J9 CEREBROVASC DIS JI Cerebrovasc. Dis. PY 2006 VL 21 IS 1-2 BP 106 EP 111 DI 10.1159/000090208 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 996JG UT WOS:000234169600017 PM 16340185 ER PT J AU Pessah, IN Hansen, LG Albertson, TE Garner, CE Ta, TA Do, Z Kim, KH Wong, PW AF Pessah, IN Hansen, LG Albertson, TE Garner, CE Ta, TA Do, Z Kim, KH Wong, PW TI Structure-activity relationship for noncoplanar polychlorinated biphenyl congeners toward the ryanodine receptor-Ca2+ channel complex type 1 (RyR1) SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MIXTURE AROCLOR 1242; GREAT-LAKES FISH; CARDIAC SARCOPLASMIC-RETICULUM; MICROSOMAL CALCIUM-TRANSPORT; SUBSTITUTED PCB CONGENERS; CEREBELLAR GRANULE CELLS; PREPUBERTAL FEMALE RATS; 2,2',3,5',6-PENTACHLOROBIPHENYL PCB-95; PROTEIN-PHOSPHORYLATION; CONTAMINATED LANDFILL AB Ryanodine receptor isoforms are expressed in both excitable and nonexcitable tissues where they form microsomal Ca2+ release channels broadly involved in shaping cellular signaling. In this report, we provide a detailed structure-activity relationship (SAR) for polychlorinated biphenyl (PCB) congeners and metabolites necessary for enhancing ryanodine receptor type 1 (RyR1) activity using [H-3]ryanodine ([H-3]Ry) binding analysis. The 2,3,6-Cl PCB configuration is most important for optimal recognition by the RyR1 complex and/or critical for sensitizing its activation. Para substitution(s) diminishes the activity with para-chloro having a higher potency than the corresponding para-hydroxy derivative. The addition of a more bulky para-methyl-sulfonyl group eliminates the activity toward RyR1, supporting the importance of the para positions in binding RyR1. The requirement for an intact major T cell immunophilin FKBP12-RyR1 complex was observed with each of 12 active PCB congeners indicating a common mechanism requiring an immunophilin-regulated Ca2+ release channel. An excellent correlation between the relative potencies for doubling [H-3]Ry binding and the corresponding initial rates of PCB-induced Ca2+ efflux indicates that [H-3]Ry binding analysis provides a measure of dysregulation of microsomal Ca2+ transport. The SAR for activating RyR1 is consistent with those previously reported in several in vivo and in vitro studies, suggesting that a common mechanism may contribute to the toxicity of noncoplanar PCBs. A practical application of the receptor-based screen developed here with RyR1 is that it provides a quantitative SAR that may be useful in predicting biological activity and risk of mixtures containing noncoplanar PCB congeners that have low or a lack of aryl hydrocarbon receptor activity. C1 Univ Calif Davis, Sch Med, Dept VM Mol Biosci, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Ctr Childrens Environm Hlth, Davis, CA 95616 USA. Univ Calif Davis, Sch Med, Dept Internal Med, Div Pulm & Crit Care Med, Davis, CA 95616 USA. Univ Illinois, Dept Vet Biosci, Coll Vet Med, Urbana, IL 61802 USA. NIEHS, Lab Pharmacol & Chem, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Pessah, IN (reprint author), Univ Calif Davis, Sch Med, Dept VM Mol Biosci, Davis, CA 95616 USA. EM inpessah@ucdavis.edu FU NIEHS NIH HHS [ES11269, ES05707, ES04699, ES07059] NR 69 TC 72 Z9 72 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2006 VL 19 IS 1 BP 92 EP 101 DI 10.1021/tx050196m PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 005LB UT WOS:000234822600012 PM 16411661 ER PT J AU Peterson, KE Chesebro, B AF Peterson, KE Chesebro, B TI Influence of proinflammatory cytokines and chemokines on the neuropathogenesis of oncornavirus and immunosuppressive lentivirus infections SO CHEMOKINES AND VIRAL INFECTION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; MURINE LEUKEMIA-VIRUS; NECROSIS-FACTOR-ALPHA; BLOOD-BRAIN-BARRIER; ENDOPLASMIC-RETICULUM STRESS; NEURAL PROGENITOR CELLS; HIV-ASSOCIATED DEMENTIA; NEUROLOGICAL DISEASE; HIPPOCAMPAL NEUROGENESIS AB Retroviral infection of the CNS can lead to severe debilitating neurological diseases in humans and other animals. Four general types of pathogenic effects with various retroviruses have been observed including: hemorrhage (TR1.3), spongiform encephalopathy (CasBrE, FrCasE, PVC211, NT40, Mol-ts1), demyelination with inflammatory lesions (HTLV-1, visna, CAEV), and encephalopathy with gliosis and proinflammatory chemokines and cytokines, usually with microglial giant cells and nodules [human immunodeficiency virus (HIV), feline immunodeficiency virus (FIV), simian immunodeficiency virus (SIV), Fr98]. This review focuses on this fourth group of retroviruses. In this latter group, proinflammatory cytokine and chemokine upregulation accompanies the disease process, and may influence pathogenesis by direct effects on resident CNS cells. The review first discusses the Fr98 murine polytropic virus system with particular reference to the roles of cytokines and chemokines in the pathogenic process. The Fr98 data are then compared and contrasted to the cytokine and chemokine data in the lentivirus systems, HIV, SIV, and FIV. Finally, various mechanisms are presented by which tumor necrosis factor (TNF) and several chemokines may alter the pathogenesis of retrovirus infection of the CNS. C1 Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Peterson, KE (reprint author), Louisiana State Univ, Sch Vet Med, Dept Pathobiol Sci, Baton Rouge, LA 70803 USA. EM kpeterson@vetmed.lsu.edu RI Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 130 TC 12 Z9 12 U1 2 U2 4 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 303 BP 67 EP 95 DI 10.1007/978-3-540-33397-5_4 PG 29 WC Immunology; Microbiology SC Immunology; Microbiology GA BEK63 UT WOS:000237591600004 PM 16570857 ER PT J AU Mencoboni, M Olivieri, R Vannozzi, MO Schettini, G Viazzi, F Ghio, R AF Mencoboni, M Olivieri, R Vannozzi, MO Schettini, G Viazzi, F Ghio, R TI Docetaxel pharmacokinetics with pre- and post-dialysis administration in a hemodyalized patient SO CHEMOTHERAPY LA English DT Article DE taxotere; dialysis; docetaxel; pharmacokinetics ID STAGE RENAL-DISEASE; OVARIAN-CANCER; HEMODIALYSIS; PACLITAXEL; CARCINOMA; CISPLATIN AB Background. Docetaxel has a proven significant activity against breast, non-small cell lung, ovarian, head and neck, and hormone refractory prostate cancer. Preclinical pharmacokinetic studies have shown that hepatobiliary extraction is the major route of elimination. We conducted this study to elucidate the feasibility and safety of the use of docetaxel in hemodialysis patients. Patient and Methods: In a 72-year-old hormone refractory prostate cancer patient on hemodialysis for diabetic nephropathy for 3 years, a first dose (35 mg/m(2) iv) of docetaxel was completed 30 min before starting dialysis, while a second dose was administered 30 min after completion of a different hemodialysis session. Pharmacokinetic analysis was performed following both infusions. Results: No apparent differences could be seen in the plasma concentration-time curves of docetaxel administered before or after dialysis. The patient experienced no significant toxicity after either administration of docetaxel. Conclusions: Docetaxel is safe in dialysis patients and does not require dose reduction. Dialysis does not remove this drug from blood. C1 Villa Scassi Hosp, Oncol Unit, IT-16100 Genoa, Italy. Univ Genoa, Dept Internal Med, I-16126 Genoa, Italy. Natl Canc Inst, Dept Pharmacol Toxicol, Genoa, Italy. RP Mencoboni, M (reprint author), Villa Scassi Hosp, Oncol Unit, Corso Onofrio Scassi 1, IT-16100 Genoa, Italy. EM manlio.mencoboni@fastwebnet.it NR 14 TC 7 Z9 8 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PY 2006 VL 52 IS 3 BP 147 EP 150 DI 10.1159/000092903 PG 4 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 045TS UT WOS:000237766000007 PM 16636537 ER PT J AU De Lucca, AJ Blanda, JM Boue, S Vigo, CB Cleveland, TE Walsh, TJ AF De Lucca, A. J. Blanda, J. M. Boue, S. Vigo, C. B. Cleveland, T. E. Walsh, T. J. TI Synergism of CAY-1 with amphotericin B and itraconazole SO CHEMOTHERAPY LA English DT Article DE saponin; synergism; amphotericin B; itraconazole; additive-synergistic effect ID RESISTANCE AB Background: CAY-1 is a fungicidal saponin from cayenne pepper whose mode of action differs from amphotericin B (AB) and itraconazole (IT). This work determined CAY-1 synergism with AB or IT. Methods: CAY-1 was purified and used in checkerboard microdilution studies where CAY-1 and AB or IT were mixed with nongerminated (NG) and germinating (G) conidia of three Aspergillus species and Candida, albicans. Inhibition was visually determined at 24 and 48 h. Results: CAY-1 had predominantly additive-synergistic interaction with AB or IT against the Aspergillus NG and G conidia. Excellent synergy between CAY-1 and AB occurred at 24 and 48 h against C. albicans. Results suggest CAY-1 enhances AB and IT efficacy. Copyright (c) 2006 S. Karger AG, Basel. C1 USDA ARS, So Reg Res Ctr, New Orleans, LA 70124 USA. NCI, NIH, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP De Lucca, AJ (reprint author), USDA ARS, So Reg Res Ctr, 1100 Robert E Lee Blvd, New Orleans, LA 70124 USA. EM adelucca@srrc.ars.usda.gov NR 7 TC 6 Z9 6 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PY 2006 VL 52 IS 6 BP 285 EP 287 DI 10.1159/000095959 PG 3 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 097OE UT WOS:000241456500004 PM 17008779 ER PT J AU Vitiello, B AF Vitiello, B TI An update on publicly funded multisite trials in pediatric psychopharmacology SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; OBSESSIVE-COMPULSIVE DISORDER; HEALTH MULTIMODAL TREATMENT; RANDOMIZED CONTROLLED-TRIAL; TREATMENT STRATEGIES; CLINICAL-TRIAL; ADOLESCENTS; CHILDREN; DEPRESSION; COMBINATION AB The field of pediatric psychopharmacology has undergone major changes during the last 10 years. As the clinical use of psychotropic medications to treat children and adolescents has grown, so has research to evaluate the efficacy and safety of this practice. This article provides an update of multisite clinical trials in pediatric psychopharmacology that recently have been funded by the National Institute of Mental Health (NIMH). Included are controlled trials of psychotropic medications conducted in subjects under age 19 years and involving three or more separate clinical sites. This article includes (1) a summary of the changing clinical and regulatory context relevant to pediatric psychopharmacology; (2) a commentary on how publicly funded and industry-funded research can best collaborate and complement each other while avoiding duplication; (3) an update on the status of selected NIMH-funded multisite trials (Table 1), and (4) a discussion of the limitations of current multisite trials as a step toward developing novel approaches. C1 NIMH, Bethesda, MD 20892 USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd,MSC 9633, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov NR 23 TC 6 Z9 6 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD JAN PY 2006 VL 15 IS 1 BP 1 EP + DI 10.1016/j.chc.2005.08.010 PG 13 WC Psychiatry SC Psychiatry GA 001GU UT WOS:000234522400003 PM 16321723 ER PT J AU Roma, PG Champoux, M Suomi, SJ AF Roma, PG Champoux, M Suomi, SJ TI Environmental control, social context, and individual differences in behavioral and cortisol responses to novelty in infant rhesus monkeys SO CHILD DEVELOPMENT LA English DT Article ID CHILD-CARE; SALIVARY CORTISOL; ADRENOCORTICAL ACTIVITY; MACACA-NEMESTRINA; YOUNG-CHILDREN; STRESS; TEMPERAMENT; REACTIVITY; NEUROENDOCRINE; PRESCHOOLERS AB The effects of appetitive controllability on behavioral and cortisol reactivity to novelty in 12 infant rhesus monkeys were studied. Surrogate-peer-reared infants had homecage access to food treats contingently via lever pressing ("master") or noncontingently ("yoked") for 12 weeks from postnatal month 2. Masters lever-pressed more, but did not differ in baseline cortisol. At month 5, infants were exposed to a novel environment in social groups and individually. Masters were significantly more active and exhibited significantly lower cortisol reactivity to the novel environment, but only in the individual context. Also, individual differences in operant behavior were positively correlated with behavioral activity and negatively correlated with cortisol reactivity to the novel environment. The results reveal context-specific benefits of contingent stimulation in infancy. C1 NICHHD, Bethesda, MD 20892 USA. RP Roma, PG (reprint author), American Univ, Dept Psychol, Psychopharmacol Lab, 4400 Massachusetts Ave NW, Washington, DC 20016 USA. EM PeteRoma@gmail.com FU Intramural NIH HHS NR 57 TC 8 Z9 8 U1 4 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-3920 J9 CHILD DEV JI Child Dev. PD JAN-FEB PY 2006 VL 77 IS 1 BP 118 EP 131 DI 10.1111/j.1467-8624.2006.00860.x PG 14 WC Psychology, Educational; Psychology, Developmental SC Psychology GA 010EN UT WOS:000235169800009 PM 16460529 ER PT J AU Klein, DC AF Klein, DC TI Evolution of the vertebrate pineal gland: The AANAT hypothesis SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article; Proceedings Paper CT 10th Congress of the European-Pineal-and-Biological-Rhythms-Society CY SEP 01-05, 2005 CL Frankfurt, GERMANY SP European Pineal Biolog Rhythms Soc DE pineal; evolution; melatonin; retina; AANAT; vertebrates ID SEROTONIN N-ACETYLTRANSFERASE; HYDROXYINDOLE-O-METHYLTRANSFERASE; RETINOID-BINDING PROTEIN; LIGHT-INDUCED DECREASE; MELATONIN SYNTHESIS; CHICK PINEAL; S-ANTIGEN; PHOTONEUROENDOCRINE TRANSDUCTION; IMMUNOCYTOCHEMICAL DEMONSTRATION; EPITHELIAL-CELLS AB The defining feature of the pineal gland is the capacity to function as a melatonin factory that operates on a greater than or similar to 24 h schedule, reflecting the unique synthetic capacities of the pinealocyte. Melatonin synthesis is typically elevated at night and serves to provide the organism with a signal of nighttime. Melatonin levels can be viewed as hands of the clock. Issues relating to the evolutionary events leading up to the immergence of this system have not received significant attention. When did melatonin synthesis appear in the evolutionary line leading to vertebrates? When did a distinct pineal gland first appear? What were the forces driving this evolutionary trend? As more knowledge has grown about the pinealocyte and the relationship it has to retinal photoreceptors, it has become possible to generate a plausible hypothesis to explain how the pineal gland and the melatonin rhythm evolved. At the heart of the hypothesis is the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (AANAT). The advances supporting the hypothesis will be reviewed here and expanded beyond the original foundation; the hypothesis and its implications will be addressed. C1 NICHHD, US Dept HHS, Sect Neuroendocrinol, Off Sci Director,NIH, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHHD, US Dept HHS, Sect Neuroendocrinol, Off Sci Director,NIH, Bethesda, MD 20892 USA. EM kleind@mail.nih.gov FU Intramural NIH HHS NR 109 TC 39 Z9 39 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PY 2006 VL 23 IS 1-2 BP 5 EP 20 DI 10.1080/07420520500545839 PG 16 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 040NN UT WOS:000237385700002 PM 16687276 ER PT J AU Moller, M Rath, MF Klein, DC AF Moller, M Rath, MF Klein, DC TI The perivascular phagocyte of the mouse pineal gland: An antigen-presenting cell SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article; Proceedings Paper CT 10th Congress of the European-Pineal-and-Biological-Rhythms-Society CY SEP 01-05, 2005 CL Frankfurt, GERMANY SP European Pineal Biolog Rhythms Soc DE pineal; phagocyte; acid phosphatase; houseradish peroxidas; mouse ID S-ANTIGEN; RAT; MACROPHAGES/MICROGLIA; EXPRESSION; LYMPHOCYTES; COMPLEX; ORGAN AB The perivascular space of the rat pineal gland is known to contain phagocytic cells that are immunoreactive for leukocyte antigens, and thus they appear to belong to the macrophage/microglial cell line. These cells also contain MHC class II proteins. We investigated this cell type in the pineal gland of mice. Actively phagocytosing cells with a prominent lysosomal system were found in the pericapillary spaces of the mouse pineal gland following intravenous injection of horseradish peroxidase. The cells also exhibited strong acid phosphatase activity. Perivascular cells were immunopositive for MHC class II protein and for CD68, a marker of monocytes/phagocytes. This study verifies that perivascular phagocytes with antigen-presenting properties are present in the mouse pineal gland. C1 Univ Copenhagen, Panum Inst, Inst Med Anat, DK-2200 Copenhagen, Denmark. NICHD, Sect Neuroendocrinol, NIH, Bethesda, MD USA. RP Moller, M (reprint author), Univ Copenhagen, Panum Inst, Inst Med Anat, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM morten.m@mai.ku.dk OI Rath, Martin/0000-0002-4047-6324 NR 24 TC 5 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PY 2006 VL 23 IS 1-2 BP 393 EP 401 DI 10.1080/07420520500521855 PG 9 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 040NN UT WOS:000237385700037 PM 16687312 ER PT J AU Shaw, BR Hawkins, R Arora, N McTavish, F Pingree, S Gustafson, DH AF Shaw, BR Hawkins, R Arora, N McTavish, F Pingree, S Gustafson, DH TI An exploratory study of predictors of participation in a computer support group for women with breast cancer SO CIN-COMPUTERS INFORMATICS NURSING LA English DT Article ID ONLINE; VALIDATION; INFORMATION; ADJUSTMENT; DISTRESS; HIGHWAY; SYSTEM; SCALE; HELP AB This study examined what characteristics predict participation in online support groups for women with breast cancer when users are provided free training, computer hardware, and Internet service removing lack of access as a barrier to use. The only significant difference between active and inactive participants was that active users were more likely at pretest to consider themselves active participants in their healthcare. Among active participants, being white and having a higher energy level predicted higher volumes of writing. There were also trends toward the following characteristics predictive of a higher volume of words written, including having a more positive relationship with their doctors, fewer breast cancer concerns, higher perceived health competence, and greater social/family well-being. Implications for improving psychosocial interventions for women with breast cancer are discussed, and future research objectives are suggested. C1 Univ Wisconsin, Ctr Excellence Canc Commun Res, Madison, WI 53706 USA. Univ Wisconsin, Sch Journalism & Mass Commun, Madison, WI 53706 USA. Univ Wisconsin, Sch Ind Engn, Madison, WI 53706 USA. Univ Wisconsin, Sch Prevent Med, Madison, WI 53706 USA. NCI, Washington, DC USA. RP Shaw, BR (reprint author), Univ Wisconsin, Ctr Excellence Canc Commun Res, Madison, WI 53706 USA. EM bretshaw@chsra.wisc.edu NR 45 TC 35 Z9 35 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1538-2931 J9 CIN-COMPUT INFORM NU JI CIN-Comput. Inform. Nurs. PD JAN-FEB PY 2006 VL 24 IS 1 BP 18 EP 27 DI 10.1097/00024665-200601000-00007 PG 10 WC Computer Science, Interdisciplinary Applications; Medical Informatics; Nursing SC Computer Science; Medical Informatics; Nursing GA 009UT UT WOS:000235139600004 PM 16436908 ER PT J AU Csako, G AF Csako, G TI From real-time PCR to nanotechnology: Rapid and/or high-throughput diagnostic methods for nucleic acids - Foreword SO CLINICA CHIMICA ACTA LA English DT Editorial Material C1 NIH, Dept Lab Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Csako, G (reprint author), NIH, Dept Lab Med, WG Magnuson Clin Ctr, Bldg 10,Room 2C-407, Bethesda, MD 20892 USA. EM gcsako@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2006 VL 363 IS 1-2 BP 5 EP 5 DI 10.1016/j.cccn.2005.04.039 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 001LW UT WOS:000234535600001 PM 16112100 ER PT J AU Csako, G AF Csako, G TI Present and future of rapid and/or high-throughput methods for nucleic acid testing SO CLINICA CHIMICA ACTA LA English DT Review DE gene expression profiling; genotyping; real-time quantitative PCR; reverse transcriptase; sequencing; single nucleotide polymorphism (SNP) ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; WHOLE GENOME AMPLIFICATION; RESONANCE ENERGY-TRANSFER; MULTIPLE DISPLACEMENT AMPLIFICATION; HUMAN MITOCHONDRIAL GENOME; STEM-CELL TRANSPLANTATION; DEPENDENT DNA POLYMERASE; TOF MASS-SPECTROMETRY; QUANTITATIVE PCR AB Background: Behind the success of 'completing' the human genome project was a more than 30-year history of technical innovations for nucleic acid testing. Methods: Discovery of specific restriction endonucleases and reverse transcriptase was followed shortly by the development of the first diagnostic nucleic acid tests in the early 1970s. Introduction of Southern, Northern and dot blotting and DNA sequencing later in the 1970s considerably advanced the diagnostic capabilities. Nevertheless, it was the discovery of the polymerase chain reaction (PCR) in 1985 that led to an exponential growth in molecular biology and the introduction of practicable nucleic acid tests in the routine laboratory. The past two decades witnessed a continuing explosion of technological innovations in molecular diagnostics. In addition to classic PCR and reverse transcriptase PCR, numerous variations of PCR and alternative amplification techniques along with an ever-increasing variety of detection chemistries, closed tube (homogeneous) assays, and automated systems were developed. Discovery of real-time quantitative PCR and the development of oligonucleotide microarrays, the 'DNA chip', in the 1990s heralded the beginning of another revolution in molecular biology and diagnostics that is still in progress. Published by Elsevier B.V. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Csako, G (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Lab Med, Bldg 10,Rm 2C-407, Bethesda, MD 20892 USA. EM gcsako@nih.gov NR 242 TC 39 Z9 42 U1 0 U2 22 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2006 VL 363 IS 1-2 BP 6 EP 31 DI 10.1016/j.ccn.2005.07.009 PG 26 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 001LW UT WOS:000234535600002 PM 16102738 ER PT J AU Wu, YY Csako, G AF Wu, YY Csako, G TI Rapid and/or high-throughput genotyping for human red blood cell, platelet and leukocyte antigens, and forensic applications SO CLINICA CHIMICA ACTA LA English DT Review DE real-time PCR; pyrosequencing; microarray; mass spectrometry; mitochondrial DNA; short tandem repeats (STRs) ID REAL-TIME PCR; POLYMERASE-CHAIN-REACTION; HUMAN MITOCHONDRIAL-DNA; MELTING CURVE ANALYSIS; FETAL RHD STATUS; MATERNAL PLASMA; QUANTITATIVE PCR; HYBRIDIZATION PROBES; DETECTION SYSTEM; ARRAY FORMAT AB Background: Traditionally, transfusion medicine, platelet and human leukocyte antigen (HLA) typing, and forensic medicine relied on serologic studies. Methods: In recent years, molecular testing on nucleic acids has been increasingly applied to these areas. Although conventional molecular diagnostic methods such as PCR-sequence-specific priming, PCR-restriction fragment-length polymorphism, PCR-single-strand conformation polymorphism, sequence-based typing, and DNA fingerprinting have been shown to perform well, their use is limited by long turnaround times, high cost, labor-intensiveness, the need for special technical skills, and/or the high risk of amplicon contamination. With advance of fast and/or high-throughput methods and platforms that often combine amplification and detection, a new era of molecular genotyping is emerging in these fields dominated by serology for a century. As new targets, short tandem repeats. mitochondrial DNA and Y-chromosome sequences were introduced for forensic applications. This article reviews the current status of the application of rapid and/or high-throughput genotyping methods to these areas. Results: The results are already promising with real-time PCR, pyrosequencing, microarrays, and mass spectrometry and show high concordance rates with classic serologic and earlier manual molecular diagnostic methods. Exploration of other emerging methodologies will likely further enhance the diagnostic utility of molecular testing in these areas. Published by Elsevier B.V. C1 Yale Univ, Sch Med, Dept Lab Med, New Haven, CT 06510 USA. NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD 20892 USA. RP Wu, YY (reprint author), Yale Univ, Sch Med, Dept Lab Med, 50 Lab St,CB459, New Haven, CT 06510 USA. EM yan.wu@yale.edu NR 70 TC 23 Z9 26 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2006 VL 363 IS 1-2 BP 165 EP 176 DI 10.1016/j.cccn.2005.07.010 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 001LW UT WOS:000234535600015 PM 16154123 ER PT J AU Albrecht, J Atzeni, F Baldini, C Bombardieri, S Dalakas, MC Demirkesens, C Yazici, H Mat, C Werth, VP Sarzi-Puttini, P AF Albrecht, J Atzeni, F Baldini, C Bombardieri, S Dalakas, MC Demirkesens, C Yazici, H Mat, C Werth, VP Sarzi-Puttini, P TI Skin involvement and outcome measures in systemic autoimmune diseases SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Review DE cutaneous lupus erythematosus; dermatomyositis; rheumatoid arthritis; primary Sjogren's syndrome; Behcet's syndrome; rheumatoid nodules ID PRIMARY SJOGRENS-SYNDROME; RHEUMATOID-ARTHRITIS; CUTANEOUS VASCULITIS; JUVENILE DERMATOMYOSITIS; LUPUS-ERYTHEMATOSUS; ATOPIC-DERMATITIS; BEHCETS-SYNDROME; SEVERITY; SPECTRUM; LESIONS AB This paper focuses on skin manifestations that can be observed in autoimmune diseases such as rheumatoid arthritis (RA), Sjogren syndrome (SS), dermatomyositis (DM) and Behcet syndrome (BS). In RA the most widely recognized skin lesion is the rheumatoid nodule. Other cutaneous manifestations can be observed either non-specific or related to the disease itself and/or to the commonly used drugs. Cutaneous manifestations are considered one of the most typical extraglandular features of primary SS, generally they are distinguished in vasculitic and non vasculitic lesions. Among non-vasculitc lesions, skin dryness (xerosis) has been shown to be very common in pSS while vasculitis lesions include typically flat and palpable purpura and urticarial vasculits. In DM the skin manifestations are also frequent and include a heliotrope rash (blue-purple discoloration) on the upper eyelids with edema, a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron rash). The most frequent mucocutaneous finding in BS is aphthous stomatitis which can not usually be differentiated from idiopatic reccurrent aphthous stomatitis on clinical grounds. The most typical skin manifestations are nodular lesions, which are commonly seen in BS and may be due to panniculitis [erythema nodosum (EN)-like lesions] or superficial thrombophlebitis. C1 Univ Milan, L Sacco Hosp Vialba, Rheumatol Unit, I-20157 Milan, Italy. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Univ Pisa, Dept Internal Med, Rheumatol Unit, Pisa, Italy. NINDS, NIH, Bethesda, MD 20892 USA. Univ Istanbul, Dept Dermatol, Istanbul, Turkey. Univ Istanbul, Dept Pathol, Istanbul, Turkey. Univ Istanbul, Cerraphasa Med Fac, Dept Internal Med, Istanbul, Turkey. RP Sarzi-Puttini, P (reprint author), Univ Milan, L Sacco Hosp Vialba, Rheumatol Unit, Via GB Grassi 74, I-20157 Milan, Italy. EM sarzi@tiscali.it NR 54 TC 19 Z9 20 U1 0 U2 0 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JAN-FEB PY 2006 VL 24 IS 1 SU 40 BP S52 EP S59 PG 8 WC Rheumatology SC Rheumatology GA 024PN UT WOS:000236208500008 PM 16466625 ER PT J AU Bidus, MA Risinger, JI Chandramouli, GVR Dainty, LA Litzi, TJ Berchuck, A Barrett, JC Maxwell, GL AF Bidus, MA Risinger, JI Chandramouli, GVR Dainty, LA Litzi, TJ Berchuck, A Barrett, JC Maxwell, GL TI Prediction of lymph node metastasis in patients with endometrioid endometrial cancer using expression microarray SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 07-11, 2004 CL San Diego, CA SP Soc Gynecol Oncol ID CYCLIN-DEPENDENT KINASES; CARCINOMA; MUTATION; CA-125; MEDULLOBLASTOMA; OVEREXPRESSION; PROTEINS; ZIC2; P53 AB Purpose: To characterize the gene expression profiles of endometrioid endometrial cancers associated with lymph node metastasis in an effort to identify genes associated with metastatic spread. Experimental Design: Tumors from 41 patients with endometrioid endometrial cancer grossly confined to the uterine cavity were evaluated. Positive lymph nodes were noted in 12 of 41 patients. RNA was analyzed for gene expression using the Affymetrix HG133A and HG133B GeneChip set, representing 45,000 array features covering > 28,000 UniGene clusters. Data analysis was done using multidimensional scaling, binary comparison, and hierarchical clustering. Gene expression for several differentially expressed genes was examined using quantitative PCR. Results: Gene expression data was obtained from 30,964 genes that were detected in at least 5% of the cases. Supervised analysis of node-positive versus node-negative cases indicated that 450 genes were significantly differentially expressed between the two classes at P < 0.005, 81 of which were differentially expressed by at least 2-fold at P < 0.005. Overexpressed genes included two cell cycle checkpoint genes, CDC2 and MAD2L1, which have previously been described in association with lymph node metastasis in other cancer types. The Z/C2 zinc finger gene was overexpressed in endometrial cancers with positive nodes versus those with negative nodes. Conclusion: Gene expression profiling of the primary tumors in patients with endometrioid endometrial cancers seems promising for identifying genes associated with lymph node metastasis. Future studies should address whether the status of nodal metastasis can be determined from the expression profiles of preoperative tissue specimens. C1 Walter Reed Army Med Ctr, Div Gynecol Oncol, Washington, DC 20307 USA. US Mil Canc Inst, Washington, DC USA. Natl Canc Inst, Lab Biosyst & Canc, Bethesda, MD USA. Duke Univ, Div Gynecol Oncol, Dept Obstet & Gynecol, Durham, NC USA. RP Maxwell, GL (reprint author), Walter Reed Army Med Ctr, Div Gynecol Oncol, 6900 Georgia Ave, Washington, DC 20307 USA. EM george.maxwell@na.amedd.army.mil FU Intramural NIH HHS NR 33 TC 38 Z9 40 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2006 VL 12 IS 1 BP 83 EP 88 DI 10.1158/1078-0432.CCR-05-0835 PG 6 WC Oncology SC Oncology GA 001AG UT WOS:000234503700014 PM 16397028 ER PT J AU Henrich, KO Fischer, M Mertens, D Benner, A Wiedemeyer, R Brors, B Oberthuer, A Berthold, F Wei, JS Khan, J Schwab, M Westermann, F AF Henrich, KO Fischer, M Mertens, D Benner, A Wiedemeyer, R Brors, B Oberthuer, A Berthold, F Wei, JS Khan, J Schwab, M Westermann, F TI Reduced expression of CAMTA1 correlates with adverse outcome in neuroblastoma patients SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENES; HOMOZYGOUSLY DELETED REGION; MUTATIONAL ANALYSIS; GENOMIC STRUCTURE; CHROMOSOME 1P; SHORT ARM; N-MYC; IDENTIFICATION; 1P36.2; HETEROZYGOSITY AB Purpose: A distal portion of 1p is frequently deleted in human neuroblastomas, and it is generally assumed that this region harbors at least one gene relevant for neuroblastoma development. A 1p36.3 commonly deleted region, bordered by D1S2731 and D1S214 has been defined. The present study surveys whether expression of genes mapping to this region is associated with tumor behavior. Experimental Design: Candidate genes localized within the deleted region were identified by sequence data analysis. Their expression was assessed in a cohort of 49 primary neuroblastomas using cDNA microarray analysis. Gene expression patterns associated with known prognostic markers and patient outcome were further evaluated by quantitative real-time reverse transcription-PCR in a cohort of 102 neuroblastomas. Results: The commonly deleted region spans 261 kb and encompasses two genes, FLJ10737 and CAMTA1. We found no evidence for an association of FLJ10737 expression with established prognostic variables or outcome. In contrast, low CAMTA1 expression characterized tumors with 1p deletion, MYCN amplification, and advanced tumor stages 3 and 4. Moreover, low CAMTA1 expression was significantly associated with poor outcome (P < 0.001). In multivariate analysis of event-free survival, the prognostic information of low CAMTA1 expression was independent of 1p status, MYCN status, tumor stage, and age of the patient at diagnosis (hazard ratio, 3.52; 95% confidence interval, 1.21-10.28; P = 0.02). Conclusions: Our data suggest that assessment of CAMTA1 expression may improve the prognostic models for neuroblastoma and that it will be important to define the biological function of CAMTA1 in this disease. C1 Deutsch Krebsforschungszentrum, Dept Tumour Genet B030, D-69120 Heidelberg, Germany. Deutsch Krebsforschungszentrum, Dept Mol Genet B060, D-69120 Heidelberg, Germany. Deutsch Krebsforschungszentrum, Dept Theoret Bioinformat B080, D-69120 Heidelberg, Germany. Deutsch Krebsforschungszentrum, Cent Unit Biostat, D-69120 Heidelberg, Germany. Univ Cologne, Childrens Hosp, Dept Pediat Oncol, Cologne, Germany. Natl Canc Inst, Pediat Oncol Branch, Oncogenom Sect, Gaithersburg, MD USA. RP Henrich, KO (reprint author), Deutsch Krebsforschungszentrum, Dept Tumour Genet B030, Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM k.henrich@dkfz.de RI Brors, Benedikt/E-5620-2013; Khan, Javed/P-9157-2014; Mertens, Daniel/F-4681-2011 OI Brors, Benedikt/0000-0001-5940-3101; Khan, Javed/0000-0002-5858-0488; Mertens, Daniel/0000-0003-0227-7188 NR 55 TC 43 Z9 49 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2006 VL 12 IS 1 BP 131 EP 138 DI 10.1158/1078-0432.CCR-05-1431 PG 8 WC Oncology SC Oncology GA 001AG UT WOS:000234503700020 PM 16397034 ER PT J AU Lee, GD Longo, DL Wang, Y Rifkind, JM Abdul-Raman, L Mamczarz, JA Duffy, KB Spangler, EL Taub, DD Mattson, MP Ingram, DK AF Lee, GD Longo, DL Wang, Y Rifkind, JM Abdul-Raman, L Mamczarz, JA Duffy, KB Spangler, EL Taub, DD Mattson, MP Ingram, DK TI Transient improvement in cognitive function and synaptic plasticity in rats following cancer chemotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID MORRIS WATER MAZE; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; IMPAIRMENT; CYCLOPHOSPHAMIDE; NEUROTOXICITY; INVOLVEMENT; PERFORMANCE; MECHANISMS; CARCINOMA AB Background: Cancer chemotherapy has been associated with cognitive impairment. Several issues complicate such findings including the patients' health, use of multiple chemotherapeutic agents, and proper assessment of cognition. To control these factors, we conducted cognitive studies in female rats receiving cyclophosphamide or 5-fluorouracil (5FU). Methods: Young (7 months) female Fischer-344 rats received five injections of cyclophosphamide (100 mg/kg), 5FU (150 mg/kg), or saline i.p. every 4 weeks for a total of 18 weeks. Aged (18 months) female Fischer-344 rats were treated with cyclophosphamide (80 mg/kg i.p.) for 16 weeks. After 8 to 10 weeks of recovery, rats were tested in two maze learning tasks, the Morris water maze and the Stone 14-unit T-maze. Neuronal synaptic function was assessed by examining long-term potentiation (LTP) in hippocampal slices obtained from young cyclophosphamide-treated rats. Results: Despite the toxic effects induced by chemotherapy, cyclophosphamide- and 5FU-treated rats showed significantly better maze performance compared with controls. Following 29 to 42 weeks of recovery from chemotherapy, no significant effects were observed on maze performance. In aged rats, cyclophosphamide treatment for 14 weeks also produced toxicity, but no impairment in Stone maze learning after 16 weeks of recovery. When assessed during cyclophosphamide treatment, evidence of impaired LTP emerged; however, with 8 weeks of recovery following five cyclophosphamide treatments, we observed enhanced LTP. Conclusion: Despite toxicity accompanying chemotherapy, no evidence of impaired cognitive performance emerged after recovery. Indeed, following 7 to 9 weeks of recovery, we noted evidence of improved learning and LTP. C1 NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Mol Dynam Sect, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Immunol Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Ingram, DK (reprint author), NIA, Lab Expt Gerontol, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ingramd@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 29 TC 55 Z9 57 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2006 VL 12 IS 1 BP 198 EP 205 DI 10.1158/1078-0432.CCR-05-1286 PG 8 WC Oncology SC Oncology GA 001AG UT WOS:000234503700029 PM 16397043 ER PT J AU Myers, GL Miller, WG Coresh, J Fleming, J Greenberg, N Greene, T Hostetter, T Levey, AS Panteghini, M Welch, M Eckfeldt, JH AF Myers, GL Miller, WG Coresh, J Fleming, J Greenberg, N Greene, T Hostetter, T Levey, AS Panteghini, M Welch, M Eckfeldt, JH CA Natl Kidney Dis Educ Program Lab W TI Recommendations for improving serum creatinine measurement: A report from the laboratory working group of the National Kidney Disease Education Program SO CLINICAL CHEMISTRY LA English DT Review ID GLOMERULAR-FILTRATION-RATE; PERFORMANCE-LIQUID-CHROMATOGRAPHY; EXTERNAL QUALITY-ASSESSMENT; KINETIC JAFFE METHOD; DILUTION MASS-SPECTROMETRY; CANDIDATE REFERENCE METHOD; BILIRUBIN INTERFERENCE; CLINICAL-CHEMISTRY; PLASMA CREATININE; RENAL-DISEASE AB Background: Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given. Methods: The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement. Results: The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study. Conclusions: The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [< 133 mu mol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [< 60 mL (.) min(-1) (.) (1.73 m(2))(-1)]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed. (c) 2006 American Association for Clinical Chemistry C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. Virginia Commonwealth Univ, Dept Pathol, Richmond, VA USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Lab Corp Amer, Dept Sci & Technol, Elon College, NC USA. Ortho Clin Diagnost, Rochester, NY USA. Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. NIDDKD, Natl Kidney Dis Educ Program, Bethesda, MD 20892 USA. Tufts New England Med Ctr, Div Nephrol, Boston, MA USA. Univ Milan, Dept Clin Sci Luigi Sacco, Milan, Italy. NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. RP Myers, GL (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. EM GMyers@cdc.gov NR 136 TC 595 Z9 638 U1 5 U2 44 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JAN PY 2006 VL 52 IS 1 BP 5 EP 18 DI 10.1373/clinchem.2005.052514 PG 14 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 998SE UT WOS:000234338800003 PM 16332993 ER PT J AU Plebani, M Marincola, FM AF Plebani, Mario Marincola, Francesco M. TI Research translation: a new frontier for clinical laboratories SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Review DE biomarkers; clinical practice; genomics laboratory information; proteomics; scientific knowledge; translational research ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; RECOMBINANT ALLERGENS; PROTEOMIC PATTERNS; D-DIMER; VENOUS THROMBOSIS; PROSTATE-CANCER; DIAGNOSIS; FUTURE; BIOMARKERS AB Translational research and translational medicine (referred to hereafter as translational research) are interchangeable terms that underline the pressing need to translate into practical benefits for those affected by disease the extensive investments divested by the private and public sectors in biomedical research. For people more directly involved in clinical practice (physicians, clinical laboratory professionals and patients), translational research responds to the need to accelerate the capture of benefits of research, closing the gap between what we know and what we practice. This basically means the transfer of diagnostic and therapeutic advances proven effective in large, well-conducted trials (and, therefore, evidence-based) to daily medical practice. Translational research should be regarded as a two-way road: bench to bedside, and bedside to bench. In particular, to make possible a more effective translation process, a new road map should be implemented through interaction and cooperation between basic researchers, clinicians, laboratory professionals and manufacturers. Some examples of recent developments in clinical laboratory testing, including markers of cardiovascular diseases, clinical proteomics and recombinant allergens, may explain the importance of careful evaluation of all variables that allow the introduction of such new insights into clinical practice to assure better clinical outcomes. The vital role of laboratory medicine in the delivery of safer and more effective healthcare requires more careful evaluation not only of the analytical characteristics, but also of any other variable that may affect the clinical usefulness and diagnostic performances of laboratory tests, thus allowing more accurate interpretation and utilization of laboratory information. C1 Univ Hos Padova, Dept Lab Med, I-35128 Padua, Italy. Ctr Biomed Res, Castelfranco Veneto, TV, Italy. NIH, Dept Transfus Med, Ctr Clin, Immunogenet Sect, Bethesda, MD 20892 USA. RP Plebani, M (reprint author), Univ Hos Padova, Dept Lab Med, Via Giustiniani,2, I-35128 Padua, Italy. EM mario.plebani@unipd.it NR 82 TC 34 Z9 34 U1 0 U2 5 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PY 2006 VL 44 IS 11 BP 1303 EP 1312 DI 10.1515/CCLM.2006.238 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 112NJ UT WOS:000242532800002 PM 17087640 ER PT J AU Hussain, N Quezado, M Huizing, M Geho, D White, JG Gahl, W Mannon, P AF Hussain, N Quezado, M Huizing, M Geho, D White, JG Gahl, W Mannon, P TI Intestinal disease in Hermansky-Pudlak syndrome: Occurrence of colitis and relation to genotype SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID LYSOSOME-RELATED ORGANELLES; PULMONARY-FIBROSIS; PROTEIN COMPLEX; GRANULOMATOUS COLITIS; VESICLE FORMATION; SYNDROME TYPE-5; BIOGENESIS; HPS4; MUTATIONS; ADAPTER AB Background & Aims: Hermansky-Pudlak syndrome (HPS), a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction, results from mutations in 1 of at least 7 different genes. Some patients develop a fatal pulmonary fibrosis and others a disabling colitis. This study aimed to document the occurrence of colitis among HPS patients, characterize gastrointestinal tract involvement in HPS, and analyze the distribution of colitis among HPS genotypes. Methods: Of the 122 HPS patients followed at the National Institutes of Health Clinical Center between 1993 and 2005, 24 were evaluated by endoscopy for gastrointestinal complaints. The histology of gastrointestinal biopsies was retrospectively examined to assess for inflammatory changes, granulomata, and pigmented macrophages. These data were compared with symptoms and HPS genetic subtypes. Results: At colonoscopy, 7 of 23 patients (30%) had endoscopic mucosal abnormalities, including nodularity, erythema, petechiae, or erosions. Six of these 7 patients (86%) had findings of colitis on biopsy. Of the 16 patients with normal-appearing colonic mucosa, 2 patients (12%) had colitis on biopsy. Pigmented macrophages were also observed in the colonic lamina propria in 16 of the 23 patients (70%). Of the 8 patients with confirmed colitis, 7 had the HPS-1 subtype, and 1 had the HPS-4 subtype. Conclusions: There is an increased frequency of colitis in our population of 122 HPS patients (8/122, 7%) and in HPS patients referred specifically for symptom evaluation (8/24, 33%). Colitis was found in patients with HPS-1 and HPS-4 genotypes. C1 NIAID, Mucosal Immun Sect, Clin Invest Lab, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Gastroenterol, Washington, DC USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. RP Mannon, P (reprint author), NIAID, Mucosal Immun Sect, Clin Invest Lab, Bldg 10-CRC,Room 6-3742,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pmannon@niaid.nih.gov FU Intramural NIH HHS NR 40 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD JAN PY 2006 VL 4 IS 1 BP 73 EP 80 DI 10.1053/S1542-3565(05)00858-X PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 007TI UT WOS:000234992300015 PM 16431308 ER PT J AU Biesecker, BB AF Biesecker, BB TI Genetic counseling for mental illness: goals resemble counseling goals for other common conditions SO CLINICAL GENETICS LA English DT Letter C1 NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, Bldg 2,Room 4W17,Msc 0249,2 Ctr Dr, Bethesda, MD 20892 USA. EM barbarab@mail.nib.gov NR 9 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JAN PY 2006 VL 69 IS 1 BP 93 EP 94 DI 10.1111/j.1399-0004.2006.00554a.x PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 008IR UT WOS:000235034500017 PM 16451142 ER PT J AU Agarwal, R Viley, A Silver, P Grajewski, R Kronenberg, M Murray, P Rutschman, R Chan, CC Caspi, R AF Agarwal, Rojeev Viley, Angelia Silver, Phyllis Grajewski, Rafael Kronenberg, Mitchell Murray, Peter Rutschman, Robert Chan, Chi-Chao Caspi, Rachel TI Abrogation of anti-retinal autoimmunity in IL-10 transgenic mice due to inhibition of priming and effector function of auto-reactive T-cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD USA. La Jolla Inst Allergy & Immunol, Div Dev Immunol, San Diego, CA USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38101 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S41 EP S41 DI 10.1016/j.clim.2006.04.403 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300099 ER PT J AU Blanca, I Marquez, M Ortaldo, J AF Blanca, Isaac Marquez, Maria Ortaldo, John TI B lymphocyte activation pathways induced by interaction with NK cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Cent Univ Venezuela, Inst Inmunol, Caracas, Venezuela. NCI Frederick, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S151 EP S152 DI 10.1016/j.clim.2006.04.063 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300405 ER PT J AU Dissanayake, S Rosenthal, D Hewitt, K Yang, S Wade, M Taub, D Nickoloff, B Trent, J Bittner, M Riker, A Weeraratna, A AF Dissanayake, Samudra Rosenthal, Devin Hewitt, Kyle Yang, Sherry Wade, Michael Taub, Dennis Nickoloff, Brian Trent, Jeffrey Bittner, Michael Riker, Adam Weeraratna, Ashani TI Wnt5a regulates melanoma antigen recognized by T-cells-1 (MART-1), a predominant antigen in melanoma cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIA, NIH, Baltimore, MD 21224 USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Translat Gen Inst, Phoenix, AZ USA. Moffitt Canc Ctr, Tampa, FL USA. RI Riker, Adam/A-6065-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S90 EP S90 DI 10.1016/j.clim.2006.04.153 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300235 ER PT J AU Jaimes, M Darden, J D'Souza, P Lathey, J Maecker, H AF Jaimes, Maria Darden, Janice D'Souza, Patricia Lathey, Janet Maecker, Holden TI Standardization of cytokine flow cytometry assays: NIH/NIAID, SeraCare and BD biosciences Quality Assurance Program. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 BD Biosci, San Jose, CA USA. NIAID, Off Policy Clin Res Operat, NIH, Bethesda, MD 20892 USA. SeraCare Bioserv, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S192 EP S192 DI 10.1016/j.clim.2006.04.522 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300516 ER PT J AU Kushnir-Sukhov, N Brown, J Wu, YL Kirshenbaum, A Metcalfe, D AF Kushnir-Sukhov, Nataliya Brown, Jared Wu, Yalin Kirshenbaum, Arnold Metcalfe, Dean TI Serotonin synthesis, storage and transport in human mast cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIAID, LAD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S53 EP S53 DI 10.1016/j.clim.2006.04.048 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300130 ER PT J AU Lathey, J Oden, N Gregory, S Cox, J Ferrari, G Zimmermann, S Koup, R D'Souza, MP Rodriguez-Chavez, I AF Lathey, Janet Oden, Neat Gregory, Scott Cox, Josephine Ferrari, Guido Zimmermann, Susan Koup, Richard D'Souza, M. Patricia Rodriguez-Chavez, Isaac TI ELISpot proficiency testing for international laboratories participating in HIV vaccine trials. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 SeraCare BioServ, Virol Immunol, Gaithersburg, MD USA. EMMES, Rockville, MD USA. WRAIR, HIV Res Program, Rockville, MD USA. Duke Univ, Med Ctr, HVTN, Durham, NC USA. FHCRC, HVTN, Seattle, WA USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S152 EP S152 DI 10.1016/j.clim.2006.04.365 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300407 ER PT J AU Li, ZQ Sankaranarayana, M Liu, BY Chan, CC Shen, DF Pastan, I Nussenblatt, R AF Li, Zhuqing Sankaranarayana, Mahesh Liu, Baoying Chan, Chi-Chao Shen, DeFeng Pastan, Ira Nussenblatt, Robert TI Eradication of tumor colonization and invasion by a B-cell specific immunotoxin in a murine model for human primary intraocular lymphoma (PIOL). SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S203 EP S203 DI 10.1016/j.clim.2006.04.554 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300548 ER PT J AU Mannon, P Fuss, I Groden, C Friend, J Yang, ZQ Yi, CL Dickensheets, H Hornung, R Donnelly, R Strober, W AF Mannon, Peter Fuss, Ivan Groden, Catherine Friend, Julia Yang, Zhiqiong Yi, Chuli Dickensheets, Harold Hornung, Ronald Donnelly, Raymond Strober, Warren TI Decreased IL-13 production by lamina propria mononuclear cells (LPMCS) accompanies ulcerative colitis (UC) remission and clinical response induced by interferon-beta treatment. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIAID, NIH, Bethesda, MD USA. US FDA, CBER, Bethesda, MD USA. SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S33 EP S34 DI 10.1016/j.clim.2006.04.382 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300078 ER PT J AU Osborne, C Jagannathan, P Royce, C Tilton, J Connors, M Migueles, S AF Osborne, Christine Jagannathan, Prosanna Royce, Cassandra Tilton, John Connors, Mark Migueles, Stephen TI Immunodominance of HLA B57-restricted CD8+ T-cell responses in CMV/HIV co-infected B*57+ long-term nonprogressors is unique to HIV. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIAID, LIR, CMRS, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S184 EP S184 DI 10.1016/j.clim.2006.04.499 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300493 ER PT J AU Perruche, S Chen, WJ AF Perruche, Sytvain Chen, Wanjun TI Apoptotic cell injection as an immuno-regulatory cell-based therapy in SCW-induced arthritis model. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIDCR, Mucosal Immunol Unit, OIIB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S67 EP S68 DI 10.1016/j.clim.2006.04.089 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300171 ER PT J AU Quandt, J Huh, J Pinilla, C Lto, K Martin, R AF Quandt, Jacqueline Huh, Jaebong Pinilla, Clemencia Lto, Kouichi Martin, Roland TI The range of potential targets in antigen-specific therapy are expanded with degenerate autoantigen recognition by T-cells. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIH, Neuroimmunol Branch, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies, Div Immunol, San Diego, CA USA. Univ Med & Dent New Jersey, Dept Neurol, Piscataway, NJ 08854 USA. Univ Autonoma Barcelona, E-08193 Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S106 EP S107 DI 10.1016/j.clim.2006.04.237 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300279 ER PT J AU Shearer, W Deville, J Samson, P Moye, J Fletcher, C Church, J Spiegel, H Palumbo, P Fenton, T Smith, E Graham, B Kraimer, J Olson, W AF Shearer, William Deville, Jaime Samson, Pearl Moye, John, Jr. Fletcher, Courtney Church, Joseph Spiegel, Hans Palumbo, Paul Fenton, Terence Smith, Elizabeth Graham, Bobbie Kraimer, Joyce Olson, William TI Susceptibility of viral isolates of Pediatric AIDS Clinical Trials Group Protocol 351 to Pro 542 (RCD4-IGG2) and PRO 140 (mAB to CCR5). SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Denver, CO USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NIAID, Pediat Med Branch, Div AIDS, Bethesda, MD 20892 USA. Frontier Sci Fdn, Pediat ACTG, Amherst, NY USA. Social & Sci Syst Inc, Pediat ACTG, Silver Spring, MD USA. Progen Pharmaceut Inc, Res & Dev, Tarrytown, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S131 EP S131 DI 10.1016/j.clim.2006.04.307 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300349 ER PT J AU Su, SB Grajewski, R Agarwal, R Silver, P Tang, J Chan, CC Caspi, R AF Su, Shao-Bo Grajewski, Rafael Agarwal, Rajeev Silver, Phyllis Tang, Jun Chan, Chi-Chao Caspi, Rachel TI Interferon-gamma influences manifestations of autoimmune disease by regulating chemokines. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S125 EP S125 DI 10.1016/j.clim.2006.04.291 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300333 ER PT J AU Thomas, J Goodwin, K Rodriguez, C Balgansuren, G Asiedu, C Andrades, P Neville, D AF Thomas, Judith Goodwin, Karen Rodriguez, Celina Balgansuren, Gansuvd Asiedu, Clement Andrades, Patricia Neville, David TI IL-10 and Tregs in rhesus macaques (Rm) with resolute, drug-free, pancreas islet allograft (PITx) tolerance for > 6 years. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 Univ Alabama, Birmingham, AL USA. NIMH, Biophys Chem Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S41 EP S42 DI 10.1016/j.clim.2006.04.404 PG 2 WC Immunology SC Immunology GA 048CD UT WOS:000237924300100 ER PT J AU Uzel, G Patel, S Routes, J Holland, S AF Uzel, Gulbu Patel, Smita Routes, John Holland, Steven TI V61Q mutation supports partial IFN-gamma receptor 1 function. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 6th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 01-05, 2006 CL San Francisco, CA SP Federat Clin Immunol Soc C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Natl Jewish Med Res Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2006 VL 119 SU S BP S138 EP S138 DI 10.1016/j.clim.2006.04.326 PG 1 WC Immunology SC Immunology GA 048CD UT WOS:000237924300368 ER PT J AU Vacek, MM Schaffer, AA Davis, J Fischer, RE Dale, JK Adams, S Straus, SE Puck, JM AF Vacek, MM Schaffer, AA Davis, J Fischer, RE Dale, JK Adams, S Straus, SE Puck, JM TI HLA B44 is associated with decreased severity of autoimmune lymphoproliferative syndrome in patients with CD95 defects (ALPS type Ia) SO CLINICAL IMMUNOLOGY LA English DT Article DE apoptosis; autoimmune lymphoproliferative syndrome; complex inheritance; genetic modifier; fas mutation; HLA; B44 allele; B44 subtypes ID T-CELL RECOGNITION; SINGLE AMINO-ACID; LYMPHOCYTE APOPTOSIS; DISEASE; FAS; MUTATIONS; ANTIGEN; EXPRESSION; POPULATION; INFECTIONS AB Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte apoptosis characterized by non-malignant lymphadenopathy and splenomegaly, expansion of T cells without either CD4 or CD8 surface markers, and increased incidence of autoimmune diseases and lymphoma. Most patients with ALPS have dominant heterozygous imitations in tumor necrosis factor receptor superfamily member 6 (TNFRSF6), which encodes CD95, also known as Fas, a mediator of apoptosis. Penetrance and range of disease manifestations in ALPS are highly variable, even among family members who share the same dominant TNFRSF6 mutation. To evaluate HLA as a candidate modifier locus, we typed HLA A, B (including subtypes), and DQB alleles in 356 individuals from 63 unrelated families with defined TNFRSF6 mutations associated with ALPS. We also developed a quantitative severity score and performed statistical analysis. Among the healthier, mutation-bearing individuals, transmission of HLA B44 was significantly overrepresented (nominal P < 0.0074) as compared to transmission in patients with severe clinical features of ALPS. The B44 allele may exert a protective role ill ALPS. Published by Elsevier Inc. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Natl Ctr Biotechnol Informat, Computat Biol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, HLA Lab, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Room 4A14, Bethesda, MD 20892 USA. EM jpuck@mail.nih.gov RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS NR 38 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JAN PY 2006 VL 118 IS 1 BP 59 EP 65 DI 10.1016/j.clim.2005.09.006 PG 7 WC Immunology SC Immunology GA 006BF UT WOS:000234869400008 PM 16257267 ER PT J AU Briggs, JP Hostetter, TH AF Briggs, Josephine P. Hostetter, Thomas H. TI Opening words for CJASN SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material ID MEMBRANOUS NEPHROPATHY; PROTOCOL BIOPSIES; KIDNEY-DISEASE; TRIAL; PROGRESSION; COHORT C1 NIDDK, KUH Div, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, New York, NY USA. RP Briggs, JP (reprint author), NIDDK, KUH Div, NIH, Bldg 31C,Room 9A17,31 Ctr Dr, Bethesda, MD 20892 USA. EM briggsj@extra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 NR 13 TC 0 Z9 0 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2006 VL 1 IS 1 BP 3 EP 5 DI 10.2215/CJN.01261005 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 106DA UT WOS:000242080000002 PM 17699184 ER PT J AU Bae, KT Zhu, F Chapman, AB Torres, VE Grantham, JJ Guay-Woodford, LM Baumgarten, DA King, BF Wetzel, LH Kenney, PJ Brummer, ME Bennett, WM Klahr, S Meyers, CM Zhang, XL Thompson, PA Miller, JP AF Bae, Kyongtae T. Zhu, Fang Chapman, Arlene B. Torres, Vicente E. Grantham, Jared J. Guay-Woodford, Lisa M. Baumgarten, Deborah A. King, Bernard F., Jr. Wetzel, Louis H. Kenney, Philip J. Brummer, Marijn E. Bennett, William M. Klahr, Saulo Meyers, Catherine M. Zhang, Xiaoling Thompson, Paul A. Miller, J. Philip CA Consortium Radiologic TI Magnetic resonance imaging evaluation of hepatic cysts in early autosomal-dominant polycystic kidney disease: The consortium for radiologic imaging studies of polycystic kidney disease cohort SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID LIVER CYSTS; EXTRARENAL MANIFESTATIONS; COMPUTED-TOMOGRAPHY; PREVALENCE; STEREOLOGY; CT AB The objective of this study was to investigate the prevalence of hepatic cysts by age and gender in patients with early autosomal-dominant polycystic kidney disease (ADPKD) and to determine whether hepatic cyst volume is related to renal and renal cyst volumes by using magnetic resonance imaging (MRI). A total of 230 patients with ADPKD (94 men and 136 women) who were aged 15 to 46 yr and had relatively preserved renal function were studied. MRI images of the kidney and liver were obtained to measure renal, renal cyst, and hepatic cyst volumes. These volume measurements and hepatic cyst prevalence were compared in all patients and in subgroups on the basis of gender and age (15 to 24, 25 to 34, and 35 to 46 yr). The overall prevalence of hepatic cysts was 83%; the prevalence was 58, 85, and 94% in the sequential age groups and 85% in women and 79% in men. The prevalence was related directly to renal volume (chi(2) = 4.30, P = 0.04) and to renal cyst volume (chi(2) = 5.59, P = 0.02). The total hepatic cyst volume was significantly greater in women than in men (a logarithmic transformation mean of 5.27 versus 1.94 ml; P = 0.003). The average hepatic cyst volume was 0.25, 5.75, and 22.78 ml in sequential age groups. Hepatic cysts are evident in 94% of patients who are older than 35 yr and in 55% of individuals who are younger than 25 yr. Hepatic cysts are more prevalent and larger in total cyst volume in women than in men. Hepatic cyst prevalence and aggregate total hepatic cyst volume increased with age. C1 Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Div Biostat, St Louis, MO 63110 USA. Emory Univ, Sch Med, Atlanta, GA USA. Mayo Fdn, Rochester, MN USA. Univ Alabama, Dept Med, Div Renal, Birmingham, AL USA. Univ Alabama, Dept Radiol, Birmingham, AL USA. Univ Kansas, Med Ctr, Kansas City, MO USA. NW Renal Clin, Portland, OR USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Bae, KT (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, Dept Radiol, 510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM baet@mir.wustl.edu OI Miller, J Philip/0000-0003-4568-6846 FU NCRR NIH HHS [M01-RR00039, M01-RR00052, M01-RR00585] NR 26 TC 128 Z9 132 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2006 VL 1 IS 1 BP 64 EP 69 DI 10.2215/CJN.00080605 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 106DA UT WOS:000242080000010 PM 17699192 ER PT J AU Baker, SD Sparreboom, A Verweij, J AF Baker, SD Sparreboom, A Verweij, J TI Clinical pharmalcokinetics of docetaxel - Recent developments SO CLINICAL PHARMACOKINETICS LA English DT Review ID METASTATIC BREAST-CANCER; PERFORMANCE LIQUID-CHROMATOGRAPHY; CELL LUNG-CANCER; ADVANCED SOLID TUMORS; PHASE-I TRIAL; TANDEM MASS-SPECTROMETRY; PEGYLATED LIPOSOMAL DOXORUBICIN; P-GLYCOPROTEIN INHIBITOR; HUMAN PLASMA; ORAL BIOAVAILABILITY AB Docetaxel belongs to the class of taxane antineoplastic agents that act by inducing microtubular stability and disrupting the dynamics of the microtubular network. The drug has shown a broad spectrum of antitumour activity in preclinical models as well as clinically, with responses observed in various disease types, including advanced breast cancer and non-small cell lung cancer. The pharmacokinetics and metabolism of docetaxel are extremely complex and have been the subject of intensive investigation in recent years. Docetaxel is subject to extensive metabolic conversion by the cytochrome P450 (CYP) 3A isoenzymes, which results in several pharmacologically inactive oxidation products. Elimination routes of docetaxel are also dependent on the presence of drug-transporting proteins, notably P-glycoprotein, present on the bile canalicular membrane. The various processes mediating drug elimination, either through metabolic breakdown or excretion, impact substantially on interindividual variability in drug handling. Strategies to individualise docetaxel administration schedules based phenotypic or genotype-dependent differences in CYP3A expression are underway and may ultimately lead to more selective chemotherapeutic use of this agent. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. Natl Canc Inst, Bethesda, MD USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RP Baker, SD (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. EM sbaker7@jhmi.edu RI Sparreboom, Alex/B-3247-2008 NR 134 TC 87 Z9 89 U1 3 U2 13 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2006 VL 45 IS 3 BP 235 EP 252 DI 10.2165/00003088-200645030-00002 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023ZM UT WOS:000236164700002 PM 16509758 ER PT J AU Figg, WD AF Figg, WD TI The 2005 Leon I. Goldberg Young Investigator Award Lecture: Development of thalidomide as an angiogenesis inhibitor for the treatment of androgen-independent prostate cancer SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID PHASE-II TRIAL; DOCETAXEL; ESTRAMUSTINE C1 NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 27 TC 4 Z9 5 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2006 VL 79 IS 1 BP 1 EP 8 DI 10.1016/j.clpt.2005.09.006 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 006SE UT WOS:000234916500001 PM 16413236 ER PT J AU Baker, SG Kramer, BS McIntosh, M Patterson, BH Shyr, Y Skates, S AF Baker, SG Kramer, BS McIntosh, M Patterson, BH Shyr, Y Skates, S TI Evaluating markers for the early detection of cancer: overview of study designs and methods SO CLINICAL TRIALS LA English DT Review ID PROSTATE-SPECIFIC ANTIGEN; BREAST-CANCER; SCREENING STRATEGIES; EARLY INTERVENTION; DIAGNOSTIC-TESTS; CUMULATIVE RISK; OVARIAN-CANCER; FECAL DNA; BIOMARKERS; EFFICACY AB Background: The field of cancer biomarker development has been evolving rapidly. New developments both in the biologic and statistical realms are providing increasing opportunities for evaluation of markers for both early detection and diagnosis of cancer. Purpose: To review the major conceptual and methodological issues in cancer biomarker evaluation, with an emphasis on recent developments in statistical methods together with practical recommendations. Methods: We organized this review by type of study: preliminary performance, retrospective performance, prospective performance and cancer screening evaluation. Results: For each type of study, we discuss methodologic issues, provide examples and discuss strengths and limitations. Conclusion: Preliminary performance studies are useful for quickly winnowing down the number of candidate markers; however their results may not apply to the ultimate target population, asymptomatic subjects. If stored specimens from cohort studies with clinical cancer endpoints are available, retrospective studies provide a quick and valid way to evaluate performance of the markers or changes in the markers prior to the onset of clinical symptoms. Prospective studies have a restricted role because they require large sample sizes, and, if the endpoint is cancer on biopsy, there may be bias due to overdiagnosis. Cancer screening studies require very large sample sizes and long follow-up, but are necessary for evaluating the marker as a trigger of early intervention. C1 Natl Inst Hlth, Bethesda, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Baker, SG (reprint author), NCI, EPN 3131,6130 Execut Blvd MSC 7354, Bethesda, MD 20892 USA. EM sb16i@nih.gov NR 76 TC 45 Z9 46 U1 2 U2 10 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 1 BP 43 EP 56 DI 10.1191/1740774506cn130oa PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 017XJ UT WOS:000235726300005 PM 16539089 ER PT J AU Czaja, SJ Schulz, R Belle, SH Burgio, LD Armstrong, N Gitlin, LN Coon, DW Martindale-Adams, J Klinger, J Stahl, SM AF Czaja, SJ Schulz, R Belle, SH Burgio, LD Armstrong, N Gitlin, LN Coon, DW Martindale-Adams, J Klinger, J Stahl, SM TI Data and safety monitoring in social behavioral intervention trials: the REACH II experience SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIAL; WELL AB Background Psychosocial and behavioral interventions trials targeting a broad range of complex social and behavioral problems such as smoking, obesity and family caregiving have proliferated in the past 30 years. At the same time the use of Data and Safety Monitoring Boards (DSMBs) to monitor the progress and quality of intervention trials and the safety of study participants has increased substantially. Most of the existing literature and guidelines for safety monitoring and reporting of adverse events focuses on medical interventions. Consequently, there is little guidance for investigators conducting social and behavior trials. Purpose This paper summarizes how issues associated with safety monitoring and adverse event reporting were handled in the Resources for Enhancing Alzheimer's Caregiver Health (REACH II) program, a multi-site randomized clinical trial, funded by the National Institutes on Aging (NIA) and the National Institutes of Nursing Research (NINR), that tested the efficacy of a multicomponent social/behavioral intervention for caregivers of persons with Alzheimer's disease. Methods A task force was formed to define adverse events for the trial and protocols for reporting and resolving events that occurred. The task force conducted a review of existing polices and protocols for data and safety monitoring and adverse event reporting and identified potential risks particular to the study population. An informal survey regarding data and safety monitoring procedures with investigators on psychosocial intervention trials was also conducted. Results Two categories of events were defined for both caregivers and patients; adverse events and safety alerts. A distinction was also made between events detected at baseline assessment and those detected post-randomization. Standardized protocols were also developed for the reporting and resolution of events that occurred and training of study personnel. Results from the informal survey indicated wide variability in practices for data safety and monitoring across psychosocial intervention trials. Conclusions Overall, the REACH II experience demonstrates that existing guidelines regarding safety monitoring and adverse event reporting pose unique challenges for social/behavioral intervention trials. Challenges encountered in the REACH 11 program included defining and classifying adverse events, defining "resolution" of adverse events and attributing causes for events that occurred. These challenges are highlighted and recommendations for addressing them in future studies are discussed. C1 Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. Univ Miami, Miller Sch Med, Ctr Aging, Miami, FL 33136 USA. Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Alabama, Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. NINR, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Ctr Appl Res Aging & Hlth, Philadelphia, PA 19107 USA. Arizona State Univ, Dept Social & Behav Sci, Glendale, AZ USA. Univ Tennessee, Ctr Hlth Sci, VA Med Ctr, Memphis, TN 38163 USA. NIA, Behav & Social Res Program, NIH, Bethesda, MD 20892 USA. RP Czaja, SJ (reprint author), Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, 1695 NW 9th Ave,Suite 3204, Miami, FL 33136 USA. EM sczaja@med.miami.edu FU NIA NIH HHS [AG13289, AG13265, AG13305, AG13313, AG20277, U01 AG013265, U01 AG013289, U01 AG013305, U01 AG013313, U01 AG020274]; NINR NIH HHS [NR004261, U01 NR004261, U01 NR004261-07] NR 17 TC 13 Z9 13 U1 0 U2 1 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 2 BP 107 EP 118 DI 10.1191/1740774506cn136oa PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 051CL UT WOS:000238138000008 PM 16773953 ER PT J AU Lai, GY Gary, TL Tilburt, J Bolen, S Baffi, C Wilson, RF Howerton, MW Gibbons, MC Tanpitukpongse, TP Powe, NR Bass, EB Ford, JG AF Lai, GY Gary, TL Tilburt, J Bolen, S Baffi, C Wilson, RF Howerton, MW Gibbons, MC Tanpitukpongse, TP Powe, NR Bass, EB Ford, JG TI Effectiveness of strategies to recruit underrepresented populations into cancer clinical trials SO CLINICAL TRIALS LA English DT Review ID PARTICIPATION; PREVENTION; WOMEN; OLDER; INTERVENTION; DISPARITIES; CHALLENGES; ENROLLMENT; PROGRAMS; AGE AB Background Certain populations, including racial and ethnic minorities and older persons, have had a history of low participation in cancer-related trials, yet there has been little information reported on recruitment strategies tailored to improve their enrollment. Methods We conducted a systematic literature review to examine the methods used to study recruitment of underrepresented populations into cancer prevention and treatment trials and examined the studies that compared the efficacy and/or effectiveness of different recruitment strategies. We performed an electronic search through multiple databases including PubMed and a hand search of 34 journals. Potential studies were pulled and underwent title, abstract, and article review by at least two investigators. Results Fourteen articles examined recruitment of underrepresented populations into cancer trials and, of these, five compared efficacy or effectiveness of different strategies for recruitment of underrepresented populations into randomized or concurrent controlled trials. These five studies used various strategies but only three reported that specific recruitment strategies, such as media campaigns and church-based project sessions, resulted in improvement in accrual to cancer trials. Conclusion There is limited evidence for efficacious or effective strategies to recruit underrepresented populations in cancer-related trials. The available evidence cannot be generalized to these heterogeneous groups. Further study is needed on efficacious strategies for recruitment of underrepresented populations into cancer-related trials. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD USA. NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Evidence Based Practice Ctr, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. Johns Hopkins Univ, Urban Hlth Inst, Baltimore, MD USA. RP Gary, TL (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St E6531, Baltimore, MD 21205 USA. EM tgary@jhsph.edu FU PHS HHS [290-02-0018] NR 27 TC 44 Z9 44 U1 0 U2 5 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 2 BP 133 EP 141 DI 10.1191/1740774506cn143oa PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 051CL UT WOS:000238138000010 PM 16773955 ER PT J AU Dixon, DO Freedman, RS Herson, J Hughes, M Kim, K Silverman, MH Tangen, CM AF Dixon, Dennis O. Freedman, Ralph S. Herson, Jay Hughes, Michael Kim, KyungMann Silverman, Michael H. Tangen, Catherine M. CA SCT Working Grp Data Monitoring TI Guidelines for data and safety monitoring for clinical trials not requiring traditional data monitoring committees SO CLINICAL TRIALS LA English DT Article AB This is a commissioned report by a writing committee formed by the Society for Clinical Trials. The committee was formed with the objectives of I) reviewing data monitoring guidelines for confirmatory (phase III) trials published by the National Institutes of Health, US Food and Drug Administration, Veterans Administration, and the International Conference on Harmonisation and 2) proposing corresponding guidelines for exploratory clinical trials (ie, most phase I and phase II trials and others not requiring a fully independent data monitoring committee). These trials typically involve fewer subjects and are of shorter duration than phase III trials. Nevertheless there are safety concerns, especially because these are often the first human trials for a new intervention. Recommendations are given for appropriate elements of a data monitoring plan, decision criteria for institution of a data monitoring committee (DMC), and critical elements for a DMC to consider in exploratory trials. Review and approval of data monitoring plans are suggested to fall under Institutional Review Board purview. Forming a committee with all the characteristics of a traditional phase III trial monitoring committee may be warranted for a small fraction of exploratory trials. Such a panel could consist of both trial investigators and outside members. The paper concludes with examples of data and safety monitoring practice from the University of Wisconsin Comprehensive Cancer Center and the AIDS Clinical Trials Groups. C1 NIAID, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. BioStrateg Consulting Ltd, Marblehead, MA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Dixon, DO (reprint author), NIAID, NIH, MSC 7609, Bethesda, MD 20892 USA. EM dd23a@nih.giv NR 14 TC 9 Z9 9 U1 0 U2 2 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 3 BP 314 EP 319 DI 10.1191/1740774506cn149oa PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 068ND UT WOS:000239380100006 ER PT J AU Espeland, MA Dotson, K Jaramillo, SA Kahn, SE Harrison, B Montez, M Foreyt, JP Montgomery, B Knowler, WC AF Espeland, M. A. Dotson, K. Jaramillo, S. A. Kahn, S. E. Harrison, B. Montez, M. Foreyt, J. P. Montgomery, B. Knowler, W. C. CA Look Ahead Res Grp TI Consent for genetics studies among clinical trial participants: findings from Action for Health in Diabetes (Look AHEAD) SO CLINICAL TRIALS LA English DT Article ID INFORMED CONSENT; RECRUITMENT; POPULATION; SAMPLES; COHORT AB Background: Increasingly, genetic specimens are collected to expand the value of clinical trials through study of genetic effects on disease incidence, progression or response to interventions. Purpose and methods: We describe the experience obtaining IRB-approved DNA consent forms across the 19 institutions in the Action for Health in Diabetes (Look AHEAD), a clinical trial examining the effect of a lifestyle intervention for weight loss on the risk of serious cardiovascular events among individuals with type 2 diabetes. We document the rates participants provided consent for DNA research, identify participant characteristics associated with consent, and discuss implications for genetics research. Results: IRB approval to participate was obtained from 17 of 19 institutions. The overall rate of consent was 89.6% among the 15 institutions that had completed consenting at the time of our analysis, which was higher than reported for other types of cohort studies. Consent rates were associated with factors expected to be associated with weight loss and cardiovascular disease and to affect the distribution of candidate genes. Non-consent occurred more frequently among participants grouped as African-American, Hispanic, female, more highly educated or not dyslipidemic. Limitations: The generalizabilty of results is limited by the inclusion/exclusion criteria of the trial. Conclusions: Barriers to obtaining consent to participate in genetic studies may differ from other recruitment settings. Because of the potentially complex associations between personal characteristics related to adherence, outcomes and gene distributions, differential rates of consent may introduce biases in estimates of genetic relationships. C1 Wake Forest Univ, Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. NIDDK, Bethesda, MD USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Baylor Coll Med, Behav Med Res Ctr, Houston, TX 77030 USA. NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. RP Espeland, MA (reprint author), Wake Forest Univ, Sch Med, Dept Biostat Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mespelan@wfubmc.edu OI Kriska, Andrea/0000-0002-3522-0869; Kahn, Steven/0000-0001-7307-9002; Redmon, J. Bruce/0000-0002-1883-9467 FU Intramural NIH HHS; NCRR NIH HHS [M01 RR000051, M01 RR000056, M01 RR000056 44, M01 RR000211, M01 RR00051, M01 RR001066, M01 RR002719, M01-RR-01066, M01-RR-02719, M01RR00211-40]; NIDDK NIH HHS [DK57154, DK 046204, DK56990, DK56992, DK57002, DK57008, DK57078, DK57131, DK57135, DK57136, DK57149, DK57151, DK57171, DK57177, DK57178, DK57182, DK57219, P30 DK046204, P30 DK048520, P30DK48520, U01 DK056990, U01 DK056992, U01 DK057002, U01 DK057008, U01 DK057078, U01 DK057131, U01 DK057135, U01 DK057136, U01 DK057136-09, U01 DK057149, U01 DK057151, U01 DK057154, U01 DK057171, U01 DK057177, U01 DK057178, U01 DK057182, U01 DK057219] NR 25 TC 21 Z9 21 U1 2 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 5 BP 443 EP 456 DI 10.1177/1740774506070727 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 109TK UT WOS:000242331500004 PM 17060218 ER PT J AU Chen-Mok, M VanRaden, MJ Higgs, ES Dominik, R AF Chen-Mok, M. VanRaden, M. J. Higgs, E. S. Dominik, R. TI Experiences and challenges in data monitoring for clinical trials within an international tropical disease research network SO CLINICAL TRIALS LA English DT Article ID DATA SAFETY; STATISTICIAN; COMMITTEES; ISSUES; INDEPENDENCE; SPONSOR; BOARDS AB Background. Models for the structure and procedures of data and safety monitoring boards (DSMBs) continue to evolve in response to issues of new and of old concern. Some authors have called for an open dialogue on these questions through publication of the experiences of DSMBs in addressing them. Purpose. The goal of this paper is to add to the current discussion about acceptable models for establishing, serving on, and reporting to monitoring committees, particularly those that oversee multiple studies in less developed countries. The paper seeks to do so by describing the establishment and subsequent operation of one such multi-trial DSMB over a five-year period. This DSMB was formed to monitor trials conducted by members of the International Centers for Tropical Disease Research (ICTDR) network of the National Institute of Allergy and Infectious Diseases (NIAID). Methods. The operational model and experiences are summarized by the authors, who had immediate responsibilities for directing the DSMB's activities. Results. The board played an active, traditional role in assuring that patient safety was maintained and that current standards for clinical research were met. In addition, both MAID and the board members viewed education of investigators to be an important role for the board to play in this particular setting. This affected the threshold for identifying which trials would be monitored, and it impacted several procedures adopted by the board. Limitations. This report reflects the observations of those involved in managing the DSMB, including comments offered by the DSMB and by investigators, but not data gathered in a systematic way. Conclusions. The operational model described here has allowed the DSMB to fulfill its role in the oversight of the trials. We hope that the ideas we present may help others facing similar situations and may stimulate further critical thinking about DSMB structure and function. C1 Family Hlth Int, Durham, NC USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Chen-Mok, M (reprint author), Family Hlth Int, POB 13950, Res Triangle Pk, NC 27709 USA. FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [N01-AI-05403, N01AI05403] NR 32 TC 9 Z9 9 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2006 VL 3 IS 5 BP 469 EP 477 DI 10.1177/1740774506070710 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 109TK UT WOS:000242331500006 PM 17060220 ER PT J AU Marenco, S Weinberger, DR AF Marenco, S Weinberger, DR TI Therapeutic potential of positive AMPA receptor modulators in the treatment of neuropsychiatric disorders SO CNS DRUGS LA English DT Review ID CEREBRAL GLUCOSE-UTILIZATION; SPORADIC ALZHEIMERS-DISEASE; NEUROTROPHIC FACTOR GENE; TO-SAMPLE PERFORMANCE; ANIRACETAM RO 13-5057; SHORT-TERM-MEMORY; GLUTAMATE RECEPTORS; PARKINSONS-DISEASE; RAT HIPPOCAMPUS; SENILE DEMENTIA AB Drugs that potentiate the activity of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor cause a complex cascade of consequences in experimental models, ranging from enhancement of long-term potentiation to induction of neurotrophic factors. Animal studies characterising the pharmacological and behavioural effects of these substances have provided the rationale for several initial attempts to use these drugs in neuropsychiatric clinical settings. Applications in schizophrenia, Alzheimer's disease and mild cognitive impairment have been initiated. Other trials with these compounds include the treatment of Fragile X syndrome, and possible future applications may be in the field of Parkinson's disease. The literature published to date is limited mostly to small phase I or II trials, so there is no conclusive evidence for or against the use of these drugs. Substantial questions remain concerning which compounds to use, in what dose, for what condition and for how long. C1 NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Marenco, S (reprint author), NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, 10 Ctr Dr,Bldg 10,Room 4S235, Bethesda, MD 20892 USA. EM marencos@mail.nih.gov RI Marenco, Stefano/A-2409-2008 OI Marenco, Stefano/0000-0002-2488-2365 NR 100 TC 28 Z9 30 U1 2 U2 3 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2006 VL 20 IS 3 BP 173 EP 185 DI 10.2165/00023210-200620030-00001 PG 13 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 038RF UT WOS:000237240000001 PM 16529524 ER PT J AU Gottesman, S McCullen, CA Guillier, M Vanderpool, CK Majdalani, N Benhammou, J Thompson, KM FitzGerald, PC Sowa, NA FitzGerald, DJ AF Gottesman, S. McCullen, C. A. Guillier, M. Vanderpool, C. K. Majdalani, N. Benhammou, J. Thompson, K. M. FitzGerald, P. C. Sowa, N. A. FitzGerald, D. J. TI Small RNA regulators and the bacterial response to stress SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Proceedings Paper CT 71th Cold Spring Harbor Symposium on Quantitative Biology CY MAY 31-JUN 05, 2006 CL Cold Spring, NY ID SM-LIKE PROTEIN; SMALL NONCODING RNAS; HF-I PROTEIN; ESCHERICHIA-COLI; MESSENGER-RNA; VIBRIO-CHOLERAE; PSEUDOMONAS-AERUGINOSA; RPOS TRANSLATION; ANTISENSE RNA; POSTTRANSCRIPTIONAL REGULATION AB Recent studies have uncovered dozens of regulatory small RNAs in bacteria. A large number of these small RNAs act by pairing to their target mRNAs. The outcome of pairing can be either stimulation or inhibition of translation. pairing in vivo frequently depends on the RNA-binding protein Hfq. Synthesis of these small RNAs is tightly regulated at the level of transcription; many of the well-studied stress response regulons have now been found to include a regulatory RNA. Expression of the small RNA can help the cell cope with environmental stress by redirecting cellular metabolism, exemplified by RyhB, a small RNA expressed upon iron starvation. Although small RNAs found in Escherichia coli can usually be identified by sequence comparison to closely related enterobacteria, other approaches are necessary to find the equivalent RNAs in other bacterial species, Nonetheless, it is becoming increasingly clear that many if not all bacteria encode significant numbers of these important regulators. Tracing their evolution through bacterial genomes remains a challenge. C1 NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Genome Anal Unit, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z01 BC008714-30] NR 80 TC 118 Z9 119 U1 2 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2006 VL 71 BP 1 EP 11 DI 10.1101/sqb.2006.71.016 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 160SO UT WOS:000245962800002 PM 17381274 ER PT J AU Storz, G Opdyke, JA Wassarman, KM AF Storz, G. Opdyke, J. A. Wassarman, K. M. TI Regulating bacterial transcription with small RNAs SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Proceedings Paper CT 71th Cold Spring Harbor Symposium on Quantitative Biology CY MAY 31-JUN 05, 2006 CL Cold Spring, NY ID POLYMERASE-II TRANSCRIPTION; ANTISENSE-RNA; 6S RNA; ESCHERICHIA-COLI; ATTENUATION MECHANISM; PLASMID PIP501; CELL-SURVIVAL; HEAT-SHOCK; IN-VITRO; GENE AB In recent years, the combinations of computational and molecular approaches have led to the identification of an increasing number of small, noncoding RNAs encoded by bacteria and their plasmids and phages. Most of the characterized small RNAs have been shown to operate at a posttranscriptional level, modulating mRNA stability or translation by base-pairing with the 5' regions of the target mRNAs. However, a subset of small RNAs has been found to regulate transcription. One example is tire abundant 6S RNA that has been proposed to compete for DNA binding of RNA polymerase by mimicking the open conformation of promoter DNA. Other small RNAs affect transcription termination via base-pairing interactions with sequences in the mRNA. Here, we discus current understanding and questions regarding the roles of small RNAs in regulating transcription. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA. RP Storz, G (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. OI Storz, Gisela/0000-0001-6698-1241 NR 37 TC 19 Z9 21 U1 1 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2006 VL 71 BP 269 EP 273 DI 10.1101/sqb.2006.71.033 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 160SO UT WOS:000245962800035 PM 17381306 ER PT J AU Zofall, M Grewal, SIS AF Zofall, M. Grewal, S. I. S. TI RNAi-mediated heterochromatin assembly in fission yeast SO COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY LA English DT Proceedings Paper CT 71th Cold Spring Harbor Symposium on Quantitative Biology CY MAY 31-JUN 05, 2006 CL Cold Spring, NY ID MATING-TYPE REGION; HISTONE H3 LYSINE-9; BINDING-PROTEIN TAZ1; JMJC DOMAIN PROTEIN; DOUBLE-STRANDED-RNA; SCHIZOSACCHAROMYCES-POMBE; EPIGENETIC CONTROL; PERICENTRIC HETEROCHROMATIN; CHROMOSOMAL LOCATIONS; REPRESS TRANSCRIPTION AB The organization of DNA into heterochromatin domains is critical for a variety of chromosomal functions, including gene silencing, recombination suppression, and chromosome segregation. In fission yeast, factors involved in the RNAi pathway such as Argonaute, Dicer, and RNA-dependent RNA polymerase are required for assembly of heterochromatin structures. The RNAi N-gonaute-containing RITS complex and RNA-dependent RNA polymerase localize throughout heterochromatin domains. These factors are important components of a self-reinforcing loop mechanism operating in cis to process repeat transcripts into siRNAs, which involve in heterochromatin assembly. Ill this paper, we describe our results suggesting that slicing of repeat transcripts by the Argonaute is an important step in their conversion into siRNAs and heterochromatic silencing. Mutation; in conserved residues known to be essential for slicer activity of Argonautes result in loss of siRNAs corresponding to centromeric repeats, accumulation of repeat transcripts, and defects in heterochromatin assembly. We also discuss Our recent finding that heterochromatin proteins such as Swi6/HP1 serve as it platform that could recruit both silencing and anti-silencing factors to heterochromatic loci. C1 NIH, NCI, Mol Cell Biol Lab, Bethesda, MD 20892 USA. RP Zofall, M (reprint author), NIH, NCI, Mol Cell Biol Lab, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 97 TC 39 Z9 42 U1 0 U2 6 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0091-7451 J9 COLD SPRING HARB SYM JI Cold Spring Harbor Symp. Quant. Biol. PY 2006 VL 71 BP 487 EP 496 DI 10.1101/sqb.2006.71.059 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 160SO UT WOS:000245962800060 PM 17381331 ER PT J AU Besada, P Mamedova, LK Palaniappan, KK Gao, ZG Joshi, BV Jeong, LS Civan, MM Jacobson, KA AF Besada, Pedro Mamedova, Liaman K. Palaniappan, Krishnan K. Gao, Zhan-Guo Joshi, Bhalchandra V. Jeong, Lak Shin Civan, Mortimer M. Jacobson, Kenneth A. TI Nucleoside prodrugs of A(3) adenosine receptor agonists and antagonists SO COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS LA English DT Article DE purines; nucleosides; G protein-coupled receptors; adenosine receptors; receptor binding assays; adenylate cyclase; prodrugs ID INTRAOCULAR-PRESSURE; HIGHLY POTENT; LIGANDS; DERIVATIVES; A(1); CARDIOPROTECTION; CF101; RAT AB 9-(beta-D-Ribosfuranosyluronamide)adenine derivatives that are selective agonists and antagonists of the A(3) adenosine receptor (AR) have been derivatized as prodrugs for in vivo delivery. The free hydroxy groups at the 2' and 3' positions of the agonists 2-chloro-N-6-(3-iodobenzyl)-9-(N-methyl-(beta-D-ribosfuranosyluronamide)adenine 2b, the corresponding 4'-thio nucleoside 2c, and antagonists 4a and 4b (5'-N,N-dimethylamides related to 2b and 2c, respectively) were derivatized through simple acylation reactions. The prodrug derivatives were tested in radioligand binding assays at ARs and in a functional assay of adenylate cyclase at the A(3)AR and found to be considerably less active than the parent drugs. The hydrolysis of nucleoside 2',3'-diesters to regenerate the parent compound in the presence of human blood was demonstrated. 2',3'-Dipropionate esters of 2b and 4a were readily cleaved in a two-step reaction to regenerate the parent drug, on a time scale of two hours. The cleavage of a 2',3'-dihexanoate ester occurred at a slower rate. This indicates that the prodrugs are suitable as masked forms of the biologically active A(3)AR agonists and antagonists for future evaluation in vivo. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. Univ Penn, Dept Physiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM pedrop@intra.niddk.nih.gov; mamedoval@intra.niddk.nih.gov; palaniappank@mail.nih.gov; zhanguog@intra.niddk.nih.gov; balachandraj@intra.niddk.nih.gov; lakjeong@ewha.ac.kr; civan@mail.med.upenn.edu; kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063 NR 29 TC 2 Z9 2 U1 0 U2 3 PU INST ORGANIC CHEM AND BIOCHEM PI PRAGUE 6 PA ACAD SCI CZECH REPUBLIC, FLEMINGOVO NAM 2, PRAGUE 6 166 10, CZECH REPUBLIC SN 0010-0765 J9 COLLECT CZECH CHEM C JI Collect. Czech. Chem. Commun. PY 2006 VL 71 IS 6 BP 912 EP 928 DI 10.1135/cccc20060912 PG 17 WC Chemistry, Multidisciplinary SC Chemistry GA 054ZZ UT WOS:000238419500013 ER PT J AU Matthews, AG Betensky, RA Anton-Culver, H Bowen, D Griffin, C Isaacs, C Kasten, C Mineau, G Nayfield, S Schildkraut, J Strong, L Weber, B Finkelstein, DM AF Matthews, AG Betensky, RA Anton-Culver, H Bowen, D Griffin, C Isaacs, C Kasten, C Mineau, G Nayfield, S Schildkraut, J Strong, L Weber, B Finkelstein, DM TI Analysis of co-aggregation of cancer based on registry data SO COMMUNITY GENETICS LA English DT Article DE familial aggregation; association; family study; Cancer Genetics Network ID COLORECTAL-CANCER; OVARIAN-CANCER; FAMILY-HISTORY; LUNG-CANCER; BREAST; SUSCEPTIBILITY; RISKS; AGGREGATION; LEUKEMIA; MODELS AB Objective: An exploratory analysis of co-aggregation of cancers using registry-based data. Methods:We utilized sibships from over 18,000 families who had been recruited to the NCI-sponsored multi-institutional Cancer Genetics Network. The analysis assesses co-aggregation at the individual and family level and adjusts for ascertainment. Results: We found statistically significant familial co-aggregation of lung cancer with pancreatic (adjusted p < 0.001), prostate (adjusted p < 0.003), and colorectal cancers (adjusted p = 0.004). In addition, we found significant familial co-aggregation of pancreatic and colorectal cancers (adjusted p = 0.018), and co-aggregation of hematopoietic and (non-ovarian) gynecologic cancers (adjusted p = 0.01). Conclusion: This analysis identified familial aggregation of cancers for which a genetic component has yet to be established. Copyright (C) 2006 S. Karger AG, Basel. C1 Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Calif Irvine, Irvine, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Johns Hopkins Univ, Baltimore, MD USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Penn, Philadelphia, PA 19104 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. EM dfinkelstein@partners.org FU NCI NIH HHS [CA 74302, CA 75971] NR 32 TC 3 Z9 3 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2006 VL 9 IS 2 BP 87 EP 92 DI 10.1159/000091485 PG 6 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 031EY UT WOS:000236688200003 PM 16612058 ER PT J AU Fomous, C Mitchell, JA McCray, A AF Fomous, Cathy Mitchell, Joyce A. McCray, Alexa TI 'Genetics home reference': Helping patients understand the role of genetics in health and disease SO COMMUNITY GENETICS LA English DT Article DE consumer information, genetics; chromosomal disorders; medical informatics applications ID INFORMATION; INTERNET AB The surge of information generated by the Human Genome Project has left many health professionals and their patients struggling to understand the role of genetics in health and disease. To aid the lay public and health professionals, the US National Library of Medicine developed an online resource called 'Genetics Home Reference' (GHR), located at http://ghr.nlm.nih.gov/. Launched in April 2003, GHR's goal is to help the public interpret the health implications of the Human Genome Project. It bridges the clinical questions of consumers and the rich technical data emerging from the sequenced human genome. The GHR web site is designed for easy navigation among summaries for genetic conditions and the related gene(s) and chromosome(s). This design strategy enhances the user's appreciation of how genes, chromosomes, and conditions are interrelated. Copyright (C) 2006 S. Karger AG, Basel. C1 Natl Lib Med, Bethesda, MD 20894 USA. Univ Utah, Sch Med, Salt Lake City, UT USA. Harvard Univ, Sch Med, Boston, MA USA. RP Fomous, C (reprint author), Natl Lib Med, 8600 Rockville Pike,Bldg 38A,Room 7S704, Bethesda, MD 20894 USA. EM fomous@nlm.nih.gov NR 29 TC 4 Z9 4 U1 0 U2 3 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2006 VL 9 IS 4 BP 274 EP 278 DI 10.1159/000094477 PG 5 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 089RH UT WOS:000240897800010 PM 17003538 ER PT J AU Nestadt, G Hsu, FC Samuels, J Bienvenu, OJ Reti, I Costa, PT Eaton, WW AF Nestadt, G Hsu, FC Samuels, J Bienvenu, OJ Reti, I Costa, PT Eaton, WW TI Latent structure of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition personality disorder criteria SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID DSM-III-R; AREA FOLLOW-UP; COMMUNITY SAMPLE; PSYCHOPATHOLOGY; PREVALENCE; SYMPTOMS; RATINGS; HEALTH AB Aims: This study investigated the internal construct validity of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition(DSM-IV) personality disorders and explored alternative models to characterize the personality disorder traits. The relationship between the obtained personality disorder dimensions and measures of functioning and disability was examined. Methods: The subjects in the study were 742 community-residing individuals who participated in the Hopkins Epidemiology of Personality Disorders Study. The presence of DSM-IV personality disorder traits was assessed by psychologists using the International Personality Disorder Examination (IPDE). Confirmatory factor analysis was performed on all the IPDE criteria for each of the 10 personality disorders using the Mplus program. Exploratory factor analysis of all personality disorder traits was completed using the same program. Factor scores were correlated with subjects' GAF ratings and number of missed days from work for physical and psychological reasons.. Results: A single underlying factor was found for the IPDE item criteria of avoidant and dependent personality disorder, with less evidence for the other 8 personality disorders. Five factors were retained as the dimensional accounting for the personality disorder. criteria. These factors were named compulsive, neurotic avoidant, aloof, impulsive callous, and egocentric. Of the five factors, 4 were associated with evidence of diminished functioning. Conclusions: The IPDE pathological personality traits did not empirically cluster according to the current DSM-IV axis. II diagnostic system but instead defined 5 relatively independent PD symptom dimensions that were related to functional impairments. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Johns Hopkins Sch Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712 FU NIMH NIH HHS [MH50616, MH47447, K23-MH64543] NR 35 TC 52 Z9 52 U1 4 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD JAN-FEB PY 2006 VL 47 IS 1 BP 54 EP 62 DI 10.1016/j.comppsych.2005.03.005 PG 9 WC Psychiatry SC Psychiatry GA 996MM UT WOS:000234178000008 PM 16324903 ER PT S AU Przytycka, TM AF Przytycka, Teresa M. BE Alexandrov, VN VanAlbada, GD Sloot, PMA TI Chordal graphs in computational biology - New insights and applications SO COMPUTATIONAL SCIENCE - ICCS 2006, PT 2, PROCEEDINGS SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 6th International Conference on Computational Science (ICCS 2006) CY MAY 28-31, 2006 CL Reading, ENGLAND SP Intel Corp, IBM, SGI, Microsoft Res, EPSRC, Springer, ACET Ctr, Univ Reading, SIAM, IMACS, UK e Sci Programme C1 NIH, NCBI, Natl Lib Med, Bethesda, MD 20892 USA. RP Przytycka, TM (reprint author), NIH, NCBI, Natl Lib Med, 9000 Rockville Pike,Bldg 1,Rm 126, Bethesda, MD 20892 USA. EM przytyck@ncbi.nlm.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-34381-4 J9 LECT NOTES COMPUT SC PY 2006 VL 3992 BP 620 EP 621 PG 2 WC Computer Science, Theory & Methods SC Computer Science GA BEO13 UT WOS:000238389400084 ER PT J AU Woods, JW Sneiderman, CA Hameed, K Ackerman, MJ Hatton, C AF Woods, JW Sneiderman, CA Hameed, K Ackerman, MJ Hatton, C TI Using UMLS metathesaurus concepts to describe medical images: dermatology vocabulary SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE vocabulary; dermatology; UMLS; Metathesaurus; indexing; WWW; Internet; semantics; concept name ID RETRIEVAL; SUPPORT AB Web servers at the National Library of Medicine (NLM) displayed images of ten skin lesions to practicing dermatologists and provided an online form for capturing text they used to describe the pictures. The terms were submitted to the UMLS Metathesaurus (Meta). Concepts retrieved, their semantic types, definitions and synonyms, were returned to each subject in a second web-based form. Subjects rated the concepts against their own descriptive terms. They submitted 825 terms, 346 of which were unique and 300 mapped to UMLS concepts. The dermatologists rated 295 concepts as `Exact Match' and they accomplished both tasks in about 30 min. Published by Elsevier Ltd. C1 Natl Lib Med, Ackerman Off High Performance Comp & Commun, Bethesda, MD 20894 USA. Aga Khan Univ, Natl Lib Med, Dept Med, Off High Performance Comp & Commun, Karachi, Pakistan. RP Woods, JW (reprint author), Natl Lib Med, Ackerman Off High Performance Comp & Commun, 38A-B1N30F1, Bethesda, MD 20894 USA. EM woodsj@mail.nlm.nih.gov NR 13 TC 5 Z9 5 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JAN PY 2006 VL 36 IS 1 BP 89 EP 100 DI 10.1016/j.compbiomed.2004.08.003 PG 12 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA 998OB UT WOS:000234327300006 PM 16324910 ER PT S AU Brazhnik, O AF Brazhnik, Olga BE Embley, DW Olive, A Ram, S TI Geometry of concepts SO CONCEPTUAL MODELING - ER 2006, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 25th International Conference on Conceptual Modeling CY NOV 06-09, 2006 CL Tucson, AZ SP ER Inst, ACM SIGMIS, ACM SIGMOD, Univ Arizona, Eller Coll Management C1 [Brazhnik, Olga] Ctr Informat Technol, NIH, 10401 Fernwood Rd, Bethesda, MD 20897 USA. RP Brazhnik, O (reprint author), Ctr Informat Technol, NIH, 10401 Fernwood Rd, Bethesda, MD 20897 USA. EM brazhnik@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-47224-X J9 LECT NOTES COMPUT SC PY 2006 VL 4215 BP 587 EP 587 PG 1 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BFM79 UT WOS:000243115800052 ER PT J AU Matot, I Weiniger, CF Zeira, E Galun, E Joshi, BV Jacobson, KA AF Matot, Idit Weiniger, Carolyn F. Zeira, Evelyne Galun, Eithan Joshi, Bhalchandra V. Jacobson, Kenneth A. TI A(3) adenosine receptors and mitogen-activated protein kinases in lung injury following in vivo reperfusion SO CRITICAL CARE LA English DT Article ID ISCHEMIA-REPERFUSION; PULSATILE FLOW; CARDIOPULMONARY BYPASS; MOLECULAR-CLONING; CONSCIOUS RABBITS; INDUCED APOPTOSIS; CARDIAC-SURGERY; PERFUSED HEART; MAP KINASES; RAT LUNG AB Introduction Although activation of A(3) adenosine receptors attenuates reperfusion lung injury and associated apoptosis, the signaling pathway that mediates this protection remains unclear. Adenosine agonists activate mitogen-activated protein kinases, and these kinases have been implicated in ischemia/reperfusion injury; the purpose of this study was therefore to determine whether A(3) adenosine receptor stimulation with reperfusion modulates expression of the different mitogen-activated protein kinases. In addition, we compared the effect of the A(3) adenosine agonist IB-MECA with the newly synthesized, highly selective A(3) adenosine receptor agonist MRS3558 on injury in reperfused lung. Method Studies were performed in an in vivo spontaneously breathing cat model, in which the left lower lobe of the lung was isolated and subjected to 2 hours of ischemia and 3 hours of reperfusion. The selective A(3) adenosine receptor agonists IB-MECA (0.05 mg/kg, 0.1 mg/kg, or 0.3 mg/kg) and MRS3558 ( 0.05 mg/kg or 0.1 mg/kg) were administered before reperfusion. Results Both A(3) adenosine receptor agonists administered before reperfusion markedly ( P < 0.01) attenuated indices of injury and apoptosis, including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, TUNEL ( in situ TdT-mediated dUTP nick end labeling)-positive cells, and caspase 3 activity and expression. The more pronounced effects at low doses were observed with MRS3558. Increases in phosphorylated c-Jun amino-terminal protein kinase ( JNK), p38, and extracellular signal-regulated kinase (ERK) 1/2 levels were observed by the end of reperfusion compared with controls. Pretreatment with the A(3) agonists upregulated phosphorylated ERK1/2 levels but did not modify phosphorylated JNK and p38 levels. Conclusion The protective effects of A(3) adenosine receptor activation are mediated in part through upregulation of phosphorylated ERK. Also, MRS3558 was found to be more potent than IB-MECA in attenuating reperfusion lung injury. The results suggest not only that enhancement of the ERK pathway may shift the balance between cell death and survival toward cell survival, but also that A(3) agonists have potential as an effective therapy for ischemia/reperfusion-induced lung injury. C1 Hebrew Univ Jerusalem, Hadassah Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Univ Med Ctr, Goldyne Savad Inst Gene Therapy, Jerusalem, Israel. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Matot, I (reprint author), Hebrew Univ Jerusalem, Hadassah Univ Med Ctr, Dept Anesthesiol & Crit Care Med, Jerusalem, Israel. EM iditm@hadassah.org.il RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 54 TC 34 Z9 35 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PY 2006 VL 10 IS 2 AR R65 DI 10.1186/cc4893 PG 11 WC Critical Care Medicine SC General & Internal Medicine GA 083DP UT WOS:000240436400026 PM 16623960 ER PT J AU Nylen, ES Seam, N Khosla, R AF Nylen, ES Seam, N Khosla, R TI Endocrine markers of severity and prognosis in critical illness SO CRITICAL CARE CLINICS LA English DT Review ID C-REACTIVE PROTEIN; INFLAMMATORY RESPONSE SYNDROME; MIGRATION INHIBITORY FACTOR; ACUTE MYOCARDIAL-INFARCTION; PLATELET-ACTIVATING-FACTOR; BRAIN NATRIURETIC PEPTIDE; MULTIPLE ORGAN DYSFUNCTION; INTENSIVE INSULIN THERAPY; INDEPENDENT RISK-FACTOR; INCREASED PLASMA-LEVELS AB The cellular processes that unfold in critical illness involve a variety of circulating substances, that may provide clinically relevant insight into the severity and outcome. Among hormonal markers, cortisol, several thyroid-related substances, as well as natriuretic peptides are discussed in this review. Glucose and lipids constitute metabolic markers, the identification and treatment of the former has been of particular importance. Among immune markers, both proinflammatory and anti-inflammatory cytokines, such as interleukin-6, contribute essential prognostic information. Finally, the complement and coagulation pathways also provide unique insight into this complex and heterogeneous process. C1 Vet Affairs Med Ctr, Washington, DC 20422 USA. George Washington Univ, Sch Med, Washington, DC 20037 USA. NIH, Bethesda, MD USA. RP Nylen, ES (reprint author), Vet Affairs Med Ctr, 50 Irving St NW, Washington, DC 20422 USA. EM eric.nylen@med.va.gov NR 153 TC 2 Z9 2 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0704 J9 CRIT CARE CLIN JI Crit. Care Clin. PD JAN PY 2006 VL 22 IS 1 BP 161 EP + DI 10.1016/j.ccc.2005.08.002 PG 20 WC Critical Care Medicine SC General & Internal Medicine GA 008EZ UT WOS:000235024300012 PM 16399026 ER PT J AU Morris, A Masur, H Huang, L AF Morris, A Masur, H Huang, L TI Current issues in critical care of the human immunodeficiency virus-infected patient SO CRITICAL CARE MEDICINE LA English DT Review DE intensive care; human immunodeficiency virus; acquired immunodeficiency syndrome; antiretroviral therapy; epidemiology ID ACTIVE ANTIRETROVIRAL THERAPY; PNEUMOCYSTIS-CARINII-PNEUMONIA; ACUTE RESPIRATORY-FAILURE; INDUCED LACTIC-ACIDOSIS; INTENSIVE-CARE; PROTEASE INHIBITORS; HIV PATIENTS; RISK-FACTORS; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY COMPLICATIONS AB Objective: To provide current information on the epidemiology of human immunodeficiency virus (HIV)-infected patients admitted to the intensive care unit during the era of combination antiretroviral therapy and to review issues related to the administration of antiretroviral therapy that are relevant to the intensivist. Design: Review of literature related to intensive care of HIV-infected patients. Results: Overall mortality of HIV-infected patients in the intensive care unit has decreased in the era of combination antiretroviral therapy, and patients are more commonly admitted with non-HIV-related illnesses. Use of antiretroviral therapy in the intensive care unit is difficult but may be associated with improved outcomes. Conclusions: HIV-infected patients are less likely to be admitted to the intensive care unit with opportunistic infections but more likely to be admitted with problems unrelated to HIV infection or with conditions related to antiretroviral therapy. With current management strategies, more patients survive intensive care unit admission. Intensivists need to be familiar with antiretroviral therapy to recognize life-threatening toxicities unique to these drugs; to avoid drug interactions, which are extremely common and potentially life-threatening; and to avoid enhancing HIV drug resistance, an occurrence that could have devastating consequences for the patient following intensive care unit discharge. C1 Univ So Calif, Dept Med, Div Pulm & Crit Care Med, Keck Sch Med, Los Angeles, CA 90089 USA. NIH, Crit Care Med Clin Ctr, Bethesda, MD 20892 USA. Univ Calif San Francisco, AIDS Chest Clin, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA 94143 USA. San Francisco Gen Hosp, HIV AIDS Div, San Francisco, CA 94110 USA. RP Morris, A (reprint author), Univ So Calif, Dept Med, Div Pulm & Crit Care Med, Keck Sch Med, Los Angeles, CA 90089 USA. RI Andrade, Hugo/M-6631-2013; OI Andrade, Hugo/0000-0001-6781-6125; Huang, Laurence/0000-0003-3888-2195 FU NHLBI NIH HHS [HL072117, HL072837, K23 HL072117, K23 HL072117-03] NR 62 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2006 VL 34 IS 1 BP 42 EP 49 DI 10.1097/01.CCM.0000194539.50905.81 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 999IB UT WOS:000234381900006 PM 16374154 ER PT J AU Deans, KJ Minneci, PC Banks, SM Natanson, C Eichacker, PQ AF Deans, KJ Minneci, PC Banks, SM Natanson, C Eichacker, PQ TI Tidal volumes in acute respiratory distress syndrome - One size does not fit all - The authors reply SO CRITICAL CARE MEDICINE LA English DT Letter ID ACUTE LUNG INJURY; MECHANICAL VENTILATION; THERAPY C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Deans, KJ (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 12 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JAN PY 2006 VL 34 IS 1 BP 264 EP 267 DI 10.1097/01.CCM.0000191120.08246.E3 PG 4 WC Critical Care Medicine SC General & Internal Medicine GA 999IB UT WOS:000234381900052 ER PT J AU Sun, Y Li, H Yang, H Rao, MS Zhan, M AF Sun, Yu Li, Huai Yang, Henry Rao, Mahendra S. Zhan, Ming TI Mechanisms controlling embryonic stem cell self-renewal and differentiation SO CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION LA English DT Review DE embryonic stem cells; self-renewal; pluripotency; regulatory network; LIF; Wnt; Nodal; Nanog; Oct4; Sox2; Myc; p53 ID GLYCOGEN-SYNTHASE KINASE-3-BETA; ES CELLS; GENE-EXPRESSION; MOLECULAR SIGNATURE; MOUSE EMBRYOS; ID PROTEINS; VERTEBRATE DEVELOPMENT; DEFINED CONDITIONS; PLURIPOTENT CELLS; FEEDER LAYERS AB Embryonic stem (ES) cells are pluripotent cells with indefinite replication potential and ability to differentiate into all types of cells. An understanding of the regulatory mechanisms responsible for pluripotency in ES cells is critical for realizing their potential in regenerative medicine and science. Cross-species studies on ES cells have identified pathways and networks that are either fundamental to or species-specific for self-renewal and differentiation. Although pluripotency as an essential function in multicellular organisms is conserved through evolution, mechanisms primed for differentiation contribute substantially to the differences among stem cells derived from different tissues or species. Transcriptome mapping analysis has determined the chromosomal domains of gene coexpression patterns specific to the ES state and demonstrated that regulation of ES cell development is operative at both the local chromosomal domain level and global level. Combinatorial signals from multiple pathways regulate the expression of key intrinsic factors critical for ES cell fate determination. The regulatory core formed by Oct4, Sox2, and Nanog, in particular, activates genes critical for self-renewal and represses genes initiating differentiation, controlling ES cell pluripotency. Here, we review recent findings on mechanisms controlling ES cell development. By integrating data from different sources, we present a global picture of how ES cells reach the decision of self-renewal or differentiation. C1 NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. Bioinformat Inst, Singapore 138671, Singapore. Johns Hopkins Univ, Sch Med, Neurosci Program, Baltimore, MD 21224 USA. Invitorgen Corp, CRL, Carlsbad, CA 92008 USA. RP Zhan, M (reprint author), NIA, Bioinformat Unit, Res Resources Branch, NIH, Baltimore, MD 21224 USA. EM zhanmi@mail.nih.gov FU Intramural NIH HHS NR 110 TC 31 Z9 40 U1 3 U2 10 PU BEGELL HOUSE INC PI REDDING PA 50 CROSS HIGHWAY, REDDING, CT 06896 USA SN 1045-4403 J9 CRIT REV EUKAR GENE JI Crit. Rev. Eukaryot. Gene Expr. PY 2006 VL 16 IS 3 BP 211 EP 231 PG 21 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 097IX UT WOS:000241441800002 PM 17073552 ER PT J AU Brydges, S Kastner, DL AF Brydges, S Kastner, DL TI The systemic autoinflammatory diseases: Inborn errors of the innate immune system SO CURRENT CONCEPTS IN AUTOIMMUNITY AND CHRONIC INFLAMATION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID FAMILIAL MEDITERRANEAN FEVER; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MULTISYSTEM INFLAMMATORY DISEASE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; DEATH-DOMAIN-FOLD; CONTAINING APAF1-LIKE PROTEIN; BACTERIAL MURAMYL DIPEPTIDE; CASPASE RECRUITMENT DOMAIN; ENCODING MEVALONATE KINASE AB The autoinflammatory syndromes are a newly recognized group of immune disorders that lack the high titers of self-reactive antibodies and T cells characteristic of classic autoimmune disease. Nevertheless, patients with these illnesses experience unprovoked inflammatory disease in the absence of underlying infection. Here we discuss recent advances in eight Mendelian autoinflammatory diseases. The causative genes and the proteins they encode play a critical role in the regulation of innate immunity. Both pyrin and cryopyrin, the proteins mutated in familial Mediterranean fever and the cryopyrinopathies, respectively, are involved in regulation of the proinflammatory cytokine, IL-1 beta, and may influence the activity of the transcription factor, NF kappa B. NOD2, the Blau syndrome protein, shares certain domains with cryopyrin and appears to be a sensor of intracellular bacteria. PSTPIP1, mutated in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne, interacts both with pyrin and a protein tyrosine phosphatase to regulate innate and adaptive immune responses. Somewhat unexpectedly, mutations in the p55 TNF receptor lead not to immunodeficiency but to dramatic inflammatory disease, the mechanisms of which are still under investigation. Finally, the discovery of the genetic basis of the hyper-immunoglobulinemia D with periodic fever syndrome has provided a fascinating but incompletely understood link between cholesterol biosynthesis and autoinflammation. In this manuscript, we summarize the current state of the art with regard to the diagnosis, pathogenesis, and treatment of these inborn errors of the innate immune system. C1 NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. RP Brydges, S (reprint author), NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. EM brydgess@mail.nih.gov NR 175 TC 48 Z9 49 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 305 BP 127 EP 160 DI 10.1007/3-540-29714-6_7 PG 34 WC Immunology; Microbiology SC Immunology; Microbiology GA BEM88 UT WOS:000238216500007 PM 16724804 ER PT J AU Skapenko, A Lipsky, PE Schulze-Koops, H AF Skapenko, A Lipsky, PE Schulze-Koops, H TI T cell activation as starter and motor of rheumatic inflammation SO CURRENT CONCEPTS IN AUTOIMMUNITY AND CHRONIC INFLAMATION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID COLLAGEN-INDUCED ARTHRITIS; MONOCLONAL-ANTIBODY; SYNOVIAL-FLUID; PERIPHERAL-CIRCULATION; CYTOKINE PATTERNS; INTERFERON-GAMMA; GERMINAL-CENTERS; MESSENGER-RNA; DOUBLE-BLIND; TH1 AB Rheumatic inflammation is driven by sustained specific immunity against self-antigens, resulting in local inflammation and cellular infiltration and, subsequently, in tissue damage. Although the specific autoantigen(s) eliciting the detrimental immune reactions in rheumatic diseases have rarely been defined, it has become clear that the mechanisms resulting in the destruction of tissue and the loss of organ function during the course of the diseases are essentially the same as in protective immunity against invasive microorganisms. Of fundamental importance in initiating, controlling, and driving these specific immune responses are CD4 T cells. Currently available data provide compelling evidence for a major role of CD4 T cells in the initiation and perpetuation of chronic rheumatic inflammation. Consequently, T cell-directed therapies have been employed with substantial clinical success in the treatment of rheumatic diseases. Here, we review current knowledge based on which CD4 T cells can be implicated as the motor of rheumatic inflammation. C1 Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, Dept Internal Med 3, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany. NIAMSD, Bethesda, MD 20892 USA. RP Schulze-Koops, H (reprint author), Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, Dept Internal Med 3, Gluckstr 6, D-91054 Erlangen, Germany. EM Schulze-Koops@med3.imed.uni-erlangen.de NR 58 TC 13 Z9 15 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 305 BP 195 EP 211 DI 10.1007/3-540-29714-6_10 PG 17 WC Immunology; Microbiology SC Immunology; Microbiology GA BEM88 UT WOS:000238216500010 PM 16724807 ER PT J AU Dorner, T Lipsky, PE AF Dorner, T Lipsky, PE TI Signalling pathways in B cells: Implications for autoimmunity SO CURRENT CONCEPTS IN AUTOIMMUNITY AND CHRONIC INFLAMATION SE CURRENT TOPICS IN MICROBIOLOGY AND IMMUNOLOGY LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; PRIMARY SJOGRENS-SYNDROME; HEAVY-CHAIN REPERTOIRE; VIABLE MOTH-EATEN; FC-GAMMA-RIIB; RHEUMATOID-ARTHRITIS; LYMPHOCYTE DEPLETION; DEPRESSED PERCENTAGE; SUSCEPTIBILITY GENES; PERIPHERAL TOLERANCE AB Following investigations of the pathogenic role of autoantibodies in rheumatic diseases, preclinical and clinical studies suggest a more central role of B cells in the maintenance of the disease process beyond just being precursors of (auto) antibody-producing plasma cells. Detailed analyses have implicated a number of surface molecules and subsequent downstream signalling pathways in the regulation of the events induced by BCR engagement. In this review, we discuss the potential role of molecules involved in altered B cell longevity, especially molecules involved in apoptosis (bcl-2, bcl-x, mutations in the Fas/Fas-L pathway), as well as molecules that might alter activation thresholds of B cells (CD19, CD21, CD22, lyn, SHP, SHIP-1) in the development of autoimmunity. Although focused on intrinsic B cell abnormalities, the complexity of interactions of B cells with other immune cells also makes it possible that increased B cell activation can be induced by distortions in the interaction with other cells. Further delineation of these alterations of B cell function in autoimmune conditions will allow development of more precise B cell-directed therapies beyond drastic B cell depletion, with the potential to improve the risk-benefit ratio of the treatments of autoimmune diseases. C1 Charite Univ Med Berlin, Coagulat Unit, Inst Transfus Med, D-10098 Berlin, Germany. NIAMS, NIH, Bethesda, MD USA. RP Dorner, T (reprint author), Charite Univ Med Berlin, Coagulat Unit, Inst Transfus Med, Campus Mitte,Schumannstr 20-21, D-10098 Berlin, Germany. EM thomas.doerner@charite.de NR 104 TC 32 Z9 33 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2006 VL 305 BP 213 EP 240 DI 10.1007/3-540-29714-6_11 PG 28 WC Immunology; Microbiology SC Immunology; Microbiology GA BEM88 UT WOS:000238216500011 PM 16724808 ER PT B AU Ludlow, CL AF Ludlow, Christy L. BE Ratner, NB Tetnowski, J TI Neuropharmacology of stuttering: Concepts and current findings SO Current Issues in Stuttering Research and Practice LA English DT Proceedings Paper CT Annual Convention of the American-Speech-Language-Hearing-Association CY NOV 13-15, 2003 CL Chicago, IL SP Amer Speech Language Hearing Assoc ID PARKINSONS-DISEASE; HALOPERIDOL; PAROXETINE; CLOZAPINE; SPEECH; CLOMIPRAMINE; DESIPRAMINE; RISPERIDONE; SEVERITY; DOPAMINE C1 Natl Inst Neurol Disorders & Stroke, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. NR 36 TC 3 Z9 4 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-5201-8 PY 2006 BP 239 EP 254 PG 16 WC Linguistics; Rehabilitation SC Linguistics; Rehabilitation GA BFB97 UT WOS:000240945100010 ER PT J AU Labinskyy, N Csiszar, A Veress, G Stef, G Pacher, P Oroszi, G Wu, J Ungvari, Z AF Labinskyy, N Csiszar, A Veress, G Stef, G Pacher, P Oroszi, G Wu, J Ungvari, Z TI Vascular dysfunction in aging: Potential effects of resveratrol, an anti-inflammatory phytoestrogen SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE polyphenol; endothelium; heart; coronary circulation; senescence; inflammation; gene expression; NF-kappa B ID NF-KAPPA-B; CARDIOVASCULAR-DISEASE ENTERPRISES; NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; NATURAL POLYPHENOLIC COMPOUND; HUMAN ENDOTHELIAL-CELLS; AGGREGATION IN-VIVO; RED WINE; OXIDATIVE STRESS; PLATELET-AGGREGATION AB Epidemiological studies demonstrated that even in the absence of other risk factors (e.g. diabetes, hypertension, hyperhomocysteinemia, hypercholesterolemia), advanced age itself significantly increases cardiovascular morbidity by enhancing Vascular oxidative stress and inflammation. Because the population in the Western world is rapidly aging, there is a substantial need for pharmacological interventions that delay the functional decline of the cardiovascular system. Resveratrol is ail atoxic phytoestrogen found in more than 70 plants including grapevine and berries. Recent data suggest that nutritional intake of resveratrol and other polyphenol compounds may contribute to the "French paradox", the unexpectedly low cardiovascular morbidity in the Mediterranean population. There is increasing evidence that resveratrol exerts multifaceted anti-oxidant and/or anti-inflammatory effects in various disease models. Importantly, resveratrol was reported to slow aging and increase lifespan in simple organisms and has been suggested as a potential calorie restriction mimetic. Resveratrol has also been reported to activate NAD-dependent historic deacetylases (sirtuins), which may contribute to its anti-aging effects. This review focuses on the role of oxidative stress and inflammation in cardiovascular dysfunction in aging, and on emerging anti-aging therapeutic strategies offered by resveratrol and other polyphenol compounds. C1 New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. State Hosp Cardiol, H-8230 Balatonfured, Hungary. NIAAA, Lab Physiol Studies & Neurogenet, NIH, Bethesda, MD 20892 USA. New York Med Coll, Dept Biochem, Valhalla, NY 10595 USA. RP Ungvari, Z (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. EM zoltan_ungvari@nymc.edu RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 99 TC 80 Z9 87 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2006 VL 13 IS 9 BP 989 EP 996 DI 10.2174/092986706776360987 PG 8 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 038FP UT WOS:000237204600002 PM 16611080 ER PT J AU Souza, F Freeby, M Hultman, K Simpson, N Herron, A Witkowsky, P Liu, E Maffei, A Harris, PE AF Souza, Fabiola Freeby, Matthew Hultman, Kristi Simpson, Norman Herron, Alan Witkowsky, Piotr Liu, Eric Maffei, Antonella Harris, Paul E. TI Current progress in non-invasive imaging of beta cell mass of the endocrine pancreas SO CURRENT MEDICINAL CHEMISTRY LA English DT Review DE non-invasive beta cell imaging; diabetes; Islet transplantation; pancreas ID VESICULAR MONOAMINE TRANSPORTER; TYPE-1 DIABETES-MELLITUS; PULSATILE INSULIN-SECRETION; IMPAIRED GLUCOSE-TOLERANCE; BOVINE CHROMAFFIN GRANULES; BODY-FAT DISTRIBUTION; ISLET TRANSPLANTATION; IN-VIVO; MONOCLONAL-ANTIBODY; NEURONAL TRAITS AB The, increasing incidence of diabetes requires a better understanding of the pathogenesis of the clinical disease. Studies in prevention and treatment have been hampered by the single end-point of diagnosis of diabetes and hyperglycemia. The common pathology in both type 1 and type 2 diabetes is insufficient beta-cell mass to meet the metabolic demand. Unfortunately, current diagnostic methods rely on metabolic responses that do not accurately reflect true beta-cell mass. Recent advances in beta-cell imaging have utilized multiple modalities in experimental and clinical settings. While no "gold-standard" exists to measure beta-cell mass, modalities such as single photon emission computed tomography, optical and fluorescent imaging, magnetic resonance imaging, and positron emission tomography have been used with mixed success. Many of the methods are limited by the inability to translate to the clinical setting, poor discrimination between the exocrine and endocrine pancreas, or a poor measurement of beta-cell mass. However, promising new "neurofunctional imaging" approaches have emerged as improved measures of beta-cell mass. We review the current understanding of the pathogenesis and evaluation of diabetes, as well as experimental approaches to assessing beta-cell mass. C1 Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. Columbia Univ, Dept Appl Phys & Appl Math, New York, NY 10032 USA. Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10032 USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20854 USA. CNR, Inst Genet & Biophys Adriano Buzzati Traverso, I-80131 Naples, Italy. RP Harris, PE (reprint author), Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA. EM peh1@columbia.edu RI Maffei, Antonella/C-1181-2015 OI Maffei, Antonella/0000-0001-5637-6523 FU Intramural NIH HHS; NIDDK NIH HHS [R01 DK063567, R01 DK077493, 2 R01 DK63567-03, 5 P30 DK063608-02]; NINDS NIH HHS [2R01 NS15655] NR 113 TC 51 Z9 53 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PY 2006 VL 13 IS 23 BP 2761 EP 2773 DI 10.2174/092986706778521940 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 083JY UT WOS:000240453400004 PM 17073627 ER PT J AU Barrett, J Rezvani, K AF Barrett, J Rezvani, K TI Neutrophil granule proteins as targets of leukemia-specific immune responses SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE cellular immunity; leukemia-specific T cells; leukemia vaccines; neutrophil elastase; PR1; primary granule proteins; proteinase 3 ID CHRONIC MYELOGENOUS LEUKEMIA; CD8(+) T-CELLS; SEVERE CONGENITAL NEUTROPENIA; WEGENERS-GRANULOMATOSIS WG; IN-VITRO; BINDING-PROTEIN; PROMYELOCYTIC LEUKEMIA; SYSTEMIC VASCULITIS; TUMOR REJECTION; ELASTASE GENE AB Purpose of review. Recent progress in the identification of leukemia antigens has stimulated the development of vaccines to treat hematological malignancies. Here we review the identification and characterization of the myeloid leukemia-specific antigens proteinase 3 and neutrophil elastase found in the primary (azurophil) granule proteins of granulocytes and their precursors. A peptide 'PR1' derived from these proteins induces powerful HLA-A0201 restricted CD8 T-cell proliferation. PR1-specific T cells are cytotoxic to leukemia and myelodysplastic syndrome progenitors, and occur at low frequencies in normal individuals, Frequencies are higher in patients with myeloid leukemias, and highest in patients with chronic myeloid leukemia entering molecular remission after allogeneic stem cell transplantation. Recent findings. These observations, together with the known association of autoimmunity to proteinase 3 and neutrophil elastase in Wegener's granulomatosis, support the concept that there is a natural immunity to primary granule proteins which can be boosted to enhance immunity to leukemia. Preliminary reports indicate that PR1 peptide vaccination induces significant increases in PR1-specific cytotoxic T cells with rapid and durable remissions in some patients with advanced myeloid leukemias. Summary. These promising developments in antileukemia vaccines have stimulated research to optimize vaccine delivery and modify regulation of natural T-cell immunity to primary granule proteins to improve treatment of otherwise refractory myeloid leukemias and myelodysplastic syndrome. C1 NHLBI, Stem Cell Allotransportat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransportat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov NR 76 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD JAN PY 2006 VL 13 IS 1 BP 15 EP 20 DI 10.1097/01.moh.0000190112.92908.3e PG 6 WC Hematology SC Hematology GA 995CZ UT WOS:000234078800003 PM 16319682 ER PT J AU Mattapallil, JJ Roederer, M AF Mattapallil, Joseph J. Roederer, Mario TI Acute HIV infection: it takes more than guts SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE acute infection; blood; CCR5; CD4 T cell; gut; HIV; immunodeficiency; intestine; mucosa; rhesus; SIV; T cell AB Purpose of review To understand the cellular and molecular mechanisms of acute HIV pathogenesis. Recent findings Recent studies have given us new insights into the mechanisms of acute HIV pathogenesis by demonstrating the 'systemic' destruction of the CD4 memory T cell compartment. This destruction occurs well before the emergence of a strong and broad immune response, highlighting the failure of the immune response to contain early viral infection and destruction. However, recent data also suggest that very few founder populations of cells are infected early, at the portal of entry, making them ideal targets for vaccine-induced immune responses that may aid in the effective control of early infection and transmission. Summary HIV causes a massive destruction of memory CD4 T cells during the early acute phase of infection. This destruction proceeds largely in the absence of emerging antiviral immune responses, and severely disables the ability of the immune system to generate secondary immune responses. Early preservation of the memory CD4 compartment by shifting emphasis of antiretroviral therapeutic strategies to early treatment, and development of vaccines that can induce strong and broad immune responses, will be critical to prevent the destructive effects of early HIV infection. C1 [Mattapallil, Joseph J.; Roederer, Mario] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mattapallil, JJ (reprint author), 40 Convent Dr,Room 5610, Bethesda, MD 20895 USA. EM jmattapallil@mail.nih.gov NR 49 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2006 VL 1 IS 1 BP 10 EP 15 DI 10.1097/01.COH.0000191896.70685.74 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NL UT WOS:000208417000003 PM 19372777 ER PT J AU Migueles, SA Tilton, JC Connors, M AF Migueles, Stephen A. Tilton, John C. Connors, Mark TI Qualitative host factors associated with immunological control of HIV infection by CD8 T cells SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE CD8 T cells; long-term non-progressors; proliferation AB Purpose of review Despite significant technical advances that have permitted an increasingly more quantitative and detailed study of virus-specific cellular immunity over the past few years, our understanding of the nature of immunological control in rare cases of non-progressive HIV infection and diminished control in the majority of untreated chronically infected patients remains incomplete. This review will summarize recent findings and points of controversy within areas of active investigation of the cellular immune response to HIV. Recent findings It is now appreciated that high frequencies of virus-specific CD8 T cells are readily detectable in chronic HIV infection, but do not restrict viral replication. For this reason, attention has shifted to qualitative features of the host immune response that might accurately determine the restriction of viral replication. A number of qualitative changes in the phenotype, cytokine secretion, and proliferative capacity of HIV-specific CD8 T cells of progressors have recently been described. Summary Given that the desired response to the majority of vaccines in pre-clinical or clinical testing is to stimulate cellular immunity in an attempt to alter disease progression, understanding these qualitative features is of particular relevance. Further study will probably yield critical information for the means to stimulate effective immunity in vaccinees, prevent the loss of control of viral replication upon infection of vaccinees, or induce durable immunological control in humans already infected with HIV. C1 [Migueles, Stephen A.; Tilton, John C.; Connors, Mark] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Connors, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11B-09,10 Ctr Dr,MSC 1876, Bethesda, MD 20892 USA. EM mconnors@niaid.nih.gov NR 50 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2006 VL 1 IS 1 BP 28 EP 33 DI 10.1097/01.COH.0000194108.14601.69 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NL UT WOS:000208417000006 PM 19372780 ER PT J AU Davey, RT AF Davey, Richard T., Jr. TI Straying from the path? SO CURRENT OPINION IN HIV AND AIDS LA English DT Editorial Material C1 NIAID, Off Clin Res, NIH, DHHS, Bethesda, MD 20892 USA. RP Davey, RT (reprint author), NIAID, Off Clin Res, NIH, DHHS, 10 Ctr Dr,Rm 4-1479,MSC 1460, Bethesda, MD 20892 USA. EM rdavey@niaid.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD JAN PY 2006 VL 1 IS 1 BP 40 EP 42 DI 10.1097/01.COH.0000194100.82320.ab PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24NL UT WOS:000208417000008 PM 19372782 ER PT J AU Kuo, CK Li, WJ Mauck, RL Tuan, RS AF Kuo, CK Li, WJ Mauck, RL Tuan, RS TI Cartilage tissue engineering: its potential and uses SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE bioreactor; cartilage; gene therapy; mesenchymal stem cell; tissue engineering; scaffold ID MESENCHYMAL STEM-CELLS; INTERMITTENT PHYSIOLOGICAL PRESSURE; EXTRACELLULAR-MATRIX PRODUCTION; CONCENTRIC CYLINDER BIOREACTOR; FIBROBLAST-GROWTH-FACTOR; IN-VITRO; CHONDROGENIC DIFFERENTIATION; ARTICULAR CHONDROCYTES; HYALURONIC-ACID; GENE-THERAPY AB Purpose of review The prevalent nature of osteoarthritis, a cartilage degenerative diseases that results in the erosion of joint surfaces and loss of mobility, underscores the importance of developing functional articular cartilage replacement. Recent research efforts have focused on tissue engineering as a promising approach for cartilage regeneration and repair. Tissue engineering is a multidisciplinary research area that incorporates both biological and engineering principles for the purpose of generating new, living tissues to replace the diseased/damaged tissue and restore tissue/organ function. This review surveys and highlights the current concepts and recent progress in cartilage tissue engineering , and discusses the challenges and potential of this rapidly advancing field of biomedical research. Recent findings Cartilage tissue engineering is critically dependent on selection of appropriate cells (differentiated or progenitor cells); fabrication and utilization of biocompatible and mechanically suitable scaffolds for cell delivery; stimulation with chondrogenically bioactive molecules introduced in the form of recombinant proteins or via gene transfer; and application of dynamic, mechanical loading regimens for conditioning of the engineered tissue constructs, including the design of specialized biomechanically active bioreactors. Summary Cell selection, scaffold design and biological stimulation remain the challenges of function tissue engineering. Successful regeneration or replacement of damaged or diseased cartilage will depend on future advances in our understanding of the biology of cartilage and stem cells and technological development in engineering. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Orthopaed Surg, Philadelphia, PA 19104 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 50,Room 1523,50 South Dr,MSC 8022, Bethesda, MD 20892 USA. EM Tuanr@mail.nih.gov RI Li, Wan-Ju/A-7002-2008 FU Intramural NIH HHS NR 95 TC 164 Z9 181 U1 4 U2 56 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JAN PY 2006 VL 18 IS 1 BP 64 EP 73 DI 10.1097/01.bor.0000198005.88568.df PG 10 WC Rheumatology SC Rheumatology GA 999IO UT WOS:000234383200010 PM 16344621 ER PT J AU Oz, M AF Oz, M TI Receptor-independent effects of endocannabinoids on ion channels SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE endocannabinoids; cannabinoids; ion channels; cannabinoids; fatty acids; arachidonic acid; prostaglandins ID POLYUNSATURATED FATTY-ACIDS; T-TUBULE MEMBRANES; NICOTINIC ACETYLCHOLINE-RECEPTOR; ENDOGENOUS CANNABINOID ANANDAMIDE; DEPENDENT CA2+ FLUXES; ROOT GANGLION NEURONS; RECTIFYING POTASSIUM CHANNELS; ACTIVATED CALCIUM-CHANNELS; CHAIN N-ACYLETHANOLAMINES; RAT HIPPOCAMPAL-NEURONS AB Endogenous cannabinoids (endocannabinoids), produced from membrane-bound precursors via calcium and/or G-protein dependent processes, mimic the effects of cannabinoids by activating cannabinoid CB1 and/or CB2 receptors. Several reports however, also indicate that endocannabinoids can produce effects that are independent of cannabinoid receptors. Thus, in pharmacologically relevant concentrations, endocannabinoids have been demonstrated to modulate the functional properties of voltage-gated ion channels including Ca2+ channels, Na+ channels and various types of K+ channels, and ligand-gated ion channels such as 5-HT3, and nicotinic ACh receptors. In addition, the functional modulations by endocannabinoids of other ion-transporting membrane proteins such as transient potential receptor-class channels, gap junctions, and neurotransmitter transporters have also been reported. These findings indicate that additional molecular targets for endocannabinoids exist and that these targets may represent important sites for cannabinoids to alter either the excitability of the neurons or the response of the neuronal systems. This review focuses on the results of recent studies indicating that beyond their receptor-mediated effects, endocannabinoids alter the function of ion channels directly. C1 NIDA, IRP, Cellular Neurobiol Branch, US Dept HHS,Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Oz, M (reprint author), NIDA, IRP, Cellular Neurobiol Branch, US Dept HHS,Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 153 TC 49 Z9 50 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 2 BP 227 EP 239 DI 10.2174/138161206775193073 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 992YB UT WOS:000233918800010 PM 16454739 ER PT J AU Garnett, CT Greiner, JW Tsang, KY Kudo-Saito, C Grosenbach, DW Chakraborty, M Gulley, JL Arlen, PM Schlom, J Hodge, JW AF Garnett, CT Greiner, JW Tsang, KY Kudo-Saito, C Grosenbach, DW Chakraborty, M Gulley, JL Arlen, PM Schlom, J Hodge, JW TI TRICOM vector based cancer vaccines SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE TRICOM; costimulation; vaccination; TAA; cancer immunotherapy ID HUMAN CARCINOEMBRYONIC ANTIGEN; MULTIPLE INTESTINAL NEOPLASIA; T-LYMPHOCYTE EPITOPE; COSTIMULATORY MOLECULES; IMMUNE-RESPONSES; ENHANCED ACTIVATION; ANTITUMOR-ACTIVITY; DIVERSIFIED PRIME; GENE-EXPRESSION; DENDRITIC CELLS AB For the immune system to mount an effective antitumor T-cell response, an adequate number of T-cells specific for the antigens expressed by the malignancy must be activated [1]. Since most antigens expressed by tumors are "self"-antigens, tumor antigens often lack endogenous immunogenicity and thus do not sufficiently activate T-cells to levels that can mediate tumor eradication, In addition, virtually all solid tumor cells lack the costimulatory molecules necessary to activate tumor-specific T-cells. Approaches that stimulate immune responses to these tumor antigens have the potential to alter this poor responsiveness. This theory has promoted the use of active immunotherapy to generate immune responses against tumor-associated antigens (TAAs) for the treatment of cancer. As one such vaccine strategy, we have utilized poxviruses as delivery vehicles for TAAs in combination with T-cell costimulatory molecules. Initial studies have demonstrated that the insertion of costimulatory molecule trangenes into viral vectors, along with a TAA transgene, greatly enhances the immune response to the antigen. Using this approach, a TRIad of COstimulatory Molecules (TRICOM; B7-1, ICAM-I and LFA-3) has been shown to enhance T-cell responses to TAAs to levels far greater than any one or two of the costimulatory molecules in combination. In this article, preclinical findings and recent clinical applications of TRICOM-based vaccines as a cancer immunotherapy are reviewed. C1 NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Bldg 10,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015; Gulley, James/K-4139-2016; OI Hodge, James/0000-0001-5282-3154; Gulley, James/0000-0002-6569-2912; Garnett-Benson, Charlie/0000-0002-0238-3303 NR 52 TC 32 Z9 32 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 3 BP 351 EP 361 DI 10.2174/138161206775201929 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995BH UT WOS:000234074400008 PM 16454749 ER PT J AU Cardones, AR Banez, LL AF Cardones, AR Banez, LL TI VEGF inhibitors in cancer therapy SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; RENAL-CELL CARCINOMA; VASCULAR-PERMEABILITY FACTOR; TYROSINE KINASE INHIBITOR; VESSEL CO-OPTION; METASTATIC COLORECTAL-CANCER; PHASE-III TRIAL; TUMOR ANGIOGENESIS; SOLID TUMORS; ANTIANGIOGENIC THERAPY AB Vascular endothelial growth factor (VEGF)-mediated angiogenesis is thought to play a critical role in tumor growth and metastasis. Consequently, anti-VEGF therapies are being actively investigated as potential anti-cancer treatments, either as alternatives or adjuncts to conventional chemo or radiation therapy. Among the techniques used to block the VEGF pathway are: 1) neutralizing monoclonal antibodies against VEGF or its receptor, 2) small molecule tyrosine kinase inhibitors of VEGF receptors, 3) soluble VEGF receptors which act as decoy receptors for VEGF, and 4) ribozymes which specifically target VEGF mRNA. Recent evidence from phase III clinical trials led to the approval of bevacizumab, an anti-VEGF monoclonal antibody, by the FDA as first line therapy in metastatic colorectal carcinoma in combination with other chemotherapeutic agents. However, may challenges still remain, and the role of anti-VEGF therapy in the treatment of other solid tumors remains to be elucidated. The aim of this article is to review the progress of clinical investigations involving VEGF inhibitors in the treatment of different types of solid tumors. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Rockville, MD 20852 USA. RP Cardones, AR (reprint author), 10 Ctr Dr,Rm 12N246, Bethesda, MD 20892 USA. EM cardonea@mail.nih.gov NR 123 TC 76 Z9 82 U1 2 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 3 BP 387 EP 394 DI 10.2174/138161206775201910 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 995BH UT WOS:000234074400011 PM 16454752 ER PT J AU Roth, BL Kroeze, WK AF Roth, Bryan L. Kroeze, Wesley K. TI Screening the receptorome yields validated molecular targets for drug discovery SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review ID PROTEIN-COUPLED RECEPTORS; VALVULAR HEART-DISEASE; APPETITE-SUPPRESSANT DRUGS; PLACEBO-CONTROLLED TRIAL; INDUCED WEIGHT-GAIN; OLFACTORY RECEPTOR; NERVOUS-SYSTEM; HUMAN GENOME; SCHIZOAFFECTIVE DISORDER; ANTIPSYCHOTIC-DRUGS AB With the recently completed sequencing and annotation of the human genome, it has become clear that a significant portion of the genome encodes signal-transducing molecules including receptors, protein kinases, ion channels, transporters and coupling proteins. This review focuses on membrane-localized receptors, which represent the largest single group of signal-transducing molecules. Indeed, one can estimate that nearly 10% of the human genome encodes membrane-localized receptors (e.g. G-protein coupled receptors, ligand-gated ion channels and transporters). We have defined that portion of the human genome that encodes 'receptors' the receptorome. In this article, we will demonstrate how the massively parallel screening of the receptorome provides a facile and under-utilized screening platform for drug discovers. Using case studies, we will show how receptorome-based screening elucidates the mechanisms responsible for serious side-effects of both approved and investigational medications. Additionally, we will provide evidence that receptorome-based screening provides insights into novel therapeutic indications of approved medications and serves to validate targets for therapeutic drug discovery. C1 Case Western Reserve Univ, Sch Med, Dept Biochem,Natl Inst Mental Hlth Psychoact Drug, CASE Comprehens Canc Ctr, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem,Natl Inst Mental Hlth Psychoact Drug, CASE Comprehens Canc Ctr, RM W441,2109 Adelbert Rd, Cleveland, OH 44106 USA. EM bryan.roth@case.edu RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01DA01677]; NIMH NIH HHS [R01MH61887, R01MH57635, KO2MH01366] NR 124 TC 11 Z9 11 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 14 BP 1785 EP 1795 DI 10.2174/138161206776873680 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 051YZ UT WOS:000238198900008 PM 16712488 ER PT J AU Paganelli, R Di Iorio, A Cherubini, A Lauretani, F Mussi, C Volpato, S Abate, M Abate, G Ferrucci, L AF Paganelli, R. Di Iorio, A. Cherubini, A. Lauretani, F. Mussi, C. Volpato, S. Abate, M. Abate, G. Ferrucci, L. TI Frailty of older age: The role of the endocrine - Immune interaction SO CURRENT PHARMACEUTICAL DESIGN LA English DT Review DE frailty; hormones; cytokines; disability; aging ID ESTROGEN-REPLACEMENT THERAPY; RANDOMIZED CONTROLLED-TRIAL; PITUITARY-ADRENAL AXIS; SKELETAL-MUSCLE MASS; GROWTH-FACTOR-I; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; ALZHEIMERS-DISEASE PATIENTS; LOWER-EXTREMITY FUNCTION; BONE-MINERAL DENSITY; SULFATE DHEA-S AB The so-called demographic transition has changed the age structure of the population worldwide, with profound effects on societal organization. The growing number and percentage of old and very old people has compelled the scientific community to focus on age related diseases and peculiar consequences of aging itself such as disability and frailty. Understanding the pathophysiology of frailty, a syndrome characterized by a reduced functional reserve and impaired adaptive capacity that results from cumulative declines of multiple subsystems, and causes increased vulnerability to adverse outcomes, is a major topic in aging research. Aging processes induce multiple changes in the hormones network (menopause, andropause, somatopause and adrenopause), in the immune system, and can modulate their efficiency and effectiveness in determining a response to stressors. These triggering events can unmask frailty-in older people. Starting from these assumptions, we analyzed the relationship of the endocrine and immune networks in aging and in the different domains that are characteristically associated with the frailty syndrome, such as disability and sarcopenia, as well as in diseases related to aging such as Alzheimer's dementia and Congestive Heart Failure. C1 Univ GD Annunzio, Dept Med & Sci Aging, Allergy & Clin Immunol Sect, Lab Immunol & Allergy, I-66013 Chieti, Italy. Univ GD Annunzio, Lab Clin Epidemiol, Dept Med & Sci Aging, I-66013 Chieti, Italy. Univ Perugia, Inst Gerontol & Geriatr, I-06100 Perugia, Italy. Tuscany Reg Hlth Agcy, Lab Clin Epidemiol, Florence, Italy. Univ Modena & Reggio Emilia, Geriatr Unit, Modena, Italy. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Univ GD Annunzio, Dept Med & Sci Aging, Lab Phys Med & Rehabil, I-66013 Chieti, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. Univ GD Annunzio, CESI Fdn, I-66013 Chieti, Italy. RP Paganelli, R (reprint author), Univ GD Annunzio, Dept Med & Sci Aging, Allergy & Clin Immunol Sect, Lab Immunol & Allergy, Via Vestini 5, I-66013 Chieti, Italy. EM rpaganel@unich.it RI Mussi, Chiara/G-3955-2016; VOLPATO, STEFANO/H-2977-2014; Lauretani, Fulvio/K-5115-2016 OI Cherubini, Antonio/0000-0003-0261-9897; Mussi, Chiara/0000-0001-5598-9969; VOLPATO, STEFANO/0000-0003-4335-6034; Lauretani, Fulvio/0000-0002-5287-9972 NR 166 TC 35 Z9 38 U1 3 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1381-6128 J9 CURR PHARM DESIGN JI Curr. Pharm. Design PY 2006 VL 12 IS 24 BP 3147 EP 3159 DI 10.2174/138161206777947533 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 069XL UT WOS:000239482500013 PM 16918440 ER PT J AU Mahadeo, DC Parent, CA AF Mahadeo, Dana C. Parent, Carole A. TI Signal relay during the life cycle of Dictyostelium SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 73 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID NUMBER-COUNTING FACTOR; NUCLEOTIDE PHOSPHODIESTERASE GENE; DIFFERENTIATION-INDUCING-FACTOR; ACTIN TYROSINE PHOSPHORYLATION; PROTEIN-MEDIATED ACTIVATION; ADENYLYL-CYCLASE; SPORE GERMINATION; CAMP RECEPTOR; TERMINAL DIFFERENTIATION; TRANSDUCTION PATHWAYS AB A fundamental property of multicellular organisms is signal relay, the process by which information is transmitted from one cell to another. The integration of external information, such as nutritional status or developmental cues, is critical to the function of organisms. In addition, the spatial organizations of multicellular organisms require intricate signal relay mechanisms. Signal relay is remarkably exhibited during the life cycle of the social amoebae Dictyostelium discoideum, a eukaryote that retains a simple way of life, yet it has greatly contributed to our knowledge of the mechanisms cells use to communicate and integrate information. This chapter focuses on the molecules and mechanisms that Dictyostelium employs during its life cycle to relay temporal and spatial cues that are required for survival. C1 NCI, Cellular & Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mahadeo, DC (reprint author), NCI, Cellular & Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 120 TC 26 Z9 27 U1 2 U2 12 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2006 VL 73 BP 115 EP + DI 10.1016/S0070-2153(05)73004-0 PG 29 WC Developmental Biology SC Developmental Biology GA BEP76 UT WOS:000238776000004 PM 16782457 ER PT J AU Cerna, D Camphausen, K Tofilon, PJ AF Cerna, David Camphausen, Kevin Tofilon, Philip J. TI Histone deacetylation as a target for radiosensitization SO CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY, VOL 73 SE CURRENT TOPICS IN DEVELOPMENTAL BIOLOGY LA English DT Review ID COLON TUMOR-CELLS; NUCLEAR HORMONE-RECEPTORS; VIVO ANTITUMOR-ACTIVITY; HYDROXAMIC ACID SAHA; HUMAN LEUKEMIA-CELLS; STRAND BREAK REPAIR; DNA-DAMAGE RESPONSE; IN-VIVO; SODIUM-BUTYRATE; VALPROIC ACID AB Due to an increase in the understanding of molecular radiobiology, strategies for enhancing tumor radiosensitivity have begun to focus on targeting the molecules and processes that regulate cellular radioresponse. Toward this end, histone acetylation has begun to receive considerable attention as a potential target for radio sensitization. Histone acetylation, which is determined by the competing actions of historic acetylases (HATs) and histone deacetylases (HDACs), plays a role in regulating chromatin structure and gene expression-two parameters that have long been considered determinants of radioresponse. As a means of modifying histone acetylation status, considerable effort has been put into the development of inhibitors of HDAC activity, which is often aberrant in tumor cells. This has led to the generation of a relatively large number of structurally diverse compounds that inhibit HDAC activity and result in historic hyperacetylation, and importantly, are applicable to patient treatment. Whereas a number of these HDAC inhibitors have antitumor activity in preclinical cancer models when delivered as single agents, recent studies have indicated that these compounds also significantly enhance tumor cell radiosensitivity. A structurally diverse set of HDAC inhibitors have been shown to enhance the in vitro radiosensitivity of human tumor cell lines generated from a spectrum of solid tumors. Moreover, HDAC inhibitors increased the radiosensitivity of human tumor xenografts. Although the mechanism responsible for this radio sensitization has not been definitely elucidated, data suggest that inhibiting the repair of radiation-induced DNA damage may be involved. Whereas HDAC inhibitors are currently in clinical trials as single modalities and in combination with chemotherapeutic agents, recent results suggest that these compounds may also enhance the antitumor effectiveness of radiotherapy. (c) 2006, Elsevier Inc. C1 NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Cerna, D (reprint author), NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NR 113 TC 41 Z9 41 U1 2 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0070-2153 J9 CURR TOP DEV BIOL PY 2006 VL 73 BP 173 EP 204 DI 10.1016/S0070-2153(05)73006-4 PG 32 WC Developmental Biology SC Developmental Biology GA BEP76 UT WOS:000238776000006 PM 16782459 ER PT J AU Simons, SS AF Simons, SS TI How much is enough? Modulation of dose-response curve for steroid receptor-regrulated gene expression by changing concentrations of transcription factor SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID LIGAND-BINDING DOMAIN; TYROSINE AMINOTRANSFERASE GENE; HUMAN ESTROGEN-RECEPTOR; RETINOIC ACID RECEPTOR; BREAST-CANCER-CELLS; MOUSE GLUCOCORTICOID-RECEPTOR; UBIQUITIN-CONJUGATING ENZYME; HUMAN PROGESTERONE-RECEPTORS; PARTIAL AGONIST ACTIVITY; ANDROGEN RECEPTOR AB The position of the dose-response curve for steroid-regulated gene expression determines how much variation in response will accompany the normal physiological changes in circulating steroid. Over the last several years, it has become clear that the concentration of steroid hormone required for half-maximal induction or repression by a given receptor-steroid complex, which is normally called the EC50, is not constant for all responsive genes. Thus, the position of the dose-response curve can change so that a single concentration of steroid produces very different percentages of maximal activity. This, in turn, allows for the differential expression of genes by a common steroid hormone concentration during development, differentiation, and homeostasis. Here we review the variety of factors that influence the EC50 and position of the dose-response curve for steroid hormone receptors, discuss what is known about the mechanisms, and highlight promising areas for future research. C1 NIDDK, Steroid Hormones Sect, CEB, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, Steroid Hormones Sect, CEB, NIH, Bldg 10,Room 8N307B, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov FU Intramural NIH HHS NR 166 TC 27 Z9 27 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 3 BP 271 EP 285 DI 10.2174/156802606776173465 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 041LW UT WOS:000237458700006 PM 16515481 ER PT J AU Neckers, L AF Neckers, Len TI Using natural product inhibitors to validate Hsp90 as a molecular target in cancer SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE molecular chaperones; heat shock protein 90; kinase inhibitors; benzoquinone ansamycins; radicicol; novobiocin; geldanamycin; molecularly targeted therapeutics ID HEAT-SHOCK-PROTEIN; C-TERMINAL DOMAIN; STEROID-HORMONE RECEPTORS; DT-DIAPHORASE EXPRESSION; ATP-BINDING SITE; TYROSINE KINASE; BREAST-CANCER; IN-VIVO; ANDROGEN RECEPTOR; CRYSTAL-STRUCTURE AB Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for stability and function of multiple mutated, chimeric, and over-expressed signaling proteins that promote cancer cell growth and/or survival. Hsp90 client proteins include telomerase, mutated p53, Bcr-Ab1, Raf-1, Akt, HER21Neu (ErbB2), mutated B-Raf, mutated EGF receptor, and HIF-1 alpha. Hsp90 inhibitors, by interacting specifically with a single molecular target, cause inactivation, destabilization and eventual degradation of Hsp90 client proteins, and they have shown promising anti-tumor activity in various preclinical tumor models. One Hsp90 inhibitor, 17-AAG, is currently in Phase II clinical trial and other inhibitors will shortly be entering the clinic. Hsp90 inhibitors are unique in that, although they are directed towards a specific molecular target, they simultaneously inhibit multiple signaling pathways on which cancer cells depend for growth and survival. Identification of benzoquinone ansamycins as the first Hsp90 inhibitors allowed investigators to determine the biologic effects, at first in vitro and then in vivo, of pharmacologic inhibition of Hsp90. These studies rapidly enhanced our understanding of Hsp90 function and led to the identification of radicicol as a structurally distinct Hsp90 inhibitor. Additional target-based screening uncovered novobiocin as a third structurally distinct small molecule with Hsp90 inhibitory properties. Use of novobiocin, in turn, led to identification of a previously uncharacterized C-terminal ATP binding site in the chaperone. Small molecule inhibitors of Hsp90 have been very useful in understanding Hsp90 biology and in validating this protein as a molecular target for anti-cancer drug development. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Neckers, L (reprint author), NCI, Urol Oncol Branch, NIH, 9000 Rockvillle Pike,Bldg 10,Room 1-5940, Bethesda, MD 20892 USA. EM len@helix.nih.gov NR 110 TC 62 Z9 67 U1 2 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 11 BP 1163 EP 1171 DI 10.2174/156802606777811979 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079UO UT WOS:000240203600008 PM 16842153 ER PT J AU Kirk, KL AF Kirk, Kenneth L. TI The use of selective fluorination in drug design and development SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Editorial Material C1 NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 13 Z9 13 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 14 BP 1445 EP 1445 DI 10.2174/156802606777951118 PG 1 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079UW UT WOS:000240204400001 ER PT J AU Kirk, KL AF Kirk, Kenneth L. TI Selective fluorination in drug design and development: An overview of biochemical rationales SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID POTENT; INHIBITORS; MECHANISM; ANALOG; METHYLTRANSFERASE; PROSTACYCLIN; ORIENTATION; PERSPECTIVE; METABOLISM; REDUCTASE AB Several strategies used in the rational design and synthesis of fluorinated compounds as potential therapeutic agents are reviewed. Applications of fluorine substitution in empirical SAR studies for lead development also are discussed, along with the implications with respect to fluorine target interactions that can be derived from biological activities. C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Kirk, KL (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bldg 8A,Room B1A-02,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM kennethk@bdg8.niddk.nih.gov FU Intramural NIH HHS NR 49 TC 83 Z9 83 U1 3 U2 27 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 14 BP 1447 EP 1456 DI 10.2174/156802606777951073 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079UW UT WOS:000240204400002 PM 16918460 ER PT J AU Burke, TR AF Burke, Terrence R., Jr. TI Design and synthesis of phosphonodifluoromethyl phenylalanine (F(2)Pmp): A useful phosphotyrosyl mimetic SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review ID PROTEIN-TYROSINE PHOSPHATASES; SOLID-PHASE SYNTHESIS; SIGNAL-TRANSDUCTION INHIBITORS; O-PHOSPHOTYROSINE; SH2 DOMAIN; NONHYDROLYZABLE MIMETICS; SUBSTRATE-SPECIFICITY; ARYL IODIDES; N-BOC; PEPTIDE AB Hydrolytically-stable phosphotyrosyl (pTyr) mimetics can be useful tools for the study of cellular signal transduction processes. Among pTyr mimetics reported to date, phosphono(diflouromethyl)phenylalanine (F(2)Pmp) has shown particular utility when dealing with protein-tyrosine phosphatases (PTPs). The current overview presents the development of F2Pmp and a summary of approaches toward its synthesis and use. C1 NCI, Lab Med Chem, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, Lab Med Chem, Ctr Canc Res, NIH, POB B,Bldg 376 Boyles St, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 FU Intramural NIH HHS NR 43 TC 17 Z9 18 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 14 BP 1465 EP 1471 DI 10.2174/156802606777951091 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079UW UT WOS:000240204400004 PM 16918462 ER PT J AU Thomas, CJ AF Thomas, Craig J. TI Fluorinated natural products with clinical significance SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE natural products; fluorine; camptothecin; artemisinin; Vinca alkaloids; taxanes; epothilones ID MICROTUBULE-STABILIZING AGENTS; VINBLASTINE-TYPE ALKALOIDS; RING-MODIFIED CAMPTOTHECIN; POTENT ANTITUMOR-ACTIVITY; DRUG DISCOVERY PROCESS; DNA TOPOISOMERASE-I; VINCA ALKALOIDS; MEDICINAL CHEMISTRY; BIOLOGICAL-ACTIVITY; ANTIMALARIAL ACTIVITY AB The modification of natural products in an effort to alter their biochemical capacity is a common technique utilized by synthetic and medicinal chemists. Fluorine substitution imparts unique and advantageous physiochemical properties that can be shrewdly employed to constructively alter pharmacological agents. The adornment of natural products with fluorine has proven beneficial in several examples. This overview discusses several of the most relevant fluorinated natural products under current examination. C1 NIDDK, NIH, Chem Biol Core, Bethesda, MD 20892 USA. RP Thomas, CJ (reprint author), NIDDK, NIH, Chem Biol Core, 9000 Rockville Pike,Bldg 8,Room 117, Bethesda, MD 20892 USA. EM craigt@niddk.nih.gov FU Intramural NIH HHS [Z01 DK070005-04] NR 133 TC 23 Z9 23 U1 2 U2 17 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 14 BP 1529 EP 1543 DI 10.2174/156802606777951109 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 079UW UT WOS:000240204400008 PM 16918466 ER PT J AU Rothman, RB Baumann, MH AF Rothman, Richard B. Baumann, Michael H. TI Therapeutic potential of monoamine transporter substrates SO CURRENT TOPICS IN MEDICINAL CHEMISTRY LA English DT Review DE transporters; dopamine; serotonin; release; amphetamine; PAL-287 ID BIOGENIC-AMINE TRANSPORTERS; CENTRAL-NERVOUS-SYSTEM; PROGRESSIVE-RATIO SCHEDULE; SEROTONIN-RELEASING AGENTS; D-AMPHETAMINE TREATMENT; NEUROTRANSMITTER TRANSPORTERS; PULMONARY-HYPERTENSION; RHESUS-MONKEYS; COCAINE-DEPENDENCE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA AB Monoamine transporter proteins are targets for many psychoactive compounds, including therapeutic and abused stimulant drugs. This paper reviews recent work from our laboratory investigating the interaction of stimulants with transporters in brain tissue. We illustrate how determining the precise mechanism of stimulant drug action (uptake inhibitor vs. substrate) can provide unique opportunities for medication discovery. An important lesson learned from this work is that drugs which display equipotent substrate activity at dopamine (DA) and serotonin (5-HT) transporters have minimal abuse liability and few stimulant side-effects, yet are able to suppress ongoing drug-seeking behavior. As a specific example, we describe the development of PAL-287 (alpha-methylnapthylethylamine), a dual DA/5-HT releasing agent that suppresses cocaine self-administration in rhesus monkeys, without the adverse effects associated with older phenylethylamine 5-HT releasers (e.g., fenfluramine) and DA releasers (e.g., amphetamine). Our findings demonstrate the feasibility of developing non-amphetamine releasing agents as potential treatments for substance abuse disorders and other psychiatric conditions. C1 NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Clin Psychopharmacol Sect, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov FU Intramural NIH HHS NR 94 TC 36 Z9 36 U1 0 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0266 J9 CURR TOP MED CHEM JI Curr. Top. Med. Chem. PY 2006 VL 6 IS 17 BP 1845 EP 1859 DI 10.2174/156802606778249766 PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 086IR UT WOS:000240667500004 PM 17017961 ER PT J AU Wagner, ML Raudsepp, T Goh, G Agarwala, R Schaffer, AA Dranchak, PK Brinkmeyer-Langford, C Skow, LC Chowdhary, BP Mickelson, JR AF Wagner, ML Raudsepp, T Goh, G Agarwala, R Schaffer, AA Dranchak, PK Brinkmeyer-Langford, C Skow, LC Chowdhary, BP Mickelson, JR TI A 1.3-Mb interval map of equine homologs of HSA2 SO CYTOGENETIC AND GENOME RESEARCH LA English DT Article ID RADIATION HYBRID MAP; HORSE REFERENCE FAMILIES; SEQUENCE-TAGGED SITES; WHITE FOAL SYNDROME; MICROSATELLITE LOCI; LINKAGE MAP; 2 3-GENERATION; PHYSICAL MAP; CHROMOSOME; GENOME AB A comparative approach that utilizes information from more densely mapped or sequenced genomes is a proven and efficient means to increase our knowledge of the structure of the horse genome. Human chromosome 2 ( HSA2), the second largest human chromosome, comprising 243 Mb, and containing 1246 known genes, corresponds to all or parts of three equine chromosomes. This report describes the assignment of 140 new markers ( 78 genes and 62 microsatellites) to the equine radiation hybrid ( RH) map, and the anchoring of 24 of these markers to horse chromosomes by FISH. The updated equine RH maps for ECA6p, ECA15, and ECA18 resulting from this work have one, two, and three RH linkage groups, respectively, per chromosome/chromosomearm. These maps have a three-fold increase in the number of mapped markers compared to previous maps of these chromosomes, and an increase in the average marker density to one marker per 1.3 Mb. Comparative maps of ECA6p, ECA15, and ECA18 with human, chimpanzee, dog, mouse, rat, and chicken genomes reveal blocks of conserved synteny across mammals and vertebrates. C1 Univ Minnesota, Coll Vet Med, Dept Vet Biosci, St Paul, MN 55108 USA. Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, College Stn, TX USA. NCBI, NIH, US Dept HHS, Bethesda, MD USA. RP Mickelson, JR (reprint author), Univ Minnesota, Coll Vet Med, Dept Vet Biosci, 1998 Fitch Ave, St Paul, MN 55108 USA. EM micke001@umn.edu RI Schaffer, Alejandro/F-2902-2012 NR 33 TC 8 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1424-8581 J9 CYTOGENET GENOME RES JI Cytogenet. Genome Res. PY 2006 VL 112 IS 3-4 BP 227 EP 234 DI 10.1159/000089875 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 011ZZ UT WOS:000235309300009 PM 16484777 ER PT J AU Rackwitz, L Mauck, RL Byers, BA Tuan, RS AF Rackwitz, L. Mauck, R. L. Byers, B. A. Tuan, R. S. TI Integration of chondrocyte-laden agarose constructs in a bovine in vitro cartilage defect model SO CYTOTHERAPY LA English DT Meeting Abstract C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, HHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 2 MA 021 BP 8 EP 8 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YD UT WOS:000239337800022 ER PT J AU Tuan, RS AF Tuan, R. S. TI Application of nanofibrous scaffold for skeletal tissue engineering SO CYTOTHERAPY LA English DT Meeting Abstract C1 NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 2 MA 098 BP 27 EP 27 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YD UT WOS:000239337800096 ER PT J AU Muller, M Li, WJ Taboas, J Chen, F Tuan, RS AF Muller, M. Li, W. J. Taboas, J. Chen, F. Tuan, R. S. TI Influence of cyclic hydrostatic pressure on multiline-age differentiation of human mesenchymal stem cells SO CYTOTHERAPY LA English DT Meeting Abstract C1 NIAMSD, Cartilage Biol & Orthoped Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 2 MA P-86 BP 58 EP 58 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YD UT WOS:000239337800210 ER PT J AU Bozorgmehrl, F Laufs, S Sellers, SE Zeller, WJ Dunbar, CE Fruehauf, S AF Bozorgmehrl, F. Laufs, S. Sellers, S. E. Zeller, W. J. Dunbar, C. E. Fruehauf, S. TI Multidrug-resistance 1 gene transfer to rhesus macaque hematopoietic stem cells results in polyclonal hematopoiesis without incidence of leukemia after long-term follow-up. SO CYTOTHERAPY LA English DT Meeting Abstract C1 German Canc Res Ctr, D-6900 Heidelberg, Germany. NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 1 MA 256 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YB UT WOS:000239337600255 ER PT J AU Freed, WJ Schoen, CJ Shen, L Lee, CT Chen, J Harvey, BK Howard, D Wang, Y Shen, J Laabs, T Geller, H Sanchez, JF AF Freed, W. J. Schoen, C. J. Shen, L. Lee, C. T. Chen, J. Harvey, B. K. Howard, D. Wang, Y. Shen, J. Laabs, T. Geller, H. Sanchez, J. F. TI An immortalizing construct comprised of a fusion gene combining telomerase and a T antigen fragment which is capable of immortalizing human protoplasmic astrocytes SO CYTOTHERAPY LA English DT Meeting Abstract C1 NIDA, Cellular Neurobiol Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. ScienCell Res Labs, San Diego, CA USA. NIDA, Mol Neuropsychiat Res Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. NHLBI, Dev Neurobiol Grp, DIR, NIH,DHHS, Bethesda, MD 20892 USA. RI Harvey, Brandon/A-5559-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 1 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YB UT WOS:000239337600004 ER PT J AU Sanchez, JF Vazin, T Shen, S Lee, CT Schoen, CJ Spivak, C Shen, J Freed, WJ AF Sanchez, J. F. Vazin, T. Shen, S. Lee, C. T. Schoen, C. J. Spivak, C. Shen, J. Freed, W. J. TI 5-HT-containing neurons can be differentiated from human neural progenitor cells. SO CYTOTHERAPY LA English DT Meeting Abstract C1 NIDA, Cellular Neurobiol Res Branch, IRP, DHHS,NIH, Baltimore, MD 21224 USA. ScienCell Res Labs, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2006 VL 8 SU 1 MA 163 PG 1 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 067YB UT WOS:000239337600162 ER PT J AU Huey, ED Mirza, N Putnam, KT Soares, H Csako, G Levy, JA Copenhaver, B Cohen, RM Sunderland, T AF Huey, Edward D. Mirza, Nadeem Putnam, Karen T. Soares, Holly Csako, Gyorgy Levy, James A. Copenhaver, Brittany Cohen, Robert M. Sunderland, Trey TI Stability of CSF beta-amyloid(1-42) and tau levels by APOE genotype in Alzheimer patients SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE Alzheimer disease diagnostic tests; cerebrospinal fluid biomarker; beta-amyloid; tau; APOE genotype ID CEREBROSPINAL-FLUID TAU; FOLLOW-UP; CLINICAL-DIAGNOSIS; DISEASE; PROTEIN; DEMENTIA; ALLELE; EPSILON-4; MARKER; SCALE AB Background: Cerebrospinal fluid (CSF) measures of beta-amyloid(1-42) and tau differ between patients with Alzheimer's Disease ( AD) and elderly normal controls. The effect of time and APOE genotype on these biomarkers continues to be elucidated. Methods: We assessed CSF beta-amyloid(1-42) and tau in 20 mild-to-moderate AD patients, 11 APOE epsilon 4+ and 9 APOE epsilon 4 -, over a mean time of 3.8 years ( range 1 - 11.1 years). Results: Over the period measured, CSF beta-amyloid(1-42) levels were lower in APOE epsilon 4+ compared to APOE epsilon 4 - patients, and the levels decreased over time. Tau levels were stable over time and did not show an effect of APOE allele. Conclusions: While this is a limited clinical sample, the further decrease in CSF beta-amyloid(1-42) (i.e., more abnormal) combined with the CSF tau stability over a mean period of almost 4 years suggests that beta-amyloid(1-42) and tau maintain their potential usefulness as diagnostic biomarkers over time. These findings should be taken into account if CSF beta-amyloid(1-42) and tau are used as measures of treatment response. Copyright (C) 2006 S. Karger AG, Basel. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Dept Lab Med, WG Magnuson Clin Ctr, Bethesda, MD 20892 USA. Pfizer Inc, Pfizer Cent Res, Pharmacogenom & Clin Biochem Measurements Div, Groton, CT 06340 USA. EM hueye@ninds.nih.gov FU NIMH NIH HHS [Z01 MH00330-14] NR 24 TC 14 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PY 2006 VL 22 IS 1 BP 48 EP 53 DI 10.1159/000093261 PG 6 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 107JJ UT WOS:000242166700008 PM 16682793 ER PT J AU Zouboulis, CC Stratakis, CA AF Zouboulis, Christos C. Stratakis, Constantine A. TI Laminin alpha(1)-chain may have a role in adnexal morphogenesis SO DERMATOLOGY LA English DT Letter DE laminin alpha(1)-chain; adnexal morphogenesis ID ULERYTHEMA-OPHRYOGENES; KERATOSIS PILARIS; ORGAN-CULTURE; 18P DELETION; HUMAN SKIN; EXPRESSION; GROWTH; TRANSLOCATION; INHIBITION; RECEPTOR C1 Dessau Med Ctr, Dept Dermatol, D-06847 Dessau, Germany. Dessau Med Ctr, Dept Immunol, D-06847 Dessau, Germany. Charite Univ Med Berlin, Inst Clin Pharmacol & Toxicol, Res Grp Biogerontol Dermatopharmacol & Dermatoend, Berlin, Germany. NICHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD USA. RP Zouboulis, CC (reprint author), Dessau Med Ctr, Dept Dermatol, Auenweg 38, D-06847 Dessau, Germany. EM christos.zouboulis@klinikum-dessau.de RI Dr. Zouboulis, Christos/I-4493-2013 OI Dr. Zouboulis, Christos/0000-0003-1646-2608 NR 16 TC 1 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-8665 J9 DERMATOLOGY JI Dermatology PY 2006 VL 213 IS 2 BP 175 EP 176 DI 10.1159/000093864 PG 2 WC Dermatology SC Dermatology GA 073SM UT WOS:000239762900021 PM 16902302 ER PT J AU Mage, RG Lanning, D Knight, KL AF Mage, RG Lanning, D Knight, KL TI B cell and antibody repertoire development in rabbits: The requirement of gut-associated lymphoid tissues SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article ID HEAVY-CHAIN LOCUS; H-MUTANT RABBITS; C-ALPHA-GENES; LIGHT-CHAIN; V-H; SOMATIC DIVERSIFICATION; ALLOTYPE SUPPRESSION; SEQUENCE-ANALYSIS; PRE-B; IMMUNOGLOBULIN ALLOTYPES AB The antibody repertoire of rabbits has interested immunologists for decades, in part because of the ease with which large quantities of high affinity antibodies can be obtained in serum, and in part because of the presence of genetic variants, allotypes, within V-H, CH and CL regions. Studies of these allotypes led to the initial descriptions of allelic exclusion, and neonatal suppression of serum Ig production (allotype suppression), and were instrumental in demonstrating that V and C regions are encoded by separate genes and are usually expressed in cis. The immune system of rabbit continues to be of interest primarily because of the use of both gene conversion and somatic hypermutation to diversify rearranged heavy and light chain genes and the role that gut-associated lymphoid tissues (GALT) and intestinal flora play in developing the primary (preimmune) antibody repertoire. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Loyola Univ, Dept Microbiol & Immunol, Maywood, IL USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM rmage@niaid.nih.gov NR 79 TC 55 Z9 58 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2006 VL 30 IS 1-2 BP 137 EP 153 DI 10.1016/j.dci.2005.06.017 PG 17 WC Immunology; Zoology SC Immunology; Zoology GA 991QQ UT WOS:000233829100009 PM 16098588 ER PT J AU Okun, E Saida, H Albeck, M Sredni, B Avtalion, RR AF Okun, E Saida, H Albeck, M Sredni, B Avtalion, RR TI Upregulation of carp GDNF mRNA by the immunomodulator AS101 SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE GDNF; carp; IL-10; PBL; AS101; fish ID NEUROTROPHIC FACTOR; DOPAMINERGIC-NEURONS; TNF-ALPHA; EXPRESSION; IL-10; BRAIN; MICE; MICROGLIA; SUGGESTS; SYSTEM AB Although the glia derived neurotrophic factor (GDNF) is defined as a molecule that maintains neuronal cells, it possesses a range of functions outside the nervous system. For example, it is essential for uretric branching in kidney morphogenesis and for regulating the differentiation of stern cells during spermatogenesis, cardiac, hair follicle and vascular differentiation and the maintenance of immune cells. In the present work, the presence of GDNF in carp peripheral blood leukocytes (PBL) and head kidney cells (HK) was evidenced and its evolutionary importance in both neural and immune systems development was suggested. Using the northern-blot technique, we could observe the expression of two different transcripts of this gene. GDNF upregulation was detected using semi-quantitative PCR, following ex vivo treatment of PBL and HK cells with the immunomodulator AS 101 which was previously shown to inhibit IL-10 and to up-regulate GDNF protein levels in human SVG astrocyte cell line, in 6-OHDA hemi-parkinsonian mice in vivo and in rat glomerular mesengial cells in vitro. (c) 2005 Elsevier Ltd. All rights reserved. C1 Bar Ilan Univ, Fac Life Sci, CAIR Inst, IL-52900 Ramat Gan, Israel. Natl Inst Aging Intramural Res Program, Lab Neurosci, Baltimore, MD 21224 USA. Bar Ilan Univ, Dept Chem, Fac Exact Sci, Ramat Gan, Israel. Bar Ilan Univ, Lab Fish Genet & Immunol, Fac Life Sci, Ramat Gan, Israel. RP Okun, E (reprint author), Bar Ilan Univ, Fac Life Sci, CAIR Inst, IL-52900 Ramat Gan, Israel. EM redgingi@yahoo.com RI okun, eitan/K-1314-2016 OI okun, eitan/0000-0001-8474-1487 NR 27 TC 10 Z9 10 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2006 VL 30 IS 5 BP 441 EP 446 DI 10.1016/j.dci.2005.07.002 PG 6 WC Immunology; Zoology SC Immunology; Zoology GA 028KD UT WOS:000236485200001 PM 16169589 ER PT J AU Pospisil, R Alexander, CB Obiakor, H Sinha, RK Mage, RG AF Pospisil, R Alexander, CB Obiakor, H Sinha, RK Mage, RG TI CD5(+) B cells are preferentially expanded in rabbit appendix: The role of CD5 in B cell development and selection SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE rabbit; B-cells; CD5; appendix; trafficking; VH-mutant alilali; gene conversion; superantigens ID SPLENIC GERMINAL-CENTERS; MUTANT ALICIA RABBITS; V-H GENE; HEAVY-CHAIN; REGION SEQUENCES; CONVERSION; RECEPTOR; EXPRESSION; DIVERSIFICATION; SUPERANTIGENS AB Although only a small proportion of mouse and human B cells are CD5(+), most adult rabbit B cells express CD5. However, CD5 was not detectable on the majority of B cells in neonatal appendix 1 and 3 days after birth. Cell trafficking studies demonstrated that CD5(+) and CD5(-) CD62L(+) B cells from bone marrow migrated into appendix. There, CD5(+) B cells were preferentially expanded and predominated by similar to 2 weeks of age. In mutant alilali rabbits, VHa2(+) B cells develop through gene conversion-like alteration of rearranged VH genes upstream of deleted VH1a2. Correlated appearance of individual CD5(+) germinal centers and VHa2(+) Bcells in mutant appendix suggests that CD5 binding positively selects cells with a2(+) framework regions that bind CD5. Following negative and positive selection, cells with diversified rearranged heavy- and light-chain sequences exit appendix, migrate to peripheral tissues and constitute the preimmune repertoire of CD5(+) B cells that encounter foreign antigens. Published by Elsevier Ltd. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10 11 N 311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM rin3z@nih.gov RI Pospisil, Richard/B-7467-2012 NR 39 TC 5 Z9 5 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2006 VL 30 IS 8 BP 711 EP 722 DI 10.1016/j.dci.2005.10.001 PG 12 WC Immunology; Zoology SC Immunology; Zoology GA 056MW UT WOS:000238528500004 PM 16375969 ER PT J AU Gomez-Anduro, GA Barillas-Mury, CV Peregrino-Uriarte, AB Gupta, L Gollas-Galvan, T Hernandez-Lopez, J Yepiz-Plascencia, G AF Gomez-Anduro, Gracia A. Barillas-Mury, Carolina-V. Peregrino-Uriarte, Alma B. Gupta, Lalita Gollas-Galvan, Teresa Hernandez-Lopez, Jorge Yepiz-Plascencia, Gloria TI The cytosolic manganese superoxide dismutase from the shrimp Litopenaeus vannamei: Molecular cloning and expression SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY LA English DT Article DE antioxidant; cytoplasmic MnSOD; cDNA; expression; WSSV ID SPOT SYNDROME VIRUS; VIBRIO-ALGINOLYTICUS; ANTIOXIDANT ENZYMES; IMMUNE-RESPONSE; SYSTEM; SUSCEPTIBILITY; MITOCHONDRIA; STREPTOMYCES; ALIGNMENT; CELLS AB Manganese containing superoxide dismutase (SOD) is normally a nuclear-encoded mitochondrial enzyme in eukaryotic organisms; however, a cytoplasmic manganese SOD (cMnSOD) was found in crustaceans that use hemocyanin as oxygen carrier. The complete cDNA and deduced amino acid sequence of a cMnSOD from Litopenaeus vannamei were determined. The coding sequence predicts a 287 residues protein with a unique 61 amino acids extension at the N-terminus and lacking a mitochondrial-targeting sequence. Phylogenetic analysis clusters cMnSODs and mitochondrial MnSODs in two separate groups. cMnSOD transcripts were detected in hemocytes, heart, hepatopancreas, intestine, nervous system, muscle. pleopods and gills. Since hemocytes are key defense cells and their reactions produce superoxide radicals, the infection by white spot syndrome virus on the cMnSOD transcript levels were investigated and found to increase transiently 1 h post-infection and then decrease as the viral infection progressed to levels significantly lower than uninfected controls by 12 h post-infection. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ctr Invest Alimentac & Desarrollo, Aquat Mol Biol Lab, Hermosillo 83000, Sonora, Mexico. NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. Unidad Hermosillo, Ctr Invest Biol Noroeste, Hermosillo 83260, Sonora, Mexico. RP Yepiz-Plascencia, G (reprint author), Ctr Invest Alimentac & Desarrollo, Aquat Mol Biol Lab, AC,POB 1735, Hermosillo 83000, Sonora, Mexico. EM gyepiz@cascabel.ciad.mx NR 29 TC 76 Z9 80 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-305X J9 DEV COMP IMMUNOL JI Dev. Comp. Immunol. PY 2006 VL 30 IS 10 BP 893 EP 900 DI 10.1016/j.dci.2006.01.002 PG 8 WC Immunology; Zoology SC Immunology; Zoology GA 079KD UT WOS:000240173900004 PM 16504292 ER PT J AU Pollard, SM Parsons, MJ Kamei, M Kettleborough, RNW Thomas, KA Pham, VN Bae, MK Scott, A Weinstein, BM Stemple, DL AF Pollard, SM Parsons, MJ Kamei, M Kettleborough, RNW Thomas, KA Pham, VN Bae, MK Scott, A Weinstein, BM Stemple, DL TI Essential and overlapping roles for laminin alpha chains in notochord and blood vessel formation SO DEVELOPMENTAL BIOLOGY LA English DT Article DE laminin; notochord; blood vessels; basement membrane; cell differentiation ID CONGENITAL MUSCULAR-DYSTROPHY; ONE-EYED PINHEAD; EPIDERMOLYSIS-BULLOSA; VASCULAR DEVELOPMENT; BASEMENT-MEMBRANES; ZEBRAFISH EMBRYOS; GROWTH-FACTOR; BETA-3 CHAIN; MOUSE EMBRYO; LAMC1 GENE AB Laminins are mal. or constituents of basement membranes and have wide ranging functions during development and in the adult. They are a family of heterotrimeric molecules created through association of an alpha, beta and gamma chain. We previously reported that two zebrafish loci, grumpy (gup) and sleepy (sly), encode laminin beta 1 and gamma 1, which are important both for notochord differentiation and for proper intersegmental blood vessel (ISV) formation. In this study we show that bashful (bal) encodes laminin alpha 1 (lama 1). Although the strongest allele, bal(m190), is fully penetrant, when compared to gup or sly mutant embryos, bal mutants are not as severely affected, as only anterior notochord fails to differentiate and ISVs are unaffected. This suggests that other a chains, and hence other isoforms, act redundantly to laminin 1 in posterior notochord and ISV development. We identified cDNA sequences for lama2, lama4 and lama5 and disrupted the expression of each alone or in mutant embryos also lacking laminin alpha 1. When expression of laminin alpha 4 and laminin alpha 1 are simultaneously disrupted, notochord differentiation and ISVs are as severely affected as sly or gup mutants. Moreover, live imaging of transgenic embryos expressing enhanced green fluorescent protein in forming ISVs reveals that the vascular defects in these embryos are due to an inability of ISV sprouts to migrate correctly along the intersegmental, normally laminin-rich regions. (c) 2005 Elsevier Inc. All rights reserved. C1 Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Med Res, Div Dev Biol, London NW7 1AA, England. RP Stemple, DL (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Gen Campus, Cambridge CB10 1SA, England. EM ds4@sanger.ac.uk RI Pollard, Steven/B-7966-2010 OI Pollard, Steven/0000-0001-6428-0492 FU Intramural NIH HHS NR 60 TC 63 Z9 63 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JAN 1 PY 2006 VL 289 IS 1 BP 64 EP 76 DI 10.1016/j.ydbio.2005.10.006 PG 13 WC Developmental Biology SC Developmental Biology GA 000IZ UT WOS:000234456200007 PM 16321372 ER PT J AU Meshorer, E Yellajoshula, D George, E Scambler, PJ Brown, DT Mistell, T AF Meshorer, E Yellajoshula, D George, E Scambler, PJ Brown, DT Mistell, T TI Hyperdynamic plasticity in pluripotent embryonic of chromatin proteins stem cells SO DEVELOPMENTAL CELL LA English DT Article ID IN-VITRO DIFFERENTIATION; LIVING HUMAN-CELLS; GENE-EXPRESSION; HINDBRAIN NEURONS; MAMMALIAN-CELLS; RAPID EXCHANGE; DNA-SYNTHESIS; HISTONE H1; HETEROCHROMATIN; VIVO AB Differentiation of embryonicstem (ES)cells from a pluripotent to a committed state involves global changes in genome expression patterns. Gene activity is critically determined by chromatin structure and interactions of chromatin binding proteins. Here, we show that major architectural chromatin proteins are hyperdynamic and bind loosely to chromatin in ES cells. Upon differentiation, the hyperdynamic proteins become immobilized on chromatin. Hyperdynamic binding is a property of pluripotent cells, but not of undifferentiated cells that are already lineage committed. ES cells lacking the nucleosome assembly factor HirA exhibit elevated levels of unbound histones, and formation of embryold bodies is accelerated. In contrast, ES cells, in which the dynamic exchange of H1 is restricted, display differentiation arrest. We suggest that hyperdynamic binding of structural chromatin proteins is a functionally important hallmark of pluripotent ES cells that contributes to the maintenance of plasticity in undifferentiated ES cells and to establishing higher-order chromatin structure. C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Inst Child Hlth, London WC1N 1EH, England. RP Mistell, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov RI Scambler, Peter/C-4998-2008 OI Scambler, Peter/0000-0002-1487-4628 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010309-07] NR 38 TC 589 Z9 602 U1 2 U2 19 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2006 VL 10 IS 1 BP 105 EP 116 DI 10.1016/j.devcel.2005.10.017 PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 006ZC UT WOS:000234935500014 PM 16399082 ER PT J AU Wang, H Singh, SR Zheng, ZY Oh, SW Chen, X Edwards, K Hou, SX AF Wang, H Singh, SR Zheng, ZY Oh, SW Chen, X Edwards, K Hou, SX TI Rap-GEF signaling controls stem cell anchoring to their niche through regulating DE-cadherin-mediated cell adhesion in the Drosophila testis SO DEVELOPMENTAL CELL LA English DT Article ID EXCHANGE FACTOR; SELF-RENEWAL; IN-VIVO; GERMLINE; PROTEIN; GTPASE; SPERMATOGENESIS; PROLIFERATION; ORIENTATION; YEAST AB Stem cells will undergo self-renewal to produce new stem cells if they are maintained in their niches. The regulatory mechanisms that recruit and maintain stem cells in their niches are not well understood. In Drosophilatestes, a group of 12 nondividing somatic cells, called the hub, identifies the stem cell niche by producing the growth factor Unpaired (Upd). Here, we show that Rap-GEF/Rap signaling controls stem cell anchoring to the niche through regulating DE-cadherin-mediated cell adhesion. Loss of function of a Drosophila Rap-GEF (Gef26) results in loss of both germline and somatic stem cells. The Gef26 mutation specifically impairs adherens junctions at the hub-stem cell interface, which results in the stem cells "drifting away" from the niche and losing stem cell identity. Thus, the Rap signal ing/E-cadherin pathway may represent one mechanism that regulates polarized niche formation and stem cell anchoring. C1 NCI, Immunobiol Lab, NIH, Frederick, MD 21702 USA. Illinois State Univ, Dept Biol Sci, Normal, IL 61790 USA. RP Hou, SX (reprint author), NCI, Immunobiol Lab, NIH, Frederick, MD 21702 USA. EM shou@mail.ncifcrf.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999] NR 38 TC 56 Z9 61 U1 3 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2006 VL 10 IS 1 BP 117 EP 126 DI 10.1016/j.devcel.2005.11.004 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 006ZC UT WOS:000234935500015 PM 16399083 ER PT J AU Sugimura, I Lilly, MA AF Sugimura, I Lilly, MA TI Bruno inhibits the expression of mitotic cyclins during the prophase I meiotic arrest of Drosophila oocytes SO DEVELOPMENTAL CELL LA English DT Article ID OSKAR MESSENGER-RNA; GERMLINE CYST FORMATION; TRANSLATIONAL REPRESSOR BRUNO; CELL-CYCLE; SYNAPTONEMAL COMPLEX; RECOMBINATION NODULES; MELANOGASTER FEMALES; BINDING-PROTEIN; WILD-TYPE; S-PHASE AB Animal oocytes undergo a highly conserved developmental arrest in prophase of meiosis 1. The maintenance of the prophase I arrest requires the silencing of Cdk1 activity. Drosophila oocytes inhibit the accumulation of the mitotic cyclins, the activating subunits of Cdk1, via a poorly defined posttranscriptional mechanism. Here, we demonstrate that the translational repressor Bruno binds the 3' UTR and inhibits the translation of the mitotic cyclin Cyclin A during prophase of meiosis I. In the absence of Bruno, ovarian cysts enter melosis but rapidly accumulate high levels of mitotic cyclins and return to the mitotic cycle. Based on our results, we propose a model in which Bruno and the anaphase-promoting complex/cyclosome act together to restrict the accumulation of the mitotic cyclins, and thus Cdk1 activity, during the prophase I arrest of the Drosophila oocyte. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lilly, MA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM mlilly@helix.nih.gov OI Lilly, Mary/0000-0003-1564-619X FU Intramural NIH HHS NR 50 TC 45 Z9 45 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JAN PY 2006 VL 10 IS 1 BP 127 EP 135 DI 10.1016/j.devcel.2005.10.018 PG 9 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 006ZC UT WOS:000234935500016 PM 16399084 ER PT J AU Martin, SC Wolters, PL Toledo-Tamula, MA Zeichner, SL Hazra, R Civitello, L AF Martin, Staci C. Wolters, Pamela L. Toledo-Tamula, Mary Anne Zeichner, Steven L. Hazra, Rohan Civitello, Lucy TI Cognitive functioning in school-aged children with vertically acquired HIV infection being treated with highly active antiretroviral therapy (HAART) SO DEVELOPMENTAL NEUROPSYCHOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CENTRAL-NERVOUS-SYSTEM; HIV-1-INFECTED CHILDREN; COMBINATION THERAPY; REPORTED ADHERENCE; BASAL GANGLIA; VIRAL LOAD; FOLLOW-UP; DISEASE; AIDS AB In today's era of highly active antiretroviral therapy (HAART), few children with HIV-1 infection experience severe central nervous system (CNS) manifestations indicative of encephalopathy. However, little is known about the neurocognitive strengths and weaknesses of HIV-infected children treated with HAART. This cross-sectional study is the first to systematically investigate the relation between cognitive functioning and medical markers in HIV-infected children and adolescents treated with HAART with varying levels of computed tomography (CT) brain scan abnormalities. The Wechsler Intelligence Scale for Children-Third Edition was administered to 41 vertically infected children (mean age = 11.2 years) treated with HAART for at least 1 year. Other procedures at the time of testing included CT brain scans and collection of CD4 cell counts and plasma HIV-1 RNA PCR. Although global cognitive functioning among participants was in the Average range, children with minimal to moderate CT brain scan abnormalities scored significantly lower than children with normal scans on composite measures of cognitive functioning and five specific subtests, especially tasks involving executive functions. Furthermore, children with worse immune status (CD4+ counts <= 500) scored lower on subtests measuring processing speed. Viral load was unrelated to cognitive test scores. Thus, children with HIV being treated with HAART remain at risk for developing CNS disease. Findings emphasize the importance of conducting neuropsychological assessments in this population, particularly for children with cortical atrophy and absolute CD4+ cell counts <= 500. C1 NCI, Neuropsychol Grp, HIV & AIDS Malignancy Branch, Bethesda, MD 20814 USA. Med Illness Counseling Ctr, Chevy Chase, MD USA. Childrens Natl Med Ctr, Washington, DC USA. RP Martin, SC (reprint author), NCI, Neuropsychol Grp, HIV & AIDS Malignancy Branch, 9030 Old Georgetown Rd, Bethesda, MD 20814 USA. EM martins@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01 SC 07006] NR 72 TC 39 Z9 42 U1 2 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 8756-5641 J9 DEV NEUROPSYCHOL JI Dev. Neuropsychol. PY 2006 VL 30 IS 2 BP 633 EP 657 DI 10.1207/s15326942dn3002_1 PG 25 WC Psychology, Developmental; Psychology; Psychology, Experimental SC Psychology GA 097YF UT WOS:000241485300001 PM 16995830 ER PT J AU Heindel, JJ Lawler, C AF Heindel, Jerrold J. Lawler, Cindy BE Gluckman, P Hanson, M TI Role of exposure to environmental chemicals in developmental origins of health and disease SO DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE LA English DT Article; Book Chapter ID ESTROGEN-RECEPTOR-ALPHA; BISPHENOL-A ALTERS; ENDOCRINE DISRUPTORS; PERINATAL EXPOSURE; PRENATAL EXPOSURE; IN-UTERO; NEONATAL EXPOSURE; OBESITY EPIDEMIC; MATERNAL SMOKING; DNA METHYLATION C1 [Heindel, Jerrold J.; Lawler, Cindy] NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. RP Heindel, JJ (reprint author), NIEHS, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. NR 88 TC 4 Z9 4 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52184-743-8 PY 2006 BP 82 EP 97 DI 10.1017/CBO9780511544699.008 D2 10.2277/ 0521847435 PG 16 WC Medicine, General & Internal; Pediatrics SC General & Internal Medicine; Pediatrics GA BXX29 UT WOS:000297341600008 ER PT J AU Belsky, J Booth-LaForce, CL Bradley, R Brownell, CA Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Kelly, JF McCartney, K O'Brien, M Phillips, D Weinraub, M AF Belsky, J Booth-LaForce, CL Bradley, R Brownell, CA Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Kelly, JF McCartney, K O'Brien, M Phillips, D Weinraub, M CA NICHD Early Child Care Res Net TI Infant-mother attachment classification: Risk and protection in relation to changing maternal caregiving quality SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE early attachment security; risks and protection; behavior problems in preschoolers; maternal sensitivity; continuity from infancy to preschool ID DISRUPTIVE BEHAVIOR PROBLEMS; EARLY CHILD-CARE; DISORGANIZED ATTACHMENT; PRESCHOOL ATTACHMENT; EXTERNALIZING PROBLEMS; INDIVIDUAL ADAPTATION; MIDDLE CHILDHOOD; SECURITY; PREDICTORS; PSYCHOPATHOLOGY AB The relations between early infant-mother attachment and children's social competence and behavior problems during the preschool and early school-age period were examined in more than 1,000 children under conditions of decreasing, stable, and increasing maternal parenting quality. Infants' Strange Situation attachment classifications predicted mothers' reports of children's social competence and teachers' reports of externalizing and internalizing behaviors from preschool age through 1st grade. These relations appeared to be mediated by parenting quality; main effects of attachment classification disappeared when effects of parenting quality were controlled. Interactions were also observed. For example, when parenting quality improved over time, teachers rated children with insecure infant-mother attachments lower on externalizing behaviors; when parenting quality decreased, teachers rated insecure children higher on externalizing behaviors. In contrast, children classified as securely attached in infancy did not appear to be affected by declining or improving parenting quality. C1 NICHD, Early Child Care Res Network, Rockville, MD 20852 USA. RP Belsky, J (reprint author), NICHD, Early Child Care Res Network, 6100 Execut Blvd, Rockville, MD 20852 USA. OI Belsky, Jay/0000-0003-2191-2503 NR 77 TC 102 Z9 103 U1 7 U2 48 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD JAN PY 2006 VL 42 IS 1 BP 38 EP 58 DI 10.1037/0012-1649.42.1.38 PG 21 WC Psychology, Developmental SC Psychology GA 005SM UT WOS:000234844100004 ER PT J AU Asghar, Z Yau, D Chan, F LeRoith, D Chan, CB Wheeler, MB AF Asghar, Z Yau, D Chan, F LeRoith, D Chan, CB Wheeler, MB TI Insulin resistance causes increased beta-cell mass but defective glucose-stimulated insulin secretion in a murine model of type 2 diabetes SO DIABETOLOGIA LA English DT Article DE beta cell compensation; beta cell dysfunction; insulin resistance; insulin secretion ID METABOLIC SYNDROME; TRANSGENIC MICE; PIMA-INDIANS; MALONYL-COA; RECEPTOR; MUSCLE; DYSFUNCTION; KNOCKOUT; HYPERGLYCEMIA; DISRUPTION AB Aims/hypothesis: Although insulin resistance induces compensatory increases in beta cell mass and function to maintain normoglycaemia, it is not clear whether insulin resistance can precipitate beta cell dysfunction and hyperglycaemia without a pre-existing beta cell susceptibility. We therefore examined the beta cell phenotype in the MKR mouse, a model in which expression of a dominant-negative IGF 1 receptor (IGF1R) in skeletal muscle leads to systemic insulin resistance and diabetes. Materials and methods: Circulating glucose, insulin and glucagon concentrations were measured. Insulin sensitivity, glucose tolerance and insulin release in vivo were assessed by i.p. insulin and glucose tolerance tests. Beta cell function was assessed via insulin secretion from isolated islets and the glucose gradient in the perfused pancreas. Beta cell morphology was examined via immunohistochemistry. MKR mice were fed a high-fat diet containing sucrose (HFSD) to test metabolic capacity and beta cell function. Results: Insulin-resistant MKR mice developed hyperglycaemia and a loss of insulin responsiveness in vivo. Basal insulin secretion from the perfused pancreas was elevated, with no response to glucose. Despite the demand on insulin secretion, MKR mice had increased pancreatic insulin content and beta cell mass mediated through hyperplasia and hypertrophy. The HFSD worsened hyperglycaemia in MKR mice but, despite increased food intake in these mice, failed to induce the obesity observed in wild-type mice. Conclusions/interpretation: Our studies demonstrate that insulin resistance of sufficient severity can impair glucose-stimulated insulin secretion, thereby undermining beta cell compensation and leading to hyperglycaemia. Moreover, because insulin stores were intact, the secretory defects reflect an early stage of beta cell dysfunction. C1 Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med, Toronto, ON, Canada. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Prince Edward Isl, Atlantic Vet Coll, Dept Biomed Sci, Charlottetown, PE C1A 4P3, Canada. RP Wheeler, MB (reprint author), Univ Toronto, Dept Physiol, 1 Kings Coll Circle Room 3352, Toronto, ON M5S 1A8, Canada. EM michael.wheeler@utoronto.ca RI Chan, Catherine/C-1162-2011; OI Wheeler, Michael/0000-0002-7480-7267; Chan, Catherine/0000-0003-3882-0592 NR 38 TC 41 Z9 45 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD JAN PY 2006 VL 49 IS 1 BP 90 EP 99 DI 10.1007/s00125-005-0045-y PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 006UT UT WOS:000234923700015 PM 16362284 ER PT J AU Abati, A Greene, MH Filie, A Loud, J Prindiville, S Danforth, D Giusti, RM AF Abati, A Greene, MH Filie, A Loud, J Prindiville, S Danforth, D Giusti, RM TI Quantification of the cellular components of breast duct lavage samples SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Letter ID ABNORMAL-CYTOLOGY; CANCER RISK; WOMEN; MASTECTOMY; FLUID; UTILITY; ATYPIA C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Clin Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM abatia@mail.nih.gov NR 17 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD JAN PY 2006 VL 34 IS 1 BP 78 EP 81 DI 10.1002/dc.20371 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 999MT UT WOS:000234394400016 PM 16355383 ER PT S AU Thoma, GR Ford, G Chung, M Vasudevan, K Antani, S AF Thoma, GR Ford, G Chung, M Vasudevan, K Antani, S BE Allebach, JP Chao, H TI Interactive publications: creation and usage - art. no. 607603 SO Digital Publishing SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Digital Publishing CY JAN 16-17, 2006 CL San Jose, CA SP Soc Imaging Sci & Technol, SPIE DE interactive publication; dynamic table; multimedia document; biomedical media ID CARDIAC-SURGERY AB As envisioned here, an "interactive publication" has similarities to multimedia documents that have been in existence for a decade or more, but possesses specific differentiating characteristics. In common usage,. the latter refers to online entities that, in addition to text, consist of files of images and video clips residing separately in databases, rarely providing immediate context to the document text. While an interactive publication has many media objects as does the "traditional" multimedia document, it is a self-contained document, either as a single file with media files embedded within it, or as a "folder" containing tightly linked media files. The main characteristic that differentiates an interactive publication from a traditional multimedia document is that the reader would be able to reuse the media content for analysis and presentation, and to check the underlying data and possibly derive alternative conclusions leading, for example, to more in-depth peer reviews. We have created prototype publications containing paginated text and several media types encountered in the biomedical literature: 3D animations of anatomic structures; graphs, charts and tabular data; cell development images (video sequences); and clinical images such as CT, MRI and ultrasound in the DICOM format. This paper presents developments to date including: a tool to convert static tables or graphs into interactive entities, authoring procedures followed to create prototypes, and advantages and drawbacks of each of these platforms. It also outlines future work including meeting the challenge of network distribution for these large files. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Thoma, GR (reprint author), Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 12 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-6116-4 J9 P SOC PHOTO-OPT INS PY 2006 VL 6076 BP 7603 EP 7603 AR 607603 DI 10.1117/12.641252 PG 8 WC Imaging Science & Photographic Technology SC Imaging Science & Photographic Technology GA BEE61 UT WOS:000236973100002 ER PT J AU Costa, P AF Costa, Paul, Jr. BE Widiger, TA Simonsen, E Sirovatka, PJ Regier, DA TI COMMENTARY ON TRULL Just Do It: Replace Axis II With a Diagnostic System Based on the Five-Factor Model of Personality SO DIMENSIONAL MODELS OF PERSONALITY DISORDERS: REFINING THE RESEARCH AGENDA FOR DSM-V LA English DT Proceedings Paper CT Conference on Dimensional Models of Personality Disorder CY DEC 01-13, 2004 CL Arlington, VA SP Amer Psychiat Assoc C1 [Costa, Paul, Jr.] NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA BN 978-0-89042-296-0 PY 2006 BP 195 EP 198 PG 4 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA BWL80 UT WOS:000294204100022 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tated, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tated, DG TI Rehabilitation medicine summit: Building research capacity SO DISABILITY AND REHABILITATION LA English DT Article C1 Harvard Univ, Spaulding Rehabil Hosp, Sch Med, Boston, MA 02114 USA. NIH, Bethesda, MD USA. Boston Univ, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Florida, Gainesville, FL 32611 USA. Univ Texas, Med Branch, Galveston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rehabil Inst Chicago, Chicago, IL USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Spaulding Rehabil Hosp, Sch Med, 125 Nashua St, Boston, MA 02114 USA. EM wfrontera@partners.org OI Jette, Alan/0000-0002-2117-9973 NR 3 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0963-8288 J9 DISABIL REHABIL JI Disabil. Rehabil. PY 2006 VL 28 IS 1 BP 71 EP 75 DI 10.1080/09638280500407175 PG 5 WC Rehabilitation SC Rehabilitation GA 997SI UT WOS:000234267600009 PM 16393836 ER PT J AU Solarsh, G Hofman, KJ AF Solarsh, Geoff Hofman, Karen J. BE Jamison, DT Feachem, RG Makgoba, MW Bos, ER Baingana, FK Hofman, KJ Rogo, KO TI Developmental Disabilities SO DISEASE AND MORTALITY IN SUB-SAHARAN AFRICA, 2ND EDITION LA English DT Article; Book Chapter ID HUMAN-IMMUNODEFICIENCY-VIRUS; CONGENITAL-RUBELLA SYNDROME; FETAL ALCOHOL SYNDROME; ADJUSTED LIFE YEARS; INTRAUTERINE GROWTH-RETARDATION; RANDOMIZED CONTROLLED-TRIAL; PRIMARY-SCHOOL CHILDREN; BIRTH-WEIGHT INFANTS; 10 QUESTIONS SCREEN; SUB-SAHARAN AFRICA C1 [Solarsh, Geoff] Monash Univ, Sch Rural Hlth, Bendigo, Australia. [Hofman, Karen J.] NIH, Div Adv Studies & Policy Anal, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Solarsh, G (reprint author), Monash Univ, Sch Rural Hlth, Bendigo, Australia. NR 143 TC 8 Z9 8 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6398-0 PY 2006 BP 125 EP 147 D2 10.1596/978-0-8213-6397-3 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAH98 UT WOS:000304199700011 ER PT J AU Miller, MA Sentz, JT AF Miller, Mark A. Sentz, John T. BE Jamison, DT Feachem, RG Makgoba, MW Bos, ER Baingana, FK Hofman, KJ Rogo, KO TI Vaccine-Preventable Diseases SO DISEASE AND MORTALITY IN SUB-SAHARAN AFRICA, 2ND EDITION LA English DT Article; Book Chapter ID SUB-SAHARAN AFRICA; INFLUENZAE TYPE-B; NEONATAL TETANUS; MENINGOCOCCAL MENINGITIS; PERTUSSIS; POLIOMYELITIS; IMMUNIZATION; EPIDEMIOLOGY; DIPHTHERIA; CONJUGATE C1 [Miller, Mark A.; Sentz, John T.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Miller, MA (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 73 TC 5 Z9 5 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6398-0 PY 2006 BP 163 EP 177 D2 10.1596/978-0-8213-6397-3 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAH98 UT WOS:000304199700013 ER PT J AU Bloom, BR Michaud, CM La Montagne, JR Simonsen, L AF Bloom, Barry R. Michaud, Catherine M. La Montagne, John R. Simonsen, Lone BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Priorities for Global Research and Development of Interventions SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID HEALTH C1 [Bloom, Barry R.; Michaud, Catherine M.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [La Montagne, John R.; Simonsen, Lone] NIAID, NIH, Bethesda, MD USA. RP Bloom, BR (reprint author), Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 26 TC 11 Z9 12 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 103 EP 118 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100006 ER PT J AU Nugent, R Knaul, F AF Nugent, Rachel Knaul, Felicia BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Fiscal Policies for Health Promotion and Disease Prevention SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID DIARRHEA PREVENTION; SAFE STORAGE; SUBSIDIES; POVERTY; INDIA; COST C1 [Nugent, Rachel] Populat Reference Bur, Washington, DC 20009 USA. [Nugent, Rachel] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Knaul, Felicia] Fdn Mexicana Salud, Mexico City, DF, Mexico. [Knaul, Felicia] Secretaria Educ Publ Medico, Mexico City, DF, Mexico. RP Nugent, R (reprint author), Populat Reference Bur, Washington, DC 20009 USA. NR 53 TC 4 Z9 4 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 211 EP 223 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100013 ER PT J AU Brenzel, L Wolfson, LJ Fox-Rushby, J Miller, M Halsey, NA AF Brenzel, Logan Wolfson, Lara J. Fox-Rushby, Julia Miller, Mark Halsey, Neal A. BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Vaccine-Preventable Diseases SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID INFLUENZAE TYPE-B; INACTIVATED POLIOVIRUS VACCINE; COST-EFFECTIVENESS ANALYSIS; MIDDLE-INCOME COUNTRIES; HEPATITIS-B; IMMUNIZATION SERVICES; ECONOMIC EVALUATIONS; ROUTINE IMMUNIZATION; CONJUGATE VACCINE; NEONATAL TETANUS C1 [Brenzel, Logan] World Bank, Washington, DC 20433 USA. [Wolfson, Lara J.] WHO, Geneva, Switzerland. [Fox-Rushby, Julia] Brunel Univ, Uxbridge UB8 3PH, Middx, England. [Miller, Mark] NIH, Fogarty Int Ctr, Bethesda, MD USA. [Halsey, Neal A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. RP Brenzel, L (reprint author), World Bank, Washington, DC 20433 USA. NR 97 TC 48 Z9 48 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 389 EP 411 PG 23 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100022 ER PT J AU Breman, JG Mills, A Snow, RW Mulligan, JA Lengeler, C Mendis, K Sharp, B Morel, C Marchesini, P White, NJ Steketee, RW Doumbo, OK AF Breman, Joel G. Mills, Anne Snow, Robert W. Mulligan, Jo-Ann Lengeler, Christian Mendis, Kamini Sharp, Brian Morel, Chantal Marchesini, Paola White, Nicholas J. Steketee, Richard W. Doumbo, Ogobara K. BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Conquering Malaria SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID INTERMITTENT PREVENTIVE TREATMENT; PLASMODIUM-FALCIPARUM MALARIA; INSECTICIDE-TREATED NETS; SUB-SAHARAN AFRICA; ANTIMALARIAL-DRUGS; ARTEMETHER-LUMEFANTRINE; COST-EFFECTIVENESS; CLINICAL EPISODES; RANDOMIZED-TRIAL; ECONOMIC-IMPACT C1 [Breman, Joel G.] NIH, Fogarty Int Ctr, Bethesda, MD 20814 USA. [Breman, Joel G.] Dis Control Prior Project, Washington, DC USA. [Mills, Anne] London Sch Hyg & Trop Med, London, England. [Snow, Robert W.] Univ Oxford, Ctr Trop Med, Oxford OX1 2JD, England. [Snow, Robert W.] Kenya Govt Med Res Ctr, Nairobi, Kenya. [Mulligan, Jo-Ann; Morel, Chantal] London Sch Hyg & Trop Med, London, England. [Lengeler, Christian] Swiss Trop Inst, Basel, Switzerland. [Mendis, Kamini; Marchesini, Paola] WHO, Geneva, Switzerland. [Sharp, Brian] MRC, London W1N 4AL, England. [Morel, Chantal] Oxford Outcomes, Oxford, England. [White, Nicholas J.] US Ctr Dis Control & Prevent, Atlanta, GA USA. [Steketee, Richard W.] PATH, Seattle, WA USA. [Doumbo, Ogobara K.] Univ Bamako, Bamako, Mali. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20814 USA. NR 109 TC 37 Z9 37 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 413 EP 431 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100023 ER PT J AU Brown, ML Goldie, SJ Draisma, G Harford, J Lipscomb, J AF Brown, Martin L. Goldie, Sue J. Draisma, Gerrit Harford, Joe Lipscomb, Joseph BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Health Service Interventions for Cancer Control in Developing Countries SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID COST-EFFECTIVENESS ANALYSIS; RANDOMIZED CONTROLLED-TRIAL; POSTMASTECTOMY RADIATION-THERAPY; HELICOBACTER-PYLORI ERADICATION; HUMAN-PAPILLOMAVIRUS TYPE-16; HEPATITIS-B VACCINATION; EARLY BREAST-CANCER; CERVICAL-CANCER; COLORECTAL-CANCER; LUNG-CANCER C1 [Brown, Martin L.; Harford, Joe] NCI, NIH, Bethesda, MD 20892 USA. [Goldie, Sue J.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Lipscomb, Joseph] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. RP Brown, ML (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 124 TC 19 Z9 19 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 569 EP 589 PG 21 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100031 ER PT J AU Chandra, V Pandav, R Laxminarayan, R Tanner, C Manyam, B Rajkumar, S Silberberg, D Brayne, C Chow, J Herman, S Hourihan, F Kasner, S Morillo, L Ogunniyi, A Theodore, W Zhang, ZX AF Chandra, Vijay Pandav, Rajesh Laxminarayan, Ramanan Tanner, Caroline Manyam, Bala Rajkumar, Sadanand Silberberg, Donald Brayne, Carol Chow, Jeffrey Herman, Susan Hourihan, Fleur Kasner, Scott Morillo, Luis Ogunniyi, Adesola Theodore, William Zhang, Zhen-Xin BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Neurological Disorders SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID ACUTE ISCHEMIC-STROKE; RANDOMIZED CONTROLLED-TRIAL; AMERICAN-HEART-ASSOCIATION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; CAROTID-ENDARTERECTOMY; RISK-FACTORS; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; DEVELOPING-COUNTRIES C1 [Chandra, Vijay; Pandav, Rajesh] WHO, Reg Off SE Asia, Geneva, Switzerland. [Manyam, Bala] Texas A&M Univ, HSC Sch Med, College Stn, TX 77843 USA. [Rajkumar, Sadanand; Hourihan, Fleur] Univ Newcastle, Callaghan, NSW 2308, Australia. [Rajkumar, Sadanand] Bloomfield Hosp, Bloomfield, NJ USA. [Silberberg, Donald; Herman, Susan; Kasner, Scott] Univ Penn, Philadelphia, PA 19104 USA. [Brayne, Carol] Univ Cambridge, Cambridge CB2 1TN, England. [Morillo, Luis] Javeriana Univ, Bogota, Colombia. [Ogunniyi, Adesola] Univ Ibadan, Ibadan, Nigeria. [Theodore, William] NINDS, NIH, Bethesda, MD 20892 USA. [Zhang, Zhen-Xin] Beijing Union Med Coll Hosp, Beijing, Peoples R China. [Zhang, Zhen-Xin] Chinese Acad Med Sci, Beijing, Peoples R China. RP Chandra, V (reprint author), WHO, Reg Off SE Asia, Geneva, Switzerland. NR 84 TC 12 Z9 12 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 627 EP 643 PG 17 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100034 ER PT J AU Willett, WC Koplan, JP Nugent, R Dusenbury, C Puska, P Gaziano, TA AF Willett, Walter C. Koplan, Jeffrey P. Nugent, Rachel Dusenbury, Courtenay Puska, Pekka Gaziano, Thomas A. BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Prevention of Chronic Disease by Means of Diet and Lifestyle Changes SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID CORONARY-HEART-DISEASE; ALPHA-LINOLENIC ACID; ACUTE MYOCARDIAL-INFARCTION; IMPAIRED GLUCOSE-TOLERANCE; TYPE-2 DIABETES-MELLITUS; PROMOTING SAFE WALKING; PHYSICAL-ACTIVITY; PUBLIC-HEALTH; URBAN SPRAWL; COST-EFFECTIVENESS C1 [Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Willett, Walter C.; Gaziano, Thomas A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Koplan, Jeffrey P.; Dusenbury, Courtenay] Emory Univ, Atlanta, GA 30322 USA. [Nugent, Rachel] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Gaziano, Thomas A.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Willett, WC (reprint author), Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. NR 92 TC 59 Z9 60 U1 2 U2 3 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 833 EP 850 PG 18 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100046 ER PT J AU Durkin, MS Schneider, H Pathania, VS Nelson, KB Solarsh, GC Bellows, N Scheffler, RM Hofman, KJ AF Durkin, Maureen S. Schneider, Helen Pathania, Vikram S. Nelson, Karin B. Solarsh, Geoffrey C. Bellows, Nicole Scheffler, Richard M. Hofman, Karen J. BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Learning and Developmental Disabilities SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID COMMUNITY-BASED REHABILITATION; FETAL ALCOHOL SYNDROME; RANDOMIZED CONTROLLED-TRIAL; COST-BENEFIT-ANALYSIS; RUBELLA SYNDROME CRS; CEREBRAL-PALSY; DOWNS-SYNDROME; CONGENITAL HYPOTHYROIDISM; DEVELOPING-COUNTRIES; GESTATIONAL-AGE C1 [Durkin, Maureen S.] Univ Wisconsin, Sch Med, Madison, WI 53706 USA. [Schneider, Helen] Univ Witwatersrand, ZA-2050 Wits, South Africa. [Pathania, Vikram S.; Bellows, Nicole; Scheffler, Richard M.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Nelson, Karin B.] NINDS, NIH, Bethesda, MD 20892 USA. [Solarsh, Geoffrey C.] Monash Univ, Clayton, Vic 3800, Australia. [Hofman, Karen J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Durkin, MS (reprint author), Univ Wisconsin, Sch Med, Madison, WI 53706 USA. RI Durkin, Maureen/B-7834-2015 NR 77 TC 8 Z9 8 U1 0 U2 0 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 933 EP 951 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100051 ER PT J AU Miller, M Barrett, S Henderson, DA AF Miller, Mark Barrett, Scott Henderson, D. A. BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Control and Eradication SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID DISEASE ERADICATION; POLIO ERADICATION; COST-ANALYSIS; POLIOMYELITIS; ELIMINATION; POLICIES; MEASLES C1 [Miller, Mark] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. [Barrett, Scott] Johns Hopkins Univ, Baltimore, MD 21218 USA. [Henderson, D. A.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. RP Miller, M (reprint author), NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NR 74 TC 22 Z9 23 U1 0 U2 1 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 1163 EP 1176 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100064 ER PT J AU Debas, HT Laxminarayan, R Straus, SE AF Debas, Haile T. Laxminarayan, Ramanan Straus, Stephen E. BE Jamison, DT Breman, JG Measham, AR Alleyne, G Claeson, M Evans, DB Jha, P Mills, A Musgrove, P TI Complementary and Alternative Medicine SO DISEASE CONTROL PRIORITIES IN DEVELOPING COUNTRIES, 2ND EDITION LA English DT Article; Book Chapter ID RANDOMIZED CONTROLLED-TRIAL; ST-JOHNS-WORT; HEALTH-CARE; BEHAVIORAL MEDICINE; BACK-PAIN; FOLLOW-UP; PSYCHOSOCIAL TREATMENT; CLINICAL-TRIAL; UNITED-STATES; COST C1 [Debas, Haile T.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Laxminarayan, Ramanan] Resources Future Inc, Bristol, Avon, England. [Straus, Stephen E.] NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. RP Debas, HT (reprint author), Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 77 TC 3 Z9 3 U1 2 U2 2 PU WORLD BANK INST PI WASHINGTON PA 1818 H ST NW, WASHINGTON, DC 20433 USA BN 978-0-8213-6180-1 PY 2006 BP 1281 EP 1291 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BAV21 UT WOS:000305583100071 ER PT J AU Martin, R Bielekova, B Hohlfeld, R Utz, U AF Martin, Roland Bielekova, Bibiana Hohlfeld, Reinhard Utz, Ursula TI Biomarkers in multiple sclerosis SO DISEASE MARKERS LA English DT Editorial Material C1 NINDS, NIH, Neurosci Ctr, Div Extramural Res, Bethesda, MD 20892 USA. Hosp Univ Hebron, Catalan Inst Res & Adv Studies, Barcelona, Spain. Hosp Univ Hebron, Unidad Neuroimmunol Clin, Barcelona, Spain. Univ Cincinnati, Dept Neurol, Waddel Ctr MS, Cincinnati, OH USA. Inst Neurosci, Cincinnati, OH USA. Max Planck Inst Neurobiol, Dept Neuroimmunol, Munich, Germany. RP Utz, U (reprint author), NINDS, NIH, Neurosci Ctr, Div Extramural Res, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM utzu@ninds.nih.gov NR 5 TC 13 Z9 16 U1 0 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2006 VL 22 IS 4 BP 183 EP 185 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 167SR UT WOS:000246472100001 PM 17124339 ER PT B AU Lee, JS Thorgeirsson, SS AF Lee, J. -S. Thorgeirsson, S. S. BE Galle, PR Schmidt, WE Gerken, G Wiedenmann, B TI Gene expression profiling of hepatocellular carcinoma: past, present and future SO Disease Progression and Disease Prevention in Hepatology and Gastroenterology SE FALK SYMPOSIUM LA English DT Proceedings Paper CT Falk Symposium 150 on Disease Progression and Disease Prevention in Hepatology and Gastroenterology CY OCT 03-04, 2005 CL Berlin, GERMANY SP Falk Fdn ID COMPARATIVE FUNCTIONAL GENOMICS; HUMAN CANCER; PREDICTION; MICROARRAY; IDENTIFICATION; SIGNATURE; SURVIVAL; MODELS C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Bldg 37,Rm 4146, Bethesda, MD 20892 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-5109-3 J9 FALK SYMP PY 2006 VL 150 BP 233 EP 237 PG 5 WC Oncology; Gastroenterology & Hepatology SC Oncology; Gastroenterology & Hepatology GA BFB99 UT WOS:000240947500022 ER PT S AU Witschi, MA Pokorski, JK Appella, DH AF Witschi, Mark A. Pokorski, Jonathan K. Appella, Daniel H. BE Kimmel, A Oliver, B TI Peptide nucleic acid microarrays made with (S,S)-trans-cyclopentane-constrained peptide nucleic acids SO DNA MICROARRAYS PART A: ARRAY PLATFORMS AND WET-BENCH PROTOCOLS SE Methods in Enzymology LA English DT Review; Book Chapter ID SPECIFICITY; AFFINITY; BINDING; PNA; DNA AB Procedures to attach trans-cyclopentane-modified peptide nucleic acid oligomers to a glass slide are described. Peptide nucleic acids can offer distinct advantages to DNA detection compared to typically used DNA microarrays, especially with regard to chemical stability and quality of data. The trans-cyclopentane modification incorporated into the peptide nucleic acid is, in some cases, essential for successful DNA detection. It is hoped that these peptide nucleic acid-bearing glass slides will find application in several areas of DNA microarray technology. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Dept Chem, Evanston, IL USA. RP Witschi, MA (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-182815-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 410 BP 189 EP 200 DI 10.1016/S0076-6879(06)10009-9 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFT39 UT WOS:000244504800009 PM 16938552 ER PT S AU Hewitt, SM AF Hewitt, Stephen M. BE Kimmel, A Oliver, B TI The application of tissue microarrays in the validation of microarray results SO DNA MICROARRAYS PART A: ARRAY PLATFORMS AND WET-BENCH PROTOCOLS SE Methods in Enzymology LA English DT Review; Book Chapter ID METASTATIC BREAST-CANCER; GENE; AMPLIFICATION; LOCALIZATION; EXPRESSION; CELLS; COLON; END AB Microarray experiments produce a large volume of data that require validation. The validation of these experiments can be carried out in many fashions. In the reduction to clinical utility, the use of tissue microarrays has become a common tool to both validate and generalize the results of microarray experiments. A tissue microarray is a collection of tissue specimens presented on a glass slide in a grid layout. Tissue microarrays contain between tens and hundreds of samples allowing the generalization of microarray findings to a large number of samples. Tissue microarrays can be used for in situ hybridization and immunohistochemical analysis, confirming the results of microarray experiments at both the transcriptional and the proteomic level. This chapter reviews the theory and application of tissue microarrays in the validation of microarray experiments. C1 NCI, NIH, Tissue Array Res Program, Lab Pathol,CCRC,TARP Lab,Adv Technol Ctr, Bethesda, MD 20892 USA. RP Hewitt, SM (reprint author), NCI, NIH, Tissue Array Res Program, Lab Pathol,CCRC,TARP Lab,Adv Technol Ctr, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 26 TC 25 Z9 28 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-182815-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 410 BP 400 EP 415 DI 10.1016/S0076-6879(06)10020-8 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFT39 UT WOS:000244504800020 PM 16938563 ER PT S AU Clark, DJ Shen, CH AF Clark, David J. Shen, Chang-Hui BE Kimmel, A Oliver, B TI Mapping histone modifications by nucleosome immunoprecipitation SO DNA MICROARRAYS PART A: ARRAY PLATFORMS AND WET-BENCH PROTOCOLS SE Methods in Enzymology LA English DT Review; Book Chapter ID YEAST CUP1 CHROMATIN; IN-VITRO; SACCHAROMYCES-CEREVISIAE; H3 PHOSPHORYLATION; GLOBIN GENE; DNA; ACETYLATION; POSITIONS; METHYLATION; ACTIVATOR AB Studies of histone modification patterns and their role in gene regulation have led to the proposal that there is a "histone code." We have developed a method for nucleosome immunoprecipitation that can precisely identify the specific nucleosomes that carry a posttranslational modification of interest. The process involves the isolation and micrococcal nuclease digestion of minichromosomes to generate nucleosome core particles. These are then used in immunoprecipitation reactions with an antibody directed against the histone modification of interest. Subsequently, nucleosome core particle DNA is purified and end labeled. The original locations of the nucleosomes in the immunoprecipitate can be determined at low resolution (using a modified Southern blot hybridization procedure) or at maximal resolution (using the monomer extension method). Using the latter method, the positions of specific nucleosomes that carry the posttranslational modification of interest can be identified precisely. This method is sensitive, provides maximal resolution, and is inexpensive. The approach described here may serve as a paradigm for the study of histone-modifying patterns. C1 NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD USA. CUNY Coll Staten Isl, Inst Macromol Assemblies, Dept Biol, Staten Isl, NY USA. RP Clark, DJ (reprint author), NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD USA. FU Intramural NIH HHS; NIGMS NIH HHS [1R15GM67730-01] NR 21 TC 14 Z9 14 U1 2 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-182815-8 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 410 BP 416 EP 430 DI 10.1016/S0076-6879(06)10021-X PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFT39 UT WOS:000244504800021 PM 16938564 ER PT S AU Yang, IV AF Yang, Ivana V. BE Kimmel, A Oluver, B TI Use of external controls in microarray experiments SO DNA MICROARRAYS, PART B: DATABASES AND STATISTICS SE Methods in Enzymology LA English DT Review; Book Chapter ID DIFFERENTIAL EXPRESSION; GENE-EXPRESSION; OLIGONUCLEOTIDE; NORMALIZATION; PERFORMANCE AB DNA microarray analysis has become the most widely used technique for the study of gene expression patterns on a genomic scale. Microarray analysis is a complex technique involving many steps, and a number of commercial and in-house developed arrays and protocols for data collection and analysis are used in different laboratories. Inclusion of external or spike-in RNA controls allows one to evaluate the variability in gene expression measurements and to facilitate the comparison of data collected using different platforms and protocols. This chapter describes what external controls are, which collections of spike-in controls are available to researchers, and how they are implemented in the laboratory. Applications of external controls in the assessment of microarray performance, normalization strategies, the evaluation of algorithms for gene expression analysis, and the potential to quantify absolute mRNA levels are discussed. C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA. RP Yang, IV (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC USA. NR 25 TC 8 Z9 9 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-182816-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 411 BP 50 EP + DI 10.1016/S0076-6879(06)11004-6 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFT40 UT WOS:000244506300004 PM 16939785 ER PT S AU Reimers, M Carey, VJ AF Reimers, Mark Carey, Vincent J. BE Kimmel, A Oluver, B TI Bioconductor: An open source framework for bioinformatics and computational biology SO DNA MICROARRAYS, PART B: DATABASES AND STATISTICS SE Methods in Enzymology LA English DT Review; Book Chapter ID DISCOVERY AB This chapter describes the Bioconductor project and details of its open source facilities for analysis of microarray and other high-throughput biological experiments. Particular attention is paid to concepts of container and workflow design, connections of biological metadata to statistical analysis products, support for statistical quality assessment, and calibration of inference uncertainty measures when tens of thousands of simultaneous statistical tests are performed. C1 NCI, Bethesda, MD 20892 USA. RP Reimers, M (reprint author), NCI, Bethesda, MD 20892 USA. FU NHGRI NIH HHS [1R33 HG002708] NR 12 TC 134 Z9 141 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-182816-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 411 BP 119 EP + DI 10.1016/S0076-6879(06)11008-3 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFT40 UT WOS:000244506300008 PM 16939789 ER PT S AU Barrett, T Edgar, R AF Barrett, Tanya Edgar, Ron BE Kimmel, A Oluver, B TI Gene expression omnibus: Microarray data storage, submission, retrieval, and analysis SO DNA MICROARRAYS, PART B: DATABASES AND STATISTICS SE Methods in Enzymology LA English DT Review; Book Chapter ID INTEGRATION; NETWORK; INFORMATION AB The Gene Expression Omnibus (GEO) repository at the National Center for Biotechnology Information archives and freely distributes high-throughput molecular abundance data, predominantly gene expression data generated by DNA microarray technology. The database has a flexible design that can handle diverse styles of both unprocessed and processed data in a Minimum Information About a Microarray Experiment-supportive infrastructure that promotes fully annotated submissions. GEO currently stores about a billion individual gene expression measurements, derived from over 100 organisms, submitted by over 1500 laboratories, addressing a wide range of biological phenomena. To maximize the utility of these data, several user-friendly web-based interfaces and applications have been implemented that enable effective exploration, query, and visualization of these data at the level of individual genes or entire studies. This chapter describes how data are stored, submission procedures, and mechanisms for data retrieval and query. GEO is publicly accessible at http://www.ncbi.nlm.nih.gov/projects/geo/. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Barrett, T (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 20 TC 232 Z9 243 U1 2 U2 13 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 978-0-12-182816-5 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 411 BP 352 EP 369 DI 10.1016/S0076-6879(06)11019-8 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFT40 UT WOS:000244506300019 PM 16939800 ER PT S AU Brosh, RM Opresko, PL Bohr, VA AF Brosh, Robert M., Jr. Opresko, Patricia L. Bohr, Vilhelm A. BE Campbell, JL Modrich, P TI Enzymatic mechanism of the WRN helicase/nuclease SO DNA REPAIR, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID WERNER-SYNDROME PROTEIN; SINGLE-STRANDED-DNA; HELICASES DISPLACE STREPTAVIDIN; BLOOM-SYNDROME HELICASES; SYNDROME GENE-PRODUCT; REPLICATION ARREST; FUNCTIONAL INTERACTION; ANNEALING ACTIVITIES; EXONUCLEASE ACTIVITY; HOLLIDAY JUNCTIONS AB Werner syndrome (WS) is a premature aging disorder characterized by genomic instability and increased cancer risk (Martin, 1978). The WRN gene product defective in WS belongs to the RecQ family of DNA helicases (Yu et al, 1996). Mutations in RecQ family members BLM and RecQ4 result in two other disorders associated with elevated chromosomal instability and cancer, Bloom syndrome and Rothmund-Thomson syndrome, respectively (for review see Opresko et al., 2004a). RecQ helicase mutants display defects in DNA replication, recombination, and repair, suggesting a role for RecQ helicases in maintaining genomic integrity. The WRN gene encodes a 1432 amino acid protein that has several catalytic activities (Brosh and Bohr, 2002) (Fig. 1). WRN is a DNA-dependent ATPase and utilizes the energy from ATP hydrolysis to unwind double-stranded DNA. WRN is also a 31 to 51 exonuclease, consistent with the presence of three conserved exonuclease motifs homologous to the exonuclease domain of Escherichia coli DNA polymerase I and RNase D. Most recently, WRN (Machwe et al., 2005) and other human RecQ helicases (Garcia et al., 2004; Machwe et al., 2005; Sharma et al., 2005) have been reported to possess an intrinsic single-strand annealing activity. In addition to its catalytic activities, WRN interacts with a number of proteins involved in various aspects of DNA metabolism. To understand the role of WRN in the maintenance of genome stability, a number of laboratories have undertaken a thorough characterization of its molecular and cellular functions. Here, we describe methods and approaches used for the functional and mechanistic analysis of WRN helicase or exonuclease activity. Protocols for measuring ATP hydrolysis, DNA binding, and catalytic unwinding or exonuclease activity of WRN protein are provided. Application of these procedures should enable the researcher to address fundamental questions regarding the biochemical properties of WRN or related helicases or nucleases, which would serve as a platform for further investigation of its molecular and cellular functions. C1 NIA, Lab Mol Gerontol, IRP, NIH, Baltimore, MD 21224 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Environm & Occupat Hlth, Pittsburgh, PA 15261 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, IRP, NIH, Baltimore, MD 21224 USA. OI Opresko, Patricia/0000-0002-6470-2189 NR 60 TC 24 Z9 24 U1 1 U2 7 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182814-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 409 BP 52 EP + DI 10.1016/S0076-6879(05)09004-X PG 35 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEN83 UT WOS:000238354800004 PM 16793395 ER PT S AU Nakamura, A Sedelnikova, OA Redon, C Pilch, DR Sinogeeva, NI Shroff, R Lichten, M Bonner, WM AF Nakamura, Asako Sedelnikova, Olga A. Redon, Christophe Pilch, Duane R. Sinogeeva, Natasha I. Shroff, Robert Lichten, Michael Bonner, William M. BE Campbell, JL Modrich, P TI Techniques for gamma-H2AX detection SO DNA REPAIR, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID DOUBLE-STRAND BREAKS; METAPHASE CHROMOSOMES; DNA; PHOSPHORYLATION; PROTEINS; ARREST AB When a double-strand break (DSB) forms in DNA, many molecules of histone H2AX present in the chromatin flanking the break site are rapidly phosphorylated. The phosphorylated derivative of H2AX is named gamma-H2AX, and the phosphorylation site is a conserved serine four residues from the C-terminus, 139 in mammals and 129 in budding yeast. An antibody to gamma-H2AX reveals that the molecules form a gamma-focus at the DSB site. The gamma-focus increases in size rapidly for 10-30 min after formation, and remains until the break is repaired. Studies have revealed that small numbers of gamma-foci are present in cells even without the purposeful introduction of DNA DSBs. These cryptogenic foci increase in number during senescence in culture and aging in mice. This chapter presents techniques for revealing gamma-H2AX foci in cultured cells, in metaphase spreads from cultured cells, in tissues, and in yeast. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Nakamura, A (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RI Lichten, Michael/C-5795-2013 OI Lichten, Michael/0000-0001-9707-2956 NR 13 TC 54 Z9 59 U1 1 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182814-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 409 BP 236 EP + DI 10.1016/S0076-6879(05)09014-2 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEN83 UT WOS:000238354800014 PM 16793405 ER PT S AU Storici, F Resnick, MA AF Storici, Francesca Resnick, Michael A. BE Campbell, JL Modrich, P TI The delitto perfetto approach to in vivo site-directed mutagenesis and chromosome rearrangements with synthetic oligonucleotides in yeast SO DNA REPAIR, PT B SE Methods in Enzymology LA English DT Review; Book Chapter ID SACCHAROMYCES-CEREVISIAE; MUTATIONS; ENDONUCLEASE; REPLACEMENT; REPAIR AB In vivo genome manipulation through site-directed mutagenesis and chromosome rearrangements has been hindered by the difficulty in achieving high frequencies of targeting and the intensive labor required to create altered genomes that do not contain any heterologous sequence. Here we describe our approach, referred to as delitto perfetto, that combines the versatility of synthetic oligonucleotides for targeting with the practicality of a general selection system. It provides for an enormously wide variety of genome modifications via homologous recombination. Exceptional high frequencies of mutations are reached when a site-specific double-strand break (DSB) is induced within the locus targeted by the synthetic oligonucleotides. Presented in this chapter is an in-depth description of a series of applications of the delitto perfetto strategy for mutagenesis and chromosome modification both with and without the induction of a DSB, along with the procedures and materials. C1 NIH, Chromosome Stabil Sect, Mol Genet Lab, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Storici, F (reprint author), NIH, Chromosome Stabil Sect, Mol Genet Lab, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 18 TC 121 Z9 121 U1 4 U2 11 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182814-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 2006 VL 409 BP 329 EP + DI 10.1016/S0076-6879(05)09019-1 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BEN83 UT WOS:000238354800019 PM 16793410 ER PT S AU Parker, HG Sutter, NB Ostrander, EA AF Parker, Heidi G. Sutter, Nathan B. Ostrander, Elaine A. BE Ostrander, EA Giger, U LindbladToh, K TI Understanding Genetic Relationships among Purebred Dogs: The PhyDo Project SO DOG AND ITS GENOME SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID SINGLE NUCLEOTIDE POLYMORPHISMS; LINKAGE DISEQUILIBRIUM; DOMESTIC DOG; HUMAN GENOME; MICROSATELLITE MARKERS; MULTILOCUS GENOTYPES; POPULATION-STRUCTURE; BREEDS; DISEASE; IDENTIFICATION C1 [Parker, Heidi G.; Sutter, Nathan B.; Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Parker, HG (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 46 TC 0 Z9 0 U1 2 U2 3 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-781-5 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 44 BP 141 EP 157 PG 17 WC Genetics & Heredity; Veterinary Sciences SC Genetics & Heredity; Veterinary Sciences GA BNJ27 UT WOS:000274725700011 ER PT S AU Khanna, C Paoloni, MC AF Khanna, Chand Paoloni, Melissa C. BE Ostrander, EA Giger, U LindbladToh, K TI Cancer Biology in Dogs SO DOG AND ITS GENOME SE Cold Spring Harbor Monograph Series LA English DT Article; Book Chapter ID MAST-CELL TUMORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; GENE-EXPRESSION SIGNATURES; CANINE OSTEOSARCOMA; SUPPRESSOR GENE; FACTOR-RECEPTOR; ACTIVATING MUTATIONS; CDNA MICROARRAYS; LUNG-CANCER; C-KIT C1 [Khanna, Chand; Paoloni, Melissa C.] NCI, Ctr Canc Res, NIH, Rockville, MD 20850 USA. RP Khanna, C (reprint author), NCI, Ctr Canc Res, NIH, Rockville, MD 20850 USA. NR 88 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LABORATORY PRESS PI PLAINVIEW PA 10 SKYLINE DRIVE, PLAINVIEW, NY 11803-2500 USA SN 0270-1847 BN 978-0-87969-781-5 J9 COLD SPRING HARB MON JI Cold Spring Harbor Monogr. Ser. PY 2006 VL 44 BP 451 EP 472 PG 22 WC Genetics & Heredity; Veterinary Sciences SC Genetics & Heredity; Veterinary Sciences GA BNJ27 UT WOS:000274725700025 ER PT J AU Shamoo, AE Resnik, DB AF Shamoo, Adil E. Resnik, David B. TI Ethical issues for clinical research managers SO DRUG INFORMATION JOURNAL LA English DT Article DE clinical research; managers; ethics; principles ID BOARDS AB Clinical research managers have many scientific, legal, institutional, financial, and ethical responsibilities, such as ensuring the quality and integrity of the research process, protecting human subjects, complying with regulations, and using resources effectively. To fulfill these responsibilities, clinical research managers must exhibit leadership and moral integrity. In this article, we examine the ethics of clinical research managers. We explicate ethical concepts and principles that apply to managing clinical research, identify the ethical duties of managers, explore ethical issues that arise in clinical research management at the trenches, describe a process for making ethical decisions, and analyze a hypothetical case scenario. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Shamoo, AE (reprint author), Univ Maryland, Sch Med, 108 N Greene St, Baltimore, MD 21201 USA. EM ashamoo@umaryland.edu NR 35 TC 1 Z9 1 U1 2 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2006 VL 40 IS 4 BP 371 EP 383 PG 13 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 104KE UT WOS:000241956500002 ER PT J AU Miyata, M Matsuda, Y Tsuchiya, H Kitada, H Akase, T Shimada, M Nagata, K Gonzalez, FJ Yamazoe, Y AF Miyata, Masaaki Matsuda, Yoshiki Tsuchiya, Hiroyuki Kitada, Hirotaka Akase, Takanori Shimada, Miki Nagata, Kiyoshi Gonzalez, Frank J. Yamazoe, Yasushi TI Chenodeoxycholic acid-mediated activation of the farnesoid X receptor negatively regulates hydroxysteroid sulfotransferase SO DRUG METABOLISM AND PHARMACOKINETICS LA English DT Article DE hydroxysteroid sulfotransferase; FXR; bile acid; sulfation; negative regulation; Sult2a ID HUMAN CYTOSOLIC SULFOTRANSFERASES; CONSTITUTIVE ANDROSTANE RECEPTOR; INDUCED LIVER TOXICITY; NUCLEAR RECEPTOR; BILE-ACID; MOLECULAR-CLONING; DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; ENZYMATIC CHARACTERIZATION; FEEDBACK-REGULATION; MOUSE-LIVER AB Hydroxysteroid sulfotransferase catalyzing bile acid sulfation plays an essential role in protection against lithocholic acid (LCA)-induced liver toxicity. Hepatic levels of Sult2a is up to 8-fold higher in farnesoid X receptor-null mice than in the wild-type mice. Thus, the influence of FXR ligand (chenodeoxycholic acid (CDCA) and LCA) feeding on hepatic Sult2a expression was examined in FXR-null and wild-type mice. Hepatic Sult2a protein content was elevated in FXR-null and wild-type mice fed a LCA (1% and 0.5%) diet. Treatment with 0.5% CDCA diet decreased hepatic Sult2a to 20% of the control in wild-type mice, but increased the content in FXR-null mice. Liver Sult2a1 (St2a4) mRNA levels were reduced to 26% in wild-type mice after feeding of a CDCA diet, while no decrease was observed on Sult2a1 mRNA levels in FXR-null mice after CDCA feeding. A significant inverse relationship (r(2) = 0.523) was found between hepatic Sult2a protein content and small heterodimer partner (SHP) mRNA level. PCN-mediated increase in Sult2a protein levels were attenuated by CDCA feeding in wild-type mice, but not in FXR-null mice. Human SULT2A1 protein and mRNA levels were decreased in HepG2 cells treated with the FXR agonists, CDCA or GW4064 in dose-dependent manners, although SHP mRNA levels were increased. These results suggest that SULT2A is negatively regulated through CDCA-mediated FXR activation in mice and humans. C1 Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Sendai, Miyagi 9808578, Japan. NIH, NCI, Lab Metab, Bethesda, MD 20892 USA. Tohoku Univ, 21st Century Ctr Excellence Program, CRESCENDO, Sendai, Miyagi 980, Japan. RP Miyata, M (reprint author), Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Aoba Ku, 6-3,Aoba,Aramaki, Sendai, Miyagi 9808578, Japan. EM miyata@mail.pharm.tohoku.ac.jp NR 36 TC 25 Z9 26 U1 0 U2 1 PU JAP SOC STUDY XENOBIOTICS PI TOKYO PA INT MED INF CENTER SHINANOMACHI RENGAKAN, 35 SHINANO-MACHI SHINJUKU-KU, TOKYO, 160-0016, JAPAN SN 1347-4367 J9 DRUG METAB PHARMACOK JI Drug Metab. Pharmacokinet. PY 2006 VL 21 IS 4 BP 315 EP 323 DI 10.2133/dmpk.21.315 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 226FU UT WOS:000250574100007 PM 16946559 ER PT J AU Miyata, M Nomoto, M Yamazoe, Y Gonzalez, FJ AF Miyata, Masaaki Nomoto, Masahiro Yamazoe, Yasushi Gonzalez, Frank J. TI FXR-dependent enhancement of biliary lipid excretion is a critical determinant for protection against cholic acidinduced liver toxicity SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 1st Asia Pacific Meeting of the International-Society-for-the-Study-of-Xenobiotics CY MAY 25-27, 2006 CL Cheju Isl, SOUTH KOREA SP Bristol Myers Squibb, Cypex, Pfizer, Global REs & Dev, Amgen, Hoffman LaRoche, Dept Non Clin Drug Safety, Novartis Pharmaceut Corp, Wyeth Res, Avagadro, Bioanalyt Syst, Eli Lilly, Organon C1 Tohoku Univ, Grad Sch Pharmaceut Sci, Sendai, Miyagi 980, Japan. Natl Canc Inst, Lab Metab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 3 BP 17 EP 18 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110UN UT WOS:000242406900031 ER PT J AU Loewen, G Usuki, E Parkinson, O Parkinson, A Wang, MZ Saulter, J Bridges, AS Tidwel, RR Paine, MF Hall, JE Cheung, YL Hall, M Stephens, CE Boykin, DW Allen, JL Zeldin, DC AF Loewen, Greg Usuki, Etsuko Parkinson, Oliver Parkinson, Andrew Wang, Michael Z. Saulter, Janelle Bridges, Arlene S. Tidwell, Richard R. Paine, Mary F. Hall, James E. Cheung, Yen-Ling Hall, Michael Stephens, Chad E. Boykin, David W. Allen, James L. Zeldin, Darryl C. TI CYP4F enzymes are the major enzymes in human liver microsomes that catalyze the O-demethylation of the antiparasitic prodrug DB289 SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 XenoTech LLC, Lenexa, KS USA. Univ N Carolina, Chapel Hill, NC USA. Huntingdon Life Sci Ltd, Huntingdon, England. Georgia State Univ, Atlanta, GA 30303 USA. Immtech Int Inc, Vernon Hills, IL USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RI BRIDGES, ARLENE/N-4534-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 2 MA 87 BP 51 EP 52 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600080 ER PT J AU Kang-Sickel, JC Gold, A Ball, LM Karupiah, J Nylander-French, LA Parron, V Klapper, DG French, JE AF Kang-Sickel, J. Connie Gold, Avram Ball, Louise M. Karupiah, Jayaraj Nylander-French, Leena A. Parron, Vandy Klapper, David G. French, John E. TI Detection of naphthalene keratin adducts in human skin using ELISA SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Mol Toxicol Lab, Res Triangle Pk, NC USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 2 MA 112 BP 67 EP 68 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600105 ER PT J AU Kodama, S Negishi, M AF Kodama, S Negishi, M TI Phenobarbital confers its diverse effects by activating the orphan nuclear receptor car SO DRUG METABOLISM REVIEWS LA English DT Review DE liver; CAR; nuclear receptors; hepatic metabolism; gluconeogenesis; hepatocellular carcinoma; gene transcription; cytochrome P450 ID CONSTITUTIVE ANDROSTANE RECEPTOR; PREGNANE-X-RECEPTOR; THYROID-HORMONE METABOLISM; RAT CYP2B2 GENE; TRANSCRIPTION FACTOR; PROTEIN-KINASE; BILE-ACID; INSULIN SENSITIVITY; DRUG-METABOLISM; DIABETIC RATS AB In the early 1960s, phenobarbital (PB) was shown to induce hepatic drug metabolism and the induction was implicated in the molecular mechanism of drug tolerance development. Since then, it has become evident that PB not only induces drug metabolism, but also triggers pleiotropic effects on liver function., such as cell growth and communication, proliferation of the endoplasmic reticulum, tumor promotion, glucose metabolism, steroid/thyroid hormone metabolism, and bile acid synthesis. Upon activation by PB and numerous PB-type inducers, the nuclear receptor CAR mediates those pleiotropic actions by regulating various hepatic genes, utilizing multiple regulatory mechanisms. C1 Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), Natl Inst Environm Hlth Sci, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 62 TC 54 Z9 56 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 IS 1-2 BP 75 EP 87 DI 10.1080/03602530600569851 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036YH UT WOS:000237112800007 PM 16684649 ER PT J AU Ji, E Kim, M Kim, S Kim, K Oh, J Kimchi-Sarfaty, C Kim, I Ambudkar, S Gottesman, M AF Ji, E. Kim, M. Kim, S. Kim, K. Oh, J. Kimchi-Sarfaty, C. Kim, I. Ambudkar, S. Gottesman, M. TI Functional characterization of SNP and haplotype of human MDR1 gene using a vaccina virus expression system SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 1st Asia Pacific Meeting of the International-Society-for-the-Study-of-Xenobiotics CY MAY 25-27, 2006 CL Cheju Isl, SOUTH KOREA SP Bristol Myers Squibb, Cypex, Pfizer, Global REs & Dev, Amgen, Hoffman LaRoche, Dept Non Clin Drug Safety, Novartis Pharmaceut Corp, Wyeth Res, Avagadro, Bioanalyt Syst, Eli Lilly, Organon C1 Seoul Natl Univ, Seoul, South Korea. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 3 BP 80 EP 80 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110UN UT WOS:000242406900144 ER PT J AU Wang, HB Faucette, S Zhang, TC Omiecinski, CJ LeCluyse, EL Negishi, M AF Wang, Hongbing Faucette, Stephanie Zhang, Tong-Cun Omiecinski, Curtis John LeCluyse, Edward L. Negishi, Masahiko TI Validation of a human car variant (hCAR3) as the in vitro predictor for PXR independent CYP2B6/CYP3A4 induction SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 Univ N Carolina, Sch Pharm, Div Mol Pharmaceut, Chapel Hill, NC USA. Penn State Univ, Dept Ctr Mol Toxicol, University Pk, PA 16802 USA. CellzDirect Inc, Dept Chief Sci Officer, Pittsboro, NC USA. NIEHS, Lab Pharmacol & Chem Pharmacogen Sec, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 2 MA 179 BP 115 EP 115 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600172 ER PT J AU Wang, TCZH Sueyoshi, T Negishi, M LeCluyse, EL AF Wang, Tong-Cun Zhangand Hongbing Sueyoshi, Tatsuya Negishi, Masahiko LeCluyse, Edward L. TI Differential mechanisms involved in the nuclear activation of hCAR by direct and indirect activators SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. NIEHS, Lab Pharmacol & Chem Pharmacogen Sec, NIH, Res Triangle Pk, NC 27709 USA. CellzDirect Inc, Dept Chief Sci Officer, Pittsboro, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 2 MA 207 BP 134 EP 134 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600200 ER PT J AU Yang, L Wang, Y Stein, WD AF Yang, Ling Wang, Yulin Stein, Wilfred D. TI Quantitative determination of the anti-MDR activities of ginsenosides SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 1st Asia Pacific Meeting of the International-Society-for-the-Study-of-Xenobiotics CY MAY 25-27, 2006 CL Cheju Isl, SOUTH KOREA SP Bristol Myers Squibb, Cypex, Pfizer, Global REs & Dev, Amgen, Hoffman LaRoche, Dept Non Clin Drug Safety, Novartis Pharmaceut Corp, Wyeth Res, Avagadro, Bioanalyt Syst, Eli Lilly, Organon C1 Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 3 BP 138 EP 139 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110UN UT WOS:000242406900251 ER PT J AU Yang, L Wang, Y Stein, WD AF Yang, Ling Wang, Yulin Stein, Wilfred D. TI A kinetic study of Rhodamine 123 pumping by P-glycoprotein SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 1st Asia Pacific Meeting of the International-Society-for-the-Study-of-Xenobiotics CY MAY 25-27, 2006 CL Cheju Isl, SOUTH KOREA SP Bristol Myers Squibb, Cypex, Pfizer, Global REs & Dev, Amgen, Hoffman LaRoche, Dept Non Clin Drug Safety, Novartis Pharmaceut Corp, Wyeth Res, Avagadro, Bioanalyt Syst, Eli Lilly, Organon C1 Chinese Acad Sci, Dalian Inst Chem Phys, Lab Pharmaceut Resource Discovery, Dalian, Peoples R China. NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 3 BP 139 EP 139 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 110UN UT WOS:000242406900252 ER PT J AU Stern, ST McNeil, SE AF Stern, Stephan T. McNeil, Scott E. TI Protection against cisplatin-induced apoptosis in LLC-PK1 cells by dendritic fullerenes SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 NCI, Nanotechnol Characterizat Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 2 MA 254 BP 164 EP 165 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600246 ER PT J AU Kikuchi, R Kusuhara, H Sugiyama, Y Hattori, N Shiota, K Kim, I Gonzalez, FJ AF Kikuchi, Ryota Kusuhara, Hiroyuki Sugiyama, Yuichi Hattori, Naka Shiota, Kunio Kim, Insook Gonzalez, Frank J. TI Regulation of the expression of human organic anion transporter 3 by hepatocyte nuclear factor 1 alpha/beta and DNA methylation SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 14th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics CY OCT 22-26, 2006 CL Rio Grande, PR SP Int Soc Study Xenobiot C1 Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Mol Pharmacokinet, Tokyo, Japan. Univ Tokyo, Lab Cellular Biochem, Dept Anim Resource Sci, Tokyo, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2006 VL 38 SU 2 MA 378 BP 245 EP 246 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 098FO UT WOS:000241506600370 ER PT J AU Uhl, K Cox, E Rogan, R Zeldis, JB Hixon, D Furlong, LA Singer, S Holliman, T Beyer, J Woolever, W AF Uhl, K Cox, E Rogan, R Zeldis, JB Hixon, D Furlong, LA Singer, S Holliman, T Beyer, J Woolever, W TI Thalidomide use in the US - Experience with pregnancy testing in the STEPS (R) programme SO DRUG SAFETY LA English DT Article ID DISEASE AB Introduction: In 1998, thalidomide (Thalomid(R)), a known human teratogen, was approved by the US FDA for the treatment of erythema nodosum leprosum. To prevent fetal exposure to thalidomide, a restricted distribution risk management programme, the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.(R)), was implemented. All clinicians, pharmacists and patients who prescribe, dispense and receive thalidomide, respectively, are required to enrol in S.T.E.P.S.(R). Sexually active females of childbearing potential must use two methods of birth control before, during and after treatment. These patients must also have a negative pregnancy test within 24 hours before beginning therapy and periodically while on therapy. The objective of this report is to summarise the patterns of thalidomide use and to describe the occurrence of positive pregnancy tests in females of childbearing potential while they were using thalidomide in the S.T.E.P.S.(R) programme in the US. Study design/methods: A retrospective review of patients receiving thalidomide within the S.T.E.P.S.(R) programme from September 1998 to 31 December 2004 to determine the occurrence of positive pregnancy tests whilst on treatment. Results: Approximately 124 000 (43% female) patients were registered within the S.T.E.P.S.(R) programme between September 1998 and 31 December 2004. Approximately 6000 patients were females of childbearing potential, representing 5% of all patients and 11% of all female patients. Between 30 July 2001 and 31 December 2004, >88% of thalidomide use was for oncological conditions. There were 72 females of childbearing potential who had positive pregnancy tests. Sixty-nine of these patients had false positive pregnancy tests. Of the remaining three, one woman was pregnant while on thalidomide. This patient had an initial negative test and received thalidomide. Therapy was stopped when she had a positive pregnancy test. This pregnancy resulted in a miscarriage. Two additional patients were determined to be pregnant before receiving thalidomide. Conclusions: The S.T.E.P.S.(R) programme is critical to managing the risks of thalidomide-associated teratogenicity. Sustained vigilance among healthcare providers and patients receiving thalidomide is essential to its continued success. Healthcare providers should be aware of the occurrence of false-positive pregnancy tests in females of childbearing potential receiving thalidomide. C1 US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Task Force, Silver Spring, MD 20993 USA. Celgene Corp, Summit, NJ USA. NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Task Force, 10903 New Hampshire Ave,Bldg 22,Room 6460, Silver Spring, MD 20993 USA. EM kathleen.uhl@oc.fda.gov NR 10 TC 29 Z9 29 U1 2 U2 10 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2006 VL 29 IS 4 BP 321 EP 329 DI 10.2165/00002018-200629040-00003 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 033UH UT WOS:000236875000003 PM 16569081 ER PT J AU Watts, DH AF Watts, DH TI Treating HIV during pregnancy - An update on safety issues SO DRUG SAFETY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; MOTHER-TO-CHILD; COMBINATION ANTIRETROVIRAL THERAPY; SINGLE-DOSE NEVIRAPINE; RANDOMIZED CONTROLLED-TRIAL; PERSISTENT MITOCHONDRIAL DYSFUNCTION; REVERSE-TRANSCRIPTASE INHIBITORS; MATERNAL-INFANT TRANSMISSION; IN-UTERO EXPOSURE; ACUTE FATTY LIVER AB The expanded use of multiple antiretroviral drugs during pregnancy has led to a reduction in the occurrence of perinatal transmission of HIV to < 2%, but has led to concerns regarding both short-term toxicity and the long-term impact on the woman and her child. Enhanced toxicity of nevirapine has been noted among women with CD4+ lymphocyte counts > 250 cells/mu L at treatment initiation and among pregnant women on long-term didanosine and stavudine. These drugs should be avoided in such situations if alternatives are available. Efavirenz has been associated with birth defects in monkeys, and several cases of neural tube defects have been reported in humans after first trimester exposure, so treatment with this drug should be avoided during the first trimester. Protease inhibitors have been associated with an increased risk of maternal glucose intolerance, pre-eclampsia and preterm birth in some, but not all, studies. Pregnancies exposed to antiretroviral therapy should be registered with the Antiretroviral Pregnancy Registry as early in pregnancy as possible in order to provide data on the risk of birth defects after exposure. The pharmacokinetics of nucleoside and non-nucleoside reverse transcriptase inhibitors are not significantly changed in pregnancy, so standard dosing may be used. However, concentrations of several protease inhibitors are lower in pregnancy, so ritonavir-boosting or increased doses are required. Of great theoretical concern is the impact of resistance mutations that develop following single-dose nevirapine therapy on the response to later therapy among women and their infected infants. The use of dual nucleoside therapy for 3-7 days after single-dose nevirapine in the mother reduces but does not eliminate the risk of nevirapine resistance; alternative regimens for prevention of resistance are under study, as are the subsequent responses of the mother and her infant to therapy. Short courses of prophylactic zidovudine and nevirapine have been well tolerated in neonates. Concern has been raised, however, that these exposures may lead to persistent mitochondrial dysfunction or later cancers, underscoring the need for long-term surveillance of antiretroviral-exposed, HIV-uninfected infants. C1 NICHHD, Ctr Res Mothers & Children, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. RP Watts, DH (reprint author), NICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH, 6100 Execut Blvd,Room 4B11,MSC 7510, Bethesda, MD 20892 USA. EM wattsh@mail.nih.gov NR 101 TC 35 Z9 35 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2006 VL 29 IS 6 BP 467 EP 490 DI 10.2165/00002018-200629060-00002 PG 24 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 056XJ UT WOS:000238558100002 PM 16752931 ER PT J AU Misra, RN AF Misra, RN TI Clinical progress of selective cyclin-dependent kinase (CDK) inhibitors SO DRUGS OF THE FUTURE LA English DT Review ID PHASE-II TRIAL; CONTINUOUS-INFUSION FLAVOPIRIDOL; 72-HOUR CONTINUOUS-INFUSION; MANTLE-CELL LYMPHOMA; CARCINOMA-CELLS; BREAST-CANCER; P27(KIP1); ROSCOVITINE; POTENT; COMBINATION AB Cyclin-dependent kinases (CDKs) are cellular proteins that control cell proliferation. Due to their central role in controlling cell growth and to their dysregulation in many cancers, CDKs have become an important molecular target for oncology drug development programs. The clinical progress of the first-generation compound alvocidib and three second-generation inhibitors (SNS-032, seliciclib and Ro-4584820) is reviewed here. In order to fully evaluate the clinical utility of these agents, dosing schedules and routes of administration continue to be optimized with the goals of minimizing toxicities and maximizing exposure. To date, single-agent phase II efficacy trials in cancer patients using alvocidib have been disappointing, possibly due to dosing limitations resulting from competing toxicities. Recent clinical results, however, indicate that alvocidib may still find niche utilities as single-agent therapy employing finely tailored dosing schedules for particularly susceptible cancers, such as chronic lymphocytic leukemia (CLL). Evaluation of second-generation compounds with greater potency, reduced toxicity and oral activity is continuing in single-agent trials. Clinical applications for combinations with other cytotoxic agents are also being pursued for both alvocidib and the second-generation agents. The clinical role of these agents continues to be explored, although the general clinical validation of the target in cancer therapy is possibly still several years away. In fact, these agents are more likely to be used clinically in combination with other cytotoxic agents than as stand-alone therapy. C1 NCI, Pharmaceut Resources Branch, Dev Therapeut Program, Div Canc Therapeut & Diag,NIH, Rockville, MD 20852 USA. RP Misra, RN (reprint author), NCI, Pharmaceut Resources Branch, Dev Therapeut Program, Div Canc Therapeut & Diag,NIH, 6130 Execut Blvd,EPN 8025, Rockville, MD 20852 USA. EM misrara@mail.nih.gov NR 93 TC 12 Z9 13 U1 1 U2 7 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JAN PY 2006 VL 31 IS 1 BP 43 EP 52 DI 10.1358/dof.2006.031.01.953584 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 025TI UT WOS:000236289400007 ER PT J AU Smirnova, E Goldberg, EB Makarova, KS Lin, L Brown, WJ Jackson, CL AF Smirnova, E Goldberg, EB Makarova, KS Lin, L Brown, WJ Jackson, CL TI ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells SO EMBO REPORTS LA English DT Article DE adipose triglyceride lipase; lipid droplet; adiposome; patatin domain; adiposome triglyceride lipase ID HORMONE-SENSITIVE LIPASE; TRIACYLGLYCEROL LIPASE; PROTEIN; TIP47; IDENTIFICATION; MOBILIZATION; DROPLETS AB Lipid droplets (LDs), also called adiposomes, are found in many eukaryotic cells, and are highly upregulated in lipid-storage cells, such as adipocytes. The mechanism by which adiposomes and their component neutral lipids are degraded is an important health issue with the rapidly spreading epidemic of obesity. Recently, a novel triglyceride lipase (adipose triglyceride lipase (ATGL)) that catalyses the initial step in triglyceride hydrolysis in adipocyte LDs was identified. Here, we show that ATGL also functions in non-adipocyte cells, and has an important role in LD degradation in these cells. Overexpression of wild-type ATGL causes a marked decrease in LD size, whereas a catalytically inactive mutant retains the ability to localize to LDs, but is unable to decrease their size. Depletion of ATGL by RNA interference leads to a significant increase in the size of LDs. These results show that ATGL has an important role in LD/adiposome turnover in mammalian cells. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Jackson, CL (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM cathyj@helix.nih.gov OI Jackson, Catherine/0000-0002-0843-145X NR 19 TC 146 Z9 159 U1 0 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD JAN PY 2006 VL 7 IS 1 BP 106 EP 113 DI 10.1038/sj.embor.7400559 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 023QV UT WOS:000236142200022 PM 16239926 ER PT J AU Taubenberger, JK Morens, DM AF Taubenberger, JK Morens, DM TI Influenza revisited SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material ID PANDEMIC INFLUENZA; AMINO-ACID; VIRUS C1 Armed Forces Inst Pathol, Dept Mol Pathol, Rockville, MD 20850 USA. NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), Armed Forces Inst Pathol, Dept Mol Pathol, 1413 Res Blvd,Bldg 101,Rm 1057, Rockville, MD 20850 USA. EM taubenberger@afip.osd.mil NR 8 TC 27 Z9 30 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2006 VL 12 IS 1 BP 1 EP 2 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999VU UT WOS:000234419700001 PM 16610160 ER PT J AU Taubenberger, JK Morens, DM AF Taubenberger, JK Morens, DM TI 1918 influenza: the mother of all pandemics SO EMERGING INFECTIOUS DISEASES LA English DT Article ID SPANISH INFLUENZA; VIRUS HEMAGGLUTININ; A VIRUSES; RECEPTOR; GENE; MORTALITY; EVOLUTION; SEQUENCES; STRAINS; SEGMENT AB The "Spanish" influenza pandemic of 1918-1919, which caused 50 million deaths worldwide, remains an ominous warning to public health. Many questions about its origins, its unusual epiclemiologic features, and the basis of its pathogenicity remain unanswered. The public health implications of the pandemic therefore remain in doubt even as we now grapple with the feared emergence of a pandemic caused by H5N1 or other virus. However, new information about the 1918 virus is emerging, for example, sequencing of the entire genome from archival autopsy tissues. But, the viral genome alone is unlikely to provide answers to some critical questions. Understanding the 1918 pandemic and its implications for future pandemics requires careful experimentation and in-depth historical analysis. C1 Armed Forces Inst Pathol, Dept Mol Pathol, Rockville, MD 20850 USA. NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), Armed Forces Inst Pathol, Dept Mol Pathol, 1413 Res Blvd,Bldg 101,Rm 1057, Rockville, MD 20850 USA. EM taubenberger@afip.osd.mil NR 39 TC 571 Z9 622 U1 6 U2 88 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2006 VL 12 IS 1 BP 15 EP 22 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999VU UT WOS:000234419700004 PM 16494711 ER PT J AU Krause, R AF Krause, R TI The swine flu episode and the fog of epidemics SO EMERGING INFECTIOUS DISEASES LA English DT Article AB The 1918 influenza pandemic has shaped research and public health for nearly a century. In 1976, the specter of 1918 loomed large when a pandemic threatened the country again. Public health officials initiated a mass vaccination campaign, but the anticipated pandemic failed to occur. An examination of the available data in 1976 and the decision to vaccinate, as well as lessons learned from the HIV/AIDS epidemic in the early 1980s, may help shape an appropriate public health response to future threats from avian influenza or other infectious diseases. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Krause, R (reprint author), NIAID, NIH, Bldg 16,Rm 202,16 Ctr Dr, Bethesda, MD 20892 USA. EM richard_krause@nih.gov FU Intramural NIH HHS NR 7 TC 16 Z9 17 U1 1 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2006 VL 12 IS 1 BP 40 EP 43 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999VU UT WOS:000234419700008 PM 16494715 ER PT J AU Luke, CJ Subbarao, K AF Luke, CJ Subbarao, K TI Vaccines for pandemic influenza SO EMERGING INFECTIOUS DISEASES LA English DT Article ID COLD-ADAPTED INFLUENZA; A/DUCK/SINGAPORE/97 H5N3 VACCINE; REVERSE GENETICS; A VIRUS; HONG-KONG; MF59-ADJUVANTED INFLUENZA; HUMAN INFECTION; H9N2; CANDIDATE; REASSORTANT AB Recent outbreaks of highly pathogenic avian influenza in Asia and associated human infections have led to a heightened level of awareness and preparation for a possible influenza pandemic. Vaccination is the best option by which spread of a pandemic virus could be prevented and severity of disease reduced. Production of live attenuated and inactivated vaccine seed viruses against avian influenza viruses, which have the potential to cause pandemics, and their testing in preclinical studies and clinical trials will establish the principles and ensure manufacturing experience that will be critical in the event of the emergence of such a virus into the human population. Studies of such vaccines will also add to our understanding of the biology of avian influenza viruses and their behavior in mammalian hosts. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Rm 6132,50,S Dr, Bethesda, MD 20892 USA. EM ksubbarao@niaid.nih.gov FU Intramural NIH HHS NR 38 TC 85 Z9 96 U1 0 U2 3 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2006 VL 12 IS 1 BP 66 EP 72 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999VU UT WOS:000234419700013 PM 16494720 ER PT J AU Fauci, AS AF Fauci, AS TI Pandemic influenza threat and preparedness SO EMERGING INFECTIOUS DISEASES LA English DT Article ID AVIAN INFLUENZA; A VIRUS; H5N1 INFLUENZA; VACCINE; INFECTION; TRANSMISSION; OUTBREAK; LESSONS; SARS; H9N2 AB The threat of a human influenza pandemic has greatly increased over the past several years with the emergence of highly virulent avian influenza viruses, notably H5N1 viruses, which have infected humans in several Asian and European countries. Previous influenza pandemics have arrived with little or no warning, but the current widespread circulation of H5N1 viruses among avian populations and their potential for increased transmission to humans and other mammalian species may afford us an unprecedented opportunity to prepare for the next pandemic threat. The US Department of Health and Human Services is coordinating a national strategy to respond to an influenza pandemic that involves multiple agencies, including the Centers for Disease Control and Prevention, the Food and Drug Administration, and the National Institutes of Health (NIH). Within NIH, the National Institute of Allergy and Infectious Diseases (NIAID) conducts basic and clinical research to develop new vaccine technologies and antiviral drugs against influenza viruses. We describe recent research progress in preparing for pandemic influenza. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, Bldg 31,Room 7A03,MSC 2520, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 39 TC 100 Z9 103 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2006 VL 12 IS 1 BP 73 EP 77 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999VU UT WOS:000234419700014 PM 16494721 ER PT J AU Morens, DM Taubenberger, JK AF Morens, DM Taubenberger, JK TI Influenza and the origins of the Phillips Collection, Washington, DC SO EMERGING INFECTIOUS DISEASES LA English DT Article C1 NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Morens, DM (reprint author), NIH, 6610 Rockledge Dr,Room 4097, Bethesda, MD 20892 USA. EM dm270q@nih.gov NR 4 TC 1 Z9 1 U1 0 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN PY 2006 VL 12 IS 1 BP 78 EP 80 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999VU UT WOS:000234419700015 PM 16502565 ER PT B AU Max, MB Buzas, B AF Max, MB Buzas, B BE Campbell, JN Basbaum, AI Dray, A Dubner, R Dworkin, RH Sang, CN TI Dissecting molecular causes of the components of chronic neuropathic pain syndromes SO Emerging Strategies for the Treatment of Neuropathic Pain LA English DT Proceedings Paper CT Meeting on Emerging Strategies for the Treatment of Neuropathic Pain CY APR 13, 2005 CL Scottsdale, AZ ID POSTHERPETIC NEURALGIA; PSYCHIATRIC-DISORDERS; CEREBROSPINAL-FLUID; CANDIDATE GENE; CYSTATIN-C; BACK-PAIN; POLYMORPHISMS; DEPRESSION; DISEASE; SLEEP C1 Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Dept Hlth & Human Sci, Bethesda, MD 20892 USA. RP Max, MB (reprint author), Natl Inst Dent & Craniofacial Res, Pain & Neurosensory Mech Branch, NIH, Dept Hlth & Human Sci, Bldg 10,3C-405, Bethesda, MD 20892 USA. NR 52 TC 0 Z9 0 U1 0 U2 0 PU INT ASSOC STUDY PAIN (IASP) PRESS PI SEATTLE PA 909 NE 43RD ST, SUITE 304, SEATTLE, WA 98105 USA BN 0-931092-61-2 PY 2006 BP 327 EP 349 PG 23 WC Medicine, General & Internal; Clinical Neurology SC General & Internal Medicine; Neurosciences & Neurology GA BEE85 UT WOS:000237010800015 ER PT J AU Teff, K AF Teff, K TI Learning hunger: Conditioned anticipatory ghrelin responses in energy homeostasis SO ENDOCRINOLOGY LA English DT Editorial Material ID CEPHALIC-PHASE INSULIN; FOOD-INTAKE; RELEASE; HUMANS; RAT; SECRETION; VAGOTOMY; APPETITE; STOMACH; GLUCOSE C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Teff, K (reprint author), Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 USA. EM kteff@pobox.upenn.edu NR 29 TC 5 Z9 5 U1 1 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2006 VL 147 IS 1 BP 20 EP 22 DI 10.1210/en.2005-1345 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 994TG UT WOS:000234053500005 PM 16365141 ER PT J AU Yanik, T Dominguez, G Kuhar, MJ Del Giudice, EM Loh, YP AF Yanik, T Dominguez, G Kuhar, MJ Del Giudice, EM Loh, YP TI The Leu34Phe proCART mutation leads to cocaine- and amphetamine-regulated transcript (CART) deficiency: A possible cause for obesity in humans SO ENDOCRINOLOGY LA English DT Article ID SECRETORY PATHWAY; PROOPIOMELANOCORTIN; PRECURSORS; PEPTIDES; GENE; MICE AB Cocaine- and amphetamine-regulated transcript ( CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wildtype proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART. C1 NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Seconda Univ Napoli, Dipartimento Pediat, I-80138 Naples, Italy. Emory Univ, Yerkes Natl Primate Ctr, Atlanta, GA 30329 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, NIH, Bldg 49,Room 5A22, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov FU Intramural NIH HHS; NIDA NIH HHS [DA15162] NR 17 TC 21 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2006 VL 147 IS 1 BP 39 EP 43 DI 10.1210/en.2005-0812 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 994TG UT WOS:000234053500008 PM 16210370 ER PT J AU Taylor, RA Cowin, P Couse, JF Korach, KS Risbridger, GP AF Taylor, RA Cowin, P Couse, JF Korach, KS Risbridger, GP TI 17 beta-Estradiol induces apoptosis in the developing rodent prostate independently of ER alpha or ER beta SO ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-BETA; MESSENGER-RNA EXPRESSION; MOUSE VENTRAL PROSTATE; ANDROGEN RECEPTOR; REPRODUCTIVE PHENOTYPES; STEROID-HORMONES; RAT; LIGANDS; GLAND; MICE AB Estrogens induce both proliferative and antiproliferative responses in the prostate gland. To date, antiproliferative effects of estrogens are generally considered to be due to systemic antiandrogenic actions. However, estrogen action mediated through estrogen receptor (ER)beta was recently suggested as another mechanism of induction of apoptosis in the prostate. This study aimed to explore the hypothesis that the antiproliferative effects of estrogen are directly mediated through ER beta using a prostate organ culture system. We previously reported effects of 17 beta-estradiol (E-2) using rat ventral prostate (VP) tissues, and adapted the system for culturing mouse tissues. In both rat and mouse models, estrogen-induced apoptosis was detected that was spatially and regionally localized to the epithelium of the distal tips. Using organ cultures of alpha ER knockout (alpha ERKO) and beta ERKO prostates, we failed to demonstrate that apoptosis induced by E-2 was mediated through either receptor subtype. Activation of ER-selective ligands (ER alpha, propyl pyrazole triol, ER beta, diaryl-proprionitrile, and 5 alpha-androstane- 3 beta, 17 beta-diol) in organ culture experiments failed to induce apoptosis, as did the membrane impermeable conjugate E-2:BSA, discounting the possibility of nongenomic effects. Consequently, E-2 regulation of androgen receptor (AR) expression was examined and, in the presence of nanomolar testosterone levels, E-2 caused a specific reduction in AR protein expression in wild-type, alpha ERKO, and beta ERKO mice, particularly in the distal region where apoptosis was detected. This down-regulation of AR protein provides a possible mechanism for the proapoptotic action of E-2 that is independent of ERs or nongenomic effects. C1 Monash Univ, Monash Inst Reprod & Dev, Clayton, Vic 3168, Australia. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Risbridger, GP (reprint author), Monash Univ, Monash Inst Med Res, 27-31 Wright St, Clayton, Vic 3168, Australia. EM gail.risbridger@med.monash.edu.au RI Taylor, Renea/A-5022-2009; Risbridger, Gail/B-8655-2008; OI Taylor, Renea/0000-0003-2609-2380; Risbridger, Gail/0000-0003-3089-4028; Korach, Kenneth/0000-0002-7765-418X NR 49 TC 22 Z9 22 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JAN PY 2006 VL 147 IS 1 BP 191 EP 200 DI 10.1210/en.2005-0683 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 994TG UT WOS:000234053500023 PM 16223864 ER PT J AU Schwartz, DA AF Schwartz, DA TI Environmental genomics: An opportunity for the NIEHS SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. NTP, Res Triangle Pk, NC USA. RP Schwartz, DA (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov NR 8 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2006 VL 114 IS 1 BP A14 EP A14 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 999NR UT WOS:000234396800002 PM 16393638 ER PT B AU Jeng, JJ Goldman, D Eriksson, CJP Kallarakal, AT Wang, TTY Weiner, H Song, BJ AF Jeng, JJ Goldman, D Eriksson, CJP Kallarakal, AT Wang, TTY Weiner, H Song, BJ BE Weiner, H Plapp, B Lindahl, R Maser, E TI Accumulation of hepatic acetaldehyde and reduced alcohol drinking in transgenic mice carrying the oriental variant of the human aldehyde dehydrogenase 2 gene SO Enzymology and Molecular Biology of Carbonyl Metabolism 12 SE ENZYMOLOGY AND MOLECULAR BIOLOGY OF CARBONYL METABOLISM - SERIES LA English DT Proceedings Paper CT 12th Meeting on Enzymology and Molecular Biology of Carbonyl Metabolism CY JUL 06-11, 2004 CL Burlington, VT DE aldehyde dehydrogenase; human mutation; transgenic mice; acetaldehyde; drinking behavior ID PREFERENCE; RAT; SENSITIVITY; DEFICIENCY; METABOLISM; GENOTYPES; MUTATION; JAPANESE; ETHANOL; CLONING AB Mitochondrial aldehyde dehydrogenase (ALDH2) is the major ALDH isozyme involved in acetaldehyde metabolism. It is well established that a single nucleotide substitution (G to A) leads to the amino acid change (Glu487Lys) and dominant inactivation of ALDH2 activity. Inactivation of ALDH2 activity causes the aversive reactions associated with "flushing" response observed in many East Asian people following alcohol intake. Although the ALDH2(2) allele (Lys487) has been shown to have a protective role against the development of alcoholism, the physiological and behavioral consequences of altered aldehyde metabolism remain unclear. The purpose of this study was to investigate the role of ALDH2 in acetaldehyde accumulation and alcohol drinking behavior in transgenic mice carrying the human ALDH2(2) allele (Lys487), which would form heterotetramers with mouse ALDH2, thus inactivating it. We produced transgenic mice carrying the human ALDH2(2) variant (hALDH22) using a pcDNA3 vector containing the full-length cDNA for the hALDH2(2) coding region and the mitochondrial leader sequence under the control of cytomegalovirus promoter. Expression of hALDH2(2) in liver and brain of transgenic mice was detected by RTPCR of mRNA, enzyme assays and immunoblot analyses using polyclonal antibodies directed against ALDH2. In transgenic mice, human ALDH2(2) protein was expressed at low levels in all tissues examined. Mouse ALDH2 enzyme activity was slightly inhibited in these animals. Although there was no significant difference in liver or brain pathology in mice treated with 20% ethanol (4 g/kg/day) for 2 weeks, hepatic acetaldehyde levels in transgenic mice were increased 50% at 2 h after ethanol injection (p < 0.03) relative to control mice while hepatic alcohol concentrations were unchanged. Female transgenic mice, but not males, drank less alcohol than did control mice (p < 0.03). The data indicates that transgenic mice carrying the hALDH2(2) might be able to be used as a model to study the role of ALDH in alcohol preference, acetaldehyde accumulation, and acetaldehyde-mediated tissue damage after long-term alcohol treatment. C1 NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Dept Mental Hlth & Alcohol Res, Helsinki, Finland. USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, Beltsville, MD 20705 USA. Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Rockville, MD 20852 USA. NR 27 TC 0 Z9 0 U1 1 U2 3 PU PURDUE UNIV PRESS PI W LAFAYETTE PA SOUTH CAMPUS COURTS D, W LAFAYETTE, IN 47907 USA BN 1-55753-384-9 J9 ENZYMOL MOL BIOL CAR PY 2006 VL 12 BP 42 EP 49 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDP63 UT WOS:000234795000006 ER PT J AU Infante-Rivard, C Weinberg, CR Guiguet, M AF Infante-Rivard, C Weinberg, CR Guiguet, M TI Xenobiotic-metabolizing genes and small-for-gestational-age births - Interaction with maternal smoking SO EPIDEMIOLOGY LA English DT Article ID CASE-PARENT TRIADS; INTRAUTERINE GROWTH RESTRICTION; GLUTATHIONE-S-TRANSFERASE; POLYMERASE-CHAIN-REACTION; OXIDATIVE STRESS; CYTOCHROME-P450 ENZYMES; LINKAGE DISEQUILIBRIUM; CIGARETTE-SMOKING; HUMAN-PLACENTA; TOBACCO-SMOKE AB Background: Little is known about the role of xenobiotic-metabolizing gene variants as risk factors for small-for-gestational-age (SGA) births or as modifiers for the effects of exposures such as maternal smoking. Methods: We conducted 2 joint studies: a case-control design including 493 cases (birth weight below the 10th percentile according to gestational age and sex) and 472 controls (at or above the 10th percentile) and a family-based study (mother, father, and newborn) with approximately 250 case trios and a similar number of control trios. Logistic regression and a log-linear model were used to analyze the association between genetic variants such as CYP1A1*2A, CYP1A1*2B, CYP1A1*4, GSTT1, GSTM1, and XRCC3 and SGA. The interaction between genetic variants and maternal smoking was also studied. Results: The odds ratio (OR) for the association of complete maternal GSTT1 deletion with SGA was 0.63 (95% confidence interval = 0.41-0.97), and that for the complete newborn GSTM1 deletion was 0.74 (0.55-0.98). Newborns with the partial GSTT1 deletion had an OR of 1.40 (1.01-1.95), and newborns homozygous for CYP1A1*2A had an OR of 4.28 (1.02-18.0). These results were coherent with the trio-based results. Significant interactions were observed between maternal smoking in the third trimester and CYP1A1*2A (P = 0.03), XRCC3 (P = 0.03), and newborn GSTT1 (P = 0.01). Conclusions: Certain genetic variants involved in the metabolism of xenobiotics increase the risk of SGA, as well as modify the effects of maternal smoking by increasing or decreasing its risk. C1 McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A3, Canada. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. INSERM, Paris, France. RP Infante-Rivard, C (reprint author), McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, 1110 Pine Ave W, Montreal, PQ H3A 1A3, Canada. EM claire.infante-rivard@mcgill.ca NR 49 TC 32 Z9 32 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JAN PY 2006 VL 17 IS 1 BP 38 EP 46 DI 10.1097/01.ede.0000187669.34003.b1 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 996SQ UT WOS:000234195400009 PM 16357593 ER PT J AU Heindel, JJ McAllister, KA Worth, L Tyson, FL AF Heindel, Jerrold J. McAllister, Kimberly A. Worth, Leroy, Jr. Tyson, Frederick L. TI Environmental Epigenomics, Imprinting and Disease Susceptibility SO EPIGENETICS LA English DT Article DE epigenomic targets; environmental exposures; fetal basis of disease; imprinting; susceptibility C1 [Tyson, Frederick L.] NIEHS, Populat Hlth & Susceptibil Branch, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA. RP Tyson, FL (reprint author), NIEHS, Populat Hlth & Susceptibil Branch, Div Extramural Res & Training, 79 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM tyson2@niehs.nih.gov NR 0 TC 9 Z9 9 U1 0 U2 9 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1559-2294 J9 EPIGENETICS-US JI Epigenetics PD JAN-MAR PY 2006 VL 1 IS 1 BP 1 EP 6 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V04MP UT WOS:000207062800002 PM 17998808 ER PT J AU Masur, D Shinnar, S Cnaan, A O'Dell, C Shabbout, M Levisohn, PM Hirtz, D Adamson, PC Glauser, TA AF Masur, David Shinnar, Shlomo Cnaan, Avital O'Dell, Christine Shabbout, Mayadah Levisohn, Paul M. Hirtz, Deborah Adamson, Peter C. Glauser, Tracy A. CA CAE Study Team TI Cognition and attention in childhood absence epilepsy (CAE)-baseline data from the NIHCAE trial SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Hosp, Denver, CO 80218 USA. Natl Inst Neurol Disorders & Stroke, Rockville, MD USA. Childrens Hosp, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 17 EP 18 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500048 ER PT J AU Liew, CJ Kaler, SG Greenfield, JC Duran, M Sato, S AF Liew, Clarissa J. Kaler, Stephen G. Greenfield, Jackie C. Duran, Michael Sato, Susumu TI Serial EEGs in prospectively diagnosed classical Menkes disease patients treated with very early copper histidine SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, EEG Sect, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 50 EP 51 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500141 ER PT J AU Rosenberger, LR Berl, MM Ritzl, EK Moore, EN Fieldstone, S Weber, DA Pearl, PL Conry, JA Weinstein, SL Sato, S Theodore, WH Gaillard, WD AF Rosenberger, Lisa R. Berl, Madison M. Ritzl, Eva K. Moore, Erin N. Fieldstone, Shaina Weber, Deborah A. Pearl, Philip L. Conry, Joan A. Weinstein, Steve L. Sato, Susumu Theodore, William H. Gaillard, William D. TI Atypical frontal language activation occurs in the right homologue of Broca's area SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NINDS, NIH, Clin Epilepsy Sect, Bethesda, MD USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 91 EP 91 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500255 ER PT J AU O'Dell, C Shinnar, S Cnaan, A Masur, D Shabbout, M Levisohn, PM Hirtz, D Adamson, PC Glauser, T AF O'Dell, Christine Shinnar, Shlomo Cnaan, Avital Masur, David Shabbout, Mayadah Levisohn, Paul M. Hirtz, Deborah Adamson, Peter C. Glauser, TracyA. CA CAE Study Team TI Behavior and quality of life in Childhood Absence Epilepsy (CAE) - Baseline data from the NIHCAE trial SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Montefiore Med Ctr, Albert Einstein Coll Med, Bronx, NY 10467 USA. Childrens Hosp Philadelphia, Div Biostat & Epidemiol, Philadelphia, PA 19104 USA. Childrens Hosp, Denver, CO 80218 USA. NINDS, Rockville, MD USA. Cincinnati Childrens Hosp, Cincinnati, OH USA. NR 0 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 126 EP 126 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500353 ER PT J AU Berg, AT Vickrey, BG Testa, FM Levy, SR Shinnar, S Smith, SN Beckerman, B DiMario, F AF Berg, Anne T. Vickrey, Barbara G. Testa, Francine M. Levy, Susan R. Shinnar, Shlomo Smith, Susan N. Beckerman, Barbara DiMario, Francis TI Seizure outcome in childhood epilepsy: It can be a bumby ride SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NIH, De Kalb, IL USA. Univ Calif Los Angeles, Los Angeles, CA USA. Yale Univ, New Haven, CT USA. Montefiore Med Ctr, Bronx, NY USA. CCMC, Hartford, CT 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 131 EP 131 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385500368 ER PT J AU Gasior, M Yankura, J French, A Yonekawa, W Hartman, A Rogawski, MA AF Gasior, Maciej Yankura, Jessica French, Amy Yonekawa, Wayne Hartman, Adam Rogawski, Michael A. TI Anticonvulsant effects of 1,3-butanediol, a metabolic precursor of ketone bodies SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 214 EP 215 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501083 ER PT J AU Motamedi, GK Rogawski, MA Vicini, S AF Motamedi, Gholam K. Rogawski, Michael A. Vicini, Stefano TI Rapid cooling terminates epileptiform discharges in hippocampal neurons through synaptic and non-synaptic mechanisms SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Georgetown Univ, Dept Neurol, Washington, DC USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. NINDS, NIH, Epilepsy Res Sect, Bethesda, MD USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 228 EP 228 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501123 ER PT J AU Potschka, H Winter, J Bauer, B Hartz, AMS Miller, DS AF Potschka, Heidrun Winter, Judith Bauer, Bjoern Hartz, Anika M. S. Miller, David S. TI Prevention of seizure-induced P-glycoprotein upregulation by cyclooxygenase inhibition SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Univ Vet Med Hannover, Dept Pharmacol Toxicol & Pharm, Hannover, Germany. NIEHS, NIH, Lab Pharmacol & Chem, Res Triangle Pk, NC 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 232 EP 232 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501134 ER PT J AU Shamim, SA Hasler, G Kelley, K Theodore, WH AF Shamim, Sadat A. Hasler, Gregor Kelley, Kathleen Theodore, William H. TI Effect of depression on hippocampal volumes in epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 283 EP 283 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501284 ER PT J AU Fritsch, B Gasior, M Kaminski, RM Rogawski, MA AF Fritsch, Brita Gasior, Maciej Kaminski, Rafal M. Rogawski, Michael A. TI Role of kainate receptor subunits in seizure induction as assessed with kainate receptor knockout mice SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 2 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 305 EP 305 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501345 ER PT J AU Kaminski, RM Sheikhi, H Rogawski, MA AF Kaminski, Rafal M. Sheikhi, Hamid Rogawski, Michael A. TI Inhibitors of 11-beta hydroxylase protect against 6 Hz seizures in mice: Are neurosteroids involved? SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 311 EP 311 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501364 ER PT J AU Schachter, SC White, HS Murphree, L Stables, J AF Schachter, Steven C. White, H. Steve Murphree, Lauren Stables, James TI Anticonvulsant activity of huperzine A, an alkaloid extract of Chinese club moss (Huperzia serrata), in the 6-Hz model of psychomotor seizures SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Univ Utah, Salt Lake City, UT USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. SRA Int, Fairfax, VA USA. NINDS, Anticonvulsant Screening Project, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 319 EP 320 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501387 ER PT J AU Sucher, N Schachter, SC Baek, NI Lee, B Park, J Jensen, F White, HS Murphree, L Stables, J AF Sucher, Nikolaus Schachter, Steven C. Baek, Nam-In Lee, Bombi Park, Jongbae Jensen, Frances White, H. Steve Murphree, Lauren Stables, James TI Preclinical evaluation of compounds isolated from an Asian herb used for epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Osher Inst, Boston, MA USA. Kyung Hee Univ, Grad Sch Biotechnol & Plant Metab Res Ctr, Seoul, South Korea. Univ Utah, Salt Lake City, UT USA. SRA Int, Fairfax, VA USA. NINDS, Anticonvulsant Screening Project, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 323 EP 323 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501395 ER PT J AU Snively, C Carney, PR Liu, Z Ringdahl, D Winger, K Jackson, C Singh, T Little, LE Borum, PR AF Snively, Christie Carney, Paul R. Liu, Zhao Ringdahl, Debbie Winger, Kelly Jackson, Crystal Singh, Thameshwarie Little, Lauren E. Borum, Peggy R. TI Developing an evidence-based ketogenic therapy program for treatment of epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 338 EP 338 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501439 ER PT J AU Yankura, JA French, A Rogawski, MA Hartman, A Gasior, M AF Yankura, Jessica A. French, Amy Rogawski, Michael A. Hartman, Adam Gasior, Maciej TI Assessment of the role of glucose deprivation in the ketogenic diet with 2-deoxyglucose SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NINDS, Epilepsy Res Sect, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Pediat Epilepsy Ctr, Baltimore, MD 21287 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 2 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 338 EP 339 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501440 ER PT J AU Ottman, R Kamberakis, K Wiggs, E Reeves-Tyer, P Baker, EH Butman, JA Shamin, S Theodore, WH AF Ottman, Ruth Kamberakis, Kay Wiggs, Edyth Reeves-Tyer, Pat Baker, Eva H. Butman, John A. Shamin, Sadat Theodore, William H. TI No structural brain abnormalities detected on high-resolution MRI in families with mutations in LGII SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; Ottman, Ruth/O-2371-2013 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 367 EP 367 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501525 ER PT J AU Theodore, WH Epstein, L Jacobson, S Bien, CG AF Theodore, William H. Epstein, Leon Jacobson, Steven Bien, C. G. TI Viruses in human epilepsyle SO EPILEPSIA LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Epilepsy-Society CY DEC 01-05, 2006 CL San Diego, CA SP Amer Epilepsy Soc C1 NIH, Bethesda, MD 20892 USA. Northwestern Univ, Chicago, IL 60611 USA. NINDS, NIH, Bethesda, MD 20892 USA. Univ Bonn, D-5300 Bonn, Germany. RI Bien, Christian/D-2633-2012 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 0013-9580 J9 EPILEPSIA JI Epilepsia PY 2006 VL 47 SU 4 BP 374 EP 374 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 096OA UT WOS:000241385501547 ER PT J AU Rogawski, MA AF Rogawski, MA TI Molecular targets versus models for new antiepileptic drug discovery SO EPILEPSY RESEARCH LA English DT Article; Proceedings Paper CT 8th Conference on Antiepileptic Drug Trials CY MAR 17-19, 2005 CL Key Biscayne, FL ID ANTICONVULSANT DRUG; ALPHA(2)-DELTA PROTEIN; UCB L059; LEVETIRACETAM; EPILEPSY; PROFILE; GABAPENTIN; CURRENTS; NEURONS; NEUROBIOLOGY AB Animal models have played a key role in the discovery and characterization of all marketed antiepileptic drugs (AED). The conventional wisdom is that the standard animal screening models are becoming obsolete because they fail to identify compounds that act in mechanistically new ways and as a result do not offer therapeutic advantages over presently available agents. In fact, far from only detecting me-too drugs, the models often uncover compounds with distinctive profiles of activity in various types of epilepsy and in addition have unexpected efficacy in non-epilepsy conditions, such as neuropathic pain, bipolar disorder, and migraine. Moreover, the animal models-because they are unbiased with respect to mechanism-provide an opportunity to uncover drugs that act in new ways and through new targets, such as alpha 28 and SV2A. In vitro testing is not likely to replace screening in animal models because in vitro systems cannot model the specific pharmacodynamic actions required for seizure protection, and do not assess bioavailability and brain accessibility. C1 NINDS, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 1C-1002,35 Convent Dr MSC 3702, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 FU NINDS NIH HHS [Z01 NS002732-19, Z01 NS002877-13] NR 22 TC 76 Z9 79 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2006 VL 68 IS 1 BP 22 EP 28 DI 10.1016/j.eplepsyres.2005.09.012 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 009SU UT WOS:000235133800004 PM 16377151 ER PT J AU Kelly, KM Nadon, NL Morrison, JH Thibault, O Barnes, CA Blalock, EM AF Kelly, KM Nadon, NL Morrison, JH Thibault, O Barnes, CA Blalock, EM TI The neurobiology of aging SO EPILEPSY RESEARCH LA English DT Article DE geriatric; epilepsy; elderly; again brain; PK; clinical trials ID HIPPOCAMPAL ZIPPER SLICES; LONG-TERM POTENTIATION; SUBUNIT MESSENGER-RNA; CA2+ CHANNEL ACTIVITY; ENVIRONMENTAL ENRICHMENT; ALZHEIMERS-DISEASE; SYNAPTIC TRANSMISSION; SINGLE NEURONS; RHESUS-MONKEYS; AGED RATS AB Basic principles of the neurobiology of aging were reviewed within selected topic areas chosen for their potential relevance to epileptogenesis in the aging brain. The availability of National Institute on Aging-supported aged mouse and rat strains and other biological resources for studies of aging and age-associated diseases was presented, and general principles of animal use in gerontological research were discussed. Neurobiological changes during normal brain aging were compared and contrasted with neuropathological events of Alzheimer's disease (AD) and age-associated memory impairment (AAMI). Major themes addressed were the loss of synaptic connections as vulnerable neurons die and circuits deteriorate in AD, the absence of significant neuron loss but potential synaptic alteration in the same circuits in AAMI, and the effects of decreased estrogen on normal aging. The 11 calcium hypothesis of brain aging" was examined by a review of calcium dyshomeostasis and synaptic communication in aged hippocampus, with particular emphasis on the role of L-type voltage-gated calcium channels during normal aging. Established and potential mechanisms of hippocampal plasticity during aging were discussed, including long-term potentiation, changes in functional connectivity, and increased gap junctions, the latter possibly being related to enhanced network excitability. Lastly, application of microarray gene chip technology to aging brain studies was presented and use of the hippocampal "zipper slice" preparation to study aged neurons was described. (c) 2005 Elsevier B.V. All rights reserved. C1 Drexel Univ, Dept Neurol, Coll Med, Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NIA, Off Biol Resources, Bethesda, MD 20892 USA. Mt Sinai Med Ctr, Neurobiol & Aging Labs, New York, NY 10029 USA. Univ Kentucky, Med Ctr, Dept Mol & Biomed Pharmacol, Lexington, KY USA. Univ Arizona, Div Neural Syst Memory & Aging, Tucson, AZ USA. RP Kelly, KM (reprint author), Drexel Univ, Dept Neurol, Coll Med, Allegheny Gen Hosp, 940 S Tower,320 E N Ave, Pittsburgh, PA 15212 USA. EM kelly@wpahs.org RI Morrison, John/F-9229-2012 NR 48 TC 55 Z9 58 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2006 VL 68 SU 1 BP S5 EP S20 DI 10.1016/j.eplepsyres.2005.07.015 PG 16 WC Clinical Neurology SC Neurosciences & Neurology GA 021LF UT WOS:000235984000002 PM 16386406 ER PT J AU Leppik, IE Brodie, MJ Saetre, ER Rowan, AJ Ramsay, RE Jacobs, MP AF Leppik, IE Brodie, MJ Saetre, ER Rowan, AJ Ramsay, RE Jacobs, MP TI Outcomes research: Clinical trials in the elderly SO EPILEPSY RESEARCH LA English DT Article DE epilepsy; elderly; clinical trials; antiepileptic drugs ID EPILEPSY; CARBAMAZEPINE; LAMOTRIGINE AB Very few clinical trials have been done in the elderly. This report reviews results of two completed studies and describes one in progress. The largest published study was a United States Veterans Affairs Administration study in newly diagnosed patients with epilepsy. It compared carbamazepine to gabapentin and lamotrigine, and found that, although equivalent in efficacy, the newer antiepileptic drugs (AEDs) were better tolerated. This study also highlighted many of the difficulties in recruiting and retaining elderly patients in studies, the large number of comorbidifies, and the problems of distinguishing seizures in the elderly from other symptoms. Another study of new-onset epilepsy suggested that a large percentage of elderly patients respond to initial AED therapy, but side effect profiles differ. More studies are needed to better define the risk/benefit relationships in elderly patients. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. Univ Glasgow, Glasgow, Lanark, Scotland. Univ Oslo, Rikshosp, N-0027 Oslo, Norway. Mt Sinai Hosp, New York, NY 10029 USA. Univ Miami, Miami, FL 33152 USA. NIH, Bethesda, MD 20892 USA. RP Leppik, IE (reprint author), Univ Minnesota, Coll Pharm, 308 Harvard St SE, Minneapolis, MN 55455 USA. EM leppi001@umn.edu RI Ramsay, R. Eugene/D-4491-2011 NR 7 TC 22 Z9 22 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD JAN PY 2006 VL 68 SU 1 BP S71 EP S76 DI 10.1016/j.eplepsyres.2005.07.019 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 021LF UT WOS:000235984000007 PM 16413171 ER PT S AU Rossouw, JE AF Rossouw, Jacques E. BE Bradlow, HL Carruba, G TI Implications of recent clinical trials of postmenopausal hormone therapy for management of cardiovascular disease SO ESTROGENS AND HUMAN DISEASES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Estrogens and Human Diseases CY MAY 15-21, 2006 CL Erice, ITALY SP Ettore Majorana Fdn, Ctr Sci Culture DE estrogen; progestin; postmenopausal hormone therapy; cardiovascular disease; women ID CORONARY-HEART-DISEASE; ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; CONJUGATED EQUINE ESTROGENS; QUALITY-OF-LIFE; REPLACEMENT THERAPY; ARTERY ATHEROSCLEROSIS; ENDOMETRIAL CARCINOMA; SECONDARY PREVENTION; WOMEN AB Estrogen therapy, originally used for the treatment of menopausal vasomotor symptoms, had by 1990 become a mainstay for the prevention of coronary heart disease (CHD) in postmenopausal women. The recommendations for use of estrogen in CHD were based on epidemiologic, animal, and laboratory data. However, a series of clinical trials published from 1998 onward have failed uniformly to confirm a CHD benefit. When the disappointing results of the secondary prevention trials were announced, there was widespread anticipation of more promising results from the primary prevention trials of the Women's Health Initiative (WHI). The WHI trials in generally healthy women also did not provide evidence of benefit, and the use of HT for disease prevention is now discouraged. In response, some commentators have incorrectly stated that the WHI was not a true primary prevention trial. A more appropriate way to frame the question is whether the effects of HT on cardiovascular disease (CVD) differ by age or years since menopause. Some preliminary data suggest that more recently menopausal women starting HT could be at lower risk of CHD (but not stroke) than women more distant from the menopause. However, even if ongoing studies provide evidence that HT can slow the initiation of early atherosclerosis in younger women, this is unlikely to translate into a reconsideration of the use of HT for the prevention of disease, because the long-term effects on cardiovascular events are unknown and unknowable, HT has other adverse effects, and there are more effective and safer ways of preventing cardiovascular disease. C1 NHLBI, Womens Hlth Initiat, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, Rockledge 2,Room 8106,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM rossouwj@nih.gov NR 40 TC 13 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-669-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2006 VL 1089 BP 444 EP 453 DI 10.1196/annals.1386.046 PG 10 WC Oncology; Endocrinology & Metabolism; Multidisciplinary Sciences SC Oncology; Endocrinology & Metabolism; Science & Technology - Other Topics GA BFU92 UT WOS:000244736800036 PM 17261787 ER PT J AU Mielke, S Sparreboom, A Mross, K AF Mielke, S Sparreboom, A Mross, K TI Peripheral neuropathy: A persisting challenge in paclitaxel-based regimes SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE peripheral neuropathy; paclitaxel; cremophor EL; pharmacodynamics ID METASTATIC BREAST-CANCER; TAXOL-INDUCED NEUROPATHY; HIGH-DOSE PACLITAXEL; CELL LUNG-CANCER; RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; CREMOPHOR-EL; NONLINEAR PHARMACOKINETICS; NANOPARTICLE FORMULATION; COMBINATION CHEMOTHERAPY AB Cumulative peripheral neuropathy (PNP) still remains a limitation to optimal treatment with paclitaxel (PAC), especially in more dose-dense schedules. This primary sensory PNP may affect the majority of patients after administration of certain cumulative dosages of PAC, while the exact mechanisms of PAC-induced PNP are not known. While a number of preclinical models revealed its vehicle Cremophor EL (CrEL) to be mainly responsible for ganglionopathy, axonopathy and demyelination, clinical data also supports a strong and independent effect of PAC itself, which is most likely based on disturbances in the microtubules in perikaryons, axons and glia cells. Indeed, clinical trials of CrEL-free formulations of PAC still report grade III neurotoxicity as dose-limiting. As treatment options of PAC-induced PNP are rare the use of specific scoring systems for screening purposes is strongly encouraged. In this report we review and discuss the pathogenesis, incidence, risk factors, diagnosis, pharmacodynamics and treatment options for PAC-induced PNP. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Freiburg, Med Ctr, Dept Hematol & Oncol, Freiburg, Germany. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. ERasmus MC, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Univ Freiburg, Tumor Biol Ctr Freiburg, Freiburg, Germany. RP Mielke, S (reprint author), NHLBI, DIR, Hematol Branch, Stem Cell Allogen Transplant Sect,NIH, Bldg 10,CRC Room 3-5288,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhlbi.nih.gov RI Sparreboom, Alex/B-3247-2008 NR 81 TC 95 Z9 98 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2006 VL 42 IS 1 BP 24 EP 30 DI 10.1016/j.ejca.2005.06.030 PG 7 WC Oncology SC Oncology GA 006VU UT WOS:000234926600019 PM 16293411 ER PT J AU Hou, LF Ji, BT Blair, A Dai, Q Gao, YT Potter, JD Chow, WH AF Hou, LF Ji, BT Blair, A Dai, Q Gao, YT Potter, JD Chow, WH TI Body mass index and colon cancer risk in Chinese people: Menopause as an effect modifier SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE BMI; menopause; colon cancer risk ID LARGE-BOWEL-CANCER; COLORECTAL-CANCER; PHYSICAL-ACTIVITY; UNITED-STATES; FAT DISTRIBUTION; WOMEN; OBESITY; SIZE; OVERWEIGHT; ASSOCIATIONS AB High body mass index (BMI) has consistently been associated with increased colon cancer risk in men, but not in women. it is hypothesised that menopause-related changes in oestrogen levels play a role in gender-specific risk patterns. Most studies have been conducted in Western countries, where high incidence rates are coupled with a high prevalence of obesity and relatively common use of hormone replacement therapy (HRT) in post-menopausal women. This study evaluated the correlation between body mass index (BMI) and colon cancer risk in a relatively lean population, comprising 931 cases and 1552 controls, in Shanghai, China, where HRT use was extremely rare among women, during 1990-1993. Among men, colon cancer risk significantly increased with increasing BMI (P-trend = 0.005). Among women, the risk varied with age and menopause status in a similar pattern. Within each menopause stratum, however, the BMI-related risk was similar for those aged under 55 years and those aged 55 years and over, indicating a menopause rather than age effect. Among pre-menopausal women, the odds ratios (ORs) for subjects in the highest versus lowest quintile were 1.9 (95% CI 1.1-4.9) for those under 55 years of age, and 2.2 (95% CI 1.4-8.2) for those aged 55 years and over. Among post-menopausal women, the corresponding ORs were 0.6 (95% CI 0.5-0.91) and 0.7 (95% CI 0.5-0.9S), respectively. Our findings suggest that BMI predicts colon cancer risk in both genders. Among women, however, the risk is modified by menopause status, possibly through altered endogenous oestrogen levels. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Dept Human & Hlth Serv, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Med, Div Gen Med, Hlth Serv Res Ctr, Nashville, TN USA. Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Hou, LF (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Human & Hlth Serv, 6120 Execut Blvd,EPS Suite 511,MSC 7240, Bethesda, MD 20892 USA. EM lifangh2@mail.nih.gov OI Potter, John/0000-0001-5439-1500 FU NCI NIH HHS [Z01 CP010120-10] NR 48 TC 32 Z9 35 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JAN PY 2006 VL 42 IS 1 BP 84 EP 90 DI 10.1016/j.ejca.2005.09.014 PG 7 WC Oncology SC Oncology GA 006VU UT WOS:000234926600027 PM 16321519 ER PT J AU Bassen, CR Lamb, ME AF Bassen, Cecile R. Lamb, Michael E. TI Gender differences in adolescents' self-concepts of assertion and affiliation SO EUROPEAN JOURNAL OF DEVELOPMENTAL PSYCHOLOGY LA English DT Article AB In order to assess gender differences and developmental changes in self-perceptions of affiliation, negative affiliation, and assertiveness in adolescence, 55 American 7th graders (13-year-olds) and 35 American 10th graders (16-year-olds) were interviewed annually for four and three years, respectively. Rating themselves in 11 different roles, girls perceived themselves as more affiliative and less negatively affiliative in many roles than boys did, but gender differences in assertion were not reliable and girls' assertiveness did not decline over time. These results contrast with popular claims regarding girls' ''loss of voice'' in adolescence. Gender differences were context-specific, and were most pronounced in ratings of ''myself as a boy/girl'' and ''myself with a close same-sex peer.'' C1 [Lamb, Michael E.] Univ Cambridge, Dept Social & Dev Psychol, Fac Social & Polit Sci, Cambridge CB2 3RQ, England. [Bassen, Cecile R.] NICHHD, Bethesda, MD 20892 USA. RP Lamb, ME (reprint author), Univ Cambridge, Dept Social & Dev Psychol, Fac Social & Polit Sci, Free Sch Lane, Cambridge CB2 3RQ, England. EM mel37@cam.ac.uk NR 87 TC 2 Z9 4 U1 2 U2 4 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 1740-5629 J9 EUR J DEV PSYCHOL JI Eur. J. Dev. Psychol. PY 2006 VL 3 IS 1 BP 71 EP 94 DI 10.1080/17405620500368212 PG 24 WC Psychology, Developmental SC Psychology GA V86XP UT WOS:000205874900005 ER PT J AU Schaap, LA Visser, M Pluijm, MF Deeg, DJH Penninx, BWJH Nicklas, BJ Newman, AB Harris, TB Cauley, JA Goodpaster, BH Tylavsky, FA Yaffe, K Kritchevsky, SB AF Schaap, L. A. Visser, M. Pluijm, M. F. Deeg, D. J. H. Penninx, B. W. J. H. Nicklas, B. J. Newman, A. B. Harris, T. B. Cauley, J. A. Goodpaster, B. H. Tylavsky, F. A. Yaffe, K. Kritchevsky, S. B. TI Low total and free testosterone levels and decline in physical performance and muscle strength in older men and women SO EUROPEAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 VU Univ, Med Ctr, Amsterdam, Netherlands. Erasmus MC, Rotterdam, Netherlands. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Knoxville, TN 37996 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Newman, Anne/C-6408-2013; Cauley, Jane/N-4836-2015 OI Newman, Anne/0000-0002-0106-1150; Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0393-2990 J9 EUR J EPIDEMIOL JI Eur. J. Epidemiol. PY 2006 VL 21 SU S BP 31 EP 31 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 066QP UT WOS:000239245500042 ER PT J AU Venturini, S Allicotti, G Zhao, YD Simon, R Burton, DR Pinilla, C Poignard, P AF Venturini, S Allicotti, G Zhao, YD Simon, R Burton, DR Pinilla, C Poignard, P TI Identification of peptides from human pathogens able to cross-activate an HIV-1-gag-specific CD4(+) T cell clone SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE cross-reactivity; epitope specificity; HIV; T cells; combinatorial libraries ID BURKHOLDERIA-CEPACIA COMPLEX; HETEROLOGOUS ANTIVIRAL IMMUNITY; CYSTIC-FIBROSIS PATIENTS; COMBINATORIAL LIBRARIES; RALSTONIA-PICKETTII; ANTIGEN RECOGNITION; GAG P24; HIV; RESPONSES; MEMORY AB Antigen recognition by T cells is degenerate both at the MHC and the TCR level. In this study, we analyzed the cross-reactivity of a human HIV-1 gag p24-specific CD4(+) T cell clone obtained from an HIV-1-seronegative donor using a positional scanning synthetic combinatorial peptide library (PS-SCL)-based biometrical analysis. A number of decapeptides able to activate the HIV-1 gag-specific clone were identified and shown to correspond to sequences found in other human pathogens. Two of these peptides activated the T cell clone with the same stimulatory potency as the original HIV-1 gag p24 peptide. These findings show that an HIV-1-specific human T helper clone can react efficiently with peptides from other pathogens and suggest that cellular immune responses identified as being specific for one human pathogen (HIV-1) could arise from exposure to other pathogens. C1 Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Torrey Pines Inst Mol Studies, San Diego, CA USA. NCI, Bethesda, MD 20892 USA. RP Poignard, P (reprint author), Scripps Res Inst, Dept Immunol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM cpinilla@tpims.org; poignard@scripps.edu RI poignard, pascal/N-6678-2013 FU NHLBI NIH HHS [HL59727]; NIAID NIH HHS [AI45357, AI45376] NR 41 TC 4 Z9 4 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2006 VL 36 IS 1 BP 27 EP 36 DI 10.1002/eji.200425767 PG 10 WC Immunology SC Immunology GA 002NF UT WOS:000234617500004 PM 16323241 ER PT J AU Kovacik, V Bekesova, S Patoprsty, V Rehulka, P Chmelik, J Kovac, P AF Kovacik, Vladimir Bekesova, Slavka Patoprsty, Vladimir Rehulka, Pavel Chmelik, Josef Kovac, Pavol TI Positive-ion fragmentation in matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry of synthetic analogs of the O-specific polysaccharide of Vibrio cholerae O : 1. SO EUROPEAN JOURNAL OF MASS SPECTROMETRY LA English DT Article DE matrix assisted laser desorption/ionization time of flight/time of flight; MALDI ToF/ToF positive tandem mass spectra; oligosaccharides from lipopolysaccharide of Vibrio cholerae O : 1 ID METHYL ALPHA-GLYCOSIDES; SEROTYPE-OGAWA; ANTIGEN; INABA; LIPOPOLYSACCHARIDE; VIBRIO-CHOLERAE-O-1; TRISACCHARIDE; ELECTROSPRAY; DISACCHARIDE; MIMICKING AB Saccharides (mono- to hexamers) that mimic the terminal epitopes of O-antigens of Vibrio cholerae O:1, serotypes Ogawa and Inaba have been studied by matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI ToF/ToF) mass spectrometry (MS). Cationized adducts are the characteristic ions formed through the capture of sodium or potassium cations under MALDI MS conditions. Three characteristic pathways dominate in the fragmentation of model substances under MALDI ToF/ToF collision-induced dissociation MS/MS conditions of measurement. The first is the elimination which shortens the length of the oligosaccharide. In this way, conversion of the Ogawa to Inaba fragments takes place under the conditions of measurement. In the second, the conjugated transfer of electrons in the upstream unit of oligosaccharides takes place. The third route brings about the elimination of one alpha-hydroxy-gamma-butyrolactone molecule from the 4-(3-deoxy-L-glycero-tetronamido) group. The MALDI ToF/ToF MS/MS provided sufficient information about molecular mass, the number of saccharide residues, the structure of saccharides, the C(4)- amide of 3-deoxy-L-glycero-tetronic acid (DGT) of the compounds investigated and allows Ogawa and Inaba serotypes to be distinguished. C1 Slovak Acad Sci, Inst Chem, Bratislava 84538, Slovakia. Acad Sci Czech Republ, Inst Analyt Chem, CS-61142 Brno, Czech Republic. NIDDK, NIH, Bethesda, MD 20892 USA. RP Kovacik, V (reprint author), Slovak Acad Sci, Inst Chem, Dubravska Cesta 9, Bratislava 84538, Slovakia. EM chemvkov@savba.sk NR 17 TC 4 Z9 5 U1 0 U2 1 PU IM PUBLICATIONS PI W SUSSEX PA 6 CHARLTON MILL, CHARLTON, CHICHESTER,, W SUSSEX PO18 0HY, ENGLAND SN 1469-0667 J9 EUR J MASS SPECTROM JI Eur. J. Mass Spectrom. PY 2006 VL 12 IS 4 BP 247 EP 252 DI 10.1255/ejms.807 PG 6 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 102DE UT WOS:000241790300004 PM 17057281 ER PT J AU Chefer, VI Shippenberg, TS AF Chefer, VI Shippenberg, TS TI Paradoxical effects of prodynorphin gene deletion on basal and cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE accumbens; dopamine; dynorphin; kappa opioid receptor; mouse ID KAPPA-OPIOID RECEPTOR; MESSENGER-RNA EXPRESSION; KNOCKOUT MICE; EXTRACELLULAR DOPAMINE; UP-REGULATION; QUANTITATIVE MICRODIALYSIS; INVIVO MICRODIALYSIS; TRANSIENT CONDITIONS; SINGLE INJECTION; RAT STRIATUM AB Quantitative and conventional microdialysis were used to investigate the effects of constitutive deletion of the prodynorphin gene on basal dopamine (DA) dynamics in the nucleus accumbens (NAc) and the responsiveness of DA neurons to an acute cocaine challenge. Saline- and cocaine-evoked locomotor activity were also assessed. Quantitative microdialysis revealed that basal extracellular DA levels were decreased, while the DA extraction fraction, an indirect measure of DA uptake, was unchanged in dynorphin (DYN) knockout (KO) mice. The ability of cocaine to increase NAc DA levels was reduced in KO. Similarly, cocaine-evoked locomotor activity was decreased in KO. The selective kappa opioid receptor agonist U-69593 decreased NAc dialysate DA levels in wildtype mice and this effect was enhanced in KO. Administration of the selective kappa opioid receptor (KOPr) antagonist nor-binaltorphimine to KO mice attenuated the decrease in cocaine-induced DA levels. However, it was ineffective in altering the decreased locomotor response to cocaine. These studies demonstrate that constitutive deletion of prodynorphin is associated with a reduction of extracellular NAc DA levels and a decreased responsiveness to acute cocaine. Data regarding the effects of U-69593 and nor-binaltorphimine in KO suggest that the kappa opioid receptor is up-regulated as a consequence of prodynorphin gene deletion and that this adaptation underlies the decrease in basal DA dynamics and cocaine-evoked DA levels observed in DYN KO mice. These findings suggest that the phenotype of DYN KO mice is not solely due to loss of endogenous opioid peptide but also reflects developmental compensations that occur at the level of the opioid receptor. C1 NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, DHHS,NIH,IRP,BNRB,INS, Baltimore, MD 21224 USA. RP Chefer, VI (reprint author), NIDA, Integrat Neurosci Sect, Behav Neurosci Branch, DHHS,NIH,IRP,BNRB,INS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vchefer@intra.nida.nih.gov FU Intramural NIH HHS NR 48 TC 23 Z9 24 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JAN PY 2006 VL 23 IS 1 BP 229 EP 238 DI 10.1111/j.1460-9568.2005.04525.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 008PG UT WOS:000235052400023 PM 16420432 ER PT J AU McCrae, RR Terracciano, A Costa, PT Ozer, DJ AF McCrae, RR Terracciano, A Costa, PT Ozer, DJ TI Person-factors in the California adult Q-set: Closing the door on personality trait types? SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article ID 5-FACTOR MODEL; REPLICABILITY; RESILIENT; CHILDHOOD; PATTERNS; PROTOTYPES; INVENTORY; VALIDITY; BEHAVIOR; ROTATION AB To investigate recent hypotheses of replicable personality types, we examined data from 1540 self sorts on the California Adult Q-Set (CAQ). Conventional factor analysis of the items showed the expected Five-Factor Model (FFM). Inverse factor analysis across random subsamples showed that none of the previously reported person-factors were replicated. Only two factors were replicable, and, most importantly, these factors were contaminated by mean level differences in item endorsement. Results were not due to sample size or age heterogeneity Subsequent inverse factor analysis of standardized items revealed at least three replicable factors; when five person-factors were extracted, they could be aligned precisely with the dimensions of the FFM. The major factors of person similarity can be accounted for entirely in terms of the FFM, consistent with the hypothesis that there are no replicable personality types in the CAQ. Published in 2006 by John Wiley & Sons, Ltd. C1 Natl Inst Aging, DHHS, NIH, Baltimore, MD USA. Univ Calif Riverside, Riverside, CA 92521 USA. RP McCrae, RR (reprint author), Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; OI Costa, Paul/0000-0003-4375-1712 NR 39 TC 21 Z9 21 U1 12 U2 15 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD JAN PY 2006 VL 20 IS 1 BP 29 EP 44 DI 10.1002/per.553 PG 16 WC Psychology, Social SC Psychology GA 021DM UT WOS:000235963800003 ER PT J AU McCrae, RR Terracciano, A Costa, PT Ozer, DJ AF McCrae, RR Terracciano, A Costa, PT Ozer, DJ TI From types to typological thinking: A reply to Asendorpf SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Editorial Material AB We continue to disagree with Asendorpf (2006) on the best way to analyse Q-sort data and on our priorities for personality research. We believe on statistical grounds that the large first factor found in inverse factor analyses of raw CAQ items tells its much about response norms, but little or nothing about individual differences. These emerge more clearly in analyses of standardised items, which show the familiar dimensions of the Five-Factor Model. Based on our research on types and the mixed results reported by other researchers, we do not believe that replicable empirical types are likely to be found, and suggest that a more profitable line of research would focus on the heuristics of types and the configural interpretation of traits. Published in 2006 by John Wiley & Sons, Ltd. C1 Natl Inst Aging, DHHS, NIH, Baltimore, MD USA. Univ Calif Riverside, Riverside, CA 92521 USA. RP McCrae, RR (reprint author), Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 03, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; OI Costa, Paul/0000-0003-4375-1712 NR 6 TC 2 Z9 2 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD JAN PY 2006 VL 20 IS 1 BP 49 EP 51 DI 10.1002/per.571 PG 3 WC Psychology, Social SC Psychology GA 021DM UT WOS:000235963800005 ER PT J AU Blanco, I de Serres, FJ Fernandez-Bustillo, E Lara, B Miravitlles, M AF Blanco, I de Serres, FJ Fernandez-Bustillo, E Lara, B Miravitlles, M TI Estimated numbers and prevalence of PI*S and PI*Z alleles of alpha-antitrypsin deficiency in European countries SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE alpha(1)-antitrypsin deficiency; alpha(1)-protease inhibitor; Europe; genetic epidemiology; protease inhibitor phenotypes ID OBSTRUCTIVE PULMONARY-DISEASE; ALPHA-1-ANTITRYPSIN PI; ALPHA(1)-ANTITRYPSIN DEFICIENCY; GENETIC-VARIANTS; SERUM ALPHA1-ANTITRYPSIN; RARE VARIANTS; PHENOTYPES; POPULATION; SUBTYPES; POLYMORPHISM AB The current study focuses on developing estimates of the numbers of individuals carrying the two most common deficiency alleles, PI*S and PI*Z, for alpha(1)-antitrypsin deficiency D) in Europe. Criteria for selection of epidemiological studies were: 1) AT phencityping performed by isoelectrofocusing or antigen-anti body crossed electrophoresis; 2) rejection of "screening studies"; 12) statistical precision factor score of >= 5 for Southwest, Western and Northern Europe, >= 4 for Central Europe, >= 3 for Eastern Europe; and 4) samples representative of the general population. A total of 75,390 individuals were selected from 21 European countries (one each from Austria, Belgium, Latvia, Hungary, Serbia-Montenegro, Sweden and Switzerland; two each from Denmark, Estonia and Lithuania; three each from Portugal and the UK; four each from Finland, the Netherlands, Norway and Spain; five each from Russia and Germany; six from Poland; eight from Italy; and nine from France). The total AT-D populations of a particular phenotype in the countries selected were: 124,594 ZZ; 560,515 SZ; 16,323,226 MZ; 630,401 SS; and 36,716,819 MS. The largest number of ZZ (5,000-15,000) were in Italy, Spain, Germany, France, the UK, Latvia, Sweden and Denmark, followed by Belgium, Portugal, Serbia-Montenegro, Russia, The Netherlands, Norway and Austria (1,000-2,000), with <1,000 in each of the remaining countries. A remarkable lack in number of reliable epidemiological studies and marked differences among these European countries and regions within a given country was also found. C1 Hosp Valle Nalon, Dept Internal Med, Resp Dis Branch, Div Internal Med, Langero 33920, Principado Astu, Spain. Hosp Univ Cent Asturias, Biostat Unit, Oviedo, Principado Astu, Spain. Hosp Clin Barcelona, Serv Pneumol, Inst Clin Torax,IDIBAPS, Barcelona, Catalonia, Spain. NIEHS, Mol Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Blanco, I (reprint author), Hosp Valle Nalon, Dept Internal Med, Resp Dis Branch, Div Internal Med, Langero 33920, Principado Astu, Spain. EM ignacio.blanco@sespa.princast.es NR 70 TC 90 Z9 92 U1 0 U2 1 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD JAN PY 2006 VL 27 IS 1 BP 77 EP 84 DI 10.1183/09031936.06.00062305 PG 8 WC Respiratory System SC Respiratory System GA 002TT UT WOS:000234635100014 PM 16387939 ER PT J AU Birbaumer, N Weber, C Neuper, C Buch, E Haagen, K Cohen, L AF Birbaumer, Niels Weber, Cornelia Neuper, Christa Buch, Ethan Haagen, Klaus Cohen, Leonardo TI Physiological regulation of thinking: brain-computer interface (BCI) research SO EVENT-RELATED DYNAMICS OF BRAIN OSCILLATIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Review DE sensorimotor rhythm (SMR); brain machine interface (BMI); EEG; paralysis; locked-in syndrome ID SLOW CORTICAL POTENTIALS; RESONANCE-IMAGING FMRI; FOREBRAIN INHIBITORY MECHANISMS; AMYOTROPHIC-LATERAL-SCLEROSIS; THOUGHT-TRANSLATION DEVICE; REAL-TIME FMRI; SELF-REGULATION; MOTOR FUNCTION; MOVEMENT SIGNAL; COMMUNICATION AB The discovery of event-related desynchronization (ERD) and event-related synchronization (ERS) by Pfurtscheller paved the way for the development of brain computer interfaces (BCIs). BCIs allow control of computers or external devices with the regulation of brain activity only. Two different research traditions produced two different types of BCIs: invasive BCIs, realized with implanted electrodes in brain tissue and noninvasive BCIs using electrophysiological recordings in humans such as electroencephalography (EEG) and magnetoencephalography (MEG) and metabolic changes such as functional magnetic resonance imaging (fMRI) and near infrared spectroscopy (NIRS). Clinical applications were reserved with few exceptions for the noninvasive approach: communication with the completely paralyzed and locked-in syndrome with slow cortical potentials (SCPs), sensorimotor rhythms (SMRs), and P300 and restoration of movement and cortical reorganization in high spinal cord lesions and chronic stroke. It was demonstrated that noninvasive EEG-based BCIs allow brain-derived Communication in paralyzed and locked-in patients. Movement restoration was achieved with noninvasive BCIs based on SMRs control in single cases with spinal cord lesions and chronic stroke. At present no firm conclusion about the clinical utility of BCI for the control of voluntary movement can be made. Invasive multielectrode BCIs in otherwise healthy animals allowed execution of reaching, grasping, and force variations from spike patterns and extracellular field potentials. Whether invasive approaches allow superior brain control of motor responses compared to noninvasive BCI with intelligent peripheral devices and electrical muscle stimulation and EMG feedback remains to be demonstrated. The newly developed fMRI-BCIs and NIRS-BCIs offer promise for the learned regulation of emotional disorders and also disorders of small children (in the case of NIRS). C1 Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Graz Univ, Inst Psychol, Graz, Austria. Univ Trent, Dept Econ, Trento, Italy. RP Birbaumer, N (reprint author), Univ Tubingen, Inst Med Psychol & Behav Neurobiol, Tubingen, Germany. EM niels.birbaumer@uni-tuebingen.de RI Buch, Ethan/G-1981-2011 NR 119 TC 40 Z9 41 U1 4 U2 30 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 J9 PROG BRAIN RES PY 2006 VL 159 BP 369 EP 391 DI 10.1016/S0079-6123(06)59024-7 PG 23 WC Neurosciences SC Neurosciences & Neurology GA BGH64 UT WOS:000247003900024 PM 17071243 ER PT J AU Marino-Ramirez, L Bodenreider, O Kantz, N Jordan, IK AF Marino-Ramirez, Leonardo Bodenreider, Olivier Kantz, Natalie Jordan, I. King TI Co-evolutionary Rates of Functionally Related Yeast Genes SO EVOLUTIONARY BIOINFORMATICS LA English DT Article DE Functional inference; Co-evolution; natural selection; genome evolution; gene ontology AB Evolutionary knowledge is often used to facilitate computational attempts at gene function prediction. One rich source of evolutionary information is the relative rates of gene sequence divergence, and in this report we explore the connection between gene evolutionary rates and function. We performed a genome-scale evaluation of the relationship between evolutionary rates and functional annotations for the yeast Saccharomyces cerevisiae. Non-synonymous (dN) and synonymous (dS) substitution rates were calculated for 1,095 orthologous gene sets common to S. cerevisiae and six other closely related yeast species. Differences in evolutionary rates between pairs of genes (Delta dN & Delta dS) were then compared to their functional similarities (sGO), which were measured using Gene Ontology (GO) annotations. Substantial and statistically significant correlations were found between. dN and sGO, whereas there is no apparent relationship between. dS and sGO. These results are consistent with a mode of action for natural selection that is based on similar rates of elimination of deleterious protein coding sequence variants for functionally related genes. The connection between gene evolutionary rates and function was stronger than seen for phylogenetic profiles, which have previously been employed to inform functional inference. The co-evolution of functionally related yeast genes points to the relevance of specific function for the efficacy of natural selection and underscores the utility of gene evolutionary rates for functional predictions. C1 [Jordan, I. King] Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. [Marino-Ramirez, Leonardo; Kantz, Natalie] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. [Bodenreider, Olivier] Natl Inst Hlth, Natl Lib Med, Bethesda, MD 20894 USA. RP Jordan, IK (reprint author), Georgia Inst Technol, Sch Biol, 310 Ferst Dr, Atlanta, GA 30332 USA. EM king.jordan@biology.gatech.edu RI Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 FU Intramural Research Program of the NIH; NLM; NCBI; School of Biology at the Georgia Institute of Technology FX The authors would like to thank David Landsman for important suggestions and helpful discussions. This study utilized the high-performance computational capabilities of the Biowulf PC/Linux cluster at the National Institutes of Health, Bethesda, MD (http://biowulf.nih.gov). This research was supported by the Intramural Research Program of the NIH, NLM, NCBI and the School of Biology at the Georgia Institute of Technology. NR 21 TC 3 Z9 3 U1 0 U2 0 PU BIOINFORMATICS INST PI AUCKLAND PA UNIV AUCKLAND, PRIVATE BAG, AUCKLAND, 00000, NEW ZEALAND SN 1176-9343 J9 EVOL BIOINFORM JI Evol. Bioinform. PY 2006 VL 2 BP 271 EP 276 PG 6 WC Evolutionary Biology; Mathematical & Computational Biology SC Evolutionary Biology; Mathematical & Computational Biology GA V84VI UT WOS:000205733800024 PM 18345352 ER PT J AU Schneider, BG John-Aryankalayil, M Rowsey, JJ Dushku, N Reid, TW AF Schneider, BG John-Aryankalayil, M Rowsey, JJ Dushku, N Reid, TW TI Accumulation of p53 protein in pterygia is not accompanied by TP53 gene mutation SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE TP53; p53; pterygia; laser capture microdissection; RT-PCR ID TUMOR-SUPPRESSOR GENE; EPITHELIAL BASAL CELLS; MUTANT P53; GASTRIC-CANCER; LIMBAL TUMORS; LUNG-CANCER; STEM-CELLS; EXPRESSION; SKIN; DIFFERENTIATION AB Previously, we reported that pterygial epithelial cells show positive p53 staining by immunohistochemistry, and that they do not demonstrate apoptosis. We wished to determine whether the accumulation of p53 protein was caused by missense mutations in exons 5-8 of the TP53 gene, as is frequently the case in malignant tumours that contain high levels of abnormal p53. From 11 pterygia, epithelial cells were isolated by laser capture microdissection, or manually, in order to reduce the contribution of TP53 from normal cells. DNA from pterygial epithelial cells was amplified across exons 5-8 in 10 pterygia and across exons 5,7 and 8 in another pterygium. In 2 pterygia, all translated exons (2-11) were sequenced. No mutations were found, although normal polymorphisms in codon 72 were readily detected in 2 pterygia. RT-PCR was used to compare amounts of TP53 mRNA isolated from normal conjunctiva and pterygia from eight additional patients. We detected an approximate two-fold increase of TP53 RNA in pterygia compared to that in normal conjunctiva. Western blotting was used to compare amounts of p53 protein in pterygia and normal conjunctiva. Consistent with our previous immunohistochemical studies, amounts of p53 protein in pterygia, detected by the western blotting, were elevated compared to those detected in normal conjunctiva and corneal limbal epithelium. However, the TP53 gene in pterygia is not imitated, and therefore, the elevated levels of p53 protein must result from a different mechanism than that seen in malignant tumours containing TP53 missense mutations. The increased amount of p53 protein in pterygial cells does not cause apoptosis or block cell proliferation, suggesting that these normal p53 functions are inactivated in pterygia. (C) 2005 Elsevier Ltd. All rights reserved. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, New Orleans, LA 70112 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. St Lukes Cataract & Laser Inst, Tarpon Springs, FL 34688 USA. Kaiser Permanente Med Ctr, Sacramento, CA 95815 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Ophthalmol, Lubbock, TX 79430 USA. Texas Tech Univ, Hlth Sci Ctr, Dept Visual Sci, Lubbock, TX 79430 USA. RP Schneider, BG (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Pathol, 1901 Perdido St, New Orleans, LA 70112 USA. EM bschne@lsuhsc.edu OI Schneider, Barbara/0000-0003-4421-1355 NR 53 TC 13 Z9 13 U1 0 U2 1 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD JAN PY 2006 VL 82 IS 1 BP 91 EP 98 DI 10.1016/j.exer.2005.05.006 PG 8 WC Ophthalmology SC Ophthalmology GA 007BN UT WOS:000234942500012 PM 16005868 ER PT J AU Sapko, MT Guidetti, P Yu, P Tagle, DA Pellicciari, R Schwarcz, R AF Sapko, MT Guidetti, P Yu, P Tagle, DA Pellicciari, R Schwarcz, R TI Endogenous kynurenate controls the vulnerability of striatal neurons to quinolinate: Implications for Huntington's disease SO EXPERIMENTAL NEUROLOGY LA English DT Article DE excitotoxicity; kainic acid; kynurenine 3-hydroxylase; kynurenines; neuroprotection; NMDA receptor ID RAT-BRAIN; AMINOTRANSFERASE-II; (M-NITROBENZOYL)-ALANINE MNBA; THERAPEUTIC TARGET; AMINO-ACID; CELL-DEATH; RO 61-8048; METABOLISM; RECEPTOR; 3-HYDROXYKYNURENINE AB Excessive activation of NMDA receptors results in excitotoxic nerve cell loss, which is believed to play a critical role in the pathophysiology of Huntington's disease (HD) and several other catastrophic neurodegenerative diseases. Kynurenic acid (KYNA), a neuroinibitory tryptophan metabolite, has neuroprotective properties and may serve as an endogenous anti-excitotoxic agent. This hypothesis was tested in the striatum, using mice with a targeted deletion of kynurenine aminotransferase II (KAT II), a major biosynthetic enzyme of KYNA in the mammalian brain. Oil post-natal day (PND) 14, the striatum of mkat-2(-/-) mice showed a reduction in KYNA levels but contained normal concentrations of the metabolically related neurotoxins 3-hydroxykynurenine and quinolinic acid (QUIN). Intrastriatal injections of QUIN, a NMDA receptor agonist, caused significantly larger lesions in these immature mutant mice than in age-matched wildtype animals. This lesion enlargement was not observed when mkat-2(-/-) mice were acutely pre-treated with the kynurenine 3-hydroxylase inhibitor UPF 648, which counteracted the striatal KYNA deficit. Moreover, no increased Vulnerability to QUIN was observed in 2-month-old mkat-2(-/-) mice, which present with normal brain KYNA levels. Intrastriatal injections of the non-NMDA receptor agonist kainate caused similar lesion sizes in both genotypes regardless of age. These results indicate that endogenons KYNA preferentially controls the vulnerability of striatal neurons to QUIN. Our data suggest that timely pharmacological interventions resulting in an up-regulation of brain KYNA levels may benefit patients suffering from HD or other neurodegenerative diseases. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Catonsville, MD 21228 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Perugia, Dipartimento Chim & Tecnol Farmaco, I-06100 Perugia, Italy. RP Schwarcz, R (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, POB 21247, Catonsville, MD 21228 USA. EM rschwarc@mprc.umaryland.edu FU NICHD NIH HHS [HD 16596]; NINDS NIH HHS [NS 42487] NR 57 TC 75 Z9 76 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 EI 1090-2430 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2006 VL 197 IS 1 BP 31 EP 40 DI 10.1016/j.expneurol.2005.07.004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 001LI UT WOS:000234534200005 PM 16099455 ER PT J AU Tai, CF Smerin, SE de Groat, WC Roppolo, JR AF Tai, CF Smerin, SE de Groat, WC Roppolo, JR TI Pudendal-to-bladder reflex in chronic spinal-cord-injured cats SO EXPERIMENTAL NEUROLOGY LA English DT Article DE pudendal nerve; bladder; electrical stimulation; spinal cord injury; cat ID EXTERNAL URETHRAL SPHINCTER; SACRAL NERVE-STIMULATION; ANTERIOR ROOT STIMULATOR; ELECTRICAL-STIMULATION; DETRUSOR HYPERREFLEXIA; MICTURITION REFLEX; URINARY-BLADDER; INHIBITION; INCONTINENCE; AFFERENTS AB The effects of pudendal nerve stimulation on reflex bladder activity were investigated in cats with chronic spinal cord injury (6- 12 months) under alpha-chloralose anesthesia. Electrical stimulation of the pudendal nerve on one side at different frequencies and intensities induced either inhibitory or excitatory effects on bladder activity. The inhibitory effect peaked at a stimulation frequency of 3 Hz and gradually decreased at lower or higher frequencies. The inhibitory effect could occur at stimulation intensities between 0.3 and 1 V (pulse width 0.1 ms) and increased at intensities tip to 10 V Stimulation of the central end of transected pudendal nerve also inhibited bladder activity, indicating that afferent axons in pudendal nerve are involved. Nerve transections also showed that both hypogastric and pelvic nerves might be involved in the inhibitory pudendal-to-bladder spinal reflex. Pudendal nerve stimulation at 20 Hz and at the same intensities (1 - 10 V) elicited a bladder excitatory response. Although this excitatory effect Could not sustain a long lasting bladder contraction at small bladder volumes, it did induce continuous rhythmic bladder contractions at large bladder Volumes. This study indicated the possibility of developing a neuroprosthetic device based on pudendal nerve electrical stimulation to restore micturition function after spinal cord injury. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. NINDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, Bethesda, MD 20892 USA. RP Tai, CF (reprint author), Univ Pittsburgh, Dept Pharmacol, W1354 Biomed Sci Tower, Pittsburgh, PA 15261 USA. EM cftai@pitt.edu FU NICHD NIH HHS [1PO1-HD-39768-02]; NIDDK NIH HHS [R56 DK068566, R01 DK068566, R01 DK068566-01, R01 DK068566-03, R01 DK068566-04A2, R56 DK068566-04A1, R01 DK068566-02, 1R01-DK-068566-01]; NINDS NIH HHS [1R01-NS-045078-01] NR 33 TC 50 Z9 51 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD JAN PY 2006 VL 197 IS 1 BP 225 EP 234 DI 10.1016/j.expneurol.2005.09.013 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 001LI UT WOS:000234534200023 PM 16271266 ER PT J AU Lemonnier, L Trebak, M Lievremont, JP Bird, GS Putney, JW AF Lemonnier, L Trebak, M Lievremont, JP Bird, GS Putney, JW TI Protection of TRPC7 cation channels from calcium inhibition by closely associated SERCA pumps SO FASEB JOURNAL LA English DT Article DE calcium channels; calcium signaling; ion channels; TRPC channels ID CAPACITATIVE CA2+ ENTRY; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; STORE-OPERATED CHANNEL; TRANSIENT RECEPTOR; DROSOPHILA TRP; FUNCTIONAL-CHARACTERIZATION; TRISPHOSPHATE RECEPTOR; ENDOPLASMIC-RETICULUM; SIGNALING MECHANISM; MOLECULAR-CLONING AB Numerous studies have demonstrated that members of the transient receptor potential (TRP) superfamily of channels are involved in regulated Ca2+ entry. Additionally, most Ca2+-permeable channels are themselves regulated by Ca2+, often in complex ways. In the current study, we have investigated the regulation of TRPC7, a channel known to be potentially activated by both store-operated mechanisms and non-store-operated mechanisms involving diacylglycerols. Surprisingly, we found that activation of TRPC7 channels by diacylglycerol was blocked by the SERCA pump inhibitor thapsigargin. The structurally related channel, TRPC3, was similarly inhibited. This effect depended on extracellular calcium and on the driving force for Ca2+ entry. The inhibition is not due to calcium entry through store-operated channels but rather results from calcium entry through TRPC7 channels themselves. The effect of thapsigargin was prevented by inhibition of calmodulin and was mimicked by pharmacological disruption of the actin cytoskeleton. Our results suggest the presence of a novel mechanism involving negative regulation of TRPC channels by calcium entering through the channels. Under physiological conditions, this negative feedback by calcium is attenuated by the presence of closely associated SERCA pumps. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov RI Trebak, Mohamed/E-7405-2014 FU Intramural NIH HHS NR 39 TC 26 Z9 26 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2006 VL 20 IS 1 BP 503 EP + DI 10.1096/fj.05-4714fje PG 25 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 021PU UT WOS:000235996000032 PM 16401641 ER PT J AU Sotiriou, SN Orlova, VV Al-Fakhri, N Ihanus, E Economopoulou, M Isermann, B Bdeir, K Nawroth, PP Preissner, KT Gahmberg, CG Koschinsky, ML Chavakis, T AF Sotiriou, SN Orlova, VV Al-Fakhri, N Ihanus, E Economopoulou, M Isermann, B Bdeir, K Nawroth, PP Preissner, KT Gahmberg, CG Koschinsky, ML Chavakis, T TI Lipoprotein(a) in atherosclerotic plaques recruits inflammatory cells through interaction with Mac-1 integrin SO FASEB JOURNAL LA English DT Article DE plasminogen/angiostatin kringle 4; coronary arteries; prothrombotic tissue factor ID FACTOR-KAPPA-B; TISSUE FACTOR; ANTIINFLAMMATORY FACTOR; LEUKOCYTE RECRUITMENT; TRANSCRIPTION FACTOR; ADHESION MOLECULES; BETA(2) INTEGRINS; TRANSGENIC MICE; APOLIPOPROTEIN(A); ATHEROGENESIS AB Lipoprotein(a) [Lp(a)], consisting of LDL and the unique constituent apolipoprotein(a) [apo(a)], which contains multiple repeats resembling plasminogen kringle 4, is considered a risk factor for the development of atherosclerotic disorders. However, the underlying mechanisms for the atherogenicity of Lp(a) are not completely understood. Here, we define a novel function of Lp(a) in promoting inflammatory cell recruitment that may contribute to its atherogenicity. Through its apo(a) moiety Lp(a) specifically interacts with the beta 2-integrin Mac-1, thereby promoting the adhesion of monocytes and their transendothelial migration in a Mac-1-dependent manner. Interestingly, the interaction between Mac-1 and Lp(a) was strengthened in the presence of proatherogenic homocysteine and was blocked by plasminogen/angiostatin kringle 4. Through its interaction with Mac-1, Lp(a) induced activation of the proinflammatory transcription factor NF kappa B, as well as the NF kappa B-related expression of prothrombotic tissue factor. In atherosclerotic coronary arteries Lp(a) was found to be localized in close proximity to Mac-1 on infiltrating mononuclear cells. Taken together, our data demonstrate that Lp(a), via its apo(a) moiety, is a ligand for the beta 2-integrin Mac-1, thereby facilitating inflammatory cell recruitment to atherosclerotic plaques. These observations suggest a novel mechanism for the atherogenic properties of Lp(a). C1 Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Internal Med 1, Heidelberg, Germany. Univ Marburg, Dept Clin Chem & Mol Diagnost, Marburg, Germany. Univ Helsinki, Fac Biosci, Div Biochem, FIN-00014 Helsinki, Finland. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Giessen, Inst Biochem, Giessen, Germany. Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. RP Chavakis, T (reprint author), Natl Canc Inst, Expt Immunol Branch, NIH, 10 Ctr Dr,Rm 4B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Orlova, Valeria/C-6065-2014; OI Orlova, Valeria/0000-0002-1169-2802; Gahmberg, Carl/0000-0001-9892-9296 NR 58 TC 60 Z9 78 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JAN PY 2006 VL 20 IS 1 BP 559 EP + DI 10.1096/fj.05-4857fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 021PU UT WOS:000235996000026 PM 16403785 ER PT J AU Hearns-Stokes, R Mayers, C Zahn, C Cruess, D Gustafsson, JA Segars, J Nieman, L AF Hearns-Stokes, R Mayers, C Zahn, C Cruess, D Gustafsson, JA Segars, J Nieman, L TI Expression of the proto-oncoprotein breast cancer nuclear receptor auxiliary factor (Brx) is altered in eutopic endometrium of women with endometriosis SO FERTILITY AND STERILITY LA English DT Article DE Brx; estrogen receptor alpha; estrogen receptor beta; endometrium; endometriosis; menstrual cycle; immunohistochemistry ID ESTROGEN-RECEPTOR; MENSTRUAL-CYCLE; SIGNALING COMPLEXES; MESSENGER-RNA; DBL FAMILY; KINASE-A; BETA; ALPHA; CELLS; PHOSPHORYLATION AB Objective: To evaluate the expression of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta), and breast cancer nuclear receptor auxiliary factor (Brx) in eutopic endometrium of normal women and women with endometriosis. Design: Prospective observational study. Setting: Tertiary care and research center. Patient(s): Twenty-nine women with endometriosis and 35 healthy ovulatory volunteers of similar ages. Intervention(s): Endometrial biopsy. Main Outcome Measure(s): Expression of immunohistochemical staining intensity and localization of ER alpha, ER beta, and Brx proteins in eutopic endometrium during the menstrual cycle. Result(s): Expression of ER alpha and ER beta was highest in the proliferative phase and was similar in both groups. Brx expression differed between healthy volunteers and those with endometriosis. During the proliferative phase, immunostaining intensity of Brx was greater in both the glandular and the stromal compartments of biopsies from patients with endometriosis compared to healthy volunteers; nuclear stromal Brx staining was more common in patients with endometriosis. Conclusion(s): The spatiotemporal expression of Brx was altered in eutopic endometrium of women with endometriosis. These findings suggest a fundamental alteration in the endometrium of women who have endometriosis. The role of Brx in ectopic implantation of endometrium deserves further study. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Combined Fed Fellowship Reprod Endocrinol, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Genet & IVF Inst, Fairfax, VA 22039 USA. Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. Karolinska Inst, Huddinge, Sweden. RP Nieman, L (reprint author), Bldg 10,CRC,1 East,Rm 1-3140,10 Ctr Dr,MSC 1109, Bethesda, MD 20892 USA. EM niemanl@nih.gov FU Intramural NIH HHS NR 39 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2006 VL 85 IS 1 BP 63 EP 70 DI 10.1016/j.fertnstert.2005.06.053 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 006QX UT WOS:000234913100015 PM 16412732 ER PT J AU Gustofson, RL Larsen, FW Bush, MR Segars, JH AF Gustofson, RL Larsen, FW Bush, MR Segars, JH TI Treatment with gonadotropin-releasing hormone (GnRH) antagonists in women suppressed with GnRH agonist may avoid cycle cancellation in patients at risk for ovarian hyperstimulation syndrome SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med ID IN-VITRO FERTILIZATION; FOLLICLE-STIMULATING-HORMONE; SERUM ESTRADIOL; CONTROLLED-TRIAL; OOCYTE NUMBER; MATURATION; CONCEPTION; GANIRELIX; EFFICACY; LEVEL AB Forty-seven patients at high risk for ovarian hyperstimulation syndrome because of markedly elevated serum E-2 levels on either long-luteal or microdose flare leuprolide acetate regimens were treated with ganirelix acetate. Despite being pretreated with GnRH agonist and without withholding gonadotropins, serum E-2 decreased by 49.5% and 41.0% of pretreatment values (long luteal and microdose flare, respectively) after initiation of ganirelix, and 68.1% of the patients became pregnant. C1 NICHHD, RBMB, NIH, Bethesda, MD 20892 USA. USN Natl Med Ctr, Combined Fed Fellowship Reprod Endocrinol Infer, NIH, Walter Reed Army Med Ctr, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Segars, JH (reprint author), NICHHD, RBMB, NIH, 10 Ctr Dr MSC 1109,Bldg 10,CRC,1E-3140, Bethesda, MD 20892 USA. EM segarsj@mail.nih.gov FU Intramural NIH HHS NR 25 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JAN PY 2006 VL 85 IS 1 BP 251 EP 254 DI 10.1016/j.fertnstert.2005.07.1291 PG 4 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 006QX UT WOS:000234913100048 PM 16412770 ER PT J AU Santolaya-Forgas, J De Leon-Luis, J Espinoza, J Goncalves, LF Romero, R AF Santolaya-Forgas, J De Leon-Luis, J Espinoza, J Goncalves, LF Romero, R TI Solutes in maternal circulation and gestational sac compartments during early human development SO FETAL DIAGNOSIS AND THERAPY LA English DT Article DE amniotic fluid; extra-embryonic celom; celocentesis; amniocentesis ID EARLY HUMAN-PREGNANCY; TRIMESTER HUMAN PLACENTA; 1ST TRIMESTER; YOLK-SAC; FLUID COMPARTMENTS; AMNIOTIC FLUIDS; RHESUS-MONKEY; FETAL FLUIDS; HUMAN FETUS; VASCULARIZATION AB Objectives:The aim of this study was to review previous work reporting the concentration of solutes measured in maternal circulation, extra-embryonic celomic fluid, and amniotic fluid, to gain insights into the mechanism that could lead to compartmentalization of fluid and solutes within the gestational sac prior to the 12th week of pregnancy. Methods: We conducted a Medline and PubMed literature search from January 1990 through March 2004 using the key words amniotic fluid, celomic fluid, coelomic fluid, celocentesis, coelocentesis, amniocentesis, yolk sac and embryonic cavities. We selected those articles describing solutes that had been measured in the same patient in samples obtained prior to 12 weeks' gestation from maternal circulation, celomic fluid and amniotic fluid. Information extracted from these publications included: gestational age at sampling, number of samples evaluated, mean concentration of the solutes in each of the three fluids and bibliographic citation. Results: We found 73 publications with the key words and selected 13 that met the inclusion criteria. The concentration of 31 solutes reported in each of the three compartments was documented and gradients among compartmental interfaces calculated. Conclusion: This study describes the concentration of solutes measured in maternal circulation, extracelomic fluid and amniotic fluid early in human development. Analysis of calculated gradients across the compartmental interfaces suggests that the shift of fluid may depend on the biophysical properties of the placenta and yolk sac and on graded changes in hydrostatic pressures across compartments. Copyright (c) 2006 S. Karger AG, Basel. C1 Wayne State Univ, Dept Obstet & Gynecol, Perinatol Res Branch, Detroit, MI USA. Texas Tech Univ, Hlth Sci Ctr, Amarillo Womens Hlth Res Inst, Amarillo, TX USA. RP Santolaya-Forgas, J (reprint author), NICHD, DHHS, Perinatol Res Branch, Hutzel Womens Hosp,NIH, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM jsantol@med.wayne.edu NR 37 TC 10 Z9 10 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1015-3837 J9 FETAL DIAGN THER JI Fetal Diagn. Ther. PY 2006 VL 21 IS 3 BP 287 EP 292 DI 10.1159/000091358 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 031WT UT WOS:000236736600011 PM 16601340 ER PT J AU Kajava, AV Steven, AC AF Kajava, Andrey V. Steven, Alasdair C. TI beta-rolls, beta-helices, and other beta-solenoid proteins SO FIBROUS PROTEINS: AMYLOIDS, PRIONS AND BETA PROTEINS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID LEUCINE-RICH REPEAT; N-ACETYLGLUCOSAMINE ACYLTRANSFERASE; P22 TAILSPIKE PROTEIN; SHORT TAIL-FIBER; PECTATE LYASE-C; CRYSTAL-STRUCTURE; 3-DIMENSIONAL STRUCTURE; ERWINIA-CHRYSANTHEMI; BORDETELLA-PERTUSSIS; ACTIVE-SITE AB beta-Rolls and beta-helices belong to a larger group of topologically similar proteins with solenoid folds: because their regular secondary structure elements are exclusively beta-strands, they are referred to as beta-solenoids. The number of beta-solenoids whose structures are known is now large enough to support a systematic analysis. Here we survey the distinguishing structural features of beta-solenoids, also documenting their notable diversity. Appraisal of these structures suggests a classification based on handedness, twist, oligomerization state, and coil shape. In addition, beta-solenoids are distinguished by the number of chains that wind around a common axis: the majority are single-stranded but there is a recently discovered subset of triple-stranded P-solenoids. This survey has revealed some relationships of the amino acid sequences of beta-solenoids with their structures and functions-in particular, the repetitive character of the coil sequences and conformations that recur in tracts of tandem repeats. We have proposed the term beta-arc for the distinctive turns found in beta-solenoids and beta-arch for the corresponding strand-turn-strand motifs. The evolutionary mechanisms underlying these proteins are also discussed. This analysis has direct implications for sequence-based detection, structural prediction, and de novo design of other beta-solenoid proteins. The abundance of virulence factors, toxins and allergens among beta-solenoids, as well as commonalities of beta-solenoids with amyloid fibrils, imply that this class of folds may have a broader role in human diseases than was previously recognized. Thus, identification of genes with putative beta-solenoid domains promises to be a fertile direction in the search for viable targets in the development of new antibiotics and vaccines. C1 Ctr Rech Biochim Macromol, CNRS, FRE 2593, F-34293 Montpellier 5, France. NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kajava, AV (reprint author), Ctr Rech Biochim Macromol, CNRS, FRE 2593, 1919 Route Mende, F-34293 Montpellier 5, France. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 FU Intramural NIH HHS NR 108 TC 71 Z9 71 U1 3 U2 20 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2006 VL 73 BP 55 EP + DI 10.1016/S0065-3233(06)73003-0 PG 49 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFO41 UT WOS:000243421200003 PM 17190611 ER PT J AU Baxa, U Cassese, T Kajava, AV Steven, AC AF Baxa, Ulrich Cassese, Todd Kajava, Andrey V. Steven, Alasdair C. TI Structure, function, and amyloidogenesis of fungal prions: Filament polymorphism and prion variants SO FIBROUS PROTEINS: AMYLOIDS, PRIONS AND BETA PROTEINS SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID HET-S PRION; YEAST SACCHAROMYCES-CEREVISIAE; INTRINSICALLY UNSTRUCTURED PROTEINS; SUPERPLEATED BETA-STRUCTURE; ALPHA-HELICAL CONFORMATION; NATIVELY UNFOLDED PROTEINS; AMYLOID-LIKE FIBRILS; SOLID-STATE NMR; IN-VITRO; PODOSPORA-ANSERINA AB Infectious proteins (prions) became an important medical issue when they were identified as agents of the transmissible spongiform encephalopathies. More recently, prions have been found in fungi and their investigation has been facilitated by greater experimental tractability. In each case, the normal form of the prion protein may be converted into the infectious form (the prion itself) in an autocatalytic process; conversion may either occur spontaneously or by transmission from an already infected cell. Four fungal prion proteins have been studied in some depth-Ure2p, Sup35p, and Rnq1p of Saccharomyces cerevisiae and HET-s of Podospora anserina. Each has a "prion domain" that governs infectivity and a "functional domain" that contributes the protein's activity in a wild-type cell, if it has one. This activity is repressed in prion-infected cells for loss-of-activity prions, [URE3] (the prion of Ure2p) and [PSI] (the prion of Sup35p). For gain-of-activity prions, [PIN] (the prion of Rnq1p) and [Het-s] (the prion of HET-s), the prion domain is also involved in generating a new activity in infected cells. In prion conversion, prion domains polymerize into an amyloid filament, switching from a "natively unfolded" conformation into an amyloid conformation (stable, protease-resistant, rich in cross-beta structure). For Ure2p and probably also Sup35p, the functional domain retains its globular fold but is inactivated by a steric mechanism. We review the evidence on which this scenario is based with emphasis on filament structure, summarizing current experimental constraints and appraising proposed models. We conclude that the parallel superpleated beta-structure and a specific beta-helical formulation are valid candidates while other proposals are excluded. In both the Ure2p and Sup35p systems, prion domain amyloid filaments exhibit polymorphic variation. However, once a certain structure is nucleated, it is maintained throughout that filament. Electron microscopy of several Ure2p-related constructs indicates that the basis for polymorphism lies mainly if not entirely in the prion domain. Filament polymorphism appears to underlie the phenomenon of prion "variants" which differ in the severity of their phenotype, that is, for Ure2p and Sup35p, the stringency with which their activity is switched off. We discuss a possible structural basis for this phenomenon. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20814 USA. Ctr Rech Biochim Macromol, CNRS, FRE 2593, F-34293 Montpellier, France. RP Baxa, U (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 FU Intramural NIH HHS NR 149 TC 41 Z9 43 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2006 VL 73 BP 125 EP + DI 10.1016/S0065-3233(06)73005-4 PG 63 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BFO41 UT WOS:000243421200005 PM 17190613 ER PT J AU Liby, P Kostrouchova, M Pohludka, M Yilma, P Hrabal, P Sikora, J Brozova, E Kostrouchova, M Rall, JE Kostrouch, Z AF Liby, P. Kostrouchova, M. Pohludka, M. Yilma, P. Hrabal, P. Sikora, J. Brozova, E. Kostrouchova, M. Rall, J. E. Kostrouch, Z. TI Elevated and deregulated expression of HDAC3 in human astrocytic glial tumours SO FOLIA BIOLOGICA LA English DT Article DE cancer; HDAC3; histone; deacetylase; glioma ID HISTONE DEACETYLASE INHIBITOR; HUMAN GLIOBLASTOMA CELLS; TRANSCRIPTIONAL COACTIVATOR; HORMONE-RECEPTOR; N-COR; REPRESSION; COMPLEX; CBP; ACETYLATION; ACTIVATION AB Abnormal expression of histone deacetylases may contribute to the establishment of a cancer specific transcription profile. We examined expression of HDAC3 in human non-malignant gliosis and glial astrocytic tumours. Samples from four non-malignant gliosis and 17 astrocytic gliomas (six of grade II, one of grade III and ten of grade IV) removed for therapeutic purposes were assayed for HDAC3 expression at mRNA and protein levels. HDAC3 mRNA was detected in non-tumorous gliosis as well as in all examined glial tumours. Seven out of eleven examined high-grade tumours showed an elevated number of copies of HDAC3 mRNA. Western blot analysis detected high levels of expression of HDAC3 in the majority of the examined tumours. Immunohistochemistry and immunofluorescence made on a collection of 35 astrocytic tumours detected nuclear as well as cytoplasmic HDAC3 expression in all of those tumours. While the distribution of HDAC3 was both nuclear as well as cytoplasmic and moderate in intensity in non-malignant tissues and low-grade gliomas, high-grade tumours expressed HDAC3 in a focally deregulated pattern that included strongly pronounced cytoplasmic localization. Confocal microscopy and additional co-localization analysis detected nuclear HDAC3 in all tumours examined. We conclude that HDAC3 expression is elevated in human astrocytic tumours and its expression pattern is deregulated at the cellular level in high-grade gliomas. C1 Charles Univ, Fac Med 1, Inst Inherited Metab Dis, Lab Mol Pathol, Prague 12801 2, Czech Republic. Charles Univ, Fac Med 1, Lab Mol Biol & Genet, Prague 12801 2, Czech Republic. Charles Univ, Fac Med 1, Inst Inherited Metab Disorders, Prague 12801 2, Czech Republic. Cent Mil Hosp, Dept Pathol, Prague, Czech Republic. NIDDK, NIH, Bethesda, MD 20892 USA. RP Kostrouch, Z (reprint author), Charles Univ, Fac Med 1, Inst Inherited Metab Dis, Lab Mol Pathol, Ke Karlovu 2, Prague 12801 2, Czech Republic. EM zdenek.kostrouch@lfl.cuni.cz RI Sikora, Jakub /F-4842-2017 OI Sikora, Jakub /0000-0003-4104-2023 NR 39 TC 12 Z9 15 U1 1 U2 6 PU CHARLES UNIV PRAGUE, FIRST FACULTY MEDICINE PI PRAGUE 6 PA FLEMINGOVO NAM. 2, PRAGUE 6 166 37, CZECH REPUBLIC SN 0015-5500 J9 FOLIA BIOL-PRAGUE JI Folia Biol.-Prague PY 2006 VL 52 IS 1-2 BP 21 EP 33 PG 13 WC Biochemistry & Molecular Biology; Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Oncology; Cell Biology GA 081KX UT WOS:000240317600005 PM 17007107 ER PT J AU Liby, P Pohludka, M Vohanka, J Kostrouchova, M Kostrouch, D Kostrouchova, M Rall, JE Kostrouch, Z AF Liby, P. Pohludka, M. Vohanka, J. Kostrouchova, M. Kostrouch, D. Kostrouchova, M. Rall, J. E. Kostrouch, Z. TI BIR-1, the homologue of human survivin, regulates expression of developmentally active collagen genes in C. elegans SO FOLIA BIOLOGICA LA English DT Article DE Caenorhabditis elegans; BIR-1; survivin; transcription; development ID CAENORHABDITIS-ELEGANS; HISTONE PHOSPHORYLATION; DYNAMIC REGULATION; CRYSTAL-STRUCTURE; PROTEIN SURVIVIN; APOPTOSIS; TRANSCRIPTION; CANCER; ACETYLATION; ACTIVATION AB BIR-1 and Survivin are highly conserved members of the inhibitor of apoptosis protein family that regulate cell division in nematodes and mammals and inhibit apoptosis in mammals. In the C elegans genome, bir-1 is organized in an operon together with transcription and splicing cofactor CeSKIP (skp-1) and is highly expressed during embryogenesis as well as in non-dividing cells during larval development. Previously we have shown that BIR-1 regulates transcription and development and its loss-of-function phenotype overlaps with loss of function of CeSKIP and nuclear hormone receptor CHR3 (NHR-23). Here we searched for genes whose expression is affected by BIR-1 loss of function using whole-genome microarray experiments and identified several collagen genes as candidate targets of bir-1 inhibition in L1 larval stage. The decreased expression of selected collagen genes in bir-1-inhibited larvae was confirmed by quantitative RT-PCR. Next, we generated transgenic lines expressing bir-1 mRNA under a heat shock-regulated promoter and tested whether bir-1 overexpression has the potential to augment the expression of genes that showed decreased expression in worms treated with bir-1 RNAi. Overexpression of bir-1 resulted in a pronounced increase (2 to 5 times) of the expression of these genes. Our findings support the concept that BIR-1, a protein generally regarded as a mitotic factor, is involved in the regulation. of transcription during normal development of C. elegans and has a strong ability to affect transcription of developmentally active genes if overexpressed. C1 Charles Univ, Fac Med 1, Lab Mol Pathol, Inst Inherited Metab Disorders, Prague 12801 2, Czech Republic. Charles Univ, Fac Med 1, Lab Mol Biol & Genet, Inst Inherited Metab Disorders, Prague 12801 2, Czech Republic. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Kostrouch, Z (reprint author), Charles Univ, Fac Med 1, Lab Mol Pathol, Inst Inherited Metab Disorders, Ke Karlovu 2, Prague 12801 2, Czech Republic. EM zdenek.kostrouch@lfl.cuni.cz NR 29 TC 2 Z9 15 U1 0 U2 2 PU CHARLES UNIV PRAGUE, FIRST FACULTY MEDICINE PI PRAGUE 6 PA FLEMINGOVO NAM. 2, PRAGUE 6 166 37, CZECH REPUBLIC SN 0015-5500 J9 FOLIA BIOL-PRAGUE JI Folia Biol.-Prague PY 2006 VL 52 IS 4 BP 101 EP 108 PG 8 WC Biochemistry & Molecular Biology; Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Oncology; Cell Biology GA 098OA UT WOS:000241531100001 PM 17116281 ER PT S AU Little, E Vizenor, L AF Little, Eric Vizenor, Lowell BE Bennett, B Fellbaum, C TI Principles for the Development of Upper Ontologies in Higher-level Information Fusion Applications SO FORMAL ONTOLOGY IN INFORMATION SYSTEMS SE Frontiers in Artificial Intelligence and Applications LA English DT Proceedings Paper CT 4th International Conference on Formal Ontology in Information Systems CY 2006-2008 CL Johns Hopkins Univ, Charles Commons, Baltimore, MD SP MITRE Corp HO Johns Hopkins Univ, Charles Commons DE Ontology; Relations; Relation-types; Higher Level Fusion; Threat Ontology; STA Ontology AB The use of ontologies within many information science communities is growing at an ever-increasing rate. This is especially true of higher-level multisource information fusion applications, where there is a genuine need for an improved understanding of the complex relational items (e.g. intentions, capabilities, opportunities and vulnerabilities) typically associated with situation and threat assessment (STA). Still, most current ontology development tools lack the resources to support the sorts of ontological distinctions necessary to provide a sufficiently scalable and reusable ontology product for STA purposes. In this paper we analyze the types of complex relations typically involved in STA ontology and discuss how these distinctions can serve as a theoretical framework for the enhancement of existing ontology development tools, especially as these relate to STA ontology. C1 [Little, Eric] DYouville Coll, Doctoral Programs, Ctr Ontol & Interdisciplinaly Res, Buffalo, NY USA. [Vizenor, Lowell] Natl Lib Med, Med Ontol Res, Bethesda, MD USA. RP Little, E (reprint author), DYouville Coll, Doctoral Programs, Ctr Ontol & Interdisciplinaly Res, Buffalo, NY USA. EM little@dyc.edu NR 31 TC 0 Z9 0 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6389 BN 978-1-58603-685-0 J9 FRONT ARTIF INTEL AP PY 2006 VL 150 BP 309 EP + PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Computer Science GA BMS96 UT WOS:000273516700026 ER PT J AU Chen, Q Lee, JH Sun, A Zhang, L Espey, M Krishna, M Pooput, C Kirk, K Choyke, P Buettner, G Shacter, E Levine, M AF Chen, Qi Lee, Je-Hyuk Sun, Andrew Zhang, Liqun Espey, Michael Krishna, Murali Pooput, Chaya Kirk, Kenneth Choyke, Peter Buettner, Garry Shacter, Emily Levine, Mark TI Intravenous ascorbic acid as a pro-drug for ascorbate radical and H2O2 delivery to tissues: Implications in cancer treatment SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NIDDK, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52242 USA. US FDA, CBER, Rockville, MD 20857 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S64 EP S64 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600175 ER PT J AU Connor, KM Aderman, CM Chen, J Higuchi, A Sangiovanni, JP Serhan, CN Smith, LE AF Connor, Kip M. Aderman, Chris M. Chen, Jing Higuchi, Akiko Sangiovanni, John-Paul Serhan, Charles N. Smith, Lois E. TI Increasing dietary omega-3 PUFA reduces pathological angiogenesis via regulation of local resolvins, protectins and TNF-alpha SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 Harvard Univ, Sch Med, Childrens Hosp, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. Harvard Univ, NEI, NIH, Sch Med, Cambridge, MA 02138 USA. RI SanGiovanni, John Paul/A-7605-2008 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S86 EP S86 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600237 ER PT J AU Donzelli, S Switzer, CH Espey, MG Thomas, DD Ridnour, LA Miranda, KM Tocchetti, CG Lazzarino, G Paolocci, N Wink, DA AF Donzelli, Sonia Switzer, Christopher H. Espey, Michael G. Thomas, Douglas D. Ridnour, Lisa A. Miranda, Katrina M. Tocchetti, Carlo G. Lazzarino, Giuseppe Paolocci, Nazareno Wink, David a TI Nitroxyl formation from NH2OH and NOHA oxidation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ 85721 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Catania, I-95124 Catania, Italy. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S12 EP S13 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600023 ER PT J AU Espey, MG Wink, D AF Espey, Michael Graham Wink, David TI Mechanisms of nitrite reduction to NO in cancer SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S107 EP S107 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600290 ER PT J AU Ishii, H Hyodo, F Krishna, MC Mitchell, JB AF Ishii, Hisanari Hyodo, Fuminori Krishna, Murali C. Mitchell, James B. TI Superoxide-dependent hepatotoxicity of the Hsp-90 inhibiting anti-cancer drugs geldanamycin, and its two derivatives SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NCI, Ctr Canc Res, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S148 EP S148 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600416 ER PT J AU Noda, Y Berlett, B Stadtman, ER Aponte, A Morgan, M Shen, RF AF Noda, Yasuko Berlett, Barbara Stadtman, Earl R. Aponte, Angel Morgan, Meghan Shen, Rong-Fong TI Identification of enzymes and regulatory proteins in E-coli that are uniquely oxidized under phosphate starvation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NHLBI, LB, NIH, Bethesda, MD 20892 USA. NHLBI, PCF, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S138 EP S138 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600386 ER PT J AU Piknova, B Keszler, A Hogg, N Schechter, AN AF Piknova, Barbora Keszler, Agnes Hogg, Neil Schechter, Alan N. TI Reactions of nitrite ions with cell-free and intra-erythrocytic oxyhemoglobin and the formation of nitrosylhemoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NIDDK, NIH, Bethesda, MD USA. MCW, Milwaukee, WI 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S52 EP S53 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600150 ER PT J AU Ridnour, L Windhausen, A Isenberg, J Yeung, N Vitek, M Roberts, D Wink, D AF Ridnour, Lisa Windhausen, Alisha Isenberg, Jeffery Yeung, Nolan Vitek, Michael Roberts, David Wink, David TI Nitric oxide regulates MMP-9 activity at the protein level SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Duke Univ, Durham, NC 27706 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 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S16 EP S16 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600036 ER PT J AU Shan, Z Ren, HH Dai, ZS Mason, RP Qian, SY AF Shan, Zhen Ren, Helen H. Dai, Zhensheng Mason, Ronald P. Qian, Steven Y. TI Identification and quantification of carbon-centered free radicals formed from lipoxygenase-dependent peroxidation of EPA: LC/ESR, LC/MS, & dual spin-trapping combination study SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 N Dakota State Univ, Dept Pharmaceut Sci, Fargo, ND 58105 USA. McMaster Univ, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S140 EP S140 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600392 ER PT J AU Thomas, DD Ridnour, LA Espey, MG Wink, DA AF Thomas, Douglas David Ridnour, Lisa a Espey, Michael G. Wink, David a TI Asbestos redirects nitric oxide signaling through rapid catalytic conversion to nitrite SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S113 EP S113 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600313 ER PT J AU Wang, XD Liu, G Macarthur, P Hogg, N Gladwin, MT AF Wang, Xunde Liu, Geng Macarthur, Peter Hogg, Neil Gladwin, Mark T. TI Copper dependence of the biotin switch assay SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 13th Annual Meeting of the Society-for-Free-Radical-Biology-and-Medicine CY NOV 15-19, 2006 CL Denver, CO SP Soc Free Rad Biol & Med C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2006 VL 41 SU 1 BP S17 EP S17 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 103OC UT WOS:000241895600040 ER EF